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EMBO Reports Mar 2024The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B...
The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B localises to H3K36me3 at actively transcribing gene bodies via its PWWP domain. It also functions at heterochromatin through an unknown recruitment mechanism. Here, we find that knockout of DNMT3B causes loss of methylation predominantly at H3K9me3-marked heterochromatin and that DNMT3B PWWP domain mutations or deletion result in striking increases of methylation in H3K9me3-marked heterochromatin. Removal of the N-terminal region of DNMT3B affects its ability to methylate H3K9me3-marked regions. This region of DNMT3B directly interacts with HP1α and facilitates the bridging of DNMT3B with H3K9me3-marked nucleosomes in vitro. Our results suggest that DNMT3B is recruited to H3K9me3-marked heterochromatin in a PWWP-independent manner that is facilitated by the protein's N-terminal region through an interaction with a key heterochromatin protein. More generally, we suggest that DNMT3B plays a role in DNA methylation homeostasis at heterochromatin, a process which is disrupted in cancer, aging and Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome.
Topics: Animals; DNA Methylation; Heterochromatin; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; Mutation; Mammals; Primary Immunodeficiency Diseases; Face
PubMed: 38291337
DOI: 10.1038/s44319-024-00061-5 -
Current Opinion in Psychology Oct 2023The pattern of response times in conversation can reveal a lot about how people listen to each other. Fast response times not only telegraph eagerness but provide... (Review)
Review
The pattern of response times in conversation can reveal a lot about how people listen to each other. Fast response times not only telegraph eagerness but provide evidence of attending in such a way as to almost finish the other's sentences. In other situations, slow response times are more appropriate, such as when listening prompts deeper reflection, or to leave space for the enjoyment of an inside joke. Here we argue that close relationships are not marked exclusively by one or the other pattern, but by the ability to toggle effortlessly between the two as the conversation demands.
Topics: Humans; Communication; Reaction Time
PubMed: 37549539
DOI: 10.1016/j.copsyc.2023.101658 -
NEJM Evidence Mar 2024January 11, 2024, marked the 60th anniversary of the initial U.S. Surgeon General report "Smoking and Health," which definitively linked cigarette smoking and lung...
January 11, 2024, marked the 60th anniversary of the initial U.S. Surgeon General report "Smoking and Health," which definitively linked cigarette smoking and lung cancer. Similar to the old Virginia Slims slogan "you've come a long way, baby," smoking rates have diminished greatly since the release of that report. However, smoking still represents the leading cause of preventable deaths. Numerous countries have enacted policies aimed at decreasing conventional cigarette use, such as including warning labels on tobacco products, limiting advertising, and imposing bans on particular products. Such measures have contributed to significant reductions in cigarette use.
Topics: Humans; Infant; Animals; Advertising; Anniversaries and Special Events; Cigarette Smoking; Colubridae; Lung Neoplasms
PubMed: 38411446
DOI: 10.1056/EVIDe2400020 -
Cureus Dec 2023Teleradiology, an established telemedicine practice globally, has significantly enhanced the accessibility of high-quality radiological interpretations in remote areas...
Teleradiology, an established telemedicine practice globally, has significantly enhanced the accessibility of high-quality radiological interpretations in remote areas worldwide, especially in India, thereby improving healthcare outcomes. The utilization of teleradiology services has seen a marked increase, expanding its reach into more distant regions of the country. However, this burgeoning field faces numerous regulatory, financial, and technical challenges. The current scenario regarding teleradiology in India is a double-edged sword. There is an increasing demand for it due to the expanding population, resulting in larger imaging volumes needing radiologist services. This editorial aims to examine the prevailing challenges in teleradiology in India, with an emphasis on the compensation model for teleradiologists, which has not kept pace with the growing demand for services and often remains inequitable.
PubMed: 38288194
DOI: 10.7759/cureus.51342 -
Experimental Eye Research Dec 2023Progressive loss of retinal ganglion cells (RGCs) caused by retinal ischemia-reperfusion (IR) injury can lead to irreversible vision impairment, with neuroinflammatory...
Progressive loss of retinal ganglion cells (RGCs) caused by retinal ischemia-reperfusion (IR) injury can lead to irreversible vision impairment, with neuroinflammatory responses playing an important role in this process. COG1410, a mimetic peptide of apolipoprotein E, has demonstrated protective potential in the central nervous system, but its effects on retinal IR injury remain unexplored. In this study, we established a mouse model of retinal IR injury to investigate the effects of COG1410 on retinal microglia and RGCs. We observed CD16/32-marked and CD206-marked microglia and RGCs using immunofluorescence staining, detected the expression of inflammatory factors by PCR, and evaluated retinal apoptosis with TUNEL staining. We further investigated the potential mechanism by detecting the expression of key proteins via Western blot. The results reveal that COG1410 decreased the number of CD16/32-marked microglia and increased the number of CD206-marked microglia, alleviated the expression of IL-1β and TNF-α, and reduced the loss of RGCs by inhibiting the mitochondrial-related apoptotic pathway. COG1410 was found to increase the expression of ERK1/2 and Nr4a1 but decrease the expression of NF-κB. The expression of TREM2 showed an increasing trend after COG1410 administration, but it was not statistically significant. In conclusion, COG1410 regulates microglial states and protects RGCs in retinal IR injury, showing promising potential for the treatment of eye diseases.
Topics: Mice; Animals; Retinal Ganglion Cells; Microglia; Retina; Reperfusion Injury
PubMed: 37839665
DOI: 10.1016/j.exer.2023.109678 -
Scientific Reports Aug 2023Automated text recognition techniques have made significant advancements; however, certain tasks still present challenges. This study is motivated by the need to...
Automated text recognition techniques have made significant advancements; however, certain tasks still present challenges. This study is motivated by the need to automatically recognize hand-marked text on construction defect tags among millions of photographs. To address this challenge, we investigated three methods for automating hand-marked semantic text recognition (HMSTR)-a modified scene text recognition-based (STR) approach, a two-step HMSTR approach, and a lumped approach. The STR approach involves locating marked text using an object detection model and recognizing it using a competition-winning STR model. Similarly, the two-step HMSTR approach first localizes the marked text and then recognizes the semantic text using an image classification model. By contrast, the lumped approach performs both localization and identification of marked semantic text in a single step using object detection. Among these approaches, the two-step HMSTR approach achieved the highest F1 score (0.92) for recognizing circled text, followed by the STR approach (0.87) and the lumped approach (0.78). To validate the generalizability of the two-step HMSTR approach, subsequent experiments were conducted using check-marked text, resulting in an F1 score of 0.88. Although the proposed methods have been tested specifically with tags, they can be extended to recognize marked text in reports or books.
PubMed: 37648714
DOI: 10.1038/s41598-023-41489-4