Plant J. 2025 Mar;121(6):e70061. doi: 10.1111/tpj.70061.

ABSTRACT

Diatoms are prominent microalgae found in all aquatic environments. Over the last 20 years, thanks to the availability of genomic and genetic resources, diatom species such as Phaeodactylum tricornutum and Thalassiosira pseudonana have emerged as valuable experimental model systems for exploring topics ranging from evolution to cell biology, (eco)physiology, and biotechnology. Since the first genome sequencing projects initiated more than 20 years ago, numerous genome-enabled datasets have been generated, based on RNA-Seq and proteomics experiments, epigenomes, and ecotype variant analysis. Unfortunately, these resources, generated by various laboratories, are often in disparate formats and challenging to access and analyze. Here we present DiatOmicBase, a genome portal gathering comprehensive omics resources from P. tricornutum and T. pseudonana to facilitate the exploration of dispersed public datasets and the design of new experiments based on the prior-art. DiatOmicBase provides gene annotations, transcriptomic profiles and a genome browser with ecotype variants, histone and methylation marks, transposable elements, non-coding RNAs, and read densities from RNA-Seq experiments. We developed a semi-automatically updated transcriptomic module to explore both publicly available RNA-Seq experiments and users' private datasets. Using gene-level expression data, users can perform exploratory data analysis, differential expression, pathway analysis, biclustering, and co-expression network analysis. Users can create heatmaps to visualize pre-computed comparisons for selected gene subsets. Automatic access to other bioinformatic resources and tools for diatom comparative and functional genomics is also provided. Focusing on the resources currently centralized for P. tricornutum, we showcase several examples of how DiatOmicBase strengthens molecular research on diatoms, making these organisms accessible to a broad research community.

PMID:40089834 | DOI:10.1111/tpj.70061

BMC Infect Dis. 2025 Mar 15;25(1):363. doi: 10.1186/s12879-025-10712-0.

ABSTRACT

BACKGROUND: Mycoplasma pneumoniae (MP) is a common bacterial respiratory infection that can cause pneumonia, particularly in children. Previously published data have highlighted the high incidence of viral co-infections and the problem of increasing macrolide resistance in MP worldwide.

AIMS: (1) to estimate the impact of viral infections circulating in a local population on the spectrum of co-infection in hospitalized children with Mycoplasma pneumoniae pneumonia (MPP), (2) to determine if there are differences in resistance mutation rate for samples from hospitals of Russia located in the European and Far East, (3) to describe genomic characteristics of MP from Russian patients during the MPP outbreaks in the fall-winter of 2023-2024.

METHODS: The carriage of viral pathogens was analyzed by real-time PCR in children with MPP from the European Part and Far East of Russian Federation and compared with the infections from two control groups. The V region of the 23S gene and the quinolone resistance-determining regions (QRDRs) of the parC and gyrA genes were sequenced to detect resistance-associated mutations in MP. Whole-genome sequencing method was used to determine the genetic relationship of a Russian MP isolate with known MP isolates.

RESULTS: The 62% of patients with MPP had a viral co-infection, with HPIV and SARS-CoV-2 predominating at 47% and 12.4%, respectively. The 15% of patients were infected with two or more viruses. In the control groups, 21% of healthy children and 43% of healthy adults were infected with Coronaviruses and Human Parainfluenza Viruses (HPIV-3 and -4), respectively. The 2063 A/G mutation of the 23S gene was found in 40.8% of patients from European Russia and in 35.7% of patients from the Far East. The result of core genes demonstrates that the sequence obtained from Russia clusters with sequences from clade 1.

CONCLUSIONS: Both HPIV and SARS-CoV-2 circulated in the population among healthy children and adults in December 2023 and they also were predominated in children with MPP. The rate of macrolide resistance was ⁓40%, which is higher than in European countries and significantly lower than in patients from Asian countries. Phylogenetic analysis showed the MP genome form Russia related to P1 type 1 (clade 1).

PMID:40089690 | DOI:10.1186/s12879-025-10712-0

Oncogene. 2025 Mar 16. doi: 10.1038/s41388-025-03337-9. Online ahead of print.

ABSTRACT

Chemoresistance poses a significant challenge in colorectal cancer (CRC) treatment. However, the mechanisms underlying chemoresistance remain unclear. CBX3 promoted proliferation and metastasis in CRC. However, the role and mechanism of CBX3 in chemoresistance remain unknown. Therefore, we aimed to investigate the effects and mechanisms of CBX3 on multidrug resistance in CRC. Our studies showed that higher levels of CBX3 expression were associated with poor survival, especially in groups with progression following chemotherapy. CBX3 overexpression increased Irinotecan and Oxaliplatin resistance, whereas CBX3 knockdown suppressed multidrug resistance in CRC cells. Additionally, CBX3 inhibited ferroptosis associated with multidrug resistance, and the ferroptosis activators prevented CBX3 overexpression-mediated cell survival. RNA sequencing revealed that the NRF2-signaling pathway was involved in this process. CBX3-upregulated NRF2 protein expression by directly binding to the promoter of Cullin3 (CUL3) to suppress CUL3 transcription and CUL3-mediated NRF2 degradation. Moreover, Glutathione Peroxidase 2 (GPX2) was downstream of the CBX3-NRF2 pathway in CRC chemoresistance. ML385, an NRF2 inhibitor, suppressed GPX2 expression, and increased ferroptosis in PDX models. Our study identified CBX3/NRF2/GPX2 axis may be a novel signaling pathway that mediates multidrug resistance in CRC. This study proposes developing novel strategies for cancer treatment to overcome drug resistance in the future.

PMID:40089640 | DOI:10.1038/s41388-025-03337-9

Bioinformatics. 2025 Mar 14:btaf115. doi: 10.1093/bioinformatics/btaf115. Online ahead of print.

ABSTRACT

SUMMARY: AlphaPulldown2 streamlines protein structural modeling by automating workflows, improving code adaptability, and optimizing data management for large-scale applications. It introduces an automated Snakemake pipeline, compressed data storage, support for additional modeling backends like UniFold and AlphaLink2, and a range of other improvements. These upgrades make AlphaPulldown2 a versatile platform for predicting both binary interactions and complex multi-unit assemblies.

AVAILABILITY AND IMPLEMENTATION: AlphaPulldown2 is freely available at https://github.com/KosinskiLab/AlphaPulldown.

SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.

PMID:40088942 | DOI:10.1093/bioinformatics/btaf115

Comput Biol Med. 2025 Mar 14;189:110021. doi: 10.1016/j.compbiomed.2025.110021. Online ahead of print.

ABSTRACT

Regulatory T cells (Tregs) are critical for maintaining the stability of the immune system and facilitating tumor escape through various mechanisms. Resting T cells are involved in cell-mediated immunity and remain in a resting state until stimulated, while effector T cells promote immune responses. Here, we investigated the roles of two gene signatures, one for resting Tregs (FOXP3 and IL2RA) and another for effector Tregs (FOXP3, CTLA-4, CCR8 and TNFRSF9) in pan-cancer. Using data from The Cancer Genome Atlas (TCGA), The Cancer Proteome Atlas (TCPA) and Gene Expression Omnibus (GEO), we focused on the expression profile of the two signatures, the existence of single nucleotide variants (SNVs) and copy number variants (CNVs), methylation, infiltration of immune cells in the tumor and sensitivity to different drugs. Our analysis revealed that both signatures are differentially expressed across different cancer types, and correlate with patient survival. Furthermore, both types of Tregs influence important pathways in cancer development and progression, like apoptosis, epithelial-to-mesenchymal transition (EMT) and the DNA damage pathway. Moreover, a positive correlation was highlighted between the expression of gene markers in both resting and effector Tregs and immune cell infiltration in adrenocortical carcinoma, while mutations in both signatures correlated with enrichment of specific immune cells, mainly in skin melanoma and endometrial cancer. In addition, we reveal the existence of widespread CNVs and hypomethylation affecting both Treg signatures in most cancer types. Last, we identified a few correlations between the expression of CCR8 and TNFRSF9 and sensitivity to several drugs, including COL-3, Chlorambucil and GSK1070916, in pan-cancer. Overall, these findings highlight new evidence that both Treg signatures are crucial regulators of cancer progression, providing potential clinical outcomes for cancer therapy.

PMID:40088713 | DOI:10.1016/j.compbiomed.2025.110021

Genetics. 2025 Mar 15:iyaf040. doi: 10.1093/genetics/iyaf040. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects nearly 3% of children and has a strong genetic component. While hundreds of ASD risk genes have been identified through sequencing studies, the genetic heterogeneity of ASD makes identifying additional risk genes using these methods challenging. To predict candidate ASD risk genes, we developed a simple machine learning model, ASiDentify (ASiD), using human genomic, RNA- and protein-based features. ASiD identified over 1,300 candidate ASD risk genes, over 300 of which have not been previously predicted. ASiD made accurate predictions of ASD risk genes using six features predictive of ASD risk gene status, including mutational constraint, synapse localization and gene expression in neurons, astrocytes and non-brain tissues. Particular functional groups of proteins found to be strongly implicated in ASD include RNA-binding proteins and chromatin regulators. We constructed additional logistic regression models to make predictions and assess informative features specific to RNA-binding proteins, including mutational constraint, or chromatin regulators, for which both expression level in excitatory neurons and mutational constraint were informative. The fact that RNA-binding proteins and chromatin regulators had informative features distinct from all protein-coding genes, suggests that specific biological pathways connect risk genes with different molecular functions to ASD.

PMID:40088463 | DOI:10.1093/genetics/iyaf040

STAR Protoc. 2025 Mar 14;6(2):103699. doi: 10.1016/j.xpro.2025.103699. Online ahead of print.

ABSTRACT

As the study of central control of multiple organ function becomes more prominent, there is an increasing need for the collection of fixed brain and unfixed organs and tissues from the same experimental animal. Here, we present a protocol for performing carotid artery cannulation, organ and tissue collection, in situ brain perfusion and fixation, and brain dissection in mice. We describe steps for cannulating the carotid artery, harvesting the heart and other organs, and perfusing, fixing, and dissecting the brain.

PMID:40088450 | DOI:10.1016/j.xpro.2025.103699

Health Econ Rev. 2025 Mar 15;15(1):20. doi: 10.1186/s13561-025-00609-8.

ABSTRACT

BACKGROUND: Fertility care represents a financial burden on patients and healthcare services alike and can represent a barrier to entry for many couples. Controlled ovarian stimulation (COH) is routinely used as part of in vitro fertilization and intracytoplasmic sperm injection (ICSI) procedures, as such the use of gonadotropins is a major contributing factor to the cost of the procedure. Recent studies have shown that myo-Inositol (myo-ins) may reduce the amount of gonadotrophins required in assisted reproductive technology (ART) procedures. This retrospective study measured the effect of myo-ins on the number of recombinant follicular stimulating hormone (rFSH) units used in IVF and ICSI and the relative cost to verify if this may be a cost saving strategy. We also investigated the oocyte and embryo quality, implantation rate, abortion rate, clinical pregnancy, and ovarian hyperstimulation syndrome.

METHODS: A total of 300 women undergoing either IVF or ICSI were distributed between two distinct and equal patient groups of 150 women. In control group (group A), folic acid (FA) alone was prescribed, meanwhile the treated group (group B) were prescribed FA, myo-Inositol (myo-ins) and alpha-lactalbumin (α-LA), both groups started this oral treatment in the middle of the luteal phase.

RESULTS: Myo-Ins supplementation in the treatment group significantly reduced the number of units of rFSH used in COH vs. the control group (2526 vs. 1647, p < 0.05); however, no changes were seen in other measured outcomes, likely due to the short treatment period.

CONCLUSIONS: The use of myo-Ins presents a safe method for reducing the amount and subsequent costs of rFSH usage in ART protocols.

TRIAL REGISTRATION: The trial was retrospectively registered with the Institutional Review Board of ALMA RES IVF Center, trial number n°2/2024.

PMID:40088331 | DOI:10.1186/s13561-025-00609-8

New Phytol. 2025 Mar 15. doi: 10.1111/nph.70068. Online ahead of print.

ABSTRACT

The green seaweed Ulva compressa is a promising model for functional biology. In addition to historical research on growth and development, -omics data and molecular tools for stable transformation are available. However, more efficient tools are needed to study gene function. Here, we expand the molecular toolkit for Ulva. We screened the survival of Ulva and its mutualistic bacteria on 14 selective agents and established that Blasticidin deaminases (BSD or bsr) can be used as selectable markers to generate stable transgenic lines. We show that Cas9 and Cas12a RNPs are suitable for targeted mutagenesis and can generate genomic deletions of up to 20 kb using the marker gene ADENINE PHOSPHORIBOSYLTRANSFERASE (APT). We demonstrate that the targeted insertion of a selectable marker via homology-directed repair or co-editing with APT is possible for nonmarker genes. We evaluated 31 vector configurations and found that the bicistronic fusion of Cas9 to a resistance marker or the incorporation of introns in Cas9 led to the most mutants. We used this to generate mutants in three nonmarker genes using a co-editing strategy. This expanded molecular toolkit now enables us to reliably make gain- and loss-of-function mutants; additional optimizations will be necessary to allow for vector-based multiplex genome editing in Ulva.

PMID:40088038 | DOI:10.1111/nph.70068

Mol Microbiol. 2025 Mar 14. doi: 10.1111/mmi.15357. Online ahead of print.

ABSTRACT

The opportunistic pathogen Pseudomonas aeruginosa relies on a large collection of two-component regulatory systems (TCSs) to sense and adapt to changing environments. Among them, the Roc (regulation of cup) system is a one-of-a-kind network of branched TCSs, composed of two histidine kinases (HKs-RocS1 and RocS2) interacting with three response regulators (RRs-RocA1, RocR, and RocA2), which regulate virulence, antibiotic resistance, and biofilm formation. Based on extensive work on the Roc system, previous data suggested the existence of other key regulators yet to be discovered. In this work, we identified PA4080, renamed RocA3, as a fourth RR that is activated by RocS1 and RocS2 and that positively controls the expression of the cupB operon. Comparative genomic analysis of the locus identified a gene-rocR3-adjacent to rocA3 in a subpopulation of strains that encodes a protein with structural and functional similarity to the c-di-GMP phosphodiesterase RocR. Furthermore, we identified a fourth branch of the Roc system consisting of the PA2583 HK, renamed RocS4, and the Hpt protein HptA. Using a bacterial two-hybrid system, we showed that RocS4 interacts with HptA, which in turn interacts with RocA1, RocA2, and RocR3. Finally, we mapped the pangenomic RRs repertoire, establishing a comprehensive view of the plasticity of such regulators among clades of the species. Overall, our work provides a comprehensive inter-species definition of the Roc system, nearly doubling the number of proteins known to be involved in this interconnected network of TCSs controlling pathogenicity in Pseudomonas species.

PMID:40087830 | DOI:10.1111/mmi.15357

Genome Biol. 2025 Mar 14;26(1):56. doi: 10.1186/s13059-025-03499-5.

ABSTRACT

BACKGROUND: The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents.

RESULTS: We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell-cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells.

CONCLUSIONS: Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

PMID:40087773 | DOI:10.1186/s13059-025-03499-5

Commun Biol. 2025 Mar 15;8(1):439. doi: 10.1038/s42003-025-07875-6.

ABSTRACT

Large-scale GWAS studies have uncovered hundreds of genomic loci linked to facial and brain shape variation, but only tens associated with cranial vault shape, a largely overlooked aspect of the craniofacial complex. Surrounding the neocortex, the cranial vault plays a central role during craniofacial development and understanding its genetics are pivotal for understanding craniofacial conditions. Experimental biology and prior genetic studies have generated a wealth of knowledge that presents opportunities to aid further genetic discovery efforts. Here, we use the conditional FDR method to leverage GWAS data of facial shape, brain shape, and bone mineral density to enhance SNP discovery for cranial vault shape. This approach identified 120 independent genomic loci at 1% FDR, nearly tripling the number discovered through unconditioned analysis and implicating crucial craniofacial transcription factors and signaling pathways. These results significantly advance our genetic understanding of cranial vault shape and craniofacial development more broadly.

PMID:40087503 | DOI:10.1038/s42003-025-07875-6

Nat Commun. 2025 Mar 15;16(1):2545. doi: 10.1038/s41467-025-57809-3.

ABSTRACT

In photosynthetic organisms, light acts as an environmental signal to control their development and physiology, as well as energy source to drive the conversion of CO2 into carbohydrates used for growth or storage. The main storage carbohydrate in green algae is starch, which accumulates during the day and is broken down at night to meet cellular energy demands. The signaling role of light quality in the regulation of starch accumulation remains unexplored. Here, we identify PHOTOTROPIN-MEDIATED SIGNALING KINASE 1 (PMSK1) as a key regulator of starch metabolism in Chlamydomonas reinhardtii. In its phosphorylated form (PMSK1-P), it activates GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAP1), promoting starch biosynthesis. We show that blue light, perceived by PHOTOTROPIN, induces PMSK1 dephosphorylation that in turn represses GAP1 mRNA levels and reduces starch accumulation. These findings reveal a previously uncharacterized blue light-mediated signaling pathway that advances our understanding of photoreceptor-controlled carbon metabolism in microalgae.

PMID:40087266 | DOI:10.1038/s41467-025-57809-3

eNeuro. 2025 Mar 14:ENEURO.0448-24.2025. doi: 10.1523/ENEURO.0448-24.2025. Online ahead of print.

ABSTRACT

Delayed motor development is an early clinical sign of Fetal Alcohol Spectrum Disorders (FASD). However, changes at the neural circuit level that underlie early motor differences are underexplored. The striatum, the principal input nucleus of the basal ganglia, plays an important role in motor learning in adult animals, and the maturation of the striatal circuit has been associated with the development of early motor behaviors. Here, we briefly exposed pregnant C57BL/6 dams to ethanol (5% w/w) in a liquid diet on embryonic days (E)13.5-16.5, and assessed the mouse progeny using a series of 9 brief motor behavior tasks on postnatal days (P)2-14. Live brain slices were then obtained from behaviorally-tested mice for whole cell-voltage and current clamp electrophysiology to assess GABAergic/glutamatergic synaptic activity, and passive/active properties in two populations of striatal neurons: GABAergic interneurons and spiny striatal projection neurons. Electrophysiologically-recorded spiny striatal projection neurons were also filled intracellularly with biocytin for post-hoc analysis of dendritic morphology. We found that prenatal ethanol exposure resulted in developmental motor delays that were more severe in male mice and coincided with sex-dependent differences in the maturation of striatal neurons. Our findings indicate that prenatal ethanol exposure results in dynamic morphological and functional changes to the developmental trajectories of striatal neurons commensurate with the development of motor behaviors that differ between male and female mice.Significance Statement Developmental differences in motor behaviors are an early clinical sign of Fetal Alcohol Spectrum Disorders (FASD) but the neural circuit level changes that contribute to these differences have not yet been determined. Here we demonstrate that a brief binge exposure to ethanol alters the motor development of neonatal mice in a sex-dependent manner, and identify concurrent differences in the functional, synaptic and morphological development of striatal GABAergic interneurons and medium spiny striatal projection neurons. These data suggest that altered development of striatal neurons may contribute to differences in early motor development observed in individuals with FASD.

PMID:40086875 | DOI:10.1523/ENEURO.0448-24.2025

Biochim Biophys Acta Gen Subj. 2025 Mar 12:130793. doi: 10.1016/j.bbagen.2025.130793. Online ahead of print.

ABSTRACT

X-irradiation has extensive applications in therapy and considerable attention has been devoted to the radiosensitizing properties of nanoparticles composed of high atomic number elements, particularly gold. Low energy electrons and/or heterogenous catalysis are widely suspected to be involved in radiosensitization, but there is uncertainty about their contributions. Because of their greater surface area to volume ratio relative to spherical particles per unit mass of gold, nanostars permit more low energy electrons to escape and posses an increased catalytic activity. Condensed DNA represents a highly useful model for mammalian chromatin, particularly with respect to the types and yields of DNA damage produced by ionizing radiation. Here we describe the incorporation of spherical gold nanoparticles and of gold nanostars into a condensed DNA model system. The resulting self-assembled micron-sized co-aggregates involve an intimate association between gold and DNA, maximizing the opportunity for the production of DNA damage. After increasing the ionic strength, the co-condensate becomes disaggregated and the DNA is available for subsequent assays. This model system provides a previously unavailable tool for examining the mechanisms of radiosensitization of DNA damage by gold nanoparticles with implications for possible applications in radiotherapy.

PMID:40086767 | DOI:10.1016/j.bbagen.2025.130793

Stem Cell Reports. 2025 Mar 12:102447. doi: 10.1016/j.stemcr.2025.102447. Online ahead of print.

ABSTRACT

Nuclear reprogramming can change cellular fates. Yet, reprogramming efficiency is low, and the resulting cell types are often not functional. Here, we used nuclear transfer to eggs to follow single cells during reprogramming in vivo. We show that the differentiation success of reprogrammed cells varies across cell types and depends on the expression of genes specific to the previous cellular identity. We find subsets of reprogramming-resistant cells that fail to form functional cell types, undergo cell death, or disrupt normal body patterning. Reducing expression levels of genes specific to the cell type of origin leads to better reprogramming and improved differentiation trajectories. Thus, our work demonstrates that failing to reprogram in vivo is cell type specific and emphasizes the necessity of minimizing aberrant transcripts of the previous somatic identity for improving reprogramming.

PMID:40086446 | DOI:10.1016/j.stemcr.2025.102447

Cell Syst. 2025 Mar 11:101205. doi: 10.1016/j.cels.2025.101205. Online ahead of print.

ABSTRACT

The sparse and stochastic nature of conversion has obscured our understanding of how transcription factors (TFs) drive cells to new identities. To overcome this limit, we develop a tailored, high-efficiency conversion system that increases the direct conversion of fibroblasts to motor neurons 100-fold. By tailoring the cocktail to a minimal set of transcripts, we reduce extrinsic variation, allowing us to examine how proliferation and TFs synergistically drive conversion. We show that cell state-as set by proliferation history-defines how cells interpret the levels of TFs. Controlling for proliferation history and titrating each TF, we find that conversion correlates with levels of the pioneer TF Ngn2. By isolating cells by both their proliferation history and Ngn2 levels, we demonstrate that levels of Ngn2 expression alone are insufficient to predict conversion rates. Rather, proliferation history and TF levels combine to drive direct conversion. Finally, increasing the proliferation rate of adult human fibroblasts generates morphologically mature induced human motor neurons at high rates.

PMID:40086434 | DOI:10.1016/j.cels.2025.101205

Transl Oncol. 2025 Mar 13;55:102347. doi: 10.1016/j.tranon.2025.102347. Online ahead of print.

ABSTRACT

Patients with liver metastatic colorectal cancer (mCRC) have a poor prognosis and are the leading cause of death in colorectal cancer (CRC) patients, but the mechanisms associated with CRC metastasis have not been fully elucidated. In this study, we obtained data from the Gene Expression Omnibus database and characterized the single-cell profiles of CRC, mCRC and healthy samples at single-cell resolution, and explored the cells that influence CRC metastasis. We find that AQP1+ CRC identified as highly malignant tumor cells exhibited proliferative and metastatic characteristics. Immunosuppressive properties are present in the tumor microenvironment (TME), while NOTCH3+ Fib is identified to play a facilitating role in the metastatic colonization of CRC. Importantly, we reveal that tumor-associated macrophages (TAM) characterized by SPP1-specific high expression may be involved in TME remodeling through intercellular communication. Specifically, SPP1+ TAM mediates the generation of Fib-derived extracellular vesicle through the APOE-LRP1 axis, which in turn delivers tumor growth-promoting factors in the TME. This study deepens the understanding of the mechanism of TME in mCRC and lays the scientific foundation for the development of therapeutic regimens for mCRC patients.

PMID:40086324 | DOI:10.1016/j.tranon.2025.102347

Sci Adv. 2025 Mar 14;11(11):eads6004. doi: 10.1126/sciadv.ads6004. Epub 2025 Mar 14.

ABSTRACT

NALCN (sodium leak channel, nonselective) is vital for regulating electrical activity in neurons and other excitable cells, and mutations in the channel or its auxiliary proteins lead to severe neurodevelopmental disorders. Here, we show that the neuronal SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) complex proteins syntaxin and SNAP25 (synaptosome-associated protein 25), which enable synaptic transmission in the nervous system, inhibit the activity of the NALCN channel complex in both heterologous systems and primary neurons. The existence of this interaction suggests that the neurotransmitter release machinery can regulate electrical signaling directly and therefore modulate the threshold for its own activity. We further find that reduction of NALCN currents is sufficient to promote cell survival in syntaxin-depleted cells. This suggests that disinhibited NALCN may cause the puzzling phenomenon of rapid neuronal cell death in the absence of syntaxin. This interaction could offer opportunities for future drug development against genetic diseases linked to both NALCN- and SNARE protein-containing complexes.

PMID:40085699 | DOI:10.1126/sciadv.ads6004

Int J Syst Evol Microbiol. 2025 Mar;75(3). doi: 10.1099/ijsem.0.006716.

ABSTRACT

Streptomyces strains DSM 116494T and DSM 116496T were isolated from sediment samples of the River Oker in Braunschweig, Germany, and subjected to a polyphasic taxonomic study and genome mining for specialized secondary metabolites. Phenotypic, genetic and genomic data confirmed the assignment of these strains to the Streptomyces genus. Pairwise 16S rRNA gene sequence similarity values between the strains and validly named Streptomyces species reached 99.5 and 99.7% for strains DSM 116494T and DSM 116496T, respectively. Genome-based phylogeny demonstrated that Streptomyces pilosus and Streptomyces griseoflavus species were the close relatives to strain DSM 116494T, while Streptomyces vinaceus species was the nearest neighbour to strain DSM 116496T. Digital DNA-DNA hybridization and average nucleotide identity comparisons of the genomic sequence of the strains and their close phylogenomic relatives revealed that values were below the determined threshold of 70 and 95-96% for prokaryotic species demarcation, respectively. The strains were distinguished from their close neighbours based on biochemical, chemotaxonomic and enzymatic data. Given these results, the strains merit being affiliated to novel species within the genus Streptomyces, for which the names Streptomyces okerensis sp. nov. (=OG2.3T=DSM 116494T=KCTC 59408T) and Streptomyces stoeckheimensis sp. nov. (=OG3.14T=DSM 116496T=KCTC 59410T) are proposed. Strains DSM 116494T and DSM 116496T harboured several biosynthetic gene clusters encoding potentially novel antimicrobial and anticancer compounds. Crude extracts of strains DSM 116494T and DSM 116496T inhibited the growth of Gram-negative bacteria (Escherichia coli ΔtolC, Proteus vulgaris) and a multi-drug-resistant Gram-positive, Staphylococcus aureus.

PMID:40085491 | DOI:10.1099/ijsem.0.006716