Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart

Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition and highlighted important functional roles for non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-seq). Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations, such as mural cells and glia. Our analyses also revealed extensive networks of intercellular communication and suggested prevalent sexual dimorphism in gene expression in the heart. This study offers insights into the structure and function of the mammalian cardiac cellulome and provides an important resource that will stimulate studies in cardiac cell biology

The <em>MUC2 </em>Gene Product: Polymerisation and Post-Secretory Organisation—Current Models

\ua9 2024 by the authors.MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published previously. Recently, several significant developments have been made which either introduce new ideas or challenge previous theories. New ideas include an overhaul of the MUC2 C-terminal globular structure which is proposed to harbour several previously unobserved domains, and include a site for an extra intermolecular disulphide bridge dimer between the cysteine 4379 of adjacent MUC2 C-termini. MUC2 polymers are also now thought to be secreted attached to the epithelial surface of goblet cells in the small intestine and removed following secretion via a metalloprotease meprin β-mediated cleavage of the von Willebrand D2 domain of the N-terminus. It remains unclear whether MUC2 forms intermolecular dimers, trimers, or both, at the N-termini during polymerisation, with several articles supporting either trimer or dimer formation. The presence of a firm inner mucus layer in the small intestine is similarly unclear. Considering this recent research, this review proposes an update to the previous model of MUC2 polymerisation and secretion, considers conflicting theories and data, and highlights the importance of this research to the understanding of MUC2 mucus layers in health and disease

Effect of PET-MR Inconsistency in the Kernel Image Reconstruction Method

Anatomically driven image reconstruction algorithms have become very popular in positron emission tomography (PET) where they have demonstrated improved image resolution and quantification. This paper examines the effects of spatial inconsistency between MR and PET images in hot and cold regions of PET images using the hybrid kernelized expectation maximization (HKEM) machine learning method. Our evaluation was conducted on Jaszczak phantom and patient data acquired with the Biograph Siemens mMR. The results show that even a small shift can cause a significant change in activity concentration. In general, the PET-MR inconsistencies can induce the partial volume effect, more specifically the “spill-in” for cold regions and the “spill-out” for hot regions. The maximum change was about 100% for the cold region and 10% for the hot lesion using kernelized expectation maximization, against the 37% and 8% obtained with HKEM. The findings of this paper suggest that including PET information in the kernel enhances the robustness of the reconstruction in case of spatial inconsistency. Nevertheless, accurate registration and choice of the appropriate MR image for the creation of the kernel is essential to avoid artifacts, blurring, and bias

Apocrine Hidradenocarcinoma of the Scalp: A Classification Conundrum

Introduction The classification of malignant sweat gland lesions is complex. Traditionally, cutaneous sweat gland tumors have been classified by either eccrine or apocrine features. Methods A case report of a 33-year-old Hispanic man with a left scalp mass diagnosed as a malignancy of adnexal origin preoperatively is discussed. After presentation at our multidisciplinary tumor board, excision with ipsilateral neck dissection was undertaken. Results Final pathology revealed an apocrine hidradenocarcinoma. The classification and behavior of this entity are discussed in this report. Conclusion Apocrine hidradenocarcinoma can be viewed as an aggressive malignant lesion of cutaneous sweat glands on a spectrum that involves both eccrine and apoeccrine lesions

Hybrid PET-MR list-mode kernelized expectation maximization reconstruction for quantitative PET images of the carotid arteries

Ordered subsets expectation maximization (OSEM) has been widely used in PET imaging. Although Bayesian algorithms have been shown to perform better, they are still not used in the clinical practice due to the difficulty of choosing appropriate and robust regularization parameters. The recently introduced kernelized expectation maximization (KEM) has shown some promise to work successfully for different applications. Therefore, we propose a list mode hybrid KEM (LM-HKEM) for static reconstructions, which we implemented in the open source Software for Tomographic Image Reconstruction (STIR) library. The proposed algorithm uses both MR and PET update images to create a feature vector for each voxel in the image, which contains the information about the local neighborhood. So as not to over-smooth the reconstructed images a 3×3×3 voxels kernel was used. Three real datasets were acquired with the Siemens mMR: a phantom to validate the algorithm and two patient carotid artery studies to show the possible applications of the method. The reconstructed images are assessed and compared for different algorithms: OSEM, OSEM with median root prior (MRP), KEM and LM-HKEM. The results show better quantification performance for the phantom low count images with around 4% bias compared to 7% for KEM and over 11% for OSEM and OSEM with (MRP). Our results show that the proposed technique can be used to improve quantification at low- count condition and it shows promising performance in terms of stability as for different subsets, with comparable number of events, we used the same parameters values. Emphasis is given on the reconstruction of the carotid artery and the characterization of atherosclerosis

Hybrid PET-MR list-mode kernelized expectation maximization reconstruction

The recently introduced kernelized expectation maximization (KEM) method has shown promise across varied applications. These studies have demonstrated the benefits and drawbacks of the technique when the kernel matrix is estimated from separate anatomical information, for example from magnetic resonance (MR), or from a preliminary PET reconstruction. The contribution of this work is to propose and investigate a list-mode-hybrid KEM (LM-HKEM) reconstruction algorithm with the aim of maintaining the benefits of the anatomically-guided methods and overcome their limitations by incorporating synergistic information iteratively. The HKEM is designed to reduce negative bias associated with low-counts, the problem of PET unique feature suppression reported in the previously mentioned studies using only the MR-based kernel, and to improve contrast of lesions at different count levels. The proposed algorithm is validated using a simulation study, a phantom dataset and two clinical datasets. For each of the real datasets high and low count-levels were investigated. The reconstructed images are assessed and compared with different LM algorithms implemented in STIR. The findings obtained using simulated and real datasets show that anatomically-guided techniques provide reduced partial volume effect and higher contrast compared to standard techniques, and HKEM provides even higher contrast and reduced bias in almost all the cases. This work, therefore argues that using synergistic information, via the kernel method, increases the accuracy of the PET clinical diagnostic examination. The promising quantitative features of the HKEM method give the opportunity to explore many possible clinical applications, such as cancer and inflammation

Secondary bacterial infections of buruli ulcer lesions before and after chemotherapy with streptomycin and rifampicin

Buruli ulcer (BU), caused by Mycobacterium ulcerans is a chronic necrotizing skin disease. It usually starts with a subcutaneous nodule or plaque containing large clusters of extracellular acid-fast bacilli. Surrounding tissue is destroyed by the cytotoxic macrolide toxin mycolactone produced by microcolonies of M. ulcerans. Skin covering the destroyed subcutaneous fat and soft tissue may eventually break down leading to the formation of large ulcers that progress, if untreated, over months and years. Here we have analyzed the bacterial flora of BU lesions of three different groups of patients before, during and after daily treatment with streptomycin and rifampicin for eight weeks (SR8) and determined drug resistance of the bacteria isolated from the lesions. Before SR8 treatment, more than 60% of the examined BU lesions were infected with other bacteria, with Staphylococcus aureus and Pseudomonas aeruginosa being the most prominent ones. During treatment, 65% of all lesions were still infected, mainly with P. aeruginosa. After completion of SR8 treatment, still more than 75% of lesions clinically suspected to be infected were microbiologically confirmed as infected, mainly with P. aeruginosa or Proteus miriabilis. Drug susceptibility tests revealed especially for S. aureus a high frequency of resistance to the first line drugs used in Ghana. Our results show that secondary infection of BU lesions is common. This could lead to delayed healing and should therefore be further investigated

Hierarchically structured ZSM-5 obtained by optimized mesotemplate-free method as active catalyst for methanol to DME conversion

In the presented studies, a new method for the synthesis of hierarchical porous materials with ZSM-5 zeolite properties was applied. The proposed method is based on the acidification of the zeolite seeds slurry using HCl solution, followed by hydrothermal treatment, enabling the aggregation of zeolite nanoseeds with the formation of the interparticle mesoporous structure. The influence of the duration of zeolite parent mixture aging before and after acidification on the resulting properties of the samples was investigated. The physicochemical properties of the obtained micro-mesoporous samples were analyzed using techniques such as N-2-sorption measurements, X-ray diffraction, TG analysis, NH3-TPD and electron microscopy. In the second part of the studies, the influence of the modified zeolite sample parameters (such as porosity, acidity and crystallinity) on their catalytic activity for dimethyl ether (DME) synthesis from methanol was studied. DME is considered as a future clean alternative to diesel fuel and the development of methods for its synthesis is currently of high scientific interest. It was shown that modification of the porous structure and acidity of the zeolitic samples strongly influences their catalytic activity, selectivity and stability for the DME synthesis process. The micro-mesoporous samples, despite their significantly lower acidity, exhibited high catalytic activity (similar to conventional ZSM-5 zeolite) and enhanced selectivity towards DME, as well as higher stability in a long term catalytic test (higher resistance to the formation of coke deposits) in comparison to standard MFI-type zeolites.This work was supported by the National Science Center under grant no. 2011/03/N/ST5/04820. Part of the research was carried out with equipment purchased thanks to the financial support of the European Regional Development Fund in the framework of the Polish Innovation Economy Operational Program (contract no. POIG.02.01.00-12-023/08). U. D. gives thanks to Spanish Government by the funding (project MAT2014-52085-C2-1-P).Rutkowska, M.; Macina, D.; Piwowarska, Z.; Gajewska, M.; Díaz Morales, UM.; Chmielarz, L. (2016). Hierarchically structured ZSM-5 obtained by optimized mesotemplate-free method as active catalyst for methanol to DME conversion. Catalysis Science and Technology. 6(13):4849-4862. https://doi.org/10.1039/c6cy00040aS4849486261

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Atlantic Ocean influence on a shift in European climate in the 1990s

European climate exhibits variability on a wide range of timescales. Understanding the nature and drivers of this variability is an essential step in developing robust climate predictions and risk assessments. The Atlantic Ocean has been suggested as an important driver of variability in European climate on decadal timescales1, but the importance of this influence in recent decades has been unclear, partly because of difficulties in separating the influence of the Atlantic Ocean from other contributions, for example, from the tropical Pacific Ocean and the stratosphere. Here we analyse four data sets derived from observations to show that, during the 1990s, there was a substantial shift in European climate towards a pattern characterized by anomalously wet summers in northern Europe, and hot, dry, summers in southern Europe, with related shifts in spring and autumn. These changes in climate coincided with a substantial warming of the North Atlantic Ocean, towards a state last seen in the 1950s. The patterns of European climate change in the 1990s are consistent with earlier changes attributed to the influence of the North Atlantic Ocean, and provide compelling evidence that the Atlantic Ocean was the key driver. Our results suggest that the recent pattern of anomalies in European climate will persist as long as the North Atlantic Ocean remains anomalously warm