Colonized Aedes albopictus and its sexual performance in the wild: implications for SIT technology and containment

Background: Mating is a physiological process of crucial importance underlying the size and maintenance of mosquito populations. In sterile and incompatible insect technologies (SIT and IIT), mating is essential for mass production, persistence, and success of released individuals, and is a central parameter for judging the effectiveness of SIT/IIT programs. Some mosquitoes have an enormous reproductive potential for both themselves and pathogens and mating may contribute to persistence of infection in nature. As Aedes albopictus can transmit flaviviruses both sexually and horizontally, and as infected insects are usually derived from laboratory colonies, we investigated the implications of mating between a long-term laboratory colony of Ae. albopictus and wild populations. Methods: Through a series of mating experiments, we examined the reproductive outcomes of sexual cross-affinity between laboratory-raised and wild adults of Ae. albopictus. Results: The results indicated appreciable mating compatibility between laboratory-reared and wild adults, and equivalent levels of egg production among reciprocal crosses. We also observed comparable larval eclosion in lab females mated with wild males, and increased adult longevity in female offspring from wild females|×|laboratory males crosses. Conclusions: Taken together, these data suggest that Ae. albopictus can preserve its reproductive fitness over a long period of time in the laboratory environment and has valuable attributes for SIT application. These observations together with the ability to successfully inseminate heterospecific females indicate the potential of Ae. albopictus to act as an ecological barrier if non-sterilized males are massively released in areas occupied by Aedes aegypti. The observed substantial reproductive fitness combined with the capability to reproduce both, itself and viruses illustrates the potential of Ae. albopictus to pose a serious threat if infected and released accidentally

Elevation of dopamine level reduces hostseeking activity in the adult female mosquito Aedes albopictus

Background: Mosquito-borne viruses are transmitted to human hosts via blood-feeding behavior of female mosquitoes. Female mosquitoes seek a host to take blood meals (host-seeking behavior). In order to prevent virus infections, it is important to understand how they modulate host-seeking behavior. Dopamine (DA) in the central nervous system acts as a neuromediator that regulates a variety of behaviors in insects. In female mosquitoes, host-seeking behavior increases when DA levels in the head decline after emergence. However, it remains unclear whether DA directly modulates host-seeking behavior in female mosquitoes. The aim of this study was to examine whether changes in DA levels in the head affects host-seeking activity in the adult female mosquito Aedes albopictus (Ae. albopictus). Findings: We compared host-seeking behavior in one group of emerging female adults treated with L-β-3,4-dihydroxyphenylalanine (L-DOPA), the precursor of DA, (L-DOPA group), with that in an untreated control (control group) after confirming elevation of head DA in L-DOPA group by using high-performance liquid chromatography. The content of head DA in L-DOPA group significantly remained higher than that in controls on all days examined. The host-seeking activity in the control group showed a gradual increase over the 6-day experimental period. In contrast, there was no such increase in the host-seeking activity in the L-DOPA group. Therefore, the host-seeking activity of L-DOPA group was significantly lower than that of the controls between day 3 and 6 post-emergence. Conclusion: Our results indicate that elevation of DA level reduces host-seeking activity in adult female mosquito Ae. albopictus

Coffee and its waste repel gravid Aedes albopictus females and inhibit the development of their embryos

Background Dengue is a prevalent arboviral disease and the development of insecticide resistance among its vectors impedes endeavors to control it. Coffee is drunk by millions of people daily worldwide, which is associated with the discarding of large amounts of waste. Coffee and its waste contain large amounts of chemicals many of which are highly toxic and none of which have a history of resistance in mosquitoes. Once in solution, coffee is brownish in colour, resembling leaf infusion, which is highly attractive to gravid mosquitoes. To anticipate the environmental issues related to the increasing popularity of coffee as a drink, and also to combat insecticide resistance, we explored the deterrence potentials of coffee leachates against the ovipositing and embryonic stages of the dengue vector, Aedes albopictus. Methods In a series of choice, no-choice, and embryo toxicity bioassays, we examined changes in the ovipositional behaviours and larval eclosion of Ae. albopictus in response to coffee extracts at different concentrations. Results Oviposition responses were extremely low when ovicups holding highly concentrated extract (HCE) of coffee were the only oviposition sites. Gravid females retained increased numbers of mature eggs until 5 days post-blood feeding. When provided an opportunity to oviposit in cups containing coffee extracts and with water, egg deposition occurred at lower rates in those containing coffee, and HCE cups were far less attractive to females than those containing water only. Females that successfully developed in a coffee environment preferentially oviposited in such cups when in competition with preferred oviposition sites (water cups), but this trait did not continue into the fourth generation. Larval eclosion occurred at lower rates among eggs that matured in a coffee environment, especially among those that were maintained on HCE-moistened substrates. Conclusions The observations of the present study indicate a pronounced vulnerability of Ae. albopictus to the presence of coffee in its habitats during the early phases of its life cycle. The observations that coffee repels gravid females and inhibits larval eclosion provide novel possibilities in the search for novel oviposition deterrents and anti-larval eclosion agents against dengue vectors.This work was supported by funds (No. 096010) from the Central Research Institute of Fukuoka University and “Long Term Research Grant (LRGS) for Infectious Diseases, 2011 – 2014, Ministry of Higher Education, Malaysia” and USM (304/Pbiology/650575/U112)

Maslinic Acid Attenuates Denervation-Induced Loss of Skeletal Muscle Mass and Strength

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-β signaling in MA-treated mice. In addition, qPCR data showed that MA induced Igf1 expression and suppressed the expressions of Atrogin-1, Murf1 and Tgfb. Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength

Acute effects of empagliflozin on open-loop baroreflex function and urinary glucose excretion in rats with chronic myocardial infarction

Abstract Sodium–glucose cotransporter 2 (SGLT2) inhibitors have exerted cardioprotective effects in clinical trials, but underlying mechanisms are not fully understood. As mitigating sympathetic overactivity is of major clinical concern in the mechanisms of heart failure treatments, we examined the effects of modulation of glucose handling on baroreflex-mediated sympathetic nerve activity and arterial pressure regulations in rats with chronic myocardial infarction (n = 9). Repeated 11-min step input sequences were used for an open-loop analysis of the carotid sinus baroreflex. An SGLT2 inhibitor, empagliflozin, was intravenously administered (10 mg/kg) after the second sequence. Neither the baroreflex neural nor peripheral arc significantly changed during the last observation period (seventh and eighth sequences) compared with the baseline period although urinary glucose excretion increased from near 0 (0.0089 ± 0.0011 mg min−1 kg−1) to 1.91 ± 0.25 mg min−1 kg−1. Hence, empagliflozin does not acutely modulate the baroreflex regulations of sympathetic nerve activity and arterial pressure in this rat model of chronic myocardial infarction

The impact of ECPELLA on haemodynamics and global oxygen delivery: a comprehensive simulation of biventricular failure

Abstract Background ECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO2) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO2 into our developed cardiovascular simulation. Methods and results Both the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure–volume relationship (PV loop), and global DO2 under different VA-ECMO flows and Impella support levels. Results In the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure–volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV–PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO2 increment under ECPELLA total support conditions. Conclusions The optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO2 in total ECPELLA support conditions

Recombinant fusion protein of cholera toxin B subunit with YVAD secreted by Lactobacillus casei inhibits lipopolysaccharide-induced caspase-1 activation and subsequent IL-1 beta secretion in Caco-2 cells

BACKGROUND: Lactobacillus species are used as bacterial vectors to deliver functional peptides to the intestine because they are delivered live to the intestine, colonize the mucosal surface, and continue to produce the desired protein. Previously, we generated a recombinant Lactobacillus casei secreting the cholera toxin B subunit (CTB), which can translocate into intestinal epithelial cells (IECs) through GM1 ganglioside. Recombinant fusion proteins of CTB with functional peptides have been used as carriers for the delivery of these peptides to IECs because of the high cell permeation capacity of recombinant CTB (rCTB). However, there have been no reports of rCTB fused with peptides expressed or secreted by Lactobacillus species. In this study, we constructed L. casei secreting a recombinant fusion protein of CTB with YVAD (rCTB–YVAD). YVAD is a tetrapeptide (tyrosine–valine–alanine–aspartic acid) that specifically inhibits caspase-1, which catalyzes the production of interleukin (IL)-1β, an inflammatory cytokine, from its inactive precursor. Here, we examined whether rCTB–YVAD secreted by L. casei binds to GM1 ganglioside and inhibits caspase-1 activation in Caco-2 cells used as a model of IECs. RESULTS: We constructed the rCTB–YVAD secretion vector pSCTB–YVAD by modifying the rCTB secretion vector pSCTB. L. casei secreting rCTB–YVAD was generated by transformation with pSCTB–YVAD. Both the culture supernatant of pSCTB–YVAD-transformed L. casei and purified rCTB–YVAD bound to GM1 ganglioside, as did the culture supernatant of pSCTB-transformed L. casei and purified rCTB. Interestingly, although both purified rCTB–YVAD and rCTB translocated into Caco-2 cells, regardless of lipopolysaccharide (LPS), only purified rCTB–YVAD but not rCTB inhibited LPS-induced caspase-1 activation and subsequent IL-1β secretion in Caco-2 cells, without affecting cell viability. CONCLUSIONS: The rCTB protein fused to a functional peptide secreted by L. casei can bind to GM1 ganglioside, like rCTB, and recombinant YVAD secreted by L. casei may exert anti-inflammatory effects in the intestine. Therefore, rCTB secreted by L. casei has potential utility as a vector for the delivery of YVAD to IECs