Mate-guarding behavior enhances male reproductive success via familiarization with mating partners in medaka fish

Background: Male-male competition and female mating preference are major mechanisms of sexual selection, which influences individual fitness. How male-male competition affects female preference, however, remains poorly understood. Under laboratory conditions, medaka (Oryzias latipes) males compete to position themselves between a rival male and the female (mate-guarding) in triadic relationships (male, male, and female). In addition, females prefer to mate with visually familiar males. In the present study, to examine whether mate-guarding affects female preference via visual familiarization, we established a novel behavioral test to simultaneously quantify visual familiarization of focal males with females and mate-guarding against rival males. In addition, we investigated the effect of familiarization on male reproductive success in triadic relationships. Results: Three fish (female, male, male) were placed separately in a transparent three-chamber tank, which allowed the male in the center (near male) to maintain closer proximity to the female than the other male (far male). Placement of the wild-type male in the center blocked visual familiarization of the far male by the female via mate-guarding. In contrast, placement of an arginine-vasotocin receptor mutant male, which exhibits mate-guarding deficits, in the center, allowing for maintaining close proximity to the female, did not block familiarization of the far male by the female. We also demonstrated that the reproductive success of males was significantly decreased by depriving females visual familiarization with the males. Conclusions: Our findings indicated that, at least in triadic relationships, dominance in mate-guarding, not simply close proximity, allows males to gain familiarity with the female over their rivals, which may enhance female preference for the dominant male. These findings focusing on the triadic relationships of medaka may contribute to our understanding of the adaptive significance of persistent mate-guarding, as well as female preference for familiar mates

Mate-guarding behavior enhances male reproductive success via familiarization with mating partners in medaka fish

[Background] Male-male competition and female mating preference are major mechanisms of sexual selection, which influences individual fitness. How male-male competition affects female preference, however, remains poorly understood. Under laboratory conditions, medaka (Oryzias latipes) males compete to position themselves between a rival male and the female (mate-guarding) in triadic relationships (male, male, and female). In addition, females prefer to mate with visually familiar males. In the present study, to examine whether mate-guarding affects female preference via visual familiarization, we established a novel behavioral test to simultaneously quantify visual familiarization of focal males with females and mate-guarding against rival males. In addition, we investigated the effect of familiarization on male reproductive success in triadic relationships. [Results] Three fish (female, male, male) were placed separately in a transparent three-chamber tank, which allowed the male in the center (near male) to maintain closer proximity to the female than the other male (far male). Placement of the wild-type male in the center blocked visual familiarization of the far male by the female via mate-guarding. In contrast, placement of an arginine-vasotocin receptor mutant male, which exhibits mate-guarding deficits, in the center, allowing for maintaining close proximity to the female, did not block familiarization of the far male by the female. We also demonstrated that the reproductive success of males was significantly decreased by depriving females visual familiarization with the males. [Conclusions] Our findings indicated that, at least in triadic relationships, dominance in mate-guarding, not simply close proximity, allows males to gain familiarity with the female over their rivals, which may enhance female preference for the dominant male. These findings focusing on the triadic relationships of medaka may contribute to our understanding of the adaptive significance of persistent mate-guarding, as well as female preference for familiar mates

Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients. Trial registration numbers: JapicCTI-101339 and JapicCTI-111550

A multi-center study on low-frequency rTMS combined with intensive occupational therapy for upper limb hemiparesis in post-stroke patients

<p>Abstract</p> <p>Background</p> <p>Both low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) have been recently reported to be clinically beneficial for post-stroke patients with upper limb hemiparesis. Based on these reports, we developed an inpatient combination protocol of these two modalities for the treatment of such patients. The aims of this pilot study were to confirm the safety and feasibility of the protocol in a large number of patients from different institutions, and identify predictors of the clinical response to the treatment.</p> <p>Methods</p> <p>The study subjects were 204 post-stroke patients with upper limb hemiparesis (mean age at admission 58.5 ± 13.4 years, mean time after stroke 5.0 ± 4.5 years, ± SD) from five institutions in Japan. During 15-day hospitalization, each patient received 22 treatment sessions of 20-min low-frequency rTMS and 120-min intensive OT daily. Low-frequency rTMS of 1 Hz was applied to the contralesional hemisphere over the primary motor area. The intensive OT, consisting of 60-min one-to-one training and 60-min self-exercise, was provided after the application of low-frequency rTMS. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were performed serially. The physiatrists and occupational therapists involved in this study received training prior to the study to standardize the therapeutic protocol.</p> <p>Results</p> <p>All patients completed the protocol without any adverse effects. The FMA score increased and WMFT log performance time decreased significantly at discharge, relative to the respective values at admission (change in FMA score: median at admission, 47 points; median at discharge, 51 points; p < 0.001. change in WMFT log performance time: median at admission, 3.23; median at discharge, 2.51; p < 0.001). These changes were persistently seen up to 4 weeks after discharge in 79 patients. Linear regression analysis found no significant relationship between baseline parameters and indexes of improvement in motor function.</p> <p>Conclusions</p> <p>The 15-day inpatient rTMS plus OT protocol is a safe, feasible, and clinically useful neurorehabilitative intervention for post-stroke patients with upper limb hemiparesis. The response to the treatment was not influenced by age or time after stroke onset. The efficacy of the intervention should be confirmed in a randomized controlled study including a control group.</p

Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure

Pharmacological blockade of the N-and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of α1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2-/- mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2-/- mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2+/+ mice. Interestingly, diabetic heterozygous Cav2.2+/- mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2+/+ mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by Ω-conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-β (TGF-β) in podocytes was abolished with Ω-conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes.</p

Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy

There is a hot debate concerning actual amount of albumin filtered through glomeruli and reabsorbed at proximal tubules in normal kidneys and diabetic conditions. To overcome current technical problems, we generated a drug-inducible megalin knockout mouse line, megalin(lox/lox);Ndrg1-CreER[T2] (or iMegKO), whose protein reabsorption can be shut off anytime by tamoxifen (Tam). After Tam administration, renal megalin protein expression was reduced by 92% compared to wild-type C57BL/6J mice, and renal reabsorption of intravenously-injected retinol binding protein was almost completely abrogated. Urinary albumin excretion increased to 175 μg/day (0.460 mg/mg-creatinine), suggesting that this was the amount of total nephron albumin filtration. Glomerular sieving coefficient of albumin was 1.7 x 10[-5]. By comparing streptozotocin-induced, Tam-treated, diabetic STZ;iMegKO mice with non-STZ;iMegKO mice, we estimated that daily albumin filtration was increased by 1.9-fold, reabsorption was increased by 1.8-fold, and reabsorption efficiency was reduced to 86% by development of diabetes (versus 96% in control). Such abnormalities were well normalized after insulin treatment. Another type 1 diabetic model of Akita;iMegKO mice showed equivalent results. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy, bringing new insights into our understanding of renal albumin dynamics in hyperfiltration status of diabetic nephropath

AsiaPEX:Challenges and Prospects in Asian Precipitation Research

The Asian Precipitation Experiment (AsiaPEX) was initiated in 2019 to understand terrestrial precipitation over diverse hydroclimatological conditions for improved predictions, disaster reduction, and sustainable development across Asia under the framework of the Global Hydroclimatology Panel (GHP)/Global Energy and Water Exchanges (GEWEX). AsiaPEX is the successor to GEWEX Asian Monsoon Experiment (GAME; 1995-2005) and Monsoon Asian Hydro-Atmosphere Scientific Research and Prediction Initiative (MAHASRI; 2006-16). While retaining the key objectives of the aforementioned projects, the scientific targets of AsiaPEX focus on land-atmosphere coupling and improvements to the predictability of the Asian hydroclimatological system. AsiaPEX was designed for both fine-scale hydroclimatological processes occurring at the land surface and the integrated Asian hydroclimatological system characterized by multiscale interactions. We adopt six approaches including observation, process studies, scale interactions, high-resolution hydrological modeling, field campaigns, and climate projection, which bridge gaps in research activities conducted in different regions. Collaboration with mesoscale and global modeling researchers is one of the core methods in AsiaPEX. We review these strategies based on the literature and our initial outcomes. These include the estimation and validation of highresolution satellite precipitation, investigations of extreme rainfall mechanisms, field campaigns over the Maritime Continent and Tibetan Plateau, areas of significant impact on the entire AsiaPEX region, process studies on diurnal- to interdecadal-scale interactions, and evaluation of the predictabilities of climate models for long-term variabilities. We will conduct integrated observational and modeling initiative, the Asian Monsoon Year (AMY)-II around 2025-28, whose strategies are the subregional observation platforms and integrated global analysis.</p

Natriuretic peptide receptor guanylyl cyclase-A pathway counteracts glomerular injury evoked by aldosterone through p38 mitogen-activated protein kinase inhibition

Guanylyl cyclase-A (GC-A) signaling, a natriuretic peptide receptor, exerts renoprotective effects by stimulating natriuresis and reducing blood pressure. Previously we demonstrated massive albuminuria with hypertension in uninephrectomized, aldosterone-infused, and high salt-fed (ALDO) systemic GC-A KO mice with enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in podocytes. In the present study, we examined the interaction between p38 MAPK and GC-A signaling. The administration of FR167653, p38 MAPK inhibitor, reduced systolic blood pressure (SBP), urinary albumin excretion, segmental sclerosis, podocyte injury, and apoptosis. To further investigate the local action of natriuretic peptide and p38 MAPK in podocytes, we generated podocyte-specific (pod) GC-A conditional KO (cKO) mice. ALDO pod GC-A cKO mice demonstrated increased urinary albumin excretion with marked mesangial expansion, podocyte injury and apoptosis, but without blood pressure elevation. FR167653 also suppressed urinary albumin excretion without reducing SBP. Finally, we revealed that atrial natriuretic peptide increased phosphorylation of MAPK phosphatase-1 (MKP-1) concomitant with inhibited phosphorylation of p38 MAPK in response to MAPK kinase 3 activation, thereby resulting in decreased mRNA expression of the apoptosis-related gene, Bax, and Bax/Bcl2 ratio in cultured podocytes. These results indicate that natriuretic peptide exerts a renoprotective effect via inhibiting phosphorylation of p38 MAPK in podocytes.</p