bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractClosed-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

AbstractMulti-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

SummaryMitochondrial 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.HighlightsMitochondrial 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

AbstractDNA 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

AbstractDespite 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.
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

AbstractInterruptions 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

AbstractMicroorganisms 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

AbstractNovel 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

ABSTRACTProtein 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.
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

AbstractDuring 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

AbstractTransport 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

AbstractMotion 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

AbstractCellular 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.