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PubMed2026

Advancing the Deciphering of Host-Microbe Crosstalk with Spatial Omics: A Mini-Review.

Host-microbe crosstalk refers to the reciprocal influences between a host and its resident or invading microorganisms. This crosstalk plays important roles in maintaining host health, regulating physiological functions, and coordinating responses to infection. The rapid rise of spatial omics is transforming how this crosstalk is studied in both animals and plants. Unlike traditional bulk omics, which homogenize tissues and erase spatial context, spatial methods preserve in situ organization and can simultaneously capture molecular information from hosts and microbes. As a result, researchers can characterize the spatial organization of colonization and infection, identify spatial associations between microbial niches and host cell states, and visualize local host response gradients across intact tissues. Current spatial omics technologies encompass sequencing-based, imaging-based, and hybrid platforms. Spatial multi-omics approaches enable the joint measurement or integration of gene expression, protein abundance, and metabolite distributions. Although spatial association alone does not establish causality, spatial omics provides a high-resolution framework for characterizing host-microbe relationships within intact tissues and generating spatially constrained, testable hypotheses. When combined with perturbation experiments and complementary experimental evidence, these hypotheses can contribute to mechanistic interpretation of host-microbe crosstalk. Here, we review spatial omics technologies, compare their suitability and major trade-offs for host-microbe studies, and discuss computational strategies, analytical challenges, and future prospects.

Multiomics↗
PubMed2001

Human cortical networks for new and familiar sequences of saccades.

Visual exploration is organized in sequences of saccadic eye movements that depend on both perceptual and cognitive context. Using functional magnetic resonance imaging, we studied the neural basis of sequential oculomotor behavior and its dependence on different types of memory by analyzing cerebral activity during performance of newly learned and familiar sequences of eye movements. Compared to a resting condition, both types of sequences activated a common fronto-parietal network, including frontal and supplementary eye fields, and several parietal areas. Within this network, newly learned sequences induced stronger activation than familiar sequences, probably reflecting higher attentional demands. In addition, specific regions were recruited for the performance of new sequences, including pre-supplementary eye fields, the precuneus and the caudate nucleus. This indicates that in addition to attentional modulation, novelty of saccadic sequences requires specific cortical resources, probably related to effortful sequence preparation and coordination as well as to spatial working memory. For familiar sequences, recalled from long-term memory, we observed specific right medial temporo-occipital activation in the vicinity of the boundary between the parahippocampal and lingual gyri, as well as an activation site in the parieto-occipital fissure. We conclude that neuronal resources recruited by the gaze system can change with the familiarity of the scanpath to be executed. This study is important to better understand how the brain implements memorized scanpaths for visual exploration and orienting.

Adult↗
PubMed1991

A 3 kb sequence from the mouse cellular retinoic-acid-binding protein gene upstream region mediates spatial and temporal LacZ expression in transgenic mouse embryos.

A 3233 base pair (bp) sequence of the 5'-flanking region of the mouse cellular retinoic-acid-binding protein (CRABP) gene is determined. From this region, a 3 kb fragment located 150 bp upstream from the transcriptional initiation site is isolated and fused to a LacZ reporter sequence. Transgenic mouse embryos of this fusion gene show spatially and temporally specific expression of LacZ protein and the expression of this fusion gene at the RNA level is confirmed by RNAase protection assays, which detect specific fusion transcripts in RNA samples from tissues of transgenic mouse embryos. In contrast, transgenic mouse embryos of a shorter fusion gene containing only 583 bp from the same upstream region of the mouse CRABP gene fused to the same reporter sequence show no LacZ activities. Thus, it is concluded that the 3 kb sequence, but not the 583 bp sequence, of the mouse CRABP gene contains information for its temporally and spatially specific expression in mouse embryos.

Animals↗
PubMed2001

[Quantitative multi-slice imaging of perfusion of the brain].

AIM: To develop an MR pulse sequence that allows the determination of the quantitative perfusion of the brain by imaging the passage of a contrast agent bolus with high temporal and spatial resolution. METHODS: An EPI sequence, EPIDET (Echo Planar Imaging using Different Echo Times), was developed that allows the acquisition of different slices at different echo times. The passage of a contrast agent bolus was recorded in a slice through the large brain feeding arteries at a short echo time (TE1 = 17 ms), while brain parenchyma was imaged in up to nine additional slices at a long echo time (TE2 = 34 ms). RESULTS: The different echo times allowed the determination of the arterial input function (signal decrease to 32%-59% of baseline intensity) and gave a sufficient signal reduction (14-22%) for reliable quantification of perfusion in brain parenchyma. CONCLUSIONS: The combination of different echo times of the DUAL-FLASH sequence and the multislice capability of EPI sequences in the EPIDET sequence enables the quantification of multi-slice perfusion examinations. Compared to the DUAL-FLASH sequence EPIDET improves spatial and temporal resolution.

Blood-Brain Barrier↗
PubMed2006

Tools for integrated sequence-structure analysis with UCSF Chimera.

BACKGROUND: Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual aspects of such work, there is a need for interactive visualization tools that: (a) provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b) facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit); (c) can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d) interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals. RESULTS: The molecular graphics program UCSF Chimera includes a suite of tools for interactive analyses of sequences and structures. Structures automatically associate with sequences in imported alignments, allowing many kinds of crosstalk. A novel method is provided to superimpose structures in the absence of a pre-existing sequence alignment. The method uses both sequence and secondary structure, and can match even structures with very low sequence identity. Another tool constructs structure-based sequence alignments from superpositions of two or more proteins. Chimera is designed to be extensible, and mechanisms for incorporating user-specific data without Chimera code development are also provided. CONCLUSION: The tools described here apply to many problems involving comparison and analysis of protein structures and their sequences. Chimera includes complete documentation and is intended for use by a wide range of scientists, not just those in the computational disciplines. UCSF Chimera is free for non-commercial use and is available for Microsoft Windows, Apple Mac OS X, Linux, and other platforms from http://www.cgl.ucsf.edu/chimera.

Computer Graphics↗
PubMed2006

Long-range periodic patterns in microbial genomes indicate significant multi-scale chromosomal organization.

Genome organization can be studied through analysis of chromosome position-dependent patterns in sequence-derived parameters. A comprehensive analysis of such patterns in prokaryotic sequences and genome-scale functional data has yet to be performed. We detected spatial patterns in sequence-derived parameters for 163 chromosomes occurring in 135 bacterial and 16 archaeal organisms using wavelet analysis. Pattern strength was found to correlate with organism-specific features such as genome size, overall GC content, and the occurrence of known motility and chromosomal binding proteins. Given additional functional data for Escherichia coli, we found significant correlations among chromosome position dependent patterns in numerous properties, some of which are consistent with previously experimentally identified chromosome macrodomains. These results demonstrate that the large-scale organization of most sequenced genomes is significantly nonrandom, and, moreover, that this organization is likely linked to genome size, nucleotide composition, and information transfer processes. Constraints on genome evolution and design are thus not solely dependent upon information content, but also upon an intricate multi-parameter, multi-length-scale organization of the chromosome.

Bacterial Proteins↗
PubMed1999

Spatial regularization applied to factor analysis of medical image sequences (FAMIS).

Dynamic image sequences allow physiological mechanisms to be monitored after the injection of a tracer. Factor analysis of medical image sequences (FAMIS) hence creates a synthesis of the information in one image sequence. It estimates a limited number of structures (factor images) assuming that the tracer kinetics (factors) are similar at each point inside the structure. A spatial regularization method for computing factor images (REG-FAMIS) is proposed to remove irregularities due to noise in the original data while preserving discontinuities between structures. REG-FAMIS has been applied to two sets of simulations: (a) dynamic data with Gaussian noise and (b) dynamic studies in emission tomography (PET or SPECT), which respect real tomographic acquisition parameters and noise characteristics. Optimal regularization parameters are estimated in order to minimize the distance between reference images and regularized factor images. Compared with conventional factor images, the root mean square error between regularized images and reference factor images is improved by 3 for the first set of simulations, and by about 1.5 for the second set of simulations. In all cases, regularized factor images are qualitatively and quantitatively improved.

Algorithms↗
PubMed1991

Impairment of the visuo-spatial sketch pad.

A case study is presented of a female patient, ELD, who has difficulty in the immediate recall of short sequences of visuo-spatial material following a right-hemisphere aneurysm. Despite poor performance on tasks such as the Brooks Matrix and the Corsi Blocks, ELD is good at the immediate serial recall of letters even when presentation modality is visual and shows effects of phonological similarity and articulatory suppression. This pattern of performance represents a double dissociation from that which has been observed with the short-term memory patient PV (Vallar & Baddeley, 1984), who is extremely poor at serial recall of verbal material but shows no visual memory impairment. It is argued that ELD has an impairment to the visuo-spatial component of working memory (Baddeley, 1986) in the absence of any phonological loop deficit. Further investigation reveals that ELD performs poorly on mental rotation tasks and finds it difficult to use imagery mnemonics, but has no difficulty in retrieving visuo-spatial information from long-term memory so long as it was learnt before her illness.

Attention↗
PubMed1994

Solution structure of GAP SH3 domain by 1H NMR and spatial arrangement of essential Ras signaling-involved sequence.

Src homology 3 (SH3) domains are found in numerous cytoplasmic proteins involved in intracellular signal transduction. We used 2-D 1H NMR to determine the structure of the SH3 domain of the guanosine triphosphatase-activating protein (GAP), an essential component of the Ras signaling pathway. The structure of the GAP SH3 domain (275-350) was found to be a compact beta-barrel made of six antiparallel beta-strands arranged in two roughly perpendicular beta-sheets with the acidic residues located at the surface of the protein. The Trp317, Trp319, Thr321 and Leu323 residues belonging to the sequence (317-326), which was shown to be essential for Ras signaling, formed two nearby lipophilic bulges followed by a hydrophilic domain (Arg324-Asp326). These structural data could be used to characterize the still unidentified downstream components of GAP, which are involved in Ras signaling, and to rationally design inhibitors of this pathway.

Amino Acid Sequence↗
PubMed1996

DNA sequence variation of mitochondrial large-subunit rRNA provides support for a two-subclass organization of the Anthozoa (Cnidaria).

We have sequenced a portion of the mitochondrial 16S rRNA gene from 29 species of Anthozoa, representing six orders of the subclasses Ceriantipatharia, Hexacorallia, and Octocorallia, with the focus on deep-seamount corals (> 500-m depth). We have detected significant length variation in the gene, with homologous gene fragments ranging from 545 bp in a shallow-water scleractinian coral to 911 bp in a deep-sea antipatharian black coral. The aligned sequences were divided into five regions: three high-identity sequence blocks (HSBs) and two highly variable blocks of insertions/deletions (INDELs). Most of the length variation among species occurred as varying numbers of nucleotides in the two INDELs. Little or no intraspecific sequence variation was detected over spatial scales of up to approximately 150 km. Interspecific sequence variation was lowest among the octocorals and greatest among the ceriantipatharians. Our data indicate that the orders Ceriantharia and Antipatharia are highly divergent, and a phylogenetic reconstruction provides support for the two-subclass system of the class Anthozoa (Hexacorallia and Octocorallia).

Animals↗
PubMed2000

Learning of spatial and temporal patterns in sequential hand movements.

Speed and accuracy in performing a complex movement sequence improve with practice. To examine how the temporal and spatial patterns of movement sequence are learned, the sequence of target locations and the consistency in the timing of target presentation were manipulated independently while subjects produced a series of visually guided hand movements. When the sequence of target locations and the timing of target presentation followed a consistent pattern, performance for a particular movement sequence improved with practice for both temporal and spatial movement parameters. However, when the same temporal and spatial patterns were recombined with a phase shift, there was a small but consistent deficit in performance. These results suggest that whereas spatial and temporal patterns in a learned movement sequence can be recombined flexibly, optimal performance is obtained for a specific spatio-temporal pattern of movement sequence. Whereas subjects were largely aware of the spatial and temporal patterns, they were unaware of the phase-shift, suggesting that learning of a specific spatio-temporal pattern was implicit.

Hand↗
PubMed1993

Molecular characterization of one of the maize polygalacturonase gene family members which are expressed during late pollen development.

A gene exhibiting homology to the polygalacturonases of several species, including tomato and Oenothera, has been shown by RNA dot-blot analysis and in situ hybridization experiments to be expressed post-first microspore mitosis in maize. A 2.87 kbp section of the promoter fused to E. coli beta-glucuronidase (uidA) coding sequence conferred the correct spatial and temporal expression in transgenic tobacco plants. However, low levels of expression were detected in other tissues, and in particular in the tissues surrounding the vascular branch points of leaf nodes. The maize polygalacturonase gene is one member of a highly conserved gene family. The lack of detectable expression in sporophytic tissues and the isolation of a number of related cDNAs from maize suggests that all expressed members of this family show the same spatial and temporal regulation.

Base Sequence↗
PubMed1989

High-flux signals and spatial localization in high-resolution 1H spectroscopy with surface coils.

To perform in vivo localized proton spectroscopy with water suppression, spin-echo sequences, made of binomial pulses, are commonly used with surface coils. The frequency selective response to such a sequence is also-spatially dependent, that is dependent on the sample shape and on the pulse angle adjustment. It is consequently pointed out in this paper that quantitative analysis for relative peak intensities may be strongly affected by the contribution of the high-flux regions. In vivo proton spectroscopy of rat brain exemplifies this difficulty. It is shown that the use of selective prepulses to suppress high-flux signals may be of poor efficiency depending on chemical shift, while the use of hard nonselective prepulses works for any chemical shift.

Animals↗
PubMed1995

Differential in vitro DNA binding activity to a promoter element of the gn1 beta-1,3-glucanase gene in hypersensitively reacting tobacco plants.

In a hypersensitive reaction to pathogen infection, expression of the beta-1,3-glucanase gn1 gene is induced in cells surrounding the necrotic lesions. The 5'-flanking sequence of gn1 was examined to investigate the molecular basis controlling activation of gene expression during this plant defense response. Studies on transgenic tobacco plants containing gn1 promoter deletions fused to the beta-glucuronidase reporter gene revealed the presence of negative and positive regulatory sequences mediating both the level and the spatial distribution of gn1 expression. Promoter sequences to -138 bp were sufficient to confer increased gene expression around the necrotic lesions produced in response to Pseudomonas syringae pv. syringae inoculation. It is demonstrated by electrophoretic mobility shift assays that nuclear proteins in both healthy and hypersensitively reacting tobacco leaves interact with DNA sequences within the regulatory elements identified. Among the binding sequences characterized, the promoter region extending from -250 to -217 bp contained the DNA motif -GGCGGC- found to be conserved in most if not all promoters of genes encoding pathogenesis-related basic proteins. The activity bound by this promoter sequence was stronger in hypersensitively responding tissues than in healthy untreated tobacco leaves.

Base Sequence↗
PubMed1996

Site-directed mutagenesis and structural interpretation of the nidogen binding site of the laminin gamma1 chain.

A precise molecular map of the nidogen binding site of laminins was obtained by site-directed mutagenesis and structural analysis of the 56 residue LE module gamma1III4 of their gamma1 chain. This demonstrated the crucial importance of the sequence DPNAV (position 800-804) in the disulfide-bonded loop a, with major contributions made by all residues except P801. Different substitutions of these residues emphasized the essential role of the negative charge (D800) and carboxamide group (N802) as well as their spacings and hydrophobic contacts (V804) for interaction, and predict direct contacts of these three residues with a complementary binding region of nidogen. An inactivating A803-V substitution, however, may lead to a distorted loop structure. A lower but still significant contribution originates from the non-contiguous link/loop c sequence LKCIY (positions 815-819) which is spatially close to the loop a sequence. The link residues (L815 and K816) provide main chain hydrogen bonds to N806 and a side chain hydrogen bond to the V804 carbonyl and thus stabilize the conformation of loop a. The side chains of I818 and Y819 together with P842 from loop d form hydrophobic contacts that provide further stability but could possibly also participate in direct ligation. The nidogen binding epitope is therefore localized on a narrow ridge and has a length of approximately 17 angstroms. The data also indicate a strong conservation of the epitope in the laminin gamma1 chains of several invertebrates.

Amino Acid Sequence↗
PubMed2004

Imposing structure on a Corsi-type task: evidence for hierarchical organisation based on spatial proximity in serial-spatial memory.

Structure was imposed on a tapping task by requiring participants to reproduce sequences of responses to icons organised in spatial clusters. A first experiment featured sequences either segregated or not segregated by clusters. Accuracy was higher for sequences segregated by clusters. Moreover, inter-response times were longer at cluster boundaries than within cluster boundaries. To rule out possible confounding effects of movement length, this temporal pattern was replicated in a second experiment requiring a single response indicating the next sequential step, following the presentation of a portion of a previously practised sequence. These results suggest that sequence reproduction can be sustained by a hierarchical representation based on spatial proximity and provide a first indication of the role of spatial structure in serial-spatial memory.

Adolescent↗
PubMed2003

Revisiting the rDNA sequence diversity of a natural population of the arbuscular mycorrhizal fungus Acaulospora colossica.

In 1999, the diversity of a field population of the arbuscular mycorrhizal (AM) fungus Acaulospora colossica was characterized using DNA sequence data. Since 1999, AM fungal sequences have accumulated rapidly within public databases. Moreover, novel phylogenetic tools have been developed and can be used to interpret the data. A second analysis of those sequences collected in 1999 demonstrates that while the majority of the sequences are, in fact, sequences of A. colossica; a minority of the sequences still cannot be identified with confidence. Those sequences identified as A. colossica can be used to show that (1) the nuclear rDNA ITS regions are remarkably diverse, and (2) sequences isolated from different spores of the same site may be more closely related to each other than to sequences of other sites, so that the genetic diversity of an AM fungal field population may be spatially structured; however, identical sequences can also be recovered from different sites.

DNA, Fungal↗