Autophagic recycling of cell parts is generally termed as the opposite of cell death. Here, we explored the relation between cell death and autophagy by examining granulosa cell layers that control oocyte quality, which is important for the success of fertilization. Granulosa cell layers were collected from infertile women and morphologically divided into four types, viz., mature (MCCs), immature (ICCs), and dysmature cumulus cells (DCCs), and mural granulosa cells (MGCs). Microtubule-associated protein light chain 3 (LC3), which is involved in autophagosome formation, was expressed excessively in DCCs and MGCs, and their chromosomal DNA was highly fragmented. However, autophagy initiation was limited to MGCs, as indicated by the expression of membrane-bound LC3-II and autophagy-related protein 7 (ATG7), an enzyme that converts LC3-I to LC3-II. Although pro-LC3 was accumulated, autophagy was disabled in DCCs, resulting in cell death. Our results suggest the possibility that autophagy-independent accumulation of pro-LC3 proteins leads to the death of human granulosa cells surrounding the oocytes and presumably reduces oocyte quality and female fertility.
Quorum sensing is defined as the ability of microorganisms to sense their population density via the release of signaling molecules called autoinducers (AIs). Various types of AI analogs were prepared and their antitumor properties against chronic myeloid leukemia (CML) K562 cells were investigated. Two AI analogs induced progressive apoptosis with JNK activation and p21 induction. In addition, this induction of apoptosis is not related to bcr-abl kinase, which sustains CML proliferation. However, the progression of apoptosis was not inhibited by a caspase family inhibitor. These results suggested that AI analogs could induce caspase-independent apoptosis in CML K562.
Objective: Laparoscopic video-based educational material helps in self-training of laparoscopists. However, its effectiveness in medical students remains unclear. During the COVID-19 pandemic, we stopped clinical training at our hospital and instead provided the abovementioned educational material. In this study, we clarified its effectiveness in medical students.Methods: From July 2020 to May 2021, 87 fifth-grade medical students watched a 30-min video on total laparoscopic hysterectomy. Using the Likert scale, we interviewed the students about their impression of the material. We also asked whether it helped understand anatomy or surgical procedures and motivated students to study obstetrics and gynecology or surgery.
Results:The length and difficulty of the material were evaluated as "appropriate" by most of the students. Interest or aptitude of the material and helpfulness for learning pelvic anatomy or gynecological surgery both scored the highest.The second-best score was regarding the motivation to study obstetrics and gynecology or to join surgery. The impression of the length of the material correlated negatively with its aptitude. In contrast, the aptitude was positively correlated with helpfulness for understanding pelvic anatomy, surgery, or motivation for learning.Conclusions: In this study, laparoscopic video-based educational material was favorably accepted by medical students.However, assessments of the strength and weakness of the material are needed for improving medical education after the COVID-19 pandemic.
Purpose
Genetic factors associated with the risk of polycystic ovary syndrome (PCOS) remain largely unknown. Here, we conducted an optimal sequence kernel association test (SKAT‐O), an exome‐based rare variant association study, to clarify whether rare variants in specific genes contribute to the development of PCOS.
Methods
SKAT‐O was performed using exome data of 44 Japanese patients with PCOS and 301 control women. We analyzed frequencies of rare probably damaging variants in the genome.
Results
Rare variants of
GSTO2
were more commonly identified in the patient group than in the control group (6/44 vs. 1/301; Bonferroni‐corrected
p
‐value, 0.028), while the frequencies of variants in other genes were comparable between the two groups. The identified
GSTO2
variants were predicted to affect the function, structure, stability, hydrophobicity, and/or the formation of intrinsically disordered regions of the protein.
GSTO2
encodes a glutathione transferase that mediates the oxidative stress response and arsenic metabolism. Previously, common variants in
GSTO2
and its paralog
GSTO1
were associated with the risk of PCOS.
Conclusions
The results indicate that there are no genes whose rare variants account for a large fraction of the etiology of PCOS, although rare damaging variants in
GSTO2
may constitute a risk factor in some cases.
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