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At least 649 records · Page 36Linked to original sources

Fast 1H spectroscopic imaging using steady state free precession and spectral-spatial RF pulses.

Recently, new methods for fast (1)H spectroscopic imaging based on the condition of steady state free precession (SSFP) were introduced to achieve a high signal-to-noise ratio at short minimum measurement times. In this work, a major improvement is presented to overcome a crucial drawback in some of the former sequences: the lack of spatial selectivity. Good spectral selectivity at very high sampling efficiency can be achieved by using spectral-spatial RF pulses, and combined with localised shimming. Results are shown from both phantom experiments and in vivo studies on the rat brain acquired at 4.7 T.

Animals↗

Spatial transcriptomics-aided localization for single-cell transcriptomics with STALocator.

Single-cell RNA-sequencing (scRNA-seq) techniques can measure gene expression at single-cell resolution but lack spatial information. Spatial transcriptomics (ST) techniques simultaneously provide gene expression data and spatial information. However, the data quality of the spatial resolution or gene coverage is still much lower than the quality of the single-cell transcriptomics data. To this end, we develop a ST-Aided Locator for single-cell transcriptomics (STALocator) to localize single cells to corresponding ST data. Applications on simulated data showed that STALocator performed better than other localization methods. When applied to the human brain and squamous cell carcinoma data, STALocator could robustly reconstruct the relative spatial organization of critical cell populations. Moreover, STALocator could enhance gene expression patterns for Slide-seqV2 data and predict genome-wide gene expression data for fluorescence in situ hybridization (FISH) and Xenium data, leading to the identification of more spatially variable genes and more biologically relevant Gene Ontology (GO) terms compared with the raw data. A record of this paper's transparent peer review process is included in the supplemental information.

Single-Cell Analysis↗

Intellectual and developmental differences in external memory strategies.

External memory strategies (e.g., moving objects) were investigated in 11-year-old children with mild mental retardation and 7- and 11-year-olds without mental retardation. Participants attempted to place objects at specified spatial locations after hearing sequences of tape-recorded instructions. During baseline, children with mental retardation and 7-year-olds used external strategies more frequently than did 11-year-olds. All three groups used external strategies after prompting that represented the correct spatial locations, and all used the same tactics. In contrast to expected deficiencies in the use of strategies, results show areas of overlap in strategy capabilities among the groups.

Child↗

In vivo enhancer analysis of human conserved non-coding sequences.

Identifying the sequences that direct the spatial and temporal expression of genes and defining their function in vivo remains a significant challenge in the annotation of vertebrate genomes. One major obstacle is the lack of experimentally validated training sets. In this study, we made use of extreme evolutionary sequence conservation as a filter to identify putative gene regulatory elements, and characterized the in vivo enhancer activity of a large group of non-coding elements in the human genome that are conserved in human-pufferfish, Takifugu (Fugu) rubripes, or ultraconserved in human-mouse-rat. We tested 167 of these extremely conserved sequences in a transgenic mouse enhancer assay. Here we report that 45% of these sequences functioned reproducibly as tissue-specific enhancers of gene expression at embryonic day 11.5. While directing expression in a broad range of anatomical structures in the embryo, the majority of the 75 enhancers directed expression to various regions of the developing nervous system. We identified sequence signatures enriched in a subset of these elements that targeted forebrain expression, and used these features to rank all approximately 3,100 non-coding elements in the human genome that are conserved between human and Fugu. The testing of the top predictions in transgenic mice resulted in a threefold enrichment for sequences with forebrain enhancer activity. These data dramatically expand the catalogue of human gene enhancers that have been characterized in vivo, and illustrate the utility of such training sets for a variety of biological applications, including decoding the regulatory vocabulary of the human genome.

Animals↗

Hand movement span after mild traumatic brain injury: a longitudinal study.

This study examined whether memory span was impaired during the acute and post-acute phases following mild traumatic brain injury (mTBI). Twenty-two adults with mTBI were compared with 22 controls on computerized tasks of immediate memory for verbal, spatial, and hand movement sequences under no interference (baseline) and articulatory suppression conditions. Groups were assessed within a month and followed up 3-12 months post-injury. In the acute phase, there were no group differences across tasks under either condition. At follow-up, all spatial and verbal span scores and associated practice effects were equivalent across groups. Yet for the hand movement task, baseline movement span was worse for the mTBI group suggesting that they failed to benefit from practice to the same extent as controls. Furthermore, the fact that this group difference in span scores disappeared when articulatory suppression was imposed indicates that successful hand movement task performance involves verbal recoding.

Adult↗

Three cryptochromes are rhythmically expressed in Xenopus laevis retinal photoreceptors.

PURPOSE: To clone Xenopus laevis cryptochromes (crys) and to understand their role in the Xenopus retinal clock. METHODS: We designed degenerate PCR primers based on homology between mouse and human crys. DNA fragments generated from these PCR reactions were used to screen a Xenopus retinal cDNA library. Three independent clones were identified and sequenced. The temporal and spatial expression of these genes in retina were studied by Northern blot analysis and in situ hybridization. RESULTS: We cloned three cry homologs from Xenopus laevis retina. We named them xcry1, xcry2a, and xcry2b based on their high homology to the mouse crys. Sequence analysis shows that these Xenopus CRYs have more than 85% identity to mouse CRYs at the amino acid level. Northern blot analysis demonstrated that all three xcrys are rhythmically expressed in the retina with peaks at different times of the day. The xcrys are expressed in a variety of tissues. In retina, they are expressed predominantly in photoreceptor cells. CONCLUSIONS: Our finding of cry expression in Xenopus photoreceptor cells further supports the idea of independent circadian oscillators being present in these cells. The sequence similarities to mouse crys suggest similar functions in the circadian clock. However, their distinct temporal expression patterns suggest some unique role for xCRY in the Xenopus retina.

Amino Acid Sequence↗

A kinematic study of lingual coarticulation in VCV sequences.

Intra-articulator anticipatory and carryover coarticulation were assessed in both temporal and spatial terms. Three subjects produced VCV sequences with velar stop consonants and back vowels. Pulsed ultrasound was used to examine the vertical displacement, duration, and maximum velocity of the tongue dorsum raising (VC transition) and lowering (CV transition) gestures. Anticipatory coarticulation was primarily temporal for two subjects, with decreases in the duration of the VC transition accompanying increases in displacement for the CV transition. Carryover coarticulation was primarily spatial for all three subjects, with decreases in CV displacement and maximum velocity accompanying increases in VC displacement. It is suggested that these intra-articulator patterns can be accounted for in terms of an interaction between the raising gesture and a vowel-specific onset time of the lowering gesture towards the vowel. The implications of this kinematic characterization are discussed.

Humans↗

Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product.

The maternal gene dorsal encodes a nuclear protein acting as a morphogen that determines the size and fate of regions along the dorsal-ventral axis of the Drosophila embryo. From previous genetic and biochemical studies it was hypothesized that dorsal might be responsible for the activation of the zygotic gene twist. In this report, regulatory sequences required for correct spatial and quantitative expression of twist are defined, by using phenotypic rescue and studying twist-beta-galactosidase expression. In addition, by transient cotransfection assays, we show that the dorsal protein specifically activates expression from the twist promoter. We demonstrate that dorsal is a sequence-specific DNA-binding protein that recognizes a motif similar to that recognized by the mammalian transcriptional activator NF-kappa B.

Animals↗

Efficient parameterized algorithms for biopolymer structure-sequence alignment.

Computational alignment of a biopolymer sequence (e.g., an RNA or a protein) to a structure is an effective approach to predict and search for the structure of new sequences. To identify the structure of remote homologs, the structure-sequence alignment has to consider not only sequence similarity, but also spatially conserved conformations caused by residue interactions and, consequently, is computationally intractable. It is difficult to cope with the inefficiency without compromising alignment accuracy, especially for structure search in genomes or large databases. This paper introduces a novel method and a parameterized algorithm for structure-sequence alignment. Both the structure and the sequence are represented as graphs, where, in general, the graph for a biopolymer structure has a naturally small tree width. The algorithm constructs an optimal alignment by finding in the sequence graph the maximum valued subgraph isomorphic to the structure graph. It has the computational time complexity O[k(t)N(2)] for the structure of N residues and its tree decomposition of width t. Parameter k, small in nature, is determined by a statistical cutoff for the correspondence between the structure and the sequence. This paper demonstrates a successful application of the algorithm to RNA structure search used for noncoding RNA identification. An application to protein threading is also discussed.

Algorithms↗

Multiomics approaches to cardiovascular disease: technological innovations and clinical translation.

Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, reflecting a persistent gap between clinical phenotyping and the molecular mechanisms that govern disease initiation, progression, and interindividual variability. Recent advances in emerging technologies have fundamentally reshaped cardiovascular physiology by enabling high-resolution, cross-layer profiling of the heart and vasculature across genomic, epigenomic, transcriptomic, proteomic, metabolomic, lipidomic, glycomic, and fluxomic layers, increasingly at single-cell and spatial resolution. These approaches reveal CVD as a coordinated, multilayered process driven by dynamic interactions among cell types, regulatory programs, and metabolic states, rather than isolated gene-level defects. In this review, we synthesize how emerging multiomic, computational, and functional genomic technologies are redefining the study of cardiovascular disease across molecular, cellular, and tissue levels. We highlight recent innovations in single-cell and spatial atlases, long-read sequencing, proteomics and metabolomics, integrative data modeling, and functional omics approaches, including genome-scale perturbation screens and single-cell perturbation frameworks. These platforms enable mechanistic dissection of regulatory circuits, distinguish primary disease drivers from secondary adaptations, and directly assess therapeutic reversibility, advancing the field beyond associative biomarker discovery toward mechanism-guided target prioritization. We further discuss key methodological and translational challenges accompanying high-dimensional cardiovascular data, including preanalytical variability, control selection, temporal misalignment across molecular layers, population diversity, and reference bias. By integrating technological innovation with computational rigor and functional validation, this review frames emerging omics-enabled strategies as a unified, physiologically grounded framework for translating molecular insight into clinically meaningful cardiovascular phenotypes and advancing precision cardiovascular medicine.

Humans↗

Spatially varying steady state longitudinal magnetization in distant dipolar field-based sequences.

Sequences based on the distant dipolar field (DDF) have shown great promise for novel spectroscopy and imaging. Unless spatial variation in the longitudinal magnetization, Mz(s), is eliminated by relaxation, diffusion, or spoiling techniques by the end of a single repetition, unexpected results can be obtained due to spatial harmonics in the steady state MzSS(s) profile. This is true even in a homogeneous single-component sample. We have developed an analytical expression for the MzSS(s) profile that occurs in DDF sequences when smearing by diffusion is negligible in the TR period. The expression has been verified by directly imaging the MzSS(s) profile after establishing the steady state.

Magnetic Resonance Imaging↗

Capacity limitations in memory for visual locations.

This paper examines people's ability to make judgments which require them to know the relative positions of objects that are not simultaneously visible is examined. It has previously been shown that people can accurately perform such a task. The current experiments test the capacity limits for such tasks. Two experiments were conducted that required subjects to make spatial judgments based on sequences of points presented two at a time. It was shown that, whereas subjects can perform accurately when memory for a small number of dots (about four) is required, increasing the number of dots results in a radical reduction in performance. This argues against both the idea that spatial memory is based on a linguistic description and the idea that it is based on an image-like representation. Rather it appears that one can form an accurate representation of the spatial properties of a small number of objects.

Eye Movements↗

Enhancing and accelerating cell type deconvolution of large-scale spatial transcriptomics slices with dual network model.

MOTIVATION: Cell type deconvolution deciphers spatial distribution of mRNA transcripts at single cell level by integrating single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data to infer mixture of cell types of spots in slices. Current algorithms are criticized for neglecting connection between scRNA-seq and spatial transcriptomics data, as well as time-consuming, hampering their application to large-scale datasets. RESULTS: In this study, we propose a joint learning nonnegative matrix factorization algorithm for fast cell type deconvolution (aka jMF2D), which integrates scRNA-seq and spatial transcriptomics data with network models. To bridge scRNA-seq and spatial transcriptomics data, jMF2D jointly learns cell type similarity network to enhance quality of signatures of cell types, thereby promoting accuracy and efficiency of deconvolution. Experiments demonstrate that jMF2D outperforms state-of-the-art baselines in terms of accuracy by saving about 90% running time on various datasets generated by different platforms. Furthermore, it can also facilitates the identification of spatial domains and bio-marker genes, providing an efficient and effective model for analyzing spatial transcriptomics data. AVAILABILITY AND IMPLEMENTATION: The software is coded using python, and is free available for academic https://github.com/xkmaxidian/jMF2D.

Algorithms↗

Wavelike isomorphic prepatterns in development.

The patterns generated by these mechanisms are usually wavelike spatial patterns in the distribution of the chemical components and/or physical properties of the organism or tissue being considered. In this paper the range of patterns generated by one of these mechanisms, namely the reaction-diffusion (RD) system (Turing, 1952), is reviewed and its potential to function as a source of isomorphic prepatterns for the regulation of development in a wide range of organisms is illustrated. Examples have been chosen to show the capacity of an RD system to generate a single stationary spatial prepattern, as well as a travelling wavelike spatial prepattern. However, the full potential of an RD system to regulate development stems from its capacity to spontaneously generate a temporal sequence of isomorphic stationary wavelike spatial prepatterns, rather than just a single isomorphic stationary spatial prepattern. To demonstrate this point the examples presented include the morphogenesis of the skin and some of its appendages, as well as the early decisions in the embryogenesis of Drosophila leading to segmentation. The mini-review begins by comparing the concepts of positional information and a temporal sequence of isomorphic prepatterns, which represent two quite different approaches to understanding the spatial and temporal regulation of cellular differentiation.

Animals↗

Spatial and temporal expression of the orchid floral homeotic gene DOMADS1 is mediated by its upstream regulatory regions.

The orchid floral homeotic gene, DOMADSI, is a marker gene specifically expressed in the transitional shoot apical meristem during floral transition in Dendrobium Madame Thong-In. DOMADSI is not detectable in vegetative tissues except a weak expression in the stem. Its transcript is uniformly localized in both of the inflorescence meristem and floral primordia, and later expressed in almost all of the floral organs. We isolated and sequenced a 3.5 kb DOMADSI promoter fragment upstream of the transcription start site, demonstrating the location of several putative DNA-binding sites, through which MADS-box and class I knox genes may modulate the DOMADSI expression. To gain insight into the molecular basis of the regulation of DOMADS1, deletion analysis of the DOMADSI::beta-glucuronidase (GUS) gene fusions was performed by means of the stable orchid transformation systems. The study shows that the full-length upstream promoter sequence confers the same spatial and temporal GUS staining pattern as that of the distribution of DOMADSI RNA during orchid development. We also identified the distinct cis-acting regulatory regions required for the control of DOMADS1 expression in vegetative and reproductive tissues, as well as the shoot apical meristem during floral transition.

5' Flanking Region↗

[Diffuse infiltrative lung diseases: histological support of elementary lesions observed on tomodensitometry].

High resolution computed tomography (TDM-HR) is now the technique of choice in the diagnosis and management of diffuse infiltrative lung disease (PID). After a brief review of the technique the authors describe the normal appearance; anatomical observations and the in vivo findings have shown that TDM-HR allow for the exploration of details of structure down to the second pulmonary lobule. Thus, through the alterations that are transmitted in the lobular area, and from its contents and its limits, PID has led to the elaboration of a new semeiology. The authors review the basic computed tomographic images and correlate these in each case with the histological evidence. The spatial distribution and the time sequence of the elementary images are the two other terms in the diagnostic equation of PID. The spatial distribution of several elementary images presents in TDM-HR a superior aetiological pointer to that which is furnished by thoracic radiographs; and the time sequence may furnish a useful indication as to the progress of the treated disease. Sarcoidosis, histiocytosis X, idiopathic interstitial fibrosis and lymphangitis carcinomatosis would serve as examples. Nevertheless, the authors point out that it would be dangerous during the period of evaluation to prematurely extend to all cases of PID conclusions which are only possible to make at present in a restricted number of disorders.

Histiocytosis, Langerhans-Cell↗

Comparative genomic analysis as a tool for biological discovery.

The recent completion of the human genome sequence has enabled the identification of a large fraction of our gene catalogue and their physical chromosomal position. However, current efforts lag at defining the cis-regulatory sequences that control the spatial and temporal patterns of each gene's expression. This task remains difficult due to our lack of knowledge of the vocabulary controlling gene regulation and the vast genomic search space, with greater than 95% of our genome being noncoding. Recent comparative genomic-based strategies are beginning to aid in the identification of functional sequences based on their high levels of evolutionary conservation. This has proven successful for comparisons between closely related species such as human-primate or human-mouse, but also holds true for distant evolutionary comparisons, such as human-fish or human-bird. In this review we provide support for the utility of cross-species sequence comparisons by illustrating several applications of this strategy, including the identification of new genes and functional non-coding sequences. We also discuss emerging concepts as this field matures, such as how to properly select which species for comparison, which may differ significantly between independent studies.

Animals↗

Simultaneously recording local luminance responses, spatial and temporal interactions in the visual system with m-sequences.

In this paper, an extended multifocal VEP/ERG paradigm, referred to as the unified multifocal electroretinography and visual evoked potential paradigm (UMEV), is presented. This paradigm allows a simultaneous recording of luminance responses, temporal interactions, spatial interactions and spatial-temporal interactions. Two studies were conducted to demonstrate the capability and validity of the UMEV. The results show that the UMEV system derives a significant spatial interaction VEP in addition to a similar luminance response (mfERG) and pattern reversal VEP (mfVEP) to the VERIS system. Second, the amplitude of spatial interaction VEP is diminished by increasing the distance between two stimuli while the amplitude of temporal interaction VEP remain relatively unchanged.

Adult↗