bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxyplasma meridianum gen. nov., sp. nov., an extremely acidophilic organotrophic member of the order Thermoplasmatales
Authors: Golyshina Olga V. , Lunev Evgenii A. , Distaso Marco A. , Bargiela Rafael , Gaines Matthew C. , Daum Bertram , Ferrer Manuel , Bale Nicole J. , Koenen Michel , Damsté Jaap S. Sinninghe , Yakimov Mikhail M. , Golyshin Peter N.
Published: August 2024

A mesophilic, hyperacidophilic archaeon, strain M1T, was isolated from a rock sample from Vulcano Island, Italy. Cells of this organism were cocci with an average diameter of 1 µm. Some cells possessed filaments. The strain grew in the range of temperatures between 15 and 52 °C and pH 0.5–4.0 with growth optima at 40 °C and pH 1.0. Strain M1T was aerobic and chemoorganotrophic, growing on complex substrates, such as casamino acids, trypticase, tryptone, yeast and beef extracts. No growth at expenses of oxidation of elemental sulphur or reduced sulphur compounds, pyrite, or ferrous sulphate was observed. The core lipids were glycerol dibiphytanyl glycerol tetraether lipids (membrane spanning) with 0 to 4 cyclopentane moieties and archaeol, with trace amounts of hydroxy archaeol. The dominant quinone was MK-7 : 7. The genome size of M1T was 1.67 Mbp with a G+C content of 39.76 mol%, and both characteristics were well within the common range for Thermoplasmatales. The phylogenetic analysis based on 16S rRNA gene sequence placed the strain M1T within the order Thermoplasmatales with sequence identities of 90.9, 90.3 and 90.5% to the closest SSU rRNA gene sequences from organisms with validly published names, Thermoplasma acidophilum, Thermoplasma volcanium and Thermogymnomonas acidicola, respectively. Based on the results of our genomic, phylogenetic, physiological and chemotaxonomic studies, we propose that strain M1T (=DSM 116605T=JCM 36570T) represents a new genus and species, Oxyplasma meridianum gen. nov., sp. nov., within the order Thermoplasmatales.
'Candidatus Phytoplasma vignae’, assigning a species description to a long-known phytoplasma occurring in northern Australia
Authors: Rodrigues Jardim Bianca , Tran-Nguyen Lucy T. T. , Gambley Cherie , Webster Craig , Kehoe Monica , Bond Samantha , Rodoni Brendan , Constable Fiona E.
Published: August 2024

Gene- and genome-based approaches were used to determine whether Vigna little leaf (ViLL) phytoplasma, which occurs in northern Australia, is a distinct ‘Candidatus Phytoplasma’ species. The ViLL 16S rRNA gene sequences exhibited the highest known similarity to species in the 16SrXXIX-A and 16SrIX-D subgroups, namely ‘Candidatus Phytoplasma omanense’ (98.03–98.10%) and ‘Candidatus Phytoplasma phoenicium’ (96.87–97.20%), respectively. A total of 48 single-copy orthologue genes were identified to be shared among the two draft ViLL phytoplasma genomes, 30 publicly available phytoplasma genomes, and one Acholeplasma laidlawii genome as the outgroup taxon. Phylogenomic assessments using the 48 shared single-copy orthologue genes supported that ViLL and ‘Ca. Phytoplasma phoenicium’ were closely related yet distinct species. The 16S rRNA gene sequence analysis and phylogenomic assessment indicate that ViLL phytoplasmas are a distinct taxon. As such, a novel species, ‘Candidatus Phytoplasma vignae’, is proposed. Strain BAWM-336 (genome accession number JAUZLI000000000) detected in Momordica charantia (bitter melon) serves as the reference strain of this species, with infected plant material deposited in the Victorian Plant Pathology Herbarium (VPRI) as VPRI 44369.
Cyberlindnera qingyuanensis f.a., sp. nov., a yeast species isolated from rotting wood
Authors: Liu Shan , Cai Dan-Yang , Hui Feng-Li
Published: August 2024

Two yeast strains were isolated from rotting wood samples collected on Qingyuan Mountain, Fujian Province, PR China. Phylogenetic analysis, based on the concatenated sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit rRNA gene, revealed that these two strains represent a novel species of the genus Cyberlindnera. The proposed name for this new species is Cyberlindnera qingyuanensis f.a., sp. nov. (holotype: GDMCC 2.300; ex-type: PYCC 9925) although the formation of ascospores was not observed. The novel species differs from its close relative Cyberlindnera galapagoensis by 7.7% sequence divergence (37 substitutions and seven indels) in the D1/D2 domain and 9.7% sequence divergence (42 substitutions and 34 indels) in the ITS region, respectively. Additionally, Cyb. qingyuanensis differs from its close relative Cyb. galapagoensis by its ability to grow in cellobiose, l-rhamnose, ribitol, galactitol, and dl-lactate, its growth at 37 °C, and its inability to ferment raffinose. The Mycobank number is MB 854693.
Functional traits and soil water availability shape competitive interactions in a diploid-polyploid complex
Authors: Rodríguez-Parra Alba , López-Jurado Javier , Mateos-Naranjo Enrique , Balao Francisco
Published: August 2024

Even within those polyploid plant species that become established initially, only a few persist in the long term. Competitive interactions between polyploids and their ancestral cytotypes in secondary contact zones can contribute to local extinctions. Environmental factors such as water availability and functional trait divergence may influence these interactions.

We conducted a greenhouse competition experiment with four cytotypes (2x, 4x, 6x, and 12x) ofDianthus broteriunder two contrasting irrigation regimes. We estimated niche and fitness differences and predicted the pairwise competitive outcomes. Additionally, we explored the influence of leaf physiological functional traits (SLA, AN, gs, LDMC, Fv/Fm, andiWUE) on competitive interactions.

Soil water availability modified the competitive dynamics between cytotypes and predicted competitive exclusion. Under high water availability, lower ploidy levels (2x and 4x) outcompeted higher ploidy cytotypes (12x, 6x), while the latter exhibited greater competitive abilities under low water availability. These differences were explained by functional traits related to competitive effects (SLA) and competition tolerance (AN, Fv/Fm, andiWUE).

Synthesis:Our study emphasizes that the long-term fate of polyploids largely depends on water availability, with high polyploids having a competitive advantage in arid environments. This ultimately highlights the role of functional traits in shaping the competitive dynamics between cytotypes.
Chronic intermittent alcohol yields sex-specific disruptions in cortical-striatal-limbic oscillations
Authors: Hewitt Kelly A. , Nicholson Skylar E. , Peterson Madilyn J. , Dwiel Lucas L. , Henricks Angela M.
Published: August 2024

Background

While the neurobiology of alcohol use disorder (AUD) has been extensively researched, the vast majority of these studies included only male organisms. However, there are significant sex differences in both the causes and consequences of alcohol misuse and dependence, suggesting sex-specific neurobiological mechanisms. The current study used a rodent model to determine whether chronic alcohol exposure impacts sex-specific neural circuits, and whether these changes contribute to the development of alcohol misuse.

Methods

Male and female Sprague-Dawley rats were trained to self-administer 10% alcohol before implanting bilateral electrodes into the infralimbic medial prefrontal cortex (IL), nucleus accumbens shell (NAcSh), and central nucleus of the amygdala (CeA). Half of the rats were then exposed to four weeks of chronic intermittent alcohol (CIA) vapor (14 hours on/10 hours off). During acute withdrawal (6-8 after the vapor turns off), local field potentials (LFPs) were recorded from the IL, NAcSh, and CeA during 30-minute self-administration sessions. Using an unbiased machine learning approach, we built predictive models to determine whether/which LFP features could distinguish CIA-exposed from control rats in each sex, as well as if any of these LFP features correlated with rates of alcohol self-administration.

Results

Female rats self-administered more alcohol in general compared to males, but only males exposed to CIA showed increased alcohol intake during acute withdrawal. LFPs predicted CIA exposure in both sexes better than chance estimates, but models built on IL and NAcSh oscillations performed the best in males, while models built on IL and CeA LFPs performed best in females. High γ LFPs recorded in the NAcSh correlated with rates of alcohol self-administration in males exposed to CIA, while only left-right NAcSh β coherence correlated with drinking in control females.

Conclusions

These data provide support for the hypothesis that the neural circuits driving alcohol dependence development are sex-specific, and that high frequency oscillations in the NAcSh may be related to the increased drinking observed in males exposed to CIA. Overall, these data add to our understanding of the neurobiological underpinnings behind the sex differences observed in AUD and offer promising biomarkers for future therapeutic research.
An explainable graph neural network approach for effectively integrating multi-omics with prior knowledge to identify biomarkers from interacting biological domains
Authors: Tripathy Rohit K. , Frohock Zachary , Wang Hong , Cary Gregory A. , Keegan Stephen , Carter Gregory W. , Li Yi
Published: August 2024

The rapid growth of multi-omics datasets, in addition to the wealth of existing biological prior knowledge, necessitates the development of effective methods for their integration. Such methods are essential for building predictive models and identifying disease-related molecular markers. We propose a framework for supervised integration of multi-omics data with biological priors represented as knowledge graphs. Our framework leverages graph neural networks (GNNs) to model the relationships among features from high-dimensional ‘omics data and set transformers to integrate low-dimensional representations of ‘omics features. Furthermore, our framework incorporates explainability methods to elucidate important biomarkers and extract interaction relationships between biological quantities of interest. We demonstrate the effectiveness of our approach by applying it to Alzheimer’s disease (AD) multi-omics data from the ROSMAP cohort, showing that the integration of transcriptomics and proteomics data with AD biological domain network priors improves the prediction accuracy of AD status and highlights functional AD biomarkers.
Spatiotemporal Decomposition of Whole-Brain Alpha Traveling Waves
Authors: Li Yichao , Hong Bo
Published: August 2024

Spontaneously emerging traveling waves are present within the spatiotemporal patterns of alpha-band EEG oscillations, but current analysis methods are limited in parsing the diversity of global wave structures and their correlation with brain functions. To address this limitation, we constructed a rigorous mathematical framework, Weakly Orthogonal Conjugate Contrast Analysis (WOCCA), which decomposes the whole-brain EEG alpha oscillations into directionally independent traveling waves. For the first time, we systematically characterized propagating components in alpha-band resting-state EEG as a combination of rotational, longitudinal, and horizontal traveling wave patterns. The intensity, directionality, and morphological characteristics of these wave patterns account for the differences between cognitive states during rest and consciousness levels under sedation. Moreover, our WOCCA decomposition encompassed the state transition dynamics captured by EEG Microstate Analysis, a conventional analysis framework for alpha waves. These results not only established a novel approach for identifying and analyzing traveling waves but also provided evidence for the relationship between wave directionality and cooperative interactions in brain network.
Validating genuine changes in Heartbeat Evoked Potentials using Pseudotrials and Surrogate Procedures
Authors: Steinfath Paul , Herzog Nadine , Fourcade Antonin , Sander Christian , Nikulin Vadim , Villringer Arno
Published: August 2024

The brain continuously receives interoceptive information about the state and function of our internal organs. For instance, each time the heart beats, the brain responds by generating time-locked activity, known as heartbeat evoked potentials (HEP). When investigating HEPs, it is essential to adequately control for heartbeat-independent confounding activity to avoid false interpretation. In the present study, we highlight the pitfalls of uncontrolled analyses and advocate for the use of surrogate heartbeat analysis and pseudotrial correction, which are promising tools to control for spurious results. Surrogate heartbeat analysis involves shuffling the timing of heartbeats to verify the time-locking of HEP effects. Pseudotrial correction works by subtracting heartbeat-independent activity from HEPs. In this study we employ both procedures, validate them in simulations and apply them to real EEG data. Using EEG recordings obtained during the performance of an auditory novelty oddball task in a large population, we show that, without control analyses, pre-stimulus HEPs appear inversely related to task-related measures such as P300 event-related potential amplitudes and reaction time speed. However, these effects disappear after carefully controlling for heartbeat-unrelated EEG activity. Additionally, in real and simulated data, we show that pseudotrial correction has the potential to remove task-related confounds from HEPs, thereby uncovering real heartbeat-related effects that otherwise could be missed. This study therefore highlights issues that can arise when analyzing HEPs during tasks, provides solutions to overcome them, and gives recommendations for future studies to avoid pitfalls when analyzing and designing behavioral paradigms with HEPs.
Ischemic lesions to inferior frontal cortex alter the dynamics of conscious visual perception
Authors: Fritsch M. , Michely J. , Jaeckel L. , Rangus I. , Riegler C. , Scheitz J. , Nolte CH , Sterzer P. , Weilnhammer V.
Published: August 2024

Whether the prefrontal cortex is part of the neural correlates of conscious visual perception has been subject to longstanding debate. Recent work, using functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to induce virtual lesions, has illustrated a key role of the right inferior frontal cortex (IFC) in the detection and resolution of perceptual ambiguities. Here, we sought to validate an active role of the IFC in conscious perception by evaluating how loss-of-function in patients with ischemic stroke in this region influences processing of ambiguous visual information. To this end, twenty-three patients (11 female, mean age 70.65 ± 1.2 years) with chronic (>6 months), right-hemispheric ischemic stroke lesions within the MCA-territory (9 patients with IFC lesions, 14 without) performed a bistable perception task, having to report the perceived direction of rotation of an ambiguous random-dot-kinematogram (RDK). As hypothesized, patients with IFC lesions showed significantly fewer perceptual changes compared to patients without IFC lesions (IFC 44.9 ± 46.3 s, non-IFC 28.2 ± 37.1 s, T(182.9) =3.1, p = 2.2 x 10-3). Importantly, this effect remained significant when controlling for age, sex, stroke severity and lesion volume (T(5.97) = −2.9, p =0.026). Our results support the notion that the IFC is crucial for resolving perceptual ambiguities, suggesting an active role of frontal cortex in shaping conscious visual experience.
funkea: Functional Enrichment Analysis in Python
Authors: Tenmann Benjamin , Close Karina , Rodriguez-Martinez Andrea , Abujudeh Samer
Published: August 2024

Abstract

Advancements in Genome-wide association studies (GWAS) have led to the discovery of numerous genetic variants potentially linked to various traits, necessitating effective methods to interpret and summarise these vast data sets. We introducefunkea, a Python package designed to fill this need by providing functional enrichment analysis methods. This tool encompasses popular enrichment approaches under a unified interface and leverages Spark for virtually limitless scale. This allows researchers to conduct pathway, cell-type, and tissue enrichment analysis across diverse annotation datasets. Ultimately, thefunkeaPython package delivers a highly flexible and scalable solution for functional enrichment analysis in the context of modern genetics workflows.https://github.com/BenevolentAI/funkea
Segment AnyNeuron
Authors: Razzaq Taha , Qazi Ahmed , Iqbal Asim
Published: August 2024

Image segmentation plays an integral part in neuroimage analysis and is crucial for understanding brain disorders. Deep Learning (DL) models have shown exponential success in computer vision tasks over the years, including image segmentation. However, to achieve optimal performance, DL models require extensive annotated data for training, which is often the bottleneck to expediting brain-wide image analysis. For segmenting cellular structures such as neurons, the annotation process is cumbersome and time-consuming due to the inherent structural, intensity, and background variations present in the data caused by genetic markers, imaging techniques, etc. We propose an Active Learning-based neuron segmentation framework (Segment AnyNeuron), which incorporates state-of-the-art image segmentation modules - Detectron2 and HQ SAM, and requires minimal ground truth annotation to achieve high precision for brain-wide segmentation of neurons. Our framework can classify and segment completely unseen neuronal data by selecting the most representative samples for manual annotation, thus avoiding the cold-start problem common in Active Learning. We demonstrate the effectiveness of our framework for automated brain-wide segmentation of neurons on a variety of open-source neuron imaging datasets, acquired from different scanners and a variety of transgenic mouse lines.
Multimodal 3D Image Registration for Mapping Brain Disorders
Authors: Mahmood Hassan , Islam Syed Mohammed Shamsul , Iqbal Asim
Published: August 2024

We introduce an AI-driven approach for robust 3D brain image registration, addressing challenges posed by diverse hardware scanners and imaging sites. Our model trained using an SSIM-driven loss function, prioritizes structural coherence over voxel-wise intensity matching, making it uniquely robust to inter-scanner and intra-modality variations. This innovative end-to-end framework combines global alignment and non-rigid registration modules, specifically designed to handle structural, intensity, and domain variances in 3D brain imaging data. Our approach outperforms the baseline model in handling these shifts, achieving results that align closely with clinical ground-truth measurements. We demonstrate its efficacy on 3D brain data from healthy individuals and dementia patients, with particular success in quantifying brain atrophy, a key biomarker for Alzheimer’s disease and other brain disorders. By effectively managing variability in multisite, multi-scanner neuroimaging studies, our approach enhances the precision of atrophy measurements for clinical trials and longitudinal studies. This advancement promises to improve diagnostic and prognostic capabilities for neurodegenerative disorders.
Glymphatic clearance is enhanced during sleep
Authors: Kroesbergen Erik , Riesselmann Laurence V. , Gomolka Ryszard S. , Plá Virginia , Esmail Tina , Stenmo Visti H. , Kovács E. Rebeka , Nielsen Elise S. , Goldman Steven A. , Nedergaard Maiken , Weikop Pia , Mori Yuki
Published: August 2024

We here revisited the concept that glymphatic clearance is enhanced by sleep and anesthesia. Utilizing dynamic magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and fluorescent fiber photometry, we report brain glymphatic clearance is enhanced by both sleep and anesthesia, and sharply suppressed by wakefulness. Another key finding was that less tracer enters the brains of awake animals and that brain clearance across different brain states can only be compared after adjusting for the injected tracer dose.
Optimizing real-time phase detection in diverse rhythmic biological signals for phase-specific neuromodulation
Authors: Liufu Mengzhan , Leveroni Zachary M. , Shridhar Sameera , Zhou Nan , Yu Jai Y.
Published: August 2024

Abstract

Closed-loop, phase-specific neurostimulation is a powerful method to modulate ongoing brain activity for clinical and research applications. Phase-specific stimulation relies on estimating the phase of an ongoing oscillation in real time and issuing a control command at a target phase. Phase detection algorithms based on Fast Fourier transform (FFT) are widely used due to their computational efficiency and robustness. However, it is unclear how algorithm performance depends on the spectral properties of the input signal and how algorithm parameters can be optimized. We used offline simulation to evaluate the performance of three algorithms (endpoint-corrected Hilbert Transform, Hilbert Transform and phase mapping) on three rhythmic biological signals with distinct spectral properties (rodent hippocampal theta potential, human EEG alpha and human essential tremor). First, we found that algorithm performance was more strongly influenced by signal amplitude and frequency variation compared with signal to noise ratio. Second, our simulations showed that the size of the data window for phase estimation was critical for the performance of FFT-based algorithms, where the optimal data window corresponds to the period of the oscillation. We validated this prediction with real time phase detection of hippocampal theta oscillations in freely behaving rats performing spatial navigation. Our findings define the relationship between signal properties and algorithm performance and provide a convenient method for optimizing FFT-based phase detection algorithms.
MorphLink: Bridging Cell Morphological Behaviors and Molecular Dynamics in Multi-modal Spatial Omics
Authors: Huang Jing , Yuan Chenyang , Jiang Jiahui , Chen Jianfeng , Badve Sunil S. , Gokmen-Polar Yesim , Segura Rossana L. , Yan Xinmiao , Lazar Alexander , Gao Jianjun , Epstein Michael , Wang Linghua , Hu Jian
Published: August 2024

Multi-modal spatial omics data are invaluable for exploring complex cellular behaviors in diseases from both morphological and molecular perspectives. Current analytical methods primarily focus on clustering and classification, and do not adequately examine the relationship between cell morphology and molecular dynamics. Here, we present MorphLink, a framework designed to systematically identify disease-related morphological-molecular interplays. MorphLink has been evaluated across a wide array of datasets, showcasing its effectiveness in extracting and linking interpretable morphological features with various molecular measurements in multi-modal spatial omics analyses. These linkages provide a transparent depiction of cellular behaviors that drive transcriptomic heterogeneity and immune diversity across different regions within diseased tissues, such as cancer. Additionally, MorphLink is scalable and robust against cross-sample batch effects, making it an efficient method for integrative spatial omics data analysis across samples, cohorts, and modalities, and enhancing the interpretation of results for large-scale studies.
Mitochondrial activity-driven hematopoietic stem cell fate and lympho-myeloid lineage choice is first established in the aorta-gonad-mesonephros
Authors: Prakash Aishwarya , Inamdar Maneesha S.
Published: August 2024

Mitochondrial metabolism determines bone marrow hematopoietic stem cell (HSC) heterogeneity and influences long-term repopulation potential. However, the origin of this heterogeneity and how it regulates HSC phenotype is unclear. We show that during the endothelial-to-hematopoietic transition (EHT) in the mouse embryo, dynamic changes in mitochondrial activity drive the production of mature HSCs with differing potencies. Lowering mitochondrial activity in the AGM by pharmacological or genetic means activates Wnt signaling to promote HSC expansion. Further, mitochondrial membrane potential (MMP) gives rise to functional heterogeneity in the definitive HSC pool.In-vitroandin-vivofunctional assays, and single-cell transcriptomics on AGM HSCs showed that MMPlowHSCs are myeloid-biased, with enhanced differentiation potential, while MMPhighHSCs are lymphoid-biased with diminished differentiation potential. Mechanistically, low mitochondrial activity upregulates Phosphoinositide 3-kinase (PI3K) signaling to promote HSC differentiation. These insights into the initiation of metabolic heterogeneity could be leveraged to isolate HSCs to efficiently generate desired lineages.

Highlights

Mitochondrial changes from HSC emergence to maturation govern embryonic hematopoiesis.

Lowering mitochondrial activity promotes Wnt-dependent HSC expansion and PI3K-dependent differentiation.

Mitochondrial membrane potential determines lympho-myeloid fate choice in AGM HSCs.

Aberrant mitochondrial activity in the AGM HSCs perturbs adult hematopoiesis.
AI-based Prediction of Protein Corona Composition on DNA Nanostructures
Authors: Huzar Jared , Coreas Roxana , Landry Markita P. , Tikhomirov Grigory
Published: August 2024

DNA nanotechnology has emerged as a powerful approach to engineering biophysical tools, therapeutics, and diagnostics because it enables the construction of designer nanoscale structures with high programmability. Based on DNA base pairing rules, nanostructure size, shape, surface functionality, and structural reconfiguration can be programmed with a degree of spatial, temporal, and energetic precision that is difficult to achieve with other methods. However, the properties and structure of DNA constructs are greatly alteredin vivodue to spontaneous protein adsorption from biofluids. These adsorbed proteins, referred to as the protein corona, remain challenging to control or predict, and subsequently, their functionality and fatein vivoare difficult to engineer. To address these challenges, we prepared a library of diverse DNA nanostructures and investigated the relationship between their design features and the composition of their protein corona. We identified protein characteristics important for their adsorption to DNA nanostructures and developed a machine-learning model that predicts which proteins will be enriched on a DNA nanostructure based on the DNA structures’ design features and protein properties. Our work will help to understand and program the function of DNA nanostructuresin vivofor biophysical and biomedical applications.
Guidance for the Reporting of Bibliometric Analyses: A Scoping Review
Authors: Ng Jeremy Y. , Liu Henry , Masood Mehvish , Syed Niveen , Stephen Dimity , Ayala Ana Patricia , Sabé Michel , Solmi Marco , Waltman Ludo , Haustein Stefanie , Moher David
Published: August 2024

Despite the growth in the number of bibliometric analyses published in the peer-reviewed literature, few articles provide guidance on methods and reporting to ensure reliability, robustness, and reproducibility. Consequently, the quality of reporting in existing bibliometric studies varies greatly. In response, we are developing a preliminaryGuidance List for the repOrting of Bibliometric AnaLyses (GLOBAL), a reporting guideline for bibliometric analyses. This paper outlines a scoping review that aims to identify and categorise bibliometric recommendations from the literature to develop an initial list of candidate items for the GLOBAL. Five bibliographic databases, three preprint servers, and grey literature were systematically searched. Twenty-three out of 48,750 records fulfilled the inclusion criteria. Six documents contained bibliometric reporting recommendations based on a complete or partial literature review; all other sources (n = 17) contained opinion-based recommendations. A 32-item recommendation list that will inform the development of the GLOBAL was created. A paucity of evidence-based studies on bibliometric reporting exists in the literature, supporting the need to create a reporting guideline for bibliometric analyses. The next step in the GLOBAL project will focus on conducting a two-round Delphi study to achieve consensus on which of the 32 items should be included in GLOBAL.
Progressive changes in functional connectivity between thalamic nuclei and cortical networks across learning
Authors: Jarrett Chelsea Emma , Zwosta Katharina , Wang Xiaoyu , Wolfensteller Uta , Iglesias Juan Eugenio , von Kriegstein Katharina , Ruge Hannes
Published: August 2024

The thalamus is connected to cerebral cortex and subcortical regions, serving as a node within cognitive networks. It is a heterogeneous structure formed of functionally distinct nuclei with unique connectivity patterns. However, their contributions to cognitive functioning within networks is poorly understood. Recent animal research suggests that thalamic nuclei such as the mediodorsal nucleus play critical roles in goal-directed behaviour. Our aim was to investigate how functional integration of thalamic nuclei within cortical and subcortical networks changes whilst transitioning from more controlled goal-directed behaviour towards more automatic or habitual behaviour in humans. We analysed functional magnetic resonance imaging (fMRI) data from a stimulus-response learning study to investigate functional connectivity (FC) changes across learning between thalamic nuclei with cortical networks and subcortical structures in healthy subjects. We defined subcortical regions-of-interest (ROIs) individually in native space, segmenting the thalamus into 47 nuclei and segmenting 38 subregions within the basal ganglia and hippocampus. Additionally, we defined 12 cerebral cortex ROIs via maximum-probability network templates. Learning-related connectivity changes were examined via ROI-to-ROI functional network analysis. Our results showed that learning was associated with: 1) decreasing FC between the frontoparietal network and higher order thalamic nuclei; 2) increasing FC between the cingulo-opercular network and pulvinar nuclei, 3) decreasing FC between the default mode network (DMN) and right mediodorsal nuclei; 4) increasing FC between the DMN and left mediodorsal nuclei; 5) altered functional connectivity between thalamic nuclei and putamen subregions, and 6) increasing intrathalamic FC. Together, this suggests that several thalamic nuclei are involved in the learning-related transition from controlled to more automatic behaviour.
EEG Correlates of Cognitive Dynamics in Task Resumption after Interruptions: The Impact of Available Time and Flexibility
Authors: Ülkü Soner , Getzmann Stephan , Wascher Edmund , Schneider Daniel
Published: August 2024

Interruptions are a common aspect of everyday working life, negatively affecting both task performance and long-term psychological well-being. However, research suggests that the effects of interruptions can be mitigated in several ways, such as the opportunity to anticipate the interruptions and preparation time. Here, we used a retrospective visual working memory task to investigate the effects of duration and flexible resumption after interruptions, with 28 participants (18-30 years old) attending the experiment. For this main task participants were required to remember the orientations of a set of colored bars and retrieve one at the end of the trial in response to a retro-cue. This task was sometimes interrupted with an arithmetic task that was presented before the retro-cue. The period after the interruptions and the retro-cue was either short (no additional time), long (additional 1000 ms), or self-determined. Interruptions affected the main task performance irrespective of duration condition, while response times were shorter with the flexible condition. EEG analysis showed that having more time before resuming the interrupted task enabled stronger beta suppression which in turn modulated task performance, helping participants to safely disengage from the interrupting task, and refocus their attention back more efficiently. Further, flexibility in the timing of resumption provided additional benefits as seen in stronger oscillatory alpha and beta suppression to the retro-cue, also being related to better task performance. These results demonstrate the important role of resumption time and individual flexibility in dealing with interruptions.
FT-IR micro-spectroscopy for imaging the extracellular matrix composition in biofilms
Authors: de Bruin Stefan , Hof Carina , van Loosdrecht Mark C. M. , Sousa Diana Z. , Lin Yuemei
Published: August 2024

Microorganisms form granules by embedding themselves in an extracellular matrix through the secretion of extracellular polymeric substances (EPS). The extracellular matrix is a complex structure comprising of e.g. proteins, polysaccharides, lipids, and extracellular DNA. Understanding the function of individual EPS components within the matrix not only requires knowledge on the composition of the extracellular matrix, but also on the spatial distribution of said components. Molecular imaging like e.g. fluorescence microscopy have been used for the visualization of the extracellular matrix, but these target specific molecules. Untargeted approaches like FT-IR micro-spectroscopy would allow for a broader exploration. In this study FT-IR micro-spectroscopy analysis was implemented on sliced anaerobic granular sludge to explore the EPS distribution. Visualization of single wavenumber absorbance showed a higher polysaccharide content in the EPS at the granule perimeter, shifting to a higher protein concentration toward the centre. The boundary of this shift was approximately 150 µm from the surface, which was in accordance with the layer of fermentative bacteria described in literature. The complexity in the polymer composition meant that many functional groups were overlapping, making FT-IR annotation challenging. To address this, principal component analysis and two-dimensional correlation spectroscopy analysis were included in the analysis. These methods enabled the identification of overlapping functional groups and correlations between functional groups. Positive correlations between protein and polysaccharide functional groups suggested the presence of glycoproteins, which has been regularly described in chemical EPS analysis studies. Additionally, correlations between sulfated compounds and protein/polysaccharide functional groups indicated potential co-localization in the extracellular matrix. Differences in positive correlations of sialic acids with polysaccharides suggest variations in polysaccharide compositions, possibly caused by differences in the microbial community.
Mtbspecific HLA-E restricted T cells are induced duringMtbinfection but not after BCG administration in non-human primates and humans
Authors: Voogd Linda , van Wolfswinkel Marjolein , Satti Iman , White Andrew D. , Dijkman Karin , Gela Anele , van Meijgaarden Krista E. , Franken Kees L.M.C. , Marshall Julia L. , Ottenhoff Tom H.M. , Scriba Thomas J. , McShane Helen , Sharpe Sally A. , Verreck Frank A.W. , Joosten Simone A.
Published: August 2024

Novel vaccines targeting the world’s deadliest pathogenMycobacterium tuberculosis(Mtb) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule and HLA-E restrictedMtbspecific CD8+T cells can control intracellularMtbgrowth, making HLA-E a promising vaccine target forMtb. In this study, we evaluated the frequency and phenotype of HLA-E restrictedMtbspecific CD4+/CD8+T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. BCG vaccination followed byMtbchallenge in NHPs did not affect the frequency of circulating and local HLA-E/MtbCD4+and CD8+T cells, and we saw the same in humans receiving BCG. HLA-E/MtbT cell frequencies were significantly increased afterMtbchallenge in unvaccinated NHPs, which was correlated with higher TB pathology. Together, HLA-E/Mtbrestricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited afterMtbinfection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.
Fitness defects due to cytosolic protein misfolding inS. cerevisiaecan be alleviated by decreasing mitochondrial protein import capacity
Authors: Zaidi Zainab , Dash Devi Prasanna , Sharma Akanksha , Kundu Soumen , Bhatt Sarika , Rao Shikha , Padia Kedar , Rai Manish , Chakraborty Kausik
Published: August 2024

Protein misfolding affects cellular fitness. This can be caused due to the toxic aggregation of one species of protein or global protein misfolding events. Since the fitness defect arises due to the multi-modal effect of misfolding, there is no consensus mechanism to alleviate this fitness defect. Here, we used adaptive laboratory evolution of thermotolerance to identify pathways contributing to proteotoxic stress resistance inS. cerevisiae. Our results suggest a link between thermotolerance and proteotoxicity resistance, majorly routed through the loss of mitochondrial DNA. Loss of mitochondrial DNA decreased the association of mistargeted misfolded proteins on the mitochondrial surface and altered the cellular response to proteostasis to enhance protein quality control associated degradation. We show that a decrease in the abundance of import channels is sufficient to mimic the loss of mtDNA and increase cellular proteostasis. Thus, we uncover a cryptic interorganellar cooperation in combating proteotoxicity in yeast.
Quantitative analysis of DNA-GATA1 binding alterations linked to hematopoietic disorders
Authors: Zambo Boglarka , Morlet Bastien , Negroni Luc , Mózner Orsolya , Sarkadi Balázs , Travé Gilles , Gogl Gergo
Published: August 2024

GATA1 is a crucial transcription factor involved in hematopoiesis, and mutations in this gene are linked to severe hematological disorders, including anemia, thrombocytopenia, Down-syndrome related transient abnormal myelopoiesis (DS-TAM) and acute megakaryocytic leukemia (DS- AMKL). Despite significant clinical interest in the molecular level characterization of GATA1 mutations, a comprehensive understanding of their impact on DNA binding is limited. Efforts to conduct detailed studies on full-length recombinant GATA1 have faced significant technical challenges, while alternative approaches are limited by low throughput or qualitative nature. Here, we introduce a native holdup (nHU) assay designed to systematically quantify DNA-protein interactions and suitable for studying the impact of transcription factor mutations on DNA-binding affinity. First, we demonstrate, using the erythroid-specificATP2B4promoter as a model, that nHU can capture sequence-specific interactions and detect even subtle differences in DNA binding affinities of GATA1. Then, we quantitatively characterize the impact of pathological mutations on DNA binding affinities in the context of full-length human GATA1. Our findings reveal that the short isoform, lacking the N-terminal transactivation domain (N-TAD), binds to DNA with increased affinity, while the R307C mutation reduces binding to theATP2B4erythroid promoter. In harmony with these observations, GATA1s exhibits increased functional activity, while the R307C mutation results in decreased activity. This study demonstrates the power of the nHU assay for studying DNA interactions of transcription factor variants and providing insight into the molecular mechanism of related diseases.
Synthetic enhancers reveal design principles of cell state specific regulatory elements in hematopoiesis
Authors: Frömel Robert , Rühle Julia , Bernal Martinez Aina , Szu-Tu Chelsea , Pacheco Pastor Felix , Martinez Corral Rosa , Velten Lars
Published: August 2024

During cellular differentiation, enhancers transform overlapping gradients of transcription factors (TFs) to highly specific gene expression patterns. However, the vast complexity of regulatory DNA impedes the identification of the underlying cis-regulatory rules. Here, we have characterized 62,126 fully synthetic DNA sequences to bottom-up dissect design principles of cell-state specific enhancers in the context of the differentiation of blood stem cells to seven myeloid lineages. Focusing on binding sites for 38 TFs and their pairwise interactions, we found that identical sites displayed both repressive and activating function, as a consequence of cellular context, site combinatorics, or simply predicted occupancy of a TF on an enhancer. Surprisingly, we found that combinations of activating sites frequently neutralized each other or even gained repressive function. These negative synergies convert quantitative imbalances in transcription factor expression into binary downstream activity patterns, a principle that can be exploited to build differentiation-state specific enhancers from scratch.
Systematic Characterization of Transport Regulation inEscherichia coliacross defined environmental cues
Authors: Binsfeld Christoph , Alarcon Roberto Olayo , Wartel Morgane , Stadler Mara , Müller Christian , Brochado Ana Rita
Published: August 2024

Transport of small molecules across the bacterial cell envelope is essential to ensure nutrient uptake and protect bacteria from toxic compounds. Due to its decisive role, transport is controlled by complex regulatory networks, knowledge of which – in particular across external cues – remains poorly understood. Here we investigate transcriptional regulation of seven prominent transport genes inEscherichia coliacross 94 defined chemical cues, and simultaneously map the contributions of the key regulators MarA, SoxS and Rob to promoter activity. One third of all tested compounds triggered transcriptional changes, the vast majority of which previously unknown. Importantly, we exposed main drivers of transport control inE. coli, e.g. bacteriostatic, but not bactericidal, antibiotics trigger expression of efflux pumps, and that Rob contributes to ∼1/3 of all measured transcriptional changes, thereby emerging as a more prominent transport regulator than previously thought. We showcase the potential of our resource by elucidating the molecular mechanism of antibiotic antagonisms with widely consumed caffeine inE. coli. Altogether, our resource capitalizes on providing a quantitative overview of transport determinants across environments, and brings perspective to long-term prevailing concepts in the field.
Motion correction with subspace-based self-navigation for combined angiography, perfusion and structural imaging
Authors: Shen Qijia , Wu Wenchuan , Chiew Mark , Ji Yang , Woods Joseph G. , Okell Thomas W.
Published: August 2024

Motion artifacts are problematic in many MRI modalities. “Self-navigating” approaches are desirable, since no additional scan time or hardware is required. However, the generation of a navigator image, to estimate and correct motion, is difficult in cases where the tissue contrast is changing during the navigator acquisition window, such as in magnetization- prepared methods. Here we propose a subspace approach to reconstruct accurate navigators in the presence of time-varying tissue contrast and apply it to a combined angiography, perfusion and structural imaging method using a golden ratio 3D cones trajectory. This arterial spin labeling-based pulse sequence relies on subtraction of label and control images to isolate the relatively weak blood signal, making it particularly susceptible to motion corruption. An inversion pulse leads to time-varying tissue contrast across the readout train, but by reconstructing subspace coefficient maps directly, artifacts due to the varying contrast were alleviated. This resulted in high-quality navigator images that were subsequently registered to estimate and correct for motion. In addition, a split-update method was proposed to efficiently reconstruct from mismatched label/control k-space data with locally low rank regularization enforced on the difference image. The correction process was tested with numerical simulation and in vivo data from 8 healthy subjects with and without cued motion. In numerical simulation, the subspace- based navigator achieved an 84% reduction in RMSE of residual motion compared to without motion correction. In vivo, motion correction resulted in noise-like and background artifacts being greatly reduced and vessel sharpness being noticeably improved. Correlation of angiography, perfusion and structural images with motion-free reference images also increased by 159%, 53% and 12%, respectively, after motion correction. These results show that subspace-based navigators can effectively improve the motion robustness of MR imaging in contrast-varying acquisitions.
The conformation of the nSrc specificity-determining loops in the Src and Abl SH3 domains are modulated by a “WX” conserved sequence motif
Authors: Longshore-Neate Frederick , Ceravolo Caroline , Masuga Cole , Tahti Elise F. , Blount Jadon M. , Smith Sarah N. , Amacher Jeanine F.
Published: August 2024

Cellular signaling networks are modulated by multiple protein-protein interaction domains that coordinate extracellular inputs and processes to regulate cellular processes. Several of these domains recognize short linear motifs, or SLiMs, which are often highly conserved and are closely regulated. One such domain, the Src homology 3 (SH3) domain, typically recognizes proline-rich SLiMs and is one of the most abundant SLiM-binding domains in the human proteome. These domains are often described as quiteversatile, and indeed, SH3 domains can bind ligands in opposite orientations dependent on target sequence. Furthermore, recent work has identified diverse modes of binding for SH3 domains and a wide variety of sequence motifs that are recognized by various domains. Specificity is often attributed to the RT and nSrc loops near the peptide-binding cleft in this domain family, particularly for Class I binding, which is defined as RT and nSrc loop interactions with the N-terminus of the ligand. Here, we used the Src and Abl SH3 domains as a model to further investigate the role of the RT and nSrc loops in SH3 specificity. We created chimeric domains with the loop sequences swapped between these SH3 domains, and used fluorescence anisotropy assays to test how relative binding affinities were affected for Src SH3- and Abl SH3-specific ligands. We also used Alphafold – Multimer to model our SH3:peptide complexes. We identified a position that contributes to the nSrc loop conformation, the amino acid immediately C-terminal to a highly conserved Trp that creates a hydrophobic pocket critical for SH3 ligand recognition. We defined this as the WX motif, where X = Trp for Src and Cys for Abl. The importance of this position for orienting the ligand is supported by analyses of previously deposited SH3 structures, multiple sequence alignment of SH3 domains in the human proteome, and our biochemical data of mutant Src and Abl SH3 domains. Overall, our work uses experimental approaches and structural modeling to better understand SH3 specificity determinants.