Auto-spermatophore extrusion in male crickets

The reproductive cycle of the male cricket consists of the mating stage and the sexually refractory stage. The latter is further divided into the first refractory stage (RS1) from spermatophore extrusion in copulation to spermatophore preparation after copulation, and the second refractory stage (RS2) from spermatophore preparation to recommencement of a calling song. RS2 is time-fixed and unaffected by the female or by stress, hence RS2 is assumed to be controlled by the reproductive timer. Previously, we suggested that the timer is located in the terminal abdominal ganglion (TAG), because functional inactivation of the TAG by local cooling lengthened RS2 in proportion to cooling time. To obtain further evidence of timer localization and to examine the operation of the timer in dissected animals, we investigated the characteristics of auto-spermatophore extrusion, a phenomenon in which males eject the mature spermatophore themselves without any prior courtship. The occurrence of auto-spermatophore extrusion was 100% in dissected males with the TAG separated, compared to 1.7% in intact males. The time interval (SPaSE) between spermatophore preparation and autospermatophore extrusion was comparable to RS2 measured by the calling song. Spike recording from a genital motor neurone in the separated TAG indicated that burst discharge associated with auto-spermatophore extrusion occurred with a SPaSE comparable to RS2. Other efferent neurones, some of which were identified as dorsal unpaired median (DUM) neurones, showed a timedependent spike frequency increase during SPaSE. These results strengthen our previous conclusion that the reproductive timer is located within the TAG, and demonstrate that the timer functions normally even when the TAG is separated from the central nervous system.</p

Reconsideration of Hormonal Therapy in the Era of Next‐ Generation Hormonal Therapy

Hormonal therapy is a major and effective tool in the treatment of prostate cancer patients. This is especially true for patients in the advanced stages of disease. Unfortunately, almost all prostate cancer cells will develop into castration‐resistant prostate cancer (CRPC) despite continued therapy and suppression of testosterone levels. Up until 5–6 years ago, there was little effective therapy for the treatment of CRPC patients. However, recently, a variety of methodologies and drugs such as cabazitaxel and sipuleucel‐T have been approved globally for the treatment of CRPC. Two novel drugs, abiraterone acetate and enzartamide, have also become available as potential treatment options. However, the anticancer effects of these two drugs are not always satisfactory in terms of prolonging survival. These drugs are also associated with adverse events and are expensive when compared with the costs of previously used anticancer drugs. In this section, we pay particular attention to hormonal therapies that do not include the use of abiraterone acetate or enzartamide. We believe that a detailed understanding of the range of currently available hormonal therapies, including their associated benefits and limitations, is important for supporting the prolongation of survival in patients with advanced prostate cancer. Therefore, this section offers a valuable discussion on the treatment strategies for prostate cancer including CRPC

ONO-1301, a Sustained-Release Prostacyclin Analog, Ameliorates the Renal Alterations in a Mouse Type 2 Diabetes Model Possibly Through Its Protective Effects on Mesangial Cells

Diabetic nephropathy is the most common pathological disorder predisposing patients to end-stage renal disease. Considering the increasing prevalence of type 2 diabetes mellitus worldwide, novel therapeutic approaches are urgently needed. ONO-1301 is a novel sustained-release prostacyclin analog that inhibits thromboxane A2 synthase. Here we examined the therapeutic effects of the intermittent administration of slow-release ONO-1301 (SR-ONO) on diabetic nephropathy in obese type 2 diabetes mice, as well as its direct effects on mesangial cells. The subcutaneous injection of SR-ONO (3mg/kg) every 3 wks did not affect the obesity or hyperglycemia in the db/db obese mice used as a model of type 2 diabetes, but it significantly ameliorated their albuminuria, glomerular hypertrophy, glomerular accumulation of type IV collagen, and monocyte/macrophage infiltration, and also the increase of TGF-β1, α-smooth muscle actin (α-SMA) and MCP-1 compared to vehicle treatment. In cultured mouse mesangial cells, ONO-1301 concentration-dependently suppressed the increases in TGF-β, type IV collagen, α-SMA, MCP-1 and fibronectin induced by high ambient glucose, at least partly through prostacyclin (PGI2) receptor-mediated signaling. Taken together, these results suggest the potential therapeutic efficacy of the intermittent administration of SR-ONO against type 2 diabetic nephropathy, possibly through protective effects on mesangial cells

SURFACE MARKERS AND GENE EXPRESSION TO CHARACTERIZE THE DIFFERENTIATION OF MONOLAYER EXPANDED HUMAN ARTICULAR CHONDROCYTES

Autologous chondrocyte implantation (ACI) is a method of cartilage repair. To improve the quality of regenerated tissue by ACI, it is essential to identify surface marker expression correlated with the differentiation status of monolayer expanded human articular chondrocytes and to define the index for discriminating dedifferentiated cells from monolayer expanded human articular chondrocytes. Normal human articular chondrocytes were cultured in monolayer until passage 4. At each passage, mRNA expression of collagen type I, II, and X and aggrecan was analyzed by real-time quantitative PCR, and the surface marker expression of CD14, CD26, CD44, CD49a, CD49c, CD54, and CD151 was analyzed by fluorescence-activated cell sorting (FACS). The ratios of mRNA levels of collagen type II to I (Col II/Col I) represented the differentiation status of chondrocytes more appropriately during monolayer culture. The surface marker expression of CD44, CD49c, and CD151 was upregulated according to the dedifferentiation status, whereas that of CD14, CD49a, and CD54 was downregulated. The most appropriate combination of the ratio of Col II/Col I was CD54 and CD44. Cell sorting was performed using a magnetic cell sorting system (MACS) according to CD54 and CD44, and real-time quantitative PCR was performed for the cell subpopulations before and after cell sorting. The expression of collagen type II and aggrecan of the chondrocytes after MACS was higher than that before sorting, but not significantly. The mean fluorescence intensity (MFI) ratio of CD54 to CD44 could be an adequate candidate as the index of the differentiation status

Predisposition for borderline personality disorder with comorbid major depression is associated with that for polycystic ovary syndrome in female Japanese population

Polycystic ovary syndrome (PCOS) is a common lifestyle-related endocrinopathy in women of reproductive age and is associated with several mental health problems. We examined the genotypic distributions of IRS-1 Gly972Arg and CYP11B2 -344T/C, which were previously described as influencing PCOS, and assayed the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in a set of female patients with borderline personality disorder (BPD) with comorbid major depressive disorder (MDD) (n = 50) and age-matched control subjects (n = 100), to investigate the predisposition for BPD with MDD. The results showed that the patients were more frequently IRS-1 972Arg variant allele carriers (P = 0.013; OR 6.68; 95% CI = 1.30–34.43) and homozygous for the CYP11B2 −344C variant allele (P = 0.022; OR = 3.32; 95% CI = 1.18–9.35) than the control subjects. The IL-6 level was significantly higher in the patients than in the controls (P < 0.0001). There was no significant difference in the serum TNF-α level between patients with BPD with MDD and the healthy comparison group (P = 0.5273). In conclusion, the predisposition for BPD with MDD is associated with that for PCOS, in the female Japanese population. An elevated serum IL-6 level is considered to be a possible biomarker of BPD with MDD

Bifidobacterium response to lactulose ingestion in the gut relies on a solute-binding protein-dependent ABC transporter

ビフィズス菌がラクチュロースを利用する仕組みを解明 --ビフィズス菌の増殖作用の予測への活用も--. 京都大学プレスリリース. 2021-05-24.This study aims to understand the mechanistic basis underlying the response of Bifidobacterium to lactulose ingestion in guts of healthy Japanese subjects, with specific focus on a lactulose transporter. An in vitro assay using mutant strains of Bifidobacterium longum subsp. longum 105-A shows that a solute-binding protein with locus tag number BL105A_0502 (termed LT-SBP) is primarily involved in lactulose uptake. By quantifying faecal abundance of LT-SBP orthologues, which is defined by phylogenetic analysis, we find that subjects with 10⁷ to 10⁹ copies of the genes per gram of faeces before lactulose ingestion show a marked increase in Bifidobacterium after ingestion, suggesting the presence of thresholds between responders and non-responders to lactulose. These results help predict the prebiotics-responder and non-responder status and provide an insight into clinical interventions that test the efficacy of prebiotics

MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes

INTRODUCTION: Increased expression of aggrecanase-1 (ADAMTS-4) has emerged as an important factor in osteoarthritis (OA) and other joint diseases. This study aimed to determine whether the expression of ADAMTS-4 in human chondrocytes is regulated by miRNA. METHODS: MiRNA targets were identified using bioinformatics. Chondrocytes were isolated from knee cartilage and treated with interleukin-1 beta (IL-1β). Gene expression was quantified using TaqMan assays and protein production was determined by immunoblotting. Luciferase reporter assay was used to verify interaction between miRNA and target messenger RNA (mRNA). RESULTS: In silico analysis predicted putative target sequence of miR-125b on ADAMTS-4. MiR-125b was expressed in both normal and OA chondrocytes, with significantly lower expression in OA chondrocytes than in normal chondrocytes. Furthermore, IL-1β-induced upregulation of ADAMTS-4 was suppressed by overexpression of miR-125b in human OA chondrocytes. In the luciferase reporter assay, mutation of the putative miR-125b binding site in the ADAMTS-4 3'UTR abrogated the suppressive effect of miR125. CONCLUSIONS: Our results indicate that miR-125b plays an important role in regulating the expression of ADAMTS-4 in human chondrocytes and this identifies miR-125b as a novel therapeutic target in OA