Pola Chemical Industries (Japan)

BackgroundDNA polymerase κ (Polk), a member of Y-family DNA polymerases, plays an important role in translesion DNA synthesis (TLS), allowing DNA replication forks to bypass DNA damage or DNA adducts to continue daughter strand synthesis. Polk is also believed to contribute to the replication-independent repair of DNA lesions such as cross-links. TLS circumvents stalls of DNA replication and promotes gap filling in DNA repair which would otherwise result in DNA double-strand breaks (DSBs) and cell death. Mitomycin C (MMC) is a widely used chemotherapeutic drug which generates DNA cross-links and induces DSBs. To clarify how Polk contributes to the prevention of MMC-induced DSB in various organs or tissues, immunohistochemical staining of γH2AX was conducted in catalytically inactivated Polk knock-in (Polk KI) mice and Polk wild-type (Polk+) mice treated with MMC or saline.ResultsThe γH2AX induction by MMC was enhanced by inactivation of Polk across many organs or tissues to varying degrees. Obvious enhancement was observed in liver, bladder, adrenal cortex, thyroid, and spermatids, whereas less enhancement was shown in brain and retina. The results suggest that Polk plays a role in preventing DSBs caused by MMC in most organs or tissues. Elevated DSB frequencies were observed in both proliferative cells, such as bladder epithelium cells, and less or slowly proliferative cells, such as hepatocytes. Increased DSB levels in inactivated Polk KI mice relative to Polk+ mice were also observed in saline-treated mice in the adrenal cortex and other tissues.ConclusionPolk plays a systemic role in mitigating MMC-induced DSBs, likely through both DNA replication-dependent and -independent mechanisms. Furthermore, Polk appears to protect against DSBs caused by endogenous mutagens in some organs such as the adrenal cortex, prostate, and retina.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41021-025-00343-x.

The hair cycle is a valuable model for studying tissue remodeling processes in adult mammals. Time course single-cell transcriptomics offers a powerful approach for characterizing changes in cellular states and interactions; however, its application in human tissues remains challenging. Here, we performed single-cell RNA sequencing on 19 human skin tissues, each containing a single hair follicle. We reconstructed a pseudotemporal progression of the hair cycle-termed the "pseudo-hair cycle"-by computationally ordering samples according to their gene expression profiles. The pseudo-hair cycle delineates the continuum of gene expression changes occurring in 16 distinct epithelial and dermal cell populations throughout the hair cycle, revealing specific cellular states and interactions. We identified hair follicle keratinocytes, dermal sheath fibroblasts, vascular endothelial cells, and leukocytes as key contributors to tissue remodeling during catagen. Our study provides a high-resolution temporal dataset for investigating the dynamic molecular and cellular mechanisms underlying skin remodeling in humans.

The incidence of bullying in Indonesia has increased significantly from the previous year, one of which is West Java.Adolescence is an important phase in the search for identity, where individuals try to find who they are and direct their life goals, while exploring the roles they will play.However, one of the negative impacts of bullying is the emergence of feelings of inferiority and antisocial behavior in victims.Someone who has low self-esteem often has difficulty in building healthy social relationships.Therefore, this study aims to understand the relationship between bullying behavior and self-esteem in adolescents at SMAN 6 Bandung.This study uses a quantitative approach with a descriptive correlational method and a crosssectional design.Sampling, using probability sampling techniques with simple random sampling, and the number of respondents involved in this study was 86 people.The results of the study using chi-square test analysis, there is a relationship between bullying behavior and self-esteem ( = 0.000).The conclusion of this study is that there is a significant relationship between bullying behavior and self-esteem in adolescents at SMAN 6 Bandung.Therefore, it is necessary to provide guidance and efforts by teachers in providing education at school to students as a strategy to prevent bullying.

Melanocytes are surrounded by diverse cells, including sensory neurons in our skin, but their interaction and functional importance have been poorly investigated. In this study, we find that melanocytes and nociceptive neurons contact more in human skin color patch tissue than control. Co-culture with human iPSC-derived sensory neurons significantly induces morphogenesis and pigmentation of human melanocytes. To reveal melanocyte-stimulating factors secreted from neurons, we perform proteomic analyses and identify RGMB in the sensory neuron-conditioned medium. RGMB protein induces morphogenesis and melanin production of melanocytes, demonstrating that RGMB is a melanocyte-stimulating factor released from sensory neurons. Transcriptome analysis suggests that the melanosome transport machinery can be controlled by RGMB, leading us to identify the vesicle production response of melanocytes upon RGMB treatment. This study discovers a role of sensory neurons in modulating multiple aspects of human melanocytes through secretion of a key factor: RGMB.

We form impressions of others by observing their constant and dynamically-shifting facial expressions during conversation and other daily life activities. However, conventional aging research has mainly considered the changing characteristics of the skin, such as wrinkles and age-spots, within very limited states of static faces. In order to elucidate the range of aging impressions that we make in daily life, it is necessary to consider the effects of facial movement. This study investigated the effects of facial movement on age impressions. An age perception test using Japanese women as face models was employed to verify the effects of the models’ age-dependent facial movements on age impression in 112 participants (all women, aged 20–49 years) as observers. Further, the observers’ gaze was analyzed to identify the facial areas of interests during age perception. The results showed that cheek movement affects age impressions, and that the impressions increase depending on the model’s age. These findings will facilitate the development of new means of provoking a more youthful impression by approaching anti-aging from a different viewpoint of facial movement.