bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Amiloride-Sensitive Na+ Channel in Taste Cells Really ENaC?
Authors: Vandenbeuch Aurelie , Kinnamon Sue C
Published: February 2020

Among the 5 taste qualities, salt is the least understood. The receptors, their expression pattern in taste cells, and the transduction mechanisms for salt taste are still unclear. Previous studies have suggested that low concentrations of NaCl are detected by the amiloride-sensitive epithelial Na+ channel (ENaC), which in other systems requires assembly of 3 homologous subunits (α, β, and γ) to form a functional channel. However, a new study from Lossow and colleagues, published in this issue of Chemical Senses, challenges that hypothesis by examining expression levels of the 3 ENaC subunits in individual taste cells using gene-targeted mice in combination with immunohistochemistry and in situ hybridization. Results show a lack of colocalization of ENaC subunits in taste cells as well as expression of subunits in taste cells that show no amiloride sensitivity. These new results question the molecular identity of the amiloride-sensitive Na+ conductance in taste cells.
Frequency and Predictors of Tenofovir-diphosphate Detection Among Young Kenyan Women in a Real-world Pre-exposure Prophylaxis Implementation Program
Authors: Pintye Jillian , Kinuthia John , Abuna Felix , Mugwanya Kenneth , Lagat Harison , Dettinger Julia C , Odinga Daniel , Sila Joseph , Anderson Peter L , John-Stewart Grace , Baeten Jared M
Published: February 2020

In a pre-exposure prophylaxis program for Kenyan women, we detected tenofovir-diphosphate in 61% (125/201) of randomly selected dried blood spots collected at the first follow-up visit. Tenofovir-diphosphate was detected more frequently among women who had partners living with human immunodeficiency virus, who were not pregnant, and who were ≥24 years.
Advances in Diagnosis of Progressive Pulmonary and Disseminated Coccidioidomycosis
Authors: Kassis Christelle , Durkin Michelle , Holbrook Eric , Myers Robert , Wheat Lawrence
Published: February 2020

Background

Antibody detection is the main method for diagnosis of coccidioidomycosis, but it has limitations. The Coccidioides antigen enzyme immunoassay is recommended for testing cerebrospinal fluid in suspected meningitis. Reports on urine and serum antigen detection evaluated small numbers of patients who were mostly immunocompromised. The purpose of this study was to assess the accuracy of combined antibody and antigen detection for diagnosis.

Methods

A retrospective study, including all patients in whom Coccidioides antigen detection in serum was performed between January 2013 and May 2017, was conducted at Valleywise Health Medical Center (formerly Maricopa Integrated Health System). Sensitivity and specificity of antigen and antibody were evaluated in 158 cases and 487 controls.

Results

The sensitivity of antibody detection by immunodiffusion (ID) was 84.2%. The sensitivity of antigen detection was 57.0% if both urine and serum were tested and 36.7% if urine alone was tested. The sensitivity of combining antigen and ID antibody detection was 93.0%. The sensitivity of urine and serum antigen detection was 55.4% in proven and 58.7% in probable cases, 79.1% in disseminated and 41.6% in pulmonary cases, and 74.7% in immunocompromised and 40.0% in immunocompetent patients. Specificity was 99.4% for antigen detection and 96.5% for ID antibody detection. Diagnostic accuracy was 95.4% for ID antibody and antigen detection, 93.6% for ID antibody alone, and 89.1% for pathology or culture.

Conclusions

These findings support combined antibody and antigen detection for diagnosis of progressive coccidioidomycosis. The diagnosis may have been missed if antigen detection was not performed.
Burden of Candidemia in the United States, 2017
Authors: Tsay Sharon V , Mu Yi , Williams Sabrina , Epson Erin , Nadle Joelle , Bamberg Wendy M , Barter Devra M , Johnston Helen L , Farley Monica M , Harb Sasha , Thomas Stepy , Bonner Lindsay A , Harrison Lee H , Hollick Rosemary , Marceaux Kaytlynn , Mody Rajal K , Pattee Brittany , Shrum Davis Sarah , Phipps Erin C , Tesini Brenda L , Gellert Anita B , Zhang Alexia Y , Schaffner William , Hillis Sherry , Ndi Danielle , Graber Caroline R , Jackson Brendan R , Chiller Tom , Magill Shelley , Vallabhaneni Snigdha
Published: February 2020

Background

Candidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States (US).

Methods

In 2017, the Centers for Disease Control and Prevention conducted active population-based surveillance for candidemia through the Emerging Infections Program in 45 counties in 9 states encompassing approximately 17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida, and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality were estimated by extrapolating surveillance area cases to national numbers using 2017 national census data.

Results

We identified 1226 candidemia cases across 9 surveillance sites in 2017. Based on this, we estimated that 22 660 (95% confidence interval [CI], 20 210–25 110) cases of candidemia occurred in the US in 2017. Overall estimated incidence was 7.0 cases per 100 000 persons, with highest rates in adults aged ≥ 65 years (20.1/100 000), males (7.9/100 000), and those of black race (12.3/100 000). An estimated 3380 (95% CI, 1318–5442) deaths occurred within 7 days of a positive Candida blood culture, and 5628 (95% CI, 2465–8791) deaths occurred during the hospitalization with candidemia.

Conclusions

Our analysis highlights the substantial burden of candidemia in the US. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions.
A Prospective, Population-based Study to Determine the Incidence and Bacteriology of Bacterial Conjunctivitis in Children <2 Years of Age Following 7-Valent and 13-Valent Pneumococcal Conjugate Vaccine Sequential Implementation
Authors: Dagan Ron , Ben-Shimol Shalom , Greenberg David , Givon-Lavi Noga
Published: February 2020

Background

Bacterial conjunctivitis is most commonly caused by nontypeable Haemophilus influenzae (NTHi), followed by Streptococcus pneumoniae. No population-based data on the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of bacterial conjunctivitis have been published. We assessed rate dynamics of overall, pneumococcal, and NTHi conjunctivitis in children aged 2–23 months in southern Israel before and after PCV implementation.

Methods

This is a 12-year prospective, population-based surveillance, from July 2004 through June 2017. Our medical center serves a captive population of approximately 30 000 children < 2 years of age, and its clinical microbiology laboratory processes > 80% of all community-derived cultures, enabling incidence calculation. The 7-valent and 13-valent PCVs (PCV7 and PCV13, respectively) were implemented in the national immunization program in July 2009 and November 2010, respectively. Pneumococci, NTHi, Moraxella catarrhalis, and Streptococcus pyogenes were considered pathogens. Continuous annual incidences and incidence rate ratios comparing the PCV13 period (2015–2017) to the pre-PCV period (2004–2008) were calculated.

Results

Disease caused by PCV13 serotypes declined by 93%, without significant replacement with non-PCV13 serotypes. Rates of pneumococcal, NTHi, and overall culture-positive episodes declined by 59%, 41%, and 42%, respectively, while rates of culture-negative and other pathogens episodes did not change significantly. An overall reduction in all submitted culture rates of 35% was observed. This pattern was seen across all ages, including infants aged 2–5 months.

Conclusions

PCV7/PCV13 implementation resulted in a marked and significant decline in pneumococcal, NTHi, and overall conjunctivitis rates in children < 2 years of age. The impact on NTHi episodes alludes to the role of pneumococcus–NTHi interaction in conjunctivitis. The impact in infants aged < 6 months suggests herd protection.
A Case Series of Children With 2019 Novel Coronavirus Infection: Clinical and Epidemiological Features
Authors: Jiehao Cai , Jin Xu , Daojiong Lin , Zhi Yang , Lei Xu , Zhenghai Qu , Yuehua Zhang , Hua Zhang , Ran Jia , Pengcheng Liu , Xiangshi Wang , Yanling Ge , Aimei Xia , He Tian , Hailing Chang , Chuning Wang , Jingjing Li , Jianshe Wang , Mei Zeng
Published: February 2020

We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.
A Well Infant With Coronavirus Disease 2019 With High Viral Load
Authors: Kam Kai-qian , Yung Chee Fu , Cui Lin , Tzer Pin Lin Raymond , Mak Tze Minn , Maiwald Matthias , Li Jiahui , Chong Chia Yin , Nadua Karen , Tan Natalie Woon Hui , Thoon Koh Cheng
Published: February 2020

A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs up to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19, as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community.
Epigenomics and gene regulation in mammalian social systems
Authors: Guerrero Tania P , Fickel Jörns , Benhaiem Sarah , Weyrich Alexandra
Published: February 2020

Social epigenomics is a new field of research that studies how the social environment shapes the epigenome and how in turn the epigenome modulates behavior. We focus on describing known gene–environment interactions (GEIs) and epigenetic mechanisms in different mammalian social systems. To illustrate how epigenetic mechanisms integrate GEIs, we highlight examples where epigenetic mechanisms are associated with social behaviors and with their maintenance through neuroendocrine, locomotor, and metabolic responses. We discuss future research trajectories and open questions for the emerging field of social epigenomics in nonmodel and naturally occurring social systems. Finally, we outline the technological advances that aid the study of epigenetic mechanisms in the establishment of GEIs and vice versa.
The Limits of “Communication Mode” as a Construct
Authors: Hall Matthew L , Dills Sheila
Published: February 2020

Questions about communication mode (a.k.a. “communication options” or “communication opportunities”) remain among the most controversial issues in the many fields that are concerned with the development and well-being of children (and adults) who are d/Deaf or hard of hearing. In this manuscript, we argue that a large part of the reason that this debate persists is due to limitations of the construct itself. We focus on what we term “the crucial question”: namely, what kind of experience with linguistic input during infancy and toddlerhood is most likely to result in mastery of at least one language (spoken or signed) by school entry. We argue that the construct of communication mode—as currently construed—actively prevents the discovery of compelling answers to that question. To substantiate our argument, we present a review of a relevant subset of the recent empirical literature and document the prevalence of our concerns. We conclude by articulating the desiderata of an alternative construct that, if appropriately measured, would have the potential to yield answers to what we identify as “the crucial question.”
Ulcerative Colitis and Cytomegalovirus Infection: From A to Z
Authors: Mourad Fadi H , Hashash Jana G , Kariyawasam Viraj C , Leong Rupert W
Published: February 2020

Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.
Outcome of extracorporeal membrane oxygenation support in patients with liver cirrhosis: a nationwide population-based cohort study
Authors: Chou An-Hsun , Wu Victor Chien-Chia , Chen Dong-Yi , Hung Kuo-Chun , Chang Shang-Hung , Chu Pao-Hsien , Chen Shao-Wei
Published: February 2020

OBJECTIVES

Extracorporeal membrane oxygenation (ECMO) is used for life support in patients with liver cirrhosis (LC). However, there have been no studies evaluating the outcome of ECMO support in patients with LC.

METHODS

Using Taiwan’s National Health Insurance (NHI) database, we retrospectively evaluated patients with LC who received veno-venous or veno-arterial ECMO between 1 January 2000 and 31 December 2013. The outcomes included ECMO-related complications, in-hospital mortality, all-cause mortality and long-term outcomes in patients with and without LC.

RESULTS

A total of 7003 patients who received ECMO, of whom 233 (3.3%) had LC, were eligible for analysis. The LC patients who received ECMO support had a significantly higher risk of in-hospital mortality than the non-LC group (76.4% vs 60.7%; odds ratio 1.97; 95% confidence interval 1.44–2.70). The LC group also had a higher risk of complications, including de novo dialysis and massive blood transfusion with >10 units of red blood cells. Patients ≥65 years of age, patients with respiratory disease, patients with hypoalbuminaemia and liver transplant patients had higher in-hospital and 1-year mortality. The mortality rates for patients with 2 or more risk factors were 90.3% and 95.8%, respectively. LC was associated with a higher incidence of all-cause mortality and liver-related outcomes during follow-up.

CONCLUSIONS

Our findings raise questions regarding the utility of ECMO for LC patients, especially when >2 risk factors have been identified. ECMO support for LC patients should be used with caution and with careful patient selection.
An EFL Teacher’s Investment in Digital Multimodal Composing
Authors: Jiang Lianjiang , Yu Shulin , Zhao Yi
Published: February 2020

Although there is a growing call for L2 teachers to invest in using digital multimodal composing (DMC) as an instructional activity, there is a paucity of research on whether and how L2 teachers invest in DMC, and the impact of DMC on their teaching and changing identities remains underexplored. This study reports on a longitudinal case study of an EFL teacher’s investment in DMC in a university-based EFL classroom in China. A qualitative analysis of the data gathered from observation, interview, and informal conversation reveals that through investing in DMC this teacher started to renegotiate herself as a composing guide, a peer mentor, and a change agent. These shifts of identity were mainly driven by her enhanced cultural and social capital after investing in DMC, despite constraints from ideology and the policing of technology, language-dominant assessment, and other institutional demands. Implications on using DMC are also discussed.
Radiomics based on artificial intelligence in liver diseases: where are we?
Authors: Hu Wenmo , Yang Huayu , Xu Haifeng , Mao Yilei
Published: February 2020

Radiomics uses computers to extract a large amount of information from different types of images, form various quantifiable features, and select relevant features using artificial-intelligence algorithms to build models, in order to predict the outcomes of clinical problems (such as diagnosis, treatment, prognosis, etc.). The study of liver diseases by radiomics will contribute to early diagnosis and treatment of liver diseases and improve survival and cure rates of liver diseases. This field is currently in the ascendant and may have great development in the future. Therefore, we summarize the progress of current research in this article and then point out the related deficiencies and the direction of future research.
Evolution and diversity of the wild rice Oryza officinalis complex, across continents genome types, and ploidy levels
Authors: Shenton Matt , Kobayashi Masaaki , Terashima Shin , Ohyanagi Hajime , Copetti Dario , Hernández-Hernández Tania , Zhang Jianwei , Ohmido Nobuko , Fujita Masahiro , Toyoda Atsushi , Ikawa Hiroshi , Fujiyama Asao , Furuumi Hiroyasu , Miyabayashi Toshie , Kubo Takahiko , Kudrna David , Wing Rod , Yano Kentaro , Nonomura Ken-ichi , Sato Yutaka , Kurata Nori
Published: February 2020

The Oryza officinalis complex is the largest species group in Oryza, with more than nine species from four continents, and is a tertiary gene pool that can be exploited in breeding programs for the improvement of cultivated rice. Most diploid and tetraploid members of this group have a C genome. Using a new reference C genome for the diploid species Oryza officinalis, and draft genomes for two other C genome diploid species O. eichingeri and O. rhizomatis, we examine the influence of transposable elements on genome structure and provide a detailed phylogeny and evolutionary history of the Oryza C genomes. The O. officinalis genome is 1.6 times larger than the A genome of cultivated O. sativa, mostly due to proliferation of Gypsy type long-terminal repeat (LTR) transposable elements, but overall syntenic relationships are maintained with other Oryza genomes (A, B and F). Draft genome assemblies of the two other C genome diploid species, O. eichingeri and O. rhizomatis, and short-read resequencing of a series of other C genome species and accessions reveal that after the divergence of the C genome progenitor, there was still a substantial degree of variation within the C genome species through proliferation and loss of both DNA and LTR transposable elements. We provide a detailed phylogeny and evolutionary history of the Oryza C genomes, and a genomic resource for the exploitation of the Oryza tertiary gene pool.
Mutational Load and the Functional Fraction of the Human Genome
Authors: Galeota-Sprung Benjamin , Sniegowski Paul , Ewens Warren
Published: February 2020

The fraction of the human genome that is functional is a question of both evolutionary and practical importance. Studies of sequence divergence have suggested that the functional fraction of the human genome is likely to be no more than ∼15%. In contrast, the ENCODE project, a systematic effort to map regions of transcription, transcription factor association, chromatin structure, and histone modification, assigned function to 80% of the human genome. In this article, we examine whether and how an analysis based on mutational load might set a limit on the functional fraction. In order to do so, we characterize the distribution of fitness of a large, finite, diploid population at mutation-selection equilibrium. In particular, if mean fitness is ∼1, the fitness of the fittest individual likely to occur cannot be unreasonably high. We find that at equilibrium, the distribution of log fitness has variance nus, where u is the per-base deleterious mutation rate, n is the number of functional sites (and hence incorporates the functional fraction f), and s is the selection coefficient of deleterious mutations. In a large (N=109) reproducing population, the fitness of the fittest individual likely to exist is ∼e5nus. These results apply to both additive and recessive fitness schemes. Our approach is different from previous work that compared mean fitness at mutation-selection equilibrium with the fitness of an individual who has no deleterious mutations; we show that such an individual is exceedingly unlikely to exist. We find that the functional fraction is not very likely to be limited substantially by mutational load, and that any such limit, if it exists, depends strongly on the selection coefficients of new deleterious mutations.
Ab Initio Construction and Evolutionary Analysis of Protein-Coding Gene Families with Partially Homologous Relationships: Closely Related Drosophila Genomes as a Case Study
Authors: Han Xia , Guo Jindan , Pang Erli , Song Hongtao , Lin Kui
Published: February 2020

How have genes evolved within a well-known genome phylogeny? Many protein-coding genes should have evolved as a whole at the gene level, and some should have evolved partly through fragments at the subgene level. To comprehensively explore such complex homologous relationships and better understand gene family evolution, here, with de novo-identified modules, the subgene units which could consecutively cover proteins within a set of closely related species, we applied a new phylogeny-based approach that considers evolutionary models with partial homology to classify all protein-coding genes in nine Drosophila genomes. Compared with two other popular methods for gene family construction, our approach improved practical gene family classifications with a more reasonable view of homology and provided a much more complete landscape of gene family evolution at the gene and subgene levels. In the case study, we found that most expanded gene families might have evolved mainly through module rearrangements rather than gene duplications and mainly generated single-module genes through partial gene duplication, suggesting that there might be pervasive subgene rearrangement in the evolution of protein-coding gene families. The use of a phylogeny-based approach with partial homology to classify and analyze protein-coding gene families may provide us with a more comprehensive landscape depicting how genes evolve within a well-known genome phylogeny.
Genomic Characterization of Newly Completed Genomes of Botulinum Neurotoxin-Producing Species from Argentina, Australia, and Africa
Authors: Smith Theresa J , Xie Gary , Williamson Charles H D , Hill Karen K , Fernández Rafael A , Sahl Jason W , Keim Paul , Johnson Shannon L
Published: February 2020

Botulinum neurotoxin-producing clostridia are diverse in the types of toxins they produce as well as in their overall genomic composition. They are globally distributed, with prevalent species and toxin types found within distinct geographic regions, but related strains containing the same toxin types may also be located on distinct continents. The mechanisms behind the spread of these bacteria and the independent movements of their bont genes may be understood through examination of their genetic backgrounds. The generation of 15 complete genomic sequences from bacteria isolated in Argentina, Australia, and Africa allows for a thorough examination of genome features, including overall relationships, bont gene cluster locations and arrangements, and plasmid comparisons, in bacteria isolated from various areas in the southern hemisphere. Insights gained from these examinations provide an understanding of the mechanisms behind the independent movements of these elements among distinct species.
Power, control, communities and health inequalities. Part II: measuring shifts in power
Authors: Ponsford Ruth , Collins Michelle , Egan Matt , Halliday Emma , Lewis Sue , Orton Lois , Powell Kate , Barnes Amy , Salway Sarah , Townsend Anne , Whitehead Margaret , Popay Jennie
Published: February 2020

In the health field, there is great interest in the role empowerment might play in reducing social inequalities in health. Empowerment is understood here as the processes of developing capabilities that individuals and/or communities need to exercise control over decisions and actions impacting on their lives and health. There is a fundamental problem, however, in identifying and measuring capabilities for collective control that emerge at the level of the collective, with much of the existing literature focusing on individual measures even where community-level processes are concerned. Collective measures need to capture the dynamics of interactions within and between groups, not simply aggregate individual-level measures. This article, Part 2 in a three-part series, takes up the challenge of identifying qualitative markers of capabilities for collective control. We applied the emancipatory power framework (EPF) reported in Part 1 of the series, to qualitative data generated during a longitudinal evaluation of a major English area-based empowerment initiative, the Big Local (BL). We identified empirical ‘markers’ of shifts towards greater collective control pertaining to each of the ‘power’ dimensions in the EPF—‘power within’, ‘power with’ and ‘power to’—and markers of communities exercising ‘power over’ other institutions/community members. These markers can usefully be applied in the evaluation planning and evaluation of empowerment initiatives. Part 3 in the series uses these markers and a second analytical framework developed during our evaluation of BL to explore how power dynamics unfold in participatory spaces in BL neighbourhoods.
Biallelic variants in PSMB1 encoding the proteasome subunit β6 cause impairment of proteasome function, microcephaly, intellectual disability, developmental delay and short stature
Authors: Ansar Muhammad , Ebstein Frédéric , Özkoç Hayriye , Paracha Sohail A , Iwaszkiewicz Justyna , Gesemann Matthias , Zoete Vincent , Ranza Emmanuelle , Santoni Federico A , Sarwar Muhammad T , Ahmed Jawad , Krüger Elke , Bachmann-Gagescu Ruxandra , Antonarakis Stylianos E
Published: February 2020

The molecular cause of the majority of rare autosomal recessive disorders remains unknown. Consanguinity due to extensive homozygosity unravels many recessive phenotypes and facilitates the detection of novel gene-disease links. Here, we report two siblings with phenotypic signs, including intellectual disability (ID), developmental delay and microcephaly from a Pakistani consanguineous family in which we have identified homozygosity for p(Tyr103His) in the PSMB1 gene (Genbank NM_002793) that segregated with the disease phenotype. PSMB1 encodes a β-type proteasome subunit (i.e. β6). Modeling of the p(Tyr103His) variant indicates that this variant weakens the interactions between PSMB1/β6 and PSMA5/α5 proteasome subunits and thus destabilizes the 20S proteasome complex. Biochemical experiments in human SHSY5Y cells revealed that the p(Tyr103His) variant affects both the processing of PSMB1/β6 and its incorporation into proteasome, thus impairing proteasome activity. CRISPR/Cas9 mutagenesis or morpholino knock-down of the single psmb1 zebrafish orthologue resulted in microcephaly, microphthalmia and reduced brain size. Genetic evidence in the family and functional experiments in human cells and zebrafish indicates that PSMB1/β6 pathogenic variants are the cause of a recessive disease with ID, microcephaly and developmental delay due to abnormal proteasome assembly.
Australia and the Abortive Convention on Territorial Asylum: A Case Study of a Cul de Sac in International Refugee and Human Rights Law
Authors: Taylor Savitri , Neumann Klaus
Published: February 2020

Focusing on the period from the adoption of the 1967 Declaration on Territorial Asylum to the 1977 Conference of Plenipotentiaries on Territorial Asylum in Geneva, this article examines attempts to arrive at an international treaty on territorial asylum. Charting the trajectory of the drafting process, it shows how the ambition of international lawyers and UNHCR to go beyond article 14 of the Universal Declaration of Human Rights and the 1967 Declaration was eventually thwarted. Australia played a significant role at the 1977 conference and particular attention is paid to the development of its position. The article argues that the discussions over the proposed convention on territorial asylum were symptomatic of States’ unwillingness to countenance a right to asylum, and their concomitant willingness to extend the principle of non-refoulement.
A New Clinical and Immunovirological Score for Predicting the Risk of Late Severe Infection in Solid Organ Transplant Recipients: The CLIV Score
Authors: San-Juan Rafael , Fernández-Ruiz Mario , Ruiz-Ruigómez María , López-Medrano Francisco , Ruiz-Merlo Tamara , Andrés Amado , Loinaz Carmelo , Len Oscar , Azancot María Antonieta , Montejo Miguel , Rodriguez-Alvarez Regino , Fortún Jesús , Escudero-Sánchez Rosa , Giménez Estela , Lora David , Albert Eliseo , Navarro David , Aguado José María ,   Spanish Network for Research in Infectious Diseases (Red Española de Investigación en Patología Infecciosa [REIPI] RD16/0016)
Published: February 2020

Background

We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in solid organ transplantation (SOT) recipients.

Methods

Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI.

Results

Overall, 309 SOT recipients were followed-up for a median of 1000 days from transplant (interquartile range, 822–1124). Late severe infection occurred in 104 patients (33.6%). The CLIV Score consisted of the following variables at month 6: high-level EBVd (>1500 IU/mL) and recurrent infection during the previous months (6 points); recipient age ≥70 years and chronic graft dysfunction (5 points); cytomegalovirus mismatch (4 points); and CD8+ T-cell count <400 cells/μL (2 points). The area under receiver operating characteristics curve was 0.77 (95% confidence interval, 0.71–0.84). The risk of LI at day 1000 was as follows: score 0, 12.6%; score 2–5, 25.5%; score 6–9, 52.7%; score ≥10, 73.5%.

Conclusions

While waiting for further external validation, the CLIV Score based on clinical and immune-virological parameters is potentially useful to stratify the risk of LI after SOT.
Domestic arbitral institutions and foreign direct investment
Authors: Yin Weiwen
Published: February 2020

Existing literature focuses on how domestic and international institutions address investor–state disputes and attract foreign direct investment (FDI). However, contractual disputes between foreign and domestic firms are largely neglected. For foreign investors, dispute resolution mechanisms that can effectively resolve contractual disputes are very important as well. In this article, I examine the effect of institutions that conduct arbitrations for disputes between foreign and domestic firms on FDI inflows. Focusing on the within-country variation of China, I find that provinces with CIETAC (China International Economic and Trade Arbitration Commission) agencies receive a higher level of FDI. These agencies attract FDI because they can credibly signal that local governments are truly willing to treat foreign investors fairly when they have disputes with local firms. In sum, this article highlights an institutional variable that has received little attention in the literature on the politics of FDI.
Comparison of DAD and FLD Detection for Identification of Selected Bisphenols in Human Breast Milk Samples and Their Quantitative Analysis by LC-MS/MS
Authors: Tuzimski Tomasz , Szubartowski Szymon , Gadzała-Kopciuch Renata , Miturski Andrzej , Wójtowicz-Marzec Monika , Kwaśniewski Wojciech , Buszewski Bogusław
Published: February 2020

Background

Determination of bisphenols released from packaging material is undoubtedly a difficult and tricky task, requiring the chemical analyst to develop an individual approach to obtain reliable analytical information.

Objective

QuECHERS (Quick, Easy, Cheap, Effective, Rugged, and Safe)/dispersive solid-phase extraction (d-SPE) technique and high performance liquid chromatography (HPLC) coupled with modern detection techniques such as diode-array detector (DAD), ﬂuorescence detector (FLD) or tandem mass spectrometry (MS/MS) for the determination of bisphenols such as bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), 2-[[4-[2-[4-(Oxiran-2-ylmethoxy)phenyl]propan-2yl]phenoxy] methyl]oxirane (BADGE), 3-[4-[2-[4-(Oxiran-2-ylmethoxy)phenyl]propan-2-yl]phenoxy]propane-1,2-diol (BADGE*H2O), 3-[4-[2-[4-(2,3-Dihydroxypropoxy)phenyl]propan-2-yl]phenoxy]propane-1,2-diol (BADGE*2H2O), 1-Chloro-3-[4-[2-[4-(3-chloro-2-hydroxypropoxy)phenyl] propan-2-yl]phenoxy]propan-2-ol (BADGE*2HCl) in human breast milk samples have been performed.

Methods

For the analysis of total analytes, prior to the extraction with acetonitrile, a deconjugation step was implemented in a tube by adding 1 mL of the enzymatic solution with the β-Glucuronidase to 5 mL of sample. The mix was homogenized and incubated for 17 h at 37°C. Ten milliliters of acetonitrile, and a QuEChERS salt packet with 4 g anhydrous MgSO4 and 1 g NaCl were added. During the d-SPE step the extract was transferred into tube with 30 mg Z-Sep and 50 mg PSA (and also 150 mg MgSO4 for LC-MS/MS analysis). MeOH–water (20:80, v/v) were added to the dry residue and the extract was reconstituted in 150 µL (25-fold analytes pre-concentration is achieved). Next bisphenols were identified by HPLC-DAD-FLD and quantified by LC-MS/MS equipment.

Conclusions

During the bisphenols HPLC-DAD-FLD analysis, from 6 min a reinforcement of 15 was used, which allowed analytes to be identified at 750 pg/mL. Application of LC-MS/MS allowed quantification of bisphenols in the range from 2.12 to 116.22 ng/mL in a total 27 human breast milk samples.

Highlights

First QuEChERS/d-SPE coupled with HPLC-DAD-FLD or LC-MS/MS method for the quantification of bisphenols and its analogues in breast milk Faster and cheaper alternative to traditional extraction methods The method was applied for the first biomonitoring of bisphenols and its analogues in breast milk.
Toxicokinetics and Analytical Toxicology of Flualprazolam: Metabolic Fate, Isozyme Mapping, Human Plasma Concentration and Main Urinary Excretion Products
Authors: Wagmann Lea , Manier Sascha K , Bambauer Thomas P , Felske Christina , Eckstein Niels , Flockerzi Veit , Meyer Markus R
Published: February 2020

An increasing number of benzodiazepine-type compounds are appearing on the new psychoactive substances market. 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine (well known as flualprazolam) represents a potent ‘designer benzodiazepine’ that has been associated with sedation, loss of consciousness, memory loss and disinhibition. The aims of the present study were to tentatively identify flualprazolam metabolites using in vitro incubations with pooled human liver S9 fraction or HepaRG cells by means of liquid-chromatography-high resolution tandem mass spectrometry. Isozymes involved in phase I and II biotransformation were identified in vitro. Results were then confirmed using human biosamples of an 18-year old male who was admitted to the emergency department after suspected flualprazolam ingestion. Furthermore, the plasma concentration was determined using the standard addition method. Seven flualprazolam metabolites were tentatively identified. Several cytochrome P450 and UDP-glucuronosyltransferase isozymes, amongst them CYP3A4 and UGT1A4, were shown to be involved in flualprazolam biotransformation reactions, and an influence of polymorphisms as well as drug–drug or drug–food interactions cannot be excluded. Alpha-hydroxy flualprazolam glucuronide, 4-hydroxy flualprazolam glucuronide and the parent glucuronide were identified as most abundant signals in urine, far more abundant than the parent compound flualprazolam. These metabolites are thus recommended as urine-screening targets. If conjugate cleavage was performed during sample preparation, the corresponding phase I metabolites should be added as targets. Both hydroxy metabolites can also be recommended for blood screening. The flualprazolam plasma concentration determined in the intoxication case was as low as 8 μg/L underlining the need of analytical methods with sufficient sensitivity for blood-screening purposes.
Spatial and interspecific comparisons of the reproductive biology of two species of co-occurring freshwater shrimps (Decapoda: Caridea: Palaemonidae) in the Three Gorges Reservoir, China
Authors: Chen Sibao , Liao Chuansong , Rypel Andrew L , Lian Yuxi , Ye Shaowen , Zhang Tanglin , Liu Jiashou
Published: February 2020

Exopalaemon modestus (Heller, 1862) and Macrobrachium nipponensis (De Haan, 1840) (Palaemonidae) are ecologically and commercially important fishery resources in the Three Gorges Reservoir (TGR), China, and co-occur in demersal habitats. Little information is available on their biology. We compared the reproductive traits of both species on the upper, middle, and lower sections of the TGR. Both species differed in mean size at maturity, which increased from upper to middle and lower sections. Sex ratios were significantly biased toward females, but no significant differences were observed among the three sites for either species. Both species displayed an obvious trade-off between embryo size and fecundity, with the size of embryos being the smallest but with the highest fecundity at the upper section, followed by the middle and lower sections. Exopalaemon modestus spawned from early April to late September, with a peak in May and June, whereas M. nipponensis spawned from late April to early October with a peak in June and July. The spatially distinct reproductive traits, which were concordant across species, are likely related to differences in habitat characteristics such as water flow. We suggest that management strategies should account for the reproductive biology of the two species in order to maintain a sustainable fishery in the reservoir.
The Estrogen-Responsive Transcriptome of Female Secondary Sexual Traits in the Gulf Pipefish
Authors: Anderson Andrew P , Rose Emily , Flanagan Sarah P , Jones Adam G
Published: February 2020

Sexual dimorphism often results from hormonally regulated trait differences between the sexes. In sex-role-reversed vertebrates, females often have ornaments used in mating competition that are expected to be under hormonal control. Males of the sex-role-reversed Gulf pipefish (Syngnathus scovelli) develop female-typical traits when they are exposed to estrogens. We aimed to identify genes whose expression levels changed during the development and maintenance of female-specific ornaments. We performed RNA-sequencing on skin and muscle tissue in male Gulf pipefish with and without exposure to estrogen to investigate the transcriptome of the sexually dimorphic ornament of vertical iridescent bands found in females and estrogen-exposed males. We further compared differential gene expression patterns between males and females to generate a list of genes putatively involved in the female secondary sex traits of bands and body depth. A detailed analysis of estrogen-receptor binding sites demonstrates that estrogen-regulated genes tend to have nearby cis-regulatory elements. Our results identified a number of genes that differed between the sexes and confirmed that many of these were estrogen-responsive. These estrogen-regulated genes may be involved in the arrangement of chromatophores for color patterning, as well as in the growth of muscles to achieve the greater body depth typical of females in this species. In addition, anaerobic respiration and adipose tissue could be involved in the rigors of female courtship and mating competition. Overall, this study generates a number of interesting hypotheses regarding the genetic basis of a female ornament in a sex-role-reversed pipefish.
Pneumatosis cystoides intestinalis in an elderly patient, better to be safe than sorry
Authors: Molina Gabriel A , Fuentes Germanico , Orejuela Monica Elizabeth , Herrera Juan Marcelo , Jiménez Galo Enrique , Pinto Johanna Carolina , Cobo Maria Mercedes
Published: February 2020

Pneumatosis cystoides intestinalis is a rare pathology with nonspecific symptoms that can be easily misdiagnosed. Clinical awareness along with close surveillance is critical to effectively diagnose and treat this condition. Current treatment is based on conservative therapy including antibiotics and oxygen. Surgery is only recommended when complications are suspected. Here, we present the case of a 72-year-old female admitted to the emergency department with abdominal pain and vomits. Pneumatosis cystoides intestinalis was diagnosed and was successfully treated. On follow-up visits, patient is recovering and doing well.
New opportunities and insights into Papaver self-incompatibility by imaging engineered Arabidopsis pollen
Authors: Wang Ludi , Triviño Marina , Lin Zongcheng , Carli José , Eaves Deborah J , Van Damme Daniёl , Nowack Moritz K , Franklin-Tong Vernonica E , Bosch Maurice
Published: February 2020

Pollen tube growth is essential for plant reproduction. Their rapid extension using polarized tip growth provides an exciting system for studying this specialized type of growth. Self-incompatibility (SI) is a genetically controlled mechanism to prevent self-fertilization. Mechanistically, one of the best-studied SI systems is that of Papaver rhoeas (poppy). This utilizes two S-determinants: stigma-expressed PrsS and pollen-expressed PrpS. Interaction of cognate PrpS–PrsS triggers a signalling network, causing rapid growth arrest and programmed cell death (PCD) in incompatible pollen. We previously demonstrated that transgenic Arabidopsis thaliana pollen expressing PrpS–green fluorescent protein (GFP) can respond to Papaver PrsS with remarkably similar responses to those observed in incompatible Papaver pollen. Here we describe recent advances using these transgenic plants combined with genetically encoded fluorescent probes to monitor SI-induced cellular alterations, including cytosolic calcium, pH, the actin cytoskeleton, clathrin-mediated endocytosis (CME), and the vacuole. This approach has allowed us to study the SI response in depth, using multiparameter live-cell imaging approaches that were not possible in Papaver. This lays the foundations for new opportunities to elucidate key mechanisms involved in SI. Here we establish that CME is disrupted in self-incompatible pollen. Moreover, we reveal new detailed information about F-actin remodelling in pollen tubes after SI.
The pivotal function of dehydroascorbate reductase in glutathione homeostasis in plants
Authors: Ding Haiyan , Wang Bipeng , Han Yi , Li Shengchun
Published: February 2020

Under natural conditions, plants are exposed to various abiotic and biotic stresses that trigger rapid changes in the production and removal of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). The ascorbate-glutathione pathway has been recognized to be a key player in H2O2 metabolism, in which reduced glutathione (GSH) regenerates ascorbate by reducing dehydroascorbate (DHA), either chemically or via DHA reductase (DHAR), an enzyme belonging to the glutathione S-transferase (GST) superfamily. Thus, DHAR has been considered to be important in maintaining the ascorbate pool and its redox state. Although some GSTs and peroxiredoxins may contribute to GSH oxidation, analysis of Arabidopsis dhar mutants has identified the key role of DHAR in coupling H2O2 to GSH oxidation. The reaction of DHAR has been proposed to proceed by a ping-pong mechanism, in which binding of DHA to the free reduced form of the enzyme is followed by binding of GSH. Information from crystal structures has shed light on the formation of sulfenic acid at the catalytic cysteine of DHAR that occurs with the reduction of DHA. In this review, we discuss the molecular properties of DHAR and its importance in coupling the ascorbate and glutathione pools with H2O2 metabolism, together with its functions in plant defense, growth, and development.
A line-binned treatment of opacities for the spectra and light curves from neutron star mergers
Authors: Fontes C J , Fryer C L , Hungerford A L , Wollaeger R T , Korobkin O
Published: February 2020

The electromagnetic observations of GW170817 were able to dramatically increase our understanding of neutron star mergers beyond what we learned from gravitational waves alone. These observations provided insight on all aspects of the merger from the nature of the gamma-ray burst to the characteristics of the ejected material. The ejecta of neutron star mergers are expected to produce such electromagnetic transients, called kilonovae or macronovae. Characteristics of the ejecta include large velocity gradients, relative to supernovae, and the presence of heavy r-process elements, which pose significant challenges to the accurate calculation of radiative opacities and radiation transport. For example, these opacities include a dense forest of bound–bound features arising from near-neutral lanthanide and actinide elements. Here we investigate the use of fine-structure, line-binned opacities that preserve the integral of the opacity over frequency. Advantages of this area-preserving approach over the traditional expansion–opacity formalism include the ability to pre-calculate opacity tables that are independent of the type of hydrodynamic expansion and thus eliminate the computational expense of calculating opacities within radiation-transport simulations. Tabular opacities are generated for all 14 lanthanides as well as a representative actinide element, uranium. We demonstrate that spectral simulations produced with the line-binned opacities agree well with results produced with the more accurate continuous Monte Carlo Sobolev approach, as well as with the commonly used expansion–opacity formalism. The agreement between the line-binned and expansion–opacity results is explained as arising from the similarity in their opacities in the limit of low optical depth, where radiation transport is important in the ejecta. Additional investigations illustrate the convergence of opacity with respect to the number of included lines, and elucidate sensitivities to different atomic physics approximations, such as fully and semirelativistic approaches.