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PubMed1985

Primary structure of the soybean nodulin-23 gene and potential regulatory elements in the 5'-flanking regions of nodulin and leghemoglobin genes.

The nodulin-23 gene of soybean is one of the most abundantly transcribed genes induced during symbiosis with Rhizobium. Using a plasmid (pNod25) from a nodule cDNA library, we have isolated the nodulin-23 gene from a soybean genomic library. Nucleotide sequence analysis of the cDNA and of the genomic clone indicated that the coding region of this gene is 669 bp long and is interrupted by a single intron of about 530 bp. The deduced protein sequence suggests that nodulin-23 may have a signal sequence. The 5'-flanking sequence of two other nodulin genes, nodulin-24 encoding for a membrane polypeptide and one of the leghemoglobin genes (LbC3), were obtained. Comparison of these sequences revealed three conserved regions, one of which, an octanucleotide (GTTTCCCT), has 100% homology. The conserved sequences are arranged in a unique fashion and have a spatial organization with respect to order and position, which may suggest a potential regulatory role in controlling the expression of nodulin and leghemoglobin genes during symbiosis.

Amino Acid Sequence↗

PubMed1999

Expression of a soybean gene encoding the tetrapyrrole-synthesis enzyme glutamyl-tRNA reductase in symbiotic root nodules.

Heme and chlorophyll accumulate to high levels in legume root nodules and in photosynthetic tissues, respectively, and they are both derived from the universal tetrapyrrole precursor delta-aminolevulinic acid (ALA). The first committed step in ALA and tetrapyrrole synthesis is catalyzed by glutamyl-tRNA reductase (GTR) in plants. A soybean (Glycine max) root-nodule cDNA encoding GTR was isolated by complementation of an Escherichia coli GTR-defective mutant for restoration of ALA prototrophy. Gtr mRNA was very low in uninfected roots but accumulated to high levels in root nodules. The induction of Gtr mRNA in developing nodules was subsequent to that of the gene Enod2 (early nodule) and coincided with leghemoglobin mRNA accumulation. Genomic analysis revealed two Gtr genes, Gtr1 and a 3' portion of Gtr2, which were isolated from the soybean genome. RNase-protection analysis using probes specific to Gtr1 and Gtr2 showed that both genes were expressed, but Gtr1 mRNA accumulated to significantly higher levels. In addition, the qualitative patterns of expression of Gtr1 and Gtr2 were similar to each other and to total Gtr mRNA in leaves and nodules of mature plants and etiolated plantlets. The data indicate that Gtr1 is universal for tetrapyrrole synthesis and that a Gtr gene specific for a tissue or tetrapyrrole is unlikely. We suggest that ALA synthesis in specialized root nodules involves an altered spatial expression of genes that are otherwise induced strongly only in photosynthetic tissues of uninfected plants.

Aldehyde Oxidoreductases↗

PubMed2026

Deep learning-based cross-attention fusion of multimodal MRI for survival prediction and risk stratification in IDH-wildtype glioblastoma: a multicenter study.

BACKGROUND: Glioblastoma (GBM) exhibits profound molecular and spatial heterogeneity, complicating prognostic evaluations. While multiparametric MRI provides crucial multidimensional biological information, conventional end-to-end deep learning integration strategies, such as early or late fusion, often fail to capture complex nonlinear cross-modal interactions. We aimed to systematically evaluate a cross-attention fusion (CAF) architecture for GBM survival prediction and quantify its incremental prognostic value relative to existing clinical tools. METHODS: In this multicenter retrospective study, 386 adults with IDH-wildtype, WHO grade 4 GBM were assembled from an institutional cohort (n = 226), the Chinese Glioma Genome Atlas (CGGA, n = 62), and The Cancer Genome Atlas (TCGA, n = 98). Using a unified 3D ResNet-18 backbone, we compared single-modality models, early fusion, late fusion, and CAF on preoperative T1-weighted, contrast-enhanced T1-weighted (T1CE), and T2-weighted MRI, and integrated the resulting deep learning risk score with routine clinical variables through multivariable Cox regression. Performance was assessed using Harrell's C-index, time-dependent AUC, and decision curve analysis. RESULTS: CAF showed numerically higher, more consistent C-index trends than early fusion, late fusion, and single-modality models (pooled C-index 0.629, 95% CI 0.594-0.664), although pairwise differences in time-dependent AUC were not statistically significant. Integrating clinical variables raised the pooled C-index to 0.691 (95% CI 0.660-0.721) in the treatment-era model, with comparable performance across the three cohorts (Local 0.688; CGGA 0.716; TCGA 0.689); a pre-treatment configuration excluding adjuvant therapy yielded a pooled C-index of 0.642. Under leave-one-cohort-out external validation, the combined model retained significant risk stratification in all held-out cohorts (C-index 0.63-0.71; all log-rank P < 0.01), albeit with attenuated discrimination. The deep learning risk score remained independent after multivariable adjustment (HR 1.41 per SD, 95% CI 1.26-1.57; P < 0.001). Kaplan-Meier analysis confirmed significant high- versus low-risk separation in all cohorts, and decision curve analysis showed greater net benefit than clinical-only and deep-learning-only models. CONCLUSION: The CAF-derived risk score offers prognostic information complementary to routine clinical variables, representing a promising noninvasive tool for individualized risk stratification when molecular profiling is incomplete or unavailable; these findings warrant prospective external validation before clinical use.

cross-attention fusion↗

PubMed2005

Variegation of the immune response with dendritic cells and pathogen recognition receptors.

One of the most fundamental questions in biology is: "How do cells differentiate in the right place, at the right time, into the right kinds?" Understanding the phenomenon of cell differentiation in its spatial and temporal framework is a prelude to understanding the development and physiology of all multicellular systems, including the immune system. Insights over the past 2300 years, since Aristotle, suggest that biological differentiation is guided by the interplay between genetic programs and specific environmental signals. This is exemplified by the mammalian immune response to pathogens, where qualitatively different types can emerge. Although it is appreciated that this type immunity is critical for optimal defense against different pathogens, the early "decision-making mechanisms" are largely obscure. Recent developments in innate immunity and genomics, especially in the biology of dendritic cells (DCs) and pathogen recognition receptors, have stimulated intense research in understanding the mechanisms guiding the differentiation of Th1, Th2, and T regulatory responses. In this study, I summarize recent findings which suggest that activation of DCs via distinct pathogen recognition receptors stimulate different gene expression programs and signaling networks in DCs that guide the variegation of immune responses.

Adaptor Proteins, Signal Transducing↗

PubMed2026

Spatial structure and growth dynamics of fairy rings formed by Marasmius oreades.

Despite the long-term fascination of fairy ring-forming fungi, many aspects of their biology remain unresolved. It is not known why the mycelium grows as an annular structure, rather than a solid disc, or why it grows radially outwards. Different theories have been suggested, but none have been tested experimentally with molecular resolution. Here, we undertook a metagenomic approach to study the growth dynamics of the fairy ring-forming fungus Marasmius oreades. We confirmed that M. oreades grows as an open ring by detecting its DNA in metagenomes of soil collected along transects from two fairy rings. We showed that the mycelia forming rings are dikaryotic by identifying two mating-type alleles and showing genome-wide heterozygosity. We tested five hypotheses for the mechanism of radial outgrowth using transplantation experiments. The results were most consistent with a transient-escape hypothesis, and suggest that the mycelium avoids inhibitory factors present at the back edge of the mycelial growth front. Our study demonstrates the power of metagenomics for studying fungi, showing that detailed genomic information can be recovered directly from soil. This approach enables the investigation of cryptic aspects of fungal biology, such as the growth of fairy ring-forming fungi, in natural settings that would otherwise remain hidden.

Marasmius↗

PubMed2002

Neurobehavioral and electroencephalographic abnormalities in Ube3a maternal-deficient mice.

Angelman syndrome (AS), characterized by motor dysfunction, mental retardation, and seizures, is caused by several genetic etiologies involving chromosome 15q11-q13, including mutations of the UBE3A gene. UBE3A encodes UBE3A/E6-AP, a ubiquitin-protein ligase, and shows brain-specific imprinting, with brain expression predominantly from the maternal allele. Lack of a functional maternal allele of UBE3A causes AS. In order to understand the causal relationship between maternal UBE3A mutations and AS, we have constructed a mouse model with targeted inactivation of Ube3a. The inactive allele contains a lacZ reporter gene for analysis of brain-specific imprinting. Maternal, but not paternal, transmission of the targeted allele leads to beta-galactosidase activity in hippocampal and cerebellar neurons. Maternal inheritance of the Ube3a mutant allele also causes impaired performance in tests of motor function and spatial learning, as well as abnormal hippocampal EEG recordings. As predicted from the dependence of UBE3A-mediated ubiquitination of p53 on HPV E6 protein, our maternal-deficient mice show normal brain p53 levels.

Angelman Syndrome↗

PubMed2003

Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells.

Y-family DNA polymerases can replicate past a variety of damaged bases in vitro but, with the exception of DNA polymerase eta (poleta), which is defective in xeroderma pigmentosum variants, there is little information on the functions of these polymerases in vivo. Here, we show that DNA polymerase iota (poliota), like poleta, associates with the replication machinery and accumulates at stalled replication forks following DNA-damaging treatment. We show that poleta and poliota foci form with identical kinetics and spatial distributions, suggesting that localization of these two polymerases is tightly co-ordinated within the nucleus. Furthermore, localization of poliota in replication foci is largely dependent on the presence of poleta. Using several different approaches, we demonstrate that poleta and poliota interact with each other physically and that the C-terminal 224 amino acids of poliota are sufficient for both the interaction with poleta and accumulation in replication foci. Our results provide strong evidence that poleta targets poliota to the replication machinery, where it may play a general role in maintaining genome integrity as well as participating in translesion DNA synthesis.

Animals↗

PubMed2001

Analysis and function of transcriptional regulatory elements: insights from Drosophila.

Analysis of gene expression is assuming an increasingly important role in elucidating the molecular basis of insect biology. Transcriptional regulation of gene expression is directed by a variety of cis-acting DNA elements that control spatial and temporal patterns of expression. This review summarizes current knowledge about properties of transcriptional regulatory elements, based largely on research in Drosophila melanogaster, and outlines ways that new technologies are providing tools to facilitate the study of transcriptional regulatory elements in other insects.

Animals↗

PubMed2026

Metagenomic insights into antibiotic resistance genes and virulence factors in sediments of river Yamuna.

Riverine sediments serve as critical reservoirs of microbial diversity and functional genes, reflecting both natural ecological processes and anthropogenic impacts. In the present study, we employed a shotgun metagenomic approach to investigate microbial community composition, antimicrobial resistance (AMR) genes, and virulence factors in sediments collected from three environmentally distinct locations of the Yamuna River near Agra, India, representing BSA, TGY, and YEA. The sediment DNA was subjected to high-throughput Illumina sequencing, followed by quality control, assembly, and open reading frame prediction. Taxonomic classification and diversity analyses were performed using MEGAN6 and R-based statistical tools, while AMR genes were identified from predicted metagenomic proteins using the Resistance Gene Identifier (RGI) against the CARD database, with high-confidence perfect and strict hits retained; ARGs were interpreted independently of species-level host assignment. Virulence factors were assessed through presence-absence profiling of functionally relevant gene categories. The results revealed pronounced spatial heterogeneity in microbial communities, with increasing taxonomic diversity, functional complexity, and evenness from BSA to TGY and YEA. TGY and YEA composite samples showed greater observed representation of high-confidence AMR gene predictions spanning multiple drug classes and resistance mechanisms, alongside a diverse repertoire of virulence-associated genes linked to motility, adhesion, and secretion systems. In contrast, the BSA site harbored a comparatively simpler resistome and virulome. Overall, this study highlights Yamuna River sediments as important reservoirs of resistance and virulence determinants and underscores the need for long-term genomic surveillance to inform risk assessment, pollution control, and sustainable river management strategies.

AMR↗

PubMed2002

Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells.

Active Transport, Cell Nucleus↗

PubMed1995

[Adenovirus, a gene therapy vector: application to lung diseases].

Due to their quiescent nature and spatial complexity, many target tissues for gene therapy will require novel strategies. An alternative to ex vivo gene transfer, providing many technical advantages and possibly allowing sufficient transfer of the therapeutic gene, is direct in vivo delivery of the vehicle. For a favorable outcome, this procedure is dependent on a high-titer vector, fully competent before post-mitotic cells. In view of the restrictions inherent in the use of retroviruses, we have investigated the potentials of adenovirus. Adenoviruses have as primary targets of infection the differentiated epithelial cell. The large DNA genome of the virus hints to a large cloning capacity. Furthermore, wildtype adenovirus and the precedent of administration to humans are suggestive of adenovirus-based gene therapy for diseases involving a variety of quiescent tissues. The use of a replication-defective adenovirus carrying a gene encoding a nuclearly-targeted beta-galactosidase demonstrated that replication-incompetent adenoviruses offer an efficient means to transfer a gene for extended periods of time to the liver, muscle, lung, and brain. Because of adenovirus' natural tropism for the lung epithelium, we have proposed that this virus be used as a CFTR gene delivery vector for the treatment of cystic fibrosis and lung cancer.

Adenoviruses, Human↗

PubMed1999

Small subfamily of olfactory receptor genes: structural features, expression pattern and genomic organization.

Olfactory receptors of the OR37 subfamily are characterized by distinct sequence features and are expressed in neurons segregated in a restricted area of the olfactory epithelium. In the present study, we have characterized the complement of OR37-like genes in the mouse. Five OR37-like genes were identified. They reside within only 60kb of DNA on chromosome 4. About 70kb distant from this cluster, two additional olfactory receptor genes are located, which are members of distinct receptor subfamilies. Phylogenetic analysis demonstrated that the two physically linked receptors are closely related to the OR37 subfamily. Studies of gene expression showed that both genes are also expressed in clustered neuron populations located in the typical OR37 region of the epithelium. These data suggest the involvement of locus-dependent mechanisms for the spatial control of OR gene expression.

Amino Acids↗

PubMed2026

Navigating nuclear space: How Rad51 filaments promote long-range homology search during homologous recombination - Lessons from budding yeast.

DNA double-strand breaks (DSBs) threaten genomic integrity, with erroneous repair leading to chromosomal rearrangements and pathologies. In eukaryotes, DSBs are primarily repaired via non-homologous end-joining (NHEJ) or homologous recombination (HR). HR restores genetic information by using an undamaged homologous sequence as a template, a process dependent on Rad51-mediated homology search. This review synthesizes recent advances in our understanding of HR, with a focus on the homology search process in mitotic cells, primarily using Saccharomyces cerevisiae as a model organism. We explore factors that limit recombination efficiency and discuss how Rad51 filament dynamics overcome spatial and temporal challenges imposed by nuclear architecture and chromatin dynamics, to ensure efficient HR. Key insights include the dynamic behavior of Rad51 filaments, which undergo cycles of compaction and extension, thereby optimizing exploration of the nuclear volume and increasing the likelihood of encountering distant homologous sequences. The interplay between long-range resection, filament elongation, and nuclear constraints further shapes the search process, balancing the need for extensive exploration with the risks of excessive DNA degradation and ectopic recombination. Collectively, these findings support an integrated model in which the efficiency and accuracy of homologous recombination are governed by regulated Rad51 filament dynamics and the constraints imposed by nuclear architecture.

Rad51 Recombinase↗

PubMed2000

Identification of a 3.2 kb 5'-flanking region of the murine keratocan gene that directs beta-galactosidase expression in the adult corneal stroma of transgenic mice.

The mouse keratocan gene (Ktcn) expression tracks the corneal morphogenesis during eye development and becomes restricted to keratocytes of the adult, implicating a cornea-specific gene regulation of the mouse Ktcn [J. Biol. Chem., 273 (1998) 22584-22588]. To examine the functionality of the mouse Ktcn promoter, we have cloned and sequenced a 3.2kb genomic DNA fragment 5' of the mouse Ktcn gene, which was used to prepare a reporter gene construct that contained the 3.2kb 5' flanking sequence, exon 1 and 0.4kb of intron 1 of Ktcn, and beta-geo hybrid reporter gene. The beta-galactosidase (betaGal) activity was assayed in tissues of two of five transgenic mouse lines obtained via microinjection. In adult transgenic mice, betaGal activity was detected only in cornea, not in other tissues (e.g. lens, retina, sclera, lung, heart, liver, diaphragm, kidney, and brain). During ocular development, the spatial-temporal expression patterns of the betaGal recapitulated that of endogenous Ktcn in transgenic mice. Using XGal staining, strong betaGal activity was first detected in periocular tissues of E13.5 embryos, and restricted to corneal keratocytes at E14.5 and thereafter. Interestingly, in addition to cornea, betaGal activity was transiently found in some non-ocular tissues, i.e. ears, snout, and limbs of embryos of E13.5 and E14.5 but was no longer detected in those tissues of E16.5 embryos. The transient expression of endogenous keratocan in non-ocular tissues during embryonic development was confirmed by in situ hybridization. Taken together, our results suggest that the 3.2kb Ktcn promoter contains sufficient cis-regulatory elements to drive heterologous minigene expression in cells expressing keratocan. The identification of keratocyte-specific expression of betaGal reporter gene in the adult transgenic mice is an important first step in characterizing the Ktcn promoter in order to use it to drive a foreign gene expression in corneal stroma.

Animals↗

PubMed2002

Expression and evolution studies of ets genes in a primitive coelomate, the polychaete annelid, Hediste (Nereis) diversicolor.

The Ets family includes numerous proteins with a highly conserved DNA-binding domain of 85 amino acids named the ETS domain. Phylogenetic analyses from ETS domains revealed that this family could be divided into 13 groups, among them are ETS and ERG. The ets genes are present in the Metazoan kingdom and we have previously characterized the Nd ets and Nd erg genes in the polychaete annelid Hediste diversicolor. Here, we isolated a fragment encoding the ETS domain from Nd Ets, by genomic library screening. By Northern blot analysis, we showed that this gene was transcribed as one major mRNA of 2.6 kb and one minor mRNA of 3.2 kb. By in situ hybridization, we observed that Nd ets was expressed in the intestine and oocytes and that Nd erg was expressed in cellular clumps present in the coelomic cavity, in an area of proliferating cells situated between the last metamere and the pygidium. Finally, we showed that Nd erg shared the expression pattern of Nd ets in oocytes. Molecular modeling studies have revealed that the spatial structure of ETS domain of Nd Ets and Nd Erg was conserved, in comparison to the murine Ets-1 and human Fli-1 proteins, respectively.

Amino Acid Sequence↗

PubMed2002

Using array hybridization to monitor gene expression at the single cell level.

Advances in high-throughput genome sequencing demand the development of more efficient ways of examining gene expression at a cellular level. During recent years, polymerase chain reaction (PCR)-based methods have been developed that allow the amplification of mRNA from small amounts of material, even from single animal cells. In parallel, several analytical tools permit a global monitoring of gene expression. To date, high throughput analysis methods have not been accessible for single plant cell samples. In the protocol described here, cDNA array hybridization (expression profiling) and an amplification strategy using reverse transcriptase PCR are merged with high spatial resolution sampling from undamaged plant tissue. This protocol gives us a new tool to examine tissue-specific gene expression patterns on a comprehensive scale. To demonstrate the usefulness of this tool, gene expression patterns in samples from Arabidopsis thaliana L. cv. C24 leaf epidermal and mesophyll cells were measured; several differentially expressed genes were identified when single cell samples were compared. The protocol described has the potential of increasing the efficiency of tissue-specific expression analysis by combining high-throughput profiling with straightforward sampling and amplification procedures.

Arabidopsis↗

PubMed1990

Different Temporal and Spatial Gene Expression Patterns Occur during Anther Development.

We studied the temporal and spatial regulation of three mRNA sequence sets that are present exclusively, or at elevated levels, in the tobacco anther. One mRNA set accumulates in the tapetum and decays as the tapetum degenerates later in anther development. The second mRNA set accumulates after the tapetal-specific mRNAs, is localized within the stomium and connective, and also decays as these cell types degenerate during anther maturation. The third mRNA sequence set persists throughout anther development and is localized within most anther tissues. A tapetal-specific gene, designated as TA29, was isolated from a tobacco genome library. Runoff transcription studies and experiments with chimeric [beta]-glucuronidase and diphtheria toxin A-chain genes showed that the TA29 gene is regulated primarily at the transcriptional level and that a 122-base pair 5[prime] region can program the tapetal-specific expression pattern. Destruction of the tapetum by the cytotoxic gene had no effect on the differentiation and/or function of surrounding sporophytic tissues but led to the production of male-sterile plants. Together, our studies show that several independent gene expression programs occur during anther development and that these programs correlate with the differentiated state of specific anther cell types.

Journal Article↗

PubMed2026

Microbial membrane transporters reveal trace metal niche adaptation in distinct water masses of the Southern Ocean.

BACKGROUND: Trace metals are co-factors for enzymes that are essential for microbial metabolism and the cycling of major elements. Membrane transporters allow microbes to sense and react to trace elements in the environment and to balance their uptake and export for the regulation of intracellular metal homeostasis. The acquisition and efflux of trace metals could lead to reciprocal feedbacks between microbes and the surrounding environment. Whether these processes vary among trace metals and across habitats is presently not known. We used membrane transporters into and out of the cell as indicators for the uptake and efflux of trace metals and provide a detailed picture of the distribution of the respective genes in distinct provinces in surface waters and in subsurface water masses across a transect in the Southern Indian Ocean. RESULTS: We observed marked spatial and vertical patterns in normalized gene abundances of transporters of iron (Fe), manganese (Mn), nickel (Ni) and copper (Cu). Changes in gene abundances were specific to the type of transporter and trace metal, and pronounced differences between surface and specific water masses emerged. We found an enrichment in genes related to efflux and homeostasis of Fe, Ni and Cu in two water masses of the deep ocean that are North Atlantic Deep Water (NADW) and Lower Circumpolar Deep Water (LCDW). This pattern was observed on the community level and for metagenome-assembled genomes (MAGs) affiliated with Alteromonadaceae and Burkholderiaceae that were abundant in these two water masses. CONCLUSIONS: The enrichment in trace metal efflux and resistance genes points to microbially mediated processes, exerted by homeostasis, with potential influence on the trace metal speciation and distribution in specific water masses in the deep ocean. The gene repertoire and distinct distribution pattern of the taxa identified as potential key players could reflect an adaptation to these old water masses with trace metals acting as selective driver. Video Abstract.

Membrane Transport Proteins↗