Innovative super-resolution in spatial transcriptomics: a transformer model exploiting histology images and spatial gene expression.

Spatial transcriptomics technologies have shed light on the complexities of tissue structures by accurately mapping spatial microenvironments. Nonetheless, a myriad of methods, especially those utilized in platforms like Visium, often relinquish spatial details owing to intrinsic resolution limitations. In response, we introduce TransformerST, an innovative, unsupervised model anchored in the Transformer architecture, which operates independently of references, thereby ensuring cost-efficiency by circumventing the need for single-cell RNA sequencing.

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration.

Parkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and ortholog dVGLUT have been implicated as modulators of DA neuron resilience.

Differential gene expression in layer 3 pyramidal neurons across 3 regions of the human cortical visual spatial working memory network.

Visual spatial working memory (vsWM) is mediated by a distributed cortical network composed of multiple nodes, including primary visual (V1), posterior parietal (PPC), and dorsolateral prefrontal (DLPFC) cortices. Feedforward and feedback information is transferred among these nodes via projections furnished by pyramidal neurons (PNs) located primarily in cortical layer 3. Morphological and electrophysiological differences among layer 3 PNs across these nodes have been reported; however, the transcriptional signatures underlying these differences have not been examined in the human brain.

Chloride channel inhibition improves neuromuscular function under conditions mimicking neuromuscular disorders.

Aim: The skeletal muscle Cl channels, the ClC-1 channels, stabilize the resting membrane potential and dampen muscle fibre excitability. This study explored whether ClC-1 inhibition can recover nerve-stimulated force in isolated muscle under conditions of compromised neuromuscular transmission akin to disorders of myasthenia gravis and Lambert-Eaton syndrome.

Methods: Nerve-muscle preparations were isolated from rats.

Long noncoding RNA functionality in imprinted domain regulation.

Genomic imprinting is a parent-of-origin dependent phenomenon that restricts transcription to predominantly one parental allele. Since the discovery of the first long noncoding RNA (lncRNA), which notably was an imprinted lncRNA, a body of knowledge has demonstrated pivotal roles for imprinted lncRNAs in regulating parental-specific expression of neighboring imprinted genes. In this Review, we will discuss the multiple functionalities attributed to lncRNAs and how they regulate imprinted gene expression.

Improving Access to Safe Anesthetic Care in Rural and Remote Communities in Affluent Countries.

Inadequate access to anesthesia and surgical services is often considered to be a problem of low- and middle-income countries. However, affluent nations, including Canada, Australia, and the United States, also face shortages of anesthesia and surgical care in rural and remote communities. Inadequate services often disproportionately affect indigenous populations.

Nucleoporin 107, 62 and 153 mediate Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells.

Genomic imprinting is a phenomenon that restricts transcription to predominantly one parental allele. How this transcriptional duality is regulated is poorly understood. Here we perform an RNA interference screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells.

Exploring fetal fibronectin testing as a predictor of labour onset: In parturient women from isolated communities.

Objective: To investigate whether the fetal fibronectin assay would be useful for determining if a woman was close to a term delivery. If effective, this test would allow parturient women to stay in their communities longer.

Design: This feasibility study used a prospective cohort design to examine the negative predictive value of the fetal fibronectin test at term.

An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences.

Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences.

Conservation of DNA Methylation Programming Between Mouse and Human Gametes and Preimplantation Embryos.

In mice, assisted reproductive technologies (ARTs) applied during gametogenesis and preimplantation development can result in disruption of genomic imprinting. In humans, these technologies and/or subfertility have been linked to perturbations in genomic imprinting. To understand how ARTs and infertility affect DNA methylation, it is important to understand DNA methylation dynamics and the role of regulatory factors at these critical stages.

Atp2c2 Is Transcribed From a Unique Transcriptional Start Site in Mouse Pancreatic Acinar Cells.

Proper regulation of cytosolic Ca(2+) is critical for pancreatic acinar cell function. Disruptions in normal Ca(2+) concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca(2+) homeostasis by promoting rapid Ca(2+) movement.

A role for chromatin topology in imprinted domain regulation.

Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression.

Cocrystalline Copolyimides of Poly(ethylene 2,6-naphthalate).

Copolycondensation of ,'-bis(2-hydroxyethyl)-biphenyl-3,4,3',4'-tetracarboxylic diimide (5-25 mol %) with bis(2-hydroxyethyl)-2,6-naphthalate affords a series of cocrystalline, poly(ethylene 2,6-naphthalate) (PEN)-based poly(ester imide)s. The glass transition temperature rises with the level of comonomer, from 118 °C for PEN itself to 148 °C for the 25% diimide copolymer. X-ray powder and fiber diffraction studies show that, when 5 mol % or more of diimide is present, the α-PEN crystal structure is replaced by a new crystalline phase arising from isomorphic substitution of biphenyldiimide for PEN residues in the polymer crystal lattice.

Epigenetic regulation of genomic imprinting from germ line to preimplantation.

Genomic imprinting is an epigenetic process that distinguishes parental alleles, resulting in parent-specific expression of a gene or cluster of genes. Imprints are acquired during gametogenesis when genome-wide epigenetic remodeling occurs. These imprints must then be maintained during preimplantation development, when another wave of genome-wide epigenetic remodeling takes place.

Compromised fertility disrupts Peg1 but not Snrpn and Peg3 imprinted methylation acquisition in mouse oocytes.

Growth and maturation of healthy oocytes within follicles requires bidirectional signaling and intercellular gap junctional communication. Aberrant endocrine signaling and loss of gap junctional communication between the oocyte and granulosa cells leads to compromised folliculogenesis, oocyte maturation, and oocyte competency, consequently impairing fertility. Given that oocyte-specific DNA methylation establishment at imprinted genes occurs during this growth phase, we determined whether compromised endocrine signaling and gap junctional communication would disrupt de novo methylation acquisition using ERβ and connexin37 genetic models.

Epigenetic mechanisms of genomic imprinting: common themes in the regulation of imprinted regions in mammals, plants, and insects.

Genomic imprinting is a form of epigenetic inheritance whereby the regulation of a gene or chromosomal region is dependent on the sex of the transmitting parent. During gametogenesis, imprinted regions of DNA are differentially marked in accordance to the sex of the parent, resulting in parent-specific expression. While mice are the primary research model used to study genomic imprinting, imprinted regions have been described in a broad variety of organisms, including other mammals, plants, and insects.

The Drosophila homolog of the mammalian imprint regulator, CTCF, maintains the maternal genomic imprint in Drosophila melanogaster.

Background: CTCF is a versatile zinc finger DNA-binding protein that functions as a highly conserved epigenetic transcriptional regulator. CTCF is known to act as a chromosomal insulator, bind promoter regions, and facilitate long-range chromatin interactions. In mammals, CTCF is active in the regulatory regions of some genes that exhibit genomic imprinting, acting as insulator on only one parental allele to facilitate parent-specific expression.

Comparison of regulated passive membrane conductance in action potential-firing fast- and slow-twitch muscle.

In several pathological and experimental conditions, the passive membrane conductance of muscle fibers (G(m)) and their excitability are inversely related. Despite this capacity of G(m) to determine muscle excitability, its regulation in active muscle fibers is largely unexplored. In this issue, our previous study (Pedersen et al.

The effect of acute hypoxia on excitability in the heart and the L-type calcium channel as a therapeutic target.

Acute hypoxia is induced during coronary occlusion or when oxygen supply does not meet demand and can trigger cardiac arrhythmia. Cardiac ion channels shape the action potential and excitability of the heart. Acute hypoxia regulates the function of cardiac ion channels including the L-type Ca(2+) channel that is the main route for Ca(2+)influx into cardiac myocytes and shapes the plateau phase of the action potential.

Effect of temperature-induced reactive oxygen species production on excitation-contraction coupling in mammalian skeletal muscle.

1. Here we review evidence obtained recently by us indicating that the poor longevity of isolated mammalian skeletal muscle preparations at temperatures in the normal physiological range is related to the increased production of reactive oxygen species (ROS) in the resting muscle. 2.

O2(*-) production at 37 degrees C plays a critical role in depressing tetanic force of isolated rat and mouse skeletal muscle.

To find out whether the decrease in muscle performance of isolated mammalian skeletal muscle associated with the increase in temperature toward physiological levels is related to the increase in muscle superoxide (O(2)(*-)) production, O(2)(*-) released extracellularly by intact isolated rat and mouse extensor digitorum longus (EDL) muscles was measured at 22, 32, and 37 degrees C in Krebs-Ringer solution, and tetanic force was measured in both preparations at 22 and 37 degrees C under the same conditions. The rate of O(2)(*-) production increased marginally when the temperature was increased from 22 to 32 degrees C, but increased fivefold when the temperature was increased from 22 to 37 degrees C in both rat and mouse preparations. This increase was accompanied by a marked decrease in tetanic force after 30 min incubation at 37 degrees C in both rat and mouse EDL muscles.

Mitochondrial superoxide production in skeletal muscle fibers of the rat and decreased fiber excitability.

Mammalian skeletal muscles generate marked amounts of superoxide (O(2)(.-)) at 37 degrees C, but it is not well understood which is the main source of O(2)(.-) production in the muscle fibers and how this interferes with muscle function.

The generation of cloned Drosophila melanogaster.

We report here the first successful use of embryonic nuclear transfer to create viable adult Drosophila melanogaster clones. Given the generation time, cost effectiveness, and relative ease of embryonic nuclear transplant in Drosophila, this method can provide an opportunity to further study the constraints on development imposed by transplanting determined or differentiated nuclei.