bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator
Authors: Lee Matthew A , Hatcher Charlie A , Hazelwood Emma , Goudswaard Lucy J , Tsilidis Konstantinos K , Vincent Emma E , Martin Richard M , Smith-Byrne Karl , Brenner Hermann , Cheng Iona , Kweon Sun-Seog , Le Marchand Loic , Newcomb Polly A , Schoen Robert E , Peters Ulrike , Gunter Marc J , Van Guelpen Bethany , Murphy Neil 
Published: February 2024

AbstractAdiposity is an established risk factor for colorectal cancer (CRC). However, the pathways underlying this relationship, and specifically the role of the circulating proteome, is unclear.Utilizing two-sample Mendelian randomization and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable (UV) associations between: (I) adiposity measures (body mass index, BMI; waist hip ratio, WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (II) adiposity measures and plasma proteins, and (III) adiposity-associated plasma proteins and CRC risk. We used multivariable MR (MVMR) to investigate the potential mediating role of adiposity- and CRC-related proteins in the adiposity-CRC association.BMI and WHR were positively associated with CRC risk, with similar associations by anatomical tumour site. 6,591 adiposity-protein (2,628 unique proteins) and 33 protein-CRC (8 unique proteins) associations were identified using UVMR and colocalization. 1 protein, GREM1 was associated with BMI only and CRC outcomes in a manner that was consistent with a potential mediating role in sex-combined and female-specific analyses. In MVMR, adjusting the BMI-CRC association for GREM1, effect estimates were attenuated - suggestive of a potential mediating role - most strongly for the BMI-overall CRC association in women.These results highlight the impact of adiposity on the plasma proteome and of adiposity-associated circulating proteins on the risk of CRC. Supported by evidence fromcis-SNP UVMR and colocalization analyses, GREM1 was identified as a potential mediator of the BMI-CRC association, particularly in women, and warrants further experimental investigation.
The ChAHP chromatin remodelling complex regulates neurodevelopmental disorder risk genes to scale the production of neocortical layers
Authors: Clémot-Dupont Samuel , Lourenço Fernandes José Alex , Larrigan Sarah , Sun Xiaoqi , Medisetti Suma , Stanley Rory , Hankouri Ziyad El , Joshi Shrilaxmi V. , Picketts David J. , Shekhar Karthik , Mattar Pierre 
Published: February 2024

AbstractAlthough chromatin remodellers are among the most important risk genes associated with neurodevelopmental disorders (NDDs), the roles of these complexes during brain development are in many cases unclear. Here, we focused on the recently discovered ChAHP chromatin remodelling complex. The zinc finger and homeodomain transcription factor ADNP is a core subunit of this complex, andde novo ADNPmutations lead to intellectual disability and autism spectrum disorder. However, germlineAdnpknockout mice were previously shown to exhibit early embryonic lethality, obscuring subsequent roles for the ChAHP complex in neurogenesis. Here, we employed single cell transcriptomics, cut&run-seq, and histological approaches to characterize mice conditionally ablated for the ChAHP subunitsAdnpandChd4. We show that during neocortical development, Adnp and Chd4 orchestrate the production of late-born, upper-layer neurons through a two-step process. First, Adnp is required to sustain progenitor proliferation specifically during the developmental window for upper-layer cortical neurogenesis. Accordingly, we found that Adnp recruits Chd4 to genes associated with progenitor proliferation. Second, in postmitotic differentiated neurons, we define a network of risk genes linked to NDDs that are regulated by Adnp and Chd4. Taken together, these data demonstrate that ChAHP is critical for driving the expansion upper-layer cortical neurons, and for regulating neuronal gene expression programs, suggesting that these processes may potentially contribute to NDD etiology.HighlightsAdnpandChd4cKOs exhibit similar deficits in cortical growthAdnp sustains the proliferation of apical progenitors to scale the production of upper-layer neuronsAdnp recruits Chd4 to genes involved in corticogenesisAdnp is a master regulator of risk genes associated with neurodevelopmental disorders
De novoORFs are more likely to shrink than to elongate during neutral evolution
Authors: Lebherz Marie Kristin , Iyengar Bharat Ravi , Bornberg-Bauer Erich 
Published: February 2024

AbstractFor protein coding genes to emergede novofrom a non-genic DNA, the DNA sequence must gain an open reading frame (ORF) and the ability to be transcribed. The newbornde novogene can further evolve to accumulate changes in its sequence. Consequently, it can also elongate or shrink with time. Existing literature shows that olderde novogenes have longer ORF, but it is not clear if they elongated with time or remained of the same length since their inception. To address this question we developed mathematical model of ORF elongation as a Markov-jump process, and show that ORFs tend to keep their length in short evolutionary timescales. We also show that if change occurs it is likely to be a truncation. Our genomics and transcriptomics data analyses of sevenDrosophila melanogasterpopulations is also in agreement with the model’s prediction. We conclude that selection could facilitate ORF length extension that may explain why longer ORFs were observed in oldde novogenes in studies analysing longer evolutionary time scales.SignificanceNew protein coding genes can emerge from non-genic DNA through a process calledde novogene emergence. Genes thus emerged usually have a small open reading frame (ORF). However, studies show thatde novogenes with an older evolutionary origin have longer ORF than younger genes. To understand how ORF length evolves, we use a combination of mathematical modeling and population level genome data analysis. We find that in the absence of evolutionary selection, ORFs tend to become shorter than becoming longer. Therefore, long ORFs are probably selected by evolution to be retained in the genome.
Sensing the bactericidal and bacteriostatic antimicrobial mode of action using Raman-Deuterium stable isotope probing (DSIP)
Authors: Karlo Jiro , Vijay Arun Sree , Phaneeswar Mahamkali Sri , Pratap Singh Surya 
Published: February 2024

AbstractThe mode of actions of antibiotics can be broadly classified as bacteriostatic and bactericidal. The bacteriostatic mode leads to the arrested growth of the cells while the bactericidal mode causes cell death. In this work, we report the applicability of Deuterium stable isotope probing (DSIP) in combination with Raman spectroscopy (Raman DSIP) for discrimination among antibiotics on the basis of their mode of action at community level. We optimized the concentration of deuterium oxide required for metabolic activity monitoring without compromising the microbial growth. We also identified a novel carbon-deuterium Raman metabolic qualitative spectral marker in the biofingerprint region. This can be used for early identification of the antibiotic’s mode of action. Our results explores the new perspective which supports the utility of Deuterium based vibrational tags in the field of clinical spectroscopy. Understanding the antibiotic’s mode of action on bacterial cells in a short and objective manner can significantly enhance the clinical management abilities of infectious diseases and may also help in personalised antimicrobial therapy.Abstract Figure
nQuack: An R package for predicting ploidal level from sequence data using site-based heterozygosity
Authors: Gaynor Michelle L. , Landis Jacob B. , O’Connor Timothy K. , Laport Robert G. , Doyle Jeff J. , Soltis Douglas E. , Ponciano José Miguel , Soltis Pamela S. 
Published: February 2024

ABSTRACTPremiseTraditional methods of ploidal level estimation are tedious; leveraging sequence data for cytotype estimation is an ideal alternative. Multiple statistical approaches to leverage DNA sequence data for ploidy prediction based on site-based heterozygosity have been developed. However, these approaches may require high-coverage sequence data, use improper probability distributions, or have additional statistical shortcomings that limit inference abilities. We introduce nQuack, an open-source R package, that addresses the main shortcomings of current methods.Methods and ResultsnQuack performs model selection for improved ploidy predictions. Here, we implement expected maximization algorithms with normal, beta, and beta-binomial distributions. Using extensive computer simulations that account for variability in sequencing depth, as well as real data sets, we demonstrate the utility and limitations of nQuack.ConclusionInferring ploidal level based on site-based heterozygosity alone is discouraged due to the low accuracy of pattern-based inference.
nanoFeatures:a cross-platform application to characterize nanoparticles from super-resolution microscopy images
Authors: Izquierdo-Lozano Cristina , van Noort Niels , van Veen Stijn , Tholen Marrit M.E. , Grisoni Francesca , Albertazzi Lorenzo 
Published: February 2024

AbstractSuper-resolution microscopy and Single-Molecule Localization Microscopy (SMLM) are a powerful tool to characterize synthetic nanomaterials used for many applications such as drug delivery. In the last decade, imaging techniques like STORM, PALM, and PAINT have been used to study nanoparticle size, structure, and composition. While imaging has progressed significantly, often image analysis did not follow accordingly and many studies are limited to qualitative and semi-quantitative analysis. Therefore, it is imperative to have a robust and accurate method to analyze SMLM images of nanoparticles and extract quantitative features from them. Here we introducenanoFeatures, a cross-platform Matlab-based app for the automatic and quantitative analysis of super-resolution images.nanoFeaturesmakes use of clustering algorithms to identify nanoparticles from the raw data (localization list) and extract quantitative information about size, shape, and molecular abundance at the single-particle and single-molecule levels. Moreover, it applies a series of quality controls, increasing data quality and avoiding artifacts.nanoFeatures, thanks to its intuitive interface is also accessible to non-experts and will facilitate analysis of super-resolution microscopy for materials scientists and nanotechnologies. This easy accessibility to expansive feature characterization at the single particle level will bring us one step closer to understanding the relationship between nanostructure features and their efficiency.https://github.com/n4nlab/nanoFeatures
Monocyte to macrophage differentiation and changes in cellular redox homeostasis promote cell type-specific HIV latency reactivation
Authors: Blanco Alexandra , Coronado Robert A. , Arun Neha , Ma Kelly , Dar Roy D. , Kieffer Collin 
Published: February 2024

AbstractHuman Immunodeficiency Virus (HIV) latency regulation in monocytes and macrophages can vary according to signals directing differentiation, polarization, and function. To investigate these processes, we generated an HIV latency model in THP-1 monocytes and showed differential levels of HIV reactivation among clonal populations. Monocyte-to-macrophage differentiation of HIV-infected primary human CD14+ and THP-1 cells induced HIV reactivation and showed that virus production increased concomitant with macrophage differentiation. We applied the HIV-infected THP-1 monocyte-to- macrophage (MLat) model to assess the biological mechanisms regulating HIV latency dynamics during monocyte-to-macrophage differentiation. We pinpointed PKC signaling pathway activation and Cyclin T1 upregulation as inherent differentiation mechanisms that regulate HIV latency reactivation. Macrophage polarization regulated latency, revealing pro-inflammatory M1 macrophages suppressed HIV reactivation while M2 macrophages promoted HIV reactivation. Because macrophages rely on reactive- oxygen species (ROS) to exert numerous cellular functions, we disrupted redox pathways and discovered that inhibitors of the thioredoxin (Trx) system acted as latency promoting agents (LPAs) in T-cells and monocytes, but opposingly acted as latency reversing agents (LRAs) in macrophages. We explored this mechanism with Auranofin, a clinical candidate for reducing HIV reservoirs, and demonstrated Trx reductase (TrxR) inhibition led to ROS induced NF-κB activity, which promoted HIV reactivation in macrophages, but not in T-cells and monocytes. Collectively, cell type-specific differences in HIV latency regulation could pose a barrier to HIV eradication strategies.
Estimating orientation in Natural scenes: A Spiking Neural Network Model of the Insect Central Complex
Authors: Stentiford Rachael , Knight James , Nowotny Thomas , Philippides Andrew , Graham Paul 
Published: February 2024

AbstractThe central complex of insects contains cells, organised as a ring attractor, that encode head direction. The ‘bump’ of activity in the ring can be updated by idiothetic cues and external sensory information. Plasticity at the synapses between these cells and the ring neurons, that are responsible for bringing sensory information into the central complex, has been proposed to form a mapping between visual cues and the heading estimate which allows for more accurate tracking of the current heading, than if only idiothetic information were used.In Drosophila, ring neurons have well characterised non-linear receptive fields. In this work we produce synthetic versions of these visual receptive fields using a combination of excitatory inputs and mutual inhibition between ring neurons. We use these receptive fields to bring visual information into a spiking neural network model of the insect central complex based on the recently published Drosophila connectome.Previous modelling work has focused on how this circuit functions as a ring attractor using the same type of simple visual cues commonly used experimentally. While we initially test the model on these simple stimuli, we then go on to apply the model to complex natural scenes containing multiple conflicting cues. We show that this simple visual filtering provided by the ring neurons is sufficient to form a mapping between heading and visual features and maintain the heading estimate in the absence of angular velocity input. The network is successful at tracking heading even when presented with videos of natural scenes containing conflicting information from environmental changes and translation of the camera.Author summaryTo navigate through the world animals require knowledge of the direction they are facing. Insects keep track of this “head direction” with a population of ‘compass’ neurons. These cells can use internal measures of angular velocity to maintain the heading estimate but this becomes inaccurate over time and needs to be stabilised by environmental cues. In this work we produce a spiking neural network model replicating the connectivity between regions of the insect brain known to be involved in keeping track of heading and the neurons which are responsible for bringing sensory information into the circuit.We show that the model replicates the dynamics of visual learning from experiments where flies learn simple visual stimuli. Then using panoramic videos of complex natural environments, we show that the learned mapping between the current estimate of heading in the compass neurons and the features of the visual scene can maintain and enforce the correct heading estimate.
Biophysical Fluid Dynamics in a Petri Dish
Authors: Fortune George T. , Lauga Eric , Goldstein Raymond E 
Published: February 2024

AbstractThe humble Petri dish is perhaps the simplest setting in which to examine the locomotion of swimming organisms, particularly those whose body size is tens of microns to millimetres. The fluid layer in such a container has a bottom no-slip surface and a stress-free upper boundary. It is of fundamental interest to understand the flow fields produced by the elementary and composite singularities of Stokes flow in this geometry. Building on the few particular cases that have previously been considered in the literature, we study here the image systems for the primary singularities of Stokes flow subject to such boundary conditions —the stokeslet, rotlet, source, rotlet dipole, source dipole and stresslet —paying particular attention to the far-field behavior. In several key situations, the depth-averaged fluid flow is accurately captured by the solution of an associated Brinkman equation whose screening length is proportional to the depth of the fluid layer. The case of hydrodynamic bound states formed by spinning microswimmers near a no-slip surface, discovered first using the algaVolvox, is reconsidered in the geometry of a Petri dish, where the powerlaw attractive interaction between microswimmers acquires unusual exponentially screened oscillations.
False alarm detection in intensive care unit for monitoring arrhythmia condition using bio-signals
Authors: Swetapadma Aleena , Manna Tishya , Samami Maryam 
Published: February 2024

PurposeA novel method has been proposed to reduce the false alarm rate of arrhythmia patients regarding life-threatening conditions in the intensive care unit. In this purpose, the atrial blood pressure, photoplethysmogram (PLETH), electrocardiogram (ECG) and respiratory (RESP) signals are considered as input signals.Design/methodology/approachThree machine learning approaches feed-forward artificial neural network (ANN), ensemble learning method and k-nearest neighbors searching methods are used to detect the false alarm. The proposed method has been implemented using Arduino and MATLAB/SIMULINK for real-time ICU-arrhythmia patients' monitoring data.FindingsThe proposed method detects the false alarm with an accuracy of 99.4 per cent during asystole, 100 per cent during ventricular flutter, 98.5 per cent during ventricular tachycardia, 99.6 per cent during bradycardia and 100 per cent during tachycardia. The proposed framework is adaptive in many scenarios, easy to implement, computationally friendly and highly accurate and robust with overfitting issue.Originality/valueAs ECG signals consisting with PQRST wave, any deviation from the normal pattern may signify some alarming conditions. These deviations can be utilized as input to classifiers for the detection of false alarms; hence, there is no need for other feature extraction techniques. Feed-forward ANN with the Lavenberg–Marquardt algorithm has shown higher rate of convergence than other neural network algorithms which helps provide better accuracy with no overfitting.
Examining perceptions of utilizing augmented reality in hybrid learning environment: instructors and students perspectives
Authors: Ironsi Chinaza Solomon 
Published: February 2024

Purpose
This study aims to explore the perceptions of language learners and instructors on using augmented reality (AR) in a hybrid learning environment.

Design/methodology/approach
Mixed-method research design was used to elicit information from 62 participants on the study’s objective. Data were collected and analyzed to examine the participants’ views on using AR in language teaching in a hybrid environment.

Findings
This study unveils that while most studies acknowledge AR as an effective instructional delivery, students and instructors perceive some setbacks. Other novel insights provided by this study reveal necessities to consider before implementing AR in classroom settings.

Research limitations/implications
This study provides insights into the widely reported effectiveness of AR in the English language-teaching domain. This study suggests that considering the dispositions of learners and instructors toward digitally enhanced learning, using AR without good teaching practices and approaches may not yield expected learning outcomes.

Originality/value
This study advances scientific knowledge on the use of AR in hybrid learning models by providing empirical evidence to show the perceived effectiveness of AR. It further provides a robust understanding of the pedagogical implications of using AR in classroom settings drawing from diverse lenses. This helps ensure that educational settings that integrate AR consider the novel findings of this study before such implementation.
The effect of breadth of external pressure on leaders in small and medium-sized enterprises: does the firm become more entrepreneurial?
Authors: Williams Chris , You Jacqueline Jing , Spielmann Nathalie 
Published: February 2024

PurposeThe study explores the relationship between the breadth of external pressures facing leaders of small and medium-sized enterprises (SMEs) and the entrepreneurial stance they adopt for their firm, that is, entrepreneurial orientation (EO).Design/methodology/approachBlending attention theory with EO literature, we argue that increasing breadth of external pressures will challenge leaders' attentions with implications for how they seek innovation, risk-taking and bold acts. We highlight an inflection point after which a negative relationship between the breadth of external pressure and EO will turn positive. We use data from a survey of 125 small-sized wineries in France to test this and capture a range of 15 external pressures on entrepreneurs.FindingsThe main tests and additional robustness tests provide support. It is the breadth of external pressures – as opposed to intensity of any one specific form of pressure – that plays a fundamental role in shaping leaders' adoption of EO in small enterprises over and above internal characteristics.Research limitations/implicationsWhile the results may be context-dependent, they provide support for an attention-based view of entrepreneurial responses by leaders of SMEs under pressure.Practical implicationsSME leaders and entrepreneurs should be aware of how their attention is challenged by breadth of pressures from external sources, as this can influence the EO they adopt for their SME.Originality/valueThis nonlinear perspective on external pressures influencing the EO of small firms has not been taken in the EO literature to date, despite some recent work that considers only a small range of external pressures.