J R Soc Interface. 2024 May;21(214):20240108. doi: 10.1098/rsif.2024.0108. Epub 2024 May 29.

ABSTRACT

Cimicidae are well-known for traumatic insemination, and males pierce females with their parameres and transfer sperm through them. The shape of parameres is relatively stable in the family, but in some genera, the paramere is elongated, appearing less resistant against lateral deflection. To understand the mechanical limitations of the paramere, we studied its penetration mechanics of the common bed bug, Cimex lectularius. We examined the post-abdominal morphology, paramere geometry and material properties and conducted breaking stress experiments on the paramere under wet and dry conditions. Mechanical property gradients are present with the paramere tip as the stiffest region and the base as the most flexible one. These mechanical properties relate to the presence of Ca, Zn and Si. The basal wing-shaped structure is flexible, enabling it to interlock with the anal region during mating. The paramere is slightly twisted; the tip region is circular in cross-section, and the geometry of the rest is rather complex. In the mechanical tests, wet parameres mainly buckled, while dried parameres broke off. The level of structural failures depended on directions from which the compression forces were applied. Structural, material and mechanical strengthening mechanisms preventing the paramere from mechanical failure are discussed.

PMID:38807525 | DOI:10.1098/rsif.2024.0108

Anal Chem. 2024 May 29. doi: 10.1021/acs.analchem.4c02035. Online ahead of print.

ABSTRACT

Can reversed-phase peptide retention be the same for C8 and C18 columns? or increase for otherwise identical columns with a smaller surface area? Can replacing trifluoroacetic acid (TFA) with formic acid (FA) improve the peak shape? According to our common understanding of peptide chromatography, absolutely not. Surprisingly, a thorough comparison of the peptide separation selectivity of 100 and 120 Å fully porous C18 sorbents to maximize the performance of our in-house proteomics LC-MS/MS setup revealed an unexpectedly higher peptide retentivity for a wider pore packing material, despite it having a smaller surface area. Concurrently, the observed increase in peptide retention─which drives variation in separation selectivity between 100 and 120 Å pore size materials─was more pronounced for smaller peptides. These findings contradict the central dogmas that underlie the development of all peptide RP-HPLC applications: (i) a larger surface area leads to higher retention and (ii) increasing the pore size should benefit the retention of larger analytes. Based on our intriguing findings, we compared reversed-phase high-performance liquid chromatography peptide retention for a total of 20 columns with pore sizes between 60 and 300 Å using FA- and TFA-based eluents. Our results unequivocally attest that the larger size of ion pairs in FA- vs TFA-based eluents leads to the observed impact on selectivity and peptide retention. For FA, peptide retention peaks at 200 Å pore size, compared to between 120 and 200 Å for TFA. However, the decrease in retention for narrow-pore particles is more profound in FA. Our findings suggest that common assumptions about analyte size and accessible surface area should be revisited for ion-pair RP separation of small peptides, typical for proteomic applications that are predominantly applying FA eluents. Hybrid silica-based materials with pore sizes of 130-200 Å should be specifically targeted for bottom-up proteomic applications to obtain both superior peak shape and peptide retentivity. This challenging task of attaining the best RPLC column for proteomics calls for closer collaboration between LC column manufacturers and proteomic LC specialists.

PMID:38807522 | DOI:10.1021/acs.analchem.4c02035

Nucleic Acids Res. 2024 May 29:gkae374. doi: 10.1093/nar/gkae374. Online ahead of print.

ABSTRACT

Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, replicates using seven essential proteins encoded by its genome. Among these, the UL30 DNA polymerase, complexed with the UL42 processivity factor, orchestrates leading and lagging strand replication of the 152 kb viral genome. UL30 polymerase is a prime target for antiviral therapy, and resistance to current drugs can arise in immunocompromised individuals. Using electron cryo-microscopy (cryo-EM), we unveil the dynamic changes of the UL30/UL42 complex with DNA in three distinct states. First, a pre-translocation state with an open fingers domain ready for nucleotide incorporation. Second, a halted elongation state where the fingers close, trapping dATP in the dNTP pocket. Third, a DNA-editing state involving significant conformational changes to allow DNA realignment for exonuclease activity. Additionally, the flexible UL30 C-terminal domain interacts with UL42, forming an extended positively charged surface binding to DNA, thereby enhancing processive synthesis. These findings highlight substantial structural shifts in the polymerase and its DNA interactions during replication, offering insights for future antiviral drug development.

PMID:38806233 | DOI:10.1093/nar/gkae374

Bioinformatics. 2024 May 28:btae339. doi: 10.1093/bioinformatics/btae339. Online ahead of print.

ABSTRACT

MOTIVATION: Recent advances in spatial transcriptomics allow spatially resolved gene expression measurements with cellular or even sub-cellular resolution, directly characterizing the complex spatiotemporal gene expression landscape and cell-to-cell interactions in their native microenvironments. Due to technology limitations, most spatial transcriptomic technologies still yield incomplete expression measurements with excessive missing values. Therefore, gene imputation is critical to filling in missing data, enhancing resolution, and improving overall interpretability. However, existing methods either require additional matched single-cell RNA-seq data, which is rarely available, or ignore spatial proximity or expression similarity information.

RESULTS: To address these issues, we introduce Impeller, a path-based heterogeneous graph learning method for spatial transcriptomic data imputation. Impeller has two unique characteristics distinct from existing approaches. First, it builds a heterogeneous graph with two types of edges representing spatial proximity and expression similarity. Therefore, Impeller can simultaneously model smooth gene expression changes across spatial dimensions and capture similar gene expression signatures of faraway cells from the same type. Moreover, Impeller incorporates both short- and long-range cell-to-cell interactions (e.g., via paracrine and endocrine) by stacking multiple GNN layers. We use a learnable path operator in Impeller to avoid the over-smoothing issue of the traditional Laplacian matrices. Extensive experiments on diverse datasets from three popular platforms and two species demonstrate the superiority of Impeller over various state-of-the-art imputation methods.

AVAILABILITY AND IMPLEMENTATION: The code and preprocessed data used in this study are available at https://github.com/aicb-ZhangLabs/Impeller and https://zenodo.org/records/11212604.

SUPPLEMENTARY INFORMATION: Additional information is shown in the supplementary file.

PMID:38806165 | DOI:10.1093/bioinformatics/btae339

Neurobiol Dis. 2024 May 26:106541. doi: 10.1016/j.nbd.2024.106541. Online ahead of print.

ABSTRACT

The field of metabolomics examines the overall composition and dynamic patterns of metabolites in living organisms. The primary methods used in metabolomics include liquid chromatography (LC), nuclear magnetic resonance (NMR), and mass spectrometry (MS) analysis. These methods enable the identification and examination of metabolite types and contents within organisms, as well as modifications to metabolic pathways and their connection to the emergence of diseases. Research in metabolomics has extensive value in basic and applied sciences. The field of metabolomics is growing quickly, with the majority of studies concentrating on biomedicine, particularly early disease diagnosis, therapeutic management of human diseases, and mechanistic knowledge of biochemical processes. Multiscale metabolomics is an approach that integrates metabolomics techniques at various scales, including the holistic, tissue, cellular, and organelle scales, to enable more thorough and in-depth studies of metabolic processes in organisms. Multiscale metabolomics can be combined with methods from systems biology and bioinformatics. In recent years, multiscale metabolomics approaches have become increasingly important in neuroscience research due to the nervous system's high metabolic demands. Multiscale metabolomics can offer novel concepts and approaches for the diagnosis, treatment, and development of medication for neurological illnesses in addition to a more thorough understanding of brain metabolism and nervous system function. In this review, we summarize the use of multiscale metabolomics techniques in neuroscience, address the promise and constraints of these techniques, and provide an overview of the metabolome and its applications in neuroscience.

PMID:38806132 | DOI:10.1016/j.nbd.2024.106541

Microbiol Res. 2024 May 15;285:127763. doi: 10.1016/j.micres.2024.127763. Online ahead of print.

ABSTRACT

Soil desertification poses a critical ecological challenge in arid and semiarid climates worldwide, leading to decreased soil productivity due to the disruption of essential microbial community processes. Fungi, as one of the most important soil microbial communities, play a crucial role in enhancing nutrient and water uptake by plants through mycorrhizal associations. However, the impact of overgrazing-induced desertification on fungal community structure, particularly in the Caatinga biome of semiarid regions, remains unclear. In this study, we assessed the changes in both the total fungal community and the arbuscular mycorrhizal fungal community (AMF) across 1. Natural vegetation (native), 2. Grazing exclusion (20 years) (restored), and 3. affected by overgrazing-induced degradation (degraded) scenarios. Our assessment, conducted during both the dry and rainy seasons in Irauçuba, Ceará, utilized Internal Transcribed Spacer (ITS) gene sequencing via Illumina® platform. Our findings highlighted the significant roles of the AMF families Glomeraceae (∼71% of the total sequences) and Acaulosporaceae (∼14% of the total sequences) as potential key taxa in mitigating climate change within dryland areas. Moreover, we identified the orders Pleosporales (∼35% of the total sequences) and Capnodiales (∼21% of the total sequences) as the most abundant soil fungal communities in the Caatinga biome. The structure of the total fungal community differed when comparing native and restored areas to degraded areas. Total fungal communities from native and restored areas clustered together, suggesting that grazing exclusion has the potential to improve soil properties and recover fungal community structure amid global climate change challenges.

PMID:38805979 | DOI:10.1016/j.micres.2024.127763

Talanta. 2024 May 27;277:126252. doi: 10.1016/j.talanta.2024.126252. Online ahead of print.

ABSTRACT

COVID-19 as an infectious disease with rapid transmission speed is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), so, early and accurate diagnostics of COVID-19 is quite challenging. In this work, the selective and sensitive self-enhanced ECL method to detect of SARS-CoV-2 protein was designed with magnetic N-doped carbon derived from dual-ligand metal-organic frameworks (MOF) (CoO@N-C) with the primary and tertiary amino groups as a novel coreactant that covalently combined with Ru(bpy)2(phen-NH2)2+ as electrochemiluminescence (ECL) emitter. Mixed-ligand strategy and selected nitrogen-containing ligands, 4,4',4''-((1,3,5-triazine-2,4,6-triyl) tris-(azanediyl)) tribenzoic acid (H3TATAB) with 2-aminoterephthalic acid (BDC-NH2) were used for synthesis of the proposed MOF. Also, magnetic CoO@N-C with high synergistically charge transfer kinetics and good stability can be used as an effective platform/coreactor on the ITO electrode which load more Ru-complex as signal producing compound and SARS-CoV-2 N protein antibody to increase the sensitivity of the immunosensor. Furthermore, (CoO@N-C) as coreactor improved the ECL signal of the Ru (II)-complex more than 2.1 folds compared to tripropylamine. In view of these competences, the novel "on-off" ECL biosensor performed with great stability and repeatability for detection of SARS-CoV-2 protein, which exhibited a broad linearity from 8 fg. mL-1 to 4 ng. mL-1 (6 order of magnitude) and an ultra-low limit of detection 1.6 fg. mL-1. Finally, this proposed method was successfully applied to detect of SARS-CoV-2 N protein in serum sample with satisfactory results, indicating the proposed immunosensor has the potential for quick analysis of SARS-CoV-2.

PMID:38805948 | DOI:10.1016/j.talanta.2024.126252

Biotechnol Biofuels Bioprod. 2024 May 28;17(1):70. doi: 10.1186/s13068-024-02506-4.

ABSTRACT

BACKGROUND: Aspergillus tubingensis is a citric acid-producing fungus that can utilize sugars in hydrolysate of lignocellulosic biomass such as sugarcane bagasse and, unlike A. niger, does not produce mycotoxins. To date, no attempt has been made to model its metabolism at genome scale.

RESULTS: Here, we utilized the whole-genome sequence (34.96 Mb length) and the measured biomass composition to reconstruct a genome-scale metabolic model (GSMM) of A. tubingensis DJU120 strain. The model, named iMK1652, consists of 1652 genes, 1657 metabolites and 2039 reactions distributed over four cellular compartments. The model has been extensively curated manually. This included removal of dead-end metabolites and generic reactions, addition of secondary metabolite pathways and several transporters. Several mycotoxin synthesis pathways were either absent or incomplete in the genome, providing a genomic basis for the non-toxinogenic nature of this species. The model was further refined based on the experimental phenotypic microarray (Biolog) data. The model closely captured DJU120 fermentative data on glucose, xylose, and phosphate consumption, as well as citric acid and biomass production, showing its applicability to capture citric acid fermentation of lignocellulosic biomass hydrolysate.

CONCLUSIONS: The model offers a framework to conduct metabolic systems biology investigations and can act as a scaffold for integrative modelling of A. tubingensis.

PMID:38807234 | DOI:10.1186/s13068-024-02506-4

Nat Genet. 2024 May 28. doi: 10.1038/s41588-024-01754-2. Online ahead of print.

ABSTRACT

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues.

PMID:38806714 | DOI:10.1038/s41588-024-01754-2

Nat Immunol. 2024 May 28. doi: 10.1038/s41590-024-01857-2. Online ahead of print.

ABSTRACT

Inflammatory pain results from the heightened sensitivity and reduced threshold of nociceptor sensory neurons due to exposure to inflammatory mediators. However, the cellular and transcriptional diversity of immune cell and sensory neuron types makes it challenging to decipher the immune mechanisms underlying pain. Here we used single-cell transcriptomics to determine the immune gene signatures associated with pain development in three skin inflammatory pain models in mice: zymosan injection, skin incision and ultraviolet burn. We found that macrophage and neutrophil recruitment closely mirrored the kinetics of pain development and identified cell-type-specific transcriptional programs associated with pain and its resolution. Using a comprehensive list of potential interactions mediated by receptors, ligands, ion channels and metabolites to generate injury-specific neuroimmune interactomes, we also uncovered that thrombospondin-1 upregulated by immune cells upon injury inhibited nociceptor sensitization. This study lays the groundwork for identifying the neuroimmune axes that modulate pain in diverse disease contexts.

PMID:38806708 | DOI:10.1038/s41590-024-01857-2

Cell Death Dis. 2024 May 28;15(5):369. doi: 10.1038/s41419-024-06749-9.

ABSTRACT

Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in patients with acute myeloid leukemia (AML). STAT3 exists in two distinct alternatively spliced isoforms, the full-length isoform STAT3α and the C-terminally truncated isoform STAT3β. While STAT3α is predominantly described as an oncogenic driver, STAT3β has been suggested to act as a tumor suppressor. To elucidate the role of STAT3β in AML, we established a mouse model of STAT3β-deficient, MLL-AF9-driven AML. STAT3β deficiency significantly shortened survival of leukemic mice confirming its role as a tumor suppressor. Furthermore, RNA sequencing revealed enhanced STAT1 expression and interferon (IFN) signaling upon loss of STAT3β. Accordingly, STAT3β-deficient leukemia cells displayed enhanced sensitivity to blockade of IFN signaling through both an IFNAR1 blocking antibody and the JAK1/2 inhibitor Ruxolitinib. Analysis of human AML patient samples confirmed that elevated expression of IFN-inducible genes correlated with poor overall survival and low STAT3β expression. Together, our data corroborate the tumor suppressive role of STAT3β in a mouse model in vivo. Moreover, they provide evidence that its tumor suppressive function is linked to repression of the STAT1-mediated IFN response. These findings suggest that the STAT3β/α mRNA ratio is a significant prognostic marker in AML and holds crucial information for targeted treatment approaches. Patients displaying a low STAT3β/α mRNA ratio and unfavorable prognosis could benefit from therapeutic interventions directed at STAT1/IFN signaling.

PMID:38806478 | DOI:10.1038/s41419-024-06749-9

BMJ Open. 2024 May 28;14(5):e083085. doi: 10.1136/bmjopen-2023-083085.

ABSTRACT

OBJECTIVE: People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition.

DESIGN: An assessor-blind, two-armed, parallel-design randomised controlled clinical trial.

SETTING: Secondary care clinics in Iran.

PARTICIPANTS: 60 men with breathlessness due to respiratory disease caused by documented mustard gas exposure, mean (SD) age 52.7 (4.36) years, MRC dyspnoea score 3.5 (0.7), St. George's Respiratory Questionnaire (SGRQ) 72.3 (15.2).

INTERVENTIONS: Participants were allocated either to a 6-week course of thrice-weekly PR (n=31) or to usual care (n=29), with 6-week data for 28 and 26, respectively.

OUTCOME MEASURES: Primary endpoint was change in cycle endurance time at 70% baseline exercise capacity at 6 weeks. Secondary endpoints included 6 min walk distance, quadriceps strength and bulk, body composition and health status. For logistical reasons, blood tests that had been originally planned were not performed and 12-month follow-up was available for only a small proportion.

RESULTS: At 6 weeks, cycle endurance time increased from 377 (140) s to 787 (343) s with PR vs 495 (171) s to 479 (159) s for usual care, effect size +383 (231) s (p<0.001). PR also improved 6 min walk distance+103.2 m (63.6-142.9) (p<0.001), MRC dyspnoea score -0.36 (-0.65 to -0.07) (p=0.016) and quality of life; SGRQ -8.43 (-13.38 to -3.48) p<0.001, as well as quadriceps strength+9.28 Nm (1.89 to 16.66) p=0.015.

CONCLUSION: These data suggest that PR can improve exercise capacity and quality of life in people with breathlessness due to mustard gas lung disease and support the wider provision of this form of care.

TRIAL REGISTRATION NUMBER: IRCT2016051127848N1.

PMID:38806414 | DOI:10.1136/bmjopen-2023-083085

G3 (Bethesda). 2024 May 28:jkae098. doi: 10.1093/g3journal/jkae098. Online ahead of print.

ABSTRACT

Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Feijoa is a rich source of bioactive compounds with anticancer, anti-inflammatory, antibacterial and antifungal activities; however, the mechanism of action of these compounds are largely not known. Here we used chemical genetic analyses in the model organism Saccharomyces cerevisiae to investigate the mechanism of action of a feijoa-derived ethanol adduct of vescalagin (EtOH-vescalagin). Genome-wide barcode sequencing (Bar-seq) analysis revealed yeast strains lacking genes in iron metabolism, zinc metabolism, retromer function or mitochondrial function were hypersensitive to 0.3 µM EtOH-vescalagin. This treatment increased expression of iron uptake proteins at the plasma membrane, which was a compensatory response to reduced intracellular iron. Likewise, EtOH-vescalagin increased expression of the Cot1 protein in the vacuolar membrane that transports zinc into the vacuole to prevent cytoplasmic accumulation of zinc. Each individual subunit in the retromer complex was required for the iron homeostatic mechanism of EtOH-vescalagin, while only the cargo recognition component in the retromer complex was required for the zinc homeostatic mechanism. Overexpression of either retromer subunits or high-affinity iron transporters suppressed EtOH-vescalagin bioactivity in a zinc-replete condition, while overexpression of only retromer subunits increased EtOH-vescalagin bioactivity in a zinc-deficient condition. Together, these results indicate that EtOH-vescalagin bioactivity begins with extracellular iron chelation and proceeds with intracellular transport of zinc via the retromer complex. More broadly, this is the first report of a bioactive compound to further characterize the poorly understood interaction between zinc metabolism and retromer function.

PMID:38805688 | DOI:10.1093/g3journal/jkae098

PLoS Comput Biol. 2024 May 28;20(5):e1012146. doi: 10.1371/journal.pcbi.1012146. Online ahead of print.

ABSTRACT

Exposure to environmental stressors, including certain antibiotics, induces stress responses in bacteria. Some of these responses increase mutagenesis and thus potentially accelerate resistance evolution. Many studies report increased mutation rates under stress, often using the standard experimental approach of fluctuation assays. However, single-cell studies have revealed that many stress responses are heterogeneously expressed in bacterial populations, which existing estimation methods have not yet addressed. We develop a population dynamic model that considers heterogeneous stress responses (subpopulations of cells with the response off or on) that impact both mutation rate and cell division rate, inspired by the DNA-damage response in Escherichia coli (SOS response). We derive the mutant count distribution arising in fluctuation assays under this model and then implement maximum likelihood estimation of the mutation-rate increase specifically associated with the expression of the stress response. Using simulated mutant count data, we show that our inference method allows for accurate and precise estimation of the mutation-rate increase, provided that this increase is sufficiently large and the induction of the response also reduces the division rate. Moreover, we find that in many cases, either heterogeneity in stress responses or mutant fitness costs could explain similar patterns in fluctuation assay data, suggesting that separate experiments would be required to identify the true underlying process. In cases where stress responses and mutation rates are heterogeneous, current methods still correctly infer the effective increase in population mean mutation rate, but we provide a novel method to infer distinct stress-induced mutation rates, which could be important for parameterising evolutionary models.

PMID:38805543 | DOI:10.1371/journal.pcbi.1012146

Acta Crystallogr D Struct Biol. 2024 Jun 1. doi: 10.1107/S2059798324004303. Online ahead of print.

ABSTRACT

The detection of specific biological macromolecules in cryogenic electron tomography data is frequently approached by applying cross-correlation-based 3D template matching. To reduce computational cost and noise, high binning is used to aggregate voxels before template matching. This remains a prevalent practice in both practical applications and methods development. Here, the relation between template size, shape and angular sampling is systematically evaluated to identify ribosomes in a ground-truth annotated data set. It is shown that at the commonly used binning, a detailed subtomogram average, a sphere and a heart emoji result in near-identical performance. These findings indicate that with current template-matching practices macromolecules can only be detected with high precision if their shape and size are sufficiently different from the background. Using theoretical considerations, the experimental results are rationalized and it is discussed why primarily low-frequency information remains at high binning and that template matching fails to be accurate because similarly shaped and sized macromolecules have similar low-frequency spectra. These challenges are discussed and potential enhancements for future template-matching methodologies are proposed.

PMID:38805246 | DOI:10.1107/S2059798324004303

ACS Chem Neurosci. 2024 May 28. doi: 10.1021/acschemneuro.4c00149. Online ahead of print.

ABSTRACT

Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channel receptors that contribute to cognition, memory, and motor control in many organisms. The pharmacological targeting of these receptors, using small molecules or peptides, presents an important strategy for the development of drugs that can treat important human diseases, including neurodegenerative disorders. The Aplysia californica acetylcholine binding protein (Ac-AChBP) is a structural surrogate of the nAChR with high homology to the extracellular ligand binding domain of homopentameric nAChRs. In this study, we optimized protein-painting-based mass spectrometry to identify regions of interaction between the Ac-AChBP and several nAChR ligands. Using molecular dyes that adhere to the surface of a solubilized Ac-AChBP complex, we identified amino acid residues that constitute a contact site within the Ac-AChBP for α-bungarotoxin, choline, nicotine, and amyloid-β 1-42. By integrating innovation in protein painting mass spectrometry with computational structural modeling, we present a new experimental tool for analyzing protein interactions of the nAChR.

PMID:38804618 | DOI:10.1021/acschemneuro.4c00149

Elife. 2024 May 28;12:RP84855. doi: 10.7554/eLife.84855.

ABSTRACT

Science journalism is a critical way for the public to learn about and benefit from scientific findings. Such journalism shapes the public's view of the current state of science and legitimizes experts. Journalists can only cite and quote a limited number of sources, who they may discover in their research, including recommendations by other scientists. Biases in either process may influence who is identified and ultimately included as a source. To examine potential biases in science journalism, we analyzed 22,001 non-research articles published by Nature and compared these with Nature-published research articles with respect to predicted gender and name origin. We extracted cited authors' names and those of quoted speakers. While citations and quotations within a piece do not reflect the entire information-gathering process, they can provide insight into the demographics of visible sources. We then predicted gender and name origin of the cited authors and speakers. We compared articles with a comparator set made up of first and last authors within primary research articles in Nature and a subset of Springer Nature articles in the same time period. In our analysis, we found a skew toward quoting men in Nature science journalism. However, quotation is trending toward equal representation at a faster rate than authorship rates in academic publishing. Gender disparity in Nature quotes was dependent on the article type. We found a significant over-representation of names with predicted Celtic/English origin and under-representation of names with a predicted East Asian origin in both in extracted quotes and journal citations but dampened in citations.

PMID:38804191 | DOI:10.7554/eLife.84855

Lab Chip. 2024 May 28. doi: 10.1039/d4lc00197d. Online ahead of print.

ABSTRACT

Despite recent advances in cancer treatment, refining therapeutic agents remains a critical task for oncologists. Precise evaluation of drug effectiveness necessitates the use of 3D cell culture instead of traditional 2D monolayers. Microfluidic platforms have enabled high-throughput drug screening with 3D models, but current viability assays for 3D cancer spheroids have limitations in reliability and cytotoxicity. This study introduces a deep learning model for non-destructive, label-free viability estimation based on phase-contrast images, providing a cost-effective, high-throughput solution for continuous spheroid monitoring in microfluidics. Microfluidic technology facilitated the creation of a high-throughput cancer spheroid platform with approximately 12 000 spheroids per chip for drug screening. Validation involved tests with eight conventional chemotherapeutic drugs, revealing a strong correlation between viability assessed via LIVE/DEAD staining and phase-contrast morphology. Extending the model's application to novel compounds and cell lines not in the training dataset yielded promising results, implying the potential for a universal viability estimation model. Experiments with an alternative microscopy setup supported the model's transferability across different laboratories. Using this method, we also tracked the dynamic changes in spheroid viability during the course of drug administration. In summary, this research integrates a robust platform with high-throughput microfluidic cancer spheroid assays and deep learning-based viability estimation, with broad applicability to various cell lines, compounds, and research settings.

PMID:38804084 | DOI:10.1039/d4lc00197d

J Am Chem Soc. 2024 May 27. doi: 10.1021/jacs.4c03148. Online ahead of print.

ABSTRACT

The construction of DNA origami nanostructures is heavily dependent on the folding of the scaffold strand, which is typically a single-stranded DNA genome extracted from a bacteriophage (M13). Custom scaffolds can be prepared in a number of methods, but they are not widely accessible to a broad user base in the DNA nanotechnology community. Here, we explored new design and construction possibilities with custom scaffolds prepared in our cost- and time-efficient production pipeline. According to the pipeline, we de novo produced a variety of scaffolds of specified local and global sequence characteristics and consequent origami constructs of modular arrangement in morphologies and functionalities. Taking advantage of this strategy of template-free scaffold production, we also designed and produced three-letter-coded scaffolds that can fold into designated morphologies rapidly at room temperature. The expanded design and construction freedom immediately brings in many new research opportunities and invites many more on the horizon.

PMID:38803270 | DOI:10.1021/jacs.4c03148

New Phytol. 2024 May 27. doi: 10.1111/nph.19855. Online ahead of print.

ABSTRACT

Forests make immense contributions to societies in the form of ecological services and sustainable industrial products. However, they face major challenges to their viability and economic use due to climate change and growing biotic and economic threats, for which recombinant DNA (rDNA) technology can sometimes provide solutions. But the application of rDNA technologies to forest trees faces major social and biological obstacles that make its societal acceptance a 'wicked' problem without straightforward solutions. We discuss the nature of these problems, and the social and biological innovations that we consider essential for progress. As case studies of biological challenges, we focus on studies of modifications in wood chemistry and transformation efficiency. We call for major innovations in regulations, and the dissolution of method-based market barriers, that together could lead to greater research investments, enable wide use of field studies, and facilitate the integration of rDNA-modified trees into conventional breeding programs. Without near-term adoption of such innovations, rDNA-based solutions will be largely unavailable to help forests adapt to the growing stresses from climate change and the proliferation of forest pests, nor will they be available to provide economic and environmental benefits from expanded use of wood and related bioproducts as part of an expanding bioeconomy.

PMID:38803120 | DOI:10.1111/nph.19855