bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly resolved network reveals the role of terrestrial herbivory in structuring aboveground food webs
Authors: Hale Kayla R. S. , Curlis John David , Auteri Giorgia G. , Bishop Sasha , French Rowan L. K. , Jones Lance E. , Mills Kirby L. , Scholtens Brian G. , Simons Meagan , Thompson Cody , Tourville Jordon , Valdovinos Fernanda S.
Published: July 2024

Comparative studies suggest remarkable similarities among food webs across habitats, including systematic changes in their structure with diversity and complexity (scale-dependence). However, historic aboveground terrestrial food webs (ATFWs) have coarsely grouped plants and insects such that these webs are generally small, and herbivory is disproportionately under-represented compared to vertebrate predator–prey interactions. Furthermore, terrestrial herbivory is thought to be structured by unique processes compared to size-structured feeding in other systems. Here, we present the richest ATFW to date, including approximately 580 000 feeding links among approximately 3800 taxonomic species, sourced from approximately 27 000 expert-vetted interaction records annotated as feeding upon one of six different resource types: leaves, flowers, seeds, wood, prey and carrion. By comparison to historical ATFWs and null ecological hypotheses, we show that our temperate forest web displays a potentially unique structure characterized by two properties: (i) a large fraction of carnivory interactions dominated by a small number of hyper-generalist, opportunistic bird and bat predators; and (ii) a smaller fraction of herbivory interactions dominated by a hyper-rich community of insects with variably sized but highly specific diets. We attribute our findings to the large-scale, even resolution of vertebrate, insect and plant guilds in our food web.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Assessing impacts of bycatch policies and fishers’ heterogeneous information on food webs and fishery sustainability
Authors: Kushal Appilineni , Springborn Michael R. , Valdovinos Fernanda S.
Published: July 2024

Ecosystem-based fisheries management (EBFM) has emerged as a promising framework for understanding and managing the long-term interactions between fisheries and the larger marine ecosystems in which they are nested. However, successful implementation of EBFM has been elusive because we still lack a comprehensive understanding of the network of interacting species in marine ecosystems (the food web) and the dynamic relationship between the food web and the humans who harvest those ecosystems. Here, we advance such understanding by developing a network framework that integrates the complexity of food webs with the economic dynamics of different management policies. Specifically, we generate hundreds of different food web models with 20–30 species, each harvested by five different fishers extracting the biomass of a target and a bycatch species, subject to two different management scenarios and exhibiting different information in terms of avoiding bycatch when harvesting the target species. We assess the different ecological and economic consequences of these policy alternatives as species extinctions and profit from sustaining the fishery. We present the results of different policies relative to a benchmark open access scenario where there are no management policies in place. The framework of our network model would allow policymakers to evaluate different management approaches without compromising on the ecological complexities of a fishery.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Cognatishimia coralii sp. nov., a marine bacterium isolated from seawater surrounding corals
Authors: Liu Xuerui , Liu Shuai , Yu Zhen , Guo Xiangrui , Zhang Rui , Sun Hao , Zhang Yanying
Published: July 2024

Coral reefs are declining due to the rising seawater temperature. Bacteria within and surrounding corals play key roles in maintaining the homeostasis of the coral holobiont. Research on coral-related bacteria could provide benefits for coral reef restoration. During the isolation of coral-associated bacteria, a Gram-stain-negative, motile bacterium (D5M38T) was isolated from seawater surrounding corals in Daya Bay, Shenzhen, PR China. Phylogenetic analysis revealed that strain D5M38T represents a novel species in the genus Cognatishimia. The temperature range for strain D5M38T growth was 10–40 °C, and the optimum temperature was 37 °C. The salinity range for the growth of this isolate was from 0 to 4.0 %, with an optimal salinity level of 0.5 %. The pH range necessary for strain D5M38T growth was between pH 5.0 and 9.0, with an optimal pH being 7.5. The predominant fatty acid was summed feature 8 (65.0 %). The major respiratory quinone was Q-10. The DNA G+C content was 56.8 %. The genome size was 3.88 Mb. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA–DNA hybridization (dDDH) values between strain D5M38T and its two closest neighbours, Cognatishimia activa LMG 29900T and Cognatishimia maritima KCTC 23347T, were 73.2/73.6%, 73.2/73.6% and 19.7/19.5%, respectively. Strain D5M38T was clearly distinct from its closest neighbours C. activa LMG 29900T and C. maritima KCTC 23347T, with 16S rRNA gene sequence similarity values of 97.5 and 97.3 %, respectively. The phylogenetic analysis, along with the ANI, AAI, and dDDH values, demonstrated that strain D5M38T is a member of the genus Cognatishimia, and is distinct from the other two recognized species within this genus. The physiological, biochemical and chemotaxonomic characteristics also supported the species novelty of strain D5M38T. Thus, strain D5M38T is considered to be classified as representing a novel species in the genus Cognatishimia, for which the name Cognatishimia coralii sp. nov. is proposed. The type strain is D5M38T (=MCCC 1K08692T=KCTC 8160T).
C-terminally encoded peptides promoting root symbiotic nodulation in legume plants also promote the root arbuscular mycorrhizal symbiotic interaction
Authors: Pedinotti Léa , Teyssendier de la Serve Juliette , Roudaire Thibault , Clemente Hélène San , Aguilar Marielle , Kohlen Wouter , Frugier Florian , Frei dit Frey Nicolas
Published: July 2024

C-terminally encoded peptides (CEPs) are small secreted signalling peptides that promote in legumes the root nitrogen-fixing nodulation symbiosis depending on soil mineral nitrogen availability1. In Medicago truncatula, their action is mediated by the Leucine-rich repeat receptor-like protein kinase COMPACT ROOT ARCHITECTURE 2 (CRA2)2–4. As most land plants, under inorganic phosphate (Pi) limitation, M. truncatula establishes another root endosymbiotic interaction with arbuscular fungi, the arbuscular mycorrhizal symbiosis (AMS). Because this interaction is beneficial for the plant but has a high energetic cost, it is tightly controlled by host plants to limit AMS infections mainly depending on Pi availability5. We show in this study that the expression of a subset of CEP encoding genes is enhanced in the low Pi conditions that favour AMS colonization, and that overexpression of the low Pi-induced MtCEP1 gene, previously shown to promote the nitrogen-fixing root nodulation symbiosis, enhances the AMS colonization from the initial entry point of the fungi. Conversely, a loss-of-function mutation of the CRA2 receptor required for mediating CEP peptides action2decreases the AMS interaction capacity from the same initial fungal entry stage. Transcriptomic analyses revealed that the cra2 mutant is negatively affected in the regulation of key Pi transport and response genes as well as in the biosynthesis of strigolactone (SL) hormones that are required for establishing the AMS interaction. Accordingly, SL contents were drastically decreased in cra2 mutant roots. Overall, we showed that the CEP/CRA2 pathway promotes, in legume plants, both root nodulation and AMS depending on soil mineral nutrients availability.

In brief

The establishment and maintenance of root nodule and arbuscular mycorrhizal symbioses (AMS) in legume plants is tightly regulated respectively by nitrogen and phosphate availability. Pedinotti and Teyssendier de la Serve et al. show that the CEP/CRA2 pathway, previously known to promote root competence to nodulate under low nitrogen conditions, also enhances AMS establishment by controlling the expression of Pi homeostasis and strigolactone (SL) hormone biosynthesis genes, as well as SL accumulation.

Highlights

A subset of M. truncatula CEP genes is induced by AMS-promoting low phosphate conditions.

The CEP1 peptides positively regulate AMS establishment, while the cra2 CEP receptor loss of function mutants display a reduced AMS colonization.

The CEP/CRA2-dependent regulation of AMS acts through downstream signals distinct from the ones involved in root nodule symbiosis regulation. The CEP/CRA2 pathway regulates AMS establishment by controlling Pi homeostasis and strigolactone (SL) hormone biosynthesis genes, as well as SL accumulation.
Microbial photoproduction of heptane
Authors: Baca-Porcel Ángel , Legeret Bertrand , Auroy-Tarrago Pascaline , Veillet Florian , Giacalone Cécile , Cuine Stephan , Samire Poutoum Palakiyém , Moulin Solène , Li-Beisson Yonghua , Beisson Fred , Sorigué Damien
Published: July 2024

Fatty Acid Photodecarboxylase (FAP) has emerged as a promising catalyst for the biological production of long-chain hydrocarbons. We have recently shown that purified FAP or FAP-expressing bacteria can efficiently convert octanoic acid into heptane, thus extending the potential applications of FAP to medium-chain hydrocarbons (i.e., solvent- or kerosene-type). The scarcity of natural sources of octanoic acid presents a challenge however. Here, we explore the heptane production capacity of a FAP-expressingE. colistrain engineered to biosynthesize octanoic acid via a specific thioesterase. Various FAPs and C8-specific thioesterases were tested. A blue-light-inducible promoter was used to avoid chemical inducers. We found that the expression of FAP fused with TrxA resulted in a 10-fold increase in heptane production. Coexpression ofCuphea hookerianathioesterase andChlorella variabilisFAP achieved the highest heptane titer (12.5 mg.L-1). Scale-up experiments in 100 mL photobioreactors allowed a constant production of heptane over two days (22 mg.L-1.day-1).

Graphical Abstract

Highlights

AnE. colistrain producing heptane under blue light is described.

Expression of FAP fused with TrxA increases heptane by 10-fold.

A blue light-inducible promoter ensures high coexpression of FAP and thioesterase.

Cuphea hookerianathioesterase andChlorella variabilisFAP give highest production

Highest reported heptane productivity (22 mg.L-1.day-1) in 100 mL photobioreactors.
Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent
Authors: Lejeune Alannah , Zhou Chunyi , Ercelen Defne , Putzel Gregory , Yao Xiaomin , Guy Alyson R , Pawline Miranda , Podkowik Magdalena , Pironti Alejandro , Torres Victor J. , Shopsin Bo , Cadwell Ken
Published: July 2024

Gastrointestinal (GI) colonization by methicillin-resistantStaphylococcus aureus(MRSA) is associated with a high risk of transmission and invasive disease in vulnerable populations. The immune and microbial factors that permit GI colonization remain unknown. Male sex is correlated with enhancedStaphylococcus aureusnasal carriage, skin and soft tissue infections, and bacterial sepsis. Here, we established a mouse model of sexual dimorphism during GI colonization by MRSA. Our results show that in contrast to male mice that were susceptible to persistent colonization, female mice rapidly cleared MRSA from the GI tract following oral inoculation in a manner dependent on the gut microbiota. This colonization resistance displayed by female mice was mediated by an increase in IL-17A+ CD4+ T cells (Th17) and dependent on neutrophils. Ovariectomy of female mice increased MRSA burden, but gonadal female mice that have the Y chromosome retained enhanced Th17 responses and colonization resistance. Our study reveals a novel intersection between sex and gut microbiota underlying colonization resistance against a major widespread pathogen.
Invariant synaptic density links neuronal activity stability and wiring optimisation principles across species
Authors: Ferreira Castro André , Cardona Albert
Published: July 2024

The nervous system scales with animal size while preserving function, yet the principles underlying this stability remain unclear. Here, we analyse the ultra-structure and connectivity of thousands of neuronal cells across species, including fly, zebrafish, mouse, and human, and found a conserved feature that stabilises neuronal responses across scales: an average of one synapse per micrometre of den-dritic cable. We show that the appropriate synaptic density is established during development through precise axon-dendrite positioning guided by molecular cues and synapt?ic activity. We find that this specific synaptic density is dictated by wiring optimisation in neurons, where dendrites minimise cable length and conduction delays. Finally, simulations demonstrate invariant synaptic density as a fundamental neuronal design principle, conserved for its ability to synergise with other cell-intrinsic properties to stabilise voltage responses across cell types and species. This work provides a new framework for understanding neuronal scaling, offering insights for the interpretation of circuit organisation across species
scEccDNAdb: an integrated single-cell eccDNA resource for human and mouse
Authors: Wang Wenqing , Zhao Xinyu , Ma Tianyu , Zhong Tengwei , Zheng Junnuo , Yang Yi , Guo Yuanbiao , Guo Zhiyun
Published: July 2024

Extrachromosomal circular DNA (eccDNA), an extrachromosomal circular structured DNA, is extensively found in eukaryotes. Exploring eccDNA at the single-cell level contributes to understanding heterogeneity, evolution, development, and specific functions within cells. Nevertheless, the high-throughput identification methods for single-cell eccDNA are complex, and currently mature and widely applicable technologies are lacking. Those factors have led to a scarcity of resources for studying eccDNA at the single-cell level. Therefore, using available single-cell whole-genome sequencing (WGS) data, we have constructed a comprehensive eccDNA database named scEccDNAdb (https://lcbb.swjtu.edu.cn/scEccDNAdb/). Presently, scEccDNAdb comprises 3,195,464 single-cell eccDNA entries from both disease/health human and mouse samples, which provides comprehensive annotations including oncogenes, typical enhancers, super-enhancers, CTCF binding sites, SNPs, chromatin accessibility, eQTLs, transcription factor binding sites, motifs, and SVs. Additionally, it provides nine online analysis and visualization tools, facilitating the generation of publication-quality figures for eccDNA analysis through the upload of customized files. Overall, scEccDNAdb represents the first comprehensive database known to us for exploring and analyzing single-cell eccDNA data in diverse cell types, tissues, and species.

Graphical abstract
Surfing beta burst waveforms to improve motor imagery-based BCI
Authors: Papadopoulos S. , Darmet L. , Szul M.J. , Congedo M. , Bonaiuto J.J. , Mattout J.
Published: July 2024

Our understanding of motor-related, macroscale brain processes has been significantly shaped by the description of the event-related desynchronization (ERD) and synchronization (ERS) phenomena in the mu and beta frequency bands prior to, during and following movement. The demonstration of reproducible, spatially-and band-limited signal power changes has, consequently, attracted the interest of non invasive brain-computer interface (BCI) research for a long time. BCIs often rely on motor imagery (MI) experimental paradigms that are expected to generate brain signal modulations analogous to movement-related ERD and ERS. However, a number of recent neuroscience studies has questioned the nature of these phenomena. Beta band activity has been shown to occur, on a single-trial level, in short, transient and heterogeneous events termed bursts rather than sustained oscillations. In a previous study, we established that an analysis of hand MI binary classification tasks based on beta bursts can be superior to beta power in terms of classification score. In this article we elaborate on this idea, proposing a signal processing algorithm that is comparable to-and compatible with state-of-the-art techniques. Our pipeline filters brain recordings by convolving them with kernels extracted from beta bursts and then applies spatial filtering before classification. This data-driven filtering allowed for a simple and efficient analysis of signals from multiple sensors thus being suitable for online applications. By adopting a time-resolved decoding approach we explored MI dynamics and showed the specificity of the new classification features. In accordance with previous results, beta bursts improved classification performance compared to beta band power, while often increasing information transfer rate compared to state-of-the-art approaches.

Significance statement

Patterns of waveform-specific burst rate comprise an alternative, neurophysiology-informed way of analyzing beta band activity during motor imagery (MI) tasks. By testing this method on multiple electroencephalography datasets and comparing its corresponding classification scores against those of conventional power-based features, this work demonstrates that brain-computer interface applications could benefit from utilizing beta burst activity. This activity gives access to a reliable decoding performance often requiring short recordings. As such, this study shows that waveform-specific beta burst rates encode information related to imagined (and presumably real) movements and serves as the first step for a real-time implementation of the proposed methodology.
Spatio-temporal dynamics of attacks around deaths of wolves: A statistical assessment of lethal control efficiency in France
Authors: Grente Oksana , Opitz Thomas , Duchamp Christophe , Drouet-Hoguet Nolwenn , Chamaille-Jammes Simon , Gimenez Olivier
Published: July 2024

The lethal control of large carnivores is criticized regarding its efficiency to deter hotspots of attacks on livestock. We evaluated the effects of wolf lethal removals on the distribution of attack intensities in the French Alps between 2011 and 2020, using a BACI approach with retrospective data. We built an original framework combining both continuous spatial and temporal scales and a 3D kernel estimation. We compared the attack intensities observed before and after 278 legal killings of wolves on a period of 90 days and on a range of 10 km, and with control situations where no removal occurred. The analysis was also corrected for livestock presence, and explored different subsets of removals in relation to their locations, seasons and proximity to other removals. This method provided efficient visual charts and trends of attack intensity variations before and after removals. A moderate decrease of attack intensity was the most common outcome after a lethal removal. Analysis scale modulated this general pattern, with decreases being generally amplified at a small spatio-temporal range. Contextual factors (e.g., geographical or seasonal variations) could also lead to deviations from this general pattern, with outcomes of subsets ranging from important decreases to moderate increases. Thus, between 2011 and 2020, lethal control of wolves in France generally contributed to manage livestock attacks but did not eliminate it, even though mainly implemented alongside non-lethal measures. Our results highlight the importance of accounting for scale in such assessments and suggest that the evaluation of the effectiveness of lethal removals in reducing livestock predation might be more relevant in a local context. As a next step, we recommend to move forward from patterns to mechanisms by linking the effects of lethal control on wolves to their effects on attacks through analysis of fine-scaled data on wolves and livestock.
Brain responses to predictable structure in auditory sequences: From complex regular patterns to tone repetition
Authors: Southwell Rosy , Tufo Candida , Chait Maria
Published: July 2024

In classical studies of auditory pattern learning, neuronal responses exhibit repetition suppression, where sequences of repeated tones show a reduced evoked response. This may be due in part to adaptation, but is also hypothesized to indicate suppression of expected stimuli. Repetition suppression is thought to form a building block of regularity learning, and is the paradigmatic example of predictive coding in humans and other animals.

However, stimuli with more complex patterns appear to show the opposite effect. Predictable regular (REG) patterns distributed over a range of frequencies show a strongly enhanced sustained brain response compared to frequency-matched random (RAND) sequences, sitting at odds with the usual reduced evoked responses to predictable stimuli. A limiting factor in reconciling these findings is that they are obtained using different stimuli and analysis methods.

This human EEG study (N=20) brings together auditory sequence predictability and repetition in a single paradigm, based on rapidly unfolding tone pip patterns, incorporating sequences consisting of exactly repeating tones at a single frequency, alongside REG and RAND of varying complexity. We demonstrate that regularity is associated with increased sustained responses, offset responses, tone locked responses and cycle-locked responses. We further show that both repetition suppression and repetition enhancement occur over different timescales, and that sustained brain responses to simple repetition show qualitatively different effects than to more complex regularities during automatic tracking of stimulus statistics. Our results indicate a system for automatic monitoring of predictability in the auditory environment, which is distinct from, but concurrent with, repetition suppression.

NEW & NOTEWORTHY

We investigate how human brain response patterns evolve as auditory patterns become progressively simplified, focusing on the impact of sequence structure on various aspects of EEG responses, both evoked and induced. By contrasting EEG responses across different phases of the stimulus—onset, sustained, and offset—we uncover the interplay between repetition suppression and predictability. This approach allows us to discern how the brain processes and adapts to changing regularities in sensory input.
Encoding of cerebellar dentate neuron activity during visual attention in rhesus macaques
Authors: Flierman Nico A. , Koay Sue Ann , van Hoogstraten Willem S. , Ruigrok Tom J.H. , Roelfsema Pieter R. , Badura Aleksandra , De Zeeuw Chris I.
Published: July 2024

The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay. We found that single unit DN neurons modulated spiking activity over the entire time-course of the task, and that their activity often bridged temporally separated intra-trial events, yet in a heterogeneous manner. To better understand the heterogeneous relationship between task structure, behavioral performance and neural dynamics, we constructed a behavioral, an encoding and a decoding model. Both NHPs showed different behavioral strategies, which influenced the performance. Activity of the DN neurons reflected the unique strategies, with the direction of the visual stimulus frequently being encoded long before an upcoming saccade. Moreover, the latency of the ramping activity of DN neurons following presentation of the visual stimulus was shorter in the better performing NHP. Labeling with the retrograde tracer CTB in the recording location in the DN indicated that these neurons predominantly receive inputs from Purkinje cells in the D1 and D2 zones of the lateral cerebellum as well as neurons of the principal olive and medial pons, all regions known to connect with neurons in the prefrontal cortex contributing to planning of saccades. Together, our results highlight that DN neurons can dynamically modulate their activity during a visual attention task, comprising not only sensorimotor but also cognitive attentional components.
Label-free multiphoton imaging reveals volumetric shifts across development in sensory-related brain regions of a miniature transparent vertebrate
Authors: Tatarsky Rose L. , Akbari Najva , Wang Ke , Xu Chris , Bass Andrew H.
Published: July 2024

Animals integrate information from different sensory modalities as they mature and perform increasingly complex behaviors. This may parallel differential investment in specific brain regions depending on the demands of changing sensory inputs. To investigate developmental changes in the volume of canonical sensory integration brain regions, we used third harmonic generation imaging for morphometric analysis of forebrain and midbrain regions from 5 to 90 days post fertilization (dpf) inDanionella dracula, a transparent, miniature teleost fish whose brain is optically accessible throughout its lifespan. Relative to whole brain volume, increased volume or investment in telencephalon, a higher order sensory integration center, and torus longitudinalis (TL), a midbrain visuomotor integration center, is relatively consistent from 5 to 30 dpf, until it increases at 60 dpf, followed by another increase at 90 dpf, as animals reach adulthood. In contrast, investment in midbrain optic tectum (TeO), a retinal-recipient target, progressively decreases from 30-90 dpf, whereas investment is relatively consistent across all stages for the midbrain torus semicircularis (TS), a secondary auditory and mechanosensory lateral line center, and the olfactory bulb (OB), a direct target of the olfactory epithelium. In sum, increased investment in higher order integration centers (telencephalon, TL) occurs as juveniles reach adulthood and exhibit more complex cognitive tasks, whereas investment in modality-dominant regions occurs in earlier stages (TeO) or is relatively consistent across development (TS, OB). Complete optical access throughoutDanionella’s lifespan provides a unique opportunity to investigate how changing brain structure over development correlates with changes in connectivity, microcircuitry, or behavior.
Self-avoidance dominates the selection of hippocampal replay
Authors: Mallory Caitlin S , Widloski John , Foster David J
Published: July 2024

Spontaneous neural activity sequences are generated by the brain in the absence of external input1–12, yet how they are produced remains unknown. During immobility, hippocampal replay sequences depict spatial paths related to the animal’s past experience or predicted future13. By recording from large ensembles of hippocampal place cells14in combination with optogenetic manipulation of cortical input in freely behaving rats, we show here that the selection of hippocampal replay is governed by a novel self-avoidance principle. Following movement cessation, replay of the animal’s past path is strongly avoided, while replay of the future path predominates. Moreover, when the past and future paths overlap, early replays avoid both and depict entirely different trajectories. Further, replays avoid self-repetition, on a shorter timescale compared to the avoidance of previous behavioral trajectories. Eventually, several seconds into the stopping period, replay of the past trajectory dominates. This temporal organization contrasts with established and recent predictions9,10,15,16but is well-recapitulated by a symmetry-breaking attractor model of sequence generation in which individual neurons adapt their firing rates over time26–35. However, while the model is sufficient to produce avoidance of recently traversed or reactivated paths, it requires an additional excitatory input into recently activated cells to produce the later window of past-dominance. We performed optogenetic perturbations to demonstrate that this input is provided by medial entorhinal cortex, revealing its role in maintaining a memory of past experience that biases hippocampal replay. Together, these data provide specific evidence for how hippocampal replays are generated.
Mesoscale chromatin confinement facilitates target search of pioneer transcription factors in live cells
Authors: Wang Zuhui , Wang Bo , Niu Di , Yin Chao , Bi Ying , Cattoglio Claudia , Loh Kyle M , Lavis Luke D , Ge Hao , Deng Wulan
Published: July 2024

Pioneer transcription factors (PTFs) possess the unique capability to access closed chromatin regions and initiate cell fate changes, yet the underlying mechanisms remain elusive. Here, we characterized the single-molecule dynamics of PTFs targeting chromatin in living cells, revealing a notable "confined target search" mechanism. PTFs like FOXA1, FOXA2, SOX2, OCT4 and KLF4 sampled chromatin more frequently than non-pioneer factor MYC, alternating between fast free diffusion in the nucleus and slower confined diffusion within mesoscale zones. Super-resolved microscopy showed closed chromatin organized as mesoscale nucleosome-dense domains, confining FOXA2 diffusion locally and enriching its binding. We pinpointed specific histone-interacting disordered regions, distinct from DNA-binding domain, crucial for confined target search kinetics and pioneer activity within closed chromatin. Fusion to other factors enhanced pioneer activity. Kinetic simulations suggested transient confinement could increase target association rate by shortening search time and binding repeatedly. Our findings illuminate how PTFs recognize and exploit closed chromatin organization to access targets, revealing a pivotal aspect of gene regulation.
Detection of pneumococcal carriage in asymptomatic healthcare workers
Authors: Waghela Pari , Davis Raechel , Campbell Melissa , Datta Rupak , Hislop Maikel S. , Vega Noel J. , Wurst Loren , Yolda-Carr Devyn , Couch Luke , Hernandez Michael , Grant Lindsay R. , Alexander-Parrish Ronika , Arguedas Adriano , Gessner Bradford D. , Martinello Richard A. , Weinberger Daniel M. , Wyllie Anne L.
Published: July 2024

Background

Healthcare workers are at increased risk of exposure to respiratory pathogens includingStreptococcus pneumoniae(pneumococcus). While little asymptomatic carriage has been reported in young-to-middle-aged adults, this may be due to non-sensitive diagnostic methods. The aim of the study was to investigate the rates of pneumococcal carriage in a large cohort of healthcare workers using saliva as a respiratory specimen.

Methods

We evaluated the prevalence of pneumococcal carriage in a convenience sample of saliva, self-collected from asymptomatic healthcare workers at Yale New Haven Hospital (CT, USA) who were testing for SARS-CoV-2 from March 30 to June 11, 2020. Samples were transported at ambient temperature and stored at −80°C within 12 hours. DNA extracted from the culture-enriched saliva was later tested using qPCR forpiaB, lytA, and serotype. Saliva samples were considered positive for pneumococcus when thepiaBCt value was <40.

Results

Study participants were 22-74 years old (mean=38.5), 75% female, 75% white, with occupations including registered nurses (48%), medical doctors (23%), and patient care assistants (5%). Overall, 138/1241 (11%) samples from 86/392 (21%) individuals testedpiaB-positive for pneumococcus at some point during the 4-month study period, with 28 (33%) colonized individuals positive at multiple time points. Carriers reflected the overall study population. No significant demographic characteristics were associated with detection of pneumococcus. Colonized individuals primarily carried serotypes 19F (25%) and 3 (12%), however, we were unable to resolve a primary serotype for 31% of all pneumococcus-positive samples identified.

Conclusions

During a period of mandatory masking, we identified a cumulative pneumococcal carriage prevalence of 21% among healthcare workers. This study highlights that healthcare workers may act as unrecognized reservoirs of pneumococcus in the population. Despite long-standing PCV7 and PCV13 pediatric immunization programs, vaccine serotypes continue to be prevalent among the adult population.
A Multi-Center Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase IIa Study to Evaluate the Efficacy, Safety and Tolerability of an Anthocyanin Rich Extract (ACRE) in Patients with Ulcerative Colitis
Authors: Biedermann Luc , Doulberis Michael , Schreiner Philipp , Nielsen Ole Haagen , The Frans Olivier , Brand Stephan , Burk Sabine , Hruz Petr , Juillerat Pascal , Krieger-Grübel Claudia , Leu Kristin , Leventhal Gabriel , Misselwitz Benjamin , Scharl Sylvie , Schoepfer Alain , Seibold Frank , Herfarth Hans , Rogler Gerhard
Published: July 2024

Abstract

Background

In an open label pilot study dried bilberries were effective in inducing clinical, endoscopic and biochemical improvement in ulcerative colitis (UC) patients. Aim was the investigation of efficacy of anthocyanin rich extract (ACRE), the presumptive active ingredient of bilberries, in a controlled clinical trial in moderate-severe UC.

Methods

We performed a multicenter randomized, placebo-controlled, double-blind study (planned initially for 100 patients; premature termination due to COVID-19 pandemic). Patients had moderate-severe active UC at screening (Mayo-score 6-12, endoscopic sub-score at least 2) and were randomized at baseline (verum: placebo, 2:1). Continuation of all UC-directed stable medical therapy was allowed. Primary endpoint was clinical response at week 8 (reduction of total Mayo-score at least 3 points). Biochemical (fecal calprotectin) and centrally-read endoscopic response were amongst the secondary endpoints.

Results

Out of 48 patients screened in six Swiss trial centers, 34 were randomized. Eighteen ACRE and eight placebo patients could be analyzed in the Per-Protocol-Set. Half (9/18) of ACRE patients and 3/8 of placebo patients revealed clinical response at week 8 (CI 0.399-6.963; p=0.278). An improvement of the Mayo-score was observed in 77.8% of ACRE treated patients (62.5% of placebo). Fecal calprotectin dropped from 1049+/-1139 to 557+/-756μg/g feces in the ACRE but not in the placebo group (947+/-1039 to 1040+/-1179; p=0.035). Adverse events were rare.

Conclusions

ACRE therapy was not significantly superior to placebo at inducing a clinical response. However, placebo response was unusual high. Moreover, there was a significant calprotectin decrease at end of treatment, indicative of ACRE biochemical efficacy in UC.

Study Highlights

What is known

Dried bilberries have been reported to ameliorate active ulcerative colitis (UC) in an uncontrolled pilot trial

Anthocyanins (flavonoids) are regarded to be the active anti-inflammatory compound of bilberries

An anthocyanin rich extract (ACRE) of bilberries was reported to ameliorate colitis in mouse models

What is new here

In a multi-center randomized, double-blind, placebo controlled, parallel group study in patients with moderate to severe active UC, ACRE did not reach the statistical endpoint of clinical response

An unusually high placebo response was observed

ACRE induced significant biochemical response with significant decrease in calprotectin levels
Analysis of B-cell receptor repertoire to evaluate the immunogenicity of SARS-CoV-2 RBD mRNA vaccine: MAFB-7256a (DS-5670d)
Authors: Ohji Goh , Funakoshi Yohei , Yakushijin Kimikazu , Matsutani Takaji , Sasaki Tomoki , Kusakabe Takahiro , Matsumoto Sakuya , Koyama Taiji , Nagatani Yoshiaki , Kurata Keiji , Kimbara Shiro , Kiyota Naomi , Minami Hironobu
Published: July 2024

A monovalent Omicron XBB.1.5 mRNA RBD analogue vaccine, MAFB-7256a (DS-5670d), was newly developed and approved in Japan in the Spring of 2024 for preventing COVID-19. However, clinical efficacy data for this vaccine are currently lacking. We previously established the Quantification of Antigen-specific Antibody Sequence (QASAS) method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assays and the Coronavirus Antibody Database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of MAFB-7256a. We analyzed repeated blood samples using the QASAS method from three healthy volunteers before and after MAFB-7256a vaccination. BCR response increased rapidly one week post-vaccination and then decreased, as with conventional vaccine. Notably, the matched sequences after MAFB-7256a vaccination specifically bound to the receptor-binding domain (RBD), with no sequences binding to other epitopes. These results validate that MAFB-7256a is an effective vaccine that exclusively induces antibodies specific for the RBD, demonstrating its targeted immunogenic effect.
Blood metabolomic shift links diet and gut microbiota to multiple health outcomes among Hispanic/Latino immigrants in the U.S.
Authors: Li Yang , Peters Brandilyn A. , Yu Bing , Perreira Krista M. , Daviglus Martha , Chan Queenie , Knight Rob , Boerwinkle Eric , Isasi Carmen R. , Burk Robert , Kaplan Robert , Wang Tao , Qi Qibin
Published: July 2024

Immigrants from less industrialized countries who are living in the U.S. often bear an elevated risk of multiple disease due to the adoption of a U.S. lifestyle. Blood metabolome holds valuable information on environmental exposure and the pathogenesis of chronic diseases, offering insights into the link between environmental factors and disease burden. Analyzing 634 serum metabolites from 7,114 Hispanics (1,141 U.S.-born, 5,973 foreign-born) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we identified profound blood metabolic shift during acculturation. Machine learning highlighted the prominent role of non-genetic factors, especially food and gut microbiota, in these changes. Immigration-related metabolites correlated with plant-based foods and beneficial gut bacteria for foreign-born Hispanics, and with meat-based or processed food and unfavorable gut bacteria for U.S.-born Hispanics. Cardiometabolic traits, liver, and kidney function exhibited a link with immigration-related metabolic changes, which were also linked to increased risk of diabetes, severe obesity, chronic kidney disease, and asthma.

Graphical abstract

Highlights

A substantial proportion of identified blood metabolites differ between U.S.-born and foreign-born Hispanics/Latinos in the U.S.

Food and gut microbiota are the major modifiable contributors to blood metabolomic difference between U.S.-born and foreign-born Hispanics/Latinos.

U.S. nativity related metabolites collectively correlate with a spectrum of clinical traits and chronic diseases.
Infant EEG microstate dynamics relate to fine-grained patterns of infant attention during naturalistic play with caregivers
Authors: Bagdasarov Armen , Markert Sarah , Gaffrey Michael S
Published: July 2024

As infants grow, they develop greater attentional control during interactions with others, shifting from patterns of attention primarily driven by caregivers (exogenous) to those that are also self-directed (endogenous). The ability to endogenously control attention during infancy is thought to reflect ongoing brain development and is influenced by patterns of joint attention between infant and caregiver. However, whether measures of infant attentional control and caregiver behavior during infant-caregiver interactions relate to patterns of infant brain activity is unknown and key for informing developmental models of attentional control. Using data from 43 infant-caregiver dyads, we quantified patterns of visual attention with dyadic, head-mounted eye tracking during infant-caregiver play and associated them with the duration of infant EEG microstate D/4 measured during rest. Importantly, microstate D/4 is a scalp potential topography thought to reflect the organization and function of attention-related brain networks. We found that microstate D/4 associated positively with infant-led joint attention rate but did not associate with caregiver-led joint attention rate, suggesting that infants' initiatives in joint attention during play may be critical for the neurobiological development of attentional control. Further, we found that microstate D/4 associated negatively with infant attention shifts rate and positively with infant sustained attention duration, suggesting that increased stability of microstate D/4 may reflect maturation of attentional control and its underlying neural substrates. Together, our findings provide novel insights into how infant attentional control abilities and infant-caregiver visual behavior during play are associated with the spatial and temporal dynamics of infant brain activity.
RNaseH-based ribodepletion of total planarian RNA improves detection of longer and non-polyadenylated transcripts
Authors: Barai Pallob , Biswas Shishir , Verma Prince , Duncan Elizabeth M.
Published: July 2024

The overwhelming majority of RNA species isolated from cells or tissues using organic extraction are ribosomal RNAs (rRNA), whereas a relatively small percentage are messenger RNAs (mRNA). For studies that seek to detect mRNA transcripts and measure changes in their expression, this lopsided ratio of desired transcripts to undesired transcripts creates a significant challenge to obtaining sensitive and reproducible results. One method for improving mRNA detection is to selectively amplify polyadenylated (polyA) mRNA molecules when generating RNA-seq libraries, a strategy that is generally very successful in many species. However, this strategy is less effective when starting with total RNA from some species e.g., the planarian speciesSchmidtea mediterranea(S.med), as it generates libraries that still contain significant and variable amounts of rRNA reads. Further, commercially available ribodepletion kits do not efficiently deplete rRNAs from these samples because their sequences are divergent from mammalian rRNAs. Here we report a customized, optimized, and economical ribodepletion strategy than allows the generation of comprehensive RNA-seq libraries with less than one percent rRNA contamination. We show that this method improves transcript detection, particularly for those without polyA tails (e.g., core histones) and those that are relatively long (e.g., microtubule motor proteins). Using this custom ribodepletion approach, we also detected many transcripts that are not represented in the most recent set of S.med gene annotations, including a subset that are likely expressed transposable elements (TEs). To facilitate future differential expression analyses of these newly identified loci, we created both an annotation file of the new loci we identified and a bioinformatic pipeline for generating additional annotations from future libraries. As significant recent research shows that TE activation is regulated and functionally important, the resources provided here will provide a starting point for investigating such mechanisms in planarians and other species with less conserved rRNA sequences.
Using Multimodal Data Collection System as a Research Tool in the Major Depressive Disorder Analysis: a cross-sectional study protocol
Authors: Li Hongbo , Ji Yifu , Xu Linxiang , Yang Jiaoyun , Du Yang , Hu Min , An Ning
Published: July 2024

Introduction

Previous studies have established that depressive syndromes can be detected using machine learning methods, with multimodal data being essential. Multimodal data facilitates the extraction of characteristics such as gaze tracking, a reliable depression indicator. Our study employs high-quality video and other multimodal data from patients diagnosed with depression. Our study uses a multimodal data collection system (MDC) to understand the complex indicators of depression.

Objective

This paper outlines our protocol for deploying a multimodal data collection system within an In-Person Clinical Assessment environment. The system gathers high-definition videos, real-time vital signs, and voice recordings for future extraction of critical information such as eye gaze patterns. We aim to scale our model to provide portable depression risk analyses, facilitating timely intervention and encouraging patients to seek professional assistance.

Methods and Analysis

We have conducted sessions with 70 participants diagnosed with depression. Each participant undergoes DSM-5 interviews and engages with our multimodal data collection system. Participants respond to five on-screen scales while being recorded. To our knowledge, no other protocol has combined multimodal data collection and various stimuli in depression data collection.

Ethics and Dissemination

Ethical approval was provided by the National Health Commission of the PRC, Hefei Fourth People’s Hospital Ethics Committee (HSY-IRB-YJ-YYYX-JYF001). Results will be published in a peer-reviewed journal and presented at academic conferences.
Combining individual and wastewater whole genome sequencing improves SARS-CoV-2 surveillance
Authors: Troendle Evan P. , Lee Andrew J. , Reyne Marina I. , Allen Danielle M. , Bridgett Stephen J. , Radulescu Clara H. , Glenn Michael , Wilkins John-Paul , Rubino Francesco , Nejad Behnam Firoozi , McSparron Cormac , Niebel Marc , Fairley Derek J. , Creevey Christopher J. , McKinley Jennifer M. , Skvortsov Timofey , Gilpin Deirdre F. , McGrath John W. , Bamford Connor G. G. , Simpson David A.
Published: July 2024

Background

Robust methods to track pathogens support public health surveillance. Both wastewater (WW) and individual whole genome sequencing (WGS) are used to assess viral variant diversity and spread. However, their relative performance and the information provided by each approach have not been sufficiently quantified. Therefore, we conducted a comparative evaluation using extensive individual and wastewater longitudinal SARS-CoV-2 WGS datasets in Northern Ireland (NI).

Methods

WGS of SARS-CoV-2 was performed on >4k WW samples and >23k individuals across NI from 14thNovember 2021 to 11thMarch 2023. SARS-CoV-2 RNA was amplified using the ARTIC nCov-2019 protocol and sequenced on an Illumina MiSeq. Wastewater data were analysed using Freyja to determine variant compositions, which were compared to individual data through time series and correlation analyses. Inter-programme agreements were evaluated by mean absolute error (MAE) calculations. WW treatment plant (WWTP) performances were ranked by mean MAE. Volatile periods were identified using numerical derivative analyses. Geospatial spreading patterns were determined by horizontal curve shifting.

Findings

Strong concordance was observed between wastewater and individual variant compositions and distributions, influenced by sequencing rate and variant diversity. Overall variant compositions derived from individual sequences and each WWTP were regionally clustered rather than dominated by local population size. Both individual and WW sequencing detected common nucleotide substitutions across many variants and complementary additional substitutions. Conserved spreading patterns were identified using both approaches.

Interpretation

Both individual and wastewater WGS effectively monitor SARS-CoV-2 variant dynamics. Combining these approaches enhances confidence in predicting the composition and spread of major variants, particularly with higher sequencing rates. Each method detects unique mutations, and their integration improves overall genome surveillance.

Funding

Individual sequencing was funded via the Belfast Health and Social Care Trust (Department of Health for Northern Ireland) and the COVID-19 Genomics UK (COG-UK) consortium, which was supported by the Medical Research Council (MRC), UK Research and Innovation (UKRI), the National Institute for Health Research (NIHR), the Department of Health and Social Care (DHSC), and the Wellcome Sanger Institute. The NI Wastewater Surveillance Programme was funded by the Department of Health for Northern Ireland. EPT was supported through the COG-UK Early Career Funding Scheme.