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At least 1,333 records · Page 74Linked to original sources

The human amygdaloid complex: a cytologic and histochemical atlas using Nissl, myelin, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining.

We examined the distribution of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase enzyme activity in the human amygdala using histochemical techniques. Both methods revealed compartments of higher or lower enzyme activity, in cells or neuropil, which corresponded to the nuclear subdivisions of the amygdala as defined with classical Nissl and myelin methods. The boundaries between the histochemical compartments were usually so sharp that the identification of these nuclear subdivisions was enhanced. There was also variation of staining intensity within many of the nuclear subdivisions, such as the lateral and central nuclei, anterior amygdaloid area and the intercalated groups. This histochemical difference corresponded to more subtle differences in Nissl and myelin staining patterns, and suggests further structural subdivisions of potential functional significance. We present a revised scheme of anatomical parcellation of the human amygdala based upon serial analysis with all four techniques. Our expectation is that this will allow the delineation of a clearer homology between the cytoarchitectonic subdivisions of the human amygdala and those of experimental animals.

Acetylcholinesterase↗

Stereotaxic atlas of the trigeminal ganglion in rat, cat, and monkey.

Stereotaxic maps of the trigeminal ganglion of rat, cat and monkey are presented. Each ganglion drawing is a composite from means of coordinates from several ganglions sampled. Depth coordinates are supplied in relation to both the dorsal surface of each ganglion and the cranial bone directly underlying the ganglion.

Animals↗

Atlas of serotonergic cell bodies in the cat brainstem: an immunocytochemical analysis.

The localization and relative number of serotonergic (5HT) cell bodies in the brainstem of the cat were studied through the use of a specific immunocytochemical technique. A surprisingly large number of 5HT cells were found in regions in addition to the classical raphe nuclei (obscurus, pallidus, magnus, centralis superior, and dorsalis). Foremost among these were: the ventral medulla, just dorsal to the pyramidal tract and inferior olivary complex, and especially the area in and around the lateral reticular nucleus; the dorsal pons, surrounding the central reticular core, and in the central gray area; and a region in the mesencephalon, in and around the interpeduncular nucleus. The advantages and disadvantages of the existing schemas for subdividing and labeling groups of brain 5HT neurons are discussed.

Animals↗

An endothelial RNA splicing atlas catalogs effects of IL-1β and identifies an alternative PROCR isoform with genetic links to pleiotropic vascular disease.

Alternative splicing (AS) alters the sequence and dynamics of mRNA but has not been comprehensively annotated in human endothelial cells (ECs). EC dysfunction is a hallmark of complex inflammatory diseases, including cancer and atherosclerosis. Therefore, we modeled inflammation in vitro using 53 genetically distinct human aortic EC lines exposed to interleukin-1β (IL-1β) or control media. This identified 1,224 differentially spliced transcripts (DSTs). DSTs were enriched for alternative first (AF) exon usage, including isoforms of several disease-associated and metabolic genes. To confirm that IL-1β-dependent AF exons were produced by alternative promoters, a quantitative measure of promoter activity was defined using epigenetic data. Ratios of histone 3 lysine 27 acetylation and binding of ERG and RELA between alternative promoters correlated RNA levels of AF exons, confirming our hypothesis. Finally, the effects of genetic variation on AS were investigated by mapping splicing quantitative trait loci (sQTLs). Significant sQTLs were tested for genetic colocalization with cardiovascular risk loci from genome-wide association studies. This identified 66 colocalized signals corresponding to 30 genes and 39 lead variants. The sQTLs identified here provide testable mechanisms explaining some of the genetic risk for vascular disease. For example, genetic association for a previously undescribed isoform of endothelial protein C receptor (PROCR) colocalized with genetic risk for deep vein thrombosis and coronary artery disease with opposing risk alleles. This study demonstrates the prevalence of inducible promoters upon inflammatory stimuli and shows that genetic risk for vascular disease may be in part governed through AS in ECs.

Humans↗

Pan-cancer single-cell atlas of immunotherapy response identifies ZNF385A as a regulator of immune evasion in small cell lung cancer.

Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of solid tumors, response rates in patients with small cell lung cancer (SCLC) remain limited, and acquired resistance is highly prevalent. The underlying mechanisms of this immunotherapy resistance remain to be fully elucidated. Clinically, SCLC typically manifests as an "immune-cold" tumor, characterized by a low abundance of CD8+ T cell infiltration and the rare formation of tertiary lymphoid structures (TLS). While DNA damage repair (DDR) is closely linked to innate immune responses, how DDR networks orchestrate the SCLC immune microenvironment remains obscure. In this study, we integrated single-cell transcriptomic data (comprising 344,447 high-quality cells) from six cancer types (BCC, CRC, HCC, HNSCC, iCCA, and SCLC). Our comparative analysis revealed a fundamental depletion of TLS-associated cellular subpopulations (e.g., CXCL13+ CD8+ T cells, HLA-DRB5+ B cells, and CXCL9+ dendritic cells) in SCLC, which was significantly correlated with aberrant DDR activity. Through high-dimensional weighted gene co-expression network analysis (hdWGCNA), we identified ZNF385A as the core hub gene within the DDR-associated module. ZNF385A is highly expressed in SCLC and is associated with poorer prognosis. In vitro, ZNF385A depletion suppressed SCLC cell proliferation and induced apoptosis, accompanied by R-loop accumulation and activation of cGAS-STING signaling, indicating a potential link between ZNF385A, genomic stability and tumor-intrinsic innate immune signaling. Collectively, these findings identify ZNF385A as a potential regulator associated with TLS deficiency and immune evasion in SCLC.

Immunotherapy resistance↗

Genome-wide epigenomic atlas and multi-omics responses of Eriocheir sinensis to natural extreme heat.

BACKGROUND: Global climate warming has led to increasingly frequent and prolonged extreme summer heat events, posing severe environmental challenges to aquaculture systems. Extreme summer heat can disrupt the performance of pond-cultured ectotherms. The Chinese mitten crab (Eriocheir sinensis) is an economically important freshwater crustacean, but coordinated molecular differences following contrasting natural summers remain incompletely characterized. RESULTS: We performed a comprehensive multi-omics analysis integrating meteorological monitoring, mRNA/lncRNA transcriptomics, small-RNA profiling of miRNAs, DNA methylomics, and LC-MS metabolomics in E. sinensis populations collected from Yancheng, China, between 2020 and 2024. Across the ten farms, survival was significantly lower in 2024, whereas yield and the proportion of large individuals showed nonsignificant downward trends. Gene-set analyses showed negative enrichment of cellular heat-response, protein-folding, oxidative-phosphorylation, and mitochondrial ATP-production terms in the 2024 cohort at the time of sampling. The integrated transcript annotation contained 72,240 lncRNAs and 63,833 mRNAs, and CpG was the predominant methylation context. Differential methylation analysis identified 73 regions and 185 cytosines, with hypomethylated events predominating within the significant subset. Metabolomic profiles differed between annual cohorts and mapped to carbohydrate, lipid, and amino-acid pathways. Cross-omics integration prioritized eight candidate genes-ADCY9, UNC79, UBN1, IFT52, ACO2, LOC126986070, LOC127001126, and LOC126997895-and qPCR reproduced the reported directions of expression for selected RNAs. CONCLUSION: This study provides the first integrative multi-omics framework for understanding chronic heat adaptation in E. sinensis. By linking transcriptomic, epigenomic, and metabolic remodeling, we elucidate the molecular mechanisms underlying energy imbalance, epigenetic reprogramming, and immune dysregulation during prolonged thermal stress. These findings offer valuable insights and genomic resources for breeding heat-tolerant crab strains and improving aquaculture resilience under ongoing climate change.

DNA methylation↗

A deep metagenomic atlas of Qinghai-Xizang Plateau lakes reveals their microbial diversity and salinity adaptation mechanisms.

The Qinghai-Xizang Plateau (QXP), harboring the planet's highest density of plateau lakes, offers an exceptional biogeographic environment for studying extremophilic microbial communities and their adaptation to salinity. Through deep metagenomic sequencing, we construct the Qinghai-Xizang Lake Sediment Genome (QXLSG) catalog, a high-resolution genomic catalog comprising 5,866 metagenome-assembled genomes (MAGs), 58.16 million non-redundant protein encoding genes, and 19,008 biosynthetic gene clusters. Notably, 80.78% of the 2,742 species-level MAGs represent undescribed taxa, significantly expanding the known microbial diversity. Salinity emerges as the primary environmental factor influencing microbial community. Functional annotation highlights that the "salt-out" strategy, particularly the uptake of glycine betaine, is the main mechanism for salinity tolerance. This strategy is prevalent in both hypersaline lake communities and the dominant microbial phyla. Overall, this study provides a crucial genetic resource for future bioprospecting and deepens our understanding of the fundamental mechanisms of microbial adaptation to extreme saline environments.

Lakes↗

Comprehensive mass spectrometry screening-derived atlas of HDAC inhibitors reveals histone-specific acetylation changes.

Histone deacetylase inhibitors (HDACis) have emerged as valuable therapeutics for cancer and other diseases; however, their effects on histone post-translational modification remain poorly characterized. Here, we applied quantitative mass spectrometry and high-throughput sequencing to systematically profile site-specific changes in histone modifications in response to a panel of HDACis. This platform enabled mapping of histone modification changes across hundreds of sites, including low-abundance histone marks. Furthermore, an integrative analysis of chromatin immunoprecipitation followed by sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) data identified genome-wide binding sites for the low-abundance histone modification of H2A.Z acetylation in HeLa and MDA-MB-231 breast cancer cells, highlighting the role of H2A.Z acetylation in regulating gene expression across diverse biological pathways, including specific genes involved in tumor suppressor pathways. Our findings provide a functional resource for identifying and quantifying histone modification changes and transcriptional regulation of histone H2A.Z acetylation following pharmacological perturbation.

Histone Deacetylase Inhibitors↗

A population-based atlas and clinical target volume for the head-and-neck lymph nodes.

PURPOSE: To develop a population-based three-dimensional lymph node target volume of the head and neck. METHODS AND MATERIALS: The T2 weighted axial magnetic resonance imaging (MRI) images of 35 patients with known head and neck cancer were reviewed. An experienced head and neck radiologist marked each lymph node (LN) electronically. The images were distributed to one of 12 axial levels of the head and neck with each level representing a distinct portion of the neck based on external contours and the presence of anatomic structures. The LNs were marked with five different symbols to distinguish the superior/inferior extent of each LN within each level. With the categorization of each image into a different superior/inferior level of the neck, the registration of the images was limited to two dimensions. Nonlinear transformation accounted for inter-patient differences although no local warping was used. The co-registration used recognizable anatomic landmarks (vertebral body, mandible, maxilla, clivus as well as the sternocleidomastoid muscle, external skin contour, spinal cord) to match the patient anatomy. RESULTS: In total, 503 images were co-registered with the baseline images. The majority of the co-registrations were of good quality; 361, 122, and 20 image co-registrations scored as global, limited, and poor co-registrations respectively. One thousand and fifty seven LNs were marked, with 122 LNs marked as submandibular and submental LN. Among the levels A, B, C, D, E, F, G, H, 22, 44, 206, 199, 196, 175, 63, 35 LN were marked respectively. Noteworthy anatomic variation was observed among the different nodal groups that are summarized in the representative baseline images. CONCLUSIONS: Image registration of a series of head and neck images generates a valuable population-based lymph node map that can be used to guide the three-dimensional delineation of the elective lymph node target volume. Significant variation in the lymph node location was seen in all LN groups. The medial border of the internal jugular vein can be used as an important landmark structure in delineating the jugular LN clinical target volume and, for that reason, intravenous contrast is recommended to improve visualization. The location of the submandibular LN appear to be limited to the space anterior and lateral to the submandibular gland and are found mostly along the inferior edge of the mandible. The location of the retropharyngeal LN does vary but their location does not appear to vary with any other recognizable axial structure. The lymph node map provides another collaborating piece of evidence in defining the head and neck LN clinical target volume.

Adolescent↗

Detection and management of pornography-seeking in an online clinical dermatology atlas.

BACKGROUND: Increased use of an online educational archive of photographic dermatology case materials (DermAtlas) indicated unexpected pornography-seeking behavior and misuse. OBJECTIVE: We sought to assess the extent of archive misuse. METHODS: Web usage/request patterns were examined over a 6-month period for requests by anatomic site, diagnosis, and age group plus anatomic site. Free-text queries and referrals from external Web sites were reviewed. RESULTS: Of 7800 images, 5.5% contain genital sites. Of all requests, 11% were for anatomic sites (37% genital sites); 62% were specified for diagnoses (12% genital sites). When age group and anatomic site were specified, the relative risk of a child being requested (vs adult) was 1.48 (95% confidence interval 1.44-1.53). Of 10000 free text queries, 12% retrieved images containing genital sites. Of all referrals, 14.3% originated from nonmedical (pornography/fetish) Web sites. LIMITATIONS: Requests are mixed with legitimate queries. CONCLUSION: Online photographic dermatology archives are vulnerable to misuse. Monitoring and intervention are necessary to preserve their availability and integrity.

Dermatology↗

A single-nucleus and spatial transcriptomic atlas of poplar leaves reveals the regulation of leaf polarity and cuticle deposition.

Leaf adaxial-abaxial polarity is fundamental for plant morphogenesis and environmental adaptation through asymmetric cell differentiation. Emerging evidence reveals dorsoventral metabolic gradients act downstream of transcriptional networks to fine-tune cellular specialization. While conserved transcription factors (e.g., HD-ZIP III and KANADI) establish initial polarity, the molecular networks driving position-specific cellular differentiation and their integration with metabolic adaptation remain unclear. Leveraging single-nucleus and spatial transcriptomics, we resolve major cell classes (mesophyll, epidermal, and vascular-associated) and their adaxial-abaxial subtypes, revealing dorsoventral polarity in transcriptional profiles and metabolic pathways. Adaxial cells are enriched in phenylpropanoid/flavonoid biosynthesis, while abaxial cells show preferential activation of stress and hormone signaling. Notably, we identify MYC2 as a key regulator of adaxial cuticle biosynthesis, binding to promoters of lipid biosynthetic and transport genes (e.g., CER10 and LTPG1) and promoting cuticle thickening. Our study uncovers how positional identity shapes transcriptional and metabolic polarity in leaves, with MYC2 emerging as a central regulator coordinating organ-specific adaptations. These findings provide insights into the spatial regulation of plant development and stress resilience, offering potential strategies for engineering stress-tolerant woody crops.

Plant Leaves↗

An atlas of non-redundant sequences and structures of transcription factor assemblies across domains of life.

Transcription factors (TFs) regulate gene expression by controlling the recruitment of transcriptional machinery to regulatory regions of the genome. Nearly 10% of the human genome encodes TFs, making them one of the largest protein families. Despite their central roles in gene regulation, TFs are historically considered challenging therapeutic targets due to their complex interactions with DNA, RNA and associated proteins. Although recent progress in studying TFs both at molecular and structural level excels our understanding on their function, yet a universal rule decoding their recognition process remains elusive. Here, we present a curated non-redundant dataset of TFs with 3570 sequences and 377 structures. We further characterize "unique interfaces" by quantifying interface identity across interacting chains in TF assemblies. Surprisingly, our data shows that the "unique interfaces" have optimal size ranging from 2000 Å2 to 4000 Å2 irrespective of their quaternary assembly. To understand the functional diversity, we integrate sequence motifs, structural domains, subcellular localization and functional enrichment of TFs. We have also catalogued association of TFs with various human diseases. Our dataset provides a comprehensive platform to perform large scale analysis of TF-assemblies and aid in computational methods for their prediction across domains of life.

Gene regulation↗

On the modeling, construction, and evaluation of a probabilistic atlas of brain perfusion.

To detect subtle, abnormal perfusion patterns in brain single photon emission computer tomography (SPECT) images, it is necessary to develop quantitative methods in which computer-aided statistical analysis takes advantage of information present in databases of normal subjects. The purpose of this study was to evaluate and examine aspects of the creation and the modeling power of three statistical models for representing brain perfusion as observed in ECD-SPECT. The first model is a local model of voxel-by-voxel mean and variance. The second model is a PCA-based global model that accounts for covariance patterns in the images. The third model is an original model that is a non-linear extension to the second model. This model is based on robust statistics for modeling abnormalities. To evaluate the models, a leave-one-out procedure combined with simulations of abnormal perfusion patterns was adopted. Abnormal perfusion patterns were simulated at different locations in the brain, with different intensities and different sizes. The procedure yields receiver operator characteristics (ROC) that present a combined measure of model-fit and model-sensitivity at detecting abnormalities. The scheme can further be used to compare models as well as the influence of different preprocessing steps. In particular, the influence of different registration approaches is studied and analyzed. The results show that the original non-linear model always performed better than the other models. Finally, location-dependent detection performance was found. Most notably, a higher variation of perfusion was observed in the right frontal cortex than in the other locations studied.

Algorithms↗