bluuebunny/crossref_metadata_2025 huggingface dataset:
Sevelamer crystals—an unusual cause of large bowel obstruction
Authors: Cockrell Hannah C , Cottrell-Cumber Sarah , Brown Kathryn , Murphy Jason G
Published: May 2021

Sevelamer is a common phosphate binder used to manage hyperphosphatemia in end-stage renal disease. The medication has a well-documented gastrointestinal side-effect profile including nausea, vomiting and abdominal pain. There are few case reports of Sevelamer crystal deposition causing gastrointestinal mucosal injury, pseudotumor or obstruction. Here, we discuss a patient on Sevelamer who required operative management of a sigmoid obstruction. Surgical pathology showed pericolonic abscess with Sevelamer crystals.
Systematic analysis of MYB gene family in Acer rubrum and functional characterization of ArMYB89 in regulating anthocyanin biosynthesis
Authors: Chen Zhu , Lu Xiaoyu , Li Qianzhong , Li Tingchun , Zhu Lu , Ma Qiuyue , Wang Jingjing , Lan Wei , Ren Jie
Published: May 2021

The v-myb avian myeloblastosis viral oncogene homolog (MYB) family of transcription factors is extensively distributed across the plant kingdom. However, the functional significance of red maple (Acer rubrum) MYB transcription factors remains unclear. Our research identified 393 MYB transcription factors in the Acer rubrum genome, and these ArMYB members were unevenly distributed across 34 chromosomes. Among them, R2R3 was the primary MYB sub-class, which was further divided into 21 sub-groups with their Arabidopsis homologs. The evolution of the ArMYB family was also investigated, with the results revealing several R2R3-MYB sub-groups with expanded membership in woody species. Here, we report on the isolation and characterization of ArMYB89 in red maple. Quantitative real-time PCR analysis revealed that ArMYB89 expression was significantly up-regulated in red leaves in contrast to green leaves. Sub-cellular localization experiments indicated that ArMYB89 was localized in the nucleus. Further experiments revealed that ArMYB89 could interact with ArSGT1 in vitro and in vivo. Overexpression of ArMYB89 in tobacco enhances the anthocyanin content of transgenic plants. In conclusion, our results contribute to the elucidation of a theoretical basis for the ArMYB gene family, and provide a foundation for further characterization of the biological roles of MYB genes in the regulation of Acer rubrum leaf color.
The case of tryptamine and serotonin in plants: a mysterious precursor for an illustrious metabolite
Authors: Negri Stefano , Commisso Mauro , Avesani Linda , Guzzo Flavia
Published: May 2021

Indolamines are tryptophan-derived specialized metabolites belonging to the huge and ubiquitous indole alkaloids group. Serotonin and melatonin are the best-characterized members of this family, given their many hormonal and physiological roles in animals. Following their discovery in plants, the study of plant indolamines has flourished and their involvement in important processes, including stress responses, growth and development, and reproduction, has been proposed, leading to their classification as a new category of phytohormones. However, the complex indolamine puzzle is far from resolved, particularly the biological roles of tryptamine, the early serotonin precursor representing the central hub of many downstream indole alkaloids. Tryptophan decarboxylase, which catalyzes the synthesis of tryptamine, strictly regulates the flux of carbon and nitrogen from the tryptophan pool into the indolamine pathway. Furthermore, tryptamine accumulates to high levels in the reproductive organs of many plant species and therefore cannot be classed as a mere intermediate but rather as an end product with potentially important functions in fruits and seeds. This review summarizes current knowledge on the role of tryptamine and its close relative serotonin, emphasizing the need for a clear understanding of the functions of, and mutual relations between, these indolamines and their biosynthesis pathways in plants.
H iintensity mapping with MeerKAT: calibration pipeline for multidish autocorrelation observations
Authors: Wang Jingying , Santos Mario G , Bull Philip , Grainge Keith , Cunnington Steven , Fonseca José , Irfan Melis O , Li Yichao , Pourtsidou Alkistis , Soares Paula S , Spinelli Marta , Bernardi Gianni , Engelbrecht Brandon
Published: May 2021

While most purpose-built 21-cm intensity mapping experiments are close-packed interferometer arrays, general-purpose dish arrays should also be capable of measuring the cosmological 21-cm signal. This can be achieved most efficiently if the array is used as a collection of scanning autocorrelation dishes rather than as an interferometer. As a first step towards demonstrating the feasibility of this observing strategy, we show that we are able to successfully calibrate dual-polarization autocorrelation data from 64 MeerKAT dishes in the L band (856–1712 MHz, 4096 channels), with 10.5 h of data retained from six nights of observing. We describe our calibration pipeline, which is based on multilevel radio frequency interference flagging, periodic noise diode injection to stabilize gain drifts, and an absolute calibration based on a multicomponent sky model. We show that it is sufficiently accurate to recover maps of diffuse celestial emission and point sources over a 10° × 30° patch of the sky overlapping with the WiggleZ 11-h field. The reconstructed maps have a good level of consistency between per-dish maps and external data sets, with the estimated thermal noise limited to 1.4 × the theoretical noise level (∼2 mK). The residual maps have rms amplitudes below 0.1 K, corresponding to $\lt 1{{\ \rm per\ cent}}$ of the model temperature. The reconstructed Galactic H i intensity map shows excellent agreement with the Effelsberg–Bonn H i Survey, and the flux of the radio galaxy 4C + 03.18 is recovered to within 3.6 per cent, which demonstrates that the autocorrelation can be successfully calibrated to give the zero-spacing flux and potentially help in the imaging of MeerKAT interferometric data. Our results provide a positive indication towards the feasibility of using MeerKAT and the future Square Kilometre Array to measure the H i intensity mapping signal and probe cosmology on degree scales and above.
Dynamical evolution of the inner asteroid belt
Authors: Dermott Stanley F , Li Dan , Christou Apostolos A , Kehoe Thomas J J , Murray Carl D , Robinson J Malcolm
Published: May 2021

A determination of the dynamical evolution of the asteroid belt is difficult because the asteroid belt has evolved since the time of asteroid formation through mechanisms that include: (1) catastrophic collisions, (2) rotational disruption, (3) chaotic orbital evolution, and (4) orbital evolution driven by Yarkovsky radiation forces. The time-scales of these loss mechanisms are uncertain and there is a need for more observational constraints. In the inner main belt (IMB), the mean size of the non-family asteroids increases with increasing inclination. Here, we use that observation to show that all IMB asteroids originate from either the known families or from ghost families, that is, old families with dispersed orbital elements. We estimate that the average age of the asteroids in the ghost families is a factor of 1/3 less than the Yarkovsky orbital evolution time-scale. However, this orbital evolution time-scale is a long-term average that must allow for the collisional evolution of the asteroids and for stochastic changes in their spin directions. By applying these constraints on the orbital evolution time-scales to the evolution of the size-frequency distribution of the Vesta asteroid family, we estimate that the age of this family is greater than 1.3 Gyr and could be comparable with the age of the Solar system. By estimating the number of ghost families, we calculate that the number of asteroids that are the root sources of the meteorites and the near-Earth asteroids that originate from the IMB is about 20.
Strongly lensed cluster substructures are not in tension with ΛCDM
Authors: Bahé Yannick M
Published: May 2021

Strong gravitational lensing observations can test structure formation models by constraining the masses and concentrations of subhaloes in massive galaxy clusters. Recent work has concluded that cluster subhaloes are more abundant and/or concentrated than predicted by Λ cold dark matter (ΛCDM) simulations; this finding has been interpreted as arising from unidentified issues with simulations or an incorrect understanding of the nature of dark matter. We test these hypotheses by comparing observed subhalo masses and maximum circular velocities vmax to predictions from the high-resolution Hydrangea galaxy cluster simulation suite, which is based on the successful EAGLE galaxy formation model. Above ${\sim}10^{11}\, \mathrm{M}_\odot$, the simulated subhalo mass distribution and mass–vmax relation agrees well with observations, due to the presence of baryons during tidal stripping. Similar agreement is found for the lower resolution IllustrisTNG300 simulation. In combination, our results suggest that the abundance and concentration of cluster substructures are not in tension with ΛCDM, but may provide useful constraints for the refinement of baryon physics models in simulations.
Trigger and Suppression of Antiviral Defenses by Grapevine Pinot Gris Virus (GPGV): Novel Insights into Virus-Host Interaction
Authors: Tarquini Giulia , Pagliari Laura , Ermacora Paolo , Musetti Rita , Firrao Giuseppe
Published: May 2021

Grapevine Pinot gris virus (GPGV) is an emerging trichovirus that has been putatively associated with a novel grapevine disease known as grapevine leaf mottling and deformation (GLMD). Yet the role of GPGV in GLMD disease is poorly understood, since it has been detected both in symptomatic and symptomless grapevines. We exploited a recently constructed GPGV infectious clone (pRI::GPGV-vir) to induce an antiviral response in Nicotiana benthamiana plants. In silico prediction of virus-derived small interfering RNAs and gene expression analyses revealed the involvement of DCL4, AGO5, and RDR6 genes during GPGV infection, suggesting the activation of the posttranscriptional gene-silencing (PTGS) pathway as a plant antiviral defense. PTGS suppression assays in transgenic N. benthamiana 16c plants revealed the ability of the GPGV coat protein to suppress RNA silencing. This work provides novel insights on the interaction between GPGV and its host, revealing the ability of the virus to trigger and suppress antiviral RNA silencing.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Population Structure of a Worldwide Phytophthora palmivora Collection Suggests Lack of Host Specificity and Reduced Genetic Diversity in South America and the Caribbean
Authors: Guo Yufang , Sakalidis Monique L. , Torres-Londono Gabriel Andres , Hausbeck Mary K.
Published: May 2021

Phytophthora palmivora (Butler) is a highly destructive plant pathogen that infects tropical hosts worldwide, many of which are economically important crops. Despite the broad host range and wide distribution, the pathogen has displayed a considerable amount of variation in morphological characters, including virulence. However, the genetic variability at a global level, which is critical to understand the center of origin and the potential pathway(s) of introduction, was unclear. Here, we mapped the genetic variation of P. palmivora using isolates representing four regions, 15 countries, and 14 host species. We designed a large set of simple sequence repeat markers from the P. palmivora genome and picked 17 selectively neutral markers to screen 98 P. palmivora isolates. We found that P. palmivora populations from our collection generally did not cluster according to host; rather, some isolates from North America were generally distinct from all other populations. Isolates from South America and the Caribbean clustered and appeared to share ancestry with isolates from Asia. Populations from North America and Asia were the most genetically diverse, while the South American and Caribbean populations exhibited similar reduced genetic diversity. The isolates collected in various plantations in Colombia did not show host or geographic specificity. Our study brought a further understanding of this important plant pathogen, although the determination for hypothesized source of origin, spread, and evolution would need further sampling. The genomic resources developed in this study would facilitate further studies on P. palmivora diagnostics and management.
How Academic Medical Centers Can Navigate the Pandemic and Its Aftermath: Solutions for 3 Major Issues
Authors: Godley Bernard F. , Lawley Thomas J. , Rubenstein Arthur , Pizzo Philip A.
Published: May 2021

The COVID-19 crisis has seriously affected academic medical centers (AMCs) on multiple levels. Combined with many trends that were already under way pre pandemic, the current situation has generated significant disruption and underscored the need for change within and across AMCs. In this article, the authors explore some of the major issues and propose actionable solutions in 3 areas of concentration. First, the impact on medical students is considered, particularly the trade-offs associated with online learning and the need to place greater pedagogical emphasis on virtual care delivery and other skills that will be increasingly in demand. Solutions described include greater utilization of technology, building more public health knowledge into the curriculum, and partnering with a wide range of academic disciplines. Second, leadership recruiting, vital to long-term success for AMCs, has been complicated by the crisis. Pressures discussed include adapting to the dynamics of competitive physician labor markets as well as attracting candidates with the skill sets to meet the requirements of a shifting AMC leadership landscape. Solutions proposed in this domain include making search processes more focused and streamlined, prioritizing creativity and flexibility as core management capabilities to be sought, and enhancing efforts with assistance from outside advisors. Finally, attention is devoted to the severe financial impact wrought by the pandemic, creating challenges whose resolution is central to planning future AMC directions. Specific challenges include recovery of lost clinical revenue and cash flow, determining how to deal with research funding, and the precarious economic balancing act engendered by the need to continue distance education. A full embrace of telehealth, collaborative policy-making among the many AMC constituencies, and committing fully to being in the vanguard of the transition to value-based care form the solution set offered.
Combined Platelet and Erythrocyte Salvage: Evaluation of a New Filtration-based Autotransfusion Device
Authors: Mansour Alexandre , Decouture Benoit , Roussel Mikaël , Lefevre Charles , Skreko Lucie , Picard Véronique , Ouattara Alexandre , Bachelot-Loza Christilla , Gaussem Pascale , Nesseler Nicolas , Gouin-Thibault Isabelle
Published: May 2021

Background

The SAME device (i-SEP, France) is an innovative filtration-based autotransfusion device able to salvage and wash both red blood cells and platelets. This study evaluated the device performances using human whole blood with the hypothesis that the device will be able to salvage platelets while achieving a erythrocyte yield of 80% and removal ratios of 90% for heparin and 80% for major plasma proteins without inducing signification activation of salvaged cells.

Methods

Thirty healthy human whole blood units (median volume, 478 ml) were diluted, heparinized, and processed by the device in two consecutive treatment cycles. Samples from the collection reservoir and the concentrated blood were analyzed. Complete blood count was performed to measure blood cell recovery rates. Flow cytometry evaluated the activation state and function of platelets and leukocytes. Heparin and plasma proteins were measured to assess washing performance.

Results

The global erythrocyte yield was 88.1% (84.1 to 91.1%; median [25th to 75th]) with posttreatment hematocrits of 48.9% (44.8 to 51.4%) and 51.4% (48.4 to 53.2%) for the first and second cycles, respectively. Ektacytometry did not show evidence of erythrocyte alteration. Platelet recovery was 36.8% (26.3 to 43.4%), with posttreatment counts of 88 × 109/l (73 to 101 × 109/l) and 115 × 109/l (95 to 135 × 109/l) for the first and second cycles, respectively. Recovered platelets showed a low basal P-selectin expression at 10.8% (8.1 to 15.2%) and a strong response to thrombin-activating peptide. Leukocyte yield was 93.0% (90.1 to 95.7%) with no activation or cell death. Global removal ratios were 98.3% (97.8 to 98.9%), 98.2% (96.9 to 98.8%), and 88.3% (86.6 to 90.7%) for heparin, albumin, and fibrinogen, respectively. The processing times were 4.4 min (4.2 to 4.6 min) and 4.4 min (4.2 to 4.7 min) for the first and second cycles, respectively.

Conclusions

This study demonstrated the performance of the SAME device. Platelets and red blood cells were salvaged without significant impact on cell integrity and function. In the meantime, leukocytes were not activated, and the washing quality of the device prevented reinfusion of high concentrations of heparin and plasma proteins.

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Female-Specific Association of Plasma N-Terminal Pro-Brain Natriuretic Peptide With Organ Dysfunction and Prognosis in Sepsis: A Retrospective Study
Authors: Yin Shuangyi , Zhang Yijie , Guo Yu , Bai Qing , Lu Zhibo , Chen Na , Miller Edmund J. , Li Wei
Published: May 2021

Objectives:

The plasma level of N-terminal pro-brain natriuretic peptide is regulated by sex hormones. It has been controversial whether N-terminal pro-brain natriuretic peptide is a prognosis marker for sepsis. The aim of this study is to examine the sex-dependent association of plasma N-terminal pro-brain natriuretic peptide with organ dysfunction and mortality of sepsis patients.

Design:

In this retrospective study, the association between plasma N-terminal pro-brain natriuretic peptide concentration on the day of sepsis diagnosis and the degree of organ dysfunction, occurrence of septic shock, or 30-day mortality in both male and female patients was analyzed.

Setting:

This study was conducted in the Sepsis Laboratory at the Huaihe Hospital of Henan University in China.

Patients:

Diagnoses of sepsis, and septic shock, were based on the recently revised criteria (Sepsis 3.0). All sepsis patients (517) hospitalized in the respiratory ICU of the Huaihe Hospital from June 2016 to December 2019 were enrolled in this study.

Interventions:

None.

Measurements and Main Results:

No significant difference was found in the age, occurrence rate of septic shock, 30-day mortality, or degree of organ dysfunction between male and female patients. Median concentration of plasma N-terminal pro-brain Natriuretic peptide was higher by 93.48% in female than male patients. A significant association was found between N-terminal pro-brain natriuretic peptide and septic shock or 30-day mortality in female, but not in male patients of community- or hospital-acquired sepsis. N-terminal pro-brain natriuretic peptide levels correlated to functional deficiencies of the cardiac and nervous systems, only in female patients.

Conclusions:

The plasma N-terminal pro-brain natriuretic peptide level is a female-specific prognosis indicator of septic shock and mortality.
Impact of Height Estimation on Tidal Volume Calculation for Protective Ventilation—A Prospective Observational Study
Authors: Alexandre André R. , Rocha Filipa R. , Landeiro Luís , Mota Pedro , Jones Joana , Gomes José A.
Published: May 2021

Objectives:

The current standard of care to deliver invasive mechanical ventilation support is the protective ventilation approach. One pillar of this approach is the limitation of tidal volume to less than 6 mL/Kg of predicted body weight. Predicted body weight is calculated from patient’s height. Yet, little is known about the potential impact of errors arising from visual height estimation, a common practice, to calculate tidal volumes. The aim of this study was to evaluate that impact on tidal volume calculation to use during protective ventilation.

Design:

Prospective observational study.

Setting:

An eight-bed polyvalent ICU.

Patients:

Adult patients (≥ 18 yr).

Interventions:

None.

Measurements and Main Results:

Tidal volumes were calculated from visual height estimates made by physicians, nurses, and patients themselves and compared with tidal volumes calculated from measured heights. Comparisons were made using the paired t test. Modified Bland-Altman plots were used to assess agreement between height estimates and measurements. One-hundred patients were recruited. Regardless of the height estimator, all the mean tidal volumes would be greater than 6 mL/Kg predicted body weight (all p < 0.001). Additionally, tidal volumes would be greater than or equal to 6.5 mL/Kg predicted body weight in 18% of patients’ estimates, 25% of physicians’ estimates, and 30% of nurses’ estimates. Patients with lower stature (< 165 cm), older age, and surgical typology of admission were at increased risk of being ventilated with tidal volumes above protective threshold.

Conclusions:

The clinical benefit of the protective ventilation strategy can be offset by using visual height estimates to calculate tidal volumes. Additionally, this approach can be harmful and potentially increase mortality by exposing patients to tidal volumes greater than or equal to 6.5 mL/Kg predicted body weight. In the interest of patient safety, every ICU patient should have his or her height accurately measured.
Microplastics pollution of seafoods and processed seafood products
distributed in Incheon area
Authors: Kim Ji Sun , Whang Kyoung Hwa , Jang Seung Eun , Song Sung Min , Im Yun Sun , Han Young Sun , Heo Myung Je
Published: May 2021

This study was intended to obtain the basic data for a wide range of
microplastics (MPs) contamination studies. The contamination of MPs in seafood
and processed seafood products distributed in Incheon area was quantified. For
this, 51 seafoods and 50 processed seafood products in Incheon were collected
randomly from January 2019 to October 2019, and the abundance, size, and type of
MPs in the samples were identified by FT-IR spectroscopy. The average MPs
content was 1.06±3.38 MPs/g and 0.89±1.29 MPs/g in seafoods and
processed seafood products, respectively. In both samples, MPs of 100-500
μm accounted for the majority of the particles, with the most common MPs
as polyethylene (PE) and polypropylene (PP). However, the level of contamination
of MPs in each of the samples was significantly different, even for the same
species. For more accurate analysis of MPs contamination in seafoods and
processed seafood products, specific information such as habitat, environment,
market supply, regional source, and production process might be required. In
addition, extensive and continuous accumulation of data is necessary for them to
be used as the basic data with a standardized method for analyzing MPs.
Effect of anticaking agents on caking and quality characteristics
of garlic cream powder sauce
Authors: Kim Jiyoon , Choi Ji-Young , Kim Jungsoo , Jeong Saeul , Lee Si-Hyeon , Oh Yujin , Moon Kwang-Deog
Published: May 2021

The caking of powder sauce is a common problem during food processing and
storage, and leads to critical issues in products quality. In this study, to
address the problem of caking of garlic cream powder sauce, an optimal sauce
mixing ratio was selected, and the quality characteristics was analyzed.
Moisture content, hygroscopicity, and caking degree were the lowest with 2%
silicon dioxide and 2% microcrystalline cellulose treatment (S2C2). In addition,
the normalized turbidity and quality characteristics of the garlic cream powder
sauce were improved. Anticaking agents (silicon dioxide and microcrystalline
cellulose) did not significantly affect the sensory quality characteristics,
such as viscosity, color value, flavor, and mouth-feel of the garlic cream
powder sauce, and neither did they affect the consumer preference. Thus, it was
concluded that S2C2 treated with a combination of silicon dioxide and
microcrystalline cellulose during long-term storage is the most effective in
preventing caking and maintaining the quality characteristics. Upon examination
with a usable range of food additives, it was found that it can also be used as
a reference for a particular method for improving the food processing and
preservation techniques in the powder sauce industry.
Quality and antioxidant characteristics of ‘Yakju’
prepared with pigmented rice flour ‘Nuruk’
Authors: Han Hong-Bi , Lee Hee-Won , Kim Bok-Seon , Kim Cheol-Min , Woo Hyo-Gyeong , Jeong Jae-Hee , Kim So-Mang , Huh Chang-Ki
Published: May 2021

A simple technology to manufacture ‘Nuruk’ with pigmented rice and
‘Yakju’ with improved quality and functionality was developed.
Yakju (designated WY and PY, respectively) was prepared with white rice flour
Nuruk (WN) and pigmented rice flour Nuruk (PN), and their qualities were
compared. The enzyme activities of Nuruk revealed that PN had higher
β-amylase activity (1,186.67 Saccharogenic acitivty, SP/g) and higher
protease activity (378.90 tyrosine mg/min) than WN. During 11 days of
fermentation, the pH of PY was steady in the range of 4.77-4.58, whereas the pH
(4.82) of WY decreased to 3.90 on day 3 of fermentation and then increased to
similar pH of PY until the fermentation was completed. The titratable acidities
of PY and WY increased to 0.40-0.48%. The ethanol content of PY and WY increased
to 13.43% ad 13.23%, respectively, on day 5, after then PY showed higher ethanol
content than WY until day 11 of fermentation. The organic acid content of PY
(1,225.87 mg%) was higher than that of WY (1,021.69 mg%). The antioxidant
activities of PY were twice as high as those of WY, and the total polyphenolics
and total flavonoid contents of PY were also higher (35.96 mg% and 19.01 mg%,
respectively) than those of WY (16.29 mg% and 6.36 mg%, respectively). Sensory
scores on color, flavor and taste, and overall preference were higher in PY than
in WY.
Quality characteristics and antioxidant activity of
‘Hwajeon’ prepared using tomato powder
Authors: Jung Yoon-Jung , Hwang Eun-Sun
Published: May 2021

The present study was conducted to investigate the quality characteristics and
antioxidant activities of ‘Hwajeon’ that was prepared by replacing
glutinous rice flour with 0, 4, 8, and 12% of tomato powder. The moisture
content in ‘Hwajeon’ was noted to be 42.60-46.59%, with the
highest moisture content present in ‘Hwajeon’ without the added
tomato powder. The addition of tomato powder revealed a decreasing tendency of
the moisture content compared to that in the control group. There was no
statistically significant difference in the crude protein levels of
‘Hwajeon’, based on the content of added tomato powder; however,
the contents of ash and crude fat increased with increasing amounts of tomato
powder. The sugar content in ‘Hwajeon’ increased in accordance
with the addition of tomato powder, whereas the pH tended to decrease. Regarding
the determination of chromaticity, the value of L* decreased and those of
a* increased with increasing levels of tomato powder. The total
polyphenol and total flavonoid contents increased with increasing levels of
tomato powder. The antioxidant properties investigated by evaluating the DPPH
and ABTS radical scavenging activities and reducing powder, were significantly
higher than those of the control, and proportionally increased with increasing
contents of tomato powder. These results suggest that the addition of 4-12% of
tomato powder could be applied in the preparation of
‘Hwajeon’.
Artificial Intelligence Sepsis Prediction Algorithm Learns to Say “I don’t know”
Authors: Shashikumar Supreeth P. , Wardi Gabriel , Malhotra Atul , Nemati Shamim
Published: May 2021

Sepsis is a leading cause of morbidity and mortality worldwide. Early identification of sepsis is important as it allows timely administration of potentially life-saving resuscitation and antimicrobial therapy. We present COMPOSER (COnformal Multidimensional Prediction Of SEpsis Risk), a deep learning model for the early prediction of sepsis, specifically designed to reduce false alarms by detecting unfamiliar patients/situations arising from erroneous data, missingness, distributional shift and data drifts. COMPOSER flags these unfamiliar cases as ‘indeterminate’ rather than making spurious predictions. Six patient cohorts (515,720 patients) curated from two healthcare systems in the United States across intensive care units (ICU) and emergency departments (ED) were used to train and externally and temporally validate this model. In a sequential prediction setting, COMPOSER achieved a consistently high area under the curve (AUC) (ICU: 0.925–0.953; ED: 0.938–0.945). Out of over 6 million prediction windows roughly 20% and 8% were identified as ‘indeterminate’ amongst non-septic and septic patients, respectively. COMPOSER provided early warning within a clinically actionable timeframe (ICU: 12.2 [3.2 22.8] and ED: 2.1 [0.8 4.5] hours prior to first antibiotics order) across all six cohorts, thus allowing for identification and prioritization of patients at high risk for sepsis.
Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain
Authors: Desai Mitul , Sharma Jitendra , Slusarczyk Adrian L. , Chapin Ashley , Wiśniowska Agata , Ohlendorf Robert , Sur Mriganka , Jasanoff Alan
Published: May 2021

Molecular imaging could have great utility for detecting, classifying, and guiding treatment of brain disorders, but existing probes offer limited capability for assessing relevant physiological parameters. Here we describe a potent approach for noninvasive mapping of cancer-associated enzyme activity using a molecular sensor that acts on the vasculature, providing a diagnostic readout via local changes in hemodynamic image contrast. The sensor is targeted at the fibroblast activation protein (FAP), an extracellular dipeptidase and clinically relevant biomarker of brain tumor biology. Optimal FAP sensor variants were identified by screening a series of prototypes for responsiveness in a cell-based bioassay. The best variant was then applied for quantitative neuroimaging of FAP activity in rats, where it reveals nanomolar-scale FAP expression by xeno-grafted tumor cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.
A comprehensive landscape of 60S ribosome biogenesis factors
Authors: Sailer Carolin , Jansen Jasmin , Erzberger Jan P. , Stengel Florian
Published: May 2021

Eukaryotic ribosome biogenesis is facilitated and regulated by numerous ribosome biogenesis factors (RBFs). High-resolution cryo-EM maps have defined the molecular interactions of RBFs during maturation, but many transient and dynamic interactions, particularly during early assembly, remain uncharacterized. Using quantitative proteomics and crosslinking coupled to mass spectrometry (XL-MS) data from a extensive set of pre-ribosomal particles, we derived a comprehensive and time-resolved interaction map of RBF engagement during 60S maturation. A novel filter that efficiently eliminates false positive interactions and integration of our MS data with known structural information allowed us to localize 22 unmapped RBFs to specific biogenesis intermediates and to identify 9 proteins that represent potentially new RBFs. Our analysis reveals an extensive interaction network for the casein kinase complex in 60S maturation and elucidates the timing and molecular function of 60S engagement by DEAD-box ATPases. Our data provide a powerful resource for future studies of 60S ribosome biogenesis.
CRISPR activation and interference screens in primary human T cells decode cytokine regulation
Authors: Schmidt Ralf , Steinhart Zachary , Layeghi Madeline , Freimer Jacob W. , Nguyen Vinh Q. , Blaeschke Franziska , Marson Alexander
Published: May 2021

The pathways that regulate cytokine responses in T cells are disrupted in autoimmunity, immune deficiencies, and cancer, and include immunotherapy targets. Systematic discovery of cytokine regulators requires both loss-of-function and gain-of-function studies, which have been challenging in primary human cells. We now have accomplished genome-wide pooled CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) screens in primary human T cells to map gene networks controlling Interleukin-2 and Interferon-γ production. Arrayed CRISPRa confirmed key hits and enabled multiplexed T cell secretome characterization, revealing reshaped cytokine responses driven by individual regulators. CRISPRa uncovered genes not canonically expressed in T cells, including the transcription factor FOXQ1, whose overexpression promoted the expression of most cytokines, while selectively dampening T helper 2 (Th2) cytokines. Paired CRISPRa and CRISPRi screens reveal signaling components that tune critical immune cell functions, which could inform design of future immunotherapies.
Neocortical Localization and Thalamocortical Modulation of Neuronal Hyperexcitability in Fragile X Syndrome
Authors: Pedapati Ernest V , Schmitt Lauren M. , Ethridge Lauren E. , Liu Rui , Smith Elizabeth , Sweeney John A , Shaffer Rebecca C. , Dominick Kelli C. , Gilbert Donald L. , Wu Steve W. , Horn Paul S. , Binder Devin , Lamy Martine , Axford Megan , Miyakoshi Makoto , Erickson Craig A.
Published: May 2021

Fragile X Syndrome (FXS) is a monogenetic form of intellectual disability and autism in which well-established knockout (KO) animal models point to neuronal hyperexcitability and abnormal gamma-frequency physiology as a basis for key disorder features. Translating these findings into patients may identify tractable treatment targets. Using source modeling of resting-state electroencephalography data, we report novel findings in FXS, including 1) increases in localized gamma activity, 2) pervasive changes of theta/alpha activity, indicative of disrupted thalamocortical modulation coupled with elevated gamma power, 3) stepwise moderation of these abnormalities based on female sex, and 4) relationship of this physiology to intellectual disability and neuropsychiatric symptoms. Our observations extend findings in Fmr1-/- KO mice to patients with FXS and raise a novel role for disrupted thalamocortical modulation in local hyperexcitability. This systems-level mechanism has received limited preclinical attention but has significant implications for understanding fundamental disease mechanisms.
One Hundred and Fifty Years of Warming on Caribbean Coral Reefs
Authors: Bove Colleen B. , Mudge Laura , Bruno John F.
Published: May 2021

Anthropogenic climate change is rapidly altering the characteristics and dynamics of biological communities. This is especially apparent in marine systems as the world’s oceans are warming at an unprecedented rate, causing dramatic changes to coastal marine systems, especially on coral reefs of the Caribbean. We used three complementary ocean temperature databases (HadISST, Pathfinder, and OISST) to quantify change in thermal characteristics of Caribbean coral reefs over the last 150 years (1871–2020). These sea surface temperature (SST) databases included combinedin situand satellite-derived SST (HadISST, OISST), as well as satellite-only observations (Pathfinder) at multiple spatial resolutions. We also compiled a Caribbean coral reef database identifying 5,326 unique reefs across the region. We found that Caribbean reefs have warmed on average by 0.20 °C per decade since 1987, the calculated year that rapid warming began on Caribbean reefs. Further, geographic variation in warming rates ranged from 0.17 °C per decade on Bahamian reefs to 0.26 °C per decade on reefs within the Southern and Eastern Caribbean ecoregions. If this linear rate of warming continues, these already threatened ecosystems would warm by anadditional1.6 °C on average by 2100. We also found that marine heatwave (MHW) events are increasing in both frequency and duration across the Caribbean. Caribbean coral reefs now experience on average 5 MHW events annually, compared to 1 per year in the early 1980s. Combined, these changes have caused a dramatic shift in the composition and function of Caribbean coral reef ecosystems. If reefs continue to warm at this rate, we are likely to lose even the remnant Caribbean coral reef communities of today in the coming decades.
Protein contact map prediction using multiple sequence alignment dropout and consistency learning for sequences with fewer homologs
Authors: Liu Xuyang , Jin Lei , Gao Shenghua , Zhao Suwen
Published: May 2021

The prediction of protein contact map needs enough normalized number of effective sequence (Nf) in multiple sequence alignment (MSA). When Nf is small, the predicted contact maps are often not satisfactory. To solve this problem, we randomly selected a small part of sequence homologs for proteins with large Nf to generate MSAs with small Nf. From these MSAs, input features were generated and were passed through a consistency learning network, aiming to get the same results when using the features generated from the MSA with large Nf. The results showed that this method effectively improves the prediction accuracy of protein contact maps with small Nf.
Patterns of serum immune biomarkers during elephant endotheliotropic herpesvirus viremia in Asian and African elephants
Authors: Edwards Katie L. , Latimer Erin M. , Siegal-Willott Jessica , Kiso Wendy , Padilla Luis R. , Sanchez Carlos R. , Schmitt Dennis , Brown Janine L.
Published: May 2021

Hemorrhagic disease (HD) caused by a group of elephant endotheliotropic herpesviruses (EEHV) is one of the leading causes of death for young elephants in human care. These viruses are widespread and typically persist latently in adult elephants with no negative effects; however, in juvenile Asian and more recently young African elephants, the onset of disease can be rapid and the mortality rate high. Measuring biomarkers associated with the immune response could be beneficial to understanding underlying disease processes, as well as the management of infection and HD. The goal of this study was to measure acute phase proteins and cytokines in serum collected from elephants infected with EEHV (13 Asian and 1 African) and compare concentrations according to presence, severity and outcome of disease. Serum amyloid A (SAA) and haptoglobin (HP) were higher in elephants with EEHV viremia than those without; concentrations increased with increasing viral load, and were higher in fatal cases compared to those that survived. In Asian elephants, SAA was also higher during EEHV1 viremia compared to EEHV5. Cytokine concentrations were typically low, and no statistical differences existed between groups, perhaps due to insufficient assay sensitivity in this age group. However, in individuals with detectable levels, longitudinal profiles indicated changes in tumor necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) that may reflect an immune response to EEHV infection. These results highlight the potential benefit of measuring circulating biomarker concentrations, such as APPs and cytokines, to improve our understanding of EEHV viremia and HD, assist with monitoring the progression of disease and determining the impact of interventions.
Gaps in global wildlife trade monitoring leave amphibians vulnerable
Authors: Hughes Alice C. , Marshall Benjamin M. , Strine Colin T.
Published: May 2021

As the biodiversity crisis continues, we must redouble efforts to understand and curb pressures pushing species closer to extinction. One major driver is the unsustainable trade of wildlife. Trade in internationally regulated species gains the most research attention, but this only accounts for a minority of traded species and we risk failing to appreciate the scale and impacts of unregulated legal trade. Despite being legal, trade puts pressure on wild species via: direct collection, introduced pathogens, and invasive species. Smaller species-rich vertebrates, such reptiles, fish, and amphibians, may be particularly vulnerable to trading because of gaps in regulations, small distributions, and demand of novel species. Here we combine data from five sources: online web searches in six languages, CITES trade database, LEMIS trade database, IUCN assessments, and a recent literature review, to characterise the global trade in amphibians, and also map use by purpose including meat, pets, medicinal and for research. We show that 1,215 species are being traded (17% of amphibian species), almost three times previous recorded numbers, 345 are threatened, and 100 data deficient or unassessed. Traded species origin hotspots include South American, China, and Central Africa; sources indicate 42% of amphibians are taken from the wild. Newly described species can be rapidly traded (mean time lag of 6.5 years), including threatened and unassessed species. The scale and limited regulation of the amphibian trade, paired with the triptych of connected pressures (collection, pathogens, invasive species), warrants a re-examination of the wildlife trade status-quo, application of the precautionary principle in regards to wildlife trade, and a renewed push to achieve global biodiversity goals.
Functional plasticity coupled with structural predispositions in auditory cortex shape successful music category learning
Authors: Mankel Kelsey , Shrestha Utsav , Tipirneni-Sajja Aaryani , Bidelman Gavin M.
Published: May 2021

Categorizing sounds into meaningful groups helps listeners more efficiently process the auditory scene and is a foundational skill for speech perception and language development. Yet, how auditory categories develop in the brain through learning, particularly for nonspeech sounds, is not well understood. Here, we asked musically naïve listeners to complete a brief (∼20 min) training session where they learned to identify sounds from a nonspeech continuum (minor-major 3rd musical intervals). We used multichannel EEG to track behaviorally relevant neuroplastic changes in the auditory event-related potentials (ERPs) pre- to post-training. To rule out mere exposure-induced changes, neural effects were evaluated against a control group of 14 nonmusicians who did not undergo training. We also compared individual categorization performance with structural volumetrics of bilateral primary auditory cortex (PAC) from MRI to evaluate neuroanatomical substrates of learning. Behavioral performance revealed steeper (i.e., more categorical) identification functions in the posttest that correlated with better training accuracy. At the neural level, improvement in learners’ behavioral identification was characterized by smaller P2 amplitudes at posttest, particularly over right hemisphere. Critically, learning-related changes in the ERPs were not observed in control listeners, ruling out mere exposure effects. Learners also showed smaller and thinner PAC bilaterally, indicating superior categorization was associated with structural differences in primary auditory brain regions. Collectively, our data suggest successful auditory categorical learning of nonspeech sounds is characterized by short-term functional changes (i.e., greater post-training efficiency) in sensory coding processes superimposed on preexisting structural differences in bilateral auditory cortex.
Phage-resistant bacteria reveal a role for potassium in root colonization
Authors: Tzipilevich Elhanan , Benfey Philip N.
Published: May 2021

Bacteriophage predation is an important factor in bacterial community dynamics and evolution. Phage-bacteria interaction has mainly been studied in lab cultures, while dynamics in natural habitats, and especially in the plant root niche are underexplored. To better understand this process, we characterized infection of the soil bacterium B. subtilis NCBI 3610 by the lytic phage SPO1 during growth in LB medium and compared it to root colonization. Resistance in vitro was primarily through modification of the phage receptor. However, this type of resistance reduced the ability to colonize the root. From a line that survived phage infection while retaining the ability to colonize the root, we identified a plant-specific phage resistance mechanism involving potassium (K+) ion influx modulation and enhanced biofilm formation.
A rapid method to quantify small-scale vegetation patch structure to complement conventional quadrat surveys
Authors: Butler Liam , Sanderson Roy A.
Published: May 2021

Aims

Vegetation sampling typically involves the use of quadrats, often 1m2, to estimate species cover-abundance. Such surveys do not generally record small-scale vegetation patch structure at sub-quadrat scales, for example 10 cm2. Here we test a simple method to quantify patch structure that complements conventional techniques. We compare the two methods, and analyse metrics derived from small-scale patch surveys with environment / management data.

Location

Northumberland, United Kingdom

Methods

We recorded cover-abundance of all species in an upland moor with 1m2 quadrats. These were divided into 100 ‘sub-quadrats’, 10 × 10 cm, and the dominant and subdominant species identified. Patch metrics (number, area and shape) for individual species recorded as dominant or subdominant in the sub-quadrat survey were analysed using multivariate generalised linear models with environmental and management data. Sub-quadrat data were also aggregated for each quadrat, to create species composition data. The two sets of compositional data, from whole-quadrat and sub-quadrat aggregations, were compared via Procrustes rotation of ordination scores.

Results

Patch number, area and shape for dominant and subdominant species were all significantly affected by soil pH, soil water content, slope and elevation. Effects of proximity to sheep tracks and drainage ditches were less consistent amongst species. Ordinations of vegetation data from conventional and sub-quadrats were similar, with significant Procrustes R-squared of 67% and 70% for dominant and subdominant species respectively.

Conclusions

Sub-quadrat surveys can easily be used to complement existing whole-quadrat surveys at little cost in time or resources. Their patch metrics can provide additional insights into the environmental and management drivers that may affect the growth of individual plants or clumps, potentially in relation to plant traits, and thus alter the overall community composition. The methods we describe can readily be adapted to other sizes of quadrats and sub-quadrats in a wide range of vegetation communities.
cAMP controls a trafficking mechanism that directs the neuron specificity and subcellular placement of electrical synapses
Authors: Palumbos Sierra , Skelton Rachel , McWhirter Rebecca , Mitchell Amanda , Swann Isaiah , Heifner Sydney , Von Stetina Steve , Miller David M
Published: May 2021

Electrical synapses are established between specific neurons and within distinct subcellular compartments, but the mechanisms that direct gap junction assembly in the nervous system are largely unknown. Here we show that a transcriptional program tunes cAMP signaling to direct the neuron-specific assembly and placement of electrical synapses in the C. elegans motor circuit. For these studies, we use live cell imaging to visualize electrical synapses in vivo and a novel optogenetic assay to confirm that they are functional. In VA motor neurons, the UNC-4 transcription factor blocks expression of cAMP antagonists that promote gap junction miswiring. In unc-4 mutants, VA electrical synapses are established with an alternative synaptic partner and are repositioned from the VA axon to soma. We show that cAMP counters these effects by driving gap junction trafficking into the VA axon for electrical synapse assembly. Thus, our experiments in an intact nervous system establish that cAMP regulates gap junction trafficking for the biogenesis of electrical synapses.