Social jetlag and menstrual symptoms among female university students

Menstrual symptoms may have a significant impact on women’s lives. Many women experience menses-related health problems, such as menstrual pain, heavy menstrual bleeding, and premenstrual syndrome, during their reproductively fertile years. Circadian misalignment in shift workers has been reported to contribute to menstrual cycle irregularity and/or painful menstruation. However, the relationship between social jetlag (SJL) and menstrual symptoms/menstrual cycle has not been elucidated. In this study, we aimed to elucidate this relationship among female university students. One-hundred and fifty female university students (mean [SD]: 18.8 [0.71]-years old) completed self-reported questionnaires consisting of menstrual symptoms and menstrual cycle, sleep quality and sleep habits, quality of life, and demographic variables. The average menstrual cycle was 32.0 [5.4] days. The percentage of students who showed menstrual cycle irregularity, having less than 25 days or more than 39 days of menstrual cycle during the previous four menstrual cycles, was 60.6%. SJL, the difference between mid-sleep time on free days and mid-sleep time on school days, was categorized into small (absolute SJL < 1 h) or large (≥1 h). Overall, 78.0% of participants had SJL ≥ 1 h. Among the menstrual symptoms, pain, behavioral change, and water retention subscale scores were significantly higher in the SJL ≥ 1 h group than in the SJL < 1 h group. However, no significant differences were found in concentration, autonomic reaction, or negative affect subscale scores between the two groups. The menstrual cycle was 31.2 [5.5] days in the SJL < 1 h group and 32.2 [5.4] days in the SJL ≥ 1 h group, without significant difference. Logistic regression analysis showed that more than 1 h of SJL was a significant associated factor with severe menstrual symptom, independently of sleep duration and late chronotype. This study indicated that SJL was a significant factor associated with severe menstrual symptoms, suggesting the possibilities of association between circadian system and reproductive function among humans.     

Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages

Shigella infection, the cause of bacillary dysentery, induces caspase-1 activation and cell death in macrophages, but the precise mechanisms of this activation remain poorly understood. We demonstrate here that caspase-1 activation and IL-1beta processing induced by Shigella are mediated through Ipaf, a cytosolic pattern-recognition receptor of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, and the adaptor protein apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC). We also show that Ipaf was critical for pyroptosis, a specialized form of caspase-1-dependent cell death induced in macrophages by bacterial infection, whereas ASC was dispensable. Unlike that observed in Salmonella and Legionella, caspase-1 activation induced by Shigella infection was independent of flagellin. Notably, infection of macrophages with Shigella induced autophagy, which was dramatically increased by the absence of caspase-1 or Ipaf, but not ASC. Autophagy induced by Shigella required an intact bacterial type III secretion system but not VirG protein, a bacterial factor required for autophagy in epithelial-infected cells. Treatment of macrophages with 3-methyladenine, an inhibitor of autophagy, enhanced pyroptosis induced by Shigella infection, suggesting that autophagy protects infected macrophages from pyroptosis. Thus, Ipaf plays a critical role in caspase-1 activation induced by Shigella independently of flagellin. Furthermore, the absence of Ipaf or caspase-1, but not ASC, regulates pyroptosis and the induction of autophagy in Shigella-infected macrophages, providing a novel function for NLR proteins in bacterial-host interactions.     

HM1.24/BST-2 is constitutively poly-ubiquitinated at the N-terminal amino acid in the cytoplasmic domain

HM1.24 (also known as BST-2, CD317, and Tetherin) is a type II single-pass transmembrane glycoprotein, which traverses membranes using an N-terminal transmembrane helix and is anchored in membrane lipid rafts via a C-terminal glycosylphosphatidylinositol (GPI). HM1.24 plays a role in diverse cellular functions, including cell signaling, immune modulation, and malignancy. In addition, it also functions as an interferon-induced cellular antiviral restriction factor that inhibits the replication and release of diverse enveloped viruses, and which is counteracted by Vpu, an HIV-1 accessory protein. Vpu induces down-regulation and ubiquitin conjugation to the cytoplasmic domain of HM1.24. However, evidence for ubiquitination site(s) of HM1.24 remains controversial. We demonstrated that HM1.24 is constitutively poly-ubiquitinated at the N-terminal cytoplasmic domain, and that the mutation of all potential ubiquitination sites, including serine, threonine, cysteine, and lysine in the cytoplasmic domain of HM1.24, does not affect the ubiquitination of HM1.24. We further demonstrated that although a GPI anchor is necessary and sufficient for HM1.24 antiviral activities and virion-trapping, the deleted mutant of GPI does not influence the ubiquitination of HM1.24. These results suggest that the lipid raft localization of HM1.24 is not a prerequisite for the ubiquitination. Collectively, our findings demonstrate that the ubiquitination of HM1.24 occurs at the N-terminal amino acid in the cytoplasmic domain and indicate that the constitutive ubiquitination machinery of HM1.24 may differ from the Vpu-induced machinery.     

Synthesis of core-class 2 O-linked glycopeptides: a benzyl-protected tetrasaccharyl serine and its derivative carrying a hydrophobic cholestanyl group

A core-class 2 tetrasaccharide-linked serine was synthesized in a convergent manner. The coupling reaction of disaccharide glycosyl donor 3 and acceptor 4 stereoselectively afforded tetrasaccharide 15, which was converted to glycosyl fluoride 20. Glycosylation of Fmoc serine allyl ester 5 with 20 produced alpha- and beta-glycosides in 40% and 33% yields, respectively. Alpha-Isomer 21 was converted into 1, a useful building block for the solid-phase synthesis of glycopeptides. On the other hand, 21 was N-deprotected and condensed with hydrophobic cholestanol through a succinyl spacer. The same compound was alternatively synthesized by coupling 20 and 28. Functional group manipulation and hydrogenation afforded core 2 tetrasaccharide-cholestanol conjugate 2.     

Assessment of Cancer-Related Fatigue,Pain, and Quality of Life in Cancer Patients at Palliative Care Team Referral: A Multicenter Observational Study (JORTC PAL-09)

Introduction

Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams.

Materials and Methods

Patients who were referred to palliative care teams at three institutions and met the inclusion criteria were invited to complete the Brief Fatigue Inventory, Brief Pain Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative.

Results

Of 183 patients recruited, the majority (85.8%) were diagnosed with recurrence or metastasis. The largest group (42.6%) comprised lung cancer patients, of whom 67.2% had an Eastern Cooperative Oncology Group Performance Status of 0–1. The mean value for global health status/quality of life was 41.4, and the highest mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative symptom item score was for pain (51.0). The mean global fatigue score was 4.1, and 9.8%, 30.6%, 38.7%, and 20.8% of patients’ fatigue severity was classified as none (score 0), mild (1–3), moderate (4–6), and severe (7–10), respectively.

Discussion

Cancer-related fatigue, considered to occur more frequently in cancer patients, was successfully assessed using patient-reported outcomes with the Brief Fatigue Inventory for the first time in Japan. Results suggested that fatigue is potentially as problematic as pain, which is the main reason for palliative care.     

The Neural Correlates of Mindful Awareness: A Possible Buffering Effect on Anxiety-Related Reduction in Subgenual Anterior Cingulate Cortex Activity

Background

Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC).

Methods

Resting brain glucose metabolism (GM) was measured using [¹⁸F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively.

Results

Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA β = −0.248, p = 0.003; ST: β = 0.250, p = 0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x = −8, y = 32, z = −8, k = 423, Z = 4.41, corrected p ^FDR = 0.030).

Conclusion

The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in individuals with a risk for or having anxiety and depressive disorders.     

Establishment of a transport system for mouse epididymal sperm at refrigerated temperatures

The exchange of genetically engineered mouse strains between research facilities requires transporting fresh mouse sperm under refrigerated temperatures. Although sperm generally maintains fertility for 48 h at cold temperatures, in vitro fertilization rates of C57BL/6 mouse sperm are low after 48-h cold storage. Furthermore, 48 h is often not sufficient for the specimens to reach their destinations. To increase the availability of this technology, we aimed to extend the cold storage period while maintaining sperm fertility. In this study, we determined the optimal medium for sperm preservation and evaluated the effect of reduced glutathione in the fertilization medium on sperm fertility after cold storage. We found that higher fertility levels were maintained after 72-h cold storage in the preservation medium Lifor compared with storage in paraffin oil, M2 medium, or CPS-1 medium. In addition, 1.0 mM glutathione enhanced sperm fertility. After transporting sperm from Asahikawa Medical University to our laboratory, embryos were efficiently produced from the cold-stored sperm. After transfer, these embryos developed normally into live pups. Finally, we tested the transport system using genetically engineered mouse strains and obtained similar high fertilization rates with all specimens. In summary, we demonstrated that cold storage of sperm in Lifor maintains fertility, and glutathione supplementation increased the in vitro fertilization rates of sperm after up to 96 h of cold storage. This improved protocol provides a simple alternative to transporting live animals or cryopreserved samples for the exchange of genetically engineered mouse strains among research facilities.     

Wnt signal transduction pathways

The Wnt signaling pathway is an ancient and evolutionarily conserved pathway that regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis during embryonic development. The Wnts are secreted glycoproteins and comprise a large family of nineteen proteins in humans hinting to a daunting complexity of signaling regulation, function and biological output. To date major signaling branches downstream of the Fz receptor have been identified including a canonical or Wnt/β-catenin dependent pathway and the non-canonical or β-catenin-independent pathway which can be further divided into the Planar Cell Polarity and the Wnt/Ca²⁺ pathways, and these branches are being actively dissected at the molecular and biochemical levels. In this review, we will summarize the most recent advances in our understanding of these Wnt signaling pathways and the role of these pathways in regulating key events during embryonic patterning and morphogenesis.Key words: Wnt, frizzled, dishevelled, canonical, non-canonical, β-catenin, Planar Cell Polarity     

CASPR2 forms a complex with GPR37 via MUPP1 but not with GPR37(R558Q), an autism spectrum disorder‐related mutation

Autism spectrum disorder (ASD) is a developmental brain disorder. Mutations in synaptic components including synaptic adhesion molecules have been found in ASD patients. Contactin‐associated protein‐like 2 (CASPR2) is one of the synaptic adhesion molecules associated with ASD. CASPR2 forms a complex with receptors via interaction with multiple PDZ domain protein 1 (MUPP1). Little is known about the relationship between impaired CASPR2‐MUPP1‐receptor complex and the pathogenesis of ASD. GPR37 is a receptor for survival factors. We recently identified mutations including R558Q in the G‐protein‐coupled receptor 37 (GPR37) gene in ASD patients. The mutated GPR37s accumulate in the endoplasmic reticulum. In this study, we show that GPR37 is a component of the CASPR2‐MUPP1 receptor complex in the mouse brain. CASPR2 and GPR37 mainly interacted with the PDZ3 and PDZ11 domains of MUPP1, respectively. Compared to GPR37, GPR37(R558Q) slightly interacted with MUPP1 and caused dendritic alteration. GPR37, but not GPR37(R558Q) nor GPR37‐deltaC which lacks its PDZ binding domain, was transported to the cell surface by MUPP1. In primary hippocampal neurons, GPR37 co‐localized with MUPP1 and CASPR2 at the synapse, but not GPR37(R558Q). Thus, ASD‐related mutation of GPR37 may cause the impaired CASPR2‐MUPP1‐GPR37 complex on the dendrites associated with one of the pathogenesis of ASD.