Nox1/4 inhibition exacerbates age dependent perivascular inflammation and fibrosis in a model of spontaneous hypertension

Hypertension is associated with oxidative stress and perivascular inflammation, critical contributors to perivascular fibrosis and accelerated vascular ageing. Oxidative stress can promote vascular inflammation, creating options for potential use of NADPH oxidase inhibitors in pharmacological targeting of perivascular inflammation and its consequences. Accordingly, we characterized age-related changes in oxidative stress and immune cell infiltration in normotensive (WKY) and spontaneously hypertensive rats (SHRs). Subsequently, we used pharmacological inhibitors of Nox1 (ML171) and Nox1/Nox4 (GKT137831; 60 mg/kg), to modulate NADPH oxidase activity at the early stage of spontaneous hypertension and investigated their effects on perivascular inflammation and fibrosis. Results: Ageing was associated with a progressive increase of blood pressure as well as an elevation of the total number of leukocytes, macrophages and NK cells infiltrating perivascular adipose tissue (PVAT) in SHRs but not in WKY. At 1 month of age, when blood pressure was not yet different, only perivascular NK cells were significantly higher in SHR. Spontaneous hypertension was also accompanied by the higher perivascular T cell accumulation, although this increase was age independent. Aortic Nox1 and Nox2 mRNA expression increased with age only in SHR but not in WKY, while age-related increase of Nox4 mRNA in the vessels has been observed in both groups, it was more pronounced in SHRs. At early stage of hypertension (3-months) the most pronounced differences were observed in Nox1 and Nox4. Surprisingly, GKT137831, dual inhibitor of Nox1/4, therapy increased both blood pressure and perivascular macrophage infiltration. Mechanistically, this was linked to increased expression of proinflammatory chemokines expression (CCL2 and CCL5) in PVAT. This inflammatory response translated to increased perivascular fibrosis. This effect was likely Nox4 dependent as the Nox1 inhibitor ML171 did not affect the development of spontaneous hypertension, perivascular macrophage accumulation, chemokine expression nor adventitial collagen deposition. In summary, spontaneous hypertension promotes ageing-associated perivascular inflammation which is exacerbated by Nox4 but not Nox1 pharmacological inhibition

Privacy in VANET using Shared Key Management

Abstract: Vehicular Ad-Hoc Networks (VANET) are very likely to be emerged in the coming years. The main objective of this paper is to provide privacy in VANET using shared distributed key management. In shared key management, a short group signature scheme is used to facilitate the revocation of malicious vehicles and heterogeneous security policies. In this framework, road side unit (RSU) acts as the key distributor. A new problem encountered is that a RSU may misbehave. A secure key distribution protocol is used to detect such misbehaved RSUs. The protocol guarantees the traceability of compromised RSUs and malicious vehicles. Moreover, the issue of large computation overhead is also addressed in this paper. A group authentication protocol is proposed to mitigate the communication and computation overhead that occur while using the group signature scheme. Here only a small number of vehicles participate in verification process. Keywords: VANET, privacy, shared key management, Road side units, ad-hoc networks I INTRODUCTION VANET is a form of ad-hoc network that enables communications between nearby vehicles (V2V communications) and the road-side infrastructure (V2I communications).In other words , VANET is a special kind of mobile ad-hoc networks where wireless equipped vehicles form a network. VANET research came into existence with the Fleet-Net project in mid 2001. The main aim of that was to develop a communication platform for inter-vehicle communication. Privacy is an important issue in VANETS II BACKGROUND KNOWLEDGE A VANET is a form of MANET which provides communication between vehicles and between vehicles and road-side base stations. A vehicle in VANET is considered to be an intelligent mobile node capable of communicating with its neighbors and other vehicles in the network. VANET is mainly designed to provide safety related information, traffic management, and infotainment services. Privacy and security are the two important issues in VANET. Without security, a Vehicular Ad Hoc Network (VANET) system is wide open to a number of attacks such as propagation of false warning messages as well as suppression of actual warning messages, thereby causing accidents. Another form of attack in VANET is tracking. This makes security and privacy a factor of major concern in building such networks. There have been several proposals for privacy preservation of VANETs. Some of them are using pseudonyms, silent period [4], mix-zones [3] etc. Each vehicle in a mix zone will keep silent in transmission, and randomly update its pseudonyms when it travels out of the mix zone and becomes reactivated. Given a reasonable large mix zone, the location privacy can be well protected due to the untraceability of location and pseudonym updating in the silent period. In the AMOEBA [5], vehicles form groups. The messages of all group members are forwarded by the group leader, which implies that the privacy of group members is protected by sacrificing the privacy of group leader. Moreover, if a malicious vehicle is selected as a group leader, all group members' privacy may be leaked by the malicious leader. While the pure pseudonym schemes do not support the secure functionality of authentication, integrity, and nonrepudiation, an anonymous signing protocol [1] is proposed to provide such functions as well as privacy. In the protocol, each vehicle preloads a large number of certificated anonymou

Structural and magnetic properties of rare-earth-free MnAl(MCNT)/Fe nanocomposite magnets processed by resin-bonding technique

In this study, the potential of multi-walled carbon nanotubes (MCNT) in processing rare-earth-free MnAl(MCNT)/Fe nanocomposite magnets was exploited through adopting a combination of surfactant-assisted milling and resin-bonding techniques. The required hard and soft magnetic phases such as MnAl(MCNT) and alpha-Fe, respectively, were individually subjected to surfactant-assisted high-energy ball milling. The surfactant-coated MnAl(MCNT) and Fe nanopowders, thus, obtained were characterized with respect to their structural and magnetic properties. Relatively, a very high coercivity, H-c (4.48 kOe), was obtained for the surfactant-coated MnAl(MCNT) powders after 6 h of milling, while in the case of Fe powders with high saturation magnetization, M-s (218.6 emu/g) was achieved at 3 h of surfactant-assisted milling. The MnAl(MCNT) powders with high H-c were mixed with the Fe powders of high M-s with different weight percentages: 0, 5 and 10. The nanocomposite powder mixtures were further milled for 1 h and then processed in the form of resin bonded magnets under aligning magnetic field of 20 kOe. The obtained bonded nanocomposite magnet, i.e. MnAl(MCNT) with 5 wt% of Fe addition demonstrated a good combination of high M-s (63.7 emu/g) and high H-c (4.46 kOe)

Nox1/4 inhibition exacerbates age dependent perivascular inflammation and fibrosis in a model of spontaneous hypertension

Hypertension is associated with oxidative stress and perivascular inflammation, critical contributors to perivascular fibrosis and accelerated vascular ageing. Oxidative stress can promote vascular inflammation, creating options for potential use of NADPH oxidase inhibitors in pharmacological targeting of perivascular inflammation and its consequences. Accordingly, we characterized age-related changes in oxidative stress and immune cell infiltration in normotensive (WKY) and spontaneously hypertensive rats (SHRs). Subsequently, we used pharmacological inhibitors of Nox1 (ML171) and Nox1/Nox4 (GKT137831; 60 mg/kg), to modulate NADPH oxidase activity at the early stage of spontaneous hypertension and investigated their effects on perivascular inflammation and fibrosis. Results: Ageing was associated with a progressive increase of blood pressure as well as an elevation of the total number of leukocytes, macrophages and NK cells infiltrating perivascular adipose tissue (PVAT) in SHRs but not in WKY. At 1 month of age, when blood pressure was not yet different, only perivascular NK cells were significantly higher in SHR. Spontaneous hypertension was also accompanied by the higher perivascular T cell accumulation, although this increase was age independent. Aortic Nox1 and Nox2 mRNA expression increased with age only in SHR but not in WKY, while age-related increase of Nox4 mRNA in the vessels has been observed in both groups, it was more pronounced in SHRs. At early stage of hypertension (3-months) the most pronounced differences were observed in Nox1 and Nox4. Surprisingly, GKT137831, dual inhibitor of Nox1/4, therapy increased both blood pressure and perivascular macrophage infiltration. Mechanistically, this was linked to increased expression of proinflammatory chemokines expression (CCL2 and CCL5) in PVAT. This inflammatory response translated to increased perivascular fibrosis. This effect was likely Nox4 dependent as the Nox1 inhibitor ML171 did not affect the development of spontaneous hypertension, perivascular macrophage accumulation, chemokine expression nor adventitial collagen deposition. In summary, spontaneous hypertension promotes ageing-associated perivascular inflammation which is exacerbated by Nox4 but not Nox1 pharmacological inhibition

Nutrigenomic and nutritional analyses reveal the effects of pelleted feeds on Asian Seabass (Lates calcarifer)

As nutrition-related expenses constitute the majority of the costs for aquaculture farms, it is essential for them to use feeds that provide an ideal combination of nutrients for the species of choice. In this study, the relative effect of consuming three different pelleted feeds (B, C and D) in comparison to frozen baitfish (A; control) were compared on juvenile Asian seabass (77.3 ± 22.4g) that were selected for increased growth rate over two generations. Our objectives were: 1) to evaluate the effects of different pelleted feeds based on overall physiological changes and nutritional quality of fillets; 2) improve our understanding of the underlying mechanisms with transcriptomic analysis; 3) if possible, identify the feed type that supports the growth of these fishes without substantially reducing the nutritional quality of fillet. The growth performance, fatty acid composition of fillet, hepatic histology and transcriptome of the fishes (Groups A-D) were analyzed. The majority of fatty acids of the fillets, except γ-linolenic acid (GLA, C18:3n6), correlated significantly with the respective diets. Asian seabass fed Feed C showed highest specific growth rate (SGR) and feed conversion efficiency (FCE) with closest histology and transcriptomic profile to control, but their fillet contained the highest n6/n3 ratio. When the liver-based transcriptomes were analyzed, a complex set of differentially expressed genes were detected between groups fed pelleted feeds and controls as well as among the pellet-fed groups themselves. Significant enrichment of genes with growth-related function tallied with the morphological data measured. When compared with control (Group A), ‘Biosynthesis of unsaturated fatty acids’ and ‘Steroid biosynthesis’ pathways were significantly enriched in pellet-fed groups. Reduced goblet cell numbers were observed in the gut of pellet-fed fish compared to controls and fads6 was found to be a suitable candidate gene to separate wild-caught Asian seabass, from pellet-fed ones. These results provide insights for researchers on the various effects of feeds on the biochemistry and global gene expression of the fish and potentially for seabass farms to make more informed feed choices

Barcoding of Asian seabass across its geographic range provides evidence for its bifurcation into two distinct species

Asian seabass or barramundi (Lates calcarifer) is an important food fish with commercial value and a wide geographic distribution. Though some reports based on molecular and/or morphological data exist, a comprehensive effort to establish species identity across its range is lacking. In order to address this issue and especially to ascertain whether the wide-spread distribution has resulted in bifurcation of the species, we collected Asian seabass samples from various locations representing the Western and Eastern Coastline of India, Andaman and Nicobar Islands, Bangladesh and Australia. Samples from Malaysia, Indonesia, Thailand and Singapore were collected as part of a previous study. DNA sequence variations, including cytochrome c oxidase subunit 1 (COI), 16S rDNA and the highly variable D-loop (or control region), were examined to establish species delineation. Data from all the sequences analyzed concordantly point to the existence of at least two distinct species—one representing the Indian subcontinent plus Myanmar, and a second, representing Southeast Asia (Singapore, Malaysia, Thailand and Indonesia) plus Northern Australia. These data are useful for conservation ecology, aquaculture management, for establishing the extent of genetic diversity in the Asian seabass and implementing selective breeding programs for members of this species complex

CMFRI Marine Fisheries Policy Series No.18; Streamlining the Supply Chain of Marine Fish in Kerala: COVID-19 and Beyond

Streamlining the Supply Chain of Marine Fish in Kerala: COVID-19 and Beyon

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma

Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract

Multi-proxy evidence for an arid shift in the climate and vegetation of the Banni grasslands of western India during the mid- to late-Holocene

Tropical semi-arid grasslands are a widespread and ecologically and economically important terrestrial biome. Here, we use paleoecology to understand woodland–grassland transitions across the mid- to late-Holocene period in the Banni grassland, western India. Multi proxy analyses involving palynology, phytoliths and elemental geochemistry were carried out on two sediment cores retrieved from wetlands (Chachi and Luna), to understand temporal fluctuations in vegetation, moisture availability and other environmental parameters. Based on the results, the Chachi core was divided into two major climatic phases. Phase 1 (4600–2500 cal. yr BP) was characterised by high precipitation and abundance of pollen types and phytolith morphotypes that indicate the presence of woody savanna, and mesic herbaceous taxa. Phase 2 (2500 cal. yr BP to the present) was characterised by lower precipitation, lower abundance of mesic taxa and an increase in grass phytolith abundance. However, the period from ~1000 cal. yr BP to the present was characterised by the increased abundance of leguminous taxa, dryland herbs/shrubs and a decline in grass phytolith abundance. The Luna core (~1000 cal. yr BP to the present) also showed results matching with the Chachi core for this latter period. Overall, moisture availability in the ecosystem appears to have declined since 4600 cal. yr BP, and the vegetation has responded to this. Although the balance between tree, shrub and grass elements has fluctuated, overall, the region has remained as an open ‘grass and shrub savanna’ with sparse woody vegetation throughout this period. Our study provides insights into the vegetation dynamics and environmental settings in a poorly understood tropical arid-grassland ecosystem from Asia during the mid-late-Holocene