Typhoid fever & vaccine development: a partially answered question

Typhoid fever is a systemic disease caused by the human specific Gram-negative pathogen Salmonella enterica serovar Typhi (S Typhi). The extra-intestinal infections caused by Salmonella are very fatal. The incidence of typhoid fever remains very high in impoverished areas and the emergence of multidrug resistance has made the situation worse. To combat and to reduce the morbidity and mortality caused by typhoid fever, many preventive measures and strategies have been employed, the most important being vaccination. In recent years, many Salmonella vaccines have been developed including live attenuated as well as DNA vaccines and their clinical trials have shown encouraging results. But with the increasing antibiotic resistance, the development of potent vaccine candidate for typhoid fever is a need of the hour. This review discusses the latest trends in the typhoid vaccine development and the clinical trials which are underway.

Statement submitted by the United States of Brazil to the President of the United States of America as arbitrator : under the provisions of the treaty concluded september 7, 1889, between Brazil and the Argentine Republic

Exposição que os Estados Unidos do Brazil apresentam ao Presidente dos Estados Unidos da América como árbitro seguindo as estipulações no Tratado de 7 de setembro de 1889, concluído entre o Brazil e a Republica Argentina.

Can a change in the spawning pattern of Argentine hake (Merluccius hubbsi) affect its recruitment?

Argentine hake (Merluccius hubbsi) inhabit waters of the Southwest Atlantic Ocean between 22° and 55°S, at depths ranging from 50 to 500 m (Cousseau and Perrota, 1998). This species has historically been among the more abundant fish resources in the Argentine Sea, where its biomass has ranged between one and two million metric tons annually since 1986 (Aubone et al., 2000). In this area, there are two identified fishing stocks, limited by the 41°S parallel. The southern group (Patagonian stock) is the more important with an abundance of about 85% of the total biomass estimated for this species in 1999 (Aubone et al., 2000). During the late 1990s, the spawning biomass of both stocks and their recruitment indices declined drastically, both of which were attributed to an increase in exploitation (Aubone et al., 2000).

Early life history of the Argentine sandperch Pseudopercis semifasciata (Pinguipedidae) off northern Patagonia

The Argentine sandperch Pseudopercis semifasciata (Pinguipedidae) sustains an important commercial and recreational fishery in the northern Patagonian gulfs of Argentina. We describe the morphological features of larvae and posttransition juveniles of P. semifasciata and analyze the abundance and distribution of early life-history stages obtained from 19 research cruises conducted on the Argentine shelf between 1978 and 2001. Pseudopercis semifasciata larvae were distinguished from other larvae by the modal number of myomeres (between 36 and 38), their elongated body, the size of their gut, and by osteological features of the neuro- and branchiocranium. Pseudopercis semifasciata and Pinguipes brasilianus (the other sympatric species of pinguipedid fishes) posttransition juveniles were distinguished by their head shape, pigmentation pattern, and by the number of spines of the dorsal fin (five in P. semifasciata and seven in P. brasilianus). The abundance and distribution of P. semifasciata at early stages indicate the existence of at least three offshore reproductive grounds between 42−43°S, 43−44°S, and 44−45°S, and a delayed spawning pulse in the southern stocks.

Maternal effects on fecundity and egg quality of the Patagonian stock of Argentine Hake (Merluccius hubbsi)

The influences of age, size, and condition of spawning females on fecundity and oocyte quality were analyzed for the Patagonian stock of Argentine Hake (Merluccius hubbsi). Samples of mature females were collected in the spawning area as part of 2 research surveys conducted in January 2010 and 2011, during the peak of the reproductive season. Batch fecundity (BF) ranged between 40,500 (29 cm total length [TL]) and 2,550,000 (95 cm TL) hydrated oocytes, and was positively correlated with TL, gutted weight, age, hepatosomatic index (HSI), and the relative condition factor (Kn). Relative fecundity ranged between 85 and 1040 hydrated oocytes g–1 and showed significant positive relationships with gutted weight, HSI, and Kn; however, coefficients of determination were low for all regressions. Dry weights of samples of 100 hydrated oocytes ranged between 1.8 and 3.95 mg and were positively correlated with all variables analyzed, including batch and relative fecundity. Multiple regression models created with data of the morphophysiological characteristics of females supported maternal influences on fecundity and egg weights. Within the studied size range (29–95 cm TL), larger individuals had better somatic and egg condition, mainly revealed by higher HSI and hydrated oocytes with larger oil droplets (275.71μm [standard error 1.49]). These results were associated with the higher feeding activity of larger females during the spawning season in comparison with the feeding activity of young individuals (<5 years old); the better nutritional state of larger females, assumed to result from more feeding, was conducive to greater production of high-quality eggs.

The innate immune response to grass carp hemorrhagic virus (GCHV) in cultured Carassius auratus blastulae (CAB) cells

Virus infection of mammalian cells activates an innate antiviral immune response characterized by production of interferon (IFN) and the subsequent transcriptional upregulation of IFN-stimulated genes (ISGs) by the JAK-STAT signaling pathway. Here, we report that a fish cell line, crucian carp (Carassius auratus L.) blastulae embryonic (CAB) cells, can produce IFN activity and then form an antiviral state after infection with UV-inactivated grass carp hemorrhagic virus (GCHV), a double-stranded (ds) RNA virus. From UV-inactivated GCHV-infected CAB cells, 15 pivotal genes were cloned and sequenced, and all of them were shown to be involved in IFN antiviral innate immune response. These IFN system genes include the dsRNA signal sensing factor TLR3, IFN, IFN signal transduction factor STAT1, IFN regulatory factor IRF7, putative IFN antiviral effectors Mx1, Mx2, PKR-like, Viperin, IFI56, and other IFN stimulated genes (ISGs) IFI58, ISG15-1, ISG15-2, USP18, Gig1 and Gig2. The identified fish IFN system genes were highly induced by active GCHV, UV-inactivated GCHV, CAB IFN or poly(I).poly(C), and showed similar expression patterns to mammals. The data indicate that an IFN antiviral innate immune response similar to that in mammals exists in the UV-inactivated GCHV-infected CAB cells, and the IFN response contributes to the formation of an antiviral state probably through JAK-STAT signaling pathway. This study provides strong evidence for existence of IFN antiviral innate immune response in fish, and will assist in elucidating the origin and evolution of vertebrate IFN system. (c) 2006 Elsevier Ltd. All rights reserved.

De novo RNA synthesis and homology modeling of the classical swine fever virus RNA polymerase

Classical swine fever virus (CSFV) non-structural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp), a key enzyme which initiates RNA replication by a de novo mechanism without a primer and is a potential target for anti-virus therapy. We expressed the NS5B protein in Escherichia coli. The rGTP can stimulate de novo initiation of RNA synthesis and mutation of the GDD motif to Gly-Asp-Asp (GAA) abolishes the RNA synthesis. To better understand the mechanism of viral RNA synthesis in CSFV, a three-dimensional model was built by homology modeling based on the alignment with several virus RdRps. The model contains 605 residues folded in the characteristic fingers, palm and thumb domains. The fingers domain contains an N-terminal region that plays an important role in conformational change. We propose that the experimentally observed promotion of polymerase efficiency by rGTP is probably due to the conformational changes of the polymerase caused by binding the rGTP. Mutation of the GDD to GAA interferes with the interaction between the residues at the polymerase active site and metal ions, and thus renders the polymerase inactive. (c) 2005 Elsevier B.V. All rights reserved.

A detection method for grass carp hemorrhagic virus (GCHV) based on a reverse transcription polymerase chain reaction

A rapid, sensitive and highly specific detection method for grass carp hemorrhagic virus (GCHV) based on a reverse transcription-polymerase chain reaction (RT-PCR) has been developed. Two pairs of PCR primers were synthesized according to the cloned cDNA sequences of the GCHV-861 strain. For each primer combination, only one specific major product was obtained when amplification was performed by using the genomic dsRNA of GCHV-861 strain. The lengths of their expected products were 320 and 223 bp, respectively. No products were obtained when nucleic acids other than GCHV-861 genomic RNA were used as RT-PCR templates. To assess the sensitivity of the method, dilutions of purified GCHV-861 dsRNA total genome (0.01 pg up to 1000 pg) were amplified and quantities of as little as 0.1 pg of purified dsRNA were detectable when the amplification product was analyzed by 1.5% agarose gel electrophoresis. This technique could detect GCHV-861 not only in infected cell culture fluids, but also in infected grass carp Ctenopharyngodon idellus and rare minnow Gobiocypris rarus with or without hemorrhagic symptoms. The results show that the RT-PCR amplification method is useful for the direct detection of GCHV.

Aesthetic campaigns and counter-campaigns. Jorge Luis Borges and a century of the Argentine detective story (1877-1977)

This cultural history of Argentine crime fiction involves a comprehensive analysis of the literary and critical traditions within the genre, paying particular attention to the series of ‘aesthetic campaigns’ waged by Jorge Luis Borges and others during the period between 1933 and 1977. The methodological approach described in the introductory chapter builds upon the critical insight that in Argentina, generic discourse has consistently been the domain, not only of literary critics in the traditional mould, but also of prominent writers of fiction and specialists from other disciplines, effectively transcending the traditional tripartite ‘division of labour’ between writers, critics and readers. Chapter One charts the early development of crime fiction, and contextualises the evolution of the classical and hardboiled variants that were to provide a durable conceptual framework for discourse in the Argentine context. Chapter Two examines a number of pioneering early works by Argentine authors, before analysing Borges’ multi-faceted aesthetic campaign on behalf of the ‘classical’ detective story. Chapter Three examines a transitional period for the Argentine crime genre, book-ended by the three Vea y Lea magazine-sponsored detective story competitions that acted as a vital stimulus to innovation among Argentine writers. It includes a substantial treatment of the work of Rodolfo Walsh, documenting his transition from crime writer and anthologist to pioneer of the non-fiction novel and investigative journalism traditions. Chapter Four examines the period in which the novela negra came to achieve dominance in Argentina, in particular the aesthetic counter-campaigns conducted by Ricardo Piglia and others on behalf of the hard-boiled variant. The study concludes with a detailed analysis of Pablo Leonardo’s La mala guita (1976), which is considered as a paradigmatic example of crime fiction in Argentina in this period. The final chapter presents conclusions and a summary of the dissertation, and recommendations for further research.

Partitioning of reproduction among queens in the Argentine ant, Linepithema humile

We investigated how queens share parentage (skew) in the Argentine ant, Linepithema humile, a social insect with multiple queens (polygyny). Overall, maternity of 546 male and female sexuals that mated successfully was determined with microsatellites in 26 colonies consisting of two queens and workers. The first main finding was that queens all contributed to sexual production. However, there was a significant departure from equal contribution to male and female sexual production in a notable proportion of colonies. Overall, reproductive skew for sexual (male and female) production was relatively low but higher than reproductive skew for egg production. The second interesting result was that there was a trade-off in the relative contribution of queens to male and female production. The queens contributing more to male production contributed significantly less to female sexual production. Finally, there was no significant association between colony productivity and the degree of reproductive skew. The relatively low reproductive skew is in line with predictions of the so-called concession models of reproductive skew because, in the Argentine ant, relatedness between queens is low and ecological constraints on dispersal nonexistent or weak. © 2001 The Association for the Study of Animal Behaviour.

Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania.

Consecutive febrile admissions were enrolled at two hospitals in Moshi, Tanzania. Confirmed acute Chikungunya virus (CHIKV), Dengue virus (DENV), and flavivirus infection were defined as a positive polymerase chain reaction (PCR) result. Presumptive acute DENV infection was defined as a positive anti-DENV immunoglobulin M (IgM) enzyme-linked immunsorbent assay (ELISA) result, and prior flavivirus exposure was defined as a positive anti-DENV IgG ELISA result. Among 870 participants, PCR testing was performed on 700 (80.5%). Of these, 55 (7.9%) had confirmed acute CHIKV infection, whereas no participants had confirmed acute DENV or flavivirus infection. Anti-DENV IgM serologic testing was performed for 747 (85.9%) participants, and of these 71 (9.5%) had presumptive acute DENV infection. Anti-DENV IgG serologic testing was performed for 751 (86.3%) participants, and of these 80 (10.7%) had prior flavivirus exposure. CHIKV infection was more common among infants and children than adults and adolescents (odds ratio [OR] 1.9, P = 0.026) and among HIV-infected patients with severe immunosuppression (OR 10.5, P = 0.007). CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania. DENV or other closely related flaviviruses are likely also circulating.