bluuebunny/crossref_metadata_2025 huggingface dataset:
Test of the Effective Stress Law for Semibrittle Deformation Using Isostatic and Triaxial Load Paths
Authors: Ding J. , Chester F. M. , Chester J. S.
Published: April 2021

For brittle friction and rock deformation, the coefficient α in the general effective stress relation σe = σ − αPp can be approximated as unity with sufficient accuracy. However, it is uncertain if α deviates from unity for semibrittle flow when both brittle and intracrystalline‐plastic deformation is involved. We conducted triaxial and isostatic compression experiments on synthetic salt‐rocks (∼300 ppm water) at room temperature to test the effective stress relation in the semibrittle regime using silicone oil and argon gas as pore fluids. Confining and pore pressures were cycled while their difference (differential pressure) was kept constant, such that changes in the mechanical behavior would indicate deviation of α from unity. Microstructural observations were used to determine the dependence of α on true area of grain contact from asperity yielding. In triaxial compression experiments, semibrittle flow involves grain boundary cracking and sliding, and intragranular dislocation glide and cracking. Flow strength remains constant for changes in pore fluid pressure of more than two orders of magnitude. In isostatic compression experiments, samples show combined processes of microcracking, grain boundary sliding, dislocation glide, and fluid‐assisted grain boundary migration recrystallization. Volumetric strain depends directly on the differential pressures (i.e., α equals one). Analysis of grain‐contact area in both experiments indicates that α is independent of the true area of contact defined by plastic yielding at grain boundaries. The observation of α effectively equals one may be explained by operation of pressure‐independent intracrystalline‐plastic mechanisms and transmission of pore pressure at grain boundaries through thin fluid films.
Dart‐Leader and K‐Leader Velocity From Initiation Site to Termination Time‐Resolved With 3D Interferometry
Authors: Jensen Daniel P. , Sonnenfeld Richard G. , Stanley Mark A. , Edens Harald E. , da Silva Caitano L. , Krehbiel Paul R.
Published: April 2021

Simultaneous data from two interferometers separated by 16 km and synchronized within 100 ns were collected for a thunderstorm near Langmuir Lab on October 23, 2018. Analysis via triangulation followed by a least squares fit to time of arrival across all six antennae produced a three‐dimensional interferometer (3DINTF) data set. Simultaneous Lightning Mapping Array data enabled an independent calculation of 3DINTF accuracy, yielding a median location uncertainty of 200 m. This is the most accurate verified result to date for a two‐station interferometer. The 3D data allowed profiling the velocity of multiple dart leaders and K leaders that followed the same channel. 3D velocities calculated from the in‐cloud initiation site to ground ranged from 3 × 106 to 20 × 106 m/s. Average velocity generally increased with subsequent leaders, consistent with increased conditioning of the channel. Also, all leaders showed a factor of 2–3 decrease in velocity as they proceeded over 15 km of channel. We speculate that the velocity decrease is consistent with energy lost in the reionization of the channel at the leader tip. This paper includes an appendix providing details of the triangulation technique used.
Pulse Coherent Doppler Profiler Measurement of Bedload Transport
Authors: Zedel Len , Hay Alex E. , Wilson Gregory W. , Hare Jenna
Published: April 2021

Prior studies demonstrate that bottom velocity measurements from Doppler sonar systems are proportional to bedload transport rates. These observations suggest that acoustically based systems offer a capability for rapid sampling of bedload transport processes. Before these measurements can be fully utilized, validation and understanding of the sampling mechanism are essential. We explore the measurement mechanism through a series of laboratory trials with a field instrument, the multi‐frequency coherent Doppler profiler (MFDop). The MFDop system is a multi‐frequency (1.2–2.2 MHz), bistatic Doppler sonar that provides three‐component ensemble‐averaged velocity profiles over a ∼30 cm depth interval with up to 1 mm resolution at a rate of 50 profiles/sec. Tests of the MFDop system were carried out in the main flume in field‐scale conditions at the St. Anthony Falls Laboratory (SAFL) using 1 ms−1 mean flows over a mobile bed of sand with median grain size d50 = 0.4 mm. We find agreement between MFDop transport measurements and measurements based on bedform migration rates, and sediment traps built into the SAFL flume. Predictions using the Meyer‐Peter and Müller (1948) empirical equation closely match our observations while in contrast, predictions using the Nielsen (1992) equation are a factor of two higher.
Why Trillions of Jellyfish Washed Ashore from Canada to California
Authors: Duncombe Jenessa
Published: April 2021

Although warming oceans may make population booms and mass strandings more common, the species may ultimately be one of the beneficiaries of climate change.
Aerosol Scientists Try to Clear the Air About COVID-19 Transmission
Authors: Duncombe Jenessa
Published: April 2021

“We are basically doing what a public health agency should be doing.”
Highly efficient THz four-wave mixing in doped silicon
Authors: Dessmann Nils , Le Nguyen H. , Eless Viktoria , Chick Steven , Saeedi Kamyar , Perez-Delgado Alberto , Pavlov Sergey G. , van der Meer Alexander F. G. , Litvinenko Konstantin L. , Galbraith Ian , Abrosimov Nikolay V. , Riemann Helge , Pidgeon Carl R. , Aeppli Gabriel , Redlich Britta , Murdin Benedict N.
Published: April 2021

Third-order non-linearities are important because they allow control over light pulses in ubiquitous high-quality centro-symmetric materials like silicon and silica. Degenerate four-wave mixing provides a direct measure of the third-order non-linear sheet susceptibility χ(3)L (where L represents the material thickness) as well as technological possibilities such as optically gated detection and emission of photons. Using picosecond pulses from a free electron laser, we show that silicon doped with P or Bi has a value of χ(3)L in the THz domain that is higher than that reported for any other material in any wavelength band. The immediate implication of our results is the efficient generation of intense coherent THz light via upconversion (also a χ(3) process), and they open the door to exploitation of non-degenerate mixing and optical nonlinearities beyond the perturbative regime.
Strawberry sweetness and consumer preference are enhanced by specific volatile compounds
Authors: Fan Zhen , Hasing Tomas , Johnson Timothy S. , Garner Drake M. , Schwieterman Michael L. , Barbey Christopher R. , Colquhoun Thomas A. , Sims Charles A. , Resende Marcio F. R. , Whitaker Vance M.
Published: April 2021

Breeding crops for improved flavor is challenging due to the high cost of sensory evaluation and the difficulty of connecting sensory experience to chemical composition. The main goal of this study was to identify the chemical drivers of sweetness and consumer liking for fresh strawberries (Fragaria × ananassa). Fruit of 148 strawberry samples from cultivars and breeding selections were grown and harvested over seven years and were subjected to both sensory and chemical analyses. Each panel consisted of at least 100 consumers, resulting in more than 15,000 sensory data points per descriptor. Three sugars, two acids and 113 volatile compounds were quantified. Consumer liking was highly associated with sweetness intensity, texture liking, and flavor intensity, but not sourness intensity. Partial least square analyses revealed 20 volatile compounds that increased sweetness perception independently of sugars; 18 volatiles that increased liking independently of sugars; and 15 volatile compounds that had positive effects on both. Machine learning-based predictive models including sugars, acids, and volatiles explained at least 25% more variation in sweetness and liking than models accounting for sugars and acids only. Volatile compounds such as γ-dodecalactone; 5-hepten-2-one, 6-methyl; and multiple medium-chain fatty acid esters may serve as targets for breeding or quality control attributes for strawberry products. A genetic association study identified two loci controlling ester production, both on linkage group 6 A. Co-segregating makers in these regions can be used for increasing multiple esters simultaneously. This study demonstrates a paradigm for improvement of fruit sweetness and flavor in which consumers drive the identification of the most important chemical targets, which in turn drives the discovery of genetic targets for marker-assisted breeding.
Preharvest long-term exposure to UV-B radiation promotes fruit ripening and modifies stage-specific anthocyanin metabolism in highbush blueberry
Authors: Li Taishan , Yamane Hisayo , Tao Ryutaro
Published: April 2021

Ultraviolet-B (UV-B) light (280–315 nm) is an important environmental signal that regulates plant development and photomorphogenesis, while also affecting the flavonoid pathway, including anthocyanin biosynthesis. Regarding the effects of UV-B radiation on fruits, the effects of a short-term or postharvest irradiation on fruit quality have been well-documented, but the effects of a long-term preharvest UV-B irradiation on fruit growth and coloration remain unclear. Thus, in this study, we investigated the effects of a long-term treatment involving an environmentally relevant UV-B dose on highbush blueberry (Vaccinium corymbosum) fruit. The preharvest UV-B treatment quickly promoted fruit growth and sugar accumulation, which is not commonly observed in other fruit tree species. The UV-B exposure also accelerated fruit ripening and coloration. The dual-luciferase assay proved that in blueberries, expression ofVcUFGTencoding anthocyanin biosynthesis key enzyme, is positively and negatively regulated byVcMYBA1andVcMYBC2, respectively. Throughout the fruit development stage, the UV-B treatment up-regulatedVcMYBPA1expression, which increasedVcUFGTexpression viaVcMYBA1. In the green fruit stage, the UV-B treatment increasedHY5encoding UV receptor, which up-regulatesVcMYBPA1and down-regulatesVcMYBC2, thereby promotes the accumulation of anthocyanins. On the other hand, excessive anthocyanin synthesis was inhibited by increasedVcMYBC2levels in mature fruits when exposed to UV-B light throughHY5-independent pathway. In conclusion, anthocyanin-related MYB activators and repressor may coordinately balance the accumulation of anthocyanins in blueberry fruits, with UV-B treatments possibly influencing their effects in a stage-specific manner. The potential utility of preharvest UV-B treatments for improving blueberry fruit quality is discussed herein.
Genome of a citrus rootstock and global DNA demethylation caused by heterografting
Authors: Huang Yue , Xu Yuantao , Jiang Xiaolin , Yu Huiwen , Jia Huihui , Tan Chunming , Hu Gang , Hu Yibo , Rao Muhammad Junaid , Deng Xiuxin , Xu Qiang
Published: April 2021

Grafting is an ancient technique used for plant propagation and improvement in horticultural crops for at least 1,500 years. Citrus plants, with a seed-to-seed cycle of 5–15 years, are among the fruit crops that were probably domesticated by grafting. Poncirus trifoliata, a widely used citrus rootstock, can promote early flowering, strengthen stress tolerance, and improve fruit quality via scion–rootstock interactions. Here, we report its genome assembly using PacBio sequencing. We obtained a final genome of 303 Mb with a contig N50 size of 1.17 Mb and annotated 25,680 protein-coding genes. DNA methylome and transcriptome analyses indicated that the strong adaptability of P. trifoliata is likely attributable to its special epigenetic modification and expression pattern of resistance-related genes. Heterografting by using sweet orange as scion and P. trifoliata as rootstock and autografting using sweet orange as both scion and rootstock were performed to investigate the genetic effects of the rootstock. Single-base methylome analysis indicated that P. trifoliata as a rootstock caused DNA demethylation and a reduction in 24-nt small RNAs (sRNAs) in scions compared to the level observed with autografting, implying the involvement of sRNA-mediated graft-transmissible epigenetic modifications in citrus grafting. Taken together, the assembled genome for the citrus rootstock and the analysis of graft-induced epigenetic modifications provide global insights into the genetic effects of rootstock–scion interactions and grafting biology.
Involvement of ethylene receptors in the salt tolerance response of Cucurbita pepo
Authors: Cebrián Gustavo , Iglesias-Moya Jessica , García Alicia , Martínez Javier , Romero Jonathan , Regalado José Javier , Martínez Cecilia , Valenzuela Juan Luis , Jamilena Manuel
Published: April 2021

Abiotic stresses have a negative effect on crop production, affecting both vegetative and reproductive development. Ethylene plays a relevant role in plant response to environmental stresses, but the specific contribution of ethylene biosynthesis and signalling components in the salt stress response differs between Arabidopsis and rice, the two most studied model plants. In this paper, we study the effect of three gain-of-function mutations affecting the ethylene receptors CpETR1B, CpETR1A, and CpETR2B of Cucurbita pepo on salt stress response during germination, seedling establishment, and subsequent vegetative growth of plants. The mutations all reduced ethylene sensitivity, but enhanced salt tolerance, during both germination and vegetative growth, demonstrating that the three ethylene receptors play a positive role in salt tolerance. Under salt stress, etr1b, etr1a, and etr2b germinate earlier than WT, and the root and shoot growth rates of both seedlings and plants were less affected in mutant than in WT. The enhanced salt tolerance response of the etr2b plants was associated with a reduced accumulation of Na+ in shoots and leaves, as well as with a higher accumulation of compatible solutes, including proline and total carbohydrates, and antioxidant compounds, such as anthocyanin. Many membrane monovalent cation transporters, including Na+/H+ and K+/H+ exchangers (NHXs), K+ efflux antiporters (KEAs), high-affinity K+ transporters (HKTs), and K+ uptake transporters (KUPs) were also highly upregulated by salt in etr2b in comparison with WT. In aggregate, these data indicate that the enhanced salt tolerance of the mutant is led by the induction of genes that exclude Na+ in photosynthetic organs, while maintaining K+/Na+ homoeostasis and osmotic adjustment. If the salt response of etr mutants occurs via the ethylene signalling pathway, our data show that ethylene is a negative regulator of salt tolerance during germination and vegetative growth. Nevertheless, the higher upregulation of genes involved in Ca2+ signalling (CpCRCK2A and CpCRCK2B) and ABA biosynthesis (CpNCED3A and CpNCED3B) in etr2b leaves under salt stress likely indicates that the function of ethylene receptors in salt stress response in C. pepo can be mediated by Ca2+ and ABA signalling pathways.
Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates
Authors: Döll Stefanie , Djalali Farahani-Kofoet Roxana , Zrenner Rita , Henze Andrea , Witzel Katja
Published: April 2021

Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as ‘lipids and lipid-like molecules’ or ‘phenylpropanoids and polyketides’. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to ‘lipid metabolism’, ‘biosynthesis of other secondary metabolites’ and ‘transport and catabolism’, reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to ‘transcription’, ‘translation’ and ‘folding, sorting and degradation’, in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function.
Differential regulation of triterpene biosynthesis induced by an early failure in cuticle formation in apple
Authors: Falginella Luigi , Andre Christelle M. , Legay Sylvain , Lin-Wang Kui , Dare Andrew P. , Deng Cecilia , Rebstock Ria , Plunkett Blue J. , Guo Lindy , Cipriani Guido , Espley Richard V.
Published: April 2021

Waxy apple cuticles predominantly accumulate ursane-type triterpenes, but the profile shifts with the induction of skin russeting towards lupane-type triterpenes. We previously characterised several key enzymes in the ursane-type and lupane-type triterpene pathways, but this switch in triterpene metabolism associated with loss of cuticle integrity is not fully understood. To analyse the relationship between triterpene biosynthesis and russeting, we used microscopy, RNA-sequencing and metabolite profiling during apple fruit development. We compared the skin of three genetically-close clones of ‘Golden Delicious’ (with waxy, partially russeted and fully russeted skin). We identified a unique molecular profile for the russet clone, including low transcript abundance of multiple cuticle-specific metabolic pathways in the early stages of fruit development. Using correlation analyses between gene transcription and metabolite concentration we found MYB transcription factors strongly associated with lupane-type triterpene biosynthesis. We showed how their transcription changed with the onset of cuticle cracking followed by russeting and that one factor, MYB66, was able to bind the promoter of the oxidosqualene cyclase OSC5, to drive the production of lupeol derivatives. These results provide insights into the breakdown of cuticle integrity leading to russet and how this drives MYB-regulated changes to triterpene biosynthesis.
Genomic analysis uncovers functional variation in the C-terminus of anthocyanin-activating MYB transcription factors
Authors: Rodrigues Jessica A. , Espley Richard V. , Allan Andrew C.
Published: April 2021

MYB transcription factors regulate diverse aspects of plant development and secondary metabolism, often by partnering in transcriptional regulatory complexes. Here, we harness genomic resources to identify novel MYBs, thereby producing an updated eudicot MYB phylogeny with revised relationships among subgroups as well as new information on sequence variation in the disordered C-terminus of anthocyanin-activating MYBs. BLAST® and hidden Markov model scans of gene annotations identified a total of 714 MYB transcription factors across the genomes of four crops that span the eudicots: apple, grape, kiwifruit and tomato. Codon model-based phylogenetic inference identified novel members of previously defined subgroups, and the function of specific anthocyanin-activating subgroup 6 members was assayed transiently in tobacco leaves. Sequence conservation within subgroup 6 highlighted one previously described and two novel short linear motifs in the disordered C-terminal region. The novel motifs have a mix of hydrophobic and acidic residues and are predicted to be relatively ordered compared with flanking protein sequences. Comparison of motifs with the Eukaryotic Linear Motif database suggests roles in protein–protein interaction. Engineering of motifs and their flanking regions from strong anthocyanin activators into weak activators, and vice versa, affected function. We conclude that, although the MYB C-terminal sequence diverges greatly even within MYB clades, variation within the C-terminus at and near relatively ordered regions offers opportunities for exploring MYB function and developing superior alleles for plant breeding.
The histone variant Sl_H2A.Z regulates carotenoid biosynthesis and gene expression during tomato fruit ripening
Authors: Yang Xuedong , Zhang Xuelian , Yang Youxin , Zhang Hui , Zhu Weimin , Nie Wen-Feng
Published: April 2021

The conserved histone variant H2A.Z is essential for transcriptional regulation; defense responses; and various biological processes in plants, such as growth, development, and flowering. However, little is known about how H2A.Z affects the developmental process and ripening of tomato fruits. Here, we utilized the CRISPR/Cas9 gene-editing system to generate a sl_hta9 sl_hta11 double-mutant, designated sl_h2a.z, and found that these two mutations led to a significant reduction in the fresh weight of tomato fruits. Subsequent messenger RNA (mRNA)-seq results showed that dysfunction of Sl_H2A.Z has profound effects on the reprogramming of genome-wide gene expression at different developmental stages of tomato fruits, indicating a ripening-dependent correlation between Sl_H2A.Z and gene expression regulation in tomato fruits. In addition, the expression of three genes, SlPSY1, SlPDS, and SlVDE, encoding the key enzymes in the biosynthesis pathway of carotenoids, was significantly upregulated in the later ripening stages, which was consistent with the increased contents of carotenoids in sl_h2a.z double-mutant fruits. Overall, our study reveals a role of Sl_H2A.Z in the regulation of carotenoids and provides a resource for the study of Sl_H2A.Z-dependent gene expression regulation. Hence, our results provide a link between epigenetic regulation via histone variants and fruit development, suggesting a conceptual framework to understand how histone variants regulate tomato fruit quality.
Silencing MdGH3-2/12 in apple reduces drought resistance by regulating AM colonization
Authors: Huang Dong , Wang Qian , Zhang Zhijun , Jing Guangquan , Ma Mengnan , Ma Fengwang , Li Chao
Published: April 2021

Drought leads to reductions in plant growth and crop yields. Arbuscular mycorrhizal fungi (AMF), which form symbioses with the roots of the most important crop species, alleviate drought stress in plants. In the present work, we identified 14 GH3 genes in apple (Malus domestica) and provided evidence that MdGH3-2 and MdGH3-12 play important roles during AM symbiosis. The expression of both MdGH3-2 and MdGH3-12 was upregulated during mycorrhization, and the silencing of MdGH3-2/12 had a negative impact on AM colonization. MdGH3-2/12 silencing resulted in the downregulation of five genes involved in strigolactone synthesis, and there was a corresponding change in root strigolactone content. Furthermore, we observed lower root dry weights in RNAi lines under AM inoculation conditions. Mycorrhizal transgenic plants showed greater sensitivity to drought stress than WT, as indicated by their higher relative electrolytic leakage and lower relative water contents, osmotic adjustment ability, ROS scavenging ability, photosynthetic capacity, chlorophyll fluorescence values, and abscisic acid contents. Taken together, these data demonstrate that MdGH3-2/12 plays an important role in AM symbiosis and drought stress tolerance in apple.
Deep intronic deletion in intron 3 of PLP1 is associated with a severe phenotype of Pelizaeus-Merzbacher disease
Authors: Yamamoto-Shimojima Keiko , Akagawa Hiroyuki , Yanagi Kumiko , Kaname Tadashi , Okamoto Nobuhiko , Yamamoto Toshiyuki
Published: April 2021

Recently, altered PLP1 splicing was confirmed as a genetic cause of hypomyelination of early myelinating structures (HEMS). A novel deep intronic deletion in intron 3 of PLP1 (NM_000533.5: c.453+59_+259del) was identified, and an in vitro minigene assay detected abnormal splicing patterns. However, the clinical and radiological findings of the patient were compatible with a severe phenotype of Pelizaeus-Merzbacher disease rather than HEMS, which may be due to undetected abnormal PLP1 splicing.
A cross-species analysis of systemic mediators of repair and complex tissue regeneration
Authors: Losner Julia , Courtemanche Katharine , Whited Jessica L.
Published: April 2021

Regeneration is an elegant and complex process informed by both local and long-range signals. Many current studies on regeneration are largely limited to investigations of local modulators within a canonical cohort of model organisms. Enhanced genetic tools increasingly enable precise temporal and spatial perturbations within these model regenerators, and these have primarily been applied to cells within the local injury site. Meanwhile, many aspects of broader spatial regulators of regeneration have not yet been examined with the same level of scrutiny. Recent studies have shed important insight into the significant effects of environmental cues and circulating factors on the regenerative process. These observations highlight that consideration of more systemic and possibly more broadly acting cues will also be critical to fully understand complex tissue regeneration. In this review, we explore the ways in which systemic cues and circulating factors affect the initiation of regeneration, the regenerative process, and its outcome. As this is a broad topic, we conceptually divide the factors based on their initial input as either external cues (for example, starvation and light/dark cycle) or internal cues (for example, hormones); however, all of these inputs ultimately lead to internal responses. We consider studies performed in a diverse set of organisms, including vertebrates and invertebrates. Through analysis of systemic mediators of regeneration, we argue that increased investigation of these “systemic factors” could reveal novel insights that may pave the way for a diverse set of therapeutic avenues.
Differential effects of changes in cardiorespiratory fitness on worst- and best- school subjects
Authors: Ishihara Toru , Morita Noriteru , Nakajima Toshihiro , Yamatsu Koji , Okita Koichi , Sagawa Masato , Kamijo Keita
Published: April 2021

Accumulating evidence shows a beneficial association between physical fitness and school children’s academic performance. However, several other studies have failed to demonstrate such an association. We reanalyzed data of a two-year longitudinal study of the association between changes in cardiorespiratory fitness and academic performance of school children by focusing on intra-individual variability in grade points as a possible source of this discrepancy. We analyzed data from 469 junior high school students to examine if improvements in cardiorespiratory fitness had a differential effect on an individual student’s worst and best grade points. Results indicated that improvements in physical fitness were associated with an improvement in the worst grade points. On the contrary, we did not observe a similar longitudinal association with the best grade points. These findings suggest that improving cardiorespiratory fitness improves the worst grade points of an individual, selectively. We suggest that intra-individual variability in grade points might moderate the association between physical fitness and academic performance changes.
A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
Authors: Atcheson Erwan , Hill Adrian V. S. , Reyes-Sandoval Arturo
Published: April 2021

Malaria continues to be a pressing global health issue, causing nearly half a million deaths per year. An effective malaria vaccine could radically improve our ability to control and eliminate this pathogen. The most advanced malaria vaccine, RTS,S, confers only 30% protective efficacy under field conditions, and hence the search continues for improved vaccines. New antigens and formulations are always first developed at a pre-clinical level. This paper describes the development of a platform to supplement existing tools of pre-clinical malaria vaccine development, by displaying linear peptides on a virus-like particle (VLP). Peptides from PfCSP, particularly from outside the normal target of neutralizing antibodies, the central NANP repeat region, are screened for evidence of protective efficacy. One peptide, recently identified as a target of potent neutralizing antibodies and lying at the junction between the N-terminal domain and the central repeat region of PfCSP, is found to confer protective efficacy against malaria sporozoite challenge in mice when presented on the Qβ VLP. The platform is also used to explore the effects of increasing numbers of NANP unit repeats, and including a universal CD4+T-cell epitope from tetanus toxin, on immunogenicity and protective efficacy. The VLP-peptide platform is shown to be of use in screening malaria peptides for protective efficacy and answering basic vaccinology questions in a pre-clinical setting.
Photophysics of DFHBI bound to RNA aptamer Baby Spinach
Authors: Dao Nguyen Thuan , Haselsberger Reinhard , Khuc Mai Thu , Phan Anh Tuân , Voityuk Alexander A. , Michel-Beyerle Maria-Elisabeth
Published: April 2021

The discovery of the GFP-type dye DFHBI that becomes fluorescent upon binding to an RNA aptamer, termed Spinach, led to the development of a variety of fluorogenic RNA systems that enable genetic encoding of living cells. In view of increasing interest in small RNA aptamers and the scarcity of their photophysical characterisation, this paper is a model study on Baby Spinach, a truncated Spinach aptamer with half its sequence. Fluorescence and fluorescence excitation spectra of DFHBI complexes of Spinach and Baby Spinach are known to be similar. Surprisingly, a significant divergence between absorption and fluorescence excitation spectra of the DFHBI/RNA complex was observed on conditions of saturation at large excess of RNA over DFHBI. Since absorption spectra were not reported for any Spinach-type aptamer, this effect is new. Quantitative modelling of the absorption spectrum based on competing dark and fluorescent binding sites could explain it. However, following reasoning of fluorescence lifetimes of bound DFHBI, femtosecond-fluorescence lifetime profiles would be more supportive of the notion that the abnormal absorption spectrum is largely caused by trans-isomers formed  within the cis-bound DFHBI/RNA complex. Independent of the origin, the unexpected discrepancy between absorption and fluorescence excitation spectra allows for easily accessed screening and insight into the efficiency of a fluorogenic dye/RNA system.
A wearable light-touch contact device for human balance support
Authors: Shima Keisuke , Shimatani Koji , Sakata Mami
Published: April 2021

There is an urgent need for the development of ways to address the major issue of falls among today’s globally aging population. The authors here outline a new approach referred to as virtual light-touch contact to mitigate postural sway during ambulatory and stationary periods, and propose a wearable light-touch (WLT) system featuring a virtual partition around the user that allows determination of virtual forces resulting from related contact. The data produced are used to create vibrotactile fingertip feedback, which supports comprehensive perception of the partition. Non-impaired subjects were recruited to support evaluation of the prototype system (incorporating tactile stimulation and motion-capture technology), with outcomes showing successful mitigation of postural sway in a heel-to-toe tandem stance. Research performed with 150 able-bodied volunteers to validate the performance of the new set-up (incorporating an acceleration sensor and a voice coil motor to render the light-touch effect) suggested that the proposed WLT approach supports human balance on a level comparable to that of the light-touch effect.
The virome of German bats: comparing virus discovery approaches
Authors: Kohl Claudia , Brinkmann Annika , Radonić Aleksandar , Dabrowski Piotr Wojtek , Mühldorfer Kristin , Nitsche Andreas , Wibbelt Gudrun , Kurth Andreas
Published: April 2021

Bats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.
Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants
Authors: Shen Jiaqi , Griffiths Paul T. , Campbell Steven J. , Utinger Battist , Kalberer Markus , Paulson Suzanne E.
Published: April 2021

Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH2and AH−) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH2/AH− + O2→ Fe(III)/Cu(II) + H2O2 + products. Rate constants are 5.7 × 104and 4.7 × 104 M−2 s−1for Fe(III) + AH2/AH−and 7.7 × 104and 2.8 × 106 M−2 s−1for Cu(II) + AH2/AH−, respectively.
Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
Authors: Fontelles Camile C. , da Cruz Raquel Santana , Gonsiewski Alexandra K. , Barin Ersilia , Tekmen Volkan , Jin Lu , Cruz M. Idalia , Loudig Olivier , Warri Anni , de Assis Sonia
Published: April 2021

We previously showed that environmentally-induced epigenetic inheritance of cancer occurs in rodent models. For instance, we reported that paternal consumption of an obesity-inducing diet (OID) increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear whether programming of breast cancer in daughters is due to systemic alterations or mammary epithelium-specific factors and whether the breast cancer predisposition in F1 progeny can be transmitted to subsequent generations. In this study, we show that mammary glands from F1 control (CO) female offspring exhibit enhanced growth when transplanted into OID females compared to CO mammary glands transplanted into CO females. Similarly, carcinogen-induced mammary tumors from F1 CO female offspring transplanted into OID females has a higher proliferation/apoptosis rate. Further, we show that granddaughters (F2) from the OID grand-paternal germline have accelerated tumor growth compared to CO granddaughters. This between-generation transmission of cancer predisposition is associated with changes in sperm tRNA fragments in OID males. Our findings indicate that systemic and mammary stromal alterations are significant contributors to programming of mammary development and likely cancer predisposition in OID daughters. Our data also show that breast cancer predisposition is transmitted to subsequent generations and may explain some familial cancers, if confirmed in humans.
Reliability of urinary charged metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry
Authors: Ishibashi Yoshiki , Harada Sei , Takeuchi Ayano , Iida Miho , Kurihara Ayako , Kato Suzuka , Kuwabara Kazuyo , Hirata Aya , Shibuki Takuma , Okamura Tomonori , Sugiyama Daisuke , Sato Asako , Amano Kaori , Hirayama Akiyoshi , Sugimoto Masahiro , Soga Tomoyoshi , Tomita Masaru , Takebayashi Toru
Published: April 2021

Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.
Accuracy of theoretical IOL formulas for Panoptix intraocular lens according to axial length
Authors: Choi Ayoung , Kwon Hyunggoo , Jeon Sohee
Published: April 2021

The accuracy of intraocular lens (IOL) calculations is suboptimal for long or short eyes, which results in a low visual quality after multifocal IOL implantation. The purpose of the present study is to evaluate the accuracy of IOL formulas (Barrett Universal II, SRK/T, Holladay 1, Hoffer Q, and Haigis) for the Acrysof IQ Panoptix TFNT IOL (Alcon Laboratories, Inc, Fort Worth, Texas, United States) implantation based on the axial length (AXL) from a large cohort of 2018 cases and identify the factors that are associated with a high mean absolute error (MAE). The Barrett Universal II showed the lowest MAE in the normal AXL group (0.30 ± 0.23), whereas the Holladay 1 and Hoffer Q showed the lowest MAE in the short AXL group (0.32 ± 0.22 D and 0.32 ± 0.21 D, respectively). The Haigis showed the lowest MAE in the long AXL group (0.24 ± 0.19 D). The Barrett Universal II did not perform well in short AXL eyes with higher astigmatism (P = 0.013), wider white-to-white (WTW; P < 0.001), and shorter AXL (P = 0.016). Study results suggest that the Barrett Universal II performed best for the TFNT IOL in the overall study population, except for the eyes with short AXL, particularly when the eyes had higher astigmatism, wider WTW, and shorter AXL.
Transverse aortic constriction induces gut barrier alterations, microbiota remodeling and systemic inflammation
Authors: Boccella Nicola , Paolillo Roberta , Coretti Lorena , D’Apice Stefania , Lama Adriano , Giugliano Giuseppe , Schiattarella Gabriele Giacomo , Cuomo Mariella , d’Aquino Ilaria , Cavaliere Gina , Paciello Orlando , Mollica Maria Pina , Mattace Raso Giuseppina , Esposito Giovanni , Lembo Francesca , Perrino Cinzia
Published: April 2021

Accumulating evidence suggests that modifications of gut function and microbiota composition might play a pivotal role in the pathophysiology of several cardiovascular diseases, including heart failure (HF). In this study we systematically analysed gut microbiota composition, intestinal barrier integrity, intestinal and serum cytokines and serum endotoxin levels in C57BL/6 mice undergoing pressure overload by transverse aortic constriction (TAC) for 1 and 4 weeks. Compared to sham-operated animals, TAC induced prompt and strong weakening of intestinal barrier integrity, long-lasting decrease of colon anti-inflammatory cytokine levels, significant increases of serum levels of bacterial lipopolysaccharide and proinflammatory cytokines. TAC also exerted effects on microbiota composition, inducing significant differences in bacterial genera inside Actinobacteria, Firmicutes, Proteobacteria and TM7 phyla as shown by 16S rDNA sequencing of fecal samples from TAC or sham mice. These results suggest that gut modifications represent an important element to be considered in the development and progression of cardiac dysfunction in response to TAC and support this animal model as a valuable tool to establish the role and mechanisms of gut-heart crosstalk in HF. Evidence arising in this field might identify new treatment options targeting gut integrity and microbiota components to face adverse cardiac events.
Toward the discovery of biological functions associated with the mechanosensor Mtl1p of Saccharomyces cerevisiae via integrative multi-OMICs analysis
Authors: Martínez-Matías Nelson , Chorna Nataliya , González-Crespo Sahily , Villanueva Lilliam , Montes-Rodríguez Ingrid , Melendez-Aponte Loyda M. , Roche-Lima Abiel , Carrasquillo-Carrión Kelvin , Santiago-Cartagena Ednalise , Rymond Brian C. , Babu Mohan , Stagljar Igor , Rodríguez-Medina José R.
Published: April 2021

Functional analysis of the Mtl1 protein in Saccharomyces cerevisiae has revealed that this transmembrane sensor endows yeast cells with resistance to oxidative stress through a signaling mechanism called the cell wall integrity pathway (CWI). We observed upregulation of multiple heat shock proteins (HSPs), proteins associated with the formation of stress granules, and the phosphatase subunit of trehalose 6-phosphate synthase which suggests that mtl1Δ strains undergo intrinsic activation of a non-lethal heat stress response. Furthermore, quantitative global proteomic analysis conducted on TMT-labeled proteins combined with metabolome analysis revealed that mtl1Δ strains exhibit decreased levels of metabolites of carboxylic acid metabolism, decreased expression of anabolic enzymes and increased expression of catabolic enzymes involved in the metabolism of amino acids, with enhanced expression of mitochondrial respirasome proteins. These observations support the idea that Mtl1 protein controls the suppression of a non-lethal heat stress response under normal conditions while it plays an important role in metabolic regulatory mechanisms linked to TORC1 signaling that are required to maintain cellular homeostasis and optimal mitochondrial function.
PaO2/FiO2 and IL-6 are risk factors of mortality for intensive care COVID-19 patients
Authors: Gu Yanli , Wang Donghui , Chen Cen , Lu Wanjun , Liu Hongbing , Lv Tangfeng , Song Yong , Zhang Fang
Published: April 2021

To identify the risk factors of mortality for the coronavirus disease 19 (COVID-19) patients admitted to intensive care units (ICUs) through a retrospective analysis. The demographic, clinical, laboratory, and chest imaging data of patients admitted to the ICU of Huoshenshan Hospital from February 10 to April 10, 2020 were retrospectively analyzed. Student's t-test and Chi-square test were used to compare the continuous and categorical variables, respectively. The logistic regression model was employed to ascertain the risk factors of mortality. This retrospective study involved 123 patients, including 64 dead and 59 survivors. Among them, 57 people were tested for interleukin-6 (IL-6) (20 died and 37 survived). In all included patients, the oxygenation index (PaO2/FiO2) was identified as an independent risk factor (odd ratio [OR] = 0.96, 95% confidence interval [CI]: 0.928–0.994, p = 0.021). The area under the curve (AUC) was 0.895 (95% CI: 0.826–0.943, p < 0.0001). Among the patients tested for IL-6, the PaO2/FiO2 (OR = 0.955, 95%CI: 0.915–0.996, p = 0.032) and IL-6 (OR = 1.013, 95%CI: 1.001–1.025, p = 0.028) were identified as independent risk factors. The AUC was 0.9 (95% CI: 0.791–0.964, p < 0.0001) for IL-6 and 0.865 (95% CI: 0.748–0.941, p < 0.0001) for PaO2/FiO2. PaO2/FiO2 and IL-6 could potentially serve as independent risk factors for predicting death in COVID-19 patients requiring intensive care.
Effects of pyrolysis temperature, feedstock type and compaction on water retention of biochar amended soil
Authors: Huang He , Reddy Narala Gangadhara , Huang Xilong , Chen Peinan , Wang Peiying , Zhang Yuantian , Huang Yuanxu , Lin Peng , Garg Ankit
Published: April 2021

Recent studies on water retention behaviour of biochar amended soil rarely considers the effect of pyrolysis temperature and also feedstock type into account. It is well known that pyrolysis temperature and feedstock type influences the physical and chemical properties of biochar due to stagewise decomposition of structure and chemical bonds. Further, soil density, which is in a loose state (in agricultural applications) and dense (in geo-environmental engineering applications) can also influence water retention behaviour of biochar amended soils. The major objective of this study is to investigate the water retention properties of soil amended with three different biochars in both loose and dense state. The biochars, i.e. water hyacinth biochar (WHB), chicken manure biochar (CMB) and wood biochar (WB) were produced in-house at different pyrolysis temperature. After then, biochars at 5% and 10% (w/w%) were amended to the soil. Water retention behaviour (soil suction and gravimetric water content) was studied under drying and wetting cycle simulated by varying relative humidity (RH, 50–90%). Results show that 10% WHB produced at 300 °C were found to possess highest water retention. CMB is found to possess higher water retention than WB for 10% amendment ratio. In general, the addition of three biochars (at both 300 °C and 600 °C) at 10% (w/w) significantly improved the water retention at all suction ranges in both loose and dense compaction state as compared to that of the bare soil. The adsorption (wetting) and desorption (drying) capacity of biochar amended soils is constant at corresponding RH.