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At least 163 records · Page 9Linked to original sources
PubMed1985

Control of DNA replication and spatial distribution of defined DNA sequences in salivary gland cells of Drosophila melanogaster.

In dividing cells, each sequence replicates exactly once in each S-phase, but in cells with polytene chromosomes, some sequences may replicate more than once or fail to replicate during S-phase. Because of this differential replication, the control of replication in polytene cells must have some unusual features. Dennhöfer (1982a) has recently concluded that the total DNA content of the polytene cells of Drosophila salivary glands exactly doubles in each S-phase. This observation, along with previous studies demonstrating satellite underreplication in salivary gland cells, led us to consider the hypothesis that there is a "doubling of DNA" mechanism for the control of DNA replication in polytene cells. With this mechanism, a doubling of DNA content, rather than the replication of each sequence, would signal the end of a cycle of DNA replication. To test this hypothesis, we have reinvestigated the replication of several sequences (satellite, ribosomal, histone and telomere) in salivary gland cells using quantitative in situ hybridization. We find that underreplication of some sequences does occur. In addition we have repeated Dennhöfer's cytophotometric and labeling studies. In contrast to Dennhöfer, we find that the total DNA contents of nonreplicating nuclei do reflect this partial replication, in accord with Rudkin's (1969) result. We conclude that DNA replication in polytene cells is controlled by modifications of the mechanism operating in dividing cells, where control is sequence autonomous, and not by a "doubling of DNA" mechanism. In situ hybridization to unbroken salivary gland nuclei reveals the distribution of specific sequences. As expected, satellite, histone and 5S sequences are usually in a single cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Dual role of calmodulin in excitable cells.

Consideration of the enzymatic reactions governing calcium channel phosphorylation and dephosphorylation leads one to deduce that there exist separate groups of enzymes, membrane-bound and cytoplasmic that are activated by a common mediator, calmodulin (CaM), whose time-dependent appearance (via diffusion) at both locales is controlled by both intracellular calcium levels and electrostatic interaction with the membrane. In brief, the change in the sign and extent of the electrical charge borne by the modulator in the presence of calcium (Ca) brings about the electrostatic attraction that enables the transport of [Ca-CaM] to the membrane. This translocation of Ca-CaM makes possible a sequential activation of cellular enzymes whose locations differ. The sequence, both spatial and temporal, of the activation of various cellular enzymes by Ca-CaM appears to be a control network shared in common by excitable cells containing a stimulus-response pathway mediated by second messengers.

Adenylyl Cyclases↗
PubMed1990

Topographic segmentation of waking EEG in medication-free schizophrenic patients.

Lehmann has demonstrated that EEG topography can be used to segment EEG map series into a sequence of spatially stationary segments characterized by location of potential maxima and minima. We employed topographic segmentation techniques to study 9 channel EEGs recorded from 11 medication-free schizophrenic patients and 10 normal controls during resting and active task conditions, retesting 8 patients after neuroleptic treatment. To define EEG segments, average reference potential maps corresponding to global field power peaks in theta, alpha, and low beta activity were classified according to locations of extreme minimum and maximum values. Normals and schizophrenics did not differ in the number or types of switches between segments, or the frequency of hemisphere crossing of potential extrema. However, EEGs of normal subjects were characterized by significantly more (P less than 0.003) unused theta segment types (of a theoretically possible 36). Moreover, medication significantly (P less than 0.02) increased the number of unused theta segment types in EEGs of schizophrenics. We interpret these findings as evidence of increased spatial variability of brain electrical activity in schizophrenics and discuss their functional implications.

Adult↗
PubMed1993

MR imaging of fat-containing tissues: valuation of two quantitative imaging techniques in comparison with localized proton spectroscopy.

Since lipid protons, consisting mainly of triacylglycerols (TAG), are rather mobile, magnetic resonance imaging (MRI) is ideally suited for the examination of fat-containing tissues such as bone marrow. In contrast to water protons, however, lipid protons are chemically distinct and give rise to at least eight resonance peaks with different T1 and T2 relaxation times in the 1H spectrum. This is why the characterization of fat-containing tissues by quantitative MRI is much more difficult than that of most other tissues. In our study we wanted to examine the accuracy and the potential of a 1H chemical shift imaging (CSI) technique and a multiple spin-echo imaging (MSEI) technique. A stimulated-echo (STEAM) sequence for spatially localized proton spectroscopy was used as the reference method. In the first part of this paper, we describe quantitative imaging experiments which were performed to assess the accuracy of the fat-water separation according to the Dixon method and the bi-exponential decomposition of the MSEI data. For that purpose, we used a two-compartment phantom filled with either an aqueous Gd-DTPA solution and vegetable oil or with two different aqueous Gd-DTPA solutions, respectively. The analysis of the 1H CSI data revealed that the presence of non-methylen protons in neutral fats leads to a slight under-estimation (of about 15%) of the relative fat fraction. The error is described theoretically and verified quantitatively by STEAM measurements. The bi-exponential analysis of the transverse relaxation data, on the other hand, yields reliable T2 values if the relative proton density of both components is higher than 15%. IN the second part of our investigation, the same techniques were applied to acquire data from the subcutaneous fatty tissue, the femoral head, and the lumbar vertebrae of three healthy volunteers. In the bone marrow spectra, only two broad resonances could be resolved; they were superpositions of diverse molecular groups with different T1 and T2 relaxation times. In these cases, localized proton spectroscopy does not provide additional information with respect to 1H CSI. The MSEI data of the three examined fat containing tissue regions were adequately fitted by a bi-exponential function despite the fact that there were much more chemically distinct protons present in fatty tissues.

Adipose Tissue↗
PubMed1996

Visualizing the spatial relationships between defined DNA sequences and the axial region of extracted metaphase chromosomes.

Using fluorescence in situ hybridization to extracted metaphase chromosomes, we present visual evidence that specific human DNA sequences occupy distinctive positions with respect to the axial region of chromosomes and that the DNA is organized into loops emanating from this region. In a stretch of unique DNA on chromosome 11, large loops of DNA can be traced and one specific region associated with the axial region of the chromosome. Within rDNA, nontranscribed spacer sequences are more closely apposed to the chromosome axis than are rRNA genes. Heterochromatic and euchromatic DNAs appear to be organized into loops of similar size. We could not detect loops at centromeres; most alphoid DNA appears to remain close to the axial region.

Centromere↗
PubMed1996

Correct Hox gene expression established independently of position in Caenorhabditis elegans.

The Hox genes are expressed in a conserved sequence of spatial domains along the anteroposterior (A/P) body axes of many organisms. In Drosophila, position-specific signals located along the A/P axis establish the pattern of Hox gene expression. In the nematode Caenorhabditis elegans, it is not known how the pattern of Hox gene expression is established. C. elegans uses lineal control mechanisms and local cell interactions to specify early blastomere identities. However, many cells expressing the same Hox gene are unrelated by lineage, suggesting that, as in Drosophila, domains of Hox gene expression may be defined by cell-extrinsic A/P positional signals. To test this, we have investigated whether posterior mesodermal and ectodermal cells will express their normal posterior Hox gene when they are mispositioned in the anterior. Surprisingly, we find that correct Hox gene expression does not depend on cell position, but is highly correlated with cell lineage. Thus, although the most striking feature of Hox gene expression is its positional specificity, in C. elegans the pattern is achieved, at least in part, by a lineage-specific control system that operates without regard to A/P position.

Animals↗
PubMed2026

Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.

Allogeneic hematopoietic cell transplantation cures hematologic diseases but is limited by acute graft‑versus‑host disease. How human T cell clones drive epithelial injury remains poorly mapped. We studied 31 transplant recipients, integrating longitudinal T cell antigen receptor (TCR) profiling with single-cell RNA sequencing/TCR sequencing and spatial transcriptomics to track T cell clonal dynamics. We developed DecompTCR to resolve temporal dynamics and adapted computational tools to map clone phenotypes and niches in tissue. Our analyses revealed that cyclophosphamide selectively depletes alloreactive clones, although insufficient early expansion leads to incomplete depletion and severe disease. Severe graft‑versus‑host disease is marked by persistent expansion of alloreactive clones, rewiring of homeostatic cell types and diversification of donor-derived CD8+ clonotypes that acquire Hobit (ZNF683)+ tissue‑resident memory T (TRM) cell programs during migration to epithelium. Spatial deconvolution identified CD8+ effector/Hobit+ TRM hubs near intestinal stem‑cell-rich crypt bases and crypt‑loss regions. This clonotype‑resolved framework links tissue‑instructed TRM cell remodeling to localized epithelial injury, nominating early-repertoire dynamics and spatial hub burden as biomarkers.

Journal Article↗
PubMed1990

Cellular sources of noncollagenous matrix proteins: role of fat-storing cells in fibrogenesis.

The main types of noncollagenous ECM proteins in liver are FN, laminin, PGs and elastin. Also present is a pure carbohydrate polymer, hyaluronic acid. Their concentrations increase during fibrogenesis in a specific sequence and spatial distribution. FN is among the first to appear. The accumulation of matrix proteins in the space of Disse (perisinusoidal fibrosis) is most important for some clinical consequences of fibrosis. Perisinusoidal FSC are the cell type responsible for exaggerated ECM formation at sites of tissue injury, since these cells synthesize at a high rate in vitro all the noncollagenous matrix components occurring in fibrotic liver matrix (FN, laminin, dermatan sulfate, chondroitin sulfate, hyaluronic acid) and since FSC proliferate and transform into myofibroblast-like cells with an enhanced matrix protein synthesis rate. Recent experimental data suggest strong cellular cooperation of these cells with activated liver macrophages or Kupffer cells, platelets, and regenerating hepatocytes, which leads via a paracrine mechanism involving TGF beta, TGF alpha/EGF, PDGF, and probably other cytokines to stimulated proteoglycan synthesis, proliferation, and transformation into myofibroblast-like cells. The latter cell type has the potential of auto-stimulation (by an autocrine process) involving secretion of TGF beta and TGF alpha/EGF. Based on these findings, a model of FSC activation is proposed (Fig. 10).

Animals↗
PubMed1988

Non-invasive measurement of pulmonary arterial pressure: II. A radionuclide method.

Pulmonary artery pulse pressure (PP) and diastolic pressure (Pd) may be obtained by applying a haemodynamic model of blood flow kinetics and wall mechanics to the pulmonary artery: Pp = rho(ws/(Ss/Sd-1))2log(Ss/Sd)-1/2 rho w2s Pd = (Sd/Ss)1/2Pp where rho is blood density, ws is peak ejection velocity, and Ss and Sd are peak maximal and end diastolic cross-sectional areas of the main pulmonary artery. The different parameters of the equations were measured from radionuclide first pass and equilibrium studies. Radionuclide first pass studies were performed in 24 patients with intravenous injection of 20 mCi of 99Tcm red blood cells with a gamma camera in a 20 degrees right anterior oblique position: data were collected in list mode, i.e. a continuous sequence of spatial and temporal coordinates of each photon. Pulmonary arterial pressure was recorded simultaneously with a microtip catheter during the first pass study. Gated first pass images of the right side of the heart were reconstructed, regions of interest drawn over the right ventricle and the main pulmonary artery (MPA) and time-activity curves generated. Peak systolic (Cs) and end diastolic (Cd) counts obtained from the MPA curve were proportional to the cross sections Ss and Sd of the MPA and Ss/Sd = Cs/Cd. The diameter (D) of the pulmonary artery was calculated as the distance between the two zeros of the second derivative of a cross-sectional profile. The averaged cross-sectional area was S = pi D2/4. ECG gated blood pool studies were performed in a LAO 40 degrees position when the tracer was at equilibrium; they were processed automatically and the right ventricular end diastolic counts (EDC) converted into volume (EDV) using an aortic volume/count ratio. Right ventricular peak ejection rate (PER) was obtained from the RV time-activity curve and the instantaneous peak ejection velocity was calculated, ws = PER X EDV/S X EDC. PP and Pd were calculated in mmHg and the radionuclide method yielded pressure values that correlated reasonably with catheterisation values: PP(rad) = 0.99 PP(cath)-0.55, r = 0.84 and Pd(rad) = 0.67 Pd(cath) + 4.91, r = 0.74. We conclude that radionuclide techniques can provide a non-invasive method based on a haemodynamic model for measuring pulmonary arterial pressure.

Adult↗
PubMed1995

Compartmentalization of specific pre-mRNA metabolism: an emerging view.

It is increasingly recognized that the mammalian interphase nucleus contains a number of non-membranous compartments in which macromolecules associated with different nuclear functions concentrate. This review focuses on the function of a major compartment consisting of domains highly enriched in pre-mRNA splicing components and poly (A) RNA, commonly identified by the splicing factor, SC-35. RNA synthesis, as judged interdomain space. However, uridine labels several types of nuclear RNA, only a fraction of which is pre-mRNA, and such studies cannot address the question of whether specific genes are transcribed in specific places. Similarly, interpretations of transcriptional inhibition studies are compromised by the global impact that inhibition has on nuclear structure and function, and by conflicting results. Localization of specific protein coding genes or RNAs circumvents these limitations. For several sequences studied thus far, a non-random relationship to SC-35 domains has been observed, with most, but not all, active genes encoding intron-containing pre-mRNAs showing a very high degree of association. In some cases this was directly demonstrated to be the site of transcription and processing. Consistent with earlier uridine incorporation studies, we have found that transcription occurs at the outer edge of the SC-35 domain, likely corresponding to the border of ultrastructures termed interchromatin granule clusters. These preliminary glimpses into gene localization strongly argue for a sequence-specific spatial association of some transcriptionally active genes with SC-35 domains, and suggest an integrated functional organization of the genome with these nuclear compartments enriched in splicing factors and poly (A) RNA.

Animals↗
PubMed1991

Resonant recognition model and protein topography. Model studies with myoglobin, hemoglobin and lysozyme.

This study describes the further extension of the resonant recognition model for the analysis and prediction of protein--protein and protein--DNA structure/function dependencies. The model is based on the significant correlation between spectra of numerical presentations of the amino acid or nucleotide sequences of proteins and their coded biological activity. According to this physico-mathematical method, it is possible to define amino acids in the sequence which are predicted to be the most critical for protein function. Using sperm whale myoglobin, human hemoglobin and hen egg white lysozyme as model protein examples, sets of predicted amino acids, or so-called 'hot spots', have been identified within the tertiary structure. It was found for each protein that the predicted 'hot spots', which are distributed along the primary sequence, are spatially grouped in a dome-like arrangement over the active site. The identified amino acids did not correspond to the amino acid residues which are involved in the chemical reaction site of these proteins. It is thus proposed that the resonant recognition model helps to identify amino acid residues which are important for the creation of the molecular structure around the catalytic active site and also the associated physical field conditions required for biorecognition, docking of the specific substrate and full biological activity.

Animals↗
PubMed2026

Follicular Lymphoma Transformation is Characterized by Cytokine-associated Remodeling of Stromal and Macrophage Compartments.

Across cancer, one of the most frequent examples of histologic transformation is the evolution of follicular lymphoma (FL) to an aggressive large cell lymphoma. Despite recent progress, understanding of the molecular and cellular underpinnings of transformation remains incomplete. Here, we dissect the interplay of tumor and microenvironment cell populations across transformation through a multimodal investigation of 95 FL and transformed FL (tFL) samples, including single-cell and bulk RNA-sequencing alongside spatial transcriptomics and proteomics, and validate findings across independent FL-tFL pairs. Upon transformation, fibroblasts and GPNMB+ macrophages increase while lymph-node organizing follicular dendritic and CCL21+ fibroblastic reticular cells were lost, resulting in an altered spatial distribution of cytokines that impacts T cell infiltration and macrophage differentiation and function. Secreted stromal and macrophage signals were further evident by non-invasive plasma proteomics. Taken together, our data reveal expansion of macrophages and fibroblasts as key features of transformation with potential diagnostic and therapeutic implications.

Journal Article↗
PubMed2026

The extracellular matrix in cancer-associated fibrosis: molecular mechanisms and clinical relevance.

The ECM is a dynamic component of the tumor microenvironment with a critical role in cancer progression, invasion, metastasis, immune exclusion, and response to therapy. Recent advances in proteomic analyses investigating the insoluble ECM fractions (termed "matrisome analysis"), along with single-cell RNA sequencing and spatial transcriptomics, have revealed cancer-specific patterns of ECM remodeling. These studies have identified a panel of recurrently upregulated ECM proteins, including annexin A1, fibrillin-1, fibronectin, periostin, and tenascin-C, actively contributing to tumor growth, invasion, angiogenesis, and immune exclusion. The expression of the cancer-associated ECM is largely driven by cancer-associated fibroblasts (CAFs), whose molecular diversity has been dissected through single-cell profiling and consolidated in emerging CAF atlases across cancers. By investigating the matrisome composition and CAF heterogeneity, these studies have unraveled the pivotal role of the stroma in shaping tumor biology. Based on these discoveries, ECM proteins and CAFs are now being explored as biomarkers and therapeutic targets. Future integration of multi-omics datasets with clinical outcomes will help to translate these insights into novel biomarkers for patient stratification and stroma-directed therapeutic interventions.

Humans↗
PubMed1994

Robust physics-based analysis of thermal and visual imagery.

Extensions to an existing physics-based approach for intersensory perception in which thermal and visual imagery of outdoor scenes is analyzed simultaneously for object recognition are discussed. The existing approach uses a model that is based on the principle of the conservation of energy at the surface of the imaged object. The model permits the computation of physically meaningful features that may be used for object classification. Two significant extensions are discussed. First, the model is used to analyze a temporal sequence of spatially registered thermal and visual imagery. Second, the energy-exchange model is used to formulate a linear-regression task in which the physical properties of the imaged object are the unknown parameters that are estimated. A statistically robust scheme is presented for this task. The robust technique minimizes sensitivity to outliers caused by segmentation errors and misregistration, which are endemic to multisensor fusion. Thus reliable physics-based features are made available by this approach.

Hot Temperature↗
PubMed2026

Microplastics and nanoplastics-related genes signature predicts prognosis in pancreatic ductal adenocarcinoma and functional validation of interleukin 1 alpha.

BACKGROUND: Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, have garnered significant attention from the global scientific community due to their potential threats to human health, particularly their association with the occurrence and development of cancer. The goal of our study is to create a predictive marker for pancreatic ductal adenocarcinoma (PAAD) based on MNPs-related genes, with the purposes of predicting survival outcomes and assessing the tumor immune microenvironment. METHODS: Using multi-cohort data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC), we assessed the association between MNPs and PAAD prognosis through the Xiantao Academic (https://www.xiantao.love/). The development of a prognostic signature was followed by an assessment of its significance through the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and decision curve analysis (DCA). The validity of the risk model was confirmed through the ICGC and GSE71729 cohorts. The model was then assessed for levels of tumor immune infiltration. To explore MNPs-related genes expression characteristics within immune cells in PAAD, we performed single-cell RNA sequencing and spatial transcriptomics analysis through the Sparkle Platform (https://grswsci.top/). Finally, in vitro experiments were conducted to investigate the biological function of interleukin 1 alpha (IL1A). RESULTS: A four-gene signature comprising XDH, IL1A, KIF20A, and ASPM, based on MNPs, was developed to stratify PAAD patients into two distinct risk groups. The high-risk group showed a significantly poorer prognosis. A similar trend was verified in the external cohorts ICGC and GSE71729. The signature risk score affected immune cell infiltration in the PAAD microenvironment. The infiltration of B cells, CD8+ T cells, cytotoxic cells, immature dendritic cells (iDCs), mast cells, plasmacytoid dendritic cell (pDC), T cells, Tem cells, T follicular helper (TFH) cells, and T helper 17 (Th17) cells had a positive correlation with the low-risk group. In contrast, high-risk patients tended to have increased number of T helper (Th2) cells and higher expression of SIGLEC15, CD274, IGSF8. Knockdown of IL1A in PAAD cells inhibited their tumor proliferation ability in vitro. CONCLUSIONS: Using MNPs-related genes, we built a prognostic model for PAAD, revealing that patients with high-risk scores are likely to have a worse prognosis. This model is designed to develop personalized treatment strategies tailored to the specific needs of each patient, thereby improving clinical outcomes for PAAD patients. Furthermore, IL1A could be a promising therapeutic candidate for PAAD.

Microplastics↗