bluuebunny/crossref_metadata_2025 huggingface dataset:
A Label-free Nanowell-based Impedance Sensor for Ten-minute SARS-CoV-2 Detection
Authors: Meng Zhuolun , White Liam , Xie Pengfei , Mahmoodi Seyed Reza , Karapiperis Aris , Lin Hao , Drazer German , Javanmard Mehdi , DeMauro Edward P.
Published: December 2024

This work explores label-free biosensing as an effective method for biomolecular analysis, ensuring the preservation of native conformation and biological activity. The focus is on a novel electronic biosensing platform utilizing micro-fabricated nanowell-based impedance sensors, offering rapid, point-of-care diagnosis for SARS-CoV-2 (COVID-19) detection. The nanowell sensor, constructed on a silica substrate through a series of microfabrication processes including deposition, patterning, and etching, features a 5×5 well array functionalized with antibodies. Real-time impedance changes within the nanowell array enable diagnostic results within ten minutes using small sample volumes (<5 μL). The research includes assays for SARS-CoV-2 spike proteins in Phosphate-buffered saline (PBS) and artificial saliva buffers to mimic real human SARS-CoV-2 samples, covering a wide range of concentrations. The sensor exhibits a detection limit of 0.2 ng/mL (1.5 pM) for spike proteins. Middle East Respiratory Syndrome (MERS-CoV) spike proteins are differentiated from SARS-CoV-2 spike proteins, demonstrating specificity.
Cross-disease modeling of peripheral blood identifies biomarkers of type 2 diabetes predictive of Alzheimer’s disease
Authors: Ball Brendan K. , Park Jee Hyun , Proctor Elizabeth A. , Brubaker Douglas K.
Published: December 2024

Type 2 diabetes (T2D) is a significant risk factor for Alzheimer’s disease (AD). Despite multiple studies reporting this connection, the mechanism by which T2D exacerbates AD is poorly understood. It is challenging to design studies that address co-occurring and comorbid diseases, limiting the number of existing evidence bases. To address this challenge, we expanded the applications of a computational framework called Translatable Components Regression (TransComp-R), initially designed for cross-species translation modeling, to perform cross-disease modeling to identify biological programs of T2D that may exacerbate AD pathology. Using TransComp-R, we combined peripheral blood-derived T2D and AD human transcriptomic data to identify T2D principal components predictive of AD status. Our model revealed genes enriched for biological pathways associated with inflammation, metabolism, and signaling pathways from T2D principal components predictive of AD. The same T2D PC predictive of AD outcomes unveiled sex-based differences across the AD datasets. We performed a gene expression correlational analysis to identify therapeutic hypotheses tailored to the T2D-AD axis. We identified six T2D and two dementia medications that induced gene expression profiles associated with a non-T2D or non-AD state. Finally, we assessed our blood-based T2DxAD biomarker signature in post-mortem human AD and control brain gene expression data from the hippocampus, entorhinal cortex, superior frontal gyrus, and postcentral gyrus. Using partial least squares discriminant analysis, we identified a subset of genes from our cross-disease blood-based biomarker panel that significantly separated AD and control brain samples. Our methodological advance in cross-disease modeling identified biological programs in T2D that may predict the future onset of AD in this population. This, paired with our therapeutic gene expression correlational analysis, also revealed alogliptin, a T2D medication that may help prevent the onset of AD in T2D patients.
Assembly of hierarchical multiphase condensates using designer surfactant proteins
Authors: Guan Muyang , Hammer Daniel A. , Good Matthew C.
Published: December 2024

Biomolecular condensates are complex fluids formed by liquid-liquid phase separation of macromolecules. Similar to other types of soft matter, they feature a range of biophysical properties that distinguish them from the cellular milieu. As a separate phase, they have an identifiable interface that dictates their interaction with the cytoplasm and other membraneless organelles. In this work, we engineer the interface of condensates to build novel hierarchical mesoscale structures from two immiscible disordered proteins: the RGG domain of LAF-1, a RNA-processing protein involved in germ granule assembly and the low complexity domain (LC) of FUS, an RNA binding protein whose aggregation is implicated in age-related neurodegeneration. RGG and FUS LC do not co-partition with one another and instead form discrete protein-rich condensed phases. Despite their apparent immiscibility, we identified conditions that can promote hierarchical assembly, either kinetically trapping one phase in the other, or using a designer surfactant protein that reduces the interfacial tension between the two phases. In addition, we studied factors that impact condensate miscibility and structure formation, including surface properties and viscoelasticity. This study probes the principles that underlie formation and assembly of complex structures from biomolecular condensates and provides a strategy for designing synthetic multiphasic materials capable of spatial partitioning.
Molecular Crowding Suppresses Mechanical Stress-Driven DNA Strand Separation
Authors: Desai Parth Rakesh , Marko John F.
Published: December 2024

Molecular crowding influences DNA mechanics and DNA - protein interactions and is ubiquitous in living cells. Quantifying the effects of molecular crowding on DNA supercoiling is essential to relatingin-vitroexperiments toin-vivoDNA supercoiling. We use single molecule magnetic tweezers to study DNA supercoiling in the presence of dehydrating or crowding co-solutes. To study DNA supercoiling, we apply a stretching force of 0.8 pN to the DNA and then rotate one end of the DNA to induce supercoiling. In a 200 mM NaCl buffer without co-solutes, negatively supercoiled DNA absorbs some of the tortional stress by forming locally melted DNA regions. The base-pairs in these locally melted regions are believed to adopt a configuration where nucleotide base pairing is disrupted. We find that the presence of dehydrating co-solutes like glycerol and ethylene glycol results in further destabilization of base-pairs in negatively supercoiled DNA. The presence of polyethylene glycol, commonly used as crowding agents, suppresses local strand separation and results in plectoneme formation even when DNA is negatively supercoiled. The results presented in this letter suggest many further directions for studies of DNA supercoiling and supercoiled DNA – protein interactions in molecular conditions that approximatein-vivomolecular composition.

SIGNIFICANCE

Accurate modelling of DNA mechanics is central to interpreting results of single molecule studies of DNA mechanics and DNA-protein interactions. While the effect of molecular conditions on short and relaxed DNA has been studied, the influence of molecular conditions on DNA supercoiling has not been explored. We present the first single molecule study of DNA supercoiling in presence of crowding and dehydrating co-solutes. We observe that co-solutes can increase or completely suppress stress-driven local strand separation in negatively supercoiled DNA. This change of DNA supercoiling is likely to significantly affect the function of DNA-binding proteins. Our results motivate the need for systematic exploration of DNA supercoiling in presence of co-solutes to accurately relatein-vitroDNA-protein interactions toin-vivoDNA-protein interactions.
Multiple-Basin Gō-Martinifor Investigating Conformational Transitions and Environmental Interactions of Proteins
Authors: Yang Song , Song Chen
Published: December 2024

Proteins are inherently dynamic molecules, and their conformational transitions among various states are essential for numerous biological processes, which are often modulated by their interactions with surrounding environments. Although molecular dynamics (MD) simulations are widely used to investigate these transitions, all-atom (AA) methods are often limited by short timescales and high computational costs, and coarse-grained (CG) implicitsolvent Gō-like models are usually incapable of studying the interactions between proteins and their environments. Here, we present an approach called Multiple-basin Gō-Martini, which combines the recent Gō-Martini model with an exponential mixing scheme to facilitate the simulation of spontaneous protein conformational transitions in explicit environments. We demonstrate the versatility of our method through five diverse case studies: GlnBP, Arc, Hinge, SemiSWEET, and TRAAK, representing ligand-binding proteins, fold-switching proteins,de novodesigned proteins, transporters, and mechanosensitive ion channels, respectively. The Multiple-basin Gō-Martini offers a new computational tool for investigating protein conformational transitions, identifying key intermediate states, and elucidating essential interactions between proteins and their environments, particularly protein-membrane interactions. In addition, this approach can efficiently generate thermodynamically meaningful datasets of protein conformational space, which may enhance deep learning-based models for predicting protein conformation distributions.
Machine Learning Models for Segmentation and Classification of Cyanobacterial Cells
Authors: Huffine Clair A. , Maas Zachary L. , Avramov Anton , Brininger Chris , Cameron Jeffrey C. , Tay Jian Wei
Published: December 2024

Timelapse microscopy has recently been employed to study the metabolism and physiology of cyanobacteria at the single-cell level. However, the identification of individual cells in brightfield images remains a significant challenge. Traditional intensity-based segmentation algorithms perform poorly when identifying individual cells in dense colonies due to a lack of contrast between neighboring cells. Here, we describe a newly developed software package called Cypose which uses machine learning (ML) models to solve two specific tasks: segmentation of individual cyanobacterial cells, and classification of cellular phenotypes. The segmentation models are based on the Cellpose framework, while classification is performed using a convolutional neural network named Cyclass. To our knowledge, these are the first developed ML-based models for cyanobacteria segmentation and classification. When compared to other methods, our segmentation models showed improved performance and were able to segment cells with varied morphological phenotypes, as well as differentiate between live and lysed cells. We also found that our models were robust to imaging artifacts, such as dust and cell debris. Additionally, the classification model was able to identify different cellular phenotypes using only images as input. Together, these models improve cell segmentation accuracy and enable high-throughput analysis of dense cyanobacterial colonies and filamentous cyanobacteria.
Androgen receptor drives polyamine synthesis creating a vulnerability for prostate cancer
Authors: Kumar Rajendra , Jonnatan Sheila , Sanin David E , Vakkala Varsha , Kadam Anoushka , Kumar Shivani , Dalrymple Susan L , Zhao Liang , Foley Jackson , Holbert Cassandra E , Nwafor Ashley , Kittane Srushti , Penner Elizabeth , Apostolova Petya , Warner Samuel , Dang Chi V , Toska Eneda , Thompson Elizabeth A , Isaacs John T , De Marzo Angelo M , Pearce Erika L , Stewart Tracy Murray , Casero Robert A , Denmeade Samuel R , Sena Laura A
Published: December 2024

Supraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models. This occurred through AR binding at enhancer sites upstream of theODC1promoter to increase abundance of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine synthesis, and de novo synthesis of polyamines from arginine. SPA-stimulated polyamines enhance prostate cancer fitness, as dCas9-KRAB-mediated inhibition of AR regulation ofODC1or direct ODC inhibition by difluoromethylornithine (DFMO) increased efficacy of SPA. Mechanistically, this occurred in part due to increased activity of S-adenosylmethionine decarboxylase 1 (AMD1), which was stimulated both by AR and by loss of negative feedback by polyamines, leading to depletion of its substrate S-adenosylmethionine and global protein methylation. These data provided the rationale for a clinical trial testing the safety and efficacy of BAT in combination with DFMO for patients with metastatic castration-resistant prostate cancer. Pharmacodynamic studies of this drug combination in the first five patients on trial indicated that the drug combination resulted in effective polyamine depletion in plasma. Thus, the AR potently stimulates polyamine synthesis, which constitutes a vulnerability in prostate cancer treated with SPA that can be targeted therapeutically.
Pasteurized retail dairy enables genomic surveillance of H5N1 avian influenza virus in United States cattle
Authors: Lail Andrew J. , Vuyk William C. , Machkovech Heather , Minor Nicholas R. , Hassan Nura R. , Dalvie Rhea , Emmen Isla E. , Wolf Sydney , Kalweit Annabelle , Wilson Nancy , Newman Christina M. , Tiburcio Patrick Barros , Weiler Andrea , Friedrich Thomas C. , O’Connor David H.
Published: December 2024

Highly pathogenic avian influenza (HPAI) viruses with H5 hemagglutinin (HA) genes (clade 2.3.4.4b) are causing an ongoing panzootic in wild birds. Circulation of these viruses is associated with spillover infections in multiple species of mammals, including a large, unprecedented outbreak in American dairy cattle. With limited testing of dairy herds, there is an unmet need for genomic surveillance. Infected cattle can shed high amounts of HPAI H5N1 viruses in milk, allowing detection in pasteurized retail dairy samples. Over a 2-month sampling period in one Midwestern city, we obtained dairy products processed in 20 different states. Here we demonstrate that a tiled-amplicon sequencing approach produced over 90% genome coverage at greater than 20x depth from 5 of 13 viral RNA positive samples. A combination of RT-qPCR testing and sequencing from retail dairy products can be a useful component of a One Health framework for responding to the avian influenza outbreak in cattle.
Estimating recent trends in UK alcohol sales from alcohol duty revenue
Authors: Angus Colin , Schöley Jonas
Published: December 2024

Background and Aims

The onset of the COVID-19 pandemic led to significant changes in individual-level alcohol consumption and a sharp increase in heavy drinking in the UK. More recently, high rates of inflation, the resulting ‘cost-of-living crisis’ and reforms to alcohol taxation have affected the affordability of alcohol, but little is understood about how these changes have impacted on alcohol sales and consumption. We aimed gain insights into recent trends in alcohol sales by assessing changes in alcohol duty revenue collected by the UK government since 2020.

Design and Setting

We used published data on UK alcohol duty revenue to model trends from 2010-2019. We forecasted these trends through to October 2024 using a novel statistical approach and compared these forecasts to observed receipts.

Measurements

Monthly inflation-adjusted alcohol duty receipts received by the UK Treasury in pounds sterling for beer, cider, spirits and wine.

Findings

During the pandemic, alcohol duty receipts fell during lockdowns and rose as restrictions were subsequently lifted. Since 2022 alcohol duty receipts have been consistently below the historical trend, with a gradually increasing deficit in wine receipts and comparable deficit in spirits receipts that began sharply in late 2022. The reforms to the alcohol duty system in August 2023 do not appear to have significantly affected these trends.

Conclusions

Our findings suggest that the ‘cost of living crisis’ in 2022/23 has led to a fall in alcohol sales relative to the pre-pandemic trend. The magnitude of this fall differs by beverage type, indicating that wine and spirits drinkers may have changed their behaviour more than beer and cider drinkers.
Structural plasticity following deep brain stimulation of the internal capsule in treatment resistant depression
Authors: Zhong Z. , Bergfeld I.O. , de Kwaasteniet B.P. , Luigjes J. , Mocking R.J.T. , van Laarhoven J. , Notten P. , Beute G. , van den Munckhof P. , Schuurman P.R. , Denys D.A.J.P. , van Wingen G.A.
Published: December 2024

Objective

Deep brain stimulation (DBS) targeting the ventral anterior limb of the internal capsule (vALIC) shows potential as treatment for treatment resistant depression (TRD). While DBS alters brain function, it is not yet known whether it also induces anatomical alterations. Here we investigated the long-term effects of vALIC DBS on brain structure using structural magnetic resonance imaging.

Methods

We included data from twelve patients with TRD before DBS surgery and after DBS parameter optimization, and from sixteen matched healthy controls at a comparable time interval to control for test-retest effects. To investigate the short-term effects of DBS deactivation after parameter optimization, thirteen patients were additionally scanned after double-blind periods of active and sham stimulation. Voxel-based morphometry analysis was used to identify volumetric differences.

Result

The group x time interaction showed significant changes in anterior thalamic gray matter volume, with a relative reduction in TRD patients compared to controls. Follow-up analysis suggested that this was related to larger thalamic volume at baseline in DBS non-responders. A direct comparison between responders and non-responders showed an additional interaction in the posterior thalamus and hippocampus, which was also related to larger volumes at baseline in non-responders. The comparison between active and sham stimulation during the crossover phase did not show significant differences.

Conclusion

These results show that long-term vALIC DBS is associated with a reduction in thalamic volume compared to healthy controls, suggesting that long-term DBS induces focal structural plasticity.
The exploration of the characteristics of lower extremity deep venous thromboembolism in patients at admission to a tertiary general hospital in a fourth-tier city in China
Authors: Pan Jianghao , Sun Jianming , Song Jiaming , Fu Guangyin , Lei Yong , Wang Le
Published: December 2024

With the acceleration of the pace of life and the change of people’s living and working habits, the incidence of venous diseases of lower extremity remains high, and even shows an upward trend year by year, which has a great impact on the quality of life and work efficiency of patients. Well, the occurrence and development of lower extremity deep vein thrombosis (LEDVT) is also related to the economic and humanistic characteristics of a certain place.

Objectives

The purpose of this paper is to retrospectively analyze the medical records of DVT patients in a general hospital of a fourth-tier city in China, and find some noteworthy characteristics, so as to provide some objective evidence for the diagnosis of DVT in similar hospitals.

Methods

Adult patients with central LEDVT with or without pulmonary embolism (PE) were retrospectively analyzed. The general condition, concomitant diseases, laboratory tests and other clinical characteristics were analyzed.

Results

A total of 100 patients’ medical records were analyzed. The age was non-normally distributed (p=0.004), which from 31 to 87 (65.3±11.5) years, and 58% of them were 65 years or older. Males (56%) were slightly more than females. Ninety of ninety-four patients’ D-dimer ≥1μgDDU/ml. Fifty-eight were definitely diagnosed with central LEDVT at admission, of which twenty-three were confirmed as PE by CT. Thirty-five patients with leg symptoms, thirty-three patients with chest symptoms, only two patients had both leg and chest symptoms, and thirty-four patients without any obvious symptoms of DVT when they were admitted to the hospital. Only twelve patients were admitted only with LEDVT, and most of the other patients were complicated with other system/organ diseases.

Conclusions

LEDVT is more common in elderly patients aged ≥ 65 years. However, the incidence of patients ≥75 years old observed in this study may be limited by the local economic situation and life expectancy. The symptoms can present as many, may be the typical leg symptoms, progression to PE may involve chest symptoms, or it may be neither leg symptoms nor chest symptoms that are masked by the symptoms of other concomitant diseases. LEDVT can be complicated with multiple system/organ diseases. It is necessary to screen for DVT in patients with abnormal D-dimer.
Comparing DXA and MRI body composition measurements in cross-sectional and longitudinal cohorts
Authors: Basty Nicolas , Thanaj Marjola , Whitcher Brandon , Bell Jimmy D , Thomas E Louise
Published: December 2024

In this study we assessed the accuracy of dual X-ray absorptiometry (DXA) compared to magnetic resonance imaging (MRI) for evaluating body composition. Using data from 32,961 participants in the UK Biobank, including 1,928 re-scanned participants after about two and a half years, we examined cross-sectional and longitudinal agreements in DXA and MRI measurements within android and gynoid regions. Our results showed that DXA reliably captured fat measurements but overestimated lean mass compared to MRI, particularly in android regions for men (4.10 vs. 1.74 kg) and women (2.92 vs. 1.10 kg). Longitudinal MRI data revealed a 4-5% muscle and lean mass decrease, undetected by DXA, which showed lean mass increases in women at the follow-up visit. Although DXA is practical for population-level fat assessments, MRI remains the preferred method for detailed and precise longitudinal body composition analysis.
Segmentation of the Human Tongue Musculature Using MRI: Field Guide and Validation in Motor Neuron Disease
Authors: Shaw Thomas B , Ribeiro Fernanda L , Zhu Xiangyun , Aiken Patrick , Bollmann Saskia , Bollmann Steffen , Chang Jeryn , Chidley Kali , Dempsey-Jones Harriet , Eftekhari Zeinab , Gillespie Jennifer , Henderson Robert D , Kiernan Matthew C , Ktena Ira , McCombe Pamela A , Ngo Shyuan T , Taubert Shana T , Whelan Brooke-Mai , Ye Xincheng , Steyn Frederik J , Tu Sicong , Barth Markus
Published: December 2024

The human tongue is a multifunctional organ with crucial roles in speech and swallowing. However, due to its anatomical characteristics, it is difficult to measure constituent muscle volumes, and few studies have investigated this aspect thoroughly. The present study introduces a novel method and datasets for automatically segmenting the musculature of the human tongue using non-invasive T1-weighted and T2-weighted MRI. We generated accurate and robust volume estimation of five intrinsic tongue muscles and developed and validated a comprehensive volume estimation method combining AI-assisted (deep learning) segmentation and atlas fusion approaches. We showcase its clinical potential in over 200 Magnetic Resonance (MR) scans including a clinically phenotyped cohort of neurodegenerative patients with motor neuron disease (MND). We describe detailed guidelines, publicly available multi-site datasets, and an externally validated normalisation strategy that removes confounding demographic characteristics and will allow generalised application across large publicly available MRI neuroimaging datasets. Results show expected differences in people living with MND; notably, those with clinical evidence of speech and swallowing dysfunction have smaller muscle volumes. As the tongue is generally covered in neuroimaging protocols, we envision that our proposed and validated analysis pipeline will allow the post-hoc analysis of a vast number of datasets. We expect this novel work to enable the investigation of tongue muscle volume as a marker in a wide range of diseases that implicate tongue function, including neurodegenerative diseases, pathological speech disorders and cancer.
Reference-free identification and pangenome analysis of accessory chromosomes in a major fungal plant pathogen
Authors: van Westerhoven Anouk C. , Fokkens Like , Wissink Kyran , Kema Gert , Rep Martijn , Seidl Michael F.
Published: December 2024

Accessory chromosomes, found in some but not all individuals of a species, play an important role in pathogenicity and host specificity in fungal plant pathogens. However, their variability complicates reference-based analysis, especially when chromosomes are missing from reference genomes. Pangenome variation graphs offer a reference-free alternative for studying these chromosomes. Here, we constructed a pangenome variation graph forFusarium oxysporum, a major fungal plant pathogen with a compartmentalized genome. To study accessory chromosomes, we constructed a chromosome similarity network and identified eleven conserved core chromosomes and many highly variable accessory chromosomes. Some of these are host-specific and are likely involved in determining host range, which we corroborate by analyzing nearly 600F. oxysporumassemblies. By a reconstruction of pangenome variation graph per homologous chromosomes, we show that these evolve due to extensive structural variation as well as the exchange of genetic material between accessory chromosomes giving rise to these mosaic accessory chromosomes. Furthermore, we show that accessory chromosomes are horizontally transferred in natural populations. We demonstrate that pangenome variation graphs are a powerful approach to elucidate the evolutionary dynamics of accessory chromosomes inF. oxysporumand provides a computational framework for similar analyses in other species that encode accessory chromosomes.
CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity
Authors: Fisher Robert J. , Park Kihyun , Lee Kwangwoon , Pinjusic Katarina , Vanasse Allison , Ennis Christina S. , Ficcaro Scott , Marto Jarrod , Stransky Stephanie , Duke-Cohan Joseph , Geethadevi Anupa , Raabe Eric , Sidoli Simone , Hicks Chad W. , Keskin Derin B. , Wu Catherine J. , Cole Philip A. , Alani Rhoda M.
Published: December 2024

ABSTRACT

Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies. Using predictive machine learning models and MHC IP-MS, we identify thousands of corin-induced neopeptides derived from unannotated splice sites which generate immunogenic splice-neoantigens. Furthermore, corin reactivates the response to immune checkpoint blockade and promotes dramatic expansion of cytotoxic T cells in an immune cold melanoma model. CoREST complex inhibition thus represents a unique therapeutic opportunity in cancer which creates tumor-associated neoantigens that enhance the immunogenicity of current therapeutics.

Statement of Significance

We identify a novel role of the CoREST transcriptional repressor complex in regulating pre-mRNA splicing and find that the small molecule inhibitor, corin, promotes alternative splicing events in cancer leading to neoantigen expression and T cell-mediated immunity. This represents a potential approach to promote immunoreactive neoantigen expression in immune-cold tumors.
Developmental rewiring of theNGAL/CUC/KLUnetwork associated with pleiotropic roles ofNGALgenes
Authors: Nicolas Antoine , Papadopoulos Panagiotis , Caroulle Mattéo , Adroher Bernard , Goussot Magali , Sarthou Anne-Sophie , Arnaud Nicolas , Maugarny Aude , Laufs Patrick
Published: December 2024

Gene Regulatory Networks (GRNs) play prominent roles in regulating developmental processes, and their modulation across species is a major source for evolutionary innovation. However, it remains poorly understood how GRNs are rewired between different organs within a single species. This question is particularly relevant for pleiotropic genes, which may exhibit organ-specific GRN modulations potentially reflecting their diverse functions. To address this, we investigated theNGATHA-like(NGAL) genes, as a model for pleiotropic genes that regulate growth or patterning in multiple Arabidopsis organs via two distinct pathways involving theCUP-SHAPED COTYLEDON(CUC) andKLUH(KLU) genes. By combining genetic analysis with gene expression characterization, we uncovered significant organ-specific rewiring of theNGAL/CUC/KLUregulatory module. Our findings highlight that changes in gene expression patterns, potentially arising from developmental constraints, play a pivotal role in the organ-specific modulation of GRNs. Furthermore, GRNs at the molecular and functional levels do not always align perfectly, potentially due to the influence of additional regulatory mechanisms. Altogether, our findings reveal significant modulation of the GRNs associated with pleiotropic genes. We propose that this flexibility in GRNs facilitates gene pleiotropy.
High-Accuracy RNA Integrity Definition for Unbiased Transcriptome Comparisons with INDEGRA
Authors: Cleynen Alice , Ravindran Agin , Sethi Aditya , Kumar Bhavika , Javaid Tanya , Mahmud Shafi , Woodward Katrina , Santos Vieira Helaine Graziele , Änkö Minna-Liisa , Weatheritt Robert , Eyras Eduardo , Robin Stéphane , Shirokikh Nikolay
Published: December 2024

RNA sample integrity variability introduces biases and obscures natural RNA degradation, posing a significant challenge in transcriptomics. To address this, we developed the Direct Transcriptome Integrity (DTI) measure, a universal and robust RNA integrity metric based on nanopore sequencing. By accurately modeling RNA fragmentation, DTI provides a reliable assessment of sample quality. Integrated into the INDEGRA package (freely available athttps://github.com/Arnaroo/INDEGRA), we provide tools to correct false discoveries and enable precise differential expression and RNA degradation analyses, even for challenging sample types.

INDEGRA software can be used to accurately measure RNA DTI stability metric, isolate biological component of RNA degradation from technical biases, compare biological RNA stability transcriptome-wide and suppress false degradation-induced differential gene expression hits to allow broad comparisons across samples of different quality

DTI offers a straightforward and accurate method for assessing RNA degradation, characterizing both overall sample integrity and transcript-specific degradation rates using direct RNA sequencing (DRS) data. Calculated through INDEGRA, DTI reveals inter- and intra-transcript variability in degradation, while INDEGRA separates RNA degradation from mapping inaccuracies, and connects degradation profiles to RNA fragmentation rates. By leveraging INDEGRA, researchers can minimize false differential transcript abundance findings caused by variations in overall sample integrity, while preserving genuine transcript-specific differences in stability and degradation.

INDEGRA supports integration with widely used differential transcript abundance tools like DESeq2, limma-voom, and edgeR, enabling seamless analysis pipelines. INDEGRA enhances the accuracy and reliability of RNA quantification in high-throughput data and simplifies comparisons across diverse transcriptomic datasets, including those derived from different tissues, species, or experimental protocols.
A Distinct Autofluorescence Distribution Pattern Marks Enzymatic Deconstruction of Plant Cell Wall
Authors: Hossein Khani Solmaz , Ould Amer Khadidja , Remy Noah , Lebas Berangère , Habrant Anouck , Faraj Ali , Malandain Grégoire , Paës Gabriel , Refahi Yassin
Published: December 2024

Achieving an economically viable transformation of plant cell walls into bioproducts requires a comprehensive understanding of enzymatic deconstruction. Microscale quantitative analysis offers a relevant approach to enhance our understanding of cell wall hydrolysis, but becomes challenging under high deconstruction conditions. This study comprehensively addresses the challenges of quantifying the impact of extensive enzymatic deconstruction on plant cell wall at microscale. Investigation of highly deconstructed spruce wood provided spatial profiles of cell walls during hydrolysis with a remarkable precision. A distinct cell wall autofluorescence distribution pattern marking enzymatic hydrolysis along with an asynchronous impact of hydrolysis on cell wall structure, with cell wall volume reduction preceding cell wall accessible surface area decrease, were revealed. This study provides novel insights into enzymatic deconstruction of cell wall at under-investigated cell scale, and a robust computational pipeline applicable to diverse biomass species and pretreatment types for assessing hydrolysis impact and efficiency.
Replication of treatment effects and differences among populations during experimental evolution of sex allocation in an annual plant
Authors: Villamil Nora , Li Xinji , Pannell John R.
Published: December 2024

Variation among replicates of experimental evolution studies that begin by sampling from a single source population can be attributed to measurement error or to random differences in the environment experienced by measured individuals. On the basis of measurements in a large common garden, Cossard et al. (2021:Current Biology7, 1-7) reported rapid evolution of enhanced ‘leaky’ sex allocation by females (which produced male flowers) in experimental populations of the dioecious herbMercurialis annuafrom which males had been removed. Their study thus demonstrated the rapid dissolution of dioecy via changes in sex allocation in response to mate limitation and strong competition for siring success. But their study also found substantial variation among replicate populations. Here, we replicated their common garden, growing plants from the same populations but under different conditions and assaying the measured variables differently. The effects (significance, magnitude and direction) of selection treatment and generation on the sex expression of females with inconstant sex expression met five definitions for successful replication. Importantly, comparisons between the two studies revealed relatively consistent differences among the replicate populations, suggesting that the among-population variation reported by Cossard et al. cannot be attributed to random noise or local differences in growing conditions in the common garden. Our study represents a rare example of the replication of a common garden study and raises interesting questions about the nature of interpopulation divergence within treatment groups of studies using experimental evolution.
Dynamic cell fate plasticity and tissue integration drive functional synovial joint regeneration
Authors: Blumenkrantz Maria , Woron Felicia , Gagarin Ernesto , Weinstein Everett , Kamel Maryam H. , Campos Leonardo , Geras Agnieszka , Anderson Troy , Mo Julia , Sherwood Desmarie , Gwin Maya , Dumitrascu Bianca , Chahine Nadeen O. , Smeeton Joanna
Published: December 2024

Adult mammalian synovial joints have limited regenerative capacity, where injuries heal with mechanically inferior fibrotic tissues. Here we developed a unilateral whole-joint resection model in adult zebrafish to advance our understanding of how to stimulate regrowth of native synovial joint tissues. Using a combination of microCT, histological, live imaging, and single-cell RNA sequencing (scRNAseq) approaches after complete removal of all joint tissues, we find de novo regeneration of articular cartilage, ligament, and synovium into a functional joint. Clonal lineage tracing and scRNAseq implicate a multipotent, neural crest-derived population in the adult skeleton as a cell source for these regenerating tissues. Together, our findings reveal latent molecular and cellular programs within the adult skeleton that are deployed to regenerate a complex joint with lubricated articular cartilage.
Deep homology of abrachyuryregulatory syntax and origin of the notochord
Authors: Fan Tzu-Pei , Lee Jun-Ru , Lin Che-Yi , Chen Yi-Chih , Cutting Ann E. , Cameron R. Andrew , Yu Jr-Kai , Su Yi-Hsien
Published: December 2024

Thebrachyurygene encodes a T-box transcription factor (TF) that is crucial for the development of the notochord, a novel trait of chordates1.Brachyuryexpression in axial mesodermal cells (notochord progenitors) is regarded as a chordate innovation2, yet it remains unclear how the chordate ancestor acquired this expression domain. By examining the sequences of previously identified notochord enhancers of several chordatebrachyurygenes3–5, we uncovered a regulatory syntax consisting of binding sites for four TFs (Su(H), Foxh1, Zic, and Ets) with a strict order and orientation. We also identified this syntax, here named SFZE, in potentialcis-regulatory modules (CRMs) ofbrachyuryorthologs in various non-chordate animals and even inCapsaspora, a close unicellular relative to animals. Reporter assays demonstrated that SFZE-containing CRMs from non-chordate organisms exhibited regulatory activity in the zebrafish notochord, and mutagenesis of the TF sites reduced the activity. Furthermore, the SFZE syntax in sea urchin confers its endoderm activity, with the TF sites functionally decoupled during gastrulation. These findings indicate that the association of the SFZE syntax withbrachyuryis ancient, likely predating the origin of animals. The emergence of axialbrachyuryexpression is therefore probably not the result of a newly acquired notochord enhancer, but is instead likely attributed to co-option of upstream signals acting on the conserved SFZE syntax, which facilitates the origin of the notochord from rudimentary endodermal cells.
Heterogeneous Cluster Energetics and Nonlinear Thermodynamic Response in Supercritical Fluids
Authors: Fan Jingcun , Ly Nguyen , Ihme Matthias
Published: December 2024

Microstructural heterogeneities arising from molecular clusters directly affect the nonlinear thermodynamic properties of supercritical fluids. We present a physical model to elucidate the relation between energy exchange and heterogeneous cluster dynamics during the transition from liquidlike to gaslike conditions. By analyzing molecular-dynamics data and employing physical principles, the model considers contributions from three key processes, namely, changing cluster density, cluster separation, and transfer of molecules between clusters. We show that the proposed model is consistent with the energetics at subcritical conditions and can be used to explain the nonlinear behavior of thermodynamic response functions, including the peak in the isobaric heat capacity.

Published by the American Physical Society
2024
Waveshape of terahertz radiation produced by two-color laser-induced air plasmas
Authors: Stathopulos A. , Skupin S. , Zhou B. , Jepsen P. U. , Bergé L.
Published: December 2024

The spatial and spectral distributions of terahertz (THz) pulses emitted by two-color air plasmas are theoretically investigated for focused laser pulses and in the filamentation regime. We derive a so-called conical emission model, which, like the one proposed by You [], involves phase matching between laser harmonics along the plasma channel, the plasma density and length, and the emitted frequency as key parameters. Our augmented model, however, treats envelope effects and accounts for transverse variations of both plasma- and Kerr-driven potential THz emitters. We highlight the importance of the characteristic spatiospectral distributions of these two conversion mechanisms in the expression of the angular radiated power. The results of our model are successfully compared with data provided by a comprehensive, fully space- and time-resolved unidirectional solver. Importantly, these numerical simulations clear up the effective plasma length along which THz emission develops, compared with the dephasing length over which the laser fundamental and second harmonic shift out-of-phase. The impact of common optical aberrations, such as sphericity, astigmatism, and coma, on the THz generation is also investigated. Aberrations are shown to generally decrease the laser-to-THz conversion efficiency and potentially induce spatial asymmetries and narrowing of the THz spectra.

Published by the American Physical Society
2024
Syntheses, structures and anticancer activities of CuII and ZnII complexes containing 1,1′-[(3-fluorophenyl)methylene]bis[3-(3-fluorophenyl)imidazo[1,5-a]pyridine]
Authors: Le Thi Hong Hai , Nguyen Van Hau , Hoang Tuan Duong , Tran Quang Hung , Dang Thanh Tuan , Van Meervelt Luc
Published: December 2024

Two novel complexes, [Cu(T4)Cl2] and [Zn(T4)Cl2], were synthesized from 1,1′-[(3-fluorophenyl)methylene]bis[3-(3-fluorophenyl)imidazo[1,5-a]pyridine] (T4), and copper(II) and zinc(II) chloride, respectively. The structures of these complexes were confirmed using ESI-MS, IR and 1H NMR spectra. The results reveal mononuclear structures in which the central metal atoms are coordinated by two N atoms from the imidazole rings and two Cl ligands. The structure of the CuT4 complex [systematic name: dichlorido{1,1′-[(3-fluorophenyl)methylene]bis[3-(3-fluorophenyl)imidazo[1,5-a]pyridine]-κ2
N,N′}copper(II), [CuCl2(C33H21F3N4)], was confirmed by single-crystal X-ray diffraction. The CuII atom adopts a distorted tetrahedral coordination environment with an N2Cl2 coordination set. The predominant features of the crystal packing are C—H...F, C—H...π and C—F...π interactions. Biological evaluations demonstrated that both complexes exhibit enhanced anticancer activity compared to the free ligand, with IC50 values ranging between 18.93 and 67.06 µM. Notably, the CuII complex displays excellent inhibitory activity against the MCF7 breast cancer cell line (IC50 = 27.99 µM), approximately twice as effective as cisplatin. Conversely, the ZnT4 complex shows greater efficacy against Hep-G2 and A549 lung cancer cell lines, with IC50 values between 18.93 and 24.83 µM. The results suggest that CuII and ZnII complexes of T4 show potential as cancer treatment agents.
Social constructs, male prejudices, tradition and culture: are these undermining female-headed farming households’ fundamental right to food security?
Authors: Reddy Mahendra
Published: December 2024

Purpose

Amidst a substantial body of research investigating gender discrimination within formal employment sectors, this study concentrates on a critical yet frequently overlooked dimension: the non-formal agriculture sector. It aims to elucidate how prevailing male prejudices and entrenched social constructs systematically disadvantage female household heads in their quest for household food security.

Design/methodology/approach

This study investigates food security status and statistical disparities between female-headed and male-headed households utilizing data from 63,601 farming households. By identifying the factors contributing to gender-based discrimination, we empirically evaluate their impact on households’ food security by applying the discrete choice ordered logit model.

Findings

The results demonstrate significantly higher levels of food insecurity among female-headed households than their male counterparts (p < 0.05). It empirically establishes that factors contributing to discrimination adversely affect female farmers’ ability to secure food. These factors include challenges in accessing markets, smaller farm sizes and receiving less government assistance than male farmers.

Originality/value

While previous studies have acknowledged gender discrimination, this research is the first to systematically demonstrate how various factors directly impact food security in female-headed households in Fiji, thereby addressing a critical gap in the literature. Focusing specifically on the intersection of gender discrimination and food security, this study provides robust empirical evidence of the profound influence of gender discrimination and male biases on the food security of these households, thereby making a significant and original contribution to the field and underlining the importance of this research.
Distinctive capabilities system in MSME’s business model adaptation: evidence of the moderating and mediating effect of adaptive capability
Authors: Arraya Marco
Published: December 2024

Purpose

This study aims to enhance the understanding of adaptive capability (ADC) as a moderating and mediating factor in the relationship between a distinctive capabilities system (DCS) and the nonfinancial and financial performance of Portuguese micro-, small- and medium-sized enterprises (MSMEs) within the context of business model adaptation in response to exogenous shocks.

Design/methodology/approach

In this study, I utilized an exploratory and quantitative methodology. Moreover, I administered a structured questionnaire to collect data from 223 Portuguese MSME respondents. To ensure the variables’ validity and reliability, I conducted a confirmatory factor analysis and employed structural equation modeling to test the proposed hypotheses.

Findings

The results demonstrate a significant direct impact of DCS on both nonfinancial and financial performance, with the former mediated by ADC. These findings suggest that MSME management practices during an exogenous shock have the potential to generate superior performance by reconfiguring DCS with ADC support. This enables MSMEs to leverage existing resources and capabilities to continuously improve and adapt their business models, defend their market share and adjust their exploitation and exploration strategies in response to exogenous shocks. Moreover, the development of proactive managerial capabilities can contribute to this combination of factors and potentially lead to superior MSME performance.

Originality/value

Literature lacks studies on strategy and management regarding the role of DCS as a predictor of MSME’s business model adaptation and the mediating effect of ADC in this relationship. The current study sought to address this deficiency by investigating the crucial role of ADC in facilitating the reconfiguration, renewal or creation of resources, capabilities, processes and routines that foster adaptation while confirming DCS’s role as a critical component of the business model. My research extends and builds on earlier findings by demonstrating how these capabilities enable MSMEs to respond effectively to exogenous shocks while maintaining their superior performance.