Mouse embryonic kidney transplantation identifies maturation defects in the medulla.

Kidney organoids are connected to the host circulation and mature after transplantation. However, they are still immature compared to the adult kidneys, and their precise maturation stages remain unclear. By transplanting the mouse embryonic kidney as a model system for organoid transplantation, we report here the maturation defects of the graft, especially in the medulla.

Impact of the COVID-19 pandemic on the incidence of cardiometabolic risk factors among workers: results from the Japan Epidemiology Collaboration on Occupational Health study.

Background: The COVID-19 pandemic and associated restrictions on human activities have greatly changed lifestyles, which might have deteriorated the cardiometabolic profile.

Objective: This study aimed to examine the effect of the COVID-19 pandemic on the incidence of cardiometabolic risk factors among Japanese workers in fiscal years (FY) 2020 and 2021 compared with the prepandemic period.

Method: This study comprised an average of 71 025 employees in Japan who underwent annual health check-ups for at least two successive years from 2015 to 2021.

Nonattendance is associated with work performance due to the side effects of COVID-19 vaccination: a cross-sectional study in a Japanese manufacturing industry.

Objectives: Although vaccines have promoted the socioeconomic normalization of COVID-19, adverse effects on work performance due to the post-vaccination side effects have been reported. Thus, we examined the relationship between the status of going to work the day following vaccination as a post-vaccination employment consideration and work performance among Japanese workers in the manufacturing industry.

Methods: Overall, 1273 employees who received the COVID-19 vaccine in a Japanese manufacturing district were surveyed using a self-administered web-based questionnaire that included fever, fatigue, workplace attendance the day after vaccination, work performance 1 week after vaccination, and demographic and occupational characteristics (age, gender, work style, and psychological distress [K6 scale]).

Changes in repair pathways of radiation-induced DNA double-strand breaks at the midblastula transition in Xenopus embryo.

Ionizing radiation (IR) causes DNA damage, particularly DNA double-strand breaks (DSBs), which have significant implications for genome stability. The major pathways of repairing DSBs are homologous recombination (HR) and nonhomologous end joining (NHEJ). However, the repair mechanism of IR-induced DSBs in embryos is not well understood, despite extensive research in somatic cells.

Risk factors for placenta accreta spectrum in pregnancies conceived after frozen-thawed embryo transfer in a hormone replacement cycle.

Objective: Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC.

Study Design: We performed a case-control study in two tertiary perinatal centres in Japan.

Repair of topoisomerase 1-induced DNA damage by tyrosyl-DNA phosphodiesterase 2 (TDP2) is dependent on its magnesium binding.

Topoisomerases are enzymes that relax DNA supercoiling during replication and transcription. Camptothecin, a topoisomerase 1 (TOP1) inhibitor, and its analogs trap TOP1 at the 3'-end of DNA as a DNA-bound intermediate, resulting in DNA damage that can kill cells. Drugs with this mechanism of action are widely used to treat cancers.

SPRTN and TDP1/TDP2 Independently Suppress 5-Aza-2'-deoxycytidine-Induced Genomic Instability in Human TK6 Cell Line.

DNA-protein cross-links (DPCs) are generated by internal factors such as cellular aldehydes that are generated during normal metabolism and external factors such as environmental mutagens. A nucleoside analog, 5-aza-2'-deoxycytidine (5-azadC), is randomly incorporated into the genome during DNA replication and binds DNA methyltransferase 1 (DNMT1) covalently to form DNMT1-DPCs without inducing DNA strand breaks. Despite the recent progress in understanding the mechanisms of DPCs repair, how DNMT1-DPCs are repaired is unclear.

Formation of clustered DNA damage in vivo upon irradiation with ionizing radiation: Visualization and analysis with atomic force microscopy.

SignificanceDNA damage causes loss of or alterations in genetic information, resulting in cell death or mutations. Ionizing radiations produce local, multiple DNA damage sites called clustered DNA damage. In this study, a complete protocol was established to analyze the damage complexity of clustered DNA damage, wherein damage-containing genomic DNA fragments were selectively concentrated via pulldown, and clustered DNA damage was visualized by atomic force microscopy.

Repair pathways for radiation DNA damage under normoxic and hypoxic conditions: Assessment with a panel of repair-deficient human TK6 cells.

Various types of DNA lesions are produced when cells are exposed to ionizing radiation (IR). The type and yield of IR-induced DNA damage is influenced by the oxygen concentration. Thus, different DNA repair mechanisms may be involved in the response of normoxic and hypoxic cells to irradiation with IR.

Interprofessional Collaborative Practice for Child Maltreatment Prevention in Japan: A Literature Review.

This literature review explored the factors promoting interprofessional collaborative practice for the child maltreatment prevention in Japan. We searched the Japanese database of ICHUSHI-web, focusing on studies published between 1990 and 2015. The studies were examined for methodological quality using the critical appraisal checklists.

Participation of TDP1 in the repair of formaldehyde-induced DNA-protein cross-links in chicken DT40 cells.

Proteins are covalently trapped on DNA to form DNA-protein cross-links (DPCs) when cells are exposed to DNA-damaging agents. Aldehyde compounds produce common types of DPCs that contain proteins in an undisrupted DNA strand. Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs topoisomerase 1 (TOPO1) that is trapped at the 3'-end of DNA.

Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase 1 DNA-protein crosslinks and 3'-blocking lesions in the absence of tyrosyl-DNA phosphodiesterase 1 (TDP1).

Topoisomerase I (TOP1) resolves DNA topology during replication and transcription. The enzyme forms an intermediate TOP1 cleavage complex (TOP1cc) through transient TOP1-DNA-protein crosslinks. Camptothecin is a frontline anticancer agent that freezes this reaction intermediate, leading to the generation of irreversible TOP1ccs that act as 3'-blocking lesions.

Direct observation of damage clustering in irradiated DNA with atomic force microscopy.

Ionizing radiation produces clustered DNA damage that contains two or more lesions in 10-20 bp. It is believed that the complexity of clustered damage (i.e.

Repair of trapped topoisomerase II covalent cleavage complexes: Novel proteasome-independent mechanisms.

Topoisomerase II (TOP2) resolves topologically entwined duplex DNA. It generates a transient DNA double-strand break intermediate, known as TOP2 cleavage complex (TOP2cc) that contains a covalent link between TOP2 and the 5'-terminus of the incised DNA duplex. Etoposide, a frontline anticancer drug, freezes the intermediate and forms irreversible TOP2ccs.

DNA-protein cross-links: Formidable challenges to maintaining genome integrity.

DNA is associated with proteins that are involved in its folding and transaction processes. When cells are exposed to chemical cross-linking agents or free radical-generating ionizing radiation, DNA-associated proteins are covalently trapped within the DNA to produce DNA-protein cross-links (DPCs). DPCs produced by these agents contain cross-linked proteins in an undisrupted DNA strand.

Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells.

Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear.

Establishment of expanded and streamlined pipeline of PITCh knock-in - a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO.

The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in.

Restriction glycosylases: involvement of endonuclease activities in the restriction process.

All restriction enzymes examined are phosphodiesterases generating 3΄-OH and 5΄-P ends, but one restriction enzyme (restriction glycosylase) excises unmethylated bases from its recognition sequence. Whether its restriction activity involves endonucleolytic cleavage remains unclear. One report on this enzyme, R.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences.

Establishment of reference costs for occupational health services and implementation of cost management in Japanese manufacturing companies.

Objectives: We developed a standardized cost estimation method for occupational health (OH) services. The purpose of this study was to set reference OH services costs and to conduct OH services cost management assessments in two workplaces by comparing actual OH services costs with the reference costs.

Methods: Data were obtained from retrospective analyses of OH services costs regarding 15 OH activities over a 1-year period in three manufacturing workplaces.

Aldehydes with high and low toxicities inactivate cells by damaging distinct cellular targets.

Aldehydes are genotoxic and cytotoxic molecules and have received considerable attention for their associations with the pathogenesis of various human diseases. In addition, exposure to anthropogenic aldehydes increases human health risks. The general mechanism of aldehyde toxicity involves adduct formation with biomolecules such as DNA and proteins.

[Development of a Crisis Management Manual for Occupational Health Experts].

When crises such as natural disasters or industrial accidents occur in workplaces, not only the workers who are injured, but also those who engage in emergency or recovery work may be exposed to various health hazards. We developed a manual to enable occupational health (OH) experts to prevent health hazards. The manual includes detailed explanations of the characteristics and necessary actions for each need in the list of "OH Needs During Crisis Management" developed after an analysis of eight cases in our previous research.

Synergistic enhancement of 5-fluorouracil cytotoxicity by deoxyuridine analogs in cancer cells.

5-Fluorouracil (FU) is a halogenated nucleobase analog that is widely used in chemotherapy. Here we show that 5-hydroxymethyl-2'-deoxyuridine (hmUdR) synergistically enhances the activity of FU in cell lines derived from solid tumors but not normal tissues. While the cytotoxicity of FU and hmUdR was not directly related to the amount of the modified bases incorporated into cellular DNA, incubation with this combination resulted in dramatic increase in the number of single strand breaks in replicating cancer cells, leading to NAD-depletion as consequence of poly(ADP-ribose) synthesis and S phase arrest.

Induction of DNA-protein cross-links by ionizing radiation and their elimination from the genome.

Ionizing radiation produces various types of DNA lesions, such as base damage, single-strand breaks, double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, DSBs are the most critical lesions underlying the lethal effects of ionizing radiation. With DPCs, proteins covalently trapped in DNA constitute strong roadblocks to replication and transcription machineries, and hence can be lethal to cells.