bluuebunny/crossref_metadata_2025 huggingface dataset:
APlasmodium falciparumgenetic cross reveals the contributions ofpfcrtandplasmepsin II/IIIto piperaquine drug resistance
Authors: Kane John , Li Xue , Kumar Sudhir , Button-Simons Katrina A. , Vendrely Brenneman Katelyn M. , Dahlhoff Haley , Sievert Mackenzie A.C. , Checkley Lisa A. , Shoue Douglas A. , Singh Puspendra P. , Abatiyow Biley A. , Haile Meseret T. , Nair Shalini , Reyes Ann , Tripura Rupam , Peto Tom , Lek Dysoley , Kappe Stefan H.I. , Dhorda Mehul , Nkhoma Standwell C , Cheeseman Ian H. , Vaughan Ashley M. , Anderson Timothy J. C. , Ferdig Michael T.
Published: June 2023

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin (DHA) as a first-line treatment against malaria parasites. Multiple genetic drivers of PPQ resistance have been reported, including mutations in thePlasmodium falciparum chloroquine resistance transporter(pfcrt) and increased copies ofplasmepsin II/III(pm2/3). We generated a cross between a Cambodia-derived multi-drug resistant KEL1/PLA1 lineage isolate (KH004) and a drug susceptible parasite isolated in Malawi (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrtallele and a single copy ofpm2/3,while KH004 has a chloroquine-resistant (Dd2-like) pfcrtallele with an additional G367C substitution and four copies ofpm2/3. We recovered 104 unique recombinant progeny and examined a targeted set of progeny representing all possible combinations of variants atpfcrt and pm2/3for detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes, including PPQ survival assay (PSA), area under the dose-response curve (AUC), and a limited point IC50(LP-IC50). We find that inheritance of the KH004pfcrtallele is required for PPQ resistance, whereas copy number variation inpm2/3further enhances resistance but does not confer resistance in the absence of PPQ-R-associated mutations inpfcrt. Deeper investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributionsof pfcrt, pm2/3,and parasite genetic background, to a range of PPQ-related traits and confirm the critical role of the PfCRT G367C substitution in PPQ resistance.

Importance

Resistance to PPQ used in combination with DHA has emerged in Cambodia and threatens to spread to other malaria-endemic regions. Understanding the causal mutations of drug resistance and their impact on parasite fitness is critical for surveillance and intervention, and can also reveal new avenues to limiting the evolution and spread of drug resistance. An experimental genetic cross is a powerful tool for pinpointing the genetic determinants of key drug resistance and fitness phenotypes and have the distinct advantage of assaying the effects of naturally evolved genetic variation. Our study was significantly strengthened because the full a range of copies of KH004pm2/3was inherited among the progeny clones, allowing us to directly test the roleof pm2/3copy number on resistance-related phenotypes in the context of a uniquepfcrtallele. Our multi-gene model suggests an important role for both loci in the evolution of this ACT resistant parasite lineage.
Does improved (Limu) maize variety adoption improves rural households’ food security: evidence from Dale Wabara district, Ethiopia
Authors: Tesfa Bikila , Eneyew Adugna , Mitiku Fikadu
Published: June 2023

Adopting improved agricultural technology is important instruments to ensure household food security. There is, however, limited empirical evidence on impacts of adoption of improved maize varieties grown by smallholder farmers. Consequently, the study examined the impact of Limu maize variety adoption on rural households’ food security in Dale Wabara District, Ethiopia. Quantitative and qualitative data were collected from both primary and secondary sources. Three-stage sampling technique was employed to select 319 households for primary data collection. Binary logit model regression model and propensity score matching model were used to investigate determinants of Limu maize variety adoption and its impact on rural households’ food security, respectively. Furthermore, daily calorie intake per adult equivalent was used to measure food security status of household in study area. According to the results of the binary logit regression model households head education, family size, total land size, frequency of extension visits, livestock ownership and availability of Limu maize seed increases the likelihood of household’s adoption of Limu maize variety. The result of propensity score matching model shows that adoption of improved Limu maize variety significantly improve household food security (daily calorie intake). Empirical evidence shows that adopter households are better-off than non-adopter households in terms of their daily calorie intake. Thus, it can be concluded that Limu maize variety adoptions significantly contribute to the economic and social development of smallholder farmers by increasing food security status in study areas. It is therefore recommended that wider distribution of Limu maize variety has to be prioritized to improve food security in study areas.
An X Chromosome Transcriptome Wide Association Study Implicates ARMCX6 in Alzheimer’s Disease
Authors: Zhang Xueyi , Gomez Lissette , Below Jennifer , Naj Adam , Martin Eden , Kunkle Brian , Bush William S.
Published: June 2023

Background

The X chromosome is often omitted in disease association studies despite containing thousands of genes which may provide insight into well-known sex differences in the risk of Alzheimer’s Disease.

Objective

To model the expression of X chromosome genes and evaluate their impact on Alzheimer’s Disease risk in a sex-stratified manner.

Methods

Using elastic net, we evaluated multiple modeling strategies in a set of 175 whole blood samples and 126 brain cortex samples, with whole genome sequencing and RNA-seq data. SNPs (MAF>0.05) within thecis-regulatory window were used to train tissue-specific models of each gene. We apply the best models in both tissues to sex-stratified summary statistics from a meta-analysis of Alzheimer’s disease Genetics Consortium (ADGC) studies to identify AD-related genes on the X chromosome.

Results

Across different model parameters, sample sex, and tissue types, we modeled the expression of 217 genes (95 genes in blood and 135 genes in brain cortex). The average model R2was 0.12 (range from 0.03 to 0.34). We also compared sex-stratified and sex-combined models on the X chromosome. We further investigated genes that escaped X chromosome inactivation (XCI) to determine if their genetic regulation patterns were distinct. We found ten genes associated with AD at p < 0.05, with onlyARMCX6in female brain cortex (p = 0.008) nearing the significance threshold after adjusting for multiple testing (α = 0.002).

Conclusions

We optimized the expression prediction of X chromosome genes, applied these models to sex-stratified AD GWAS summary statistics, and identified one putative AD risk gene,ARMCX6.
Contrasting patterns of foraging behavior in Neotropical stingless bees using pollen and honey metabarcoding
Authors: Martins Aline C. , Proença Carolyn E. B. , Vasconcelos Thais N. C. , Aguiar Antonio J. C. , Farinasso Hannah C. , de Lima Aluisio T. F. , Faria Jair E. Q. , Norrana Krissya , Costa Marcella B. R. , Carvalho Matheus M. , Dias Rodrigo L. , Bustamante Mercedes M. C. , Carvalho Fernanda A. , Keller Alexander
Published: June 2023

Stingless bees are major flower visitors in the tropics, but their foraging preferences and behavior are still poorly understood. Studying stingless bee interactions with angiosperms is methodologically challenging due to the high tropical plant diversity and inaccessibility of upper canopy flowers in forested habitats. Pollen DNA metabarcoding offers an opportunity of assessing floral visitation efficiently and was applied here to understand stingless bee floral resources spectra and foraging behavior. We analyzed pollen and honey of three distantly related species of stingless bees, with different body size and social behavior:Melipona rufiventris, Scaptotrigona posticaandTetragonisca angustula. Simultaneously, we evaluate the local floristic components through seventeen rapid botanical surveys conducted at different distances from the nests. We discovered a broad set of explored floral sources, with 46.3 plant species per bee species in honey samples and 53.67 in pollen samples. Plant families Myrtaceae, Asteraceae, Euphorbiaceae, Melastomataceae and Malpighiaceae dominated the records, indicating stingless bee preferences for abundant resources that flowers of these families provide in the region. Results also reinforce the preference of stingless bees for forest trees, even if only available at long distances. Our high-resolution results encourage future bee-plant studies using pollen and honey metabarcoding in hyper diverse tropical environments.
BOTTOM-UP EFFECTS AND DENSITY DEPENDENCE DRIVE THE DYNAMIC OF AN ANTARCTIC SEABIRD PREDATOR-PREY SYSTEM
Authors: Viollat Lise , Quéroué Maud , Delord Karine , Gimenez Olivier , Barbraud Christophe
Published: June 2023

Understanding how populations respond to variability in environmental conditions and interspecific interactions is one of the biggest challenges of population ecology, particularly in the context of global change. Although several studies have investigated population responses to climate change, very few have explicitly integrated interspecific relationships when studying these responses. Here, we aim to understand the combined effects of inter- and intraspecific interactions and environmental conditions on the demographic parameters of a prey-predator system of three sympatric seabird populations breeding in Antarctica: the south polar skua (Catharacta maccormicki), and its two main preys during the breeding season, the Adélie penguin (Pygoscelis adeliae) and the emperor penguin (Aptenodytes forsteri). We built a two-species integrated population model (IPM) with 31 years of capture-recapture and count data, and provided a framework that allows estimating demographic parameters and abundance of a predator-prey system in a context where capture-recapture data are not available for one species. Our results showed that predator–prey interactions and local environmental conditions affect differently south polar skuas depending on their breeding state of the previous year. Concerning prey-predator relationships, the number of Adélie penguin breeding pairs showed a positive effect on south polar skua survival and breeding probability, and the number of emperor penguin dead chicks showed a positive effect on the breeding success of south polar skuas. In contrast, there was no evidence for an effect of the number of south polar skuas on the demography of Adélie penguins. We also found an important impact of sea ice conditions on both the dynamics of south polar skuas and Adélie penguins. Our results suggest that this prey-predator system is mostly driven by bottom-up processes and local environmental conditions.
Localized measurements of water potential reveal large loss of conductance in living tissues of maize leaves
Authors: Jain Piyush , Huber Annika E. , Rockwell Fulton E. , Sen Sabyasachi , Holbrook N. Michele , Stroock Abraham D.
Published: June 2023

The water status of the living tissue in leaves between the xylem and stomata (outside xylem zone - OXZ) play a critical role for plant function and global mass and energy balance but has remained largely inaccessible. We resolve the local water relations of OXZ tissue using a nanogel reporter of water potential (ψ), AquaDust, that enables an in-situ, non-destructive measurement of bothψof xylem and highly localizedψat the terminus of transpiration in the OXZ. Working in maize, these localized measurements reveal gradients in the OXZ that are several fold larger than those based on conventional methods, and values ofψin the mesophyll apoplast well below the macroscopic turgor loss potential. We find a strong loss of hydraulic conductance in both the bundle sheath and the mesophyll with decreasing xylem potential but not with evaporative demand. Our measurements suggest an active role played by the OXZ in regulating the transpiration path and our methods provide novel means to study this phenomenon.
Bringing up-to-date the toolkit for the catabolism of aromatic compounds in fungi: the unexpected 1,2,3,5–tetrahydroxybenzene central pathway
Authors: Martins Tiago M. , Bento Artur , Martins Celso , Tomé Ana S. , Moreira Carlos J.S. , Pereira Cristina Silva
Published: June 2023

Saprophytic fungi are able to catabolize many plant-derived aromatics, including, for example, gallate. The catabolism of gallate in fungi is assumed to depend on the five main central pathways,i.e., of the central intermediates’ catechol, protocatechuate, hydroxyquinol, homogentisate, and gentisate, but a definitive demonstration is lacking. To shed light on this process, we analyzed the transcriptional reprograming of the growth ofAspergillus terreuson gallate compared with acetate as the control condition. Surprisingly, the results revealed that the five main central pathways did not exhibit significant positive regulation. Instead, an in-depth analysis identified four highly expressed and upregulated genes that are part of a conserved gene cluster found in numerous species of fungi, though not inAspergilli. The cluster comprises a monooxygenase gene and a fumarylacetoacetate hydrolase-likegene, which are recognized as key components of catabolic pathways responsible for aromatic compound degradation. The other two genes encode proteins with no reported enzymatic activities. Through functional analyses of gene deletion mutants, the conserved short protein with no known domains could be linked to the conversion of the novel metabolite 5-hydroxydienelatone, whereas the DUF3500 gene likely encodes a ring-cleavage enzyme for 1,2,3,5–tetrahydroxybenzene. These significant findings establish the existence of a new 1,2,3,5-tetrahydroxybenzene central pathway for the catabolism of gallate and related compounds (e.g.,2,4,6-trihydroxybenzoate) in numerous fungi where this catabolic gene cluster was observed.

IMPORTANCE

The lignin found in various economically significant plants, such as major grains like rice, wheat, and maize, comprises a substantial portion of syringyl units (up to 60%). As a result, the future utilization of residues from these plants in biorefineries will yield significant quantities of syringyl derivatives. However, our understanding of how fungi degrade these syringyl derivatives is to date scarce and mostly relies on unproven assumptions. Our study, demonstrates the existence of a new 1,2,3,5-tetrahydroxybenzene central intermediate for the catabolism of gallate in numerous fungi. This finding expands the toolkit of central pathways, proving that the generalized assumption that gallate catabolism depends on the previously known five main central pathways was incorrect. This research reveals a novel crucial central pathway of great ecological and biotechnological importance, not only for fungi but also potentially for bacteria.
Validation ofde novodesigned water-soluble and transmembrane proteins byin silicofolding and melting
Authors: Hermosilla Alvaro Martin , Berner Carolin , Ovchinnikov Sergey , Vorobieva Anastassia A.
Published: June 2023

In silicovalidation ofde novodesigned proteins with deep learning (DL)-based structure prediction algorithms has become mainstream. However, formal evidence of the relationship between a high-quality predicted model and the chance of experimental success is lacking. We used experimentally characterizedde novodesigns to show that AlphaFold2 and ESMFold excel at different tasks. ESMFold can efficiently identify designs generated based on high-quality (designable) backbones. However, only AlphaFold2 can predict which sequences have the best chance of experimentally folding among similar designs. We show that ESMFold can generate high-quality structures from just a few predicted contacts and introduce a new approach based on incremental perturbation of the prediction (“in silicomelting”), which can reveal differences in the presence of favorable contacts between designs. This study provides a new insight on DL-based structure prediction models explainability and on how they could be leveraged for the design of increasingly complex proteins; in particular membrane proteins which have historically lacked basicin silicovalidation tools.
MSModDetector: A Tool for Detecting Mass Shifts and Post-Translational Modifications in Individual Ion Mass Spectrometry Data
Authors: Faizi Marjan , Fellers Ryan T , Lu Dan , Drown Bryon S , Jambhekar Ashwini , Lahav Galit , Kelleher Neil L , Gunawardena Jeremy
Published: June 2023

Motivation

Post-translational modifications (PTMs) on proteins regulate protein structures and functions. A single protein molecule can possess multiple modification sites that can accommodate various PTM types, leading to a variety of different patterns, or combinations of PTMs, on that protein. Different PTM patterns can give rise to distinct biological functions. To facilitate the study of multiple PTMs, top-down mass spectrometry (MS) has proven to be a useful tool to measure the mass of intact proteins, thereby enabling even widely separated PTMs to be assigned to the same protein molecule and allowing determination of how many PTMs are attached to a single protein.

Results

We developed a Python module called MSModDetector that studies PTM patterns from individual ion mass spectrometry (I MS) data. I MS is an intact protein mass spectrometry approach that generates true mass spectra without the need to infer charge states. The algorithm first detects and quantifies mass shifts for a protein of interest and subsequently infers potential PTM patterns using linear programming. The algorithm is evaluated on simulated I MS data and experimental I MS data for the tumor suppressor protein p53. We show that MSModDetector is a useful tool for comparing a protein’s PTM pattern landscape across different conditions. An improved analysis of PTM patterns will enable a deeper understanding of PTM-regulated cellular processes.

Availability

The source code is available athttps://github.com/marjanfaizi/MSModDetectortogether with the scripts used for analyses and to generate the figures presented in this study.
Structural variants and short tandem repeats impact gene expression and splicing in bovine testis tissue
Authors: Bhati Meenu , Mapel Xena Marie , Lloret-Villas Audald , Pausch Hubert
Published: June 2023

Structural variants (SVs) and short tandem repeats (STRs) are significant sources of genetic variation. However, the impacts of these variants on gene regulation have not been investigated in cattle. Here, we genotyped and characterized 19,408 SVs and 374,821 STRs in 183 bovine genomes and investigated their impact on molecular phenotypes derived from testis transcriptomes. We found that 71% STRs were multiallelic. The vast majority (95%) of STRs and SVs were in intergenic and intronic regions. Only 37% SVs and 40% STRs were in high LD (R2>0.8) with surrounding SNPs/Indels, indicating that SNP-based association testing and genomic prediction are blind to a non-negligible portion of genetic variation. We showed that both SVs and STRs were more than two-fold enriched among expression and splicing QTL (e/sQTL) relative to SNPs/Indels and were often associated with differential expression and splicing of multiple genes. Deletions and duplications had larger impacts on splicing and expression than any other type of structural variant. Exonic duplications predominantly increased gene expression either through alternative splicing or other mechanisms, whereas expression- and splicing-associated STRs primarily resided in intronic regions and exhibited bimodal effects on the molecular phenotypes investigated. Most e/sQTL resided within 100 kb of the affected genes or splicing junctions. We pinpoint candidate causal STRs and SVs associated with the expression ofSLC13A4andTTC7B, and alternative splicing of a lncRNA andCAPP1. We provide a catalogue of STRs and SVs for taurine cattle and show that these variants contribute substantially to gene expression and splicing variation.
Disruption of Prostaglandin F2αReceptor Signaling Attenuates Fibrotic Remodeling and Alters Fibroblast Population Dynamics in A Preclinical Murine Model of Idiopathic Pulmonary Fibrosis
Authors: Rodriguez Luis R. , Tang Soon Yew , Barboza Willy Roque , Murthy Aditi , Tomer Yaniv , Cai Tian-Quan , Iyer Swati , Chavez Katrina , Das Ujjalkumar Subhash , Ghosh Soumita , Dimopoulos Thalia , Babu Apoorva , Connelly Caitlin , FitzGerald Garret A. , Beers Michael F.
Published: June 2023

Idiopathic Pulmonary Fibrosis (IPF) is a chronic parenchymal lung disease characterized by repetitive alveolar cell injury, myofibroblast proliferation, and excessive extracellular matrix deposition for which unmet need persists for effective therapeutics. The bioactive eicosanoid, prostaglandin F2α, and its cognate receptor FPr (Ptfgr) are implicated as a TGFβ1 independent signaling hub for IPF. To assess this, we leveraged our published murine PF model (IER−SftpcI73T) expressing a disease-associated missense mutation in the surfactant protein C (Sftpc) gene. Tamoxifen treated IER-SftpcI73Tmice develop an early multiphasic alveolitis and transition to spontaneous fibrotic remodeling by 28 days. IER-SftpcI73Tmice crossed to a Ptgfr null (FPr−/−) line showed attenuated weight loss and gene dosage dependent rescue of mortality compared to FPr+/+cohorts. IER-SftpcI73T/FPr−/−mice also showed reductions in multiple fibrotic endpoints for which administration of nintedanib was not additive. Single cell RNA sequencing, pseudotime analysis, and in vitro assays demonstratedPtgfrexpression predominantly within adventitial fibroblasts which were reprogrammed to an “inflammatory/transitional” cell state in a PGF2α/ FPr dependent manner. Collectively, the findings provide evidence for a role for PGF2αsignaling in IPF, mechanistically identify a susceptible fibroblast subpopulation, and establish a benchmark effect size for disruption of this pathway in mitigating fibrotic lung remodeling.
Genetic architecture of individual meiotic crossover rate and distribution in a large Atlantic Salmon (Salmo salar)breeding population
Authors: Brekke Cathrine , Johnston Susan E. , Knutsen Tim M. , Berg Peer
Published: June 2023

Meiotic recombination through chromosomal crossovers ensures proper segregation of homologous chromosomes in meiosis, while also breaking down linkage disequilibrium and shuffling alleles at loci located on the same chromosome. Rates of recombination can vary between species, but also between and within individuals, sex and chromosomes within species. Indeed, the Atlantic salmon genome is known to have clear sex differences in recombination with female biased heterochiasmy and markedly different landscapes of crossovers between males and females. In male meiosis, crossovers occur strictly in the telomeric regions, whereas in female meiosis crossovers tend to occur closer to the centromeres. However, little is known about the genetic control of these patterns and how this differs at the individual level. Here, we investigate genetic variation in individual measures of recombination in >5000 large full-sib families of a Norwegian Atlantic salmon breeding population with high-density SNP genotypes. We show that females had 1.6× higher crossover counts (CC) than males, with autosomal linkage maps spanning a total of 2174 cM in females and 1483 cM in males. However, because of the extreme telomeric bias of male crossovers, female recombination is much more important for generation of new haplotypes with 8x higher intra-chromosomal genetic shuffling than males. CC was heritable in females (h2= 0.11) and males (h2= 0.10), and shuffling was also heritable in both sex but with a lower heritability in females (h2= 0.06) than in males (h2= 0.11). Inter-sex genetic correlations for both traits were close to zero, suggesting that rates and distribution of crossovers are genetically distinct traits in males and females, and that there is a potential for independent genetic change in both sexes in the Atlantic Salmon. Together, these findings give novel insights into the genetic architecture of recombination in salmonids and contribute to a better understanding of how rates and distribution of recombination may evolve in eukaryotes more broadly.
Imagination as predictive perception: mental imagery predictively biases perceptual judgments of observed action kinematics
Authors: Parrotta Eleonora , McDonough Katrina L. , Bach Patric
Published: June 2023

Recent approaches conceptualize mental imagery as a simulatory mode of perceptual experience, which relies on the voluntary engagement of the same top-down prediction processes that shape our perception of the external world. If so, then imagery should induce similar predictive biases as those that are known to govern the perceptual representation of others’ behaviour. In four experiments, participants saw object-directed approach and avoidance actions and reported the hands’ last seen location after their sudden disappearance. All revealed robust predictive biases, showing that perceptual judgments are illusorily distorted towards the implied goals of the actions and away from obstacles. Importantly, the experiments also showed that prior action imagery suffices to induce similar biases, so that perceptual judgments become distorted not only towards the action’s expected next steps but also the imagined ones. These imagery-induced biases were robust across stimulus sets and measurement methods. They reflect prior knowledge of how people move and can be induced not only through imagery of the actions itself, but also through imagery of situations in which the actions are merely expected. These data show that imagery induces similar perceptual expectations as other prediction processes, in line with the proposal that imagery reflects the voluntary control of predictive pathways that govern an event’s perceptual representation. Moreover, imagery candriveprediction processes, inducing expectations about events likely to occur in the imagined (not observed) realities, suggesting shared pathways through which imagery and prediction may support mental simulation and counterfactual reasoning.

Public Significance Statement

This study uses the perception of other people’s behaviour as a testing bed to advance the hypothesis that imagery can be understood aspredictedperception: that, when people imagine, they make voluntary use of the same prediction mechanisms that otherwise allow them to anticipate – and visualise – how a situation will develop further. In four experiments, the study shows (1) that imagining another’s behaviour induces the expectation that their actions will develop in the imagined manner, (2) that imagining situations elicits expectations about how people will behave within them, (3) that these imagery-induced expectations are integrated with other expectations people have about others’ behaviour and (4) subtly distort how these behaviours are visuospatially represented. The findings demonstrate a link between imagery and predictive perceptual abilities and reveal how imagery can act as a key tool in people’s ability to anticipate relevant futures and explore counterfactual realities.
Temporal analysis of relative distances (TARDIS) is a robust, parameter-free alternative to single-particle tracking
Authors: Martens Koen J.A. , Turkowyd Bartosz , Hohlbein Johannes , Endesfelder Ulrike
Published: June 2023

In single-particle tracking (spt), individual particles are localized and tracked over time to probe their diffusion and molecular interactions. Temporal crossing of trajectories, blinking particles, and false-positive localizations present computational challenges that have remained difficult to overcome. Here, we introduce a robust, parameter-free alternative to spt: TARDIS. In TARDIS, an all-to-all distance analysis between localizations is performed with increasing temporal shifts. These pairwise distances fall in two categories: inter-particle distances not originating from the same particle, and intra-particle distances originating from the same particle. Since the distribution of inter-particle distances is unaffected by temporal shifts, the distribution of particle jump distances can be analytically fitted by analysing multiple temporal shifts. TARDIS outperforms existing tracking algorithms especially in complex conditions, and is even robust in scenarios that exceed the capabilities of current localization algorithms. Using TARDIS, we further show that measurements can be five-fold shorter without loss of information.
Comprehensive Characterization of tRNA by Ultra High-Performance Liquid Chromatography High-Resolution Accurate Mass Spectrometry
Authors: Ross Robert L , Cowley Ryan , Murphy Keeley , Gamez Roberto , Gazis Paul R , Sutton Jennifer , Du Min
Published: June 2023

Transfer ribonucleic acid (tRNA) are the smallest RNA in the translational triune and contain the greatest density of post-transcriptional modifications than any other RNA types in the cell. Due to the size of tRNA studying these modifications usually entails enzymatic digestion followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Here we report an advancement in Intact Mass Analysis for identification of tRNA through deconvolution of high resolution accurate mass spectrometry facilitated using a secondary alkylamine as an ion pairing reagent during reverse phase chromatography. We identify in isolated and totalS. cerevisiaetRNA 3’ CCA variations and show that most tRNA lack a 3’ adenosine with the lesser abundant species having the expected CCA termini. We identify a previously unknown stable demethylated Wybutosine intermediate for tRNAPHEand identify low abundant contaminating tRNAs in an isolated tRNAPHEsample. Confirmation of identities was verified through traditional mass spectrometric nucleoside and mass mapping experiments.
Sequence and epigenetic landscapes of active and silenced nucleolus organizers in Arabidopsis
Authors: Fultz Dalen , McKinlay Anastasia , Enganti Ramya , Pikaard Craig S.
Published: June 2023

Arabidopsis thalianahas two ribosomal RNA gene loci, nucleolus organizer regionsNOR2andNOR4, whose complete sequences remain undefined. Ultra-long DNA sequences assembled using an unconventional approach yielded 5.5 and 3.9 Mbp sequences forNOR2andNOR4(in the reference strain, Col-0), revealing their distinct gene subtype compositions. RNA sequencing and identification of genes associated with flow-sorted nucleoli of wild-type or silencing-defective mutant plants shows that most ofNOR4is comprised of active genes whereas most, but not all,NOR2genes are epigenetically silenced. Long intervals of low CG and CHG methylation overlap regions of gene activity and gene subtype homogenization. Collectively, the data reveal the genetic and epigenetic landscapes of the NORs and implicate transcription in rRNA gene concerted evolution.

One Sentence Summary

NOR2andNOR4sequences fill genome gaps and enable megabase-scale analyses of rRNA gene regulation and concerted evolution.
Large-scale map of RNA binding protein interactomes across the mRNA life-cycle
Authors: Street Lena , Rothamel Katherine , Brannan Kristopher , Jin Wenhao , Bokor Benjamin , Dong Kevin , Rhine Kevin , Madrigal Assael , Al-Azzam Norah , Kim Jenny Kim , Ma Yanzhe , Abdou Ahmed , Wolin Erica , Doron-Mandel Ella , Ahdout Joshua , Mujumdar Mayuresh , Jovanovic Marko , Yeo Gene W
Published: June 2023

Messenger RNAs (mRNAs) interact with RNA-binding proteins (RBPs) in diverse ribonucleoprotein complexes (RNPs) during distinct life-cycle stages for their processing and maturation. While substantial attention has focused on understanding RNA regulation by assigning proteins, particularly RBPs, to specific RNA substrates, there has been considerably less exploration leveraging protein-protein interaction (PPI) methodologies to identify and study the role of proteins in mRNA life-cycle stages. To address this gap, we generated an RNA-aware RBP-centric PPI map across the mRNA life-cycle by immunopurification (IP-MS) of ∼100 endogenous RBPs across the life-cycle in the presence or absence of RNase, augmented by size exclusion chromatography (SEC-MS). Aside from confirming 8,700 known and discovering 20,359 novel interactions between 1125 proteins, we determined that 73% of our IP interactions are regulated by the presence of RNA. Our PPI data enables us to link proteins to life-cycle stage functions, highlighting that nearly half of the proteins participate in at least two distinct stages. We show that one of the most highly interconnected proteins, ERH, engages in multiple RNA processes, including via interactions with nuclear speckles and the mRNA export machinery. We also demonstrate that the spliceosomal protein SNRNP200 participates in distinct stress granule-associated RNPs and occupies different RNA target regions in the cytoplasm during stress. Our comprehensive RBP-focused PPI network is a novel resource for identifying multi-stage RBPs and exploring RBP complexes in RNA maturation.

HIGHLIGHTS

An RBP-centric RNA-aware PPI network focuses on the mRNA life-cycle in human cells

Prey-prey correlation analysis assigns prey proteins to life-cycle stages, of which 536 proteins (half of the network) interact with multiple steps

ERH is highly connected to multiple RNPs to affect nuclear speckle organization and mRNA export

Splicing factor SNRNP200 interacts with stress granule proteins and has distinct RNA occupancy in the cytoplasm
Z-Ala–Ile-OH, a dipeptide building block suitable for the formation of orthorhombic microtubes
Authors: Gessmann Renate , Garcia-Saez Isabel , Simatos Georgios , Mitraki Anna
Published: June 2023

Self-assembling dipeptides have emerged in the last two decades as promising building blocks for the development of novel biomaterials. Among the various classes of dipeptides, aromatic dipeptides and especially diphenylalanine (Phe–Phe), which forms hexagonal nanotubes, have been the most extensively studied. However, aliphatic peptides or mixed aromatic–aliphatic dipeptides seem just as promising, exhibiting various structures ranging from amyloid fibrils to microtubes. Herein we report the single-crystal structure of an aliphatic dipeptide, alanine–isoleucine (Ala–Ile), C17H24N2O5, protected with a benzyloxycarbonyl (Z) group at the N-terminus. The protected dipeptide crystallizes in the orthorhombic space group P212121 and forms hollow microtubes with orthorhombic symmetry upon evaporation on glass surfaces, as shown by field emission scanning electron microscopy (FESEM). These findings provide an increased understanding of the correlation between the single-crystal structure of the peptide building block and its self-assembly mechanism, and expand the library of available building blocks for microtechnological applications.
Cyclopentadienone triisocyanide iron complexes: general synthesis and crystal structures of tris(2,6-dimethylphenyl isocyanide)(η4-tetraphenylcyclopentadienone)iron and tris(naphthalen-2-yl isocyanide)(η4-tetraphenylcyclopentadienone)iron acetone hemisolvate
Authors: Bütikofer André , Chen Peter
Published: June 2023

Irradiation of a toluene solution containing cyclopentadienone tricarbonyl iron complexes and isocyanides with blue LEDs afforded the formation and isolation of 12 triisocyanide complexes, two of which, namely tris(2,6-dimethylphenyl isocyanide)(η4-tetraphenylcyclopenatedienone)iron, [Fe(C9H9N)3(C29H20O)], and tris(naphthalen-2-yl isocyanide)(η4-tetraphenylcyclopenatedienone)iron acetone hemisolvate, [Fe(C11H7N)3(C29H20O)]2·C3H6O, could be characterized crystallographically. The air-stable compounds were purified by column chromatography and were characterized by 1H NMR, 13C NMR, elemental analysis and HRMS. NMR and XRD data indicate generally more electron-rich Fe0 centers compared to the corresponding tricarbonyl compounds.
Financial statement fraud litigation, material weaknesses, and board characteristics
Authors: Manry David , Huang Hua-Wei , Yan Yun-Chia
Published: June 2023

Purpose

The purpose of this study is to investigate whether the likelihood that a firm will face financial statement fraud litigation is affected by the disclosure of internal control material weaknesses (MW) and the “busyness” of a firm’s board of directors.

Design/methodology/approach

The results are derived from logistic regression models and data are collected from the Audit Analytics database augmented by data from CompuStat, the Stanford Law School website and the SEC Accounting and Auditing Enforcement Releases. The authors also test for endogeneity with a propensity score matching procedure.

Findings

The authors find that an MW report is strongly associated with the likelihood of subsequent financial statement fraud litigation, and that the influence of entity-level MW on litigation likelihood is stronger than that of account-level MW. Moreover, the number of outside board directorships significantly increases the influence of entity-level MW on the likelihood of litigation, indicating that board of directors’ busyness significantly increases the risk of litigation.

Originality/value

Previous research notes that board members holding multiple directorships cannot effectively oversee the financial reporting process and, thus, are associated with poorer governance. The authors extend this implication of board busyness to the association between disclosure of MW type and the filing of subsequent litigation alleging financial statement fraud. To the best of the authors’ knowledge, no other research has done so.
Exploring the nonlinear relationship between strategic alliances and entrepreneurial performance in Chinese new ventures: the moderating role of transactive memory systems in entrepreneurial teams
Authors: Li Wei , Feng Zhuzhu
Published: June 2023

Purpose

Over the past decades, mainstream studies have generally indicated that new ventures could improve entrepreneurial performance by adopting strategic alliances (SAs). However, recently an increasing number of new ventures appear to not realize this objective using SAs at all times and may, rather, even be stuck in the survival trap. This dilemma indicates that the causal relationship between SAs and entrepreneurial performance in new ventures is not simply linear and rather a further complex nonlinear relationship. To handle this debate, this study attempted to reveal the nonlinear relationship of two types of SAs (technology alliances and market alliances) in new ventures with entrepreneurial performance (organizational growth and customer value). In addition, the moderating effect of transactive memory system (TMS) in the entrepreneurial team under the nonlinear relationship was explored.

Design/methodology/approach

This study established a research model by considering technology alliances and market alliances as two independent variables, organizational growth and customer value as two dimensions of entrepreneurial performance, and TMS as the moderators. The survey data collected from 207 Chinese new ventures was subjected to the hierarchical linear regression method for testing the proposed hypotheses.

Findings

The results revealed that there is an inverse U-shaped relationship between technology alliances and organizational growth, while the relationship between technology alliances and customer value was U-shaped. In addition, the relationship between market alliances and organizational growth was U-shaped, while an inverse U-shaped relationship was observed between market alliances and customer value. Finally, TMS was observed to positively moderate the U-shaped relationship between technology alliances and customer value as well as the U-shaped relationship between market alliances and organizational growth.

Originality/value

This study concluded that a nonlinear relationship between SAs and entrepreneurial performance existed in new ventures, which contributes to resolving the debate on whether new ventures could adopt SAs to improve entrepreneurial performance at all times. Specifically, the findings of this study would enrich the existing literature on the outcomes of SAs in new ventures through an evaluation of the effect of the inverse nonlinear relationship between technology alliances and market alliances on entrepreneurial performance (e.g. organizational growth and customer value). In addition, the findings of this study would extend the discussions about the conditions of the above causal relationship by introducing the TMS as the core moderator.
Simulating dual solutions of coupled pore-fluid flow and chemical dissolution problems in fluid-saturated heterogeneous porous media
Authors: Zhao Chongbin , Hobbs B.E. , Ord Alison
Published: June 2023

Purpose

The objective of this paper is to establish a solution strategy for obtaining dual solutions, namely trivial (conventional) and nontrivial (unconventional) solutions, of coupled pore-fluid flow and chemical dissolution problems in heterogeneous porous media.

Design/methodology/approach

Through applying a perturbation to the pore-fluid velocity, original governing partial differential equations of a coupled pore-fluid flow and chemical dissolution problem in heterogeneous porous media are transformed into perturbed ones, which are then solved by using the semi-analytical finite element method. Through switching off and on the applied perturbation terms in the resulting perturbed governing partial differential equations, both the trivial and nontrivial solutions can be obtained for the original governing partial differential equations of the coupled pore-fluid flow and chemical dissolution problem in fluid-saturated heterogeneous porous media.

Findings

When a coupled pore-fluid flow and chemical dissolution system is in a stable state, the trivial and nontrivial solutions of the system are identical. However, if a coupled pore-fluid flow and chemical dissolution system is in an unstable state, then the trivial and nontrivial solutions of the system are totally different. This recognition can be equally used to judge whether a coupled pore-fluid flow and chemical dissolution system involving heterogeneous porous media is in a stable state or in an unstable state. The proposed solution strategy can produce dual solutions for simulating coupled pore-fluid flow and chemical dissolution problems in fluid-saturated heterogeneous porous media.

Originality/value

A solution strategy is proposed to obtain the nontrivial solution, which is often overlooked in the computational simulation of coupled pore-fluid flow and chemical dissolution problems in fluid-saturated heterogeneous porous media. The proposed solution strategy provides a useful way for understanding the underlying dynamic mechanisms of the chemical damage effect associated with the stability of structures that are built on soil foundations.
Culturally relevant approaches to fostering postsecondary readiness in the dual credit English classroom
Authors: Duncheon Julia C. , Hornbeck Dustin , Sagara Reid
Published: June 2023

Purpose

This study examines how English teachers use culturally relevant pedagogy (CRP) to support postsecondary readiness for underrepresented students in the context of dual credit (DC) coursework in the USA. Postsecondary readiness, termed “college readiness” in the USA, refers to the skills and knowledge students need to succeed at a university. DC courses are university-level classes delivered to high school students through partnerships with postsecondary institutions, most often two-year community colleges. The purpose of this study is to highlight practices and institutional conditions that enable English instructors to foster postsecondary opportunity for all.

Design/methodology/approach

Using an interpretive approach, this qualitative study analyzes data derived from in-depth interviews with five community college English instructors who teach DC to diverse high-school students and who apply CRP in their classroom practice.

Findings

Findings reveal that instructors used culturally relevant approaches not only to help students access dominant college-ready skills, but also to reimagine what constitutes college readiness to begin with. Instructors also took advantage of their unique positioning as postsecondary instructors working with secondary students, leaning on academic freedom to push boundaries with their curriculum.

Originality/value

This study shows how English instructors are uniquely positioned to enhance university preparation and build a more inclusive vision of postsecondary readiness for all students. The study also highlights institutional conditions, such as teacher autonomy, pedagogical training and administrator support, that can promote culturally relevant postsecondary preparation in English classrooms.
The key enablers of SMEs readiness in Industry 4.0: a case of Malaysia
Authors: Kee Daisy Mui Hung , Cordova Miguel , Khin Sabai
Published: June 2023

Purpose

The study sheds light on the internal enabling factors towards emerging market (EM) small and medium-sized enterprises’ (SMEs) preparedness for Industry 4.0 (I4.0) using three dimensions: managerial, operational and technological readiness.

Design/methodology/approach

The study uses convenience sampling, having online and paper-based surveys and collecting 110 responses from manufacturing Malaysian SMEs. This sample allowed assessing the relationships of the hypothesized variables through the structural model of data analysis.

Findings

This study’s findings demonstrate that financial capability and perceived benefits enhance Malaysian SMEs' managerial, operational and technological readiness.

Research limitations/implications

Using Malaysia's case, this paper extends the discussion of the key drivers that underline the decision of EM firms to adopt I4.0.

Practical implications

This study’s results provide valuable insights for policymakers to improve the digital ecosystem. Also, understanding critical drivers for I4.0 readiness would encourage SMEs in Malaysia to embrace new digital technologies.

Originality/value

Although digital transformation towards I4.0 for manufacturing SMEs would be decisive, little is known about how ready these Malaysian firms are to adopt it or the driving factors that motivate them. Meanwhile, inadequate readiness causes a high failure rate in implementing new technology, processes or organizational changes.