C. elegans PlexinA PLX-1 mediates a cell contact-dependent stop signal in vulval precursor cells

AbstractPLX-1 is a PlexinA transmembrane protein in Caenorhabditis elegans, and the transmembrane-type semaphorin, SMP-1, is a ligand for PLX-1. The SMP-1/PLX-1 system has been shown to be necessary for proper epidermal morphogenesis in the male tail and seam cells. Here, we show that the SMP-1/PLX-1 system also regulates vulval morphogenesis. In plx-1 and smp-1 mutants, hermaphrodites sometimes exhibit a protruding vulva or multiple vulva-like protrusions. Throughout the vulval development of plx-1 and smp-1 mutants, the arrangement of vulval cells is often disrupted. In the initial step of vulval morphogenesis, vulval precursor cells (VPCs) are generated normally but are subsequently arranged abnormally in mutants. Continuous observation revealed that plx-1 VPC fails to terminate longitudinal extension after making contact with neighbor VPCs. The arrangement defects of VPCs in plx-1 and smp-1 mutants are rescued by expressing the respective cDNA in VPCs. plx-1::egfp and smp-1::egfp transgenes are both expressed in all vulval cells, including VPCs, throughout vulval development. We propose that the SMP-1/PLX-1 system is responsible for a cell contact-mediated stop signal for VPC extension. Analyses using cell fate-specific markers showed that the arrangement defects of VPCs also affect cell fate specification and cell lineages, but in a relatively small fraction of plx-1 mutants

Efficacy of Brazilian Propolis against Herpes Simplex Virus Type 1 Infection in Mice and Their Modes of Antiherpetic Efficacies

Ethanol extracts (AF-06, 07, and 08, 10 mg/kg) of Brazilian propolis were administered orally to cutaneously herpes simplex virus type 1 (HSV-1)-infected mice three times daily on days 0 to 6 after infection to evaluate their efficacies against HSV-1 infection and significantly limited development of herpetic skin lesions. AF-07 and 08 significantly reduced virus titers in brain and/or skin on day 4 without toxicity, but AF-08 had no anti-HSV-1 activity in vitro. AF-06 and 08 significantly enhanced delayed-type hypersensitivity (DTH) to inactivated HSV-1 antigen in infected mice. Oral AF-08-administration significantly augmented interferon (IFN)-γ production by HSV-1 antigen from splenocytes of HSV-1-infected mice, while direct exposure of splenocytes of infected mice to AF-06 significantly elevated IFN-γ production in vitro. Thus, AF-08 might have components that are active in vivo even after oral administration and those of AF-06 might be active only in vitro. Because DTH is a major host defense for intradermal HSV-1 infection, augmentation of DTH response by AF-06 or 08, directly or indirectly, respectively, may contribute to their efficacies against HSV-1 infection. In addition, AF-06 and 07 possibly contain anti-HSV-1 components contributing to their efficacies. Such biological activities of Brazilian propolis may be useful to analyze its pharmacological actions

The Mechanism for Primordial Germ-Cell Migration Is Conserved between Japanese Eel and Zebrafish

Primordial germ cells (PGCs) are segregated and specified from somatic cells during early development. These cells arise elsewhere and have to migrate across the embryo to reach developing gonadal precursors. Several molecules associated with PGC migration (i.e. dead-end, nanos1, and cxcr4) are highly conserved across phylum boundaries. However, since cell migration is a complicated process that is regulated spatially and temporally by multiple adaptors and signal effectors, the process is unlikely to be explained by these known genes only. Indeed, it has been shown that there are variations in PGC migration pattern during development among teleost species. However, it is still unclear whether the actual mechanism of PGC migration is conserved among species. In this study, we studied the migration of PGCs in Japanese eel (Anguilla japonica) embryos and tested the migration mechanism between Japanese eel and zebrafish (Danio rerio) for conservation, by transplanting eel PGCs into zebrafish embryos. The experiments showed that eel PGCs can migrate toward the gonadal region of zebrafish embryos along with endogenous PGCs, even though the migration patterns, behaviors, and settlements of PGCs are somewhat different between these species. Our results demonstrate that the migration mechanism of PGCs during embryonic development is highly conserved between these two distantly related species (belonging to different teleost orders)

The Nanos3-3′UTR Is Required for Germ Cell Specific NANOS3 Expression in Mouse Embryos

BACKGROUND: The regulation of gene expression via a 3' untranslated region (UTR) plays essential roles in the discrimination of the germ cell lineage from somatic cells during embryogenesis. This is fundamental to the continuation of a species. Mouse NANOS3 is an essential protein required for the germ cell maintenance and is specifically expressed in these cells. However, the regulatory mechanisms that restrict the expression of this gene in the germ cells is largely unknown at present. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we show that differences in the stability of Nanos3 mRNA between germ cells and somatic cells is brought about in a 3'UTR-dependent manner in mouse embryos. Although Nanos3 is transcribed in both cell lineages, it is efficiently translated only in the germ lineage. We also find that the translational suppression of NANOS3 in somatic cells is caused by a 3'UTR-mediated mRNA destabilizing mechanism. Surprisingly, even when under the control of the CAG promoter which induces strong ubiquitous transcription in both germ cells and somatic cells, the addition of the Nanos3-3'UTR sequence to the coding region of exogenous gene was effective in restricting protein expression in germ cells. CONCLUSIONS/SIGNIFICANCE: Our current study thus suggests that Nanos3-3'UTR has an essential role in translational control in the mouse embryo

Pain related outcomes.

BackgroundEnhanced recovery is the gold standard in modern perioperative management, including that for cesarean deliveries. However, qualitative and quantitative data on the physical and psychological recovery of women after vaginal childbirth are limited. Whether neuraxial labor analgesia influences postpartum recovery is unknown.MethodsPrimiparous women anticipating a vaginal childbirth between January 2020 and May 2021 were enrolled. Women with major comorbidities or postpartum complications and those who underwent a cesarean delivery were excluded. Daily step count was measured using a wrist-worn activity tracker (FitbitTM Inspire HR) for 120 hours after vaginal childbirth. Subjective fatigue levels and health-related quality of life were assessed using the Multidimensional Fatigue Inventory (MFI) and EuroQol 5 Dimension 5 Level (EQ-5D-5L), respectively, at the 3rd trimester antenatal visit, on postpartum day 1 and 3, and at the one-month postpartum visit. Rest and dynamic pain scores and the location of pain were documented by participants during postpartum hospitalization.ResultsAmong 300 women who were enrolled antenatally, 95 and 116 had a vaginal delivery without (NCB group) and with (EPL group) epidural analgesia, respectively. The median number of steps per 24 hours increased daily in both groups, and no significant difference was detected between the groups. Postpartum pain was mild overall, with median rest and dynamic pain scores being less than 4 and similar between the groups. MFI and EQ-5D-5L scores were the worst on postpartum day 1 in both groups and gradually improved to antepartum level by the one-month postpartum visit. Higher MFI score on postpartum day 1, but not the use of epidural analgesia, was associated with lower odds of achieving adequate postpartum ambulation (defined as >3500 steps between 48 and 72 hours postpartum).ConclusionThe use of epidural analgesia was not associated with worse recovery outcomes during postpartum hospitalization.Trial registrationUMIN-CTR, #UMIN000039343, registered on January 31, 2020.</div

STROBE statement—checklist of items that should be included in reports of observational studies.

STROBE statement—checklist of items that should be included in reports of observational studies.</p

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BackgroundEnhanced recovery is the gold standard in modern perioperative management, including that for cesarean deliveries. However, qualitative and quantitative data on the physical and psychological recovery of women after vaginal childbirth are limited. Whether neuraxial labor analgesia influences postpartum recovery is unknown.MethodsPrimiparous women anticipating a vaginal childbirth between January 2020 and May 2021 were enrolled. Women with major comorbidities or postpartum complications and those who underwent a cesarean delivery were excluded. Daily step count was measured using a wrist-worn activity tracker (FitbitTM Inspire HR) for 120 hours after vaginal childbirth. Subjective fatigue levels and health-related quality of life were assessed using the Multidimensional Fatigue Inventory (MFI) and EuroQol 5 Dimension 5 Level (EQ-5D-5L), respectively, at the 3rd trimester antenatal visit, on postpartum day 1 and 3, and at the one-month postpartum visit. Rest and dynamic pain scores and the location of pain were documented by participants during postpartum hospitalization.ResultsAmong 300 women who were enrolled antenatally, 95 and 116 had a vaginal delivery without (NCB group) and with (EPL group) epidural analgesia, respectively. The median number of steps per 24 hours increased daily in both groups, and no significant difference was detected between the groups. Postpartum pain was mild overall, with median rest and dynamic pain scores being less than 4 and similar between the groups. MFI and EQ-5D-5L scores were the worst on postpartum day 1 in both groups and gradually improved to antepartum level by the one-month postpartum visit. Higher MFI score on postpartum day 1, but not the use of epidural analgesia, was associated with lower odds of achieving adequate postpartum ambulation (defined as >3500 steps between 48 and 72 hours postpartum).ConclusionThe use of epidural analgesia was not associated with worse recovery outcomes during postpartum hospitalization.Trial registrationUMIN-CTR, #UMIN000039343, registered on January 31, 2020.</div

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BackgroundEnhanced recovery is the gold standard in modern perioperative management, including that for cesarean deliveries. However, qualitative and quantitative data on the physical and psychological recovery of women after vaginal childbirth are limited. Whether neuraxial labor analgesia influences postpartum recovery is unknown.MethodsPrimiparous women anticipating a vaginal childbirth between January 2020 and May 2021 were enrolled. Women with major comorbidities or postpartum complications and those who underwent a cesarean delivery were excluded. Daily step count was measured using a wrist-worn activity tracker (FitbitTM Inspire HR) for 120 hours after vaginal childbirth. Subjective fatigue levels and health-related quality of life were assessed using the Multidimensional Fatigue Inventory (MFI) and EuroQol 5 Dimension 5 Level (EQ-5D-5L), respectively, at the 3rd trimester antenatal visit, on postpartum day 1 and 3, and at the one-month postpartum visit. Rest and dynamic pain scores and the location of pain were documented by participants during postpartum hospitalization.ResultsAmong 300 women who were enrolled antenatally, 95 and 116 had a vaginal delivery without (NCB group) and with (EPL group) epidural analgesia, respectively. The median number of steps per 24 hours increased daily in both groups, and no significant difference was detected between the groups. Postpartum pain was mild overall, with median rest and dynamic pain scores being less than 4 and similar between the groups. MFI and EQ-5D-5L scores were the worst on postpartum day 1 in both groups and gradually improved to antepartum level by the one-month postpartum visit. Higher MFI score on postpartum day 1, but not the use of epidural analgesia, was associated with lower odds of achieving adequate postpartum ambulation (defined as >3500 steps between 48 and 72 hours postpartum).ConclusionThe use of epidural analgesia was not associated with worse recovery outcomes during postpartum hospitalization.Trial registrationUMIN-CTR, #UMIN000039343, registered on January 31, 2020.</div

Fig 2 -

Postpartum trends in (A) adjusted daily steps and (B) Numeric Rating Scale (NRS) pain scores at rest and during movement. Box limits indicate the range of the central 50% of the data, with a central line marking the median value. p > 0.05 for all 24-hour periods in the comparison between the EPL and NCB groups.</p