bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in behavioural responses of sub-tropical marine fishes to experimental longline capture
Authors: Talwar Brendan S , Bouyoucos Ian A , Brooks Edward J , Brownscombe Jacob W , Suski Cory D , Cooke Steven J , Grubbs R Dean , Mandelman John W
Published: July 2020

Fishes are often caught as bycatch on longlines and subsequently discarded. The behavioural response of fishes to longline capture is poorly understood, although it may be linked to the magnitude of the physiological stress response, and, ultimately, contribute to stress-induced mortality. We used accelerometers, video cameras, and hook timers to analyse the behavioural response of 13 subtropical teleost and elasmobranch species to experimental longline capture in The Bahamas. We found that, across all species and species groups, fight intensity during a capture event was best described by a negative linear and positive quadratic response. Nurse sharks and tiger sharks had lower fight intensity values and exhibited less steepness in their quadratic response during the first 10 min of capture than other species, particularly blacktip and Caribbean reef sharks. Nurse sharks also exhibited the most consistent fight intensity during the entire capture event compared to other shark species, particularly the blacknose shark. Generally, obligate ram ventilators and mixed ventilators exhibited higher steepness in fight intensity trajectories than buccal/spiracular pumpers, which had more consistent, lower fight intensity values. Behavioural responses to longline capture are species specific but may be linked to distinct evolutionary traits such as respiratory mode.
Late inflow or outflow obstruction requiring surgical intervention after HeartMate 3 left ventricular assist device insertion
Authors: Kaku Yuji , Naka Yoshifumi , Witer Lucas , Topkara Veli , Colombo Paolo , Sayer Gabriel , Uriel Nir , Takeda Koji
Published: July 2020

Inflow or outflow obstruction is a rare, but critical complication after HeartMate 3 left ventricular assist device implantation. We retrospectively reviewed 166 patients who underwent primary HeartMate 3 implantation at our centre between November 2014 and July 2019. Three cases of inflow obstruction and 3 cases of outflow obstruction were identified. Presence of low flow alarm was the most common presenting sign and they were free from heart failure symptoms except in 1 case. They all underwent surgical correction and the median time from primary implantation to reintervention was 406.5 days. Computed tomography angiogram identified a problem in 5 out of 6 cases. Clinical symptoms and/or alarms resolved after surgery, but 1 case developed recurrent low flow alarm due to partial occlusion of inflow by fibrous tissue who eventually underwent heart transplant. All patients remain alive with median follow-up of 433.5 days. Prompt surgical intervention in late inflow and outflow obstruction after HeartMate 3 implantation resulted in favourable outcomes.
Pro- and Anti-Inflammatory Properties of Interleukin in Vitro: Relevance for Major Depression and Human Hippocampal Neurogenesis
Authors: Borsini Alessandra , Di Benedetto Maria Grazia , Giacobbe Juliette , Pariante Carmine M
Published: July 2020

Background

Although the pro-inflammatory cytokine interleukin (IL)6 has been generally regarded as “depressogenic,” recent research has started to question this assumption in light of the fact that this cytokine can also have anti-inflammatory properties. This bimodal action seems to be dependent on its concentration levels and on the concomitant presence of other pro-inflammatory cytokines.

Methods

We exposed a human hippocampal progenitor cell line, HPC0A07/03C, to cytokine levels described in depressed patients (IL6 5 pg/mL with IL1β 10 pg/mL or Macrophage Migration Inhibitory Factor (300 pg/mL) in healthy individuals (IL6 with IL1β, 1 pg/mL or Macrophage Migration Inhibitory Factor 10 pg/mL), as well as to the potentially anti-inflammatory, much higher concentrations of IL6 (50 000 pg/mL).

Results

Treatment with high concentrations of IL6 with IL1β or Macrophage Migration Inhibitory Factor (resembling depressed patients) decreases neurogenesis compared with low concentrations of the same cytokines (healthy individuals) and that this is mediated via production of, respectively, IL8 and IL1β in cell supernatant. Instead, treatment with very high, anti-inflammatory concentration of IL6 (50 000 pg/mL) together with high IL1β or Macrophage Migration Inhibitory Factor prevents decrease in neurogenesis and reduces both IL8 and IL1β. When high concentrations of both IL1β and Macrophage Migration Inhibitory Factor were used in co-treatment, as a model of treatment-resistant depression, we also demonstrated a reduction in neurogenesis and that this is mediated via a decrease in IL4; moreover, co-treatment with high IL1β and Macrophage Migration Inhibitory Factor and the very high concentration of IL6 prevented the reduction in neurogenesis and increased IL4.

Conclusions

Our results demonstrate that IL6 can exert both pro- and anti-inflammatory (potentially antidepressant) properties, depending on its concentrations and combinations with other inflammatory cytokines.
Functional Dysconnectivity of Frontal Cortex to Striatum Predicts Ketamine Infusion Response in Treatment-Resistant Depression
Authors: Chen Mu-Hong , Chang Wan-Chen , Lin Wei-Chen , Tu Pei-Chi , Li Cheng-Ta , Bai Ya-Mei , Tsai Shih-Jen , Huang Wen-Sheng , Su Tung-Ping
Published: July 2020

Background

Frontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown.

Methods

In total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls.

Results

Compared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion.

Conclusion

Reduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.
Exponential convergence of mixed hp-DGFEM for the incompressible Navier–Stokes equations in ℝ2
Authors: Schötzau Dominik , Marcati Carlo , Schwab Christoph
Published: July 2020

In a polygon $\varOmega \subset \mathbb{R}^2$ we consider mixed $hp$-discontinuous Galerkin approximations of the stationary, incompressible Navier–Stokes equations, subject to no-slip boundary conditions. We use geometrically corner-refined meshes and $hp$ spaces with linearly increasing polynomial degrees. Based on recent results on analytic regularity of velocity field and pressure of Leray solutions in $\varOmega$, we prove exponential rates of convergence of the mixed $hp$-discontinuous Galerkin finite element method, with respect to the number of degrees of freedom, for small data which is piecewise analytic.
Brownian Motions and Heat Kernel Lower Bounds on Kähler and Quaternion Kähler Manifolds
Authors: Baudoin Fabrice , Yang Guang
Published: July 2020

We study the radial parts of the Brownian motions on Kähler and quaternion Kähler manifolds. Thanks to sharp Laplacian comparison theorems, we deduce as a consequence a sharp Cheeger–Yau-type lower bound for the heat kernels of such manifolds and also sharp Cheng’s type estimates for the Dirichlet eigenvalues of metric balls.
Regularity of Weak Solution of Variational Problems Modeling the Cosserat Micropolar Elasticity
Authors: Li Yimei , Wang Changyou
Published: July 2020

In this paper, we consider weak solutions of the Euler–Lagrange equation to a variational energy functional modeling the geometrically nonlinear Cosserat micropolar elasticity of continua in dimension three, which is a system coupling between the Poisson equation and the equation of $p$-harmonic maps ($2\le p\le 3$). We show that if a weak solution is stationary, then its singular set is discrete for $2<p<3$ and has zero one-dimensional Hausdorff measure for $p=2$. If, in addition, it is a stable-stationary weak solution, then it is regular everywhere when $p\in [2, \frac{32}{15}]$.
Evaluation of the Aptima HCV Quant Dx Assay for Hepatitis C Virus RNA Detection from Fingerstick Capillary Dried Blood Spot and Venepuncture-Collected Samples
Authors: Catlett Beth , Bajis Sahar , Starr Mitchell , Dore Gregory J , Hajarizadeh Behzad , Cunningham Philip H , Applegate Tanya L , Grebely Jason
Published: July 2020

Background

Simplified diagnostic strategies are needed increase hepatitis C virus (HCV) testing to determine active infection and link people into treatment. Collection methods such as dried blood spots (DBS) have advantages over standard phlebotomy, especially within marginalized populations.

Methods

We evaluated the diagnostic performance of the Aptima HCV Quant assay for the quantification and detection of HCV RNA from paired DBS and venepuncture samples. Specimens were collected from participants enrolled in an Australian observational study. We compared HCV RNA detection from DBS against venepuncture samples (gold standard).

Results

One hundred sixty-four participants had paired samples and HCV RNA was detected in 45 (27% [95% confidence interval, 21%–35%]) by the Aptima assay in venepuncture samples. Sensitivity of the Aptima assay for HCV RNA quantification from DBS (≥10 IU/mL in plasma) was 100% and specificity was 100%. Sensitivity for HCV RNA detection from DBS was 95.6% and specificity was 94.1%. A small bias in plasma over DBS was observed with good agreement (R2 = 0.96).

Conclusions

The Aptima HCV Quant assay detects active infection from DBS samples with acceptable diagnostic performance and is clinically comparable to plasma. These data will strengthen the case for the registration of a DBS kit insert claim, enabling future clinical utility.
Analysis of Treponema pallidum Strains From China Using Improved Methods for Whole-Genome Sequencing From Primary Syphilis Chancres
Authors: Chen Wentao , Šmajs David , Hu Yongfei , Ke Wujian , Pospíšilová Petra , Hawley Kelly L , Caimano Melissa J , Radolf Justin D , Sena Arlene , Tucker Joseph D , Yang Bin , Juliano Jonathan J , Zheng Heping , Parr Jonathan B
Published: July 2020

Background

Whole-genome sequencing (WGS) of Treponema pallidum subspecies pallidum (TPA) has been constrained by the lack of in vitro cultivation methods for isolating spirochetes from patient samples.

Methods

We built upon recently developed enrichment methods to sequence TPA directly from primary syphilis chancre swabs collected in Guangzhou, China.

Results

By combining parallel, pooled whole-genome amplification with hybrid selection, we generated high-quality genomes from 4 of 8 chancre-swab samples and 2 of 2 rabbit-passaged isolates, all subjected to challenging storage conditions.

Conclusions

This approach enabled the first WGS of Chinese samples without rabbit passage and provided insights into TPA genetic diversity in China.
Reliability of Self-Sampling for Accurate Assessment of Respiratory Virus Viral and Immunologic Kinetics
Authors: Waghmare Alpana , Krantz Elizabeth M , Baral Subhasish , Vasquez Emma , Loeffelholz Tillie , Chung E Lisa , Pandey Urvashi , Kuypers Jane , Duke Elizabeth R , Jerome Keith R , Greninger Alexander L , Reeves Daniel B , Hladik Florian , Cardozo-Ojeda E Fabian , Boeckh Michael , Schiffer Joshua T
Published: July 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with mid-nasal foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate that nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.
Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals
Authors: Chimukangara Benjamin , Giandhari Jennifer , Lessells Richard , Yende-Zuma Nonhlanhla , Sartorius Benn , Samuel Reshmi , Khanyile Khulekani S , Stray-Pedersen Babill , Moodley Pravi , Metzner Karin J , Padayatchi Nesri , Naidoo Kogieleum , De Oliveira Tulio
Published: July 2020

Objectives

To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART.

Methods

We conducted a case–control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs <1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ≥20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF.

Results

We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ≥20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P = 0.210. Participants with PDR at ≥20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8–18.3) compared with those without, P = 0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ≥2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6–4.3) compared with those without, P = 0.398.

Conclusions

Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions.
Implications of antibiotics use during the COVID-19 pandemic: present and future
Authors: Miranda Carla , Silva Vanessa , Capita Rosa , Alonso-Calleja Carlos , Igrejas Gilberto , Poeta Patrícia
Published: July 2020

COVID-19 is caused by the SARS-CoV-2 virus, which has infected more than 4 million people with 278 892 deaths worldwide as of 11 May 2020. This disease, which can manifest as a severe respiratory infection, has been declared as a public health emergency of international concern and is being treated with a variety of antivirals, antibiotics and antifungals. This article highlights the administration of antimicrobials in COVID-19 patients worldwide, during the 2019–20 pandemic. It is imperative to be aware of the unreported amounts of antibiotics that have been administered worldwide in just a few months and a marked increase in antimicrobial resistance should therefore be expected. Due to the lack of data about antimicrobial use during this pandemic, the global impact on the emergence of new antimicrobial resistance is as yet unknown. This issue must be at the forefront of public health policymaking and planning in order that we are prepared for the potentially severe consequences for human and animal health and the environment.
Clinical concept normalization with a hybrid natural language processing system combining multilevel matching and machine learning ranking
Authors: Chen Long , Fu Wenbo , Gu Yu , Sun Zhiyong , Li Haodan , Li Enyu , Jiang Li , Gao Yuan , Huang Yang
Published: July 2020

Objective

Normalizing clinical mentions to concepts in standardized medical terminologies, in general, is challenging due to the complexity and variety of the terms in narrative medical records. In this article, we introduce our work on a clinical natural language processing (NLP) system to automatically normalize clinical mentions to concept unique identifier in the Unified Medical Language System. This work was part of the 2019 n2c2 (National NLP Clinical Challenges) Shared-Task and Workshop on Clinical Concept Normalization.

Materials and Methods

We developed a hybrid clinical NLP system that combines a generic multilevel matching framework, customizable matching components, and machine learning ranking systems. We explored 2 machine leaning ranking systems based on either ensemble of various similarity features extracted from pretrained encoders or a Siamese attention network, targeting at efficient and fast semantic searching/ranking. Besides, we also evaluated the performance of a general-purpose clinical NLP system based on Unstructured Information Management Architecture.

Results

The systems were evaluated as part of the 2019 n2c2 challenge, and our original best system in the challenge obtained an accuracy of 0.8101, ranked fifth in the challenge. The improved system with newly designed machine learning ranking based on Siamese attention network improved the accuracy to 0.8209.

Conclusions

We demonstrate the successful practice of combining multilevel matching and machine learning ranking for clinical concept normalization. Our results indicate the capability and interpretability of our proposed approach, as well as the limitation, suggesting the opportunities of achieving better performance by combining general clinical NLP systems.
Remote symptom monitoring integrated into electronic health records: A systematic review
Authors: Gandrup Julie , Ali Syed Mustafa , McBeth John , van der Veer Sabine N , Dixon William G
Published: July 2020

Objective

People with long-term conditions require serial clinical assessments. Digital patient-reported symptoms collected between visits can inform these, especially if integrated into electronic health records (EHRs) and clinical workflows. This systematic review identified and summarized EHR-integrated systems to remotely collect patient-reported symptoms and examined their anticipated and realized benefits in long-term conditions.

Materials and Methods

We searched Medline, Web of Science, and Embase. Inclusion criteria were symptom reporting systems in adults with long-term conditions; data integrated into the EHR; data collection outside of clinic; data used in clinical care. We synthesized data thematically. Benefits were assessed against a list of outcome indicators. We critically appraised studies using the Mixed Methods Appraisal Tool.

Results

We included 12 studies representing 10 systems. Seven were in oncology. Systems were technically and functionally heterogeneous, with the majority being fully integrated (data viewable in the EHR). Half of the systems enabled regular symptom tracking between visits. We identified 3 symptom report-guided clinical workflows: Consultation-only (data used during consultation, n = 5), alert-based (real-time alerts for providers, n = 4) and patient-initiated visits (n = 1). Few author-described anticipated benefits, primarily to improve communication and resultant health outcomes, were realized based on the study results, and were only supported by evidence from early-stage qualitative studies. Studies were primarily feasibility and pilot studies of acceptable quality.

Discussion and Conclusions

EHR-integrated remote symptom monitoring is possible, but there are few published efforts to inform development of these systems. Currently there is limited evidence that this improves care and outcomes, warranting future robust, quantitative studies of efficacy and effectiveness.
The effects of the forage-to-concentrate ratio on the conversion of digestible energy to metabolizable energy in growing beef steers
Authors: Fuller Amanda L , Wickersham Tryon A , Sawyer Jason E , Freetly Harvey C , Brown-Brandl Tami M , Hales Kristin E
Published: July 2020

Metabolizable energy (ME) is calculated from digestible energy (DE) using a constant conversion factor of 0.82. Methane and urine energy losses vary across diets and dry matter intake (DMI), suggesting that a static conversion factor fails to describe the biology. To quantify the effects of the forage-to-concentrate ratio (F:C) on the efficiency of conversion of DE to ME, 10 Angus steers were used in a 5 × 5 replicated Latin square. Dry-rolled corn was included in experimental diets at 0%, 22.5%, 45.0%, 67.5%, and 83.8% on a dry matter (DM) basis, resulting in a high F:C (HF:C), intermediate F:C (IF:C), equal F:C (EF:C), low F:C (LF:C), and a very low F:C (VLF:C), respectively. Each experimental period consisted of a 23-d diet adaption followed by 5 d of total fecal and urine collections and a 24-h gas exchange collection. Contrasts were used to test the linear and quadratic effects of the F:C. There was a tendency (P = 0.06) for DMI to increase linearly as F:C decreased. As a result, gross energy intake (GEI) increased linearly (P = 0.04) as F:C decreased. Fecal energy loss expressed as Mcal/d (P = 0.02) or as a proportion of GEI (P < 0.01) decreased as F:C decreased, such that DE (Mcal/d and Mcal/kg) increased linearly (P < 0.01) as F:C decreased. As a proportion of GEI, urine energy decreased linearly (P = 0.03) as F:C decreased. Methane energy loss as a proportion of GEI responded quadratically (P < 0.01), increasing from HF:C to IF:C then decreasing thereafter. The efficiency of DE to ME conversion increased quadratically (P < 0.01) as F:C decreased, ranging from 0.86 to 0.92. Heat production (Mcal) increased linearly (P < 0.04) as F:C decreased but was not different as a proportion of GEI (P ≥ 0.22). As a proportion of GEI, retained energy responded quadratically (P = 0.03), decreasing from HF:C to IF:C and increasing thereafter. DM, organic matter, and neutral detergent fiber digestibility increased linearly (P < 0.01) and starch digestibility decreased linearly (P < 0.01) as the F:C decreased. Total N retained tended to increase linearly as the proportion of concentrate increased in the diet (P = 0.09). In conclusion, the efficiency of conversion of DE to ME increased with decreasing F:C due to decreasing methane and urine energy loss. The relationship between DE and ME is not static, especially when differing F:C.
P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency
Authors: Rachadech Wanitcha , Kato Yusuke , Abou El-Magd Rabab M , Shishido Yuji , Kim Soo Hyeon , Sogabe Hirofumi , Maita Nobuo , Yorita Kazuko , Fukui Kiyoshi
Published: July 2020

Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7–0.9 µM) compared with wild-type (1.2–2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure–function relationship of human DAO.
Prevalence and associated factors of perceived cancer-related stigma in Japanese cancer survivors
Authors: Fujisawa Daisuke , Umezawa Shino , Fujimori Maiko , Miyashita Mitsunori
Published: July 2020

This study aimed to examine the prevalence and associated factors of perceived cancer-related stigma among Japanese cancer survivors. In this web-based survey involving 628 Japanese cancer survivors, perceived cancer-related stigma, quality of life (Quality of Life-Cancer Survivors Instrument), psychological distress (K6) and perceived social support (multidimensional scale of perceived social support) were evaluated. Perceived cancer-related stigma was endorsed by 61.2% of the participants. Perceived cancer-related stigma was significantly associated with quality of life (R = 0.35–0.37), psychological distress (R = 0.35) and perceived social support (R = 0.10). Logistic regression analysis demonstrated that cancer survivors at younger ages (odds ratio = 0.96), with low income (odds ratio = 2.49), with poorer performance status (odds ratio = 2.33), and with breast, urinary or gynecological cancers (odds ratio = 4.27, 4.01, 4.01, respectively) were at higher risk for perceived cancer-related stigma.
International transfers of health data between the EU and USA: a sector-specific approach for the USA to ensure an ‘adequate’ level of protection
Authors: Bradford Laura , Aboy Mateo , Liddell Kathleen
Published: July 2020

International health research increasingly depends on collaboration and combination using medical data to advance treatment and drug discovery. The European Union (EU), through its General Data Protection Regulation, has tightened the rules for sharing data across borders to protect individual privacy. These new rules threaten cooperation between the EU and the USA, the two largest public funders of biomedical research. This article analyzes the primary pathway for sharing research data with the USA, the US–EU Privacy Shield††, and argues that the Shield is ill-suited to support complex health studies. Its legitimacy is in question under both EU and US law, and its terms are too restrictive for the variety of exchanges underlying research, treatment, and care. As an alternative, we propose that the USA seek an additional sector-based adequacy determination based on the existing US health privacy law, the Health Insurance Portability and Accountability Act. A sector-specific approach to adequacy for health would avoid many of the most contentious issues that divide the USA and EU on data protection. It could also serve as a model for other third-party jurisdictions and facilitate international harmonization of health research practices.
MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment
Authors: Wang Bing , Lim Chuan-Bian , Yan Jiawei , Li Lizhen , Wang Jufang , Little John B , Yuan Zhi-Min
Published: July 2020

A role of tumor-suppressive activity of p53 in the tumor microenvironment (TME) has been implicated but remains fairly understudied. To address this knowledge gap, we leveraged our MdmxS314A mice as recipients to investigate how implanted tumor cells incapacitate host p53 creating a conducive TME for tumor progression. We found that tumor cell-associated stress induced p53 downregulation in peritumor cells via an MDMX-Ser314 phosphorylation-dependent manner. As a result, an immunosuppressive TME was developed, as reflected by diminished immune cell infiltration into tumors and compromised macrophage M1 polarization. Remarkably, ablation of MDMX-Ser314 phosphorylation attenuated p53 decline in peritumor cells, which was associated with mitigation of immunosuppression and significant tumor growth delay. Our data collectively uncover a novel role of p53 in regulating the tumor immune microenvironment, suggesting that p53 restoration in the TME can be exploited as a potential strategy of anticancer therapy.
Contesting Roles: Rising Powers as “Net Providers of Security”
Authors: Fung Courtney J , Lam Shing-hon
Published: July 2020

What is a “net provider of security,” or a “global security provider”? How are such roles adopted by rising powers? We define a net provider of security as a social role, when an actor provides novel, niche, and functionally differentiated security duties, supporting burden-sharing in providing public goods. The nascent literature on these US-vectored roles characterizes role adoption as largely successful. However, rising powers contest the US-designated net provider of security role. Rising powers have stated or latent foreign policy goals to shape international order in their strategic vision, reflecting ideational capacity to reconceptualize their role in global politics, or a material capacity to reposition their rank. Building upon insights from role theory, we illustrate that rising powers exploit temporal and rhetorical ambiguities and leverage their material and ideational resources to execute role differentiation through three micro-processes of role resistance—role acknowledgment, role task rejection, and role task substitution—used to promote an idiosyncratic role, casting the US-vectored role as non-functional, non-representational, and untenable. We examine crucial cases of rising powers, India and China, to develop our theoretical contribution. Our findings speak to the literatures on the logic of identity management, rhetoric in international politics, the taxonomy of contemporary ad hoc security arrangements, and the epistemological project of globalizing international relations.
Overexpression of the chloroplastic 2-oxoglutarate/malate transporter disturbs carbon and nitrogen homeostasis in rice
Authors: Zamani-Nour Shirin , Lin Hsiang-Chun , Walker Berkley J , Mettler-Altmann Tabea , Khoshravesh Roxana , Karki Shanta , Bagunu Efren , Sage Tammy L , Quick W Paul , Weber Andreas P M
Published: July 2020

The chloroplastic 2-oxaloacetate (OAA)/malate transporter (OMT1 or DiT1) takes part in the malate valve that protects chloroplasts from excessive redox poise through export of malate and import of OAA. Together with the glutamate/malate transporter (DCT1 or DiT2), it connects carbon with nitrogen assimilation, by providing 2-oxoglutarate for the GS/GOGAT (glutamine synthetase/glutamate synthase) reaction and exporting glutamate to the cytoplasm. OMT1 further plays a prominent role in C4 photosynthesis: OAA resulting from phosphoenolpyruvate carboxylation is imported into the chloroplast, reduced to malate by plastidic NADP-malate dehydrogenase, and then exported for transport to bundle sheath cells. Both transport steps are catalyzed by OMT1, at the rate of net carbon assimilation. To engineer C4 photosynthesis into C3 crops, OMT1 must be expressed in high amounts on top of core C4 metabolic enzymes. We report here high-level expression of ZmOMT1 from maize in rice (Oryza sativa ssp. indica IR64). Increased activity of the transporter in transgenic rice was confirmed by reconstitution of transporter activity into proteoliposomes. Unexpectedly, overexpression of ZmOMT1 in rice negatively affected growth, CO2 assimilation rate, total free amino acid content, tricarboxylic acid cycle metabolites, as well as sucrose and starch contents. Accumulation of high amounts of aspartate and the impaired growth phenotype of OMT1 rice lines could be suppressed by simultaneous overexpression of ZmDiT2. Implications for engineering C4 rice are discussed.
Developmentally controlled changes during Arabidopsis leaf development indicate causes for loss of stress tolerance with age
Authors: Kanojia Aakansha , Gupta Saurabh , Benina Maria , Fernie Alisdair R , Mueller-Roeber Bernd , Gechev Tsanko , Dijkwel Paul P
Published: July 2020

Leaf senescence is the final stage of leaf development and is induced by the gradual occurrence of age-related changes (ARCs). The process of leaf senescence has been well described, but the cellular events leading to this process are still poorly understood. By analysis of progressively ageing, but not yet senescing, Arabidopsis thaliana rosette leaves, we aimed to better understand processes occurring prior to the onset of senescence. Using gene expression analysis, we found that as leaves mature, genes responding to oxidative stress and genes involved in stress hormone biosynthesis and signalling were up-regulated. A decrease in primary metabolites that provide protection against oxidative stress was a possible explanation for the increased stress signature. The gene expression and metabolomics changes occurred concomitantly to a decrease in drought, salinity, and dark stress tolerance of individual leaves. Importantly, stress-related genes showed elevated expression in the early ageing mutant old5 and decreased expression in the delayed ageing mutant ore9. We propose that the decreased stress tolerance with age results from the occurrence of senescence-inducing ARCs that is integrated into the leaf developmental programme, and that this ensures a timely and certain death.
The zinc finger transcription factor ATF1 regulates aluminum tolerance in barley
Authors: Wu Liyuan , Guo Yiyi , Cai Shengguan , Kuang Liuhui , Shen Qiufang , Wu Dezhi , Zhang Guoping
Published: July 2020

Aluminum (Al) toxicity is a major abiotic stress that restricts crop production in acid soils. Plants have evolved internal and external mechanisms of tolerance, and among them it is well known that AtSTOP1 and OsART1 are key transcription factors involved in tolerance through regulation of multiple downstream genes. Here, we identified the closest homolog of these two proteins in barley, namely HvATF1, Al-tolerance Transcription Factor 1, and determined its potential function in Al stress. HvATF1 is expressed in the nucleus, and functions in transcriptional activation. The transcription of HvATF1 was found to be constitutive in different tissues, and was little affected by Al stress. Knockdown of HvATF1 by RNAi resulted in increased Al sensitivity. Transcriptomics analysis identified 64 differently expressed genes in the RNAi lines compared to the wild-type, and these were considered as candidate downstream genes regulated by HvATF1. This study provides insights into the different molecular mechanisms of Al tolerance in barley and other plants.
Plasma Cell Proliferation Is Reduced in Myeloma-Induced Hypercalcemia and in Co-Culture with Normal Healthy BM-MSCs
Authors: Vazifeh Shiran Nader , Abroun Saeid
Published: July 2020

Objective

In multiple myeloma (MM), stimulation of osteoclasts and bone marrow (BM) lesions lead to hypercalcemia, renal failure, and anemia. Co-culture of the myeloma cells in both hypocalcemia and hypercalcemia concentrations with bone marrow-mesenchymal stem cells were evaluated.

Materials and Methods

Viability and survival of myeloma cells were assessed by microculture tetrazolium test and flow cytometric assays. Mesenchymal stem cells (MSCs) were extracted from normal and myeloma patients and were co-cultured with myeloma cells.

Results

Myeloma cells showed less survival in both hypocalcaemia and hypercalcemia conditions (P <.01). The paracrine and juxtacrine conditions of demineralized bone matrix-induced hypercalcemia increased the proliferation and survival of the cells (P <.05). Unlike myeloma MSCs, normal MSCs reduced the survival of and induced apoptosis in myeloma cells (P <.1).

Conclusion

Normal healthy-MSCs do not protect myeloma cells, but inhibit them. However, increasing the ratio of myeloma cells to MSCs reduces their inhibitory effects of MSCs and leads to their myelomatous transformation.
Neolog: Reforming Judaism in a Hungarian Milieu
Authors: Lupovitch Howard
Published: July 2020

This article explores the mentality of Neolog Judaism and how its early proponents fashioned a centrist, non-ideological alternative to both Orthodoxy and German-Jewish style Reform Judaism, an alternative that emphasized Judaism’s inherent compatibility with and adaptability to the demands of citizenship. Early proponents of this Neolog mentality, such as Aron Chorin and Leopold Löw, argued that adapting Jewish practice within the framework and systemic rules of Jewish law, precedent, and custom would not undermine a commitment to traditional Judaism in any way, as Orthodox jeremiads predicted; nor would it require the sort of re-definition of Judaism that Reform Jews advocated. Four aspects of Neolog mentality, in particular, laid the foundation for this outlook: a belief that Judaism has always been inherently malleable and diverse; a willingness to see leniency as no less authentic an option than stringency (in contrast to the “humra culture” that has defined Orthodox Judaism for the last two centuries); a preference for unity over schism (contra the secession of Orthodox communities in Germany and Hungary); and the use of halachic precedent and argumentation as a mandatory part of the rationale for innovation.
High time resolution and polarization properties of ASKAP-localized fast radio bursts
Authors: Day Cherie K , Deller Adam T , Shannon Ryan M , Qiu(邱昊) Hao , Bannister Keith W , Bhandari Shivani , Ekers Ron , Flynn Chris , James Clancy W , Macquart Jean-Pierre , Mahony Elizabeth K , Phillips Chris J , Xavier Prochaska J
Published: July 2020

Combining high time and frequency resolution full-polarization spectra of fast radio bursts (FRBs) with knowledge of their host galaxy properties provides an opportunity to study both the emission mechanism generating them and the impact of their propagation through their local environment, host galaxy, and the intergalactic medium. The Australian Square Kilometre Array Pathfinder (ASKAP) telescope has provided the first ensemble of bursts with this information. In this paper, we present the high time and spectral resolution, full polarization observations of five localized FRBs to complement the results published for the previously studied ASKAP FRB 181112. We find that every FRB is highly polarized, with polarization fractions ranging from 80 to 100 per cent, and that they are generally dominated by linear polarization. While some FRBs in our sample exhibit properties associated with an emerging archetype (i.e. repeating or apparently non-repeating), others exhibit characteristic features of both, implying the existence of a continuum of FRB properties. When examined at high time resolution, we find that all FRBs in our sample have evidence for multiple subcomponents and for scattering at a level greater than expected from the Milky Way. We find no correlation between the diverse range of FRB properties (e.g. scattering time, intrinsic width, and rotation measure) and any global property of their host galaxy. The most heavily scattered bursts reside in the outskirts of their host galaxies, suggesting that the source-local environment rather than the host interstellar medium is likely the dominant origin of the scattering in our sample.
The cosmic evolution of the stellar mass–velocity dispersion relation of early-type galaxies
Authors: Cannarozzo Carlo , Sonnenfeld Alessandro , Nipoti Carlo
Published: July 2020

We study the evolution of the observed correlation between central stellar velocity dispersion σe and stellar mass M* of massive ($M_*\gtrsim 3\times 10^{10}\, \mathrm{M_\odot}$) early-type galaxies (ETGs) out to redshift z ≈ 2.5, taking advantage of a Bayesian hierarchical inference formalism. Collecting ETGs from state-of-the-art literature samples, we build a fiducial sample (0 ≲ z ≲ 1), which is obtained with homogeneous selection criteria, but also a less homogeneous extended sample (0 ≲ z ≲ 2.5). Based on the fiducial sample, we find that at z ≲ 1 the M*–σe relation is well represented by $\sigma _{\mathrm{e}}\propto M_*^{\beta }(1+z)^{\zeta}$, with β ≃ 0.18 independent of redshift and ζ ≃ 0.4 (at a given M*, σe decreases for decreasing z, for instance by a factor of ≈1.3 from z = 1 to z = 0). When the slope β is allowed to evolve, we find it increasing with redshift: β(z) ≃ 0.16 + 0.26log (1 + z) describes the data as well as constant β ≃ 0.18. The intrinsic scatter of the M*–σe relation is ≃0.08 dex in σe at given M*, independent of redshift. Our results suggest that, on average, the velocity dispersion of individual massive (M* ≳ 3 × 1011M⊙) ETGs decreases with time while they evolve from z ≈ 1 to z ≈ 0. The analysis of the extended sample, over the wider redshift range 0 ≲ z ≲ 2.5, leads to results similar to that of the fiducial sample, with slightly stronger redshift dependence of the normalization (ζ ≃ 0.5) and weaker redshift dependence of the slope (dβ/dlog (1 + z) ≃ 0.18) when β varies with time. At z = 2 ETGs with $M_*\approx 10^{11}\, \mathrm{M_\odot}$ have, on average, ≈1.7 higher σe than ETGs of similar stellar mass at z = 0.
Multimessenger observations of counterparts to IceCube-190331A
Authors: Krauß Felicia , Calamari Emily , Keivani Azadeh , Coleiro Alexis , Evans Phil A , Fox Derek B , Kennea Jamie A , Mészáros Peter , Murase Kohta , Russell Thomas D , Santander Marcos , Tohuvavohu Aaron
Published: July 2020

High-energy neutrinos are a promising tool for identifying astrophysical sources of high and ultra-high energy cosmic rays (UHECRs). Prospects of detecting neutrinos at high energies (≳TeV) from blazars have been boosted after the recent association of IceCube-170922A and TXS 0506+056. We investigate the high-energy neutrino, IceCube-190331A, a high-energy starting event (HESE) with a high likelihood of being astrophysical in origin. We initiated a Swift/XRT and UVOT tiling mosaic of the neutrino localization and followed up with ATCA radio observations, compiling a multiwavelength spectral energy distribution (SED) for the most likely source of origin. NuSTAR observations of the neutrino location and a nearby X-ray source were also performed. We find two promising counterpart in the 90 per cent confidence localization region and identify the brightest as the most likely counterpart. However, no Fermi/LAT γ-ray source and no prompt Swift/BAT source is consistent with the neutrino event. At this point, it is unclear whether any of the counterparts produced IceCube-190331A. We note that the Helix Nebula is also consistent with the position of the neutrino event and we calculate that associated particle acceleration processes cannot produce the required energies to generate a high-energy HESE neutrino.
Bi-abundance photoionization models of planetary nebulae: determining the amount of oxygen in the metal-rich component
Authors: Gómez-Llanos V , Morisset C
Published: July 2020

We study the hypothesis of high-metallicity clumps being responsible for the abundance discrepancy found in planetary nebulae between the values obtained from recombination and collisionally excited lines. We generate grids of photoionization models combining cold metal-rich clumps emitting the heavy element recombination lines, embedded in a normal metallicity region responsible for the forbidden lines. The two running parameters of the grid are the metallicity of the clumps and its volume fraction relative to the whole nebula. We determine the density and temperatures (from the Balmer jump and the [O iii] 5007/4363 Å line ratio) and the ionic abundances from the collisional and recombination lines, as an observer would do. The metallicity of the near-to-solar region is recovered, while the metallicity of the clumps is systematically underestimated by up to two orders of magnitude. This is mainly because most of the Hβ emission is coming from the ‘normal’ region, and only the small contribution emitted by the metal-rich clumps should be used. We find that a given ADF(O++) can be reproduced by a small amount of rich clumps, or a bigger amount of less rich clumps. Finally, comparing with the observations of NGC 6153, we find two models that reproduce its ADF(O++) and the observed electron temperatures. We determine the fraction of oxygen embedded in the metal-rich region (with a fraction of volume less than 1 per cent) to be roughly between 25 per cent and 60 per cent of the total amount of oxygen in the nebula (a few 10−3M⊙).
An Unbiased Molecular Approach Using 3′-UTRs Resolves the Avian Family-Level Tree of Life
Authors: Kuhl Heiner , Frankl-Vilches Carolina , Bakker Antje , Mayr Gerald , Nikolaus Gerhard , Boerno Stefan T , Klages Sven , Timmermann Bernd , Gahr Manfred
Published: July 2020

Presumably, due to a rapid early diversification, major parts of the higher-level phylogeny of birds are still resolved controversially in different analyses or are considered unresolvable. To address this problem, we produced an avian tree of life, which includes molecular sequences of one or several species of ∼90% of the currently recognized family-level taxa (429 species, 379 genera) including all 106 family-level taxa of the nonpasserines and 115 of the passerines (Passeriformes). The unconstrained analyses of noncoding 3-prime untranslated region (3′-UTR) sequences and those of coding sequences yielded different trees. In contrast to the coding sequences, the 3′-UTR sequences resulted in a well-resolved and stable tree topology. The 3′-UTR contained, unexpectedly, transcription factor binding motifs that were specific for different higher-level taxa. In this tree, grebes and flamingos are the sister clade of all other Neoaves, which are subdivided into five major clades. All nonpasserine taxa were placed with robust statistical support including the long-time enigmatic hoatzin (Opisthocomiformes), which was found being the sister taxon of the Caprimulgiformes. The comparatively late radiation of family-level clades of the songbirds (oscine Passeriformes) contrasts with the attenuated diversification of nonpasseriform taxa since the early Miocene. This correlates with the evolution of vocal production learning, an important speciation factor, which is ancestral for songbirds and evolved convergent only in hummingbirds and parrots. As 3′-UTR-based phylotranscriptomics resolved the avian family-level tree of life, we suggest that this procedure will also resolve the all-species avian tree of life