bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes and composition of microbial community during aerobic composting of household food waste
Authors: Jin Zhihua , Lu Tong , Feng Wenjun , Jin Qinchao , Wu Zhige , Yang Yu
Published: March 2021

In order to explore the effect of added bacteria on microbial community and determine the dominant bacteria in the aerobic composting process of household food waste (HFW), two groups of HFW composting experiments were conducted for 30 days. The final degradation rates of the two groups were 69.95% (group A, natural composting) and 73.52% (Group C, composting with added bacteria), respectively. 16S rRNA high-throughput sequencing was used to analyze the changes of microbial community in the composting process. As the result displays, at the classification of phylum level, the relatively abundant bacteria of two groups wereFirmicutes, ProteobacteriaandCyanobacteria. At the classification of genus level,Pediococcusis the dominant bacteria of group A, which performed better in maintaining the microbial community stable in the later stage of composting, whileWeissellaaccounted for a relatively large proportion of group C and behaved well in promoting the final degradation rate of composting. The proportion ofOchrobactrumin the early stage of group C is considerable and it is closely related to the removal of odour during composting. The relative abundance of added bacteria was always in a rather low level, suggested that the way they affect the composting process is to change the proportion of dominant bacteria in different stage of composting. This experiment provides an important reference for improving the microbial degradation efficiency of HFW.

IMPORTANCE

In recent years, food waste has gradually become a global problem, the annual waste of food is as high as 1.3 billion tons. FW, especially HFW, as a high content of organic matter waste, has a pretty good recycling value. So how to deal with and recycle it efficiently, quickly and conveniently becomes more and more important. Among many treatment and recovery methods, microbial treatment (including anaerobic digestion and aerobic composting) has gradually become a research hotspot due to its advantages of low pollution and low energy consumption, and microorganisms play a crucial role in these process.

In this study we use 16S rRNA high-throughput sequencing method to explore aerobic composting of HFW. The purpose of this study is to find out the dominant bacteria which can improve the degradation efficiency, remove the odor and prolong the treatment cycle, and then provide further theoretical reference for future HFW related research.
Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-ResistantStaphylococcus aureus(MRSA)
Authors: Huang David B. , Gaukel Eric , Kerzee Nancy , Borroto-Esoda Katyna , Lowry Simon , Xiong Yan Q. , Abdelhady Wessam , Bayer Arnold S.
Published: March 2021

MRSA endovascular infections are frequently recalcitrant to treatment with standard-of-care antibiotics. Anti-staphylococcal phage lysins represent important candidate adjunctive agents against invasive MRSA infections because of both their microbicidal and anti-biofilm properties. We utilized the rabbit model of aortic valve infective endocarditis (using the prototype MRSA strain, MW2) to examine the combined efficacy of the lysin, LSVT-1701, plus daptomycin. LSVT-1701 was given at two dose-regimens (32.5 mg/kg and 50 mg/kg) with different dose-durations (single dose vs daily dose for 2 d vs daily dose for 4 d); daptomycin was given at a sub-lethal daily dose of 4 mg/kg for 4 d to maximize potential synergistic interaction outcomes. The combination of LSVT-1701 plus daptomycin was highly effective at reducing target tissue MRSA counts (cardiac vegetations, kidneys, and spleen), especially when the lysin was given for multiple days and/or at higher daily doses. Of importance, when given for four daily doses, both lysin dose-regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as adjunctive therapy for the treatment of invasive MRSA infections.
Hypothyroidism and its influence in the development of Metabolic Syndrome (MetS)
Authors: Pinheiro D. J. L. L. , Santos T. C. , Spacini G. R. , Guerra A. P. S. , Bacci M. C. L , Nemecek M. G , Oliveira J. R. C. , Dantas R. L. M. , Cortez P. J. O. , Faber J.
Published: March 2021

Background

Metabolic syndrome (MetS) is a complex disorder that affects the cardiovascular system and it is generally associated with mental and metabolic health issues. To diagnose MetS it is essential to identify certain comorbidities related to cardiovascular diseases. Hypothyroidism, for instance, is a common disorder that reduces the basal metabolism, leading to the development of other diseases. Therefore, it is important to know how hypothyroidism can increase the chances of MetS.

Objectives

To assess whether there is an increased risk of patients with hypothyroidism developing MetS given the association of different comorbidities in a sample of an urban Brazilian population.

Methods

This was an observational, exploratory and retrospective study of patients diagnosed with hypothyroidism (using levothyroxine for hormonal reposition therapy).The incidence and prevalence of four specific comorbidities were quantified by histograms, and all comparisons were performed by using joint and conditional probabilities with their respective confident intervals.

Results

Consistent with the literature, our results also showed that there is a prevalence in women (79%) and in elderly patients (80%). Moreover, it also indicated that around 64% of the patients were women aged over 60 years and at least one comorbidity was associated with them. By analyzing the risk group for MetS, with two comorbidities, the combination with higher chances of acquiring a new comorbidity were Systemic arterial hypertension (SAH) and Diabetes Mellitus (DM), in this sample.

Conclusion

Our results indicate that hypothyroidism can increase the chances to develop MetS or may worsen its effects due to the association of common comorbidities present in both cases. Keywords: metabolic syndrome, hypothyroidism, comorbidities, statistical analysis.
Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes
Authors: Vuong Nguyen Lam , Lam Phung Khanh , Ming Damien Keng Yen , Duyen Huynh Thi Le , Nguyen Nguyet Minh , Tam Dong Thi Hoai , Kien Duong Thi Hue , Chau Nguyen Van Vinh , Chanpheaktra Ngoun , Lum Lucy Chai See , Pleités Ernesto , Simmons Cameron P. , Rosenberger Kerstin , Jaenisch Thomas , Bell David , Acestor Nathalie , Halleux Christine , Olliaro Piero L. , Wills Bridget A. , Geskus Ronald B. , Yacoub Sophie
Published: March 2021

Background

Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).

Methods

We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.

Results

On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.

Conclusions

Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.

Summary of the main point

Higher levels of any of VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP on illness days 1-3 increased the risk of developing severe/moderate dengue. The relationships differed between children and adults and some changed when assessed together.
Youth-oriented packaging and the demand for e-liquids: Evidence from data scraped from Amazon in the United Kingdom
Authors: Lawani Abdelaziz , Georgette Owusu-Amankwah , Anna-Liisa Ihuhwa
Published: March 2021

To address the threat e-cigarettes poses to public health, especially among youths, the Food and Drug Administration (FDA) issued a policy in 2020 that regulates the sale and distribution of e-cigarettes with fruit and mint flavors. Such flavors are alleged to lure youth into smoking and can increase the likelihood for addiction to other drugs. However, this regulation does not address packaging that can have a similar effect on the demand for e-cigarettes products. Indeed, certain e-liquids use youth-oriented (kiddish, cartoonish, and colorful) packaging which are attractive to youth but may also induce a no-harm perception among e-liquids users. In this paper, we examine the impact of the youth-oriented packaging on e-liquid sales. Using data scraped from Amazon, the results of our analysis reveal that youth-oriented packaging increases the sale of e-liquids. In addition, the demand for e-liquids is inelastic and the percentage of propylene glycol (PG), the rating, and the sentiment in the online reviews left by previous buyers also influence the sale of e-liquids. This research suggests that besides fruit and mint flavors, the policy goal of reducing use among youth should also include packaging. The analysis finds that taxation policies to raise prices of e-liquids will not affect appreciably the demand for e-liquids. Policies for e-liquids control should focus on designing packaging that reduces the no- or low-risk perception.
The effect of CYP3A4 genetic polymorphisms on the pharmacokinetics of calcineurin inhibitors in renal transplant recipients: a systematic review and meta-analysis protocol
Authors: Salehi Saeedeh , Abedini Fateme , Shahi Abbas , Afzali Shima , Dashti-Khavidaki Simin , Amirzargar Ali Akbar
Published: March 2021

Background

Calcineurin inhibitors (CNIs) are metabolized by CYP3A4. Polymorphisms in the CYP3A4 gene alter the activity of CYP3A4 protein and therefore affect the CNIs concentrations. Results of studies that investigated the association between CYP3A4 polymorphisms and CNIs pharmacokinetics are controversial. Therefore, this systematic review and meta-analysis will evaluate the effect of CYP3A4 polymorphisms on the pharmacokinetics of CNIs in renal transplant recipients.

Method

This protocol is developed according to the PRISMA-P guideline and registered in PROSPERO (CRD42020145219). The MeSH/Emtree terms of CYP3A4 polymorphisms and CNIs pharmacokinetics in PECO-based question will be obtained from the comprehensive literature search on PubMed/MEDLINE, Scopus, Web of Science, Embase, CENTRAL, and ProQuest without any language limitation from 1 January 1998 to 31 March 2021. Google Scholar search engine, registries, conference papers, and key journals will also be searched. Screening, selection, quality assessment, and data extraction will be performed by two independent reviewers. Statistical heterogeneity will be calculated by the Q Cochrane test and I2statistic. Publication bias and sensitivity analysis will be evaluated by appropriate tests.

Results and conclusion

According to the meta-analysis of the aggregated data from the relevant primary studies, the association between CYP3A4 polymorphisms and CNIs pharmacokinetics will be reported, which possibly help the pharmacogenetic-guided dosing approach.
Cell cycle-independent integration of stress signals promotes Non-G1/G0 quiescence entry
Authors: Argüello-Miranda Orlando , Marchand Ashley , Kennedy Taylor , Russo Marielle AX , Noh Jungsik
Published: March 2021

Cellular quiescence is a non-proliferative state required for cell survival under stress and during development. In most quiescent cells, proliferation is stopped in a reversible state of low Cdk1 kinase activity; in many organisms, however, quiescent states with high Cdk1 activity can also be established through still uncharacterized stress or developmental mechanisms. Here, we used a microfluidics approach coupled to phenotypic classification by machine learning to identify stress pathways associated with starvation-triggered high-Cdk1 quiescent states inSaccharomyces cerevisiae. We found that low- and high-Cdk1 quiescent states shared a core of stress-associated processes, such as autophagy, protein aggregation, and mitochondrial upregulation, but differed in the nuclear accumulation of the stress transcription factors Xbp1, Gln3, and Sfp1. The decision between low- or high-Cdk1 quiescence was controlled by cell cycle-independent accumulation of Xbp1, which acted as a time-delayed integrator of the duration of stress stimuli. Our results show how cell cycle-independent stress-activated factors promote cellular quiescence outside of G1/G0.
GPR15 in colon cancer development and anti-tumor immune responses
Authors: NamKoong Hong , Lee Bomi , Swaminathan Gayathri , Koh Seong-Joon , Rogalla Stephan , Mikhail David , Habtezion Aida
Published: March 2021

G protein-coupled receptor 15 (GPR15) is a chemoattractant receptor which in response to its ligand, C10orf99/GPR15L, promotes colon homing of T cells in health and colitis. The functional role of GPR15 in colon cancer is largely unexplored, motivating our current studies using murine colon cancer models and human colorectal cancer (CRC) tissues. Our initial analysis of human CRC specimen revealed significant reduction in GPR15 expression and frequency of GPR15+immune cells in tumors compared to ‘tumor-free’ surgical margins. In the AOM/DSS murine model of colitis associated colon cancer (CAC), we observed increased colonic polyps/tumor burden and lower survival rate inGpr15-deficient (KO) compared toGpr15-sufficient (Het) mice. Analysis of immune cell infiltrates in the colonic polyps showed significantly decreased CD8+T cells and increased IL-17+CD4+and IL-17+CD8+T cells inGpr15-KO than in Het mice. GPR15 deficiency thus alters the immune environment in colonic polyps to mitigate T cell-mediated anti-tumor responses resulting in severe disease. Consistent with a protective role of GPR15, administration of GPR15L to established tumors in the MC38 CRC mouse model increased CD45+cell infiltration, enhanced TNFαexpression on CD4+and CD8+T cells at the tumor site and dramatically reduced tumor burden. Our findings highlight an important, unidentified role of the GPR15-GPR15L axis in promoting a tumor-suppressive immune microenvironment and unveils a novel, colon-specific therapeutic target for CRC.
Increased Risk for Cerebral Small Vessel Disease is Associated with Quantitative Susceptibility Mapping in HIV Infected and Uninfected Individuals
Authors: Murray Kyle D. , Uddin Md Nasir , Tivarus Madalina E. , Sahin Bogachan , Wang Henry Z. , Singh Meera V. , Qiu Xing , Wang Lu , Spincemaille Pascal , Wang Yi , Maggirwar Sanjay B. , Zhong Jianhui , Schifitto Giovanni
Published: March 2021

The aim of this study was to assess in the context of cerebral small vessel disease (CSVD), cardiovascular risk factors and white matter hyperintensities (WMHs) were associated with brain tissue susceptibility as measured by quantitative susceptibility mapping (QSM). Given that CSVD is diagnosed by the presence of lacunar strokes, periventricular and deep WMHs, increased perivascular spaces, and microbleeds, we expected that QSM could capture changes in brain tissue due to underlying CSVD pathology. We compared a cohort of 101 HIV-infected individuals (mean age (SD) = 53.2 (10.9) years) with mild to moderate cardiovascular risk scores, as measured by the Reynold’s risk score, to 102 age-matched controls (mean age (SD) = 50.3 (15.7) years) with similar Reynold scores. We performed brain MRI to assess CSVD burden by acquiring 3D T1-MPRAGE, 3D FLAIR, 2D T2-TSE, and mGRE for QSM. We found that signs of CSVD are significantly higher in individuals with HIV-infection compared to controls and that WMH volumes are significantly correlated with age and cardiovascular risk scores. Regional QSM was associated with cardiovascular risk factors, age, sex, and WMH volumes but not HIV status. These results suggest that QSM may be an early imaging marker reflective of alterations in brain microcirculation.
Svep1 stabilizes developmental vascular anastomosis in reduced flow conditions
Authors: Coxam Baptiste , Padberg Yvonne , Maier Katja , Jung Simone , Bartels-Klein Eireen , Szymborska Anna , Finotto Lise , Helker Christian S.M. , Stainier Didier Y.R. , Schulte-Merker Stefan , Gerhardt Holger
Published: March 2021

We report the discovery that flow and Svep1 are modulator of vessel anastomosis during developmental angiogenesis in zebrafish embryos. We show that loss of Svep1 and blood flow reduction both contribute to defective anastomosis of intersegmental vessels. We show that this defect in primary angiogenic sprouts is associated with an expansion of Apelin-positive tip cells and with reduced formation and lumenisation of the dorsal longitudinal anastomotic vessel. Mechanistically, our results suggest that flow and Svep1 act synergistically to modulate vascular network formation in the zebrafish trunk.
Profiling epigenetic age in single cells
Authors: Trapp Alexandre , Kerepesi Csaba , Gladyshev Vadim N.
Published: March 2021

DNA methylation of a defined set of CpG dinucleotides emerged as a critical and precise biomarker of the aging process. Multi-variate machine learning models, known as epigenetic clocks, can exploit quantitative changes in the methylome to predict the age of bulk tissue with remarkable accuracy. However, intrinsic sparsity and digitized methylation in individual cells have so far precluded the assessment of aging in single cell data. Here, we present scAge, a probabilistic approach to determine the epigenetic age of single cells, and validate our results in mice. scAge tissue-specific and multi-cell type single cell clocks correctly recapitulate chronological age of the original tissue, while uncovering the inherent heterogeneity that exists at the single-cell level. The data suggest that while tissues age in a coordinated fashion, some cells age more or less rapidly than others. We show that individual embryonic stem cells exhibit an age close to zero, that certain stem cells in a tissue show a reduced age compared to their chronological age, and that early embryogenesis is associated with the reduction of epigenetic age of individual cells, the latter supporting a natural rejuvenation event during gastrulation. scAge is both robust against the low coverage that is characteristic of single cell sequencing techniques and is flexible for studying any cell type and vertebrate organism of interest. This study demonstrates for the first time the potential for accurate epigenetic age profiling at single-cell resolution.
Heat wave event facilitates defensive responses in invasive C3 plant Ambrosia artemisiifolia L. under elevated CO2concentration to the detriment of insect herbivores
Authors: Tian Zhenya , Ma Chao , Zhao Chenchen , Zhang Yan , Gao Xuyuan , Tian Zhenqi , Chen Hongsong , Guo Jianying , Zhou Zhongshi
Published: March 2021

To predict and mitigate the effects of climate change on communities and ecosystems, the joint effects of extreme climatic events on species interactions need to be understood. Using the common ragweed (Ambrosia artemisiifoliaL.)—leaf beetle (Ophraella communa) system, we investigated the effects of heat wave and elevated CO2on common ragweed growth, secondary metabolism, and the consequent impacts on the beetle. The results showed that elevated CO2and heat wave facilitatedA. Artemisiifoliagrowth; further,A. artemisiifoliaaccumulated large amounts of defensive secondary metabolites. Being fed onA. artemisiifoliagrown under elevated CO2and heat wave conditions resulted in the poor performance ofO. communa(high mortality, long development period, and low reproduction). Overall, under elevated CO2, heat wave improved the defensive ability ofA. artemisiifoliaagainst herbivores. This implies that heat wave event will relieve harm ofA. artemisiifoliato human under elevated CO2. On the other hand, super adaptability to climatic changes may aggravate invasive plant distribution, posing a challenge to the control of invasive plants in the future.
Independent mechanisms underlie the protective effect of dietary polyunsaturated fatty acid supplementation and Gαzdeficiency on the early type 1 diabetes phenotype of Non-obese diabetic (NOD) mice
Authors: Fenske Rachel J. , Wienkes Haley N. , Peter Darby C. , Schaid Michael D. , Pennati Andrea , Galipeau Jacques , Kimple Michelle E.
Published: March 2021

Non-obese diabetic (NOD) mice deficient in Gzalpha subunit (Gαz) are protected from developing hyperglycemia, even with early islet insulitis similar to wild-type mice. Similarly, wild-type (WT) NOD mice are protected from glucose intolerance when fed a diet enriched in eicosapentaneoic acid (EPA). In the beta-cell, Prostaglandin EP3 receptor (EP3), whose primary endogenous ligand is the arachidonic acid (AA) metabolite, prostaglandin E2, is specifically coupled to Gαz. In this work, we tested whether dietary EPA supplementation, thereby reducing systemic PGE2levels, would complement Gαzloss in the NOD mouse model. WT and Gαz-null NOD mice were fed an AA-enriched diet, EPA-enriched diet, or control diet upon weaning. After 12 weeks of diet feeding, glucose tolerance tests were performed and pancreatic islets and whole pancreas collected forex vivoanalyses, with the longer-term effect of an EPA-enriched diet on splenic T-cell populations quantified via flow cytometry. Our results reveal a polyunsaturated fatty acid-enriched diet, whether AA or EPA, improves wild-type NOD glucose tolerance by the same magnitude as Gαzloss, but through almost completely different physiological and cellular mechanisms. Our results shed critical light on future research into novel pharmacological and dietary adjuvant therapies for T1D.
Using synthetic MR images for distortion correction
Authors: Montez David F. , Van Andrew N. , Miller Ryland L. , Seider Nicole A. , Marek Scott , Zheng Annie , Newbold Dillan J. , Scheidter Kristen , Feczko Eric , Perrone Anders J. , Miranda-Dominguez Oscar , Earl Eric A. , Kay Benjamin P. , Jha Abhinav K. , Sotiras Aristeidis , Laumann Timothy O. , Greene Deanna J. , Gordon Evan M. , Tisdall M. Dylan , van der Kouwe Andre , Fair Damien A. , Dosenbach Nico U.F.
Published: March 2021

Functional MRI (fMRI) data acquired using echo-planar imaging (EPI) are highly distorted by magnetic field inhomogeneities. Distortion combined with underlying differences in image contrast between EPI and T1-weighted and T2-weighted (T1w/T2w) structural images makes the alignment of functional and anatomical images a challenge. Typically, separately acquired field map data are used to correct fMRI distortions and a flexible cost function insensitive to cross-modal differences in image contrast and intensity is used for aligning fMRI and anatomical images. The quality of alignment achieved with this approach can vary greatly and depends on the quality of field map data. In addition, many publicly available datasets lack field map data entirely. To address this issue, we developedSynth, a software package for distortion correction and cross-modal image registration that does not require separately acquired field map data.Synthcombines information from T1w and T2w anatomical images to construct an idealized undistorted synthetic image that has similar contrast properties to fMRI data. The undistorted synthetic image then serves as an effective reference for individual-specific nonlinear unwarping to correct fMRI distortions. We demonstrate, in both pediatric (ABCD: Adolescent Brain Cognitive Development) and adult (MSC: Midnight Scan Club) data thatSynthperforms comparably well to other leading distortion correction approaches that utilize field map data, and often outperforms them. Field map-less distortion correction withSynthallows accurate and precise registration of fMRI data with missing or corrupted field map information.
Fracture Mechanics of Human Blood Clots: Measurements of Toughness and Critical Length scales
Authors: Liu Shiyu , Bao Guangyu , Ma Zhenwei , Kastrup Christian J. , Li Jianyu
Published: March 2021

Blood coagulates to plug vascular damage and stop bleeding, and thus the function of blood clots in hemostasis depends on their resistance against rupture (toughness). Despite the significance, fracture mechanics of blood clots remains largely unexplored, particularly the measurements of toughness and critical length scales governing clot fracture. Here, we study the fracture behavior of human whole blood clots and platelet-poor plasma clots. The fracture energy of whole blood clots and platelet-poor plasma clots determined using modified lap-shear method is 5.90±1.18 J/m2 and 0.96±0.90 J/m2, respectively. We find that the measured toughness is independent of the specimen geometry and loading conditions. These results reveal a significant contribution of blood cells to the clot fracture, as well as the dissipative length scale and nonlinear elastic length scale governing clot fracture.
Updating the steady state model of C4photosynthesis
Authors: von Caemmerer Susanne
Published: March 2021

C4plants play a key role in world agriculture. For example, C4crops such as maize and sorghum are major contributors to both first and third world food production and the C4grasses sugarcane; miscanthus and switchgrass are major plant sources of bioenergy. In the challenge to manipulate and enhance C4photosynthesis, steady state models of leaf photosynthesis provide and important tool for gas exchange analysis and thought experiments that can explore photosynthetic pathway changes. Here the C4photosynthetic model by von Caemmerer and Furbank (1999) has been updated with new kinetic parameterisation and temperature dependencies added. The parameterisation was derived from experiments on the C4monocot,Setaria viridis, which for the first time provides a cohesive parametrisation. Mesophyll conductance and its temperature dependence have also been included, as this is an important step in the quantitative correlation between the initial slope of the CO2response curve of CO2assimilation and in vitro PEP carboxylase activity. Furthermore, the equations for chloroplast electron transport have been updated to include cyclic electron transport flow and equations have been added to calculate electron transport rate from measured CO2assimilation rates.

Highlight

The C4photosynthesis model by von Caemmerer and Furbank (1999) has been updated. It now includes temperature dependencies and equations to calculate electron transport rate from measured CO2assimilation rates.
Anatomical phenotyping and staging of brain tumors
Authors: Akeret Kevin , Vasella Flavio , Staartjes Victor E. , Velz Julia , Müller Timothy , Neidert Marian Christoph , Weller Michael , Regli Luca , Serra Carlo , Krayenbühl Niklaus
Published: March 2021

In contrast to most other tumors, the anatomical extent of brain tumors is not objectified and quantified through staging. Staging systems are built on the understanding of the anatomical sequence of tumor progression and its relation to histopathological dedifferentiation and survival. While major advances in the understanding of primary brain tumors at a histological, cellular and molecular level have been achieved in recent decades, our understanding at a macroscopic anatomical level is limited. The aim of this study was to describe the anatomical phenotype of the most frequent brain tumor entities based on topographic probability and growth behavior analysis. The association of anatomical tumor features with survival probability was assessed and a prototypical staging system for WHO grade II-IV glioma was proposed based on the hypothesized anatomical sequence of tumor progression. The analysis is based on data from a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumor. On preoperative MRI, the relative tumor density (RTD) of different topographic, phylogenetic and ontogenetic parcellation units was derived through normalization of the relative tumor prevalence to the relative volume of the respective structure. While primary central nervous system lymphoma (PCNSL) showed a high RTD along white matter tracts, the RTD in metastases was highest along terminal arterial flow areas. Neuroepithelial tumors (NT) demonstrated a high and homogeneous RTD along all sectors of the ventriculo-cortical axis, avoiding adjacent units, consistent with a transpallial behavior within phylo-ontogenetic radial units. Additionally, the topographic probability in NT correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. The anatomical tumor growth behavior was analyzed by comparing pre- and postoperative MRI, showing that a ventriculofugal growth dominates in NT. With progressive histopathological dedifferentiation of NT, a gradual deviation from this neuroepithelial anatomical behavior was found. By comparing survival probability, we identified prognostically critical steps in the anatomical behavior of NT. Based on a hypothesized sequence of anatomical tumor progression, we developed a three-level prototypical staging system for WHO grade II-IV glioma. This staging system proved to be accurate across histological, molecular, radiomorphological and clinical strata based on Kaplan Meier curves and multivariable survival analysis. Similar to staging systems for other tumors, a staging system such as this one may have the potential to inform stage-adapted treatment decisions.
Monitoring the rise of the SARS-CoV-2 lineage B.1.1.7 in Tenerife (Spain) since mid-December 2020
Authors: Alcoba-Florez Julia , Lorenzo-Salazar Jose M. , Gil-Campesino Helena , Íñigo-Campos Antonio , de Artola Diego García-Martínez , García-Olivares Victor , Díez-Gil Oscar , Valenzuela-Fernández Agustín , Ciuffeda Laura , González-Montelongo Rafaela , Flores Carlos
Published: March 2021

Starting in December 2020, a sharp increase of COVID-19 cases occurred in Tenerife compared to the rest of the Canary Islands (Spain). Because of the direct touristic connections between Tenerife and the UK, and the rapid transmission and dominance of the SARS-CoV-2 B.1.1.7 variant of concern (VOC-202012/01) by the end of November 2020 in South England, here we measured the proportion of B.1.1.7 cases occurring between the 18th of December 2020 and the 25th of February 2021. Out of the 2,091 COVID-19 positive nasopharyngeal swab samples assessed, 226 showed a spike gene target failure (SGTF). Subsequent viral genome sequencing further confirmed that 93.2% of them corresponded to the B.1.1.7 lineage. Furthermore, a rapid increase in the proportion of SGTF variants was detected in up to 10.7% of positive cases during the Christmas season despite stricter measures for containing the transmission were imposed in Tenerife in the period. These results support the local transmission of SARS-CoV-2 B.1.1.7 lineage in Tenerife since late December 2020 although it is not yet dominant.
Rootstocks influence the response of ripening grape berries to leafroll associated viruses
Authors: Vondras Amanda M. , Lerno Larry , Massonnet Mélanie , Minio Andrea , Rowhani Adib , Liang Dingren , Garcia Jadran , Quiroz Daniela , Figueroa-Balderas Rosa , Golino Deborah A. , Ebeler Susan E. , Al Rwahnih Maher , Cantu Dario
Published: March 2021

Grapevine leafroll-associated virus (GLRaV) infections are accompanied by symptoms with varying severity. Using a dedicated experimental vineyard, we studied the responses to GLRaVs in ripening berries from Cabernet franc grapevines grafted to different rootstocks and with zero, one, or pairs of leafroll infection(s). RNA sequencing data were mapped to a high-quality Cabernet franc genome reference assembled to carry out this study and integrated with hormone and metabolite abundance data. This study identified several molecular levers that participate in responses to GLRaVs, including those that are condition-dependent. This included describing common responses to GLRaVs that were reproduced in two consecutive years, in plants grafted to different rootstocks, and in more than one infection condition. Though different infections were inconsistently distinguishable from one another overall, the effects of infections in plants grafted to different rootstocks were distinct at each developmental stage. Conserved responses included the modulation of pathogen detecting genes, increases in abscisic acid signaling and cytoskeleton remodeling gene expression. The abundance of abscisic acid (ABA), related metabolites, ABA and hormone signaling-related gene expression, and the expression of several transcription factor families differentiated rootstocks overall. These data show that rootstock influences the effect of GLRaVs in ripening berries.
A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission
Authors: Yang Zhenke , Shi Yang , Cui Huiting , Yang Shuzhen , Gao Han , Yuan Jing
Published: March 2021

Mosquito midgut epithelium traversal is an essential component of transmission of malaria parasites. Phospholipid flippases are eukaryotic type IV ATPases (P4-ATPases), which in association with CDC50 cofactors, translocate phospholipids across lipid bilayers to maintain the membrane asymmetry. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasiteP. yoelii. Disruption of ATP7 results in block of parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are motile and capable of invading the midgut, they are quickly eliminated within the epithelial cells by a process that is independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase co-factor CDC50C. Importantly, depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to translocate phosphatidylcholine (PC) across the plasma membrane, resulting in PC exposure at the ookinete surface. Lastly, ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifiesPlasmodiumflippase as a novel mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.
A free-living protist that lacks canonical eukaryotic DNA replication and segregation systems
Authors: Salas-Leiva Dayana E. , Tromer Eelco C. , Curtis Bruce A. , Jerlström-Hultqvist Jon , Kolisko Martin , Yi Zhenzhen , Salas-Leiva Joan S. , Gallot-Lavallée Lucie , Kops Geert J. P. L. , Archibald John M. , Simpson Alastair G. B. , Roger Andrew J.
Published: March 2021

Cells must replicate and segregate their DNA with precision. In eukaryotes, these processes are part of a regulated cell-cycle that begins at S-phase with the replication of DNA and ends after M-phase. Previous studies showed that these processes were present in the last eukaryotic common ancestor and the core parts of their molecular systems are conserved across eukaryotic diversity. However, some unicellular parasites, such as the metamonadGiardia intestinalis, have secondarily lost components of the DNA processing and segregation apparatuses. To clarify the evolutionary history of these systems in these unusual eukaryotes, we generated a high-quality draft genome assembly for the free-living metamonadCarpediemonas membraniferaand carried out a comparative genomics analysis. We found that parasitic and free-living metamonads harbor a conspicuously incomplete set of canonical proteins for processing and segregating DNA. Unexpectedly,Carpediemonasspecies are further streamlined, lacking the origin recognition complex, Cdc6 and other replisome components, most structural kinetochore subunits including the Ndc80 complex, as well as several canonical cell-cycle checkpoint proteins.Carpediemonasis the first eukaryote known to have lost this large suite of conserved complexes, suggesting that it has a highly unusual cell cycle and that unlike any other known eukaryote, it must rely on novel or alternative set of mechanisms to carry out these fundamental processes.
Comparative immunogenicity of bacterially expressed soluble trimers and nanoparticle displayed influenza hemagglutinin stem immunogens
Authors: Kar Uddipan , Khaleeq Sara , Garg Priyanka , Bhat Madhuraj , Reddy Poorvi , Vignesh Venkada Subramanian , Upadhyaya Aditya , Das Mili , Chakshusmathi Ghadiyaram , Pandey Suman , Dutta Somnath , Varadarajan Raghavan
Published: March 2021

Current influenza vaccines need to be updated annually due to mutations in the globular head of the viral surface protein, hemagglutinin (HA). To address this, vaccine candidates have been designed based on the relatively conserved HA stem domain and have shown protective efficacy in animal models. Oligomerization of the antigens either by fusion to oligomerization motifs or display on self-assembling nanoparticle scaffolds, can induce more potent immune responses compared to the corresponding monomeric antigen due to multivalent engagement of B-cells. Since nanoparticle display can increase manufacturing complexity, and often involves one or more mammalian cell expressed components, it is important to characterize and compare various display and oligomerization scaffolds. Using a structure guided approach, we successfully displayed multiple copies of a previously designed soluble, trimeric influenza stem domain immunogen, pH1HA10, on the ferritin like protein, MsDps2 (12 copies), Ferritin (24 copies) and Encapsulin (180 copies). All proteins were expressed inEscherichia coli. The nanoparticle fusion immunogens were found to be well folded and bound to the influenza stem directed broadly neutralizing antibodies with high affinity. An 8.5 Å Cryo-EM map of Msdps2-pH1HA10 confirmed the successful design of the nanoparticle fusion immunogen. Mice immunization studies with the soluble trimeric stem and nanoparticle fusion constructs revealed that all of them were immunogenic, and protected mice against homologous (A/Belgium/145-MA/2009) and heterologous (A/Puerto Rico/8/1934) challenge with 10MLD50mouse adapted virus. Although nanoparticle display conferred a small but statistically significant improvement in protection relative to the soluble trimer in a homologous challenge, heterologous protection was similar in both nanoparticle-stem immunized and trimeric stem immunized groups. Such rapidly producible, bacterially expressed antigens and nanoparticle scaffolds are useful modalities to tackle future influenza pandemics.
Hülle-cell-mediated protection of fungal reproductive and overwintering structures against fungivorous animals
Authors: Liu Li , Dirnberger Benedict , Valerius Oliver , Fekete-Szücs Enikő , Harting Rebekka , Sasse Christoph , Nordzieke Daniela E. , Pöggeler Stefanie , Karlovsky Petr , Gerke Jennifer , Braus Gerhard H.
Published: March 2021

Fungal Hülle cells with nuclear storage and developmental backup functions are reminiscent of multipotent stem cells. In the soil, Hülle cells nurse the overwintering fruiting bodies ofAspergillus nidulans. The genome ofA. nidulansharbors genes for the biosynthesis of xanthones. We show that enzymes and metabolites of this biosynthetic pathway accumulate in Hülle cells under the control of the regulatory velvet complex, which coordinates development and secondary metabolism. Deletion strains blocked in the conversion of anthraquinones to xanthones are delayed in maturation and growth of fruiting bodies. Xanthones are not required for sexual development but exert antifeedant effects on fungivorous animals such as springtails and woodlice. These findings reveal a novel role of Hülle cells in establishing secure niches forA. nidulansby accumulating metabolites with antifeedant activity that protect reproductive structures from animal predators.
Community Evaluation of Glycoproteomics Informatics Solutions Reveals High-Performance Search Strategies of SerumN- andO-Glycopeptide Data
Authors: Kawahara Rebeca , Chernykh Anastasia , Alagesan Kathirvel , Bern Marshall , Cao Weiqian , Chalkley Robert J. , Cheng Kai , Choo Matthew S. , Edwards Nathan , Goldman Radoslav , Hoffmann Marcus , Hu Yingwei , Huang Yifan , Kim Jin Young , Kletter Doron , Liquet-Weiland Benoit , Liu Mingqi , Mechref Yehia , Meng Bo , Neelamegham Sriram , Nguyen-Khuong Terry , Nilsson Jonas , Pap Adam , Park Gun Wook , Parker Benjamin L. , Pegg Cassandra L. , Penninger Josef M. , Phung Toan K. , Pioch Markus , Rapp Erdmann , Sakalli Enes , Sanda Miloslav , Schulz Benjamin L. , Scott Nichollas E. , Sofronov Georgy , Stadlmann Johannes , Vakhrushev Sergey Y. , Woo Christina M. , Wu Hung-Yi , Yang Pengyuan , Ying Wantao , Zhang Hui , Zhang Yong , Zhao Jingfu , Zaia Joseph , Haslam Stuart M. , Palmisano Giuseppe , Yoo Jong Shin , Larson Göran , Khoo Kai-Hooi , Medzihradszky Katalin F. , Kolarich Daniel , Packer Nicolle H. , Thaysen-Andersen Morten
Published: March 2021

Glycoproteome profiling (glycoproteomics) is a powerful yet analytically challenging research tool. The complex tandem mass spectra generated from glycopeptide mixtures require sophisticated analysis pipelines for structural determination. Diverse software aiding the process have appeared, but their relative performance remains untested. Conducted through the HUPO Human Proteome Project – Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates the performance of informatics solutions for system-wide glycopeptide analysis. Mass spectrometry-based glycoproteomics datasets from human serum were shared with all teams. The relative team performance forN- andO-glycopeptide data analysis was comprehensively established and validated through orthogonal performance tests. Excitingly, several high-performance glycoproteomics informatics solutions were identified. While the study illustrated that significant informatics challenges remain, as indicated by a high discordance between annotated glycopeptides, lists of high-confidence (consensus) glycopeptides were compiled from the standardised team reports. Deep analysis of the performance data revealed key performance-associated search variables and led to recommendations for improved “high coverage” and “high accuracy” glycoproteomics search strategies. This study concludes that diverse software for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies, and specifies key variables that may guide future software developments and assist informatics decision-making in glycoproteomics.
RNA-Binding Proteins Direct Myogenic Cell Fate Decisions
Authors: Wheeler Joshua R. , Whitney Oscar N. , Vogler Thomas O. , Nguyen Eric D. , Pawlikowski Bradley , Lester Evan , Cutler Alicia , Elston Tiffany , Betta Nicole Dalla , Parker Kevin R. , Yost Kathryn E. , Vogel Hannes , Rando Thomas A. , Chang Howard Y. , Johnson Aaron M. , Parker Roy , Olwin Bradley B.
Published: March 2021

RNA-binding proteins (RBPs) are essential for skeletal muscle regeneration and RBP dysfunction causes muscle degeneration and neuromuscular disease. How ubiquitously expressed RBPs orchestrate complex tissue regeneration and direct cell fate decisions in skeletal muscle remains poorly understood. Single cell RNA-sequencing of regenerating skeletal muscle reveals that RBP expression, including numerous neuromuscular disease-associated RBPs, is temporally regulated in skeletal muscle stem cells and correlates to stages of myogenic differentiation. By combining machine learning with RBP engagement scoring, we discover that the neuromuscular disease associated RBP Hnrnpa2b1 is a differentiation-specifying regulator of myogenesis controlling myogenic cell fate transitions during terminal differentiation. The timing of RBP expression specifies cell fate transitions by providing a layer of post-transcriptional regulation needed to coordinate stem cell fate decisions during complex tissue regeneration.
Natural variants with 2D correlation genetics identify domains coordinating sarcomere proteins during contraction
Authors: Burghardt Thomas P.
Published: March 2021

Muscle proteins assemble in a sarcomere then by coordinated action produce contraction force to shorten muscle. In the human heart ventriculum, cardiac myosin motor (βmys) repetitively converts ATP free energy into work. Cardiac myosin binding protein C (MYBPC3) in complex with βmys regulates contraction power generation. Their bimolecular complex βmys/MYBPC3 models the contractile system and is used here to study protein coupling. The database for single nucleotide variants (SNVs) in βmys and MYBPC3 surveys human populations worldwide. It consistently records SNV physical characteristics including substituted residue location in the protein functional domain, the side chain substitution, substitution frequency, and human population group, but inconsistently records SNV implicated phenotype and pathology outcomes. A selected consistent subset of the data trains and validates a feed-forward neural network modeling the contraction mechanism. The full database is completed using the model then interpreted probabilistically with a discrete Bayes network to give the SNV probability for a functional domain location given pathogenicity and human population. Co-domains, intra-protein domains coupling βmys and MYBPC3, are identified by their population correlated SNV probability product for given pathogenicity. Divergent genetics in human populations identify co-domain correlates in this method called 2D correlation genetics. Pathogenic and benign SNV data identify three critical regulatory sites, two in MYBPC3 with links to several domains across the βmys motor, and, one in βmys with links to the known MYBPC3 regulatory domain. Critical sites in MYBPC3 are hinges (one known another proposed) sterically enabling regulatory interactions with βmys. The critical site in βmys is the actin binding C-loop, a contact sensor triggering actin-activated myosin ATPase and contraction velocity modulator coordinating also with actin bound tropomyosin. C-loop and MYBPC3 regulatory domain linkage potentially impacts multiple functions across the contractile system. Identification of co-domains in a binary protein complex implies a capacity to estimate spatial proximity constraints for specific dynamic protein interactions in vivo opening another avenue for protein complex structure/function determination.
Phagocytic “teeth” and myosin-II “jaw” power target constriction during phagocytosis
Authors: Vorselen Daan , Barger Sarah R. , Wang Yifan , Cai Wei , Theriot Julie A. , Gauthier Nils C. , Krendel Mira
Published: March 2021

Phagocytosis requires rapid actin reorganization and spatially controlled force generation to ingest targets ranging from pathogens to apoptotic cells. How actomyosin activity directs membrane extensions to engulf such diverse targets remains unclear. Here, we combine lattice light-sheet microscopy (LLSM) with microparticle traction force microscopy (MP-TFM) to quantify actin dynamics and subcellular forces during macrophage phagocytosis. We show that spatially localized forces leading to target constriction are prominent during phagocytosis of antibody-opsonized targets. This constriction is largely mediated by Arp2/3-mediated assembly of discrete actin protrusions containing myosin 1e and 1f (“teeth”) that are interconnected in a ring-like organization. Contractile myosin-II activity contributes to late-stage phagocytic force generation and progression, suggesting a specific role in phagocytic cup closure. Observations of partial target eating attempts and sudden target release via a popping mechanism suggest that constriction may be critical for resolving complexin vivotarget encounters. Overall, our findings suggest a phagocytic cup-shaping mechanism that is distinct from cytoskeletal remodeling in 2D cell motility and may contribute to mechanosensing and phagocytic plasticity.