bluuebunny/crossref_metadata_2025 huggingface dataset:
A neural modeling approach to study mechanisms underlying the heterogeneity of visual spatial frequency sensitivity in schizophrenia
Authors: Dugan Caroline , Zikopoulos Basilis , Yazdanbakhsh Arash
Published: October 2023

Patients with schizophrenia exhibit abnormalities in spatial frequency sensitivity, and it is believed that these abnormalities indicate more widespread dysfunction and dysregulation of bottom-up processing. The early visual system, including the first-order Lateral Geniculate Nucleus of the thalamus (LGN) and the primary visual cortex (V1), are key contributors to spatial frequency sensitivity. Medicated and unmedicated patients with schizophrenia exhibit contrasting changes in spatial frequency sensitivity, thus making it a useful probe for examining potential effects of the disorder and antipsychotic medications in neural processing. We constructed a parameterized, rate-based neural model of on-center/off-surround neurons in the early visual system to investigate the impacts of changes to the excitatory and inhibitory receptive field subfields. By incorporating changes in both the excitatory and inhibitory subfields that are associated with pathophysiological findings in schizophrenia, the model successfully replicated perceptual data from behavioral/functional studies involving medicated and unmedicated patients. Among several plausible mechanisms, our results highlight the dampening of excitation and/or increase in the spread and strength of the inhibitory subfield in medicated patients and the contrasting decreased spread and strength of inhibition in unmedicated patients. Given that the model was successful at replicating results from perceptual data under a variety of conditions, these elements of the receptive field may be useful markers for the imbalances seen in patients with schizophrenia.
Phylogenomics, biogeography, and trait evolution of the Boletaceae (Boletales, Agaricomycetes, Basidiomycota)
Authors: Tremble Keaton , Henkel Terry , Bradshaw Alexander , Domnauer Colin , Brown Lyda , Thám Lê Xuân , Furci Guliana , Aime Cathie , Moncalvo Jean-Marc , Dentinger Bryn
Published: October 2023

The species-rich porcini mushroom family Boletaceae is a widespread and well-known group of ectomycorrhizal (ECM) mushroom-forming fungi that has eluded intrafamilial phylogenetic resolution despite many attempts using morphological traits and multi-locus molecular datasets. In this study, we present a genome-wide molecular dataset of 1764 single-copy gene families from a global sampling of 418 Boletaceae specimens. The resulting phylogenetic analysis has strong statistical support for most branches of the tree, including the first statistically robust backbone. The enigmaticPhylloboletellus chloephorusfrom non-ECM Argentinian subtropical forests was recovered as an early diverging lineage within the Boletaceae. Time-calibrated branch lengths estimate that the family first arose in the early- to mid-Cretaceous and underwent a rapid radiation in the Eocene, possibly when the ECM nutritional mode arose with the emergence and diversification of ECM angiosperms. Biogeographic reconstructions reveal a complex history of vicariance and episodic long-distance dispersal correlated with historical geologic events, including Gondwanan origins and cladogenesis patterns that parallel its fragmentation. Ancestral state reconstruction of sporocarp morphological traits predicts that the ancestor of the Boletaceae was lamellate with ornamented basidiospores, contrary to most contemporary “bolete” morphologies. Transition rates indicated that the lamellate hymenophore and sequestrate sporocarp are reversible traits. Together, this study represents the most comprehensively sampled, data-rich molecular phylogeny of the Boletaceae to date, enabling robust inferences of trait evolution and biogeography in the group.
Collagen IV of basement membranes: I. Origin and diversification of COL4 genes enabling animal evolution and adaptation
Authors: Page-McCaw Patrick S , Pokidysheva Elena N , Darris Carl E. , Chetyrkin Sergei , Fidler Aaron L , Gallup Julianna ,   Aspirnauts, Murawala Prayag , Hudson Julie K , Boudko Sergei , Hudson Billy G
Published: October 2023

Collagen IV is a major component of basement membranes, a specialized form of extracellular matrix that enabled the assembly of multicellular epithelial tissues. In mammals, collagen IV assembles from a family of six α-chains (α1 to α6), forming three supramolecular scaffolds: Col-IVα121, Col-IVα345 and Col-IVα121-α556. The α-chains are encoded by six genes (COL4A1-6) that occur in pairs in a head-to-head arrangement. In Alport syndrome, variants in COL4A3, 4 or 5 genes, encoding Col-IVα345 scaffold in glomerular basement membrane (GBM), the kidney ultrafilter, cause progressive renal failure in millions of people worldwide. How variants cause dysfunction remains obscure. Here, we gained insights into Col-IVα345 function by determining its evolutionary lineage, as revealed from phylogenetic analyses and tissue expression of COL4 gene-pairs. We found that the COL4A⟨1|2⟩ gene-pair emerged in basal Ctenophores and Cnidaria phyla and is highly conserved across metazoans. The COL4A⟨1|2⟩ duplicated and arose as the progenitor to the COL4A⟨3|4⟩ gene-pair in cyclostomes, coinciding with emergence of kidney GBM, and expressed and conserved in jawed-vertebrates, except for amphibians, and a second duplication as the progenitor to the COL4A⟨5|6⟩ gene-pair and conserved in jawed-vertebrates. These findings revealed that Col-IVα121 is the progenitor scaffold, expressed ubiquitously in metazoan basement membranes, and which evolved into vertebrate Col-IVα345 and expressed in GBM. The Col-IVα345 scaffold, in comparison, has an increased number of cysteine residues, varying in number with osmolarity of the environment. Cysteines mediate disulfide crosslinks between protomers, an adaptation enabling a compact GBM that withstands the high hydrostatic pressure associated with glomerular ultrafiltration.
WITHDRAWN: Impaired Mitochondrial Calcium Homeostasis Induces Failed Remodeling of the Spiral Artery in Preeclampsia
Authors: Lu Xiyuan , Wang Yifan , Zou Zhiguo , Wang Chuan , Feng Xueqing , Geng Na , Wang Yuehong , Xu Zhice , Pu Jun
Published: October 2023

Withdrawal Statement

The authors have withdrawn their manuscript owing to further revisions and additional experiments are needed to ensure the accuracy and completeness of the research findings. As a result, we believe it is in the best interest of the scientific community and the integrity of the manuscript to withdraw it at this time. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Bioinfo-Bench: A Simple Benchmark Framework for LLM Bioinformatics Skills Evaluation
Authors: Chen Qiyuan , Deng Cheng
Published: October 2023

Abstract

Large Language Models (LLMs) have garnered significant recognition in the life sciences for their capacity to comprehend and utilize knowledge. The contemporary expectation in diverse industries extends beyond employing LLMs merely as chatbots; instead, there is a growing emphasis on harnessing their potential as adept analysts proficient in dissecting intricate issues within these sectors. The realm of bioinformatics is no exception to this trend. In this paper, we introduce Bioinfo-Bench, a novel yet straightforward benchmark framework suite crafted to assess the academic knowledge and data mining capabilities of foundational models in bioinformatics. Bioinfo-Benchsystematically gathered data from three distinct perspectives: knowledge acquisition, knowledge analysis, and knowledge application, facilitating a comprehensive examination of LLMs. Our evaluation encompassed prominent models ChatGPT, Llama, and Galactica. The findings revealed that these LLMs excel in knowledge acquisition, drawing heavily upon their training data for retention. However, their proficiency in addressing practical professional queries and conducting nuanced knowledge inference remains constrained. Given these insights, we are poised to delve deeper into this domain, engaging in further extensive research and discourse. It is pertinent to note that project Bioinfo-Benchis currently in progress, and all associated materials will be made publicly accessible.1
Characterization of the cryptic interspecific hybridLemna × mediterraneaby an integrated approach provides new insights into duckweed diversity
Authors: Braglia Luca , Ceschin Simona , Iannelli M. Adelaide , Bog Manuela , Fabriani Marco , Frugis Giovanna , Gavazzi Floriana , Gianì Silvia , Mariani Flaminia , Muzzi Maurizio , Pelella Emanuele , Morello Laura
Published: October 2023

Lemnaceae taxonomy is challenged by the particular morphology of these tiny free-floating angiosperms, reduced to a single leaf-like structure called frond, without or with one to few roots. Although molecular taxonomy has helped clarify the phylogenetic history of this family, inconsistency between morphological data and nuclear and plastid markers still poses challenging questions in some cases, leading to frequent misclassifications in the genusLemna. Recently, the finding thatLemna japonicais an interspecific hybrid betweenLemna minorandLemna turionifera, provided a clear explanation to one of such taxonomic questions. Here we demonstrated thatL. minoris also capable to hybridize withLemna gibba, generating a cryptic, previously unrecognized, but widespread taxon in the Mediterranean area. The nothotaxonLemna×mediterraneais described through the detailed investigation of seven hybrid clones from a living germplasm collection and compared with clones of the putative parental speciesL. minorandL. gibba. Genetic analysis revealed that two different cytotypes, diploid and triploid, originated by at least two independent hybridization events. Despite high overall similarity, morphometrical, physiological and biochemical analyses showed an intermediate position ofL.×mediterraneabetween its parental species in most qualitative and quantitative characters, and also separation of the two hybrid cytotypes by some criteria. These data provide evidence that hybridization and polyploidization, driving forces of terrestrial plant evolution, contribute to the duckweed genetic diversity and may have also shaped the phylogenetic history of these mainly asexual, aquatic plants. Further elucidation of hybridization mechanisms and flowering regulation will provide perspectives for future breeding strategies.
ClusterV-Web: A User-Friendly Tool for Profiling HIV Quasispecies and Generating Drug Resistance Reports from Nanopore Long-Read Data
Authors: Su Junhao , Li Shumin , Zheng Zhenxian , Lam Tak-Wah , Luo Ruibang
Published: October 2023

Third-generation long-read sequencing is an increasingly utilized technique for profiling HIV quasispecies and detecting drug resistance mutations due to its ability to cover the entire viral genome in individual reads. Recently, the ClusterV tool has demonstrated accurate detection of HIV quasispecies from Nanopore long-read sequencing data. However, the need for scripting skills and a computational environment may act as a barrier for many potential users. To address this issue, we have introduced ClusterV-Web, a user-friendly web-based application that enables easy configuration and execution of ClusterV, both remotely and locally. Our tool provides interactive tables and data visualizations to aid in the interpretation of results. This development is expected to democratize access to long-read sequencing data analysis, enabling a wider range of researchers and clinicians to efficiently profile HIV quasispecies and detect drug resistance mutations.

Availability and implementation

ClusterV-Web is freely available and open source, with detailed documentation accessible athttp://www.bio8.cs.hku.hk/ClusterVW/. The standalone Docker image and source code are also available athttps://github.com/HKU-BAL/ClusterV-Web.

Contact

rbluo@cs.hku.hk, Department of Computer Science, The University of Hong Kong, Hong Kong, China;jhsu@cs.hku.hk, Department of Computer Science, The University of Hong Kong, Hong Kong, China

Supplementary information

None
Role of transcription and translation during the early development of the brown algaEctocarpus
Authors: Liesner Daniel , Luthringer Rémy , Colin Sébastien , Morales Julia , Cock J. Mark , Coelho Susana M.
Published: October 2023

Background and aims

Parthenogenesis, the embryonal development of an unfused gamete, is a widespread trait within the brown algae (Phaeophyceae). We hypothesized that the parthenogenetic development of male gametes of the model brown algaEctocarpusspecies 7 would rapidly be dependent onde novotranscription and translation because of the small size of the gamete cell.

Methods

We followed the development of maleEctocarpusgametes to parthenosporophytes in the presence of either the transcription inhibitor thiolutin or the translation inhibitor emetine. Responses in morphology and growth were compared to development in inhibitor-free control conditions at three time points over 12 days. Potentially persistent inhibitor effects were then investigated by growing parthenosporophytes in an inhibitor-free post-culture for 14 days.

Key results

Thiolutin did not affect gamete germination, but growth of parthenosporophytes was significantly delayed. While almost all control parthenosporophytes had grown larger than 10 cells over 12 days, thiolutin inhibited growth beyond a size of 5-10 cells. The effects of thiolutin were reversible in the post-culture. Consequences of the emetine treatment were more severe, germination was already strongly inhibited by day 5, and on average only 27.5% of emetine-treated gametes had completed the first cell division on day 12. Emetine fully inhibited development beyond the 5-cell stage during the treatment, and induced morphological abnormalities (i.e., round cell shape and abnormal cell division planes) which persisted throughout the post-culture.

Conclusions

These results imply thatEctocarpusgametes contain sufficient proteins to germinate, and that the first cell cycles of parthenogenetic gamete development presumably utilize mRNA already present in the gametes. We discuss that storing mRNA and proteins in the developing gametes before release may be an adaptive trait inEctocarpusto ensure quick development after fertilization, or alternatively the vegetative completion of the life cycle in the absence of mates.
C9ORF72 deficiency results in degeneration of the zebrafish retinain vivo
Authors: Jaroszynska Natalia , Salzinger Andrea , Tsarouchas Themistoklis M. , Becker Catherina G. , Becker Thomas , Lyons David A. , MacDonald Ryan B. , Keatinge Marcus
Published: October 2023

G4C2 Hexanucleotide repeat expansions within the geneC9ORF72are the most common cause of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction in C9ORF72 expression levels in patients, suggesting haploinsufficiency could contribute to disease. To further understand the consequences of C9ORF72 deficiencyin vivo, we generated ac9orf72mutant zebrafish line. Analysis of the spinal cord revealed no appreciable neurodegenerative pathology such as loss of motor neurons, or increased levels of neuroinflammation. However, detailed examination ofc9orf72-/-retinas showed prominent neurodegenerative features, including a decrease in retinal thickness, gliosis, and an overall reduction in neurons of all subtypes. Structurally, analysis of rod and cone cells within the photoreceptor layer showed a disturbance in the outer cells of the retina and rhodopsin mis-localisation from rod outer segments to their cell bodies and synaptic endings. Thus, C9ORF72 may play a previously unappreciated role in retinal homeostasis and suggests C9ORF72 deficiency can induce tissue specific neuronal loss.
A matter of life and death – Hunting tactics of Southern elephant seals(Mirounga leonina)and anti-predatory behaviours of their prey
Authors: Chevallay Mathilde , Guinet Christophe , Goulet Pauline , du Dot Tiphaine Jeanniard
Published: October 2023

For air-breathing marine predators that must save energy during dives, the ability to adopt hunting tactics that minimise the risk of triggering an escape reaction from the prey is crucial for an efficient foraging. Female Southern elephant seals(Mirounga leonina,SES hereafter) forage on small mesopelagic prey that they must hunt almost continuously to meet their high-energy requirements. Here we aimed at understanding how these large time-limited deep-divers can efficiently exploit their small sized prey. To do so, we used data recorded by a new biologger, the sonar tag, deployed on SES during their post-breeding foraging trips. This tag combines an active acoustic sensor with ultra-high-resolution movement and bioluminescence sensors, offering a unique opportunity to simultaneously describe SES’ hunting tactics to capture their prey and defence mechanisms employed by prey. We analysed more than 5,800 prey capture events in nine SES and show that they adopt a “stalking” hunting behaviour allowing them to get as close as possible to their prey before attacking. The ability of SES to adopt stealth approach tactics, minimising the risk of initiating a flight reaction from their prey, might be a key factor in the success of this far-ranging generalist predator.
The Unexpected Functional Diversity of Photoexcited NAD
Authors: Kufner Corinna L. , Janicki Mikołaj J. , Lozano Gabriella G. , Sasselov Dimitar D.
Published: October 2023

Despite the vital role of nicotinamide adenine dinucleotide (NAD) as a cofactor in all living organisms, the diversity of its functions is poorly understood. Particularly in interaction with ultraviolet (UV) light, a variety of photorelaxation channels can be accessed, which current models lack to explain. In this work, for the first time, we used picosecond UV pump, mid-infrared (mIR) probe spectroscopy and accurate quantum-chemical calculations to elucidate the ultrafast photodynamics of NAD+and NADH to unify contradictory mechanisms from the past decades in the big picture. We found direct evidence for a long-lived (∼900 ps) charge-separated state in NADH, which has been unobserved previously and results in the parallel population of a fluorescent state. The photochemical pathways demonstrated here open up functions of NAD in chemistry and molecular biology, such as an electron donor, as a FRET agent or as a redox pair switch, which have not been considered previously.

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Cross-species imputation and comparison of single-cell transcriptomic profiles
Authors: Zhang Ran , Yang Mu , Schreiber Jacob , O’Day Diana R. , Turner James M. A. , Shendure Jay , Disteche Christine M. , Deng Xinxian , Noble William Stafford
Published: October 2023

Cross-species comparison and prediction of gene expression profiles are important to understand regulatory changes during evolution and to transfer knowledge learned from model organisms to humans. Single-cell RNA-seq (scRNA-seq) profiles enable us to capture gene expression profiles with respect to variations among individual cells; however, cross-species comparison of scRNA-seq profiles is challenging because of data sparsity, batch effects, and the lack of one-to-one cell matching across species. Moreover, single-cell profiles are challenging to obtain in certain biological contexts, limiting the scope of hypothesis generation. Here we developed Icebear, a neural network framework that decomposes single-cell measurements into factors representing cell identity, species, and batch factors. Icebear enables accurate prediction of single-cell gene expression profiles across species, thereby providing high-resolution cell type and disease profiles in under-characterized contexts. Icebear also facilitates direct cross-species comparison of single-cell expression profiles for conserved genes that are located on the X chromosome in eutherian mammals but on autosomes in chicken. This comparison, for the first time, revealed evolutionary and diverse adaptations of X-chromosome upregulation in mammals.
Assessing climate change risks associated with precipitation at unfavorable times in winter wheat using an improved crop calendar model incorporating vernalization and winter survival
Authors: Murakami Keach , Iizumi Toshichika , Shimoda Seiji
Published: October 2023

Crop phenology calendars are necessary for designing breeding goals and for developing effective management practices. Winter wheat is a representative biennial, the cultivation schedule of which is constrained by winter climate conditions, particularly the processes of vernalization and winter survival. Here, we present improvements to a rule-based crop phenology model by incorporating these factors so that it can be used to accurately estimate the phenological events of winter wheat from daily meteorological data. We tested the improved model in Hokkaido, the northernmost Japanese island, which is characterized by seasonal snow cover and a wet summer. The results confirmed that implementing these factors contributed to accurate estimates of peak occurrence dates of winter wheat phenological events. Furthermore, we applied the improved model to simulate wheat phenology under 2 K and 4 K warmer scenarios. The results showed a delayed sowing period up to approximately one month and slight advancements in both flowering and harvesting, leading to a shorter growth period. While this shortened period may be largely compensated by a decrease in the snow-covered period, the shifts in the vegetative and reproductive phases may have a significant influence on sink-source balance of wheat. We also assessed the risks of pollination failure and preharvest sprouting, both of which are associated with the timing of precipitation, based on the number of rainy days around flowering, and the incidence of precipitation over two consecutive days around the time of harvesting. Our simulations suggested increased risk of pollination failure and reduced risk of preharvest sprouting, leading to an increase in the probability of crop failure. These findings underscore the importance of implementing adaptive measures to mitigate precipitation-related risk under future climate scenarios. Further, the findings provide valuable insights for winter wheat breeders and agronomists, thereby facilitating crop production adaptation strategies.
DNA nanostructure-templated antibody complexes provide insights into the geometric requirements of human complement cascade activation
Authors: Abendstein Leoni , Noteborn Willem E. M. , Veenman Luc S. , Dijkstra Douwe J. , van de Bovenkamp Fleur S. , Trouw Leendert A. , Sharp Thomas H.
Published: October 2023

The classical complement pathway is activated by antigen-bound IgG antibodies. Monomeric IgG must oligomerize to activate complement via the hexameric C1q complex, and hexamerizing mutants of IgG appear as promising therapeutic candidates. However, structural data have shown that it is not necessary to bind all six C1q arms to initiate complement, revealing a symmetry mismatch between C1 and the hexameric IgG complex, which has not been adequately explained. Here we use DNA nanotechnology to produce specific nanostructures to template antigens, and thereby control IgG valency. These DNA nano-templated IgG complexes can activate complement on cell-mimetic lipid membranes, which enabled us to determine the effect of IgG valency on complement activation without the requirement to mutate antibodies. We investigated this using biophysical assays together with 3D cryo-electron tomography. Our data revealed that the cleavage of complement component C4 by the C1 complex is proportional to the number of antigens. Increased IgG valency also translated to better terminal pathway activation and membrane attack complex formation. Together, these data provide insights into how nanopatterning antigen-antibody complexes influence the activation of the C1 complex and suggest routes to modulate complement activation by antibody engineering. Furthermore, to our knowledge this is the first time DNA nanotechnology has been used to study the activation of the complement system.
Assigning credit where it’s due: An information content score to capture the clinical value of Multiplexed Assays of Variant Effect
Authors: Ranola John Michael O , Horton Carrie , Pesaran Tina , Fayer Shawn , Starita Lea M. , Shirts Brian H
Published: October 2023

Background

A variant can be pathogenic or benign with relation to a human disease. Current classification categories from benign to pathogenic reflect a probabilistic summary of current understanding. A primary metric of clinical utility for multiplexed assays of variant effect (MAVE) is the number of variants that can be reclassified from uncertain significance (VUS). However, we hypothesized that this measure of utility underrepresents the information gained from MAVEs and that an information theory approach which includes data that does not reclassify variants will better reflect true information gain. We used this information theory approach to evaluate the information gain, in bits, for MAVEs ofBRCA1, PTEN, andTP53. Here, one bit represents the amount of information required to completely classify a single variant starting from no information.

Results

BRCA1MAVEs produced a total of 831.2 bits of information, 6.58% of the total missense information inBRCA1and a 22-fold increase over the information that only contributed to VUS reclassification.PTENMAVEs produced 2059.6 bits of information which represents 32.8% of the total missense information inPTENand an 85-fold increase over the information that contributed to VUS reclassification.TP53MAVEs produced 277.8 bits of information which represents 6.22% of the total missense information inTP53and a 3.5-fold increase over the information that contributed to VUS reclassification.

Conclusions

An information content approach will more accurately portray information gained through MAVE mapping efforts than counting the number of variants reclassified. This information content approach may also help define the impact of modifying information definitions used to classify many variants, such as guideline rule changes.
A simplified disease resistance assay using YFP-expressingPotato Virus XinN. benthamianareveals a cell death-independent immune function of RBA1
Authors: Hasegawa Keiichi , Timmers Ton , Chai Jijie , Maekawa Takaki
Published: October 2023

R (resistance) proteins, such as intracellular NLRs (nucleotide-binding leucine-rich repeat receptors), are integral components of the plant innate immune system (van Wersch et al., 2020). Host responses following R protein activation include the generation of reactive oxygen species, sustained increases in cytosolic Ca2+, transcriptional reprogramming and, typically, rapid host cell death at sites of pathogen infection, which together ultimately lead to pathogen growth restriction (Wang et al., 2023). To assess the activity of R proteins, agroinfiltration-mediated transient gene expression assays have been widely used inNicotianaspecies (e.g.,N. benthamiana). In these transient assays, host cell death is often chosen as an indicator of R protein activity from the host responses mentioned above, in part because of the ease of experimentation. However, the extent to which host cell death is a proxy for disease resistance signaling has long been debated, as host cell death and pathogen growth restriction can be uncoupled in several cases (Bendahmane et al., 1999; Coll et al., 2010; Heidrich et al., 2011, Maekawa et al., 2023). To assess the disease resistance activity of R proteins, bacterial growth assays have been employed in combination with transientRgene expression inN. benthamiana(Sun et al., 2021). Bacterial growth assays, however, require multiple experimental procedures, including agroinfiltration, pathogen infection and bacterial counts, which hinders high-throughput studies ofRgene-mediated disease resistance. Here, we report a simple plate reader-based assay to assessRgene-mediated disease resistance activity against PVX (Potato virus X) that expresses YFP (PVX-YFP). Unlike bacterial pathogens, PVX proliferation inN. benthamianais not restricted by the intrinsic activity of the EDS1 signaling pathway as previously shown by virus-inducedNbEDS1gene silencing (Peart et al., 2002) and as we consistently show in this study using aNbeds1gene knockout mutant. This feature would increase the sensitivity of the assay, allowing it to capture a weak-to-moderate disease resistance activity of R proteins, as the contribution of basal immunity to PVX via theNbEDS1 pathway is negligible. Using this assay, we show that a non-cell death-inducing mutant of the R protein of RBA1 (Response to HopBA1), which lacks 2′,3′-cAMP/cGMP synthetase activity but retains NADase activity, confers PVX resistance in an EDS1 signaling pathway-dependent manner.
High-throughput and in-depth analysis of plasma proteome by UV-assisted protein digestion, 5-plex labeling and MS-based high abundance protein removal method
Authors: Wang Zhiting , Qu Boxin , Zhang Weijie , Liang Zhen , Wang Liming , Liu Jianhui , Yuan Huiming , Zhang Lihua , Zhang Yukui
Published: October 2023

Human plasma contains various proteins, some of which reflect individuals’ physiological health state or predict diseases. Therefore, plasma analysis can provide a wealth of information on novel biomarkers for clinical diagnosis and prognosis. The use of mass spectrometry (MS) for high-throughput and in-depth quantitative proteomic analysis of plasma allows for highly specific and quantitative readout, but is challenging because of the high dynamic range of protein abundances. Here, we introduce a robust, high-throughput, and in-depth workflow for plasma proteome analysis based on UV-assisted rapid protein digestion, 5-plex dimethyl labeling, and MS-based high abundance protein removal. UV-assisted protein digestion could quantify the same protein numbers as traditional enzymatic hydrolysis and achieve a low miss-cleavage rate in only 20 minutes. And the MS-based high abundance protein removed 5-plex DIA method, which does not require extra protein depletion procedures, enables quantitative analysis of more than 600 proteins using an equivalent MS analysis time of 30 minutes per sample. The average relative error was 6.9%. We believe the method is beneficial for analyzing large numbers of trace-level clinical samples and broaden a vision for the discovery of low abundance protein markers.
Genome sequencing and molecular networking analysis of the wild fungusAnthostomella pineareveal its ability to produce a diverse range of secondary metabolites
Authors: Iacovelli R. , He T. , Allen J. L. , Hackl T. , Haslinger K.
Published: October 2023

Background

Filamentous fungi are prolific producers of bioactive molecules and enzymes with important applications in industry. Yet, the vast majority of fungal species remain undiscovered or uncharacterized. Here we focus our attention to a wild fungal isolate that we identified asAnthostomella pinea. The fungus belongs to a complex polyphyletic genus in the family ofXylariaceae, which is known to comprise endophytic and pathogenic fungi that produce a plethora of interesting secondary metabolites. Despite that,Anthostomellais largely understudied and only two species have been fully sequenced and characterized at a genomic level.

Results

In this work, we used long-read sequencing to obtain the complete 53.7 Mb genome sequence including the full mitochondrial DNA. We performed extensive structural and functional annotation of coding sequences, including genes encoding enzymes with potential applications in biotechnology. Among others, we found that the genome ofA. pineaencodes 91 biosynthetic gene clusters, more than 600 CAZymes, and 164 P450s. Furthermore, untargeted metabolomics and molecular networking analysis of the cultivation extracts revealed a rich secondary metabolism, and in particular an abundance of sesquiterpenoids and sesquiterpene lactones. We also identified the polyketide antibiotic xanthoepocin, to which we attribute the anti–Gram-positive effect of the extracts that we observed in antibacterial plate assays.

Conclusions

Taken together, our results provide a first glimpse into the potential ofAnthstomella pineato provide new bioactive molecules and biocatalysts and will facilitate future research into these valuable metabolites.
Determination of Optimal Nutrient Levels in Baru Seedlings (Dipterix alata Vog.) Using the Mathematical Chance Method
Authors: Kusano Daniel , Larson Leia , Camacho Marcos Antonio
Published: October 2023

This work aimed to determine the optimal ranges by the Mathematical Chance (ChM) method in baru seedlings. To determine optimal ranges by ChM, the nutritional information from an experiment conducted in a protected environment from October 13, 2011, to February 11, 2012, in Selvíria-MS and for seedling production, used a nursery with 50% light reduction polypropylene mesh and 15 x 21.5 cm plastic bags, which have a capacity of 1.8 L, which were filled with different substrate combinations. The ranges found for macronutrients with the ChM method were, in g kg-1, from 19.06 to 28.14; 1.52 to 3.38; 17.9 to 24.0; 1.76 to 3.54; 0.74 to 1.50; 1.26 to 2.26 for N, P, K, Ca, Mg and S, respectively. The ranges found for micronutrients with the ChM method were, in mg kg 1, from 21.79 to 33.59; 1.0 to 21.40; 75 to 104.4; 14.0 to 82.8; 18.0 to 24.4 for B, Cu, Fe, Mn, and Zn, respectively.
Early root architectural traits and their relationship with yield inIpomoea batatasL
Authors: Duque L.O. , Hoffman G. , Pecota K. , Yencho G. C.
Published: October 2023

Root system architecture in storage root crops are an important component of plant growth and yield performance that has received little attention by researchers because of the inherent difficulties posed byin-situroot observation. Sweetpotato (Ipomoea batatasL.) is an important climate-resilient storage root crop of worldwide importance for both tropical and temperate regions, and identifying genotypes with advantageous root phenotypes and improved root architecture to facilitate breeding for improved storage root yield and quality characteristics in both high and low input scenarios would be beneficial. We evaluated 38 diverse sweetpotato genotypes for early root architectural traits and correlated a subset of these with storage root yield. Early root architectural traits were scanned and digitized using the RhizoVision Explorer software system. Significant genotypic variation was detected for all early root traits including root mass, total root length, root volume, root area and root length by diameter classes. Based on the values of total root length, we separated the 38 genotypes into three root sizes (small, medium, and large). Principal component analysis identified four clusters, primarily defined by shoot mass, root volume, root area, root mass, total root length and root length by diameter class. Average total and marketable yield and number of storage roots, was assessed on a subset of eight genotypes in the field. Several early root traits were positively correlated with total yield, marketable yield, and number of storage roots. These results suggest that root traits, particularly total root length and root mass could improve yield potential and should be incorporated into sweetpotato ideotypes. To help increase sweetpotato performance in challenging environments, breeding efforts may benefit through the incorporation of early root phenotyping using the idea of integrated root phenotypes.
Terpenoid balance inAspergillus nidulansunveiled by heterologous squalene synthase expression
Authors: Park Sung Chul , Steffan Breanne N. , Lim Fang Yun , Gupta Raveena , Butun Fatma Ayaloglu , Chen Hongyu , Ye Rosa , Decker Timothy , Wu Chengcang C. , Kelleher Neil L. , Bok Jin Woo , Keller Nancy P.
Published: October 2023

Filamentous fungi produce numerous uncharacterized natural products (NPs) that are often challenging to characterize due to cryptic expression in laboratory conditions. Previously, we have successfully isolated novel NPs by expressing fungal artificial chromosomes (FACs) from a variety of fungal species intoAspergillus nidulans. Here, we demonstrate a new twist to FAC utility wherein heterologous expression of aPseudogymnoascus destructansFAC inA. nidulansaltered endogenous terpene biosynthetic pathways. In contrast to wildtype, the FAC transformant produced increased levels of squalene and aspernidine type compounds, including three new nidulenes (1–2, 5), and lost nearly all ability to synthesize the majorA. nidulanscharacteristic terpene, austinol. Deletion of a squalene synthase gene in the FAC restored wildtype chemical profiles. The altered squalene to farnesyl pyrophosphate ratio leading to synthesis of nidulenes and aspernidines at the expense of farnesyl pyrophosphate derived austinols provides unexpected insight into routes of terpene synthesis in fungi.

Teaser

Reshaping terpenes: Heterologous FAC expression reroutes terpene pathways.
Respiration and growth ofParacoccus denitrificansR-1 with nitrous oxide as an electron acceptor
Authors: Zhou Jiaxian , Deng Wenfang , Wu Jiapeng , Xiang Hua , Lin Jih-Gaw , Hong Yiguo
Published: October 2023

In the nitrogen biogeochemical cycle, the reduction of nitrous oxide (N2O) to N2by N2O reductase, which is encoded bynosgene cluster, is the only biological pathway for N2O consumption. However, the capability and mechanisms of microbial N2O reduction are poorly understood. In this study, we investigated the ability to obtain energy for growth ofParacoccus denitrificansR-1 by coupling the oxidation of various electron donors to N2O reduction. This strain has strong N2O reduction capability, and the average N2O reduction rate was 5.10±0.11×10-9μmol·h-1·cell-1under anaerobic condition at 30℃ using acetate as the electron donor in a defined medium. This reduction was accompanied by the stoichiometric consumption of acetate over time when N2O served as the sole electron acceptor and the reduction can yield energy to support microbial growth, suggesting that microbial N2O reduction is an electron transport process. Cu2+, silver nanoparticles, O2, and acidic conditions can strongly inhibit the reduction, whereas NO3-or NH4+can promote it. Genomic analysis showed that the gene cluster encoding N2O reductase ofP. denitrificansR-1 was composed ofnosR,nosZ,nosD,nosF,nosY, andnosL, andnosZ, which was identified as clade I. The respiratory inhibitors test indicated that the pathway of electron transport for N2O reduction was different from that of the traditional electron transport chain for aerobic respiration. These findings suggest that modular N2O reduction byP. denitrificansR-1 is linked to the electron transport chain and energy conservation, and that dissimilatory N2O reduction is a form of microbial anaerobic respiration.

IMPOETANCE

In the nitrogen biogeochemical cycle, the reduction of N2O to N2by N2O reductase, which is encoded bynos genes, is the only biological pathway for N2O consumption. However, the capacity and mechanisms of microbial N2O reduction are poorly understood. We investigated the ability to obtain energy for growth of Paracoccus denitrificans R-1 by coupling the oxidation of various electron donors to N2O reduction. Our study showed that the nosZ type I bacterium, P. denitrificans R-1, can respire N2O as the sole electron donor. Thus, the modular N2O reduction process of clade I denitrifiers not only can consume N2O produced by themselves but can also consume the external N2O generated from non-denitrification biological or abiotic pathways under suitable conditions, which is critical for controlling the release of N2O from ecosystems into the atmosphere.
Multiplexed CRISPR/Cas9 mutagenesis of rice PSBS1 non-coding sequences for transgene-free overexpression
Authors: Patel-Tupper Dhruv , Kelikian Armen , Leipertz Anna , Maryn Nina , Tjahjadi Michelle , Karavolias Nicholas G. , Cho Myeong-Je , Niyogi Krishna K.
Published: October 2023

Understanding CRISPR/Cas9’s capacity to generate native overexpression (OX) alleles would accelerate agronomic gains achievable by gene editing. To generate OX alleles with increased RNA and protein abundance, we leveraged multiplexed CRISPR/Cas9 mutagenesis of non-coding DNA sequences located upstream of the ricePSBS1gene. We isolated 120 transgene-free, gene-edited alleles with varying NPQ capacityin vivo—ranging from complete knockout to overexpression, using a high-throughput phenotyping and transgene screening pipeline. Overexpression ofOsPSBS1increased protein abundance 2-3-fold, matching fold changes obtained by transgenesis. Increased PsbS protein abundance enhanced non-photochemical quenching capacity and improved water-use efficiency. Across our resolved genetic variation, we identify the role of 5’UTR indels and inversions in driving knockout/knockdown and overexpression phenotypes, respectively. Complex structural variants, such as the 252kb duplication/inversion generated in this study, evidence the potential of CRISPR/Cas9 to facilitate significant genomic changes with negligible off-target transcriptomic perturbations. Our results may inform future gene-editing strategies for hypermorphic alleles and have opened the door to the pursuit of gene-edited, non-transgenic rice plants with accelerated relaxation of photoprotection.
Modeling alternative translation initiation sites in plants reveals evolutionarily conservedcis-regulatory codes in eukaryotes
Authors: Wu Ting-Ying , Li Ya-Ru , Chang Kai-Jyun , Urano Daisuke , Liu Ming-Jung
Published: October 2023

mRNA translation relies on identifying translation initiation sites (TISs) in mRNAs. Alternative TISs are prevalent across plant transcriptomes, but the mechanisms for their recognition are unclear. Using ribosome profiling and machine learning, we developed models for predicting alternative TISs inArabidopsis thalianaand tomato (Solanum lycopersicum). Distinct feature sets were predictive of AUG and non-AUG TISs in 5′ untranslated regions and coding sequences, including a novel CU-rich sequence that promoted plant TIS activity, a translational enhancer found across dicots and monocots and also in humans and viruses. Our results elucidate the mechanistic and evolutionary basis of TIS recognition, wherebycis-regulatory RNA signatures affect start site selection. The TIS prediction model provides global estimates of TISs to discover neglected protein-coding genes across plant genomes. The prevalence ofcis-regulatory signatures across eukaryotes and viruses suggests their broad, critical roles in reprogramming the translational landscape in the plant–virus arms race.

Teaser

New insights into how plant ribosomes distinguish AUG and non-AUG triplets for protein synthesis via a conserved eukaryoticcis-regulatory strategy.
Shrinking the capital costs and beta risk impediments through ESG: study of an emerging market
Authors: Gupta Santushti , Aggarwal Divya
Published: October 2023

Purpose

This study aims to empirically examine environment, social, and governance (ESG) as an effective strategy to reduce major impediments for a corporation in the form of costs of capital (COC) and systematic risk, especially for emerging markets such as India.

Design/methodology/approach

A sample of 114 Indian firms from eight prominent industries based on Thomson Reuters classification (TRBC) are used in the study. A panel regression with industry-fixed effects is carried out to account for industry heterogeneity. For robustness, the authors also carry out a matched sample analysis.

Findings

The authors observe a negative and significant relationship between ESG performance with COC and systematic risk, respectively. For the pillar-wise analysis, the authors observe that only governance performance is negatively and significantly related to COC whereas the environmental and social performances are negative and insignificant. For ESG pillar level analysis for beta, the authors observe that all pillars are negative and significant, thus making a case for how firms can fine-tune their ESG strategies according to each pillar.

Research limitations/implications

As the ESG concept is still in a very nascent stage, data availability is a definite challenge in India.

Practical implications

As ESG is increasingly becoming relevant for multiple stakeholders, this study aims to provide evidence that can potentially guide the regulators, practitioners, and academicians to address the contemporary needs of these stakeholders, while also doing good for the firm in the traditional sense.

Social implications

The transition to a sustainable economy is a challenge for emerging economies, especially for a country like India where stakeholders are not only varied but also huge in number. With this study's contribution towards an incremental understanding of ESG, Indian regulators and policymakers can bring forward mandates as to ESG compliances that are rewarding for the firms and give them enough impetus towards complying with ESG norms.

Originality/value

The extant literature on ESG majorly discusses the relationship between ESG performance and financial performance. This study addresses the lacuna of the relationship of ESG with COC and beta in the Indian context.
Discussion of “the functional background of the compensation committee chair: the choice and weight of performance measures in CEO compensation”
Authors: Gong Stephen
Published: October 2023

Purpose

Nwaeze and Kalelkar (2023) examine the association between the functional background of the compensation committee chair (CC chair) and CEO compensation using S&P 500 firms from 2008 to 2018. They find that the CC chair's functional background is positively associated with the adoption of performance measures that are more aligned with such background. This discussion starts with Nwaeze and Kalelkar's (2023) incremental contribution, and offers suggestions on two areas for improvement. First, the authors could provide a more focused discussion of the conceptual framework. Second, the authors could improve their empirical design and interpretation of results. Avenues for future research are also suggested.

Design/methodology/approach

This discussion suggests methods and model specifications that may strengthen the research design, facilitate the interpretation of results, and provide additional insights.

Findings

The discussed paper could improve the reliability and rigor of the empirical tests and the conclusions by providing more contextual and granular information on firms' actual CEO compensation arrangements, using more careful testing procedures, and enhancing clarity in the writing.

Originality/value

Researchers could be interested in alternative perspectives and richer analyses of non-agency model based determinants of CEO compensation.