Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination

Dengue virus (DENV) is a flavivirus that causes marked human morbidity and mortality worldwide, and is transmitted to humans by Aedes aegypti mosquitoes. Habitat expansion of Aedes, mainly due to climate change and increasing overlap between urban and wild habitats, places nearly half of the world’s population at risk for DENV infection. After a bloodmeal from a DENV-infected host, the virus enters the mosquito midgut. Next, the virus migrates to, and replicates in, other tissues, like salivary glands. Successful viral transmission occurs when the infected mosquito takes another blood meal on a susceptible host and DENV is released from the salivary gland via saliva into the skin. During viral dissemination in the mosquito and transmission to a new mammalian host, DENV interacts with a variety of vector proteins, which are uniquely important during each phase of the viral cycle. Our study focuses on the interaction between DENV particles and protein components in the A. aegypti vector. We performed a mass spectrometry assay where we identified a set of A. aegypti salivary gland proteins which potentially interact with the DENV virion. Using dsRNA to silence gene expression, we analyzed the role of these proteins in viral infectivity. Two of these candidates, a synaptosomal-associated protein (AeSNAP) and a calcium transporter ATPase (ATPase) appear to play a role in viral replication both in vitro and in vivo, observing a ubiquitous expression of these proteins in the mosquito. These findings suggest that AeSNAP plays a protective role during DENV infection of mosquitoes and that ATPase protein is required for DENV during amplification within the vector.     

Tick-host-pathogen interactions in Lyme borreliosis

Borrelia burgdorferi, the spirochetal agent of Lyme borreliosis, is predominantly transmitted by Ixodes ticks. Spirochetes have developed many strategies to adapt to the different environments that are present in the arthropod vector and the vertebrate host. This review focuses on B. burgdorferi genes that are preferentially expressed in the tick and the vertebrate host, and describes how selected gene products facilitate spirochete survival throughout the enzootic life cycle. Interestingly, B. burgdorferi also enhances expression of specific Ixodes scapularis genes, such as TROSPA and salp15. The importance of these genes and their products for B. burgdorferi survival within the tick, and during the transmission process, will also be reviewed. Moreover, we discuss how such vector molecules could be used to develop vector-antigen-based vaccines to prevent the transmission of B. burgdorferi and, potentially, other arthropod-borne microbes.     

Foam cell‐derived 4‐hydroxynonenal induces endothelial cell senescence in a TXNIP‐dependent manner

Vascular endothelial cell (VEC) senescence is considered an early event in the development of atherosclerotic lesions. Stressful stimuli, in particular oxidative stress, have been linked to premature senescence in the vasculature. Foam cells are a major source of reactive oxygen species and may play a role in the induction of VEC senescence; hence, we investigated their involvement in the induction of VEC senescence in a co‐culture transwell system. Primary bovine aortic endothelial cells, exposed to the secretome of THP‐1 monocyte‐derived foam cells, were analysed for the induction of senescence. Senescence associated β‐galactosidase activity and the expression of p16 and p21 were increased, whereas phosphorylated retinoblastoma protein was reduced. This senescent phenotype was mediated by 4‐hydroxnonenal (4‐HNE), a lipid peroxidation product secreted from foam cells; scavenging of 4‐HNE in the co‐culture medium blunted this effect. Furthermore, both foam cells and 4‐HNE increased the expression of the pro‐oxidant thioredoxin‐interacting protein (TXNIP). Molecular manipulation of TXNIP expression confirmed its involvement in foam cell‐induced senescence. Previous studies showed that peroxisome proliferator‐activated receptor (PPAR)δ was activated by 4‐hydroalkenals, such as 4‐HNE. Pharmacological interventions supported the involvement of the 4‐HNE‐PPARδ axis in the induction of TXNIP and VEC senescence. The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells. Collectively, these findings suggest that foam cell‐released 4‐HNE activates PPARδ in VEC, leading to increased TXNIP expression and consequently to senescence.     

Sagum posteli Delamare-Deboutteville & Nunes-Ruivo, 1954 (Copepoda: Siphonostomatoida: Lernanthropidae) parasitic on Epinephelus aeneus (Geoffroy Saint-Hilaire) in Turkish waters, with a key to the species of Sagum Wilson, 1913

Sagum posteli Delamare-Deboutteville & Nunes-Ruivo, 1954 (Copepoda: Lernanthropidae) is reported from the white grouper Epinephelus aeneus Geoffroy Saint-Hilaire caught off the Turkish Mediterranean coast. This documents the first discovery of this species in the Mediterranean and is only the second record. The species is redescribed from adult females and the cephalothoracic limbs are described for the first time. The valid species of the genus Sagum Wilson, 1913 are reviewed, and the poorly described species S. poeyi Ortiz, Lalana & Suarez, 2003 is relegated as a junior synonym of S. texanum Pearse, 1952, described from the same host. A key is provided to females of the ten valid species of Sagum and the known hosts for all species are summarised.     

Structure-activity studies of a novel series of 5,6-fused heteroaromatic ureas as TRPV1 antagonists

Novel 5,6-fused heteroaromatic ureas were synthesized and evaluated for their activity as TRPV1 antagonists. It was found that 4-aminoindoles and indazoles are the preferential cores for the attachment of ureas. Bulky electron-withdrawing groups in the para-position of the aromatic ring of the urea substituents imparted the best in vitro potency at TRPV1. The most potent derivatives were assessed in in vivo inflammatory and neuropathic pain models. Compound 46, containing the indazole core and a 3,4-dichlorophenyl group appended to it via a urea linker, demonstrated in vivo analgesic activity upon oral administration. This derivative also showed selectivity versus other receptors in the CEREP screen and exhibited acceptable cardiovascular safety at levels exceeding the therapeutic dose.     

Effects of some pesticides on the vital organs of juvenile rainbow trout (Oncorhynchus mykiss)

Gill, trunk kidney, spleen, and liver of rainbow trout (Oncorhynchus mykiss) were examined after exposure to different sublethal concentrations of carbosulfan (25, 50 and 200 μg L⁻¹), propineb (3, 6 and 24 mg L⁻¹), and benomyl (2, 5 and 20 mg L⁻¹) for 14 days. Lesions were observed in gill, trunk kidney, spleen, and liver of rainbow trout exposed to either concentration of pesticides. The most important lesions were determined in the highest concentrations of pesticides. Lamellar fusion, lamellar hyperplasia, epithelial lifting, vacuolization of epithelial tissue, epithelial necrosis, hypertrophy and sloughing of epithelium were observed on fish exposed to carbosulfan, propineb and benomyl. Fish had cell necrosis, degeneration and oedemas in liver, trunk kidney and spleen. None of these lesions were seen in control fish.     

A new interpretation of P300 responses upon analysis of coherences

Previous studies on cognitive dynamics showed that oscillatory responses of P300 are composed of mainly delta and theta responses. In the present study, for the first time, the long-distance intra-hemispheric event related coherence (auditory oddball paradigm) and evoked coherence (simple sound) were compared in order to evaluate the effects of cognitive tasks on the long-distance coherences. Seventeen healthy subjects (8 female, 9 male) were included in the study. The coherence was analyzed for delta (1–3.5 Hz), theta (4–7.5 Hz) and alpha (8–13 Hz) frequency ranges for (F₃-P₃, F₄-P₄, F₃-T₇, F₄-T₈, F₃-O_1, F₄-O₂) electrode pairs. The coherence to target responses were higher than the non-target and simple auditory response coherence. This difference is significant for the delta coherence for both hemispheres and for theta coherences over the left hemisphere. The highest coherences were recorded at fronto-temporal locations for all frequency bands (delta, theta, alpha). Furthermore, fronto-parietal coherences were higher than the fronto-occipital coherences for all frequency bands (delta, theta, alpha).These results show that the fronto-temporal and fronto-parietal connections are most relevant for the identification of the target signal. This analysis open the way for a new interpretation of dynamic localization results during cognitive tasks.     

Immunogenicity of recombinant Babesia microti hsp70 homologue in mice

A Babesia microti hsp70 homologue was cloned, expressed in a prokaryotic system and tested in a pilot study for protection against lethal challenge. Results showed that 30% of the mice inoculated with recombinant protein (rBm hsp70) survived challenge, while all of the controls died. Evidence of antibody response to the hsp homologue was detected by Western blot analysis, but no protection was imparted through passive transfer of convalescent serum. Passively transferred spleen cells, from mice which survived challenge, also failed to impart protection. The mechanism of partial immunity suggested by these observations remains to be elucidated.