bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Phylogeny of Jacanas and its Implications for Morphologic and Biogeographic Evolution
Authors: Whittingham Linda A. , Sheldon Frederick H. , Emlen Stephen T.
Published: September 2019

We compared sequences of mitochondrial cytochrome-b and ND5 genes in a phylogenetic analysis of seven species of jacanas, representing all six genera and including the Greater Painted-snipe (Rostratula benghalensis) as an outgroup. When analyzed separately by parsimony and maximum-likelihood bootstrapping, the two genes produced consistent trees, although the ND5 tree was better resolved than the cytochrome-b tree. When combined, the data from the two genes produced a fully resolved tree that was identical to the ND5 tree. This tree had the following form: ((((Irediparra, Microparra), Metopidius), Actophilornis), ((Jacana jacana, J. spinosa), Hydrophasianus)), Rostratula. The phylogeny consists of two major clades that were known to traditional and phylogenetic taxonomists. It also contains sister taxa that are geographically disjunct: the New World Jacana and Asian Hydrophasianus, and the African Microparra and Australian Irediparra. We postulate that this biogeographic pattern results from the extinction of intervening African and Asian taxa, respectively.
Postbreeding Movements of American Avocets and Implications for Wetland Connectivity in the Western Great Basin
Authors: Plissner Jonathan H. , Haig Susan M. , Oring Lewis W.
Published: September 2019

Wetlands in the western Great Basin of the United States are patchily distributed and undergo extensive seasonal and annual variation in water levels. The American Avocet (Recurvirostra americana) is one of many shorebird species that use these wetlands as breeding and migratory stopover sites and must adjust to variable conditions. We used radio telemetry to determine postbreeding, premigratory movement patterns of avocets throughout the region. In 1996 and 1997, 185 breeding adults were captured and fitted with radio transmitters at five breeding areas in Oregon, California, and Nevada. Regular aerial and ground surveys were conducted at the five main study areas from June through September, or until all avocets had left a site. Other wetlands in the western Great Basin also were surveyed by aircraft for the presence of radio-marked birds. Fifty-six percent of radio-marked avocets were still detected in the region at least eight weeks after capture. Each of these individuals was detected at an average of 2.1 lakes (range 0 to 6), with 74% found at more than one lake system. Forty radio-marked individuals moved at least 200 km between wetlands prior to migration, most of which dispersed northward. Male and female patterns did not differ significantly. Overall, movements may be associated with a prebasic molt, exploitation of a superabundant food source in northern lakes, and reconnaissance for future breeding efforts or staging sites. These results also demonstrate wide-ranging patterns of dispersal in this species and suggest a need for the consideration of large-scale habitat connectivity issues in establishing conservation strategies for shorebirds in the western Great Basin.
Game of webs: species and web structure influence contest outcome in black widow spiders
Authors: Jones Cameron , Pollack Lea , DiRienzo Nicholas
Published: September 2019

Population-level trait variation within species plays an often-overlooked role in interspecific interactions. In this study, we compared among-individual variation in web phenotype and foraging behavior between native black widows (Latrodectus hesperus) and invasive brown widows (Latrodectus geometricus). We staged repeated contests whereby native widows defended their webs against intruders of both species to 1) investigate how trait variation mediates web contest outcome among native widows and 2) see whether widow behavior differs in response to an invasive spider. In only one trait, the average number of foraging lines, did black widows differ from brown widows. Black widow residents that built more structural lines were more likely to successfully defend their webs from conspecific intruders (i.e., be the sole spider remaining on the web postinteraction). This association between web structure and contest outcome did not exist in trials between black widows and invasive brown widows; however, in interspecific interactions, these same residents were more likely to have intruders remain on the web rather than drive them away. Surprisingly, brown widows did not usurp black widows. Brown widows were never observed signaling, yet black widow residents signaled equally to intruders of both species. Our results suggest that among-individual variation among native species can influence the response toward invasive competitors and outcome of these interactions.
Carry-over effects of resource competition and social environment on aggression
Authors: Kilgour R J , Norris D R , McAdam A G
Published: September 2019

Aggressive behavior is common in many species and is often adaptive because it enables individuals to gain access to limited resources. However, aggression is also highly plastic and the degree of plasticity could be influenced by factors such as resource limitation and the social environment. In this study, we examined how the effects of social experience and resource limitation could persist to affect future aggressive interactions. Using naturally inbred strains of Drosophila melanogaster that differ in aggressiveness, we manipulated the level of available resources by varying fly density (two treatments: high and low per capita resources) and group composition by varying strain frequency (five treatments: homogeneous strains, or mixed at 1:3, 1:1 or 3:1 ratios of the more aggressive to less-aggressive strain). For each treatment group, we measured aggression before and after flies were placed through a 4-day period of fixed resources. There was no consistent effect of resource competition on aggression. Instead, changes in aggression depended on resource availability in combination with group composition. In homogeneous groups made up of only one strain, all males became more aggressive following the fixed-resource period, regardless of fly density. In mixed-strain treatments at high density, we observed plastic shifts in aggression of males from both strains, but the direction of plastic responses depended on social composition. Our results show that aggression may not only be influenced by the intensity of previous competitive experiences caused by resource limitation, but also through social effects caused by the composition of the group.
Excitatory GABAergic signalling is associated with benzodiazepine resistance in status epilepticus
Authors: Burman Richard J , Selfe Joshua S , Lee John Hamin , van den Berg Maurits , Calin Alexandru , Codadu Neela K , Wright Rebecca , Newey Sarah E , Parrish R Ryley , Katz Arieh A , Wilmshurst Jo M , Akerman Colin J , Trevelyan Andrew J , Raimondo Joseph V
Published: September 2019

Benzodiazepine-resistant status epilepticus is an ongoing clinical challenge. Burman et al. show that longer seizure duration is a useful clinical indicator of benzodiazepine resistance, and that resistance is caused by changes in GABAA receptor-mediated synaptic transmission. The findings could help optimise current management protocols.
Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression
Authors: Fjell Anders M , Sederevicius Donatas , Sneve Markus H , de Lange Ann-Marie Glasø , Bråthen Anne CecilieSjøli , Idland Ane-Victoria , Watne Leiv Otto , Wang Yunpeng , Reinbold Céline , Dobricic Valerija , Kilpert Fabian , Blennow Kaj , Zetterbergj Henrik , Hong Shengjun , Bertram Lars , Walhovd Kristine B ,   for The Alzheimer’s Disease Neuroimaging Initiative
Published: September 2019

Sleep problems are related to the elevated levels of the Alzheimer’s disease (AD) biomarker β-amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.
A Validated Ultra-Performance Liquid Chromatographic Method for the Simultaneous Determination of Nadifloxacin, Mometasone Furoate and Miconazole Nitrate in Their Combined Dosage Form and Spiked Human Plasma Samples
Authors: Tarek Mohamed , Wagdy Hebatallah A , Elzanfaly Eman S , Amer Sawsan M
Published: September 2019

Nadifloxacin, mometasone furoate and miconazole nitrate are formulated together as a topical antifungal dosage form. In this work, a reversed-phase ultra-performance liquid chromatographic method coupled with a diode array detector (RP-UPLC-DAD) was developed and validated to determine nadifloxacin, mometasone furoate and miconazole nitrate simultaneously in their bulk powder, in pharmaceutical preparation and in spiked human plasma samples. Separation was achieved on an ACQUITY UPLC C18 column of 2.2 μm particle size (2.1 × 100 mm) via isocratic elution using a mobile phase consisting of methanol, acetonitrile and water with ratio (50:20:30; v/v/v) and 0.1 g ammonium acetate, then pH was adjusted to (7.00) using acetic acid, flow rate 0.6 mL/min, temperature 30°C and UV detection at 220 nm. The method is linear in a range from 5 to 400 μg/mL for both nadifloxacin and miconazole nitrate and from 20 to 500 μg/mL for mometasone furoate. The method was validated according to the ICH guidelines then applied successfully to determine the mentioned drugs in their pharmaceutical preparation and spiked human plasma samples. For plasma samples, the results showed that the method can determine nadifloxacin, mometasone furoate and miconazole nitrate in human plasma samples with high accuracy and precision.
Risk Factors for Brain Abscess: A Nationwide, Population-Based, Nested Case-Control Study
Authors: Bodilsen Jacob , Dalager-Pedersen Michael , van de Beek Diederik , Brouwer Matthijs C , Nielsen Henrik
Published: September 2019

Background

Knowledge on risk factors for brain abscess is limited and relies on single-center cohort studies.

Methods

We accessed nationwide medical registries to conduct a population-based, nested case-control study of risk factors for brain abscess. We applied risk-set sampling for the selection of population controls (1:10), who were individually matched by age, sex, and area of residence. Conditional logistic regression was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CIs). Population-attributable fractions were calculated.

Results

We identified 1384 brain abscess patients in Denmark from 1982 through 2016, and 13 839 matched population controls. The median age of patients was 50 years (interquartile range 33–63) and 37% were female. Cases often had Charlson comorbidity scores >2 (16%), compared with controls (3%). Our calculated aORs were 2.15 (95% CI 1.72–2.70) for head trauma; 19.3 (95% CI 14.3–26.0) for neurosurgery; 4.61 (95% CI 3.39–6.26) for dental infections; 2.57 (95% CI 1.71–3.84) for dental surgery; 3.81 (95% CI 3.11–4.67) for ear, nose, and throat infection; 2.85 (95% CI 2.21–3.70) for ear, nose, and throat surgery; 15.6 (95% CI 9.57–25.4) for congenital heart disease; 1.74 (95% CI 1.33–2.29) for diabetes mellitus; 2.22 (95% CI 1.58–3.11) for alcohol abuse; 2.37 (95% CI 1.53–3.68) for liver disease; 2.04 (95% CI 1.30–3.20) for kidney disease and 8.15 (95% CI 3.59–18.5) for lung abscess or bronchiectasis. The aORs were 4.12 (95% CI 3.37–5.04) for solid cancer; 8.77 (95% CI 5.66–13.6) for hematological cancer; 12.0 (95% CI 6.13–23.7) for human immunodeficiency virus; and 5.71 (95% CI 4.22–7.75) for immunomodulating treatments. Population-attributable fractions showed were substantial contributors to the occurrence of brain abscess neurosurgery (12%); solid cancer (11%); ear, nose, and throat infections (7%); and immunomodulating treatments (5%).

Conclusions

Important risk factors included neurosurgery; cancer; ear, nose, and throat infections; and immunomodulating treatments.
Vitamin K antagonist has a higher impact than heparin in preventing circuit clotting in chronic haemodialysis patients
Authors: Charles Pierre-Yves , Le Meur Yannick , Tanquerel Tugdual , Galinat Hubert
Published: September 2019

Background

In dialysis sessions, some data suggest that decreasing or even avoiding additional anticoagulation by heparin is possible among patients already treated with oral anticoagulation. However, the required dose of heparin may actually depend on the pre-dialysis international normalized ratio (INR), which varies from one session to another. The aim of our study was to determine the respective role of INR and heparin dosing in the risk of circuit clotting during chronic haemodialysis.

Methods

From early 2012 to July 2016, we analysed the totality of dialysis sessions performed at Brest University Hospital among haemodialysis patients treated by vitamin K antagonists (VKA). We established a prediction of circuit clotting on the basis of a simplified score obtained by combining INR and heparin dosing.

Results

In total, 7184 dialysis sessions among chronic haemodialysis patients under VKA were identified, including 233 with clotting events. The mean INR without clotting events was 2.5 versus 1.8 with clotting events (P < 0.001). Frequencies of circuit clotting were different according to INR group (INR <2.0, INR 2.0–3.0, INR >3.0; P < 0.0001). The protective role of VKA was higher than heparin, as shown by discriminant factor analysis (P < 0.0001).

Conclusion. Our study established a predictive model of thrombosis risk of dialysis circuits in patients treated by VKA for a given heparin dose and a given INR. This model shows a marginal contribution of heparin to protect against the risk of thrombosis compared with VKA. Moreover, heparin would not appear to be necessary for patients with an INR >2.2.
Byte2vec: Malware Representation and Feature Selection for Android
Authors: Yousefi-Azar Mahmood , Hamey Len , Varadharajan Vijay , Chen Shiping
Published: September 2019

Malware detection based on static features and without code disassembling is a challenging path of research. Obfuscation makes the static analysis of malware even more challenging. This paper extends static malware detection beyond byte level $n$-grams and detecting important strings. We propose a model (Byte2vec) with the capabilities of both binary file feature representation and feature selection for malware detection. Byte2vec embeds the semantic similarity of byte level codes into a feature vector (byte vector) and also into a context vector. The learned feature vectors of Byte2vec, using skip-gram with negative-sampling topology, are combined with byte-level term-frequency (tf) for malware detection. We also show that the distance between a feature vector and its corresponding context vector provides a useful measure to rank features. The top ranked features are successfully used for malware detection. We show that this feature selection algorithm is an unsupervised version of mutual information (MI). We test the proposed scheme on four freely available Android malware datasets including one obfuscated malware dataset. The model is trained only on clean APKs. The results show that the model outperforms MI in a low-dimensional feature space and is competitive with MI and other state-of-the-art models in higher dimensions. In particular, our tests show very promising results on a wide range of obfuscated malware with a false negative rate of only 0.3% and a false positive rate of 2.0%. The detection results on obfuscated malware show the advantage of the unsupervised feature selection algorithm compared with the MI-based method.
Foraging Site Selection by Nonbreeding White-Faced IBIS
Authors: Safran Rebecca J. , Colwell Mark A. , Isola Craig R. , Taft Oriane E.
Published: September 2019

We examined foraging site selection by White-faced Ibis (Plegadis chihi) wintering in the Grasslands Ecological Area, which contains the second largest population of nonbreeding ibis in California. We compared habitat variables at White-faced Ibis foraging sites with paired, random locations in managed wetlands of the Grasslands. We contrasted the density and biomass of benthic macroinvertebrates between a subsample of bird foraging locations and random sites. Compared to random locations, the foraging locations of White-faced Ibis were closer to emergent vegetation > 10 cm in height. Moreover, ibis selected foraging locations with significantly higher chironomid and lower oligochaete biomasses relative to random sites. These findings suggest that ibis foraged close to vegetation where prey abundance may be greater and illustrate the importance of maintaining the presence of emergent vegetation in freshwater wetlands.
Impaired NF-κB signalling underlies cyclophilin D-mediated mitochondrial permeability transition pore opening in doxorubicin cardiomyopathy
Authors: Dhingra Rimpy , Guberman Matthew , Rabinovich-Nikitin Inna , Gerstein Jonathon , Margulets Victoria , Gang Hongying , Madden Nicholas , Thliveris James , Kirshenbaum Lorrie A
Published: September 2019

Aims

The chemotherapy drug doxorubicin (Dox) is commonly used for treating a variety of human cancers; however, it is highly cardiotoxic and induces heart failure. We previously reported that the Bcl-2 mitochondrial death protein Bcl-2/19kDa interaction protein 3 (Bnip3), is critical for provoking mitochondrial perturbations and necrotic cell death in response to Dox; however, the underlying mechanisms had not been elucidated. Herein, we investigated mechanism that drives Bnip3 gene activation and downstream effectors of Bnip3-mediated mitochondrial perturbations and cell death in cardiac myocytes treated with Dox.

Methods and results

Nuclear factor-κB (NF-κB) signalling, which transcriptionally silences Bnip3 activation under basal states in cardiac myocytes was dramatically reduced following Dox treatment. This was accompanied by Bnip3 gene activation, mitochondrial injury including calcium influx, permeability transition pore (mPTP) opening, loss of nuclear high mobility group protein 1, reactive oxygen species production, and cell death. Interestingly, impaired NF-κB signalling in cells treated with Dox was accompanied by protein complexes between Bnip3 and cyclophilin D (CypD). Notably, Bnip3-mediated mPTP opening was suppressed by inhibition of CypD—demonstrating that CypD functionally operates downstream of Bnip3. Moreover, restoring IKKβ–NF-κB activity in cardiac myocytes treated with Dox suppressed Bnip3 expression, mitochondrial perturbations, and necrotic cell death.

Conclusions

The findings of the present study reveal a novel signalling pathway that functionally couples NF-κB and Dox cardiomyopathy to a mechanism that is mutually dependent upon and obligatorily linked to the transcriptional control of Bnip3. Our findings further demonstrate that mitochondrial injury and necrotic cell death induced by Bnip3 is contingent upon CypD. Hence, maintaining NF-κB signalling may prove beneficial in reducing mitochondrial dysfunction and heart failure in cancer patients undergoing Dox chemotherapy.
Mabellini: a genome-wide database for understanding the structural proteome and evaluating prospective antimicrobial targets of the emerging pathogen Mycobacterium abscessus
Authors: Skwark Marcin J , Torres Pedro H M , Copoiu Liviu , Bannerman Bridget , Floto R Andres , Blundell Tom L
Published: September 2019

Mycobacterium abscessus, a rapid growing, multidrug resistant, nontuberculous mycobacteria, can cause a wide range of opportunistic infections, particularly in immunocompromised individuals. M. abscessus has emerged as a growing threat to patients with cystic fibrosis, where it causes accelerated inflammatory lung damage, is difficult and sometimes impossible to treat and can prevent safe transplantation. There is therefore an urgent unmet need to develop new therapeutic strategies. The elucidation of the M. abscessus genome in 2009 opened a wide range of research possibilities in the field of drug discovery that can be more effectively exploited upon the characterization of the structural proteome. Where there are no experimental structures, we have used the available amino acid sequences to create 3D models of the majority of the remaining proteins that constitute the M. abscessus proteome (3394 proteins and over 13 000 models) using a range of up-to-date computational tools, many developed by our own group. The models are freely available for download in an on-line database, together with quality data and functional annotation. Furthermore, we have developed an intuitive and user-friendly web interface (http://www.mabellinidb.science) that enables easy browsing, querying and retrieval of the proteins of interest. We believe that this resource will be of use in evaluating the prospective targets for design of antimicrobial agents and will serve as a cornerstone to support the development of new molecules to treat M. abscessus infections.
Representing glycophenotypes: semantic unification of glycobiology resources for disease discovery
Authors: Gourdine Jean-Philippe F , Brush Matthew H , Vasilevsky Nicole A , Shefchek Kent , Köhler Sebastian , Matentzoglu Nicolas , Munoz-Torres Monica C , McMurry Julie A , Zhang Xingmin Aaron , Robinson Peter N , Haendel Melissa A
Published: September 2019

While abnormalities related to carbohydrates (glycans) are frequent for patients with rare and undiagnosed diseases as well as in many common diseases, these glycan-related phenotypes (glycophenotypes) are not well represented in knowledge bases (KBs). If glycan-related diseases were more robustly represented and curated with glycophenotypes, these could be used for molecular phenotyping to help to realize the goals of precision medicine. Diagnosis of rare diseases by computational cross-species comparison of genotype–phenotype data has been facilitated by leveraging ontological representations of clinical phenotypes, using Human Phenotype Ontology (HPO), and model organism ontologies such as Mammalian Phenotype Ontology (MP) in the context of the Monarch Initiative. In this article, we discuss the importance and complexity of glycobiology and review the structure of glycan-related content from existing KBs and biological ontologies. We show how semantically structuring knowledge about the annotation of glycophenotypes could enhance disease diagnosis, and propose a solution to integrate glycophenotypes and related diseases into the Unified Phenotype Ontology (uPheno), HPO, Monarch and other KBs. We encourage the community to practice good identifier hygiene for glycans in support of semantic analysis, and clinicians to add glycomics to their diagnostic analyses of rare diseases.
Experimental evolution of gallium resistance in Escherichia coli
Authors: Graves Joseph L , Ewunkem Akamu J , Ward Jason , Staley Constance , Thomas Misty D , Rhinehardt Kristen L , Han Jian , Harrison Scott H
Published: September 2019

Background and Objectives

Metallic antimicrobial materials are of growing interest due to their potential to control pathogenic and multidrug-resistant bacteria. Yet we do not know if utilizing these materials can lead to genetic adaptations that produce even more dangerous bacterial varieties.

Methodology

Here we utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance.

Results

By day 10 of evolution, increased gallium resistance was evident in populations cultured in medium containing a sublethal concentration of gallium. Furthermore, these populations showed increased resistance to ionic silver and iron (III), but not iron (II) and no increase in traditional antibiotic resistance compared with controls and the ancestral strain. In contrast, the control populations showed increased resistance to rifampicin relative to the gallium-resistant and ancestral population. Genomic analysis identified hard selective sweeps of mutations in several genes in the gallium (III)-resistant lines including: fecA (iron citrate outer membrane transporter), insl1 (IS30 tranposase) one intergenic mutations arsC →/→ yhiS; (arsenate reductase/pseudogene) and in one pseudogene yedN ←; (iapH/yopM family). Two additional significant intergenic polymorphisms were found at frequencies > 0.500 in fepD ←/→ entS (iron-enterobactin transporter subunit/enterobactin exporter, iron-regulated) and yfgF ←/→ yfgG (cyclic-di-GMP phosphodiesterase, anaerobic/uncharacterized protein). The control populations displayed mutations in the rpoB gene, a gene associated with rifampicin resistance.

Conclusions

This study corroborates recent results observed in experiments utilizing pathogenic Pseudomonas strains that also showed that Gram-negative bacteria can rapidly evolve resistance to an atom that mimics an essential micronutrient and shows the pleiotropic consequences associated with this adaptation.

Lay summary

We utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance.
Factors associated with improving diet and physical activity among persons with excess body weight
Authors: Reile Rainer , Leinsalu Mall
Published: September 2019

Background

As overweight and obesity are highly prevalent in Eastern Europe, the study examined the trends and factors associated with self-reported weight reducing behaviours among individuals with excess body weight in Estonia.

Methods

Study used nationally representative cross-sectional data from 2006 to 2016 including 4302 men and 3627 women aged 20–64 years with excess body weight (BMI ≥ 25). Trends in the prevalence of changing eating habits and physical activity and their sociodemographic and health-related correlates were studied using descriptive statistics and multivariable logistic regression.

Results

Among overweight or obese respondents, 41% of men and 48% of women reported improvements in dietary habits and 19% of men and women reported increase in physical activity during the past 12 months in 2016. Positive trend for 2006–2016 regarding both outcomes was observed for men whereas no statistically significant differences were found for women. Women and those with lower than tertiary education had higher odds for reporting change in eating habits whereas older age and smoking or excessive alcohol consumption reduced the odds. Improvement in physical activity was more likely among younger respondents, women, ethnic Estonians and those with tertiary education, whereas poorer health and smoking reduced the odds. Weight-related advice from health professionals or family had strong effect on both outcomes.

Conclusion

Socio-demographic and health profiles differentiate the self-reported behavioural change among persons with excess body weight. Advice from either health professionals or family may have a potential to facilitate positive changes in eating habits and physical activity among those individuals.
Molecular and isotopic evidence of the distribution of nitrogen-cycling microbial communities in the oxygen minimum zone of the Tropical Mexican Pacific
Authors: Pajares Silvia , Soto-Jiménez Martín F , Merino-Ibarra Martín
Published: September 2019

Microbial communities play a central role in the N cycle of oceanic oxygen minimum zones (OMZs), such as in the Eastern Tropical North Pacific (ETNP). We explored the spatial distribution of the genetic potential for ammonia oxidation (amoA gene for bacteria and archaea), denitrification (nirS and nirK), anammox (hzo) and DNRA (nrfA) and their relationships with the hydrological variables and isotopic composition of nitrate in the ETNP off Mexico. Oxygen concentration, the availability of N chemical forms and the upwelling shaped the distribution of N cycling genes along the water column. The high abundance of N genes and the isotopic composition of nitrate suggest the N cycling is very dynamic in the OMZ core. The accumulation of nitrite, the high abundance of archaeal amoA genes, and the deviation of the N and O isotopes of nitrate from the expected 1:1 ratio for nitrate reduction in the upper portion of this OMZ indicate that nitrification is a relevant process that fuels the denitrifier community. Conversely, the high abundances of nitrate, ammonium, and nrfA genes in the deeper layer indicate that DNRA is a crucial process enhancing anammox there. These results show the need for more detailed studies of the N processes in OMZs.
Detection of Mycobacterium tuberculosis lipoarabinomannan and CFP-10 (Rv3874) from urinary extracellular vesicles of tuberculosis patients by immuno-PCR
Authors: Dahiya Bhawna , Khan Anish , Mor Preeti , Kamra Ekta , Singh Netrapal , Gupta Krishna B , Sheoran Abhishek , Sreenivas Vishnubhatla , Mehta Promod K
Published: September 2019

Extracellular vesicles (EVs), the small circulating vesicles released from urine samples of tuberculosis (TB) patients, contain a pool of biomarkers. We recently detected Mycobacterium tuberculosis lipoarabinomannan (LAM) and CFP-10 (Rv3874) biomarkers from the urinary EVs of pulmonary TB (PTB) and extrapulmonary TB (EPTB) patients by immuno-polymerase chain reaction (I-PCR) assay and the results were compared with the analogous enzyme-linked immunosorbent assay (ELISA). The detection limits of both purified LAM and CFP-10 were determined to be 1 fg/mL with I-PCR, which was 106 times lower than ELISA. Detection of LAM and CFP-10 biomarkers in urinary EVs of TB patients by I-PCR showed superiority over ELISA. Notably, LAM I-PCR revealed sensitivities of 74.3 and 67.9% in PTB (n = 74) and EPTB (n = 53) patients, respectively, with specificities of 91.5–92.8% (n = 116). Moreover, the sensitivities attained with LAM I-PCR were significantly higher (P < 0.01) than with CFP-10 I-PCR. After further improving the sensitivity and specificity of the assay, our I-PCR based on LAM detection in urinary EVs may be used as an adjunct test for rapid diagnosis of TB.
Between Modernity and Nostalgia: The Meanings of Death in Hotels
Authors: Zitzlsperger Ulrike
Published: September 2019

This article takes its cue from the public impact of the deaths of singers, artists and writers in hotels. Particular attention is paid to the murder of Nancy Spungen in New York’s Chelsea Hotel, in 1978. A long tradition of literary and filmic hotel deaths shows similarly strong links with contemporary cultures – illustrating political, social or cultural change and questioning the impact of modernity. However, as well as responding to change, death in the context of hotels is also linked with nostalgia for an irretrievable past. Such are the two poles of cultural criticism in the topos of hotel deaths: they throw modernity into relief, celebrating or criticizing it through the symbolic structure of the hotel; or they inculcate a warm nostalgia, in critical opposition to the world outside on the street. The individual authors and directors under consideration here in exploring these points include Joseph Roth, Vicki Baum, F. W. Murnau, Giuseppi Tomasi di Lampedusa and Friedrich Glauser, highlighting the importance of the theme straddling American and European cultures.
Knots and Solenoids that Cannot Be Attractors of Self-homeomorphisms of ℝ3
Authors: Barge H , Sánchez-Gabites J J
Published: September 2019

As a 1st step to understand how complicated attractors for dynamical systems can be, one may consider the following realizability problem: given a continuum $K \subseteq \mathbb{R}^3$, decide when $K$ can be realized as an attractor for a homeomorphism of $\mathbb{R}^3$. In this paper we introduce toroidal sets as those continua $K \subseteq \mathbb{R}^3$ that have a neighbourhood basis comprised of solid tori and, generalizing the classical notion of genus of a knot, give a natural definition of the genus of toroidal sets and study some of its properties. Using these tools we exhibit knots and solenoids for which the answer to the realizability problem stated above is negative.
Transcriptional Activator OvrA Encoded in O Island 19 Modulates Virulence Gene Expression in Enterohemorrhagic Escherichia coli O157:H7
Authors: Liu Bin , Wang Junyue , Wang Lu , Ding Peng , Yang Pan , Yang Bin
Published: September 2019

The human intestinal pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes bloody diarrhea, hemorrhagic colitis, and fatal hemolytic uremic syndrome. Its genome contains 177 unique O islands (OIs), which contribute largely to the high virulence and pathogenicity although most OI genes remain uncharacterized. In the current study, we demonstrated that OI-19 is required for EHEC O157:H7 adherence to host cells. Z0442 (OI-encoded virulence regulator A [OvrA]) encoded in OI-19 positively regulated bacterial adherence by activating locus of enterocyte effacement (LEE) gene expression through direct OvrA binding to the gene promoter region of the LEE gene master regulator Ler. Mouse colonization experiments revealed that OvrA promotes EHEC O157:H7 adherence in mouse intestine, preferentially the colon. Finally, OvrA also regulated virulence in other non-O157 pathogenic E. coli, including EHEC strains O145:H28 and O157:H16 and enteropathogenic E. coli strain O55:H7. Our work markedly enriches the understanding of bacterial adherence control and provides another example of laterally acquired regulators that mediate LEE gene expression.
A step closer to nationwide electronic health record–based chronic disease surveillance: characterizing asthma prevalence and emergency department utilization from 100 million patient records through a novel multisite collaboration
Authors: Tarabichi Yasir , Goyden Jake , Liu Rujia , Lewis Steven , Sudano Joseph , Kaelber David C
Published: September 2019

Objective

The study sought to assess the feasibility of nationwide chronic disease surveillance using data aggregated through a multisite collaboration of customers of the same electronic health record (EHR) platform across the United States.

Materials and Methods

An independent confederation of customers of the same EHR platform proposed and guided the development of a program that leverages native EHR features to allow customers to securely contribute de-identified data regarding the prevalence of asthma and rate of asthma-associated emergency department visits to a vendor-managed repository. Data were stratified by state, age, sex, race, and ethnicity. Results were qualitatively compared with national survey-based estimates.

Results

The program accumulated information from 100 million health records from over 130 healthcare systems in the United States over its first 14 months. All states were represented, with a median coverage of 22.88% of an estimated state’s population (interquartile range, 12.05%-42.24%). The mean monthly prevalence of asthma was 5.27 ± 0.11%. The rate of asthma-associated emergency department visits was 1.39 ± 0.08%. Both measures mirrored national survey-based estimates.

Discussion

By organizing the program around native features of a shared EHR platform, we were able to rapidly accumulate population level measures from a sizeable cohort of health records, with representation from every state. The resulting data allowed estimates of asthma prevalence that were comparable to data from traditional epidemiologic surveys at both geographic and demographic levels.

Conclusions

Our initiative demonstrates the potential of intravendor customer collaboration and highlights an organizational approach that complements other data aggregation efforts seeking to achieve nationwide EHR-based chronic disease surveillance.
Preparation of single-chain Fv antibodies in the cytoplasm of Escherichia coli by simplified and systematic chaperone optimization
Authors: Liu Chenjiang , Kobashigawa Yoshihiro , Yamauchi Soichiro , Toyota Yuya , Teramoto Manaka , Ikeguchi Yuka , Fukuda Natsuki , Sato Takashi , Sato Yuko , Kimura Hiroshi , Morioka Hiroshi
Published: September 2019

A single-chain variable fragment (scFv) antibody is a recombinant protein in which a peptide linker connects the variable regions of the heavy chain and light chain. Due to its smaller molecular size, an scFv can be expressed using Escherichia coli. The presence of two disulphide bonds in the molecule often prevents expression of correctly folded scFv in the E. coli cytoplasm, making a refolding process necessary to regenerate scFv activity. The refolding process is time-consuming and requires large amounts of expensive reagents, such as guanidine hydrochloride, l-arginine and glutathione. Here, to conveniently obtain scFv proteins, we devised a simple and systematic method to optimize the co-expression of chaperone proteins and to combine them with specially engineered E. coli strains that permit the formation of stable disulphide bonds within the cytoplasm. Several scFv proteins were successfully obtained in a soluble form from E. coli cytoplasm. Thermal denaturation experiments and/or surface plasmon resonance measurements revealed that the thus-obtained scFvs possessed a stable tertiary structure and antigen-binding activity. The combined use of engineered E. coli with the simplified and systematic chaperone optimization can be useful for the production of scFv proteins.
The Achmea Judgment and the Applicability of the Energy Charter Treaty in Intra-EU Investment Arbitration
Authors: Basedow J Robert
Published: September 2019

The Energy Charter Treaty is the most frequently used investment treaty worldwide to launch investment arbitration against host states. The vast majority of disputes is of intra-European Union nature in that they involve an EU investor as claimant and an European Union member state as respondent. The recent Achmea judgment of the Court of Justice of the European Union may thus have ramifications for the Energy Charter Treaty. The judgment has triggered a heated legal and political debate within the European Union over the future of intra-European Union investment arbitration. In the context of this debate, the European Commission claimed that the application of the Energy Charter Treaty in intra-European Union investment disputes is based on an incorrect interpretation of this treaty. This article critically assesses the Commission’s statement by evaluating the travaux préparatoires of the Energy Charter Treaty as a supplementary means of interpretation. It finds that the European Union member states and the European Commission in all likelihood opted for a mixed ratification for legal reasons rather than to ensure its intra-European Union applicability. Indeed, the EU initially pushed for a disconnection clause to prevent the application of the Energy Charter Treaty in intra-European Union relations but dropped this request during the negotiations. At least from a historical perspective then, the Commission’s claim that the Energy Charter Treaty is not meant to apply in intra-European Union relations is inaccurate in that the European Union consciously accepted this possibility.
A continent-scale study of the social structure and phylogeography of the bent-wing bat, Miniopterus schreibersii (Mammalia: Chiroptera), using new microsatellite data
Authors: Gürün Kanat , Furman Andrzej , Juste Javier , Ramos Pereira Maria J , Palmeirim Jorge M , Puechmaille Sebastien J , Hulva Pavel , Presetnik Primoz , Hamidovic Daniela , Ibáñez Carlos , Karataş Ahmet , Allegrini Benjamin , Georgiakakis Panagiotis , Scaravelli Dino , Uhrin Marcel , Nicolaou Haris , Abi-Said Mounir R , Nagy Zoltan L , Gazaryan Suren , Bilgin Raşit
Published: September 2019

Miniopterus schreibersii is a cave-dwelling bat species with a wide distribution in the western Palearctic spanning southern and central Europe, North Africa, Anatolia, the Middle East, and the Caucasus. We investigated the social structure and its effects on the genetic makeup of this species, using 10 nuclear microsatellite markers and a partial fragment of the mitochondrial cytochrome b gene. Samples were examined from the species' entire circum-Mediterranean range. Local structuring that was previously detected among populations of M. schreibersii using mitochondrial markers was not observed for microsatellite markers, indicating male-biased dispersal for the species. Some support was found for postglacial expansions in Europe, with Anatolia potentially acting as the primary refugium during the Last Glacial Maximum (LGM). However, support for this hypothesis is not as strong as that previously detected using mitochondrial DNA markers. This is likely due to the diminishing effect of male-mediated dispersal, replenishing the nuclear diversity faster than the mitochondrial diversity in regions that are relatively far from the glacial refugia.
Factors Associated With Oncologist Discussions of the Costs of Genomic Testing and Related Treatments
Authors: Yabroff K Robin , Zhao Jingxuan , de Moor Janet S , Sineshaw Helmneh M , Freedman Andrew N , Zheng Zhiyuan , Han Xuesong , Rai Ashish , Klabunde Carrie N
Published: September 2019

Background

Use of genomic testing is increasing in the United States. Testing can be expensive, and not all tests and related treatments are covered by health insurance. Little is known about how often oncologists discuss costs of testing and treatment or about the factors associated with those discussions.

Methods

We identified 1220 oncologists who reported discussing genomic testing with their cancer patients from the 2017 National Survey of Precision Medicine in Cancer Treatment. Multivariable polytomous logistic regression analyses were used to assess associations between oncologist and practice characteristics and the frequency of cost discussions. All statistical tests were two-sided.

Results

Among oncologists who discussed genomic testing with patients, 50.0% reported often discussing the likely costs of testing and related treatments, 26.3% reported sometimes discussing costs, and 23.7% reported never or rarely discussing costs. In adjusted analyses, oncologists with training in genomic testing or working in practices with electronic medical record alerts for genomic tests were more likely to have cost discussions sometimes (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.19 to 3.69) or often (OR = 2.22, 95% CI = 1.30 to 3.79), respectively, compared to rarely or never. Other factors statistically significantly associated with more frequent cost discussions included treating solid tumors (rather than only hematological cancers), using next-generation sequencing gene panel tests, having higher patient volume, and working in practices with higher percentages of patients insured by Medicaid, or self-paid or uninsured.

Conclusions

Interventions targeting modifiable oncologist and practice factors, such as training in genomic testing and use of electronic medical record alerts, may help improve cost discussions about genomic testing and related treatments.
Combined Therapy With Hyperbaric Oxygen and Melatonin Effectively Reduce Brain Infarct Volume and Preserve Neurological Function After Acute Ischemic Infarct in Rat
Authors: Lin Kun-Chen , Chen Kuan-Hung , Wallace Christopher Glenn , Chen Yi-Ling , Ko Sheung-Fat , Lee Mel S , Yip Hon-Kan
Published: September 2019

This study tested the hypothesis that combined hyperbaric oxygen (HBO) and melatonin (Mel) was superior to either one for protecting the brain functional and parenchymal integrity from acute ischemic stroke (IS) injury. Adult-male Sprague-Dawley rats were divided into groups 1 (sham-operated control), 2 (IS), 3 (IS + HBO), 4 (IS + Mel), and 5 (IS + HBO-Mel). By day 28 after IS, the brain infarct area (BIA) was lowest in group 1, highest in group 2, significantly higher in groups 3 and 4 than in group 5, but not different between groups 3 and 4. The neurological function at day 7, 14, and 28 exhibited an opposite pattern to BIA among the 5 groups. The protein expressions of inflammatory (IL-1β/IL-6/iNOS/TNF-α/p-NF-κB), apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial Bax), mitochondrial/DNA-damaged (cytochrome-C/γ-H2AX), oxidative stress (NOX-1/NOX-2), and autophagy (i.e. ratio of CL3B-II/CL3B-I) biomarkers displayed an identical pattern of BIA among 5 groups. Cellular expressions of inflammation (F4/80+/GFAP+) and DNA-damaged biomarker (γ-H2AX+) exhibited an identical pattern, whereas the integrities of myelin sheath/neuron (MPB+/NeuN+), endothelial cell (CD31+/vWF+), and number of small vessels exhibited an opposite pattern of BIA among the 5 groups. Combined HBO-Mel therapy offered an additional benefit in protecting the brain against IS injury.