bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher order Turán inequalities for Boros-Moll sequences
Authors: Guo Jeremy
Published: June 2022

We prove that for the Boros-Moll sequences

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, the higher order Turán inequalities
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hold for

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. As a consequence, the 3rd associated Jensen polynomials
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have only real zeros.
Sources of Variability in Serum Lipidomic Measurements and Implications for Epidemiologic Studies
Authors: Naudin Sabine , Sampson Joshua N , Moore Steven C , Stolzenberg-Solomon Rachael
Published: June 2022

Epidemiological studies using lipidomic approaches can identify lipids associated with exposures and diseases. We evaluated the sources of variability of lipidomic profiles measured in blood samples and the implications when designing epidemiologic studies. We measured 918 lipid species in nonfasting baseline serum from 693 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, with 570 participants having serial blood samples separated by 1–5 years and 72 blinded replicate quality control samples. Blood samples were collected during 1993–2006. For each lipid species, we calculated the between-individual, within-individual, and technical variances, and we estimated the statistical power to detect associations in case-control studies. The technical variability was moderate, with a median intraclass correlation coefficient of 0.79. The combination of technical and within-individual variances accounted for most of the variability in 74% of the lipid species. For an average true relative risk of 3 (comparing upper and lower quartiles) after correction for multiple comparisons at the Bonferroni significance threshold (α = 0.05/918 = 5.45 ×10−5), we estimated that a study with 500, 1,000, and 5,000 total participants (1:1 case-control ratio) would have 19%, 57%, and 99% power, respectively. Epidemiologic studies examining associations between lipidomic profiles and disease require large samples sizes to detect moderate effect sizes associations.
Requirement and functional redundancy of two large ribonucleotide reductase subunit genes for cell cycle, chloroplast biogenesis and photosynthesis in tomato
Authors: Gu Mengjun , Lu Qiao , Liu Yi , Cui Man , Si Yaoqi , Wu Huilan , Chai Tuanyao , Ling Hong-Qing
Published: June 2022

Background and Aims

Ribonucleotide reductase (RNR), functioning in the de novo synthesis of deoxyribonucleoside triphosphates (dNTPs), is crucial for DNA replication and cell cycle progression. In most plants, the large subunits of RNR have more than one homologous gene. However, the different functions of these homologous genes in plant development remain unknown. In this study, we obtained the mutants of two large subunits of RNR in tomato and studied their functions.

Methods

The mutant ylc1 was obtained by ethyl methyl sulfonate (EMS) treatment. Through map-based cloning, complementation and knock-out experiments, it was confirmed that YLC1 encodes a large subunit of RNR (SlRNRL1). The expression level of the genes related to cell cycle progression, chloroplast biogenesis and photosynthesis was assessed by RNA-sequencing. In addition, we knocked out SlRNRL2 (a SlRNRL1 homologue) using CRISPR-Cas9 technology in the tomato genome, and we down-regulated SlRNRL2 expression in the genetic background of slrnrl1-1 using a tobacco rattle virus-induced gene silencing (VIGS) system.

Key results

The mutant slrnrl1 exhibited dwarf stature, chlorotic young leaves and smaller fruits. Physiological and transcriptomic analyses indicated that SlRNRL1 plays a crucial role in the regulation of cell cycle progression, chloroplast biogenesis and photosynthesis in tomato. The slrnrl2 mutant did not exhibit any visible phenotype. SlRNRL2 has a redundant function with SlRNRL1, and the double mutant slrnrl1slrnrl2 is lethal.

Conclusions

SlRNRL1 is essential for cell cycle progression, chloroplast biogenesis and photosynthesis. In addition, SlRNRL1 and SlRNRL2 possess redundant functions and at least one of these RNRLs is required for tomato survival, growth and development.
Stoichiometry versus ecology: the relationships between genome size and guanine–cytosine content, and tissue nitrogen and phosphorus in grassland herbs
Authors: Bitomský Martin , Kobrlová Lucie , Hroneš Michal , Klimešová Jitka , Duchoslav Martin
Published: June 2022

Background and Aims

Plant tissue nitrogen (N) and phosphorus (P) and genome traits, such as genome size and guanine–cytosine (GC) content, scale with growth or metabolic rates and are linked to plant ecological strategy spectra. Tissue NP stoichiometry and genome traits are reported to affect plant growth, metabolic rates or ecological strategies in contrasting ways, although the elemental costs for building and maintaining DNA are typically overlooked.

Methods

We formulated stoichiometry- and ecology-based predictions on the relationship between genome size and GC content to tissue N, P and N : P and tested them on a set of 130 herbaceous species from a temperate grassland using ordinary, phylogenetic and quantile regression.

Key Results

Genome size was only negatively linked to plant N and N : P in species with very small genomes. We found no link between genome size and plant P. GC content was negatively linked to plant N and P but we found these significant links consistently in both GC-rich and GC-poor species. Finally, GC content correlated positively with plant N : P but only in species with GC-rich genomes.

Conclusions

Our results provide stronger support for the ecology-based predictions than the stoichiometry-based predictions, and for the links between GC content and plant N and P stoichiometry than for genome size. We argue that the theories of plant metabolic rates and ecological strategies (resource-acquisitive vs. conservative or ruderal vs. stress-tolerator spectra) better explain interspecific genome-NP stoichiometry relationships at the tissue level (although relatively weakly) than the stoichiometric theory based on the elemental costs for building and maintaining DNA.
Mating competition and adult sex ratio in wild Trinidadian guppies
Authors: Chuard Pierre J C , Grant James W A , Brown Grant E
Published: June 2022

Most experimental tests of mating systems theory have been conducted in the laboratory, using operational sex ratios (ratio of ready-to-mate male to ready-to-mate female) that are often not representative of natural conditions. Here, we first measured the range of adult sex ratio (proportion of adult males to adult females; ASR) in two populations of Trinidadian guppies (Poecilia reticulata) differing in ambient predation risk (high vs. low). We then explored, under semi-wild conditions, the effect of ASR (i.e., 0.17, 0.50, 0.83) on mating competition patterns in these populations. ASR in the wild was female-biased and did not significantly differ between the two populations. The range of ASR in our experiment was representative of natural ASRs. As expected, we observed an increase in intrasexual aggression rates in both sexes as the relative abundance of competitors increased. In support of the risky competition hypothesis, all measured behaviors had lower rates in a high versus low predation-risk population, likely due to the costs of predation. In terms of mating tactics, a male-biased ASR did not lead males to favor forced mating over courtship, indicating that males did not compensate for the cost of competition by switching to a less costly alternative mating tactic. Overall, this study highlights the need for field experiments using natural ranges of ASRs to test the validity of mating systems theory in a more complex, ecologically relevant context.
Robustness of the CDC Folate Microbiologic Assay Kit During Simulated Delayed Shipping
Authors: Zhang Mindy , Fischer Christina , Jabbar Shameem , Pfeiffer Christine
Published: June 2022

Objectives

The WHO has recommended the accurate and practical microbiologic assay (MBA) to assess population folate status. To help laboratories in low-resource countries conduct folate measurements, the CDC developed a folate MBA kit containing critical reagents: calibrator, microorganism, quality control (QC), and reagent stock solutions to prepare culture medium. Shipping frozen kits internationally is complex and sometimes delayed, potentially causing materials to thaw. We investigated whether refrigerated or ambient kit temperatures affect folate results.

Methods

We conditioned 5-methyltetrahydrofolate calibrator stock solution, L. rhamnosus microorganism inoculation, serum and whole blood lysate (WBL) QC samples, and reagent stock solutions (ascorbic acid, chloramphenicol, and manganese sulfate) at 6°C ≤ 3 d and 20°C ≤ 2 d protected from light; we then compared conditioned vs. optimally stored materials (-70°C) by analyzing serum and/or WBL samples (≥3 runs).

Results

The conditioned calibrator showed a mean folate difference (range from 3 runs for 43 WBL samples) of −0.3% (−4.0 to 4.1%) at 6°C/3 d and 0.9% (−1.6% to 2.7%) at 20°C/2 d. Similarly, the conditioned microorganism showed a mean difference of 4.3% (0.7% to 8.3%) at 6°C/3 d and 0.6% (−3.5% to 4.9%) at 20°C/2 d. The conditioned reagents showed a mean difference (range from 3 runs for 5 serum and 5 WBL samples) of 0.3% (−7.4% to 9.0%) at 6°C/3 d and 3.6% (0.1% to 9.0%) at 20°C/2 d. The 2 conditioned serum QC samples (∼13 and ∼40 nmol/L) showed a mean difference (range from 6 runs) of −0.6% (−6.0% to 2.3%) at 6°C/1 d, but higher differences of −5.8%, −5.9%, and −20.7% at 6°C/3 d, 20°C/1 d, and 20°C/2 d, respectively. The conditioned low WBL QC sample (∼300 nmol/L) showed small mean differences (−1.5%, −2.4%, −1.7%, and −0.3% at 6°C/1 d, 6°C/3 d, 20°C/1 d, and 20°C/2 d, respectively), while the conditioned high WBL QC sample (∼600 nmol/L) showed higher mean differences (−3.1%, −12.4%, −6.9%, and −23.7%, respectively).

Conclusions

All kit components except for the QC materials demonstrated adequate stability (<5% change) at 6°C ≤ 3 d or at 20°C ≤ 2 d. The QC materials should not be exposed to 6°C for > 1 d to ensure stability. These findings provide important and practical information for kit shipment management.

Funding Sources

None.
Behavior Analysis-Based IoT Services For Crowd Management
Authors: Noor Talal H
Published: June 2022

With the world population growing exponentially reaching 7.8 billion people in 2020, the issue of crowd management has become more difficult especially when the situation requires social distancing (e.g. due to COVID-19). The Internet of Things (IoT) technology can help in tackling such issues. In this article, we propose a behavior analysis-based IoT services architecture for crowd management. We propose to use a behavior analysis approach based on using generative model as Hidden Markov Model to help crowd managers to make good decisions in invoking IoT services. The proposed approach is based on sectioning video segments captured from surveillance cameras of locations that require crowd management into spatio-temporal flow-blocks for marginalization of arbitrarily dense flow field. Then, each flow-block is classified as normal and abnormal. To demonstrate our approach, we used a real case study where crowd management is required namely, Muslim’s pilgrimage (i.e. Hajj and Umrah), where real dataset is used for experimenting. The results of the experiments we have conducted are promising in real-time performance. Such results are expected to compare favorably to those found in the literature by other researchers.
Investigation of active site amino acid influence on carbon and chlorine isotope fractionation during reductive dechlorination
Authors: Phillips Elizabeth , Bulka Olivia , Picott Katherine , Kümmel Steffen , Edwards Elizabeth A , Nijenhuis Ivonne , Gehre Matthias , Dworatzek Sandra , Webb Jennifer , Sherwood Lollar Barbara
Published: June 2022

Reductive dehalogenases (RDases) are corrinoid-dependent enzymes that reductively dehalogenate organohalides in respiratory processes. By comparing isotope effects in biotically catalyzed reactions to reference experiments with abiotic corrinoid catalysts, compound-specific isotope analysis (CSIA) has been shown to yield valuable insights into enzyme mechanisms and kinetics, including RDases. Here, we report isotopic fractionation (ε) during biotransformation of chloroform (CF) for carbon (εC = -1.52 ± 0.34‰) and chlorine (εCl = -1.84 ± 0.19‰), corresponding to a ΛC/Cl value of 1.13 ± 0.35. These results are highly suppressed compared to isotope effects observed both during CF biotransformation by another organism with a highly similar RDase (>95% sequence identity) at the amino acid level, and to those observed during abiotic dehalogenation of CF. Amino acid differences occur at four locations within the two different RDases’ active sites, and this study examines whether these differences potentially affect the observed εC, εCl, and ΛC/Cl. Structural protein models approximating the locations of the residues elucidate possible controls on reaction mechanisms and/or substrate binding efficiency. These four locations are not conserved among other chloroalkane reducing RDases with high amino acid similarity (>90%), suggesting that these locations may be important in determining isotope fractionation within this homologous group of RDases.
Conditional growth defect of Bordetella pertussis and Bordetella bronchiseptica ferric uptake regulator (fur) mutants
Authors: de Jonge Eline F , Tommassen Jan
Published: June 2022

Outer-membrane vesicles (OMVs) are promising tools in the development of novel vaccines against the respiratory pathogens Bordetella pertussis and Bordetella bronchiseptica. Unfortunately, vesiculation by bordetellae is too low for cost-effective vaccine production. In other bacteria, iron limitation or inactivation of the fur gene has been shown to increase OMV production, presumably by downregulation of the mla genes, which encode machinery for maintenance of lipid asymmetry in the outer membrane. Here, we followed a similar approach in bordetellae. Whereas a fur mutant was readily obtained in B. bronchiseptica, a B. pertussis fur mutant could only be obtained in iron-deplete conditions, indicating that a fur mutation is conditionally lethal in this bacterium. The fur mutants displayed a growth defect in iron-replete media, presumably because constitutive expression of iron-uptake systems resulted in iron intoxication. Accordingly, expression of the Escherichia coli ferritin FtnA to sequester intracellularly accumulated iron rescued the growth of the mutants in these media. The fur mutations led to the constitutive expression of novel vaccine candidates, such as the TonB-dependent receptors FauA for the siderophore alcaligin and BhuR for heme. However, neither inactivation of fur nor growth under iron limitation improved vesiculation, presumably because the expression of the mla genes appeared unaffected.
Implementing a Financial Decision-Making Scale in APS Financial Exploitation Investigations: Use of the PARIHS Conceptual Framework
Authors: Lichtenberg Peter A , Mandarino Joshua , Fisher Lisa , Tocco Maggie , Moray Juno , Shipp Marie
Published: June 2022

Background and Objectives

Adult protective services (APS) agencies investigate cases of financial exploitation, and a critical aspect of such investigations is often the assessment of decision-making abilities. This study examined APS workers’ implementation of a 10-item financial decision-making screening tool, the Financial Decision Tracker (FDT), across a 34-month period: pre-COVID-19, throughout COVID-19 restrictions, and for 1 year following the restrictions.

Research Design and Methods

Using the Promoting Action in Research Implementation in the Health Services implementation science conceptual framework, we examined aspects of context, facilitation, and evidence to determine how well APS workers were trained, certified, and skilled in using the FDT. Using individual and group interviews, we assessed factors often related to successful implementation (context and facilitation) and measured the number of scales used, the types of decisions under investigation, and how the tool’s scoring system aligned with the APS workers’ final ratings (evidence).

Results

Overall, implementation was sustained throughout the 34-month period. However, during COVID-19 restrictions, usage dropped to a rate 58% below that prior to and following the restrictions. A total of 839 scales were administered. Individuals with no decision-making deficits were slightly older (78.7 vs 77.1 years; t(837) = 2.54, p = .01) and had completed high school at a significantly higher rate (69% vs 59%, χ 2(1) = 5.20, p = .023) than those who had decision-making deficits.

Discussion and Implications

Overall, the implementation trial can be considered a success. The FDT was used so often and effectively that it is now an APS best practices tool, meaning that in audits, the correct use of the FDT will be assessed.
Fatty acid metabolism in T-cell function and differentiation
Authors: Endo Yusuke , Kanno Toshio , Nakajima Takahiro
Published: June 2022

Immunometabolism has recently emerged as a field of study examining the intersection between immunology and metabolism. Studies in this area have yielded new findings on the roles of a diverse range of metabolic pathways and metabolites, which have been found to control many aspects of T-cell biology, including cell differentiation, function and fate. A particularly important finding has been the discovery that to meet the energy requirements associated with their proliferation, activation and specific functions, T cells switch their metabolic signatures during differentiation. For example, whereas the induction of de novo fatty acid biosynthesis and fatty acid uptake programs are required for antigen-stimulation-induced proliferation and differentiation of effector T cells, fatty acid catabolism via β-oxidation is essential for the generation of memory T cells and the differentiation of regulatory T cells. In this review, we discuss recent advances in our understanding of the metabolism in different stages of T cells and how fatty acid metabolism in these cells controls their specific functions.
Building trust in research through information and intent transparency with health information: representative cross-sectional survey of 502 US adults
Authors: Mangal Sabrina , Park Leslie , Reading Turchioe Meghan , Choi Jacky , Niño de Rivera Stephanie , Myers Annie , Goyal Parag , Dugdale Lydia , Masterson Creber Ruth
Published: June 2022

Objective

Participation in healthcare research shapes health policy and practice; however, low trust is a barrier to participation. We evaluated whether returning health information (information transparency) and disclosing intent of data use (intent transparency) impacts trust in research.

Materials and Methods

We conducted an online survey with a representative sample of 502 US adults. We assessed baseline trust and change in trust using 6 use cases representing the Social-Ecological Model. We assessed descriptive statistics and associations between trust and sociodemographic variables using logistic and multinomial regression.

Results

Most participants (84%) want their health research information returned. Black/African American participants were more likely to increase trust in research with individual information transparency (odds ratio (OR) 2.06 [95% confidence interval (CI): 1.06–4.34]) and with intent transparency when sharing with chosen friends and family (3.66 [1.98–6.77]), doctors and nurses (1.96 [1.10–3.65]), or health tech companies (1.87 [1.02–3.40]). Asian, Native American or Alaska Native, Native Hawaiian or Pacific Islander, Multirace, and individuals with a race not listed, were more likely to increase trust when sharing with health policy makers (1.88 [1.09–3.30]). Women were less likely to increase trust when sharing with friends and family (0.55 [0.35–0.87]) or health tech companies (0.46 [0.31–0.70]).

Discussion

Participants wanted their health information returned and would increase their trust in research with transparency when sharing health information.

Conclusion

Trust in research is influenced by interrelated factors. Future research should recruit diverse samples with lower baseline trust levels to explore changes in trust, with variation on the type of information shared.
Interlocking joint shape optimization for structurally informed design of block assemblages
Authors: Mousavian Elham , Bagi Katalin , Casapulla Claudia
Published: June 2022

This paper presents a computer aided design tool that analyses the structural feasibility of interlocking assemblages with orthotropic sliding resistance and automatically adjusts the assemblage shape to remove the infeasibility. First, the static problem of limit analysis is extended to the corrugated interfaces. To model different bond patterns and openings, an assemblage is abstracted to different types of joints representing the dry joints between the blocks, joints inside the blocks, and the excluded joints where the openings are located. This problem is then reformulated to measure the structural infeasibility due to the sliding constraint violation. The so-called sliding infeasibility measure shows how far an infeasible model is to become feasible. This problem is used as the objective function of a shape optimization algorithm that minimizes the sliding infeasibility measure through automated change of the interlocking joints, by which the model becomes structurally feasible. The optimization is validated using the discrete element analysis.
Sebaceous carcinoma of trunk with bilateral axillary lymph node metastasis: a rare presentation of malignant adnexal tumor in young adult
Authors: Jaiswal Lokesh Shekher , Neupane Durga , Lageju Nimesh , Khadka Sarada , Sah Bijay , Pradhan Anju
Published: June 2022

Malignant adnexal tumors of skin are rare. Sebaceous carcinoma—a rare and aggressive cutaneous tumor—is frequently located in the periorbital region. Malignant adnexal tumors of sebaceous carcinoma type on trunk with axillary lymph node and distant metastasis in young adult is rare. The incidence of extraocular sebaceous carcinoma has been expected to be 0.06 per 100 000 person-years with an increased incidence in elderly patients and men. With a note of mimicking benign dermatologic conditions, definitive diagnosis of sebaceous carcinomas is often hindered, increasing morbidity and mortality for patients. Herein, we present a case of a 35-year-old man with a large ulcero-proliferating lesion of trunk region previously resected for a small swelling and eventually presented with the recurrent lesion and diagnosed as sebaceous carcinoma of trunk with bilateral axillary lymphnode and distant bone metastasis demonstrating several diagnostic and management challenges.
Accurate Identification of Transcription Regulatory Sequences and Genes in Coronaviruses
Authors: Zhang Chuanyi , Sashittal Palash , Xiang Michael , Zhang Yichi , Kazi Ayesha , El-Kebir Mohammed
Published: June 2022

Transcription regulatory sequences (TRSs), which occur upstream of structural and accessory genes as well as the 5′ end of a coronavirus genome, play a critical role in discontinuous transcription in coronaviruses. We introduce two problems collectively aimed at identifying these regulatory sequences as well as their associated genes. First, we formulate the TRS Identification problem of identifying TRS sites in a coronavirus genome sequence with prescribed gene locations. We introduce CORSID-A, an algorithm that solves this problem to optimality in polynomial time. We demonstrate that CORSID-A outperforms existing motif-based methods in identifying TRS sites in coronaviruses. Second, we demonstrate for the first time how TRS sites can be leveraged to identify gene locations in the coronavirus genome. To that end, we formulate the TRS and Gene Identification problem of simultaneously identifying TRS sites and gene locations in unannotated coronavirus genomes. We introduce CORSID to solve this problem, which includes a web-based visualization tool to explore the space of near-optimal solutions. We show that CORSID outperforms state-of-the-art gene finding methods in coronavirus genomes. Furthermore, we demonstrate that CORSID enables de novo identification of TRS sites and genes in previously unannotated coronavirus genomes. CORSID is the first method to perform accurate and simultaneous identification of TRS sites and genes in coronavirus genomes without the use of any prior information.
Expression of Bacillus subtilis ABCF antibiotic resistance factor VmlR is regulated by RNA polymerase pausing, transcription attenuation, translation attenuation and (p)ppGpp
Authors: Takada Hiraku , Mandell Zachary F , Yakhnin Helen , Glazyrina Anastasiya , Chiba Shinobu , Kurata Tatsuaki , Wu Kelvin J Y , Tresco Ben I C , Myers Andrew G , Aktinson Gemma C , Babitzke Paul , Hauryliuk Vasili
Published: June 2022

Since antibiotic resistance is often associated with a fitness cost, bacteria employ multi-layered regulatory mechanisms to ensure that expression of resistance factors is restricted to times of antibiotic challenge. In Bacillus subtilis, the chromosomally-encoded ABCF ATPase VmlR confers resistance to pleuromutilin, lincosamide and type A streptogramin translation inhibitors. Here we show that vmlR expression is regulated by translation attenuation and transcription attenuation mechanisms. Antibiotic-induced ribosome stalling during translation of an upstream open reading frame in the vmlR leader region prevents formation of an anti-antiterminator structure, leading to the formation of an antiterminator structure that prevents intrinsic termination. Thus, transcription in the presence of antibiotic induces vmlR expression. We also show that NusG-dependent RNA polymerase pausing in the vmlR leader prevents leaky expression in the absence of antibiotic. Furthermore, we demonstrate that induction of VmlR expression by compromised protein synthesis does not require the ability of VmlR to rescue the translational defect, as exemplified by constitutive induction of VmlR by ribosome assembly defects. Rather, the specificity of induction is determined by the antibiotic's ability to stall the ribosome on the regulatory open reading frame located within the vmlR leader. Finally, we demonstrate the involvement of (p)ppGpp-mediated signalling in antibiotic-induced VmlR expression.
The Drosophila hnRNP F/H homolog Glorund recruits dFMRP to inhibit nanos translation elongation
Authors: Peng Yingshi , Gavis Elizabeth R
Published: June 2022

Translational control of maternal mRNAs generates spatial and temporal patterns of protein expression necessary to begin animal development. Translational repression of unlocalized nanos (nos) mRNA in late-stage Drosophila oocytes by the hnRNP F/H homolog, Glorund (Glo), is important for embryonic body patterning. While previous work has suggested that repression occurs at both the translation initiation and elongation phases, the molecular mechanism by which Glo regulates nos translation remains elusive. Here, we have identified the Drosophila fragile X mental retardation protein, dFMRP, as a Glo interaction partner with links to the translational machinery. Using an oocyte-based in vitro translation system, we confirmed that Glo regulates both initiation and elongation of a nos translational reporter and showed that dFMRP specifically represses translation elongation and promotes ribosome stalling. Furthermore, we combined mutational analysis and in vivo and in vitro binding assays to show that Glo's qRRM2 domain specifically and directly interacts with dFMRP. Our findings suggest that Glo regulates nos translation elongation by recruiting dFMRP and that Glo's RNA-binding domains can also function as protein-protein interaction interfaces critical for its regulatory functions. Additionally, they reveal a mechanism for targeting dFMRP to specific transcripts.
Structural variation and parallel evolution of apomixis in citrus during domestication and diversification
Authors: Wang Nan , Song Xietian , Ye Junli , Zhang Siqi , Cao Zhen , Zhu Chenqiao , Hu Jianbing , Zhou Yin , Huang Yue , Cao Shuo , Liu Zhongjie , Wu Xiaomeng , Chai Lijun , Guo Wenwu , Xu Qiang , Gaut Brandon S , Koltunow Anna M G , Zhou Yongfeng , Deng Xiuxin
Published: June 2022

Apomixis, or asexual seed formation, is prevalent in Citrinae via a mechanism termed nucellar or adventitious embryony. Here, multiple embryos of a maternal genotype form directly from nucellar cells in the ovule and can outcompete the developing zygotic embryo as they utilize the sexually derived endosperm for growth. Whilst nucellar embryony enables the propagation of clonal plants of maternal genetic constitution, it is also a barrier to effective breeding through hybridization. To address the genetics and evolution of apomixis in Citrinae, a chromosome-level genome of the Hongkong kumquat (Fortunella hindsii) was assembled following a genome-wide variation map including structural variants (SVs) based on 234 Citrinae accessions. This map revealed that hybrid citrus cultivars shelter genome-wide deleterious mutations and SVs into heterozygous states free from recessive selection, which may explain the capability of nucellar embryony in most cultivars during Citrinae diversification. Analyses revealed that parallel evolution may explain the repeated origin of apomixis in different genera of Citrinae. Within Fortunella, we found that apomixis of some varieties originated via introgression. In apomictic Fortunella, the locus associated with apomixis contains the FhRWP gene, encoding an RWP-RK domain-containing protein previously shown to be required for nucellar embryogenesis in Citrus. We found the heterozygous SV in the FhRWP and CitRWP promoters from apomictic Citrus and Fortunella, due to either two or three miniature inverted transposon element (MITE) insertions. A transcription factor, FhARID, encoding an AT-rich interaction domain-containing protein binds to the MITEs in the promoter of apomictic varieties, which facilitates induction of nucellar embryogenesis. This study provides evolutionary genomic and molecular insights into apomixis in Citrinae and has potential ramifications for citrus breeding.
Anxieties of the Dominant: Legal, Social, and Religious in the Politics of Religious Conversion in India
Authors: Kumar Mukesh , Yadav Garima
Published: June 2022

The promulgation of the new state-level conversion laws in India or some changes in already existing ones by ordinances is premised upon various conspiracy theories of Hindu fundamentalists against Muslims. Implicit in and placed at the centre of these new anti-conversion laws and public debates thereof is the conspiracy theory of love-jihad that Muslim men lure Hindu women on the pretext of love and get them convert to Islam to eventually outnumber the Hindu majority. This article argues that the anti-conversion laws in India result from anxieties of the dominant caste and class regarding gender and caste, leading to the imposition of the mainstream orthodox religious and political will upon the marginalized. The creation of anti-conversion laws is based on assumptions, fears, conspiracy theories, and moral and religious values primarily shared by the ‘upper-caste’ section across the political spectrum. Furthermore, it also shows a growing nexus between conservative religious forces and state apparatuses that restricts religious and social mobility of the marginalized sections through legal changes.
GREEN FLUORESCENT PROTEIN variants with enhanced folding are more efficiently imported into chloroplasts
Authors: Jeong Jinseung , Moon Byeongho , Hwang Inhwan , Lee Dong Wook
Published: June 2022

Chloroplasts and mitochondria are subcellular organelles that evolved from cyanobacteria and α-proteobacteria, respectively. Although they have their own genomes, the majority of their proteins are encoded by nuclear genes, translated by cytosolic ribosomes, and imported via outer and inner membrane translocon complexes. The unfolding of mature regions of proteins is thought to be a prerequisite for the import of the proteins into these organelles. However, it is not fully understood how protein folding properties affect their import into these organelles. In this study, we examined the import behavior of chloroplast and mitochondrial reporters with normal green fluorescent protein (GFP) and two GFP variants with enhanced folding propensity, superfolder GFP (sfGFP) and extra-superfolder GFP (esGFP), which is folded better than sfGFP. sfGFP and esGFP were less dependent on the sequence motifs of the transit peptide (TP) and import machinery during protein import into Arabidopsis (Arabidopsis thaliana) chloroplasts, compared with normal GFP. sfGFP and esGFP were efficiently imported into chloroplasts by a mutant TP with an alanine substitution in the N-terminal MLM motif, whereas the same mutant TP showed a defect in importing normal GFP into chloroplasts. Moreover, sfGFP and esGFP were efficiently imported into plastid protein import 2 (ppi2) and heat shock protein 93-V (hsp93-V) plants, which have mutations in atToc159 and Hsp93-V, respectively. In contrast, the presequence-mediated mitochondrial import of sfGFP and esGFP was severely impaired. Based on these results, we propose that the chloroplast import machinery is more tolerant to different folding states of preproteins, whereas the mitochondrial machinery is more specialized in the translocation of unfolded preproteins.
Resolving deep evolutionary relationships within the RNA virus phylum Lenarviricota
Authors: Sadiq Sabrina , Chen Yan-Mei , Zhang Yong-Zhen , Holmes Edward C
Published: June 2022

The RNA virus phylum Lenarviricota is composed of the fungi-associated families Narnaviridae and Mitoviridae, the RNA bacteriophage Leviviridae, and the plant and fungi-associated Botourmiaviridae. Members of the Lenarviricota are abundant in most environments and boast remarkable phylogenetic and genomic diversity. As this phylum includes both RNA bacteriophage and fungi- and plant-associated species, the Lenarviricota likely mark a major evolutionary transition between those RNA viruses associated with prokaryotes and eukaryotes. Despite the remarkable expansion of this phylum following metagenomic studies, the phylogenetic relationships among the families within the Lenarviricota remain uncertain. Utilising a large data set of relevant viral sequences, we performed phylogenetic and genomic analyses to resolve the complex evolutionary history within this phylum and identify patterns in the evolution of virus genome organisation. Despite limitations reflecting very high levels of sequence diversity, our phylogenetic analyses suggest that the Leviviridae comprise the basal lineage within the Lenarviricota. Our phylogenetic results also support the construction of a new virus family—the Narliviridae—comprising a set of diverse and phylogenetically distinct species, including a number of uniquely encapsidated viruses. We propose a taxonomic restructuring within the Lenarviricota to better reflect the phylogenetic relationships documented here, with the Botourmiaviridae and Narliviridae combined into the order Ourlivirales, the Narnaviridae remaining in the order Wolframvirales, and these orders combined into the single class, the Amabiliviricetes. In sum, this study provides insights into the complex evolutionary relationships among the diverse families that make up the Lenarviricota.
PREDICTIVE PERFORMANCE OF MACHINE LEARNING MODELS FOR DETECTION OF INCIDENT HEART FAILURE USING MULTI-CENTRE DATA
Authors: Sabovcik Frantisek , Ntalianis Evangelos , Cauwenberghs Nicholas , Kuznetsova Tatiana
Published: June 2022

Objective:

To mitigate the health and economic burden associated with heart failure (HF), primary prevention is of utmost importance. To effectively address the diverse range of individual health profiles, prediction models must be trained and validated on a wide range of population-based cohorts. We evaluated the predictive performance of Survival Gradient Boosting (SGB) and Coxnet (CN) for the detection of incident HF. In addition, we compared the models’ performance trained only on a single-centre cohort with those trained on diverse multi-centre cohorts.

Design and method:

We utilized 6 cohorts from the Heart ‘omics’ in AGEing (HOMAGE) project to evaluate two computational approaches. The dataset consists of 31,382 individuals (mean age 66 ± 10 years old), free of HF at the baseline. During a median follow-up of 5.36 years, 1,130 non-fatal HF events occurred. SGB is a non-linear machine learning method based on training regression trees with the objective of optimizing Cox partial likelihood. Coxnet is a standard linear Cox proportional hazard model, regularized by both L1 and L2 norms. To estimate the predictive accuracy of a single-centre model on a specific test cohort, we averaged the performance of single models trained on remaining cohorts one at a time. To develop models in multi-centre settings, we used 5 cohorts in every iteration as a training set and the remaining 1 cohort as a test set. We used 33 features, including clinical, ECG, and biochemical data.

Results:

Overall, multi-centre models achieved a higher c-index than those trained on single cohorts (Figure). For example, in the FLEMENGHO cohort, multi-centre SGB achieved 0.819, while only 0.664 in a single-centre setting. Additionally, non-linear SGB achieved a considerably higher c-index than linear CN in all but one cohort, especially in multi-centre settings, for example in the HVC cohort (SGB 0.689, CN 0.614).

Conclusions:

With a greater number and variety of training cohorts, the model learns a wider range of specific individual health characteristics. Flexible machine learning algorithms such as gradient boosting can be used to capture these diverse distributions and produce more precise, personalized models for the prediction of adverse events.
TIME SERIES CLUSTERING OF LEFT ATRIAL STRAIN CURVES FOR RISK STRATIFICATION IN THE GENERAL POPULATION
Authors: Ntalianis Evangelos , Sabovcik Frantisek , Daels Yne , Couwenberghs Nicholas , Kuznetsova Tatiana
Published: June 2022

Objective:

Currently, only the peak reservoir left atrial (LA) strain has been in use while a huge amount of useful information during different phases of cardiac cycle has been ignored. In this study, therefore, we tested the hypothesis that an unsupervised time series analysis utilizing the whole LA deformation curves will identify distinct clusters associated to risk factors and improve cardiovascular (CV) risk prediction over the traditionally used covariables in the general population.

Design and method:

We prospectively studied 929 community-dwelling individuals (mean age, 51.6 years; 52.9% women), in whom we acquired clinical and echocardiographic data including LA strain traces at baseline and collected cardiac events on average 7.2 years later. We employed two unsupervised time series techniques such as Self-Organizing map and Variational Autoencoder with Convolutional Neural Network as building block to cluster spatiotemporal patterns of LA strain curves. Clinical characteristics and cardiac outcome were used to evaluate the validity of the clusters (k).

Results:

According to the quantization error value for every k, the optimal number of clusters was 5 for applied methods. Overall, both methods agreed with respect to cluster assignment. Figure (left panel) presents centroid LA strain curves which represent each cluster. The first three clusters had differences in sex distribution and heart rate, but had similar low CV risk profiles. On the other hand, cluster 5 had the worst CV risk factors combination, and higher prevalence of left ventricular remodelling and diastolic dysfunction (ie, lowest e’ velocity and highest E/e’) compared to other clusters. We also observed an increase in the risk for incidence of adverse events between cluster 5 and other clusters (Figure, right panel). After adjustment for traditional risk factors, cluster 5 had the highest risk of cardiac events as compared to cluster 1, 2 and 3 (HR: 1.34; 95%CI: 1.05–1.73); P = 0.020).

Conclusions:

Unsupervised Machine/Deep Learning algorithms employed on time series LA strain curves identifies clinically meaningful clusters of LA deformation, and provides incremental prognostic information over traditional risk stratification.
BLOOD PRESSURE RESPONSE TO STANDING IS A STRONG PREDICTOR OF MASKED HYPERTENSION
Authors: Rattazzi Marcello , Saladini Francesca , Mos Lucio , Fania Claudio , Garavelli Guido , Zanatta Nello , Spinella Paolo , Palatini Paolo
Published: June 2022

Objective:

The pathophysiologic mechanisms of masked hypertension are still debated. The aim of this study was to clarify the role of the blood pressure (BP) response to the upright posture as a potential mechanism for the development of masked hypertension in young subjects screened for stage 1 hypertension.

Design and method:

We studied 1078 young-to-middle-age (mean age 33.2 ± 8.5 years) subjects with stage I untreated hypertension at baseline. The response to standing was defined as the difference between 6 systolic BP measurements in the orthostatic and supine posture (OrthoResp). People with OrthoResp > 6.5 mmHg (upper decile) were defined as Hyperreactors. After 3 months of follow-up, 24-hour ambulatory BP was measured and the participants were classified as Normotensives (N = 120), White-coat hypertensives (N = 168), Masked hypertensives (N = 166), and Sustained hypertensives (N = 624) using the 140/90 and 130/80 mmHg cutoffs for office BP and 24-hour BP, respectively. In 591 participants, 24 h urinary epinephrine was also measured and patients were divided into four groups according to BP reactivity (>6.5 mmHg or <  = 6.5 mmHg) and 24-hour urinary epinephrine/creatinine median level (>10.5 mcg/g or < = 10.5 mcg/g). The risk of developing masked hypertension was explored in a logistic regression model adjusting for confounders.

Results:

Mean ± SEM age-and-sex-adjusted OrthoResp was -3.8 ± 0.7 mmHg in the Normotensives, -3.1 ± 0.6 mmHg in the White-coat hypertensives, -0.9 ± 0.6 mmHg in the Masked hypertensives, and -2.6 ± 0.3 mmHg in the Sustained hypertensives. OrthoResp was an independent predictor of masked hypertension after 3 months (p = 0.001). The Odds ratio for the Hyperreactors was 2.5 (95%CI,1.5–4.0, p < 0.001). In the participants stratified by OrthoResp and urinary epinephrine, the risk of masked hypertension was 4.2 (95%CI,1.8–9.9, p = 0.001) in the hyperreactors with epinephrine above the median and was 2.6 (95%CI,0.9–7.3, p = 0.069) in those with epinephrine below the median.

Conclusions:

The present findings indicate that hyperreactivity to standing is a significant predictor of masked hypertension. The risk of masked hypertension was even quadrupled in people with an OrthoResp> 6.5 mmHg and high urinary epinephrine suggesting a role of sympathoadrenergic activity in the pathogenesis of masked hypertension which may be partly mediated by hyperreactivity to standing.
BLOOD PRESSURE IN ATRIAL FIBRILLATION AND IN SINUS RHYTHM DURING 24 HOUR AMBULATORY BLOOD PRESSURE MONITORING: DATA FROM THE TEMPLAR PROJECT
Authors: Lundwall Kristina , Kahan Thomas , Omboni Stefano
Published: June 2022

Objective:

Hypertension is the most common risk factor for atrial fibrillation (AF), and accounts for a worse prognosis. Blood pressure (BP) control is accordingly essential in AF. However, the interpretation of BP levels is difficult in AF, since differences may be dependent on rhythm, particularly when using automated oscillometric devices. We used data from the TEMPLAR project to compare oscillometric ambulatory BP monitoring (ABPM) intra-individually in AF and sinus rhythm (SR).

Design and method:

Among the 4398 individuals in TEMPLAR > 65 years investigated with ABPM and Afib Microlife detector (rhythm indicated with each BP measurement), those with > 30% of readings indicating AF were selected (as previously recommended), and episodes > 30 mins for AF and SR were chosen. Systolic and diastolic BP, mean arterial pressure (MAP), pulse pressure (PP), averaged real variability (ARV), and its coefficient of variation (CV) were assessed for AF and SR, separated for 24 h, daytime, night-time, and for heart rate (HR) < = 90 and > = 90 bpm.

Results:

We included 430 individuals (mean age 78 ± 7 years, 57% females, 77% with hypertension and 72% on treatment, 4% with previous AF). Mean BP of all measurements included were 124.2/69.0, 126.3/71.1, and 119.5/64.0 mmHg, for 24 h, daytime, and night-time, respectively. There were no differences in MAP for AF vs SR (p = 0.47). Systolic BP tended to be lower in AF (24 h 123.6 ± 13.9 vs 124.7 ± 16.1 mmHg in SR, p = 0.05), and night-time diastolic BP was higher in AF (64.6 ± 10.9 vs 63.3 ± 10.4 mmHg in SR, p = 0.01). PP was lower in AF (24 h 54.6 ± 10.9 vs 55.7 ± 12.8 mmHg in SR, p = 0.002). Diastolic, but not systolic BP variability (ARV and CV) was higher in AF (24 h, p < 0.001). Results were similar with HR <  = 90 and > = 90 bpm.

Conclusions:

Using an oscillometric ABPM device, our results suggest that MAP is similar and reliable in both AF and SR. Lower systolic and higher diastolic BP in AF affects PP, which together with a high variability might impact arterial structure. However, differences in absolute numbers are small, and do not imply different BP strategies and target values in AF.