bluuebunny/crossref_metadata_2025 huggingface dataset:
Triiodothyroacetic Acid Cross-Reacts With Measurement of Triiodothyronine (T3) on Various Immunoassay Platforms
Authors: Chan Siaw Li , Refetoff Samuel , Babic Nikolina , Jin Ming , Garg Uttam , Yeo Kiang-Teck J
Published: June 2021

Objectives

Thyroid hormone analog 3,5,3'-triiodothyroacetic acid (TRIAC) is effective in reducing the hypermetabolism in monocarboxylate transporter 8 (MCT8)–deficient individuals. Because of the structural similarity between TRIAC and 3,3',5'-triiodothyronine (T3), we sought to investigate the degree of cross-reactivity of TRIAC with various commercially available total and free T3 assays.

Methods

Varying concentrations (50-1,000 ng/dL) of TRIAC (Sigma Aldrich) were added to pooled serum and assayed for total T3 (TT3) and free T3 (FT3) on the following platforms: e602 (Roche Diagnostics), Architect (Abbott Diagnostics), Centaur (Siemens Healthcare Diagnostics), IMMULITE (Siemens Healthcare Diagnostics), DxI (Beckman Coulter), and Vitros (Ortho Clinical Diagnostics). TT3 competition assay with TRIAC was performed by adding increasing amounts of T3 to pooled serum samples that contained a constant concentration of TRIAC (250 ng/dL).

Results

Significant overestimation of TT3 and FT3 assays were observed across all platforms corresponding to increasing concentrations of TRIAC. The TRIAC effect at 250 ng/dL showed a constant interference of approximately 190 ng/dL TT3.

Conclusions

All commercial TT3 and FT3 assays tested in this work cross-react significantly with TRIAC. Therefore, patients undergoing TRIAC therapy should have T3 hormone response monitored using alternative nonimmunoassay-based methods to avoid misinterpretation of thyroid function profiles.
Cutinase-like biodegradable plastic-degrading enzymes from phylloplane yeasts have cutinase activity
Authors: Ueda Hirokazu , Tabata Jun , Seshime Yasuyo , Masaki Kazuo , Sameshima-Yamashita Yuka , Kitamoto Hiroko
Published: June 2021

Phylloplane yeast genera Pseudozyma and Cryptococcus secrete biodegradable plastic (BP)-degrading enzymes, termed cutinase-like enzymes (CLEs). Although CLEs contain highly conserved catalytic sites, the whole protein exhibits ≤30% amino acid sequence homology with cutinase. In this study, we analyzed whether CLEs exhibit cutinase activity. Seventeen Cryptococcus magnus strains, which degrade BP at 15 °C, were isolated from leaves and identified the DNA sequence of the CLE in one of the strains. Cutin was prepared from tomato leaves and treated with CLEs from 3 Cryptococcus species (C. magnus, Cryptococcus flavus, and Cryptococcus laurentii) and Pseudozyma antarctia (PaE). A typical cutin monomer, 10,16-dihydroxyhexadecanoic acid, was detected in extracts of the reaction solution via gas chromatography–mass spectrometry, showing that cutin was indeed degraded by CLEs. In addition to the aforementioned monomer, separation analysis via thin-layer chromatography detected high-molecular-weight products resulting from the breakdown of cutin by PaE, indicating that PaE acts as an endo-type enzyme.
Evidence for a shift in placental HLA-G allelic dominance and the HLA-G isoform profile during a healthy pregnancy and preeclampsia
Authors: Persson Gry , Stæhr Christina Seefeldt , Klok Freja Syrach , Lebech Morten , Hviid Thomas Vauvert F
Published: June 2021

Human leukocyte antigen (HLA)-G, which belongs to a nonclassical class Ib major histocompatibility complex gene family expressed by placental trophoblast cells, plays a central role in establishing tolerance to the semiallogeneic fetus and in placentation. HLA-G exists in different soluble or membrane-bound isoforms. Preeclampsia, a major cause of fetal and maternal morbidity and mortality, has been linked to insufficient placentation and an altered immune response in pregnancy, including altered HLA-G expression. The 14 bp insertion/deletion polymorphism in the 3′ untranslated region of the gene and the isoform profile may affect HLA-G expression. The aim of the current pilot study was to characterize the expression patterns of HLAG mRNA, protein, and isoform profile in uncomplicated term pregnancies and in cases of preeclampsia. Maternal sHLA-G mRNA and protein levels were slightly reduced in preeclampsia. No difference was found for placental blood, and no correlation between peripheral and placental sHLA-G levels was found. We observed no association between neither fetal nor maternal HLA-G 14 bp insertion/deletion genotypes and preeclampsia, nor a significant difference in isoform profiles. However, in HLA-G 14 bp insertion/deletion heterozygous placental samples, we observed abundant HLA-G1 14 bp insertion allele expression in the term placentae, which is contrary to previous findings in first trimester trophoblast. Increased HLA-G1 14 bp insertion allele expression in the placenta was associated with reduced levels of placental sHLA-G and an altered isoform profile with increased relative levels of HLA-G1 and -G5 and reduced levels of HLA-G3. The results indicate that an allelic shift in heterozygous individuals could represent a novel regulatory pathway.
Pharmacokinetic Analysis of Rosmarinic Acid and its Analog in Rat Plasma Using Liquid Chromatography–Tandem Mass Spectrometry
Authors: Jiang Minjie , Fu Shujie , Chen Kebei , Li Qing , Jiang Weizhe
Published: June 2021

The anticancer effects of rosmarinic acid (RA) are a hotspot of current research. In order to enhance its pharmacological activity, N-substituted RA was prepared, and it has been shown to exhibit notable antitumor effects. In order to elucidate the underlying mechanisms of action, pharmacokinetic analysis is necessary. In the present study, liquid chromatography–tandem mass spectrometric method, was used to determine the concentrations of RA and its analog, (E)-3-(3,4-dihydroxyphenyl)-2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoic acid (A2) in plasma from rats. The analyses were divided into a C18 column (1.9 μm, 2.1 mm × 100 mm) with a security guard C18 column (5 μm, 2.1 mm × 10 mm) and a triple-quadrupole mass spectrometry with an electrospray ionization ion-source generates ions. The sample pretreatment is relevant to the one-step protein precipitation with isopropanol:ethyl acetate (v/v, 1:1) This method presented a linear association within ranges at the concentration of 5–2000 ng/mL for A2 and RA. Relative standard deviations in daily courses were <15% and the relative errors registered within 15%. The methods used in the present study make the unambiguous quantification and identification of RA and A2 possible in vivo. The present study is the first to focus on determining A2 and RA in rat plasma following oral administration. The results may provide a meaningful basis for the evaluation of the application of RA and its analog in clinical practice and also provide a reference method for the pharmacokinetic analysis of RA analogs.
Variants of Concern Are Overrepresented Among Postvaccination Breakthrough Infections of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Washington State
Authors: McEwen Abbye E , Cohen Seth , Bryson-Cahn Chloe , Liu Catherine , Pergam Steven A , Lynch John , Schippers Adrienne , Strand Kathy , Whimbey Estella , Mani Nandita S , Zelikoff Allison J , Makarewicz Vanessa A , Brown Elizabeth R , Bakhash Shah A Mohamed , Baker Noah R , Castor Jared , Livingston Robert J , Huang Meei-Li , Jerome Keith R , Greninger Alexander L , Roychoudhury Pavitra
Published: June 2021

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOCs) and had a median Ct of 20.2 (IQR, 17.1–23.3). When compared with 5174 contemporaneous samples sequenced in our laboratory, VOCs were significantly enriched among breakthrough infections (P < .05).
Time to press the reset button—can we use the COVID-19 pandemic to rethink the process of transplant assessment?
Authors: Kumar Mukesh , Dellen David van , Loughton Holly , Woywodt Alexander
Published: June 2021

Coronavirus disease 2019 has taken a severe toll on the transplant community, with significant morbidity and mortality not just among transplant patients and those on the waiting list, but also among colleagues. It is therefore not surprising that clinicians in this field have viewed the events of the last 18 months as predominantly negative. As the pandemic is gradually ebbing away, we argue that this is also a unique opportunity to rethink transplant assessment. First, we have witnessed a step-change in the use of technology and virtual assessments. Another effect of the pandemic is that we have had to make do with what was available—which has often worked surprisingly well. Finally, we have learned to think the unthinkable: maybe things do not have to continue the way they have always been. As we emerge on the other side of the pandemic, we should rethink which parts of the transplant assessment process are necessary and evidence-based. We emphasize the need to involve patients in the redesign of pathways and we argue that the assessment process could be made more transparent to patients. We describe a possible roadmap towards transplant assessment pathways that are truly fit for the 21st century.
Concomitant myocardial injury and valvular disease in Sneddon syndrome: a case report
Authors: Scadi Soukaina , Huttin Olivier , Selton Suty Christine , Wahl Denis
Published: June 2021

Background

Cardiac involvement in Sneddon syndrome (SS) is rare, the physiopathology is still unclear. We report a first case of SS without antiphospholipid antibodies who had coexisting ischaemia with no obstructive coronary arteries and aortic valve diseases.

Case summary

A 34-year-old woman with SS without antiphospholipid antibodies, was admitted for aphasia, and paresthaesia with confirmed right opercular ischaemic lesions at brain magnetic resonance imaging. Transthoracic echocardiographic examination showed akinesis of apical segments, moderate aortic valve stenosis, and moderate aortic insufficiency. Coronary angiogram was normal. Cardiac magnetic resonance showed transmural necrosis in the territory of the left anterior descending artery. Seven years later, our patient had no change or progression of myocardial ischaemic lesions or valvular disease.

Conclusion

We will discuss different hypothesis, diagnosis, treatment, and evolution of cardiac involvement in SS. Close follow-up should be regularly performed for early diagnosis, hence the importance of multimodality imaging, to guide treatment and prevent further complications.
Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study
Authors: Quispe Renato , Martin Seth Shay , Michos Erin Donelly , Lamba Isha , Blumenthal Roger Scott , Saeed Anum , Lima Joao , Puri Rishi , Nomura Sarah , Tsai Michael , Wilkins John , Ballantyne Christie Mitchell , Nicholls Stephen , Jones Steven Richard , Elshazly Mohamed Badreldin
Published: June 2021

Aims

Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD.

Methods and results

We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45–1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08–1.34). Similar results were shown when examining discordance across clinical cutpoints.

Conclusions

In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.
The iron transporter Transferrin 1 mediates homeostasis of the endosymbiotic relationship betweenDrosophila melanogasterandSpiroplasma poulsonii
Authors: Marra Alice , Masson Florent , Lemaitre Bruno
Published: June 2021

Iron is involved in numerous biological processes in both prokaryotes and eukaryotes and is therefore subject to a tug-of-war between host and microbes upon pathogenic infections. In the fruit fly Drosophila melanogaster, the iron transporter Transferrin 1 (Tsf1) mediates iron relocation from the hemolymph to the fat body upon infection as part of the nutritional immune response. The sequestration of iron in the fat body renders it less available for pathogens, hence limiting their proliferation and enhancing the host ability to fight the infection. Here we investigate the interaction between host iron homeostasis and Spiroplasma poulsonii, a facultative, vertically transmitted, endosymbiont of Drosophila. This low-pathogenicity bacterium is devoid of cell wall and is able to thrive in the host hemolymph without triggering pathogen-responsive canonical immune pathways. However, hemolymph proteomics revealed an enrichment of Tsf1 in infected flies. We find that S. poulsonii induces tsf1 expression and triggers an iron sequestration response similarly to pathogenic bacteria. We next demonstrate that free iron cannot be used by Spiroplasma while Tsf1-bound iron promotes bacterial growth, underlining the adaptation of Spiroplasma to the intra-host lifestyle where iron is mostly protein-bound. Our results show that Tsf1 is used both by the fly to sequester iron and by Spiroplasma to forage host iron, making it a central protein in endosymbiotic homeostasis.
Adaptation and Validation of the Preparation for Future Care Needs Scale for Chinese Older Adults in Hong Kong
Authors: Bai Xue , Liu Chang , Song Yajun , Sörensen Silvia
Published: June 2021

Background and Objectives

Care planning can protect against or offset potential stressors in the caregiving stage and mitigate their detrimental effects. This study aimed to translate, adapt, and validate 2 short forms of the multidimensional, theory-guided scale measuring preparation for future care needs (PFCN) among Chinese older adults in Hong Kong.

Research Design and Methods

Data were derived from a cross-sectional survey of 862 community-dwelling individuals aged 60 years and older. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to assess the structural validity of the scales. Criterion-related validity, known-groups validity, and internal consistency were also examined.

Results

EFA yielded a 14-item 4-factor (awareness, avoidance, decision making, and concrete planning) model, which was supported by CFA and explained 68.9% of the total variance. CFA also supported the structural validity of the 5-item scale. Criterion-related validity of the 2 scales was supported by their significant and positive correlations with domain-specific planning behaviors for retirement. Known-groups validity of the 2 scales was demonstrated by significant differences in scores between male and female older adults and scores between different educational levels and socioeconomic status. Cronbach’s alphas for the internal consistency of the 14-item and 5-item scales were 0.889 and 0.774, respectively.

Discussion and Implications

PFCN scales enable researchers and service practitioners to accurately understand and assess older adults’ processes and efforts in care planning, facilitate the identification of individuals at risk from inadequate planning, and inform the development of interventions to enhance care preparation in target domains.
Pervasiveness of Biological Impacts of Artificial Light at Night
Authors: Gaston Kevin J , Ackermann Simone , Bennie Jonathan , Cox Daniel T C , Phillips Benjamin B , Sánchez de Miguel Alejandro , Sanders Dirk
Published: June 2021

Artificial light at night (ALAN) and its associated biological impacts have regularly been characterized as predominantly urban issues. Although far from trivial, this would imply that these impacts only affect ecosystems that are already heavily modified by humans and are relatively limited in their spatial extent, at least as compared with some key anthropogenic pressures on the environment that attract much more scientific and public attention, such as climate change or plastic pollution. However, there are a number of reasons to believe that ALAN and its impacts are more pervasive, and therefore need to be viewed from a broader geographic perspective rather than an essentially urban one. Here we address, in turn, 11 key issues when considering the degree of spatial pervasiveness of the biological impacts of ALAN. First, the global extent of ALAN is likely itself commonly underestimated, as a consequence of limitations of available remote sensing data sources and how these are processed. Second and third, more isolated (rural) and mobile (e.g., vehicle headlight) sources of ALAN may have both very widespread and important biological influences. Fourth and fifth, the occurrence and impacts of ALAN in marine systems and other remote settings, need much greater consideration. Sixth, seventh, and eighth, there is growing evidence for important biological impacts of ALAN at low light levels, from skyglow, and over long distances (because of the altitudes from which it may be viewed by some organisms), all of which would increase the areas over which impacts are occurring. Ninth and tenth, ALAN may exert indirect biological effects that may further expand these areas, because it has a landscape ecology (modifying movement and dispersal and so hence with effects beyond the direct extent of ALAN), and because ALAN interacts with other anthropogenic pressures on the environment. Finally, ALAN is not stable, but increasing rapidly in global extent, and shifting toward wavelengths of light that often have greater biological impacts.
Connected While Distant: Networking CUREs Across Classrooms to Create Community and Empower Students
Authors: Connors Patrice K , Lanier Hayley C , Erb Liesl P , Varner Johanna , Dizney Laurie , Flaherty Elizabeth A , Duggan Jennifer M , Yahnke Christopher J , Hanson John D
Published: June 2021

Synopsis

Connections, collaborations, and community are key to the success of individual scientists as well as transformative scientific advances. Intentionally building these components into science, technology, engineering and mathematics (STEM) education can better prepare future generations of researchers. Course-based undergraduate research experiences (CUREs) are a new, fast-growing teaching practice in STEM that expand opportunities for undergraduate students to gain research skills. Because they engage all students in a course in an authentic research experience focused on a relevant scientific problem, CUREs provide an opportunity to foster community among students while promoting critical thinking skills and positively influencing their identities as scientists. Here, we review CUREs in the biological sciences that were developed as multi-institutional networks, and highlight the benefits gained by students and instructors through participation in a CURE network. Throughout, we introduce Squirrel-Net, a network of ecology-focused and field-based CUREs that intentionally create connections among students and instructors. Squirrel-Net CUREs can also be scaffolded into the curriculum to form connections between courses, and are easily transitioned to distance-based delivery. Future assessments of networked CUREs like Squirrel-Net will help elucidate how CURE networks create community and how a cultivated research community impacts students’ performance, perceptions of science, and sense of belonging. We hypothesize networked CUREs have the potential to create a broader sense of belonging among students and instructors alike, which could result in better science and more confident scientists.
Introduction to Material Displacements
Authors: Lichtman Sarah A , Traganou Jilly
Published: June 2021

This special issue on Material Displacements explores the intersection of materiality, design, and displacement, conceived of as rupture, transition, and traversal of borders, boundaries, and forms. This introduction outlines the role of displacement in various disciplines and theoretical approaches, highlighting those of new materialism, critical urbanism, deterritorialization, and border thinking. It then presents work published in the Journal of Design History by design historians and theorists who have envisioned design’s relation with displacement through diverse perspectives. Each author contributing to this issue reveals the power and role of materiality in inducing movement in/out of the borders broadly conceived, as well as materials’ susceptibility to external forces of displacement.
Wild Bee Response to Application of the Douglas-fir Beetle Anti-Aggregation Pheromone, 3-Methylcyclohex-2-En-1-One
Authors: Foote Gabriel G , Runyon Justin B , Fettig Christopher J , Foote Nathaniel E , Ross Darrell W
Published: June 2021

Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins (DFB), is the most damaging insect pest of Douglas-fir, Pseudotsuga menziesii (Mirb.) Franco, in western North America. Individual high-value trees and stands can be protected during DFB outbreaks using the beetle's anti-aggregation pheromone, 3-methylcyclohex-2-en-1-one (MCH), which is available in several commercial formulations. However, other methylcyclohexanones similar in molecular structure to MCH have been shown to repel bees from agricultural areas. In forest systems, wild bees (Hymenoptera: Apiformes) provide essential pollination services to many forb and shrub species. Therefore, it is important to determine whether resident wild bee communities are affected in forests treated with MCH. To address this, the bee community was sampled within experimental sites located in Idaho and Montana, USA in 2016. At both sites, there was no significant difference in overall bee abundance, species richness, or diversity between MCH-treated plots and untreated control plots. Overall, these results indicate that treatment of Douglas-fir with MCH does not negatively impact the resident wild bee community.
Simultaneous Morscher’s osteotomy and arthroscopic debridement in the management of Legg–Calvé–Perthes disease: a case report and literature review
Authors: Bosakhar Batool , Baldawi Hassan , Liu Kathy , Ayeni Olufemi R , Kishta Waleed
Published: June 2021

There is a lack of consensus around optimal surgical management for Legg–Calvé–Perthes Disease (LCPD). This case report discusses the benefits of combining arthroscopic femoral neck osteochondroplasty and labral repair with Morscher’s Osteotomy (MO) for LCPD. S.A. is a 17-year-old female diagnosed with LCPD at the age of 6 years and has long-standing right hip symptoms. An arthroscopic femoral neck osteochondroplasty and labral repair followed by MO was performed. The pre-operative and 8 months post-operative International Hip Outcome Tool (iHOT-12) scores were 16.3 and 79.8 out of 100, respectively, indicating better quality-of-life. Also, the femoral neck-shaft-angle (NSA) changed from 120 pre-operative to 138.7 post-operative to represent the correction of coxa vara. The literature review revealed no published reports describing combined MO with hip arthroscopic interventions in managing LCPD. Combined arthroscopic femoral neck osteochondroplasty (with labral repair) and MO provides high patient satisfaction and improves radiographic parameters in patients with LCPD.
Bilateral femoral head reshaping and mosaicplasty in Legg–Calvé–Perthes disease residual deformity
Authors: Palazón-Quevedo Ángel , Galán-Olleros María , Egea-Gámez Rosa M
Published: June 2021

Residual hip deformity secondary to Perthes disease may lead to early symptomatic joint degeneration. The altered anatomy results in biomechanical and biological problems that can be surgically addressed in adolescents or young adults with hip preservation procedures. This case report aims to demonstrate a customized surgical treatment performed on a 15-year-old male who developed painful hips with significant intra- and extra-articular impingement, secondary to bilateral Leg–Calvé–Perthes disease residual deformity. Intra-articular procedures were executed through a safe surgical dislocation of the hip, with a mosaicplasty using osteochondral autografts from the exceeding peripheral ipsilateral femoral head, a femoral head–neck osteochondroplasty and a labrum repair. A relative lengthening of the femoral neck was also carried out with a trochanteric advancement to solve the extra-articular issues. On follow-up, he referred to a substantial improvement in pain and function, being his radiographic studies satisfactory. At 4 and 5 years from surgery, the patient was able to exercise regularly with minimal complaints, with a Harris Hip Score of 85.85% and a Hip Outcome Score of 94.1% for activities of daily life and 86.1% for sports. In patients with hip deformity after healed Perthes disease, treatment strategies that address both the morphological disturbance of coxa magna, plana and breva, as well as the biological concerns arising from osteochondral injuries or labral tears, and mechanical dysfunctions lead to improvements in symptomatology, function and medium-term prognosis. Further procedures to address residual adaptative acetabular dysplasia would favor outcomes of conservative hip surgery in the sequelae of LCPD.
Identification of the JNK-Active Triple-Negative Breast Cancer Cluster Associated With an Immunosuppressive Tumor Microenvironment
Authors: Semba Takashi , Wang Xiaoping , Xie Xuemei , Cohen Evan N , Reuben James M , Dalby Kevin N , Long James P , Phi Lan Thi Hanh , Tripathy Debu , Ueno Naoto T
Published: June 2021

Background

Although an immunosuppressive tumor microenvironment (TME) is key for tumor progression, the molecular characteristics associated with the immunosuppressive TME remain unknown in triple-negative breast cancer (TNBC). Our previous functional proteomic study of TNBC tumors identified that C-JUN N-terminal kinase (JNK) pathway–related molecules were enriched in a cluster associated with the inflammatory pathway. However, the role of the JNK pathway in the TNBC TME is still unclear.

Methods

Transcriptomic analysis was conducted using The Cancer Genome Atlas datasets. The effect of JNK-IN-8, a covalent pan-JNK inhibitor, on TNBC tumor growth, lung metastasis, and the TME was measured in TNBC syngeneic mouse models (n = 13 per group). Tumor (n = 43) or serum (n = 46) samples from TNBC patients were analyzed using multiplex immunohistochemistry or Luminex assay. All statistical tests were 2-sided.

Results

CIBERSORT analysis revealed that TNBC patients with high phosphorylated JNK level (n = 47) had more regulatory T cell (Treg) infiltration than those with a low phosphorylated JNK level (n = 47) (P = .02). Inhibition of JNK signaling statistically significantly reduced tumor growth (P < .001) and tumor-infiltrating Tregs (P = .02) while increasing the infiltration of CD8+ T cells in TNBC mouse models through the reduction of C-C motif ligand 2 (CCL2). Tumor-associated macrophages were the predominant cells secreting CCL2, and inhibition of JNK signaling reduced CCL2 secretion of human primary macrophages. Moreover, in patients with TNBC (n = 43), those with high levels of CCL2+ tumor-associated macrophages had more Treg and less CD8+ T cell infiltration (P = .04), and the serum CCL2 level was associated with poor overall survival (hazard ratio = 2.65, 95% confidence interval = 1.29 to 5.44, P = .008) in TNBC patients (n = 46).

Conclusions

The JNK/C-JUN/CCL2 axis contributes to TNBC aggressiveness via forming an immunosuppressive TME and can offer novel therapeutic strategies for TNBC.
Protective and connective professionalism: What we have learned and what we still would like to learn
Authors: Noordegraaf Mirko , Brock David M
Published: June 2021

This essay begins with a contribution from Mirko Noordegraaf, author of the 2020 ‘From Protective to Connective Professionalism’ article that initiated this series of exchanges in the Journal of Professions and Organization (JPO). Then, wrapping up this series, David Brock, JPO Editor-in-Chief, looks back at protective and connective constructs in our literature, and suggests several research directions. Our aim is not to close the debate, but to open it up and connect it to promising research avenues, newly arising research strands and promising publications.
A Qa-SNARE complex contributes to soybean cyst nematode resistance via regulation of mitochondria-mediated cell death
Authors: Wang Rui , Deng Miaomiao , Yang Chao , Yu Qianqian , Zhang Lei , Zhu Qun , Guo Xiaoli
Published: June 2021

The resistance to Heterodera glycines 1 (Rhg1) locus is widely used by soybean breeders to reduce yield loss caused by soybean cyst nematode (SCN). α-SNAP (α-soluble NSF attachment protein) within Rhg1 locus contributes to SCN resistance by modulation of cell status at the SCN feeding site; however, the underlying mechanism is largely unclear. Here, we identified an α-SNAP-interacting protein, GmSYP31A, a Qa-SNARE (soluble NSF attachment protein receptor) protein from soybean. Expression of GmSYP31A significantly induced cell death in Nicotiana benthamiana leaves, and co-expression of α-SNAP and GmSYP31A could accelerate cell death. Overexpression of GmSYP31A increased SCN resistance, while silencing or overexpression of a dominant-negative form of GmSYP31A increased SCN sensitivity. GmSYP31A expression also disrupted endoplasmic reticulum-Golgi trafficking, and the exocytosis pathway. Moreover, α-SNAP was also found to interact with GmVDAC1D (voltage-dependent anion channel). The cytotoxicity induced by the expression of GmSYP31A could be relieved either with the addition of an inhibitor of VDAC protein, or by silencing the VDAC gene. Taken together, our data not only demonstrate that α-SNAP works together with GmSYP31A to increase SCN resistance through triggering cell death, but also highlight the unexplored link between the mitochondrial apoptosis pathway and vesicle trafficking.
The quiescent centre of the root apical meristem: conceptual developments from Clowes to modern times
Authors: Dubrovsky Joseph G , Ivanov Victor B
Published: June 2021

In this review we discuss the concepts of the quiescent centre (QC) of the root apical meristem (RAM) and their change over time, from their formulation by F.A.L. Clowes to the present. This review is dedicated to the 100th anniversary of the birth of Clowes, and we present his short biography and a full bibliography of Clowes’ work. Over time, the concept of the QC proved to be useful for the understanding of RAM organization and behaviour. We focus specifically on conceptual developments, from the organization of the QC to understanding its functions in RAM maintenance and activity, ranging from a model species, Arabidopsis thaliana, to crops. Concepts of initial cells, stem cells, and heterogeneity of the QC cells in the context of functional and structural stem cells are considered. We review the role of the QC in the context of cell flux in the RAM and the nature of quiescence of the QC cells. We discuss the origin of the QC and fluctuation of its size in ontogenesis and why the QC cells are more resistant to stress. Contemporary concepts of the organizer and stem cell niche are also considered. We also propose how the stem cell niche in the RAM can be defined in roots of a non-model species.
The Third Element
Authors: d'Aspremont Jean
Published: June 2021

This chapter focuses on the norm-creating character of the standard whose customary status is tested as another possible constitutive element of customary international law. It examines the third constitutive element of customary international law, which is the common recognition by international law of the enormous definitional powers to the International Court of Justice when it comes to the custom-identification criteria. It also explores the discursive performance that consists of the constant turning of a blind eye to a specific claim made by the Court in the 1969 North Sea Continental Shelve. The chapter highlights the 1969 North Sea Continental Shelf wherein the Court confirmed the dualistic approach and the consciousness of having a duty may be in order to offer an articulate definition of opinio juris for the first time. It argues that the requirement that the standard whose customary status is tested must be norm-creating as it was prescribed by the Court in the North Sea Continental Shelfcase.
System-support
Authors: d'Aspremont Jean
Published: June 2021

This chapter analyzes another common discursive performance witnessed in relation to customary international law that consists of the bestowing of a system-support function upon customary international law. It describes the various facets of discursive performance and particular ways in which customary international law is construed as playing a system-buttressing function. It also mentions how customary international law provides a guarantee for a minimum content for international. The chapter discusses the possibility for customary international law to be the formal nest of all the fundamental doctrines of international law and reviews the closure of international law through self-explanation. It cites customary international law as a system-support function that is informed by the presupposition that customary international law guarantees that there will always be some international legal rules of sort.
The Empire of Rules
Authors: d'Aspremont Jean
Published: June 2021

This chapter considers the constant deference to the idea of rule as the most ordinary discursive performance witnessed in the discourse on customary international law. It examines how the idea of rule dominates most arguments about customary international law, be them pertaining to the identification of customary international law or to the law that has been identified as having a customary status. It also cites the custom-formative process and the product of that process that are understood in terms of rules in international legal thought and practice. The chapter describes customary international law as a rule-governed rule-making process wherein there are rules on the identification of customary international law as well as rules of customary international law. It formulates some observations on the pull of the ruleness witnessed in the discourse on customary international law.
Concluding Remarks
Authors: d'Aspremont Jean
Published: June 2021

This chapter reviews the discourse on customary international law that is splendid thanks to the myriad of discursive performances that are achieved each time a claim is made about customary international law. It analyzes the anatomic account of the discourse on customary international law that contributed to an image of customary international law as a sophisticated doctrine whereby its users perform all kinds of discursive feats. It also demonstrates that textuality does not have the monopoly on discursive splendour in international law. The chapter argues that textuality is everywhere in customary international law notwithstanding as it is commonly understood as a source of unwritten law. It emphasizes that the discursive splendour of customary international law is neither a-textual nor pre-textual but rooted in the very textual materializations of customary international law.
Race, Refugees, and International Law
Authors: Tendayi Achiume E.
Published: June 2021

The experiences of refugees are heavily mediated by race and ethnicity, and international law plays a significant role in this mediation—in some cases offering important protections, and in others entrenching discrimination and exclusion. This Chapter makes four contributions. First, it articulates a structural and intersectional account of race, racial discrimination and xenophobic discrimination as essential starting points for international legal analysis of race and refugees. This analysis includes the overlap and distinctions between racial and xenophobic discrimination, as well as the role of religion, class and gender in shaping racial discrimination against refugees. Secondly, it reviews the doctrine on race and refugees in international refugee law and international human rights law, and maps the attendant academic literature analyzing this law. Thirdly, the Chapter canvasses legal scholarship that has examined the structure, history and development of the international refugee regime in relation to race. Finally, it concludes with reflections on a research agenda on race and refugees.
The Ethics of International Refugee Protection
Authors: Benhabib Seyla , Nathwani Nishin
Published: June 2021

The ethics of international refugee protection reflect the dual normative principles of state sovereignty and recognition of refugees’ international human rights which characterize the contemporary refugee regime since the 1951 Refugee Convention and its 1967 Protocol. This contribution identifies three major positions, each of which acknowledges these dual foundations while seeking to balance, synthesize, or transcend them. These positions are: liberal nationalism, which prioritizes state sovereignty and the rights of bounded political communities to protect their own culture and territory; liberal internationalism, which recognizes that state sovereignty is embedded in a system of international duties and prerogatives; and, cosmopolitanism, which seeks to transcend ‘ontology of containment’ characterizing both positions by acknowledging the radical interdependence of peoples and the fluidity of their movement across boundaries. The cosmopolitan position is further divided into agency-centric views, power-centric views, and the post-colonial perspective. The article concludes by defending jurisgenerativity and democratic iterations as political processes through which law’s normative promise and its imbrication in systems of power and domination can be brought to light and resignified to reflect the dignity and subjectivity of refugees and not merely their protection.
The Intersection of International Refugee Law and International Statelessness Law
Authors: Van Waas Laura
Published: June 2021

This chapter focuses on the intersection of international refugee law and international statelessness law. While refugee law, policy, doctrine, and research evolved, it was not until after the turn of the twenty-first century that international statelessness law started to draw much attention and to begin to emerge as a field of its own. As global interest in statelessness grows, the interaction between statelessness and forced displacement has also come back under the spotlight. Thus, the chapter provides an insight into the relationship between statelessness and forced displacement. It starts by unpacking how statelessness can manifest itself as a cause or consequence of displacement, as well as how statelessness can be a complicating factor for refugee protection and durable solutions. The chapter then offers a brief overview of key norms relating to the protection of stateless persons and the prevention and resolution of statelessness, setting out the contours of international statelessness law. It also looks at the implications of the statelessness–displacement nexus by exploring the conceptual and practical questions that arise when a refugee is also stateless, and when a stateless person is also a refugee.
The Architecture of the UN Refugee Convention and Protocol
Authors: Hathaway James C.
Published: June 2021

The architecture of the Refugee Convention and Protocol is unique in the world of international human rights law. Rather than being framed in absolutist terms, these treaties embody a principled compromise between attention to the needs of refugees, on the one hand, and recognition of the legitimate interests of host countries, on the other. Refugees are advantaged not only by the attribution of rights on the basis of a non-reservable and flexible definition of refugee status, but also by a commitment to declaratory rather than constitutive status assessment, non-exclusivity of rights accrual, and the existence of no more than constrained exceptions and derogation authority. The legitimate concerns of host countries are catered for by the structure of incremental rights acquisition through attachment and the conceptualization of most rights on a contingent basis.

Sadly, the workability of the compromise embedded in the architecture of the Refugee Convention and Protocol is today threatened by critical failures at the level of implementation: specifically, that these treaties continue to rely on ad hoc, State-by-State efforts rather than coordinated action, and that States have failed to allocate protection responsibilities and burdens on the basis of relative capacities and resources. The challenge is thus not to renegotiate the foundational refugee treaties, but rather to change the way in which protection is operationalized.
The Office of the United Nations High Commissioner for Refugees
Authors: Milner James , Ramasubramanyam Jay
Published: June 2021

This chapter addresses the role played by the Office of the United Nations High Commissioner for Refugees (UNHCR) in the making and implementation of international refugee law. It begins by considering UNHCR’s mandate responsibilities and operational functions to better understand the structures that condition the scope of UNHCR’s engagement with the functioning of international law. While UNHCR’s 1950 Statute and the Refugee Convention both mandate UNHCR to serve particular functions, such as its supervisory responsibility relating to the Refugee Convention, its Statute also places particular constraints on UNHCR, especially in terms of the scope of its activities and its reliance on voluntary contributions from States to perform its mandated functions. The chapter then looks at how the roles UNHCR has played in the making and implementation of refugee law at the global, regional, and national levels, through its operations, and how these functions have evolved over time. By illustrating the various instances where UNHCR has demonstrated power, along with those instances where UNHCR has exhibited pathologies and has been constrained by the interests of States, the chapter points to the importance of understanding international refugee law within the political environment in which it functions.
International Humanitarian Law and Refugee Protection
Authors: Ziegler Reuven (Ruvi)
Published: June 2021

The chapter considers the interrelations between international humanitarian law and international refugee law. It seeks to illustrate that, in displacement contexts, interactions between international humanitarian law and (global and regional) refugee protection regimes, which continue to apply during conflict, are rather challenging given that, whereas international humanitarian law shares international refugee law’s concern for vulnerable individuals, its frame of reference (unlike that of international refugee law) is minimization of harm. Given that the regimes have evolved at different times and with their own specific sources, institutions, and ethos, the chapter appraises how ‘regime interaction’ would (or should) work. It then assesses the scope of application of international humanitarian law norms, looking at the significance of international humanitarian law classification, including who classifies conflicts. The chapter concludes by exploring international humanitarian law displacement-related norms and the extent to which international refugee law interpretations affect them.
Customary Refugee Law
Authors: Lambert Hélène
Published: June 2021

This chapter explores customary refugee law. Refugee law is primarily treaty law. However, many of the major refugee-receiving countries are not parties to either the Refugee Convention or the Refugee Protocol, for example Bangladesh, Pakistan, India, Iran, Jordan, and Lebanon. Hence, customary international refugee law can be critically important in the identification of key principles of refugee protection and as an indication of what is permitted or not. While customary international law may not play as significant a role in refugee law as it does in other areas of international law, there are at least three practices of refugee protection aimed at safeguarding access and admission to refugee protection for which varying degrees of agreement exist in favour of a rule (or emerging rule) of customary law: non-refoulement, temporary refuge, and the right to be granted (to receive) asylum. These practices are deeply intertwined in their humanitarian purpose.
National Constitutions and Refugee Protection
Authors: Lester Eve
Published: June 2021

This chapter explores how national constitutional frameworks add a critical dimension to refugee protection. Given the variability in the protective value of national constitutions for refugees, it considers how States draw strength from their constitutions in response to refugee movements and why they do so in particular ways. The chapter seeks to elucidate some of the complexities in the relationship between constitutional law and international refugee and human rights law, considering the relevance of constitutional text and context, State perspectives on the place of international law, and the extent to which constitutional law has shaped, and continues to shape, international law. The chapter offers a taxonomy as a methodological framework for differentiating these complexities, which suggests that the relationship between constitutional law and international refugee law might be understood in one of three ways: as symbiotic, ambivalent, or antagonistic. It then applies this framework to three case studies. It suggests that this approach may help us to think more strategically about how to harness the protective possibilities of constitutional law as well as wrestle more productively with constitutional law’s limitations.
Regional Refugee Regimes
Authors: Anker Deborah
Published: June 2021

This chapter analyses refugee protection in the North American region, which includes Canada, the United States, and Mexico. The dynamics of the region, in particular the hegemonic role of the US, have often led to restrictive policies, reflecting the US’s objective of keeping asylum seekers away from its borders. Such policies can be traced back to the US’s support of violent regimes in the Northern Triangle of Central America during the 1980s and 1990s. US foreign policy contributed to the conflict and instability that generated a significant portion of the very refugees that it has since sought to keep away. But the dynamics in the region are complex, with Canada and Mexico not always aligning their policies to US interests. This chapter discusses the various international and regional refugee and human rights regimes to which Canada, the US, and Mexico are parties, and outlines the origin and evolution of specific refugee policies and practices in each of these three States. The chapter concludes by reflecting on the role of legal advocates, activists, and non-governmental organizations in holding governments accountable and ensuring that international and constitutional refugee protections are realized.