bluuebunny/crossref_metadata_2025 huggingface dataset:
Volitional Regulation and Transferable Patterns of Midbrain Oscillations
Authors: Lu Hung-Yun , Zhao Yi , Stealey Hannah M. , Barnett Cole R. , Tobler Philippe N. , Santacruz Samantha R.
Published: December 2024

Dopaminergic brain areas are crucial for cognition and their dysregulation is linked to neuropsychiatric disorders typically treated with pharmacological interventions. These treatments often have side effects and variable effectiveness, underscoring the need for alternatives. We introduce the first demonstration of neurofeedback using local field potentials (LFP) from the ventral tegmental area (VTA). This approach leverages the real-time temporal resolution of LFP and ability to target deep brain. In our study, non-human primates learned to regulate VTA beta power using a customized normalized metric to stably quantify VTA LFP signal modulation. The subjects demonstrated flexible and specific control with different strategies for specific frequency bands, revealing new insights into the plasticity of VTA neurons contributing to oscillatory activity that is functionally relevant to many aspects of cognition. Excitingly, the subjects showed transferable patterns, a key criterion for clinical applications beyond training settings. This work provides a foundation for neurofeedback-based treatments, which may be a promising alternative to conventional approaches and open new avenues for understanding and managing neuropsychiatric disorders.

Significance statement

This study demonstrates, for the first time, that neurofeedback using local field potentials (LFP) from the ventral tegmental area (VTA) is feasible in non-human primates. By leveraging the temporal resolution and ability to target deep brain regions, this approach provides a novel way to modulate brain activity linked to dopamine-related functions. The findings reveal that subjects can flexibly control VTA LFP signals and transfer learned strategies to new settings, offering potential for developing neurofeedback-based treatments. This research opens new avenues for managing neuropsychiatric disorders, presenting an alternative to traditional pharmacological interventions that often have side effects and limited effectiveness. The study highlights the plasticity of VTA neurons and their relevance to cognition and mood regulation.
Differences and similarities between human hippocampal low-frequency oscillations during navigation and mental simulation
Authors: Seger Sarah , Kriegel Jennifer , Lega Brad , Ekstrom Arne
Published: December 2024

Low frequency oscillations in the hippocampus emerge during by both spatial navigation and episodic memory function in humans. We have recently shown that in humans, memory-related processing is a stronger driver of low frequency oscillations than navigation. These findings and others support the idea that low-frequency oscillations are more strongly associated with a general memory function than with a specific role in spatial navigation. However, whether the low-frequency oscillations that support episodic memory and those during navigation could still share some similar functional roles remains unclear. In this study, patients undergoing intracranial electroencephalography (iEEG) monitoring performed a navigation task in which they navigated and performed internally directed route replay, similar to episodic memory. We trained a random forest classification model to use patterns in low-frequency power (2-12 Hz) to learn the position during navigation and subsequently used the same model to successfully decode position during mental simulation. We show that removal of background differences in power between navigation and mental simulation is critical to detecting the overlapping patterns. These results suggest that the low-frequency oscillations that emerge during navigation are more associated with a role in memory than specifically with a navigation related function.
Evaluation of the safety and tolerability of three single ascending doses of Diamine oxidase (DAO) in healthy volunteers
Authors: Molina Perelló P. , Puntes Rodríguez M. , Coimbra Hurtado J. , Garrido Sánchez M. , Castillo Ocaña M. , Martínez Bonifacio D. , Carrera Marcolin L. , Cuñé Castellana J. , Antonijoan Arbós R.
Published: December 2024

Diamine oxidase (DAO) is a key enzyme for metabolizing dietary histamine in the gastrointestinal tract. DAO deficiency can lead to histamine intolerance (HIT), manifesting as migraines, gastrointestinal disturbances, and allergic reactions. DAO supplementation has been shown to enhance histamine breakdown, alleviating these symptoms. This randomized, double-blind, single ascending dose (SAD) Phase I clinical trial aimed to evaluate the safety and tolerability of escalating doses of DAO supplementation in healthy volunteers. Thirty participants were enrolled and randomly assigned to receive DAO or placebo. Single doses of 42 mg, 84 mg, or 210 mg of DAO extract (adiDAO® Veg) were administered under fasting conditions. Vital signs, laboratory parameters, and adverse events (AEs) were monitored, and a follow-up visit assessed post-administration safety. All participants completed the study without discontinuations. No serious adverse events or clinically significant changes in vital signs, ECGs, or laboratory parameters were observed. The study demonstrated that even doses significantly exceeding typical recommendations were well-tolerated, with no safety concerns identified. This trial confirms the safety of high-dose DAO supplementation, supporting its potential use in managing DAO deficiency and HIT. Future studies are recommended to explore the effects of chronic high-dose administration and alternative dosage forms to improve convenience.
Incidence, prevalence, and survival of head and neck cancers in the United Kingdom from 2000-2021
Authors: Miquel Dominguez Andrea , Tan Eng Hooi , Burn Edward , Delmestri Antonella , Duarte-Salles Talita , Golozar Asieh , Man Wai Yi , Prieto-Alhambra Daniel , Avilés-Jurado Francesc Xavier , Newby Danielle
Published: December 2024

Importance

Incidence, prevalence, and survival are important measures to inform the management and provision of head and neck cancer care.

Objective

To calculate the incidence, prevalence, and survival rates for head and neck cancers and subsites in the UK from 2000 to 2021.

Design, Setting, and Participants

This population-based cohort study uses routinely collected primary care data from the UK. Patients aged 18 years or older with at least 1 year of history registered in Clinical Practice Research Datalink (CPRD) GOLD or Aurum were included. Data were analyzed from January 2023 to March 2024.

Main Outcomes and Measures

Head and neck cancer incidence rates (IR), period prevalence (PP), and one-, five-, and ten-year survival after diagnosis between 2000 and 2021, stratified by age and calendar years.

Results

There were 12,455 HNC patients (male 69.2%) with a median age of 64 years. Crude incidence increased from 9.08 (7.88 to 10.42) per 100 000 person-years in 2000 to 15.59 (14.07 to 17.23) in 2021 in CPRD GOLD with similar rates in Aurum. Age standardization attenuated incidence rises for HNC subsites apart from oropharynx and tongue. Prevalence increased for both databases, from 0.04% in 2000 to 0.12% in 2019. HNC five-year survival increased from 53.8% (95% CI, 51.4% - 56.3%) in 2000-2004 to 58.7% (56.5 - 60.9%) in 2015 to 2019.

Conclusions and Relevance

HNC increases over recent decades are likely due to ageing with increases in specific subsites such as oropharyngeal cancers are due to other behavioural risk factors. Small improvements in survival highlights more research is needed to improve earlier diagnosis which will lead to better patient outcomes.

KEY POINTS

Question

What is the disease burden of the head and neck cancers (HNC) in UK from 2000-2021?

Findings

For all HNC combined, incidence and prevalence have increased with five-year survival slightly improving over time. Variation in results were observed for different subsites.

Meaning

Our findings show increases in HNC are likely due to ageing with increases in certain subsites due to other behavioural risk factors. The small increase in survival highlights more research is needed to improve earlier diagnosis leading to better patient outcomes.
Intratympanic cortisone injection: an evaluation of the current data situation
Authors: Schmidt Sandra , Thomsen Milena , Lorenz Kai Johannes
Published: December 2024

Introduction

Intratympanic cortisone injections (ITI) have been established for sudden deafness for years. ITI can be used as primary therapy and, above all, as rescue therapy if systemic administration has not brought any improvement or if there are contraindications to systemic administration.

Methods

Many different forms of application, indication, duration and treatment have been used. Different local anesthetics, cortisone preparations, body and head positions are practiced.

Results

103 patients are analyzed. In 55 cases, the injection after oral therapy. In 48 cases, given immediately due to extreme hearing loss or comorbidities the injections are well tolerated with rare unpleasant side effects.

Discussion

High-dose treatment with cortisone has been used for decades. The HODOKORT study brought significant dose reductions. The KORTEBO study could not be carried out, but there is need for it. There is a lack of evidence of an optimal indication, implementation and objective proof, which is urgently needed.
Peripheral immune cell response to stimulation stratifies Parkinson’s disease progression from prodromal to clinical stages
Authors: Mark Julian R. , Titus Ann M. , Staley Hannah A. , Alvarez Stephan , Mahn Savanna , McFarland Nikolaus R. , Wallings Rebecca L. , Tansey Malú Gámez
Published: December 2024

The motor stage of idiopathic Parkinson’s disease (iPD) can be preceded for years by a prodromal stage characterized by non-motor symptoms like REM sleep behavior disorder (RBD). Here, we show that multiple stages of iPD, including the pre-motor prodromal stage, can be stratified according to the inflammatory and immunometabolic responses to stimulation of peripheral blood mononuclear cellsex vivo. We identified increased stimulation-dependent secretion of TNF, IL-1β, and IL-8 in monocytes from RBD patients and showed diminished proinflammatory cytokine secretion in monocytes and T cells in early and moderate stages of PD. Mechanistically, immune activation revealed deficits in CD8+T-cell mitochondrial health in moderate PD, and relative mitochondrial health in CD8+T cells was positively correlated with stimulation-dependent T-cell cytokine secretion across the PD spectrum. Dysregulated immunometabolism may drive peripheral inflammation and PD progression, andex vivostimulation-based assays have potential to reveal novel biomarkers for patient stratification and progression with immune endophenotypes.
ForestForward: visualizing and accessing integrated world forest data from the last fifty years
Authors: Tejada-Gutierrez Eva Luz , Mateo-Fornés Jordi , Solsona Francesc , Alves Rui
Published: December 2024

DATABASE URL:https://forestforward.udl.cat

Mitigating the effects of environmental exploitation on forests requires robust data analysis tools to inform sustainable management strategies and enhance ecosystem resilience. Access to extensive, integrated plant biodiversity data, spanning decades, is essential for this purpose. However, such data is often fragmented across diverse datasets with varying standards, posing two key challenges: first, integrating these datasets into a unified, well-structured data warehouse, and second, handling the vast volume of data using big data technologies to analyze and monitor the temporal evolution of ecosystems. To address these challenges, we developed and used an ETL (Extract, Transform, Load) protocol that curated and integrates 4,482 forestry datasets from around the world, dating back to the 18th century, into a 100GB data warehouse containing over 172 million records sourced from the GBIF (Global Biodiversity Information Facility) repository. We implemented Python scripts and a NoSQL MongoDB database to streamline and automate the ETL process, using the data warehouse to create the ForestForward web platform. ForestForward is a free, user-friendly application developed using the Django framework, which enables users to consult, download, and visualize the curated data. The platform allows users to explore data layers by year and observe the temporal evolution of ecosystems through visual representations.
Sense of control buffers against stress
Authors: Fielder Jennifer C. , Shi Jinyu , McGlade Daniel , Huys Quentin J.M. , Steinbeis Nikolaus
Published: December 2024

Stress is one of the most pervasive causes of mental ill-health across the lifespan. Subjective dimensions of stress perception, such as perceived control, are especially potent in shaping stress responses. While the impact of reduced or no control over stress is well understood, much less is known about whether heightened feelings of control buffer against the negative impact of later stress. We designed a novel paradigm with excellent psychometric properties to sensitively capture and induce different states of subjective control. Across two studies with a total of 768 neurotypical adults, we show a robust association between sense of control and stress as well as symptoms of mental ill-health. More importantly, in a subsample of 295 participants we show that compared to a neutral control group, inducing a heightened state of subjective control buffers against the impact of later stress. These findings demonstrate a causal role for a heightened sense of control in mitigating the negative impact of stressful experiences and spell out important directions for future preventative interventions.
The interplay between executive functions and updating predictive representations
Authors: Pedraza Felipe , Vékony Teodóra , Farkas Bence C. , Haesebaert Frederic , Phelipon Romane , Mihalecz Imola , Janacsek Karolina , Tillmann Barbara , Anders Royce , Plancher Gaën , Nemeth Dezso
Published: December 2024

Modifying habits, particularly unwanted behaviors, is often challenging. Cognitive research has focused on understanding the mechanisms underlying habit formation and how habits can be rewired. A key mechanism is statistical learning, the continuous, implicit extraction of probabilistic patterns from the environment, which forms the basis of predictive processing. However, the interplay between executive functions (EF) and the rewiring – or updating – of these probabilistic representations remains largely unexplored. To address this gap, we conducted an experiment consisting of four sessions: 1) Learning Phase – acquisition of probabilistic representations, 2) Rewiring Phase – updating these probabilistic representations, 3) Retrieval Phase – accessing learned representations, and 4) EF assessment, targeting five key aspects: attentional control, inhibition, working memory, flexibility, and verbal fluency. We focused on the relationship between these EF measures and the updating of previously acquired knowledge using an interindividual differences approach. Our results revealed a positive relationship between rewiring and inhibition, suggesting that better inhibitory control may facilitate the adaptive restructuring of probabilistic predictive representations. Conversely, a negative relationship was identified between rewiring and semantic fluency, implying that certain underlying aspects of verbal fluency tasks, such as access to long-term memory representations, may hinder the updating process. We interpret this relationship through the lens of competitive memory network models. Our findings indicate that the rewiring of implicit probabilistic representations is a multifaceted cognitive process requiring both the suppression of proactive interference from prior knowledge through cognitive inhibition and a strong reliance on model-free functioning.
Experimental BTV-3 and BTV-8 infection ofCulicoides sonorensisbiting midges
Authors: Zeiske Sophie , Sick Franziska , Kampen Helge , Hoffmann Bernd , Beer Martin , Wernike Kerstin
Published: December 2024

BTV-3 emerged in the Netherlands in 2023 and spread rapidly to neighboring countries. Compared to the BTV-8 outbreak in 2006, the course of the BTV-3 epizootic is more severe. Experimental infection of laboratory-rearedCulicoides sonorensismidges showed a slightly higher replication rate of BTV-3 than of BTV-8.

One sentence summary line

We experimentally infected laboratory-rearedCulicoides sonorensisbiting midges with bluetongue virus (BTV) serotypes 3 and 8 using virus-containing blood meal and found slightly higher replication rates of BTV-3.
Investigating the quaternary structure of a homomultimeric catechol 1,2-dioxygenase: An integrative structural biology study
Authors: Almeida-Juarez Arisbeth Guadalupe , Chodankar Shirish , Pardo-López Liliana , Zavala-Padilla Guadalupe , Rudiño-Piñera Enrique
Published: December 2024

The structural analysis of catechol 1,2 dioxygenase fromStutzerimonas frequensGOM2, SfC12DO, was conducted using various structural techniques. SEC-SAXS experiments revealed that SfC12DO, after lyophilization and reconstitution processes, can form multiple enzymatically active oligomers, including dimers, tetramers, and octamers. These findings differ from previous studies, which reported active dimers in homologous counterparts with available crystallographic structures, or trimers observed exclusively in solution for SfsC12DO and its homologous isoA C12DO fromAcinetobacter radioresistensunder low ionic strength conditions. In some cases, tetramers were also reported, such as for theRodococcus erythropolisC12DO. The combined results of Small-Angle X-ray Scattering, Dynamic Light Scattering, and Transmission Electron Microscopy experiments provided additional insights into these active oligomers’ shape and molecular organization in an aqueous solution. These results highlight the oligomeric structural plasticity of SfC12DO, proving that it can exist in different oligomeric forms depending on the physicochemical characteristics of the solutions in which the experiments were performed. Remarkably, regardless of its oligomeric state, SfC12DO maintains its enzymatic activity even after prior lyophilization. All these characteristics make SfC12DO a very promising candidate for extensive bioremediation applications in polluted soils or waters.
The Impact of Instrumental Music on Dual-task Interference in a Simulated Driving Environment
Authors: Khadiv Elahe , Sahlabadi Ali Salehi , Hashemirad Reza , Namdari Mahshid , Abbaszadeh Mojtaba
Published: December 2024

Numerous drivers engage in both listening to music and undertaking secondary tasks while driving. Secondary tasks have been shown to have a negative impact on driving performance. However, the effect of music on driving performance can vary, either improving or impairing it. Nevertheless, the influence of background music on dual-task interference remains uncertain. In this study, we aimed to investigate the impact of instrumental background music on dual-task performance within a simulated driving environment. Twenty-four participants performed a color-discrimination task followed by a driving lane-change task. The results indicated that music enhanced accuracy in the lane-change task without a corresponding increase in reaction time (RT), both in single- and dual-task conditions. Additionally, when the time gap between the two tasks was 600 ms, RT for the lane-change task decreased with high music tempo. However, RT for the lane-change task did not exhibit any changes in response to music tempo when the onset time between the two tasks was short (100 ms), as well as in the single-task condition. Notably, participants’ perceived workload did not significantly differ across the various task conditions. These findings emphasize the potential of background music to improve dual-task performance, particularly when considering the temporal gap between tasks.
Universal rhythmic architecture uncovers distinct modes of neural dynamics
Authors: Karvat Golan , Crespo-García Maité , Vishne Gal , Anderson Michael C , Landau Ayelet N
Published: December 2024

Understanding the organizing principles of brain activity can advance neuro-technology and medical diagnosis and treatment. A prominent principle promoted over the last century is that brain activity consists of electrical field potentials that oscillate at different frequency bands. However, this principle has been challenged on several grounds. Specifically, increasing evidence suggests that in some cases brain oscillations are manifested as transient bursts rather than sustained rhythms. In this paper, we examine the hypothesis that rhythmicity (sustained vs. bursty) is an additional dimension in the organization of brain function. To test this hypothesis, we segmented the neurophysiological spectrum of 859 participants encompassing a dozen datasets across species, recording techniques, ages 18-88, brain regions, and cognitive states in both health and disease, according to a novel measure of rhythmicity. Together with computer simulations and brain stimulation, we found a universal spectral architecture divisible into two categories: high-rhythmicity bands associated with sustained oscillations and novel low-rhythmicity bands dominated by brief oscillatory bursts. This universal architecture reveals stable features of the brain’s mode of operation: sustained bands signify maintenance of ongoing activity, whereas transient bands signify the brain’s response to change. Rhythmicity specifies a powerful, replicable, and accessible feature-set for neuro-technology and diagnosis, as well as cross-species comparisons.
Mitophagosomes induced during EV-D68 infection promote viral nonlytic release
Authors: Jassey Alagie , Paudel Bimal , Wagner Michael A. , Pollack Noah , Cheng I-Ting , Godoy-Ruiz Raquel , Weber David J. , Jackson William T.
Published: December 2024

Enterovirus-D68 (EV-D68) is a plus-strand RNA virus that primarily causes infant respiratory infections. In rare pediatric cases, infection with EV-D68 has been associated with acute flaccid myelitis, a polio-like paralytic disease. We have previously demonstrated that EV-D68 induces nonselective autophagy for its benefit. Here, we demonstrate that EV-D68 induces mitophagy, the specific autophagic degradation of mitochondria. EV-D68 infection induces mitophagosome formation and several hallmarks of mitophagy, including mitochondrial fragmentation, mitochondrial membrane potential loss, and Parkin translocation to the mitochondria were observed in EV-D68 infected cells. The 3C protease of EV-D68 cleaves the mitochondrial fusion protein, mitofusin-2, near the C-terminal HR2 domain to induce mitochondrial fragmentation, and these fragmented mitochondria colocalized with double-stranded RNA (dsRNA), which labels viral RNA replication sites after peak viral RNA replication. Depleting components of mitophagy signaling specifically reduced EV-D68 release without impacting viral intracellular titers. Our results suggest that whereas the machinery of macroautophagy supports various stages of enterovirus replication, including viral genomic RNA replication and capsid maturation, mitophagy is the specific form of autophagy that regulates the nonlytic release of enteroviruses from cells.

Significance

EV-D68 is a respiratory pathogen and a significant cause of acute respiratory illness in infants, against which no prophylactic vaccines or antivirals exist. We have previously shown that EV-D68, like other enteroviruses, triggers and benefits from nonselective autophagy. However, it was unclear whether the virus induces selective autophagy. Here, we demonstrate that EV-D68 infection induces mitophagy and uses mitophagosomes to traffic virions to the surface of cells for nonlytic release. Our findings suggest that mitophagy may constitute the specific form of autophagy that facilitates the autophagosome-mediated nonlytic release of enteroviruses from infected cells and that targeting mitophagy could be an effective strategy to impede EV-D68 nonlytic release.
Seeing speech: neural mechanisms of cued speech perception in prelingually deaf and hearing users
Authors: Sarré Annahita , Cohen Laurent
Published: December 2024

For many deaf people, lip-reading plays a major role in verbal communication. However, lip movements are by nature ambiguous, so that lip reading does not allow for a full understanding of speech. The resulting language access difficulties may have serious consequences on language, cognitive and social development. Cued speech (CS) was developed to eliminate this ambiguity by complementing lip-reading with hand gestures, giving access to the entire phonological content of speech through the visual modality alone. Despite its proven efficiency for improving linguistic and communicative abilities, the mechanisms of CS perception remain largely unknown. The goal of the present study is to delineate the brain regions involved in cued speech perception and identify their role in visual and language-related processes.

Three matched groups of participants were scanned during two fMRI experiments: Prelingually deaf users of cued speech, hearing users of cued speech, and naive hearing controls. In Experiment 1, we presented videos of silent CS sentences, isolated lip movements, isolated gestures, plus CS sentences with speech sounds and meaningless CS sentences. In Experiment 2, we presented pictures of faces, bodies, written words, tools, and houses in order to understand the contribution of category-specific visual regions to CS perception.

We delineated a number of mostly left-hemisphere brain regions involved in CS perception. We first found that language areas were activated in all groups by both silent CS sentences and isolated lip movements, and by gestures in deaf participants only. Despite overlapping activations when perceiving CS, several findings differentiated experts from novices. As such, CS expertise was associated with a leftward functional lateralization of the lateral occipital cortex, possibly driven by the expert identification of hand gestures. The Visual Word Form Area, which supports the interface between vision and language during reading, did not contribute to CS perception. Moreover, the integration of lip movements and gestures took place in a temporal language-related region in deaf users, and in movement-related regions in hearing users, reflecting their different profile of expertise in CS comprehension and production. Finally, we observed a strong involvement of the Dorsal Attentional Network in hearing users of CS, and identified the neural correlates of the variability in individual proficiency.

Cued speech constitutes a novel pathway for accessing core language processes, halfway between speech perception and reading. The current study provides a delineation of the common and specific brain structures supporting those different modalities of language input, paving the way for further research.
The role of resource defensibility in facilitating sexually-selected weapon evolution: An experimental evolution test
Authors: Audet Tyler , Wilson Audrey , Dukas Reuven , Dworkin Ian
Published: December 2024

Animal weapons have evolved multiple times primarily for battling for access to mates. Despite intra-sexual selection being common, weapon evolution has evolved relatively rarely. So why do weapons not evolve more commonly? It has been hypothesized that three precursors are necessary for the initiation of weapon evolution: high variance in reproductive success, patchy high-value resources, and spatial environments conducive to one-on-one competition. Here, we test this hypothesis by performing experimental evolution in Drosophila melanogaster, utilizing heterogeneous environments where conditions facilitating territorial defense and opportunities for competitive interactions vary. We examine changes in sexually dimorphic morphology and male aggression that are predicted to occur, based on this model. We also examine whether condition dependence for sexual dimorphism has evolved after 35 and 75 generations of experimental evolution. Aggression did increase, albeit modestly, in environments that facilitate resource defense. Morphological changes are modest although with some trait specific changes to allometry, generally in the opposite direction of our predictions. Condition dependence trends in the opposite direction from those predicted by our hypothesis as well. We discuss our results in the context of the necessary conditions for the evolution of weapons, and if, and when condition dependence of trait exaggeration may evolve.
Drip irrigation suppresses methane emissions by reshaping the rhizosphere microbiomes in rice
Authors: Lau Kenny J.X. , Ma Ali , Chen Bin , Shibu Thankaraj Salammal Maria , Ramachandran Srinivasan , Naqvi Naweed I.
Published: December 2024

The rhizosphere microbiomes of rice plants consist of a complex consortium of methanogens, methanotrophs, nitrogen- and/or sulphur-assimilating microorganisms. Controlled irrigation has been purported to be the cultivation method of choice over continuous flooding as it reduces water usage and aerates the soil to minimize the emission of the potent greenhouse gases. However, a systemic understanding of the assembly and function of microbiota in the rhizosphere under drip and flood irrigation remains unclear. Here, we report a significant reduction in methane emissions in drip irrigation compared to flooded paddies. Genotypic or varietal differences did not influence such increased methane emissions from flooded soil cultivation of rice. Using metagenomic sequencing and computational analyses, we provide a deeper understanding of how drip irrigation or continuous flooding affect the root-associated microbiomes in rice. Rhizosphere soil from two different rice varieties, Huanghuazhan and Temasek rice, grown under drip or flood conditions in a greenhouse was collected 2 months post-transplantation for metagenomic analysis. Our results reveal that drip irrigation favours microbes involved in the nitrifying-denitrifying processes while continuous flooding enriches for methanotrophs and methanogenic archaea. Syntrophic microbial clusters associated with methanogenesis were significantly reduced in drip irrigation. We identified several keystone taxa in the co-occurrence network models related to methanogenic and methanotrophic activities, as well as beneficial microbes from the soil rhizosphere, andActinomycetesfrom floodwater. Lastly, oxygen availability and redox potential were identified as key drivers that reshape rhizosphere microbiota leading to the functional differences observed between the two irrigation regimes.
A census of RNA-dependent proteins in yeast
Authors: Wäber Nadine Bianca , Seidler Johanna , Thelen Fabienne , Timm Thomas , Lochnit Günter , Sträßer Katja , Kilchert Cornelia
Published: December 2024

Understanding the roles of RNA-associated protein complexes is essential to uncovering the mechanisms driving RNA metabolism and its impact on cellular function. Here, we present a comprehensive dataset of RNA-dependent proteins and complexes in the distantly related yeastsSaccharomyces cerevisiaeandSchizosaccharomyces pombe. For this, we adapt R-DeeP—a density gradient-based method that uses quantitative mass spectrometry to profile protein sedimentation in the presence and absence of RNA. We introduce an RNA dependence index (RDI) to provide a descriptive framework for RNA dependence. This approach enables the comparative analysis of RNA dependence across hundreds of proteins in both species. Furthermore, the data support the analysis of co-sedimentation of protein complexes with known RNA-directed functions. For instance, we find that the five subunits of the THO complex only co-sediment in the absence of RNA, implying that the well-characterized pentameric complex might not represent the RNA-bound state. The two datasets, available athttps://yeast-r-deep.computational.bio/, support hypothesis-driven research in RNA biology, expanding the utility of R-DeeP to uncover conserved and organism-specific features of RNA-protein interactions across different biological systems.
Heterogeneous, temporally consistent, and plastic brain development after preterm birth
Authors: Thalhammer Melissa , Seidlitz Jakob , Neubauer Antonia , Menegaux Aurore , Schmitz-Koep Benita , Di Biase Maria A. , Schulz Julia , Dorfschmidt Lena , Bethlehem Richard A. I. , Alexander-Bloch Aaron , Adamson Chris , Ball Gareth , Zimmer Claus , Daamen Marcel , Boecker Henning , Bartmann Peter , Wolke Dieter , Hedderich Dennis M. , Sorg Christian
Published: December 2024

The current view of neurodevelopment after preterm birth presents a strong paradox: diverse neurocognitive outcomes suggest heterogeneous neurodevelopment, yet numerous brain imaging studies focusing on average dysmaturation imply largely uniform aberrations across individuals1. Here we show both, spatially heterogeneous individual brain abnormality patterns (IBAPs) but with consistent underlying biological mechanisms of injury and plasticity. Using cross-sectional structural magnetic resonance imaging data from preterm neonates and longitudinal data from preterm children and adults in a normative reference framework2, we demonstrate that brain development after preterm birth is highly heterogeneous in both severity and patterns of deviations. Individual brain abnormalities were also consistent for their extent and location along the life course, associated with glial cell underpinnings, and plastic for influences of the early social environment. Thus, IBAPs of preterm birth are spatially heterogenous, temporally consistent for extent, spatial location, and cellular underpinnings, and plastic for social-environmental impacts. Our findings extend conventional views of preterm neurodevelopment, revealing a nuanced landscape of individual variation, with consistent commonalities between subjects. This integrated perspective of preterm neurodevelopment implies more targeted theranostic intervention strategies, specifically integrating brain charts2and imaging at birth, as well as social interventions during early development3.
Assessing target genes for homing suppression gene drive
Authors: Xu Xuejiao , Fang Jialing , Chen Jingheng , Yang Jie , Yang Xiaozhen , Hou Shibo , Sun Weitang , Champer Jackson
Published: December 2024

Gene drives are engineered alleles that bias their own inheritance in offspring, enabling the spread of specific traits throughout a population. Targeting female fertility genes in a gene drive can be an efficient strategy for population suppression. In this study, we investigated nine female fertility genes inDrosophila melanogasterusing CRISPR-based homing gene drives. Employing a multiplexed gRNA approach to prevent formation of functional resistance alleles, we aimed to maintain high drive conversion efficiency with low fitness costs in female drive carriers. Drive efficiency was assessed in individual crosses and had varied performance across different target genes. Notably, drives targeting theoctopamine β2 receptor(oct) andstall(stl) genes exhibited the highest drive conversion rates and were further tested in cages. A drive targetingstlsuccessfully suppressed a cage population with a high release frequency, though suppression failed in another replicate cage with lower initial release frequency. Fitness costs in female drive carriers were observed in test cages, impacting the overall efficiency of population suppression. Further tests on the fertility of these lines using individual crosses indicated that some fitness costs were possibly due to the maternal deposition of Cas9 combined with new gRNA expression, which would only occur in progeny of drive males when testing split drives with separate Cas9 (when mimicking cages with complete drives) but not for complete drive systems. This could enable success in complete drives with higher maternal Cas9 deposition, even if cage experiments in split drives fail. Our findings underscore the potential and challenges of assessing gene drives for population control, providing valuable insights for optimizing and testing suppression gene drive designs.
RNA-mediated MYC multimerization suppresses innate immune signaling
Authors: Uhl Leonie , Aziba Amel , Löbbert Sinah , Russell Timothy , Kannan Toshitha , Valanju Omkar R. , Schülein-Völk Christina , de Martines Tim , Montesinos Francisco , Bolz Michael , Cossa Giacomo , Endres Theresa , Solvie Daniel , Krenz Bastian , Maric Hans M. , Papadopoulos Dimitrios , Vos Seychelle M. , Eilers Martin
Published: December 2024

In response to perturbed transcription elongation, the MYC oncoprotein multimerizes and undergoes a phase transition; the underlying mechanisms and their function are unknown. Here, we show that MYC re-localizes from its canonical location on DNA to RNA in response to the accumulation of intronic RNA. MYC binds RNA directly, which enhances its multimerization. MYC multimers concentrate the nuclear exosome, a 3’-5’ RNA exonuclease, and its targeting complexes around double-stranded RNA and R-loops, and promote exosome recruitment to R-loops. RNA binding of MYC suppresses activation of the innate immune kinase TBK1. Upon MYC depletion, intron-derived dsRNAs, including RNA derived from repetitive elements and small nucleolar RNAs, accumulate on TLR3, a pattern recognition receptor that activates TBK1. In MYC-depleted cells, TLR3-bound snoRNAs carry aberrant 3’-ends, indicating defective exosomal processing. Our data show that the phase transition of MYC is a RNA-driven stress response that suppresses the accumulation of immunogenic RNAs.
Disruption of LEDGF/p75-directed integration derepresses antisense transcription of the HIV-1 genome
Authors: Tedbury Philip R. , Mahboubi Darius , Puray-Chavez Maritza , Shah Raven , Ukah Obiaara B. , Wahoski Claudia C. , Fadel Hind J. , Poeschla Eric M. , Gao Xinlin , McFadden William M. , Gaitanidou Maria , Kesesidis Nikolaos , Kirby Karen A. , Vanderford Thomas H. , Kvaratskhelia Mamuka , Achuthan Vasudevan , Behrens Ryan T. , Engelman Alan N. , Sarafianos Stefan G.
Published: December 2024

Abstract

Disruption of HIV-1 Integrase (IN) interactions with the host-factor Lens Epithelium-Derived Growth Factor (LEDGF)/p75 leads to decreased, random integration, increased latent infection, and described here, accumulation of HIV-1 antisense RNA (asRNA). asRNA increase was observed following interruptions of IN-LEDGF/p75 interactions either through pharmacologic perturbations of IN-LEDGF/p75 by treatment with allosteric HIV-1 integrase inhibitors (ALLINIs) or in cell lines with LEDGF genetic knockout. Additionally, by impairing Tat-dependent HIV transcription, asRNA abundance markedly increases. Illumina sequencing characterization of asRNA transcripts in primary T cells infected in the presence of ALLINIs showed that most initiate from within the HIV-1. Overall, loss of IN-LEDGF/p75 interactions increase asRNA abundance. Understanding the relationship between ALLINIs, integration sites, asRNA, and latency could aid in future therapeutic strategies.
In vivodetection of HIV-1 antisense transcripts in untreated and ART-treated individuals
Authors: Capoferri Adam A. , Sklutuis Rachel , Famuyiwa Toluleke O. , Pathak Sachi , Li Rui , Rausch Jason W. , Luke Brian T. , Hoh Rebecca , Deeks Steven G. , Mellors John W. , Coffin John M. , Groebner Jennifer L. , Romerio Fabio , Kearney Mary F.
Published: December 2024

Natural antisense transcripts are expressed in eukaryotes, prokaryotes, and viruses and can possess regulatory functions at the transcriptional and/or post-transcriptional levels.In vitrostudies have shown that HIV-1 antisense transcripts (AST) promote viral latency through epigenetic silencing of the proviral 5′ long terminal repeat (LTR). However, expression of HIV-1 ASTin vivohave not been convincingly demonstrated. Here, we used single RNA template amplification, detection, and sequencing to demonstrate expression of AST in unstimulated PBMC collected from people with HIV-1 (PWH). We found that AST had high genetic diversity that matched proviruses in cells from blood and lymph nodes. We measured a median of 26 copies of AST per 100 infected cells in PWH on ART and a median of 2 copies per 100 infected cells in PWH not on ART. The expression of HIV-1 ASTin vivois consistent with a potential regulatory role in regulation of HIV-1 expression.
A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes
Authors: Tripplehorn Sarah A. , Shirra Margaret K. , Lardo Santana M. , Marvil Hannah G. , Hainer Sarah J. , Arndt Karen M.
Published: December 2024

The nucleosome remodeler Chd1 is required for the re-establishment of nucleosome positioning in the wake of transcription elongation by RNA Polymerase II. Previously, we found that Chd1 occupancy on gene bodies depends on the Rtf1 subunit of the Paf1 complex in yeast. Here, we identify an N-terminal region of Rtf1 and the CHCT domain of Chd1 as sufficient for their interaction and demonstrate that this interaction is direct. Mutations that disrupt the Rtf1-Chd1 interaction result in an accumulation of Chd1 at the 5’ ends of Chd1-occupied genes, increased cryptic transcription, altered nucleosome positioning, and concordant shifts in histone modification profiles. We show that a homologous region within mouse RTF1 interacts with the CHCT domains of mouse CHD1 and CHD2. This work supports a conserved mechanism for coupling Chd1 family proteins to the transcription elongation complex and identifies a cellular function for a domain within Chd1 about which little is known.
Predictable modulation of plant root development using engineered cytokinin regulators
Authors: Rattan Rohan , Alamos Simon , Szarzanowicz Matthew , Markel Kasey , Shih Patrick M.
Published: December 2024

Achieving precise control over quantitative developmental phenotypes is a key objective in plant biology. Recent advances in synthetic biology have enabled tools to reprogram entire developmental pathways; however, the complexity of designing synthetic genetic programs and the inherent interactions between various signaling processes remains a critical challenge. Here, we leverage Type-B response regulators to modulate the expression of genes involved in cytokinin-dependent growth and development processes. We rationally engineered these regulators to modulate their transcriptional activity (i.e., repression or activation), potency, and sensitivity to cytokinin. By localizing the expression of these engineered TFs using tissue-specific promoters, we can precisely tune cytokinin-regulated traits. As a proof of principle, we deployed this synthetic system inArabidopsis thalianato either decrease or increase the number of lateral roots. The simplicity and modularity of our approach makes it an ideal system for controlling other developmental phenotypes of agronomic interest in plants.
Diversity and prevalence of amino acid decarboxylase enzymes in the human gut microbiome – a bioinformatics investigation
Authors: Sandoval Matthew , Shah Dhara D.
Published: December 2024

Biogenic amines play numerous biological functions that include neuromodulation, maintenance of the gut health and motility, gastric acid secretion, regulation of immune response, cell growth, and gene expression. Therefore, it is crucial to comprehend the potential modulation of these molecules by the human gut microbiota. A primary pathway for the generation of these molecules involves the decarboxylation of amino acids, a process facilitated by enzymes known as amino acid decarboxylases (AADCs). Here, we conducted a bioinformatic analysis to understand diversity and prevalence of AADCs from the most prevalent members of the human gut microbiome. This study aims to understand how human gut microbes generate metabolites that influence health and disease, through specific enzyme activities, with a focus on recognizing the potential role of gut microbiota in neuromodulation, gastrointestinal dysfunctions, immune response regulation, and other critical biological functions. Our results indicate that AADCs are most abundant in the prominent gut microbial genera, namelyBacteroides,Parabacteroides,Alistipes, andEnterococcus. Furthermore, among AADCs, arginine decarboxylases are the most common, present in approximately 60% of the frequently found members of the human gut microbiome, followed by aspartate 1-decarboxylases and glutamate decarboxylases. We also found thatEnterococcus faecalisharbors the most variety of amino acid decarboxylases, potentially playing an important role in driving decarboxylation chemistry in the human gut. In addition, our sequence analyses of various AADCs demonstrated that a tetrad of amino acids in the PLP binding motif can provide functional identification for AADCs. We hypothesize that the diversity in AADCs and the microbes that harbor them has the potential to alter host metabolic outputs. This could provide a mechanism to use specific changes in microbial genera or species to understand possible metabolite modulations that might influence biological functions. Such studies could lay the groundwork for developing future disease markers or therapeutic interventions.
Joyful living labs – pedagogical approach for urban design thinking soft skills
Authors: Zahran Rehab Mostafa , Bahgat Hisham Amr , Abdel Aziz Tamer Mohamed , Khalil Heba Allah Essam E.
Published: December 2024

Purpose

Urban design professionals face the challenge of creating responsive human settlements amidst complex, ever-evolving interactions between numerous factors, which makes each project a “wicked problem,” requiring designers with specific skills to solve them effectively. This paper explores how integrating “Living Labs” and “Learning Playing techniques” equips urban design students with the needed competencies to address these challenges.

Design/methodology/approach

The research employed a literature review focusing on urban design theories related to “wicked problems,” design thinking and soft skills. Through this review, the authors developed the “Urban Design Thinking Soft Skills (UDTS) matrix” and identified pedagogical approaches using Living Labs and Learning Playing Techniques. An award-winning community design studio at Cairo University served as a case study to test and validate the UDTS matrix. Interviews were conducted to further investigate the effectiveness of incorporating these approaches.

Findings

The study found that integrating Living Labs principles and Learning Playing Techniques (termed “Joyful Living Labs” in this context) are effective pedagogical methods. Interviews provided evidence supporting their value within urban design curricula for the Egyptian context.

Originality/value

This paper proposes the UDTS matrix as a framework to equip students with the necessary soft skills for tackling complex urban design challenges. Furthermore, it introduces the concept of “Joyful Living Labs” as a potential pedagogical approach specifically suited for the Egyptian context.