bluuebunny/crossref_metadata_2025 huggingface dataset:
Modern wheat breeding selection synergistically improves above- and below-ground traits
Authors: Zhao Peng , Liu Zihui , Shi Xue , Hou Wenyang , Cheng Mingzhu , Liu Yuxiu , Simmonds James , Ji Wanquan , Uauy Cristobal , Xu Shengbao , Wang Xiaoming
Published: November 2023

The root system, as a fundamental organ for uptaking water and nutrients and interacting with the local environmental conditions, has been postulated to be the foundation for a second Green Revolution. However, the status of the root system during modern wheat breeding remains to be elucidated. Here, by analyzing the phenotypes of 406 wheat accessions on a large scale, we found the root systems of modern cultivars were synchronisely changed along with the above-ground traits. Furthermore, the genomic blocks with phenotypic effects on both above- and below-ground traits were observed to be enriched in the selection sweeps, highlighting that modern wheat breeding contributed to the synchronised changes. More importantly, the haplotypes selected by breeders within the selection sweeps synergistically improved both the above- and below-ground traits, suggesting that modern wheat breeding has improved the root system indirectly, which may contribute to the higher grain yields of modern wheat cultivars. Our results demonstrated that modern wheat breeding synergistically improved the above- and below-ground traits.
From museum drawer to tree: historical DNA phylogenomics clarifies the systematics of rare dung beetles (Coleoptera: Scarabaeinae) from museum collections
Authors: Lopes Fernando , Gunter Nicole , Gillett Conrad P.D.T. , Montanaro Giulio , Rossini Michele , Losacco Federica , Daniel Gimo M. , Straube Nicolas , Tarasov Sergei
Published: November 2023

Although several methods exist for extracting and sequencing historical DNA originating from drypreserved insect specimens deposited in natural history museums, no consensus exists as to what is the optimal approach. We demonstrate that a customized, low-cost archival DNA extraction protocol (∼ €10 per sample), in combination with Ultraconserved Elements (UCEs), is an effective tool for insect phylogenomic studies. We successfully tested our approach by sequencing DNA from scarab dung beetles preserved in both wet and dry collections, including unique primary type and rare historical specimens from internationally important natural history museums in London, Paris and Helsinki. The focal specimens comprise enigmatic dung beetle genera (Nesosisyphus, OnychotechusandHelictopleurus) that varied in age and preservation. The oldest specimen, the holotype of the now possibly extinct Mauritian endemicNesosisyphus rotundatus, was collected in 1944. We obtained high-quality DNA from all studied specimens to enable the generation of a UCE-based dataset that revealed an insightful and well-supported phylogenetic tree of dung beetles. The resulting phylogeny suggested the reclassification ofOnychotechus(previouslyincertae sedis) within the tribe Coprini. Our approach demonstrates the feasibility and effectiveness of combining DNA data from historic and recent museum specimens to provide novel insights. The proposed archival DNA protocol is available at DOI 10.17504/protocols.io.81wgbybqyvpk/v1

Highlights

We combined custom low-cost archival DNA extractions and Ultraconserved Element phylogenomics

DNA from rare museum specimens of enigmatic dung beetles revealed their phylogenetic connections

Genomic data was obtained from the holotype of a potentially extinct monoinsular endemic species

Genomic data allowed a rare and enigmatic species of previously unknown affinity to be classified

The morphology of museum specimens remained intact following non-destructive DNA extraction

Abstract Figure
The majority of Germany’s small agricultural streams are in poor ecological status
Authors: von Gönner Julia , Gröning Jonas , Grescho Volker , Neuer Lilian , Hänsch Veit G. , Laue Benjamin , Molsberger-Lange Eva , Wilharm Elke , Liess Matthias , Bonn Aletta
Published: November 2023

Agricultural pesticides, nutrients, and habitat degradation are major causes of insect declines in lowland streams. To effectively conserve and restore stream habitats, standardized stream monitoring data and societal support for freshwater protection are needed. Here, we sampled 137 small stream sites across Germany, 83% of which were located in agricultural catchments, with more than 900 citizen scientists in 96 monitoring groups. Sampling was carried out according to Water Framework Directive standards as part of the citizen science freshwater monitoring program FLOW in spring and summer 2021, 2022 and 2023. The biological indicator SPEARpesticideswas used to assess pesticide exposure and effects based on benthic invertebrate community composition. Overall, 58% of the monitored agricultural stream sites did not achieve a good ecological status in terms of macroinvertebrate community composition and indicated high pesticide exposure (SPEARpesticidesstatus class: 29% ‘moderate’, 19% ‘poor’, 11% ‘bad’). The indicated pesticide pressure in streams was related to the proportion of agricultural land in the catchment area (R2=0.23, p<0.001). With regards to hydromorphology, monitoring results revealed that 65% of the agricultural stream sites failed to reach a good status. The data base produced by citizen science groups was characterized by a high degree of accuracy. This was quantified by a comparative survey of SPEARpesticidesindex (R2=0.79, p<0.001) and hydromorphology index values (R2=0.72, p<0.001) by citizen scientists and professionals. Such citizen-driven monitoring of the status of watercourses could play a crucial role in monitoring and implementing the objective of the European Water Framework Directive, thus contributing to restoring and protecting freshwater ecosystems.

Graphical abstract

Highlights

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Assessment of ecological status of small agricultural streams in Germany

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Pesticides affected invertebrates (bioindicator SPEAR) in 58% of agricultural streams

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Failure to reach good hydromorphological status in 65% of agricultural streams

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Citizen science monitoring achieves high data accuracy

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Citizen science can support European Water Framework Directive monitoring
A novel phylogenomics pipeline reveals complex pattern of reticulate evolution in Cucurbitales
Authors: Ortiz Edgardo M. , Höwener Alina , Shigita Gentaro , Raza Mustafa , Maurin Olivier , Zuntini Alexandre , Forest Félix , Baker William J. , Schaefer Hanno
Published: November 2023

A diverse range of high-throughput sequencing data, such as target capture, RNA-Seq, genome skimming, and high-depth whole genome sequencing, are used for phylogenomic analyses but the integration of such mixed data types into a single phylogenomic dataset requires a number of bioinformatic tools and significant computational resources. Here, we present a novel pipeline, CAPTUS, to analyze mixed data in a fast and efficient way. CAPTUS assembles these data types, allows searching of the assemblies for loci of interest, and finally produces alignments filtered for paralogs. Compared to other software, CAPTUS allows the recovery of a greater number of more complete loci across a larger number of species. We apply CAPTUS to assemble a comprehensive mixed dataset, comprising the four types of sequencing data for the angiosperm order Cucurbitales, a clade of about 3,100 species in eight mainly tropical plant families, including begonias (Begoniaceae) and gourds (Cucurbitaceae). Our phylogenomic results support the currently accepted circumscription of Cucurbitales except for the position of the holoparasitic Apodanthaceae, which group with Rafflesiaceae in Malpighiales. A subset of mitochondrial gene regions supports the earlier position of Apodanthaceae in Cucurbitales. However, the nuclear regions and majority of mitochondrial regions place Apodanthaceae in Malpighiales. Within Cucurbitaceae, we confirm the monophyly of all currently accepted tribes but also reveal deep reticulation patterns both in Cucurbitales and within Cucurbitaceae. We show that contradicting results among earlier phylogenetic studies in Cucurbitales can be reconciled when accounting for gene tree conflict and demonstrate the efficiency of CAPTUS for complex datasets.
Pitfalls in performing genome-wide association studies on ratio traits
Authors: McCaw Zachary R , Dey Rounak , Somineni Hari , Amar David , Mukherjee Sumit , Sandor Kaitlin ,   insitro Research Team, Karaletsos Theofanis , Koller Daphne , Aschard Hugues , Davey Smith George , MacArthur Daniel , O’Dushlaine Colm , Soare Thomas W
Published: November 2023

Genome-wide association studies (GWAS) are often performed on ratios composed of a numerator trait divided by a denominator trait. Examples include body mass index (BMI) and the waist-to-hip ratio, among many others. Explicitly or implicitly, the goal of forming the ratio is typically to adjust for an association between the numerator and denominator. While forming ratios may be clinically expedient, there are several important issues with performing GWAS on ratios. Forming a ratio does not “adjust” for the denominator in the sense of conditioning on it, and it is unclear whether associations with ratios are attributable to the numerator, the denominator, or both. Here we demonstrate that associations arising in ratio GWAS can be entirely denominator-driven, implying that at least some associations uncovered by ratio GWAS may be due solely to a putative adjustment variable. In a survey of 10 common ratio traits, we find that the ratio model disagrees with the adjusted model (performing GWAS on the numerator while conditioning on the denominator) at around 1/3 of loci. Using BMI as an example, we show that variants detected by only the ratio model are more strongly associated with the denominator (height), while variants detected by only the adjusted model are more strongly associated with the numerator (weight). Although the adjusted model provides effect sizes with a clearer interpretation, it is susceptible to collider bias. We propose and validate a simple method of correcting for the genetic component of collider bias via leave-one-chromosome-out polygenic scoring.
RETINOID ORPHAN RECEPTOR GAMMA T (RORγT) PROMOTES INFLAMMATORY EOSINOPHILIA BUT IS DISPENSABLE FOR INNATE IMMUNE-MEDIATED COLITIS
Authors: Torres-Huerta Alvaro , Ruley-Haase Katelyn , Reed Theodore , Boger-May Antonia , Rubadeux Derek , Mayer Lauren , Rajashekara Arpitha Mysore , Hiller Morgan , Frech Madeleine , Roncagli Connor , Pederson Cameron , Camacho Mary Catherine , Hollmer Lauren , English Lauren , Kane Grace , Boone David L.
Published: November 2023

Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1−/−mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt−/−) mice. Rorγt−/−x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt−/−x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt−/−x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt−/−x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.
LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+T cell responsiveness
Authors: Pallavicini Isabella , Frasconi Teresa Maria , Ceccaci Elena , Tiberti Silvia , Nava Lauson Carina B , Preto Elisa , Bigogno Alberto , Mangione Marta , Sala Eleonora , Iannacone Matteo , Kuka Mirela , Nezi Luigi , Minucci Saverio , Manzo Teresa
Published: November 2023

The lysine-specific histone demethylase 1A (LSD1) has been described to play a role in antitumor immunity; however, the role of LSD1 in shaping CD8+ T cell (CTL) differentiation and function is not understood. Here, we showed that pharmacological inhibition of LSD1 (LSD1i) in CTL elicited phenotypic and functional alterations of the CTL that led to robust antitumor immunity in the context of adoptive T cell therapy (ACT). In addition, the combination of anti-PDL1 therapy with LSD1i-based ACT resulted in a complete tumor eradication and long-lasting tumor-free survival. This study demonstrated that LSD1i together with anti-PDL1 therapy complement each other’s deficiencies and produce a better tumor response in a melanoma model, in which both immune and epigenetic therapy alone have shown limited efficacy. Collectively, these results set the translational potential of modulating LSD1 to improve antitumoral responses generated by ACT and anti-PDL1 therapy, which provide a strong rationale for a combination trial of LSD1i and immunotherapy.
Acute effects of psilocybin on the dynamics of gaze fixations during visual aesthetic perception
Authors: Muller Stephanie , Cavanna Federico , de la Fuente Laura , Bruno Nicolás , D’Amelio Tomás Ariel , Pallavicini Carla , Tagliazucchi Enzo
Published: November 2023

Rationale

Serotonergic psychedelics are remarkable for their capacity to induce variable yet reproducible modifications to human consciousness The most salient acute effects of these compounds include perceptual alterations, predominantly in the visual domain, yet to date these alterations have been mostly documented only by subjective reports.

Objectives

We used eye-tracking to quantify the effects of low vs. high doses of psilocybin mushrooms on the eye movements that underlie the exploration of complex visual stimuli, focusing on the particular case of aesthetic perception.

Results

Following a double-blind placebo-controlled design under semi-naturalistic conditions, we demonstrated that high doses of psilocybin result in a more local visual exploration of paintings, and thus in a less entropic fixation probability distribution. Participants reported heightened emotional response and state of flow under the high dose condition.

Conclusions

These findings are consistent with an effect of psilocybin on gaze fixation mediated by altered perception of low-level visual information, such as textures, shapes and colors. Our work also highlights the possibility of investigating psychedelics by addressing their effect on behavior under complex naturalistic conditions, which contributes to maintaining subject engagement while also increasing the ecological validity of the findings.
Global remapping emerges as the mechanism for renewal of context-dependent behavior in a reinforcement learning model
Authors: Kappel David , Cheng Sen
Published: November 2023

The hippocampal formation exhibits complex and context-dependent activity patterns and dynamics, e.g., place cell activity during spatial navigation in rodents or remapping of place fields when the animal switches between contexts. Furthermore, rodents show context-dependent renewal of extinguished behavior. However, the link between context-dependent neural codes and context-dependent renewal is not fully understood. We use a reinforcement learning agent based on deep neural networks to study the learning dynamics that occur during spatial learning and context switching in a simulated ABA extinction and renewal paradigm in a 3D virtual environment. Despite its simplicity, the network exhibits a number of features typically found in the CA1 and CA3 regions of the hippocampus. A significant proportion of neurons in deeper layers of the network are tuned to a specific spatial position of the agent in the environment - similar to place cells in the hippocampus. These spatial representations exhibit global remapping when the agent is exposed to a new context. The spatial maps are restored when the agent returns to the previous context, accompanied by renewal of the conditioned behavior. Remapping is facilitated by memory replay of experiences during training. These complex spatial representations and dynamics occur spontaneously in the hidden layer of a deep network during learning. Our results show that integrated codes that jointly represent spatial and task-relevant contextual variables are the mechanism underlying renewal in a simulated DQN agent.
Adjusted vascular contractility relies on integrity of progranulin pathway: Insights into mitochondrial function
Authors: Singh Shubhnita , Bruder-Nascimento Ariane , Costa Rafael M. , Alves Juliano V. , Bharathi Sivakama , Goetzman Eric S. , Bruder-Nascimento Thiago
Published: November 2023

Objective

Cardiovascular disease (CVD) is a global health crisis and a leading cause of mortality. The intricate interplay between vascular contractility and mitochondrial function is central to CVD pathogenesis. The progranulin gene (GRN) encodes glycoprotein progranulin (PGRN), a ubiquitous molecule with known anti-inflammatory property. However, the role of PGRN in CVD remains enigmatic. In this study, we sought to dissect the significance of PGRN in the regulation vascular contractility and investigate the interface between PGRN and mitochondrial quality.

Method

Our investigation utilized aortae from male and female C57BL6/J wild-type (PGRN+/+) and B6(Cg)-Grntm1.1Aidi/J (PGRN−/−) mice, encompassing wire myograph assays to assess vascular contractility and primary aortic vascular smooth muscle cells (VSMCs) for mechanistic insights.

Results

Our results showed suppression of contractile activity in PGRN-/- VSMCs and aorta, followed by reduced α-smooth muscle actin expression. Mechanistically, PGRN deficiency impaired mitochondrial oxygen consumption rate (OCR), complex I activity, mitochondrial turnover, and mitochondrial redox signaling, while restoration of PGRN levels in aortae from PGRN-/- mice via lentivirus delivery ameliorated contractility and boosted OCR. In addition, VSMC overexpressing PGRN displayed higher mitochondrial respiration and complex I activity accompanied by cellular hypercontractility. Furthermore, increased PGRN triggered lysosome biogenesis by regulating transcription factor EB and accelerated mitophagy flux in VSMC, while treatment with spermidine, an autophagy inducer, improved mitochondrial phenotype and enhanced vascular contractility. Finally, angiotensin II failed to induce vascular contractility in PGRN-/- suggesting a key role of PGRN to maintain the vascular tone.

Conclusion

Our findings suggest that PGRN preserves the vascular contractility via regulating mitophagy flux, mitochondrial complex I activity, and redox signaling. Therefore, loss of PGRN function appears as a pivotal risk factor in CVD development.
Pushing the boundaries of MEG based on optically pumped magnetometers towards early human life
Authors: Corvilain Pierre , Wens Vincent , Bourguignon Mathieu , Capparini Chiara , Fourdin Lauréline , Ferez Maxime , Feys Odile , De Tiège Xavier , Bertels Julie
Published: November 2023

Characterizing the early development of the human brain is critical from both fundamental and clinical perspectives. However, existing neuroimaging techniques are either not well suited to infants or have limited spatial or temporal resolution. The advent of optically pumped magnetometers (OPMs) has revolutionized magnetoencephalography (MEG) by enabling wearable and thus more naturalistic recordings while maintaining excellent sensitivity and spatiotemporal resolution. Nevertheless, its adaptation to studying neural activity in infancy poses several challenges. In this work, we present an original close-to-scalp OPM-MEG setup that successfully recorded brain responses to sounds in newborns. We exposed one-month-old infants to continuous streams of tones and observed significant evoked responses, which peaked ∼250 ms poststimulus at bilateral auditory cortices. When tones were presented at a steady fixed pace with an oddball tone every fourth tone, significant neural responses were found both at the frequency of the standard tones (3 Hz) and of the oddball tones (0.75 Hz). The latter reflects the ability of the newborn brain to detect auditory change and synchronize to regular auditory patterns. Additional analyses support the added value of triaxial OPMs to increase the number of channels on small heads. Finally, OPM-MEG responses were validated with those obtained from the same participants using an adult-sized cryogenic MEG. This study demonstrates the applicability of OPM-MEG to study early postnatal periods; a crucial step towards future OPM investigations of typical and pathological early brain development.
Leaderless consensus decision-making determines cooperative transport direction in weaver ants
Authors: Carlesso Daniele , Stewardson Madelyne , Garnier Simon , Feinerman Ofer , Reid Chris R.
Published: November 2023

Animal groups need to achieve and maintain consensus to minimise conflict among individuals and prevent group fragmentation. An excellent example of a consensus challenge is cooperative transport, where multiple individuals cooperate to move a large item together. This behavior, regularly displayed by ants and humans only, requires individuals to agree on which direction to move in. Unlike humans, ants cannot use verbal communication but most likely rely on private information and/or mechanical forces sensed through the carried item to coordinate their behaviour. Here we investigated how groups of weaver ants achieve consensus during cooperative transport using a tethered-object protocol, where ants had to transport a prey item that was tethered in place with a thin string. This protocol allows the decoupling of the movement of informed ants from that of uninformed individuals. We showed that weaver ants pool together the opinions of all group members to increase their navigational accuracy. We confirmed this result using a symmetry-breaking task, in which we challenged ants with navigating an open-ended corridor. Weaver ants are the first reported ant species to use a ‘wisdom of the crowd’ strategy for cooperative transport, demonstrating that consensus mechanisms may differ according to the ecology of each species.
Soil health increases primary productivity across Europe
Authors: Romero Ferran , Labouyrie Maëva , Orgiazzi Alberto , Ballabio Cristiano , Panagos Panos , Jones Arwyn , Tedersoo Leho , Bahram Mohammad , Guerra Carlos A. , Eisenhauer Nico , Tao Dongxue , Delgado-Baquerizo Manuel , García-Palacios Pablo , van der Heijden Marcel G.A.
Published: November 2023

A healthy soil is at the core of sustainable management and policy, but its importance for plant productivity across environmental gradients and land-use types remains poorly understood. To address this gap, we conducted a pan-European field study including 588 sites from 27 countries to investigate the link between soil health and primary productivity across three major land-use types: woodlands, grasslands, and croplands. We found that mean soil health (a composite index based on soil properties, biodiversity, and plant disease control) in woodlands was 31.4% higher than in grasslands, and 76.1% higher than in croplands. Soil health was positively linked to cropland and grassland productivity at the continental scale. Woodland productivity was best explained by climate. Among microbial diversity indicators, we observed a positive association between the richness of Acidobacteria, Firmicutes, and Proteobacteria and primary productivity. Among microbial functional groups, we found that nitrogen-fixing bacteria and mycorrhizal fungi positively related to primary productivity in croplands and grasslands, while plant pathogens showed a negative relationship. Together, our results point to the importance of soil biodiversity and soil health for maintaining primary productivity across contrasting land-use types.
Brain Injury Knowledge Ontology (BIKO) for traumatic brain injury: Formalizing concepts and methods used in translational traumatic brain injury research
Authors: Surles-Zeigler Monique C. , Sincomb Troy , Dixon C Edward , Imam Fahim , Gillespie Tom , Grethe Jeffrey S. , Ferguson Adam R. , Martone Maryann E.
Published: November 2023

Traumatic brain injury (TBI) is an insult to the brain resulting from an external force and is a significant cause of morbidity and mortality in the United States. No effective clinical therapeutics currently exist for this injury. Although several therapies and procedures have been deemed successful for TBI treatment in preclinical research studies, they have yet to be translated into human patients. These discouraging results have left many scientists questioning the role of animal models in drug discovery for TBI.

One major hurdle in translating the knowledge obtained in the laboratory to the clinic is the methodological variance across these studies. This variance can hinder the ability to draw conclusions from conflicting studies and aggregate data across various research studies, which ultimately impedes the ability to aggregate data across these studies. Therefore, addressing this variance is crucial for bridging the gap between the laboratory and the clinic. The increasing volume of papers and associated data being published every day makes this hurdle even more difficult to overcome. The initial steps to address these knowledge gaps are identifying these studies and creating a shared knowledge framework for mapping their terminology. We are developing the Brain Injury Knowledge Ontology (BIKO) to create a standardized model to describe methods and outcome measures used within preclinical and clinical TBI therapy studies to facilitate comparison across studies and models. The first version of BIKO focuses on modeling the major preclinical TBI models, e.g., Controlled Cortical Impact Model, Fluid Percussion Model, and Weight-Drop Model), major neurological injuries related to these models and their relationship to clinical pathophysiology. We show how BIKO provides a machine-readable way to represent the methodologies used in TBI therapeutic studies to compare models across clinically relevant features.
The laminar pattern of proprioceptive activation in human primary motor cortex
Authors: Knudsen Lasse , Guo Fanhua , Huang Jiepin , Blicher Jakob U. , Lund Torben E. , Zhou Yan , Zhang Peng , Yang Yan
Published: November 2023

The primary motor cortex (M1) has traditionally been viewed as a motor output generator. However, its vital role in proprioceptive somatosensation is increasingly being recognized. Yet, our understanding of proprioceptive somatosensation in M1 at the laminar scale is limited, largely due to methodological challenges. Empirical findings in primates and rodents suggest a pronounced role of superficial cortical layers, but the involvement of deep layers has yet to be examined in humans. Submillimeter resolution fMRI has emerged in recent years, paving the way for the study of layer-dependent activity in humans (laminar fMRI). In the present study, laminar fMRI was employed to investigate the laminar pattern of proprioceptive somatosensation on M1 deep layer activation using passive finger movements as proprioceptive stimulation. Significant M1 deep layer activation was observed in response to proprioceptive stimulation across 10 healthy subjects using vascular space occupancy (VASO) at 7T. For further validation, two additional subjects were scanned using a balanced steady-state free precession (bSSFP) sequence with ultrahigh (0.3 mm) in-plane resolution, yielding converging results. These results were interpreted in the light of previous laminar fMRI studies and the active inference account of motor control. We suggest that a considerable proportion of M1 deep layer activation is due to proprioceptive influence and that deep layers of M1 constitute a key component in proprioceptive circuits.
GRable version 1.0: A software tool for site-specific glycoform analysis with improved MS1-based glycopeptide detection with parallel clustering and confidence evaluation with MS2 information
Authors: Nagai-Okatani Chiaki , Tominaga Daisuke , Tomioka Azusa , Sakaue Hiroaki , Goda Norio , Ko Shigeru , Kuno Atsushi , Kaji Hiroyuki
Published: November 2023

High-throughput intact glycopeptide analysis is crucial for elucidating the physiological and pathological status of the glycans attached to each glycoprotein. Mass spectrometry-based glycoproteomic methods are challenging because of the diversity and heterogeneity of glycan structures. Therefore, we have developed an MS1-based site-specific glycoform analysis method named “Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile (Glyco-RIDGE)” for a more comprehensive analysis. This method detects glycopeptide signals as a cluster based on the mass and chromatographic properties of glycopeptides and then searches for each combination of core peptides and glycan compositions by matching their mass and retention time differences. Here we developed a novel browser-based software named GRable for semi-automated Glyco-RIDGE analysis with significant improvements in glycopeptide detection algorithms, including “parallel clustering.” This unique function improved the comprehensiveness of glycopeptide detection and allowed the analysis to focus on specific glycan structures, such as pauci-mannose. The other notable improvement is evaluating the “confidence level” of the GRable results, especially using MS2 information. This function facilitated reduced misassignment of the core peptide and glycan composition and improved the interpretation of the results. Additional improved points are: “correction function” for accurate monoisotopic peak picking; one-to-one correspondence of clusters and core peptides even for multiply sialylated glycopeptides; and “inter-cluster analysis” function for understanding the reason for detected but unmatched clusters. The significance of these improvements was demonstrated using purified and crude glycoprotein samples, showing that GRable allowed site-specific glycoform analysis of intact sialylated glycoproteins on a large scale and in depth. Therefore, this software will help to analyze the status and changes in glycans to obtain biological and clinical insights into protein glycosylation by complementing the comprehensiveness of MS2-based glycoproteomics. GRable can run freely online using a web browser via the GlyCosmos Portal (https://glycosmos.org/grable).

Graphical Abstract
Gamma sensory stimulation and effects on the brain
Authors: Kahn Martin , Chan Diane , Wang Danying , Geigenmuller Ute , Blanco-Duque Cristina , Murdock Mitchell H. , Suk Ho-Jun , Jackson Brennan , Jakkamsetti Vikram , Niederst Emily , Brown Emery N. , Boyden Edward S. , McHugh Thomas , Adaikkan Chinnakkaruppan , Singer Annabelle C. , Hanslmayr Simon , Tsai Li-Huei
Published: November 2023

Findings by the Tsai lab and others1–8demonstrate that 40 Hz frequency sensory stimulation induces electrophysiological responses and attenuates pathology in mouse models of Alzheimer’s disease (AD). A recent study inNature Neurosciene9concluded that the stimulation does not affect endogenous gamma oscillations or amyloid burden. We welcome research investigating 40 Hz sensory stimulation, and the article by Soula et al enhances our understanding of the brain’s electrophysiological response to 40Hz. However, we respectfully suggest that the data in Soula et al are consistent with a neuronal response to 40 Hz, which we further support with new data in humans. Moreover we contend the non-significant effects on amyloid are due to technical limitations of the study.
Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer
Authors: Raynal Flavien , Sengupta Kaustav , Plewczynski Dariusz , Aliaga Benoît , Pancaldi Vera
Published: November 2023

Cancer cells are highly plastic, allowing them to adapt to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in three cell types: human embryonic stem cells, normal B-cells, and primary cells from Chronic Lymphocytic Leukemia, a B-cell malignancy. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA Polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA Polymerase II, Polycomb, and the lamina, respectively.

Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.
Molecular epidemiology of Cercospora leaf spot on resistant and susceptible sugar beet hybrids
Authors: Chen Chen , Keunecke Harald , Neu Enzo , Kopisch-Obuch Friedrich J. , McDonald Bruce A. , Stapley Jessica
Published: November 2023

Cercospora leaf spot (CLS), caused byCercospora beticola, is a major foliar disease impacting sugar beet production worldwide. The development of new resistant sugar beet hybrids is a powerful tool to better manage the disease, but it is unclear how these hybrids affect CLS epidemiology. We used a molecular epidemiology approach to study natural epidemics of CLS affecting two susceptible and two resistant sugar beet hybrids at two field sites.

Infected plants were geotagged on a weekly basis. Isolations ofC. beticolawere made from infected leaves and genotyped using six simple sequence repeat loci to identify clones. We determined that CLS epidemics had a later onset in plots planted to resistant hybrids, but once the pathogen established an infection, there was little difference between resistant and susceptible hybrids in the probability of localized spread and dispersal. We found that different clones often infected the same leaf and that clusters of infected plants were often colonized by a mixture of clones. There was little overall difference in genetic diversity between resistant and susceptible hybrids, however genotypic evenness differed at one site. In this site we found one genotype restricted to the resistant cultivars at a high frequency. At the end of the epidemic infections were not randomly distributed across the fields and we found that a single clone could spread over a distance of 100 m during a growing season.
A dipteran parasite regulates 20E synthesis and antibacterial activity of the host for development through inducing host nitric oxide production
Authors: Dai Minli , Jiang Zhe , Li Fanchi , Wei Jing , Li Bing
Published: November 2023

Parasites primarily rely on the host to survive, and have evolved diverse survival strategies. In the present study, we report a specific survival strategy of a dipteran parasiteExorista sorbillans(Diptera: Tachinidae), which is a potential biological control agent for agricultural pests and a pest in sericulture. We found that the expression levels of host nitric oxide synthase (NOS) and nitric oxide (NO) production were increased afterE. sorbillansinfection. Reducing NOS expression and NO production with a NOS inhibitor (L-NAME) in infected hosts significantly impeded the growth ofE. sorbillanslarvae. Moreover, the 20-hydroxyecdysone (20E) biosynthesis of infected hosts was elevated with increasing NO production, and inhibiting NOS expression also lowered 20E biosynthesis. More importantly, induced NO synthesis was required to eliminate intracellular bacterial pathogens that presumably competed for shared host resources. Inhibiting NOS expression down-regulated the transcription of antimicrobial peptide genes and increased the number of bacteria in infected hosts. Collectively, this study revealed a new perspective on the role of NO in host-parasite interactions and a novel mechanism for parasite regulation of host to support its development.

Author summary

Parasites are ubiquitous on earth and diverse, and have evolved various strategies to match their own specific requirements for survival within the host. In this study, we found thatExorista sorbillans, an endoparasite of many agricultural pests and the main insect pest in sericulture, used a novel strategy to manipulate its host NO synthesis for survival within its hostBombyx mori. Specifically, NOS expression and the production of NO in the host were up-regulated byE. sorbillansinfection, which benefited larvalE. sorbillansdevelopment. Meanwhile, increased NO production in host activated 20E synthesis of parasitized hosts and triggered the expression of AMPs against the invasion of pathogenic bacteria to avoid nutritional competence in the host. Our study provides innovative insights into the mechanisms by which a parasite manipulates host NO production for development and may help to expand our knowledge of other parasitic systems.
Terrestrial land cover shapes fish diversity in major subtropical rivers
Authors: Zhang Heng , Blackman Rosetta C. , Furrer Reinhard , Osathanunkul Maslin , Brantschen Jeanine , Di Muri Cristina , Harper Lynsey R. , Hänfling Bernd , Niklaus Pascal A. , Pellissier Loïc , Schaepman Michael E. , Zong Shuo , Altermatt Florian
Published: November 2023

Freshwater biodiversity is critically affected by human modifications of terrestrial land use and land cover (LULC)1,2. Yet, knowledge of the spatial extent and magnitude of LULC-aquatic biodiversity linkages is still surprisingly limited, impeding the implementation of optimal management strategies3. Here, we compiled fish diversity data across a 160,000-km2subtropical river catchment in Thailand characterized by exceptional biodiversity4yet intense anthropogenic alterations5, and attributed fish species richness and community composition to contemporary terrestrial LULC across the catchment. We estimated a spatial range of LULC effects extending up to about 20 km upstream from sampling sites, and explained nearly 60 % of the variance in the observed species richness, associated with major LULC categories including croplands, forest, and urban areas. We find that integrating both spatial range and magnitudes of LULC effects is needed to accurately predict fish species richness. Further, projected LULC changes showcase future gains and losses of fish species richness across the river network and offer a scalable basis for riverine biodiversity conservation and land management, allowing for potential mitigation of biodiversity loss in highly diverse yet data-deficient tropical to sub-tropical riverine habitats.
A single changing hypernetwork to represent (social-)ecological dynamics
Authors: Gaucherel C. , Cosme M. , Noûs C. , Pommereau F.
Published: November 2023

Abstract

To understand and manage (social-)ecological systems, we need an intuitive and rigorous way to represent them. Recent ecological studies propose to represent interaction networks into modular graphs, multiplexes and higher-order interactions. Along these lines, we argue here that non-dyadic (non-pairwise) interactions are common in ecology and environmental sciences, necessitating fresh concepts and tools for handling them. In addition, such interaction networks often change sharply, due to appearing and disappearing species and components. We illustrate in a simple example that any ecosystem can be represented by a single hypergraph, here called the ecosystem hypernetwork. Moreover, we highlight that any ecosystem hypernetwork exhibits a changing topology summarizing its long term dynamics (e.g., species extinction/invasion, pollutant or human arrival/migration). Qualitative and discrete-event models developed in computer science appear suitable for modeling hypergraph (topological) dynamics. Hypernetworks thus also provide a conceptual foundation for theoretical as well as more applied studies in ecology (at large), as they form the qualitative backbone of ever-changing ecosystems.
NREM sleep oscillations and their relations with sleep-dependent memory consolidation in early course psychosis and first-degree relatives
Authors: Denis Dan , Baran Bengi , Mylonas Dimitrios , Spitzer Courtney , Raymond Nicolas , Talbot Christine , Kohnke Erin , Stickgold Robert , Keshavan Matcheri , Manoach Dara S.
Published: November 2023

Sleep spindles are believed to mediate sleep-dependent memory consolidation, particularly when coupled to neocortical slow oscillations. Schizophrenia is characterized by a deficit in sleep spindles that correlates with reduced overnight memory consolidation. Here, we examined sleep spindle activity, slow oscillation-spindle coupling, and both motor procedural and verbal declarative memory consolidation in early course, minimally medicated psychosis patients and non-psychotic first-degree relatives. Using a four-night experimental procedure, we observed significant deficits in spindle density and amplitude in patients relative to controls that were driven by individuals with schizophrenia. Schizophrenia patients also showed reduced sleep-dependent consolidation of motor procedural memory, which correlated with spindle density. Contrary to expectations, there were no group differences in the consolidation of declarative memory on a word pairs task. Nor did the relatives of patients differ in spindle activity or memory consolidation compared with controls, however increased consistency in the timing of SO-spindle coupling were seen in both patient and relatives. Our results extend prior work by demonstrating correlated deficits in sleep spindles and sleep-dependent motor procedural memory consolidation in early course, minimally medicated patients with schizophrenia, but not in first-degree relatives. This is consistent with other work in suggesting that impaired sleep-dependent memory consolidation has some specificity for schizophrenia and is a core feature rather than reflecting the effects of medication or chronicity.

Statement of significance

We investigated sleep neurophysiology and memory consolidation in minimally-medicated, early course psychosis patients and unaffected first-degree relatives of patients in a four-night study. Early-course schizophrenia patients had a sleep spindle deficit that correlated with reduced procedural memory consolidation. Although first-degree relatives did not show any deficit in spindles or memory consolidation, the spindles of both relatives and patients showed increased consistency of the temporal coupling of spindles with slow oscillations compared with controls. These results suggest that sleep spindle and memory consolidation deficits are a core feature of schizophrenia. Spindle deficits may be a biomarker of schizophrenia modifiable by treatment, and motivate the development of targeted novel interventions.
Crossroads of assembling a moss genome: navigating contaminants and horizontal gene transfer in the mossPhyscomitrellopsis africana
Authors: Vuruputoor Vidya S. , Starovoitov Andrew , Cai Yuqing , Liu Yang , Rahmatpour Nasim , Hedderson Terry A. , Wilding Nicholas , Wegrzyn Jill L. , Goffinet Bernard
Published: November 2023

The first chromosome-scale reference genome of the rare narrow-endemic African mossPhyscomitrellopsis africanais presented here. Assembled from 73x nanopore long reads and 163x BGI-seq short reads, the 414 Mb reference comprises 26 chromosomes and 22,925 protein-coding genes (BUSCO: C:94.8%[D:13.9%]). This genome holds two genes that withstood rigorous filtration of microbial contaminants, have no homolog in other land plants and are thus interpreted as resulting from two unique horizontal gene transfers from microbes. Further,Physcomitrellopsis africanashares 176 of the 273 published HGT candidates identified inPhyscomitrium patens, but lacks 98 of these, highlighting that perhaps as many as 91 genes were acquired inP. patensin the last 40 million years following its divergence from its common ancestor withP. africana. These observations suggest rather continuous gene gains via HGT followed by potential losses, during the diversification of the Funariaceae. Our findings showcase both dynamic flux in plant HGTs over evolutionarily “short” timescales, alongside enduring impacts of successful integrations, like those still functionally maintained in extantPhyscomitrellopsis africana. Furthermore, this study describes the informatic processes employed to distinguish contaminants from candidate HGT events.

Article Summary

The first draft genome of the rare South African endemic mossPhyscomitrellopsis Africanais presented. The 414 Mb assembly contains 22,925 genes, including two uniquely horizontally transferred genes, but lacks 97 of the microbial genes previously identified in the closely related model,Physcomitrium patens- highlighting the dynamic role of HGT in the evolution of these moss genomes and loss. This study presents best practices for contamination detection and new insights into HGT identification.
Ipl1-controlled attachment maturation regulates Mps1 association with its kinetochore receptor
Authors: Pleuger Richard , Cozma Christian , Hohoff Simone , Denkhaus Christian , Dudziak Alexander , Kaschani Farnusch , Musacchio Andrea , Vetter Ingrid R. , Westermann Stefan
Published: November 2023

Faithful chromosome segregation requires that sister chromatids establish bi-oriented kinetochore-microtubule attachments. The spindle assembly checkpoint (SAC) prevents premature anaphase onset with incomplete attachments. However, how microtubule attachment and checkpoint signaling are coordinated remains unclear. The conserved kinase Mps1 initiates SAC signaling by localizing transiently to kinetochores in prometaphase and is released upon bi-orientation. Using biochemistry, structure predictions, and cellular assays, we shed light on this dynamic behaviour inSaccharomyces cerevisiae. A conserved N-terminal segment of Mps1 binds the neck region of Ndc80:Nuf2, the main microtubule receptor of kinetochores. Mutational disruption of this interface, located at the backside of the paired CH-domains and opposite the microtubule-binding site, prevents Mps1 localization, eliminates SAC signalling, and impairs growth. The same interface of Ndc80:Nuf2 binds the microtubule-associated Dam1 complex. We demonstrate that the error correction kinase Ipl1/Aurora B controls the competition between Dam1 and Mps1 for the same binding site. Thus, binding of the Dam1 complex to Ndc80:Nuf2 may release Mps1 from the kinetochore to allow anaphase onset.