Chemical containment and eradication of screw− worm incursions in Australia

Screwworms are obligate, invasive parasites of warm-blooded animals. The female flies lay batches of eggs at the edge of wounds or other lesions. These eggs hatch to larvae or screw-worms which feed on affected animals for 6-7 days, burrowing deeply into subcutaneous tissues and causing severe trauma to animals, production loss and potentially death. Susceptible sites include wounds resulting from management practices such as castration, de-horning and ear tagging and lesions caused by the activities of other parasites such as buffalo flies and ticks. The navels of the new born and the vulval region of their mothers following parturition are highly susceptible and body orifices such as nose and ears are also frequent targets for ovipositing screwworm flies. The Old World screw-worm, Chrysomya bezziana (OWS) is considered one of the most serious exotic insect pest threatening Australia's livestock industries and is endemic in a number of our closest neighbouring countries. New World screwworm (NWS), Cochliomyia hominivorax, endemic to South America, has also entered Australia on at least 2 occasions. Many tropical and subtropical areas of Australia are suitable for the establishment of OWS and the potential range is expected to increase with climate change. The Australian screwworm preparedness strategy indicates a program of containment with chemical treatments followed by eradication of OWS using sterile male release and parasiticides. However, there is no longer an operational OWS sterile insect screw-worm facility anywhere in the world and establishing a large scale production facility would most optimistically take at least 2 years. In the interim, containment would be almost totally dependent on the availability of effective chemical controls. A review of chemical formulations available for potential use against OWS in Australia found that currently only one chemical, ivermectin administered by subcutaneous injection (s.c.) is registered for use against OWS and that many of the chemicals previously shown to be effective against OWS were no longer registered for animal use in Australia.18 From this review a number of Australian-registered chemicals were recommended as a priority for testing against OWS. The Australian Pesticides and Veterinary Medicines Authority (APVMA) can issue an emergency use permit for use of pesticides if they are registered in Australia for other animal uses and shown to be effective against OWS. This project tested the therapeutic and prophylactic efficacy of chemicals with potential for use in the treatment and control of OWS.

Hantavirus glycoprotein GN in virion assembly and regulation of interferon response

Hantaviruses have a tri-segmented negative-stranded RNA genome. The S segment encodes the nucleocapsid protein (N), M segment two glycoproteins, Gn and Gc, and the L segment the RNA polymerase. Gn and Gc are co-translationally cleaved from a precursor and targeted to the cis-Golgi compartment. The Gn glycoprotein consists of an external domain, a transmembrane domain and a C-terminal cytoplasmic domain. In addition, the S segment of some hantaviruses, including Tula and Puumala virus, have an open reading frame (ORF) encoding a nonstructural potein NSs that can function as a weak interferon antagonist. The mechanisms of hantavirus-induced pathogenesis are not fully understood but it is known that both hemorrhagic fever with renal syndrome (HFRS) and hantavirus (cardio) pulmonary syndrome (HCPS) share various features such as increased capillary permeability, thrombocytopenia and upregulation of TNF-. Several hantaviruses have been reported to induce programmed cell death (apoptosis), such as TULV-infected Vero E6 cells which is known to be defective in interferon signaling. Recently reports describing properties of the hantavirus Gn cytoplasmic tail (Gn-CT) have appeared. The Gn-CT of hantaviruses contains animmunoreceptor tyrosine-based activation motif (ITAM) which directs receptor signaling in immune and endothelial cells; and contain highly conserved classical zinc finger domains which may have a role in the interaction with N protein. More functions of Gn protein have been discovered, but much still remains unknown. Our aim was to study the functions of Gn protein from several aspects: synthesis, degradation and interaction with N protein. Gn protein was reported to inhibit interferon induction and amplication. For this reason, we also carried out projects studying the mechanisms of IFN induction and evasion by hantavirus. We first showed degradation and aggresome formation of the Gn-CT of the apathogenic TULV. It was reported earlier that the degradation of Gn-CT is related to the pathogenicity of hantavirus. We found that the Gn-CT of the apathogenic hantaviruses (TULV, Prospect Hill virus) was degraded through the ubiquitin-proteasome pathway, and TULV Gn-CT formed aggresomes upon treatment with proteasomal inhibitor. Thus the results suggest that degradation and aggregation of the Gn-CT may be a general property of most hantaviruses, unrelated to pathogenicity. Second, we investigated the interaction of TULV N protein and the TULV Gn-CT. The Gn protein is located on the Golgi membrane and its interaction with N protein has been thought to determine the cargo of the hantaviral ribonucleoprotein which is an important step in virus assembly, but direct evidence has not been reported. We found that TULV Gn-CT fused with GST tag expressed in bacteria can pull-down the N protein expressed in mammalian cells; a mutagenesis assay was carried out, in which we found that the zinc finger motif in Gn-CT and RNA-binding motif in N protein are indispensable for the interaction. For the study of mechanisms of IFN induction and evasion by Old World hantavirus, we found that Old World hantaviruses do not produce detectable amounts of dsRNA in infected cells and the 5 -termini of their genomic RNAs are monophosphorylated. DsRNA and tri-phosphorylated RNA are considered to be critical activators of innate immnity response by interacting with PRRs (pattern recognition receptors). We examined systematically the 5´-termini of hantavirus genomic RNAs and the dsRNA production by different species of hantaviruses. We found that no detectable dsRNA was produced in cells infected by the two groups of the old world hantaviruses: Seoul, Dobrava, Saaremaa, Puumala and Tula. We also found that the genomic RNAs of these Old World hantaviruses carry 5´-monophosphate and are unable to trigger interferon induction. The antiviral response is mainly mediated by alpha/beta interferon. Recently the glycoproteins of the pathogenic hantaviruses Sin Nombre and New York-1 viruses were reported to regulate cellular interferon. We found that Gn-CT can inhibit the induction of IFN activation through Toll-like receptor (TLR) and retinoic acid-inducible gene I-like RNA helicases (RLH) pathway and that the inhibition target lies at the level of TANK-binding kinase 1 (TBK-1)/ IKK epislon complex and myeloid differentiation primary response gene (88) (MyD88) / interferon regulatory factor 7 (IRF-7) complex.

Makrodomeeni-inhibiittorit antiviraalisina yhdisteinä

Alfavirukset ovat positiivissäkeisiä RNA-viruksia, jotka kuuluvat Togaviridea –heimoon. Alfaviruksia levittävät Aedes –suvun hyttyset ja niitä esiintyy Etelämanteretta lukuunottamatta kaikilla mantereilla. Alfaviruksia on tähän mennessä löydetty 29 lajia ja ne voidaan jakaa uuden ja vanhan maailman viruksiin niiden maantieteellisen esiintyvyyden ja taudinaiheuttamiskyvyn mukaan. Chikunkunyavirus (CHIKV) on yksi vanhan maailman alfaviruksista, jota esiintyy muun muassa Afrikassa ja Aasiassa. Ilmaston lämmettyä se on leviämässä myös eteläiseen Eurooppaan. Ihmisessä se aiheuttaa muun muassa kuumetta, päänsärkyä, ihottumaa ja niveltulehdusta, joka voi kestää useita vuosia ja ne voivat olla hyvinkin kivuliaita. Pienillä lapsilla chikungunya on todettu aiheuttavan myös neurologisia oireita kuten aivotulehdusta. Alfaviruksen genomi koodaa neljää rakenneproteiinia ja neljää replikaatioproteiinia. Replikaatioproteiineista nsP3 sisältää makrodomeeniosan. Makrodomeeniproteiinit ovat eliökunnassa konservoituneita, mutta makrodomeeniproteiinien tarkkaa merkitystä ei vielä tunneta. Makrodomeenien on osoitettu sitovan ADP-riboosia ja sen johdannaisia ja alfaviruksen nsP3-proteiinin on osoitettu olevan tärkeä osa viruksen replikaatiossa. Tutkimuksen tavoitteena oli tutkia makrodomeeniproteiiniin sitoutuvien yhdisteiden käyttöä antiviraalisena yhdisteinä. Tietokonemallinnuksella valittiin antiviraalitutkimuksiin 45 yhdistettä, joiden oletettiin sitoutuvan makrodomeeniproteiiniin. Kilpailevassa sitoutumiskokeessa viisi yhdistettä esti yli 50 % poly-ADP-riboosia (PAR) sitoutumasta MDO1-makrodomeeniproteiiniin, jolla tietokonemallinnus oli tehty. SFV-makrodomeeniproteiinilla tehdyssä kokeessa vain yksi yhdiste esti yli 50 % poly-ADP-riboosin sitoutumisen. SFV-antiviraalikokeessa seitsemällä yhdisteellä inhibitioprosentti oli yli 50 %. Näillä yhdisteillä ei kuitenkaan ollut merkittävää vaikutusta poly-ADP-riboosin sitoutumisen estossa. CHIKV-replikonikokeessa yli 50 % inhibitioprosentti oli viidellä yhdisteellä. Muiden mahdollisia vaikutusmekanismeja tutkittiin selvittämällä estävätkö yhdisteet virusta pääsemästä solun sisään. Tässä kokeessa tutkituista yhdisteistä lähes kaikilla oli vaikutusta viruksen soluun pääsyn estossa. Yleisesti ottaen kyky estää PAR:n sitoutuminen makrodomeeniproteiineihin ja antiviraaliset vaikutukset eivät korreloineet keskenään tutkittavilla yhdisteillä. Vaikka antiviraalista vaikutusta omaavat yhdisteet eivät osoittaneetkaan makrodomeeni-inhibiitiota, työssä löydettiin potentiaalisia antiviraalisia yhdisteitä joiden käyttö viruksen soluun pääsyn estäjinä antaa aihetta jatkotutkimuksille.

Notable reacción europea ante otro intento laicista : El crucifijo en las escuelas italianas y la Corte de Estrasburgo (a propósito de la sentencia “Lautsi c. Italy”)

Resumen: Del mismo modo como hace no muchos años la ciudadanía europea se conmovió frente al planteo sobre las raíces cristianas en el momento de redactar la Constitución de la Unión Europea, dando lugar a numerosos discursos sobre la necesidad de no olvidar la verdadera cultura y enseñanza que había ennoblecido al Viejo Mundo, hace casi un año una sentencia proveniente de la Corte de Estrasburgo aplicable al Estado italiano, el caso “Lautsi c. Italy”, ha generado numerosas reacciones en diferentes sectores intelectuales permitiendo el desarrollo de notables argumentos que han intentado desenmascarar los verdaderos rostros que se encontraban velados detrás de los lugares comunes de la argumentación jurídico-política de los últimos dos siglos, especialmente los de laicidad, neutralidad, igualdad y libertad. De este modo la radicalización y desarrollo llevado al extremo de las premisas de la Ilustración ha mostrado su real fisonomía y consecuencia. Para tal propósito el análisis se concentra en la apelación a la Grande Chambre presentada por el Estado italiano y los sucesivos aportes provenientes de la doctrina europea, especialmente a través de valiosos Congresos y Jornadas dedicados a la problemática.

¿Recepción creativa en el III Concilio Provincial Mexicano?

Resumen: Repetidamente leemos en la historiografía la afirmación de que los concilios provinciales celebrados en la América hispánica durante el siglo dieciséis fueron una mera repetición o recepción de concilios y sínodos celebrados en el Viejo Mundo. En el presente artículo, de manera sumaria damos elementos que servirían para cuestionar esta afirmación a partir de los materiales de trabajo publicados recientemente sobre el Tercer Concilio Provincial Mexicano, celebrado en 1585.

Mapping chromosomal homologies between humans and two langurs (Semnopithecus francoisi and S-Phayrei) by chromosome painting

Chromosomal homologies were established between human and two Chinese langurs (Semnopithecus francoisi, 2n=44, and S. phayrei, 2n=44) by chromosome painting with chromosome-specific DNA probes of all human chromosomes except the Y. Both langur species showed identical hybridization patterns in addition to similar G-banding patterns. In total, 23 human chromosome-specific probes detected 30 homologous chromosome segments in a haploid langur genome. Except for human chromosomes 1, 2, 6, 16 and 19 probes, which each gave signals on two non-homologous langur chromosomes respectively, all other probes each hybridized to a single chromosome. The results indicate a high degree of conservation of chromosomal synteny between human and these two Chinese langurs. The human chromosome 2 probe painted the entire euchromatic regions of langur chromosomes 14 and 19. Human chromosome 1 probe hybridized to three regions on langur autosomes, one region on langur chromosome 4 and two regions on langur chromosome 5. Human 19 probe hybridized on the same pattern to one region on chromosome 4 and to two regions on langur chromosome 5, where it alternated with the human chromosome 1 probe. Human 6 and 16 probes both hybridized to one region on each of the two langur autosomes 15 and 18. Only two langur chromosomes (12 and 21) were each labelled by probes specific for two whole human chromosomes (14 and 15 and 21 and 22 respectively). Comparison of the hybridization patterns of human painting probes on these two langurs with the data on other Old World primates suggests that reciprocal and Robertsonian translocations as will as inversions could have occurred since the divergance of human and the langurs from a common ancestor. This comparison also indicates that Asian colobines are karyotypically more closely related to each other that to African colobines.

Recent origin of a hominoid-specific splice form of neuropsin, a gene involved in learning and memory

Neuropsin is a secreted-type serine protease involved in learning and memory. The type II splice form of neuropsin is abundantly expressed in the human brain but not in the mouse brain. We sequenced the type II-spliced region of neuropsin gene in humans and representative nonhuman primate species. Our comparative sequence analysis showed that only the hominoid species (humans and apes) have the intact open reading frame of the type II splice form, indicating that the type II neuropsin originated recently in the primate lineage about 18 MYA. Expression analysis using RT-PCR detected abundant expression of the type II form in the frontal lobe of the adult human brain, but no expression was detected in the brains of lesser apes and Old World monkeys, indicating that the type II form of neuropsin only became functional in recent time, and it might contribute to the progressive change of cognitive abilities during primate evolution.

Genetic evidence of a strong functional constraint of neurotrypsin during primate evolution

Neurotrypsin is one of the extra-cellular serine proteases that are predominantly expressed in the brain and involved in neuronal development and function. Mutations in humans are associated with autosomal recessive non-syndromic mental retardation (MR). We studied the molecular evolution of neurotrypsin by sequencing the coding region of neurotrypsin in 11 representative non-human primate species covering great apes, lesser apes, Old World monkeys and New World monkeys. Our results demonstrated a strong functional constraint of neurotrypsin that was caused by strong purifying selection during primate evolution, an implication of an essential functional role of neurotrypsin in primate cognition. Further analysis indicated that the purifying selection was in fact acting on the SRCR domains of neurotrypsin, which mediate the binding activity of neurotrypsin to cell surface or extracellular proteins. In addition, by comparing primates with three other mammalian orders, we demonstrated that the absence of the first copy of the SRCR domain (exon 2 and 3) in mouse and rat was due to the deletion of this segment in the murine lineage. Copyright (C) 2005 S. Karger AG, Basel.

A novel fusion gene, TRIMS-Cyclophilin A in the pig-tailed macaque determines its susceptibility to HIV-1 infection

Objective: In Old World monkeys, the tripartite motif Sec (TRIM5 alpha) protein confers resistance to HIV-1 infection following virus entry into host cells. However, the pig-tailed macaque (Macaca nemestrina) is an exception and is susceptible to HIV-1 in

Construction, characterization and chromosomal mapping of bacterial artificial chromosome (BAC) library of Yunnan snub-nosed monkey (Rhinopithecus bieti)

We constructed a high redundancy bacterial artificial chromosome library of a seriously endangered Old World Monkey, the Yunnan snub-nosed monkey (Rhinopithecus bieti) from China. This library contains a total of 136 320 BAC clones. The average insert size of BAC clones was estimated to be 148 kb. The percentage of small inserts (50-100 kb) is 2.74%, and only 2.67% non-recombinant clones were observed. Assuming a similar genome size with closely related primate species, the Yunnan snub-nosed monkey BAC library has at least six times the genome coverage. By end sequencing of randomly selected BAC clones, we generated 201 sequence tags for the library. A total of 139 end-sequenced BAC clones were mapped onto the chromosomes of Yunnan snub-nosed monkey by fluorescence in-situ hybridization, demonstrating a high degree of synteny conservation between humans and Yunnan snub-nosed monkeys. Blast search against human genome showed a good correlation between the number of hit clones and the size of the chromosomes, an indication of unbiased chromosomal distribution of the BAC library. This library and the mapped BAC clones will serve as a valuable resource in comparative genomics studies and large-scale genome sequencing of nonhuman primates. The DNA sequence data reported in this paper were deposited in GenBank and assigned the accession number CG891489-CG891703.

人猿超科和旧大陆猴7种高等灵长类FKN全基因序列的测定及进化分析

测定人猿超科(人、黑猩猩、大猩猩、红毛猩猩和长臂猿)和旧大陆猴(猕猴和叶猴)7种高等灵长类FKN全基因序列,探讨其系统进化分析.用简并引物PCR(Degenerated PCR)法分别扩增FKN的3个外显子,其产物经琼脂糖凝胶回收、纯化后测序,然后用BioEdit软件剪切拼接FKN基因全序列,用DNAStar比对后比较基因和氨基酸序列同源性,Mega软件重构FKN基因进化树,应用Datamonkey分析FKN的负选择位点.序列分析发现人猿超科较旧大陆猴FKN基因除了有散在的点突变外,还有一明显的30 bp的核苷酸缺失突变;人FKN基因序列与黑猩猩、大猩猩、红毛猩猩、长臂猿、猕猴和叶猴的同源性分别是99.2%、98.4%、98.1%、96.5%%、95.95和93.8%,由此推导的氨基酸序列同源性分别是98.5%、98.0%、97.7%、94.7%、93.7%和90.5%;FKN基因进化树表明人与黑猩猩关系更近,FKN基因进化和通常认为的物种进化一致;Datamonkey分析结果显示FKN存在3个负选择位点53Q.84D、239N.成功获得人、黑猩猩、大猩猩、红毛猩猩、长臂猿、猕猴和叶猴7种高等灵长类物种FKN全基因序列,为后续探讨FKN在高等灵长类物种进化过程中免疫学功能演变及其结构与功能的关系奠定基础. 作 者： 洪晓武 张亚平 储以微 高海峰 蒋正刚 熊思东 HONG Xiao-Wu ZHANG Ya-Ping CHU Yi-Wei GAO Hai-Feng JIANG Zheng-Gang XIONG Si-Dong 作者单位： 洪晓武,储以微,高海峰,蒋正刚,熊思东,HONG Xiao-Wu,CHU Yi-Wei,GAO Hai-Feng,JIANG Zheng-Gang,XIONG Si-Dong(复旦大学上海医学院免疫学系,免疫生物学研究所,上海,200032) 张亚平,ZHANG Ya-Ping(中国科学院昆明动物研究所细胞与分子进化开放实验室,昆明,650223) 刊 名： 遗传 ISTIC PKU 英文刊名： HEREDITAS 年，卷(期)： 2008 30(5) 分类号： Q94 关键词： 人猿超科 旧大陆猴 FKN 测序 进化分析 机标分类号： R5 S86 机标关键词： 大陆灵长类全基因序列测定系统进化分析phylogenetic analysis基因进化树黑猩猩序列同源性长臂猿物种进化猕猴红毛负选择氨基酸琼脂糖凝胶基因全序列序列分析位点软件重构 基金项目： 国家自然科学基金，复旦大学校科研和教改项目 DOI：

Phylogenetic incongruence between nuclear and mitochondrial markers in the Asian colobines and the evolution of the langurs and leaf monkeys

Evidence of incongruence between mitochondrial and nuclear gene trees is now becoming documented with increasing frequency. Among the Old World monkeys, this discordance has been well demonstrated in the Cercopithecinae, but has not yet been investigated

Parallel and Convergent Evolution of the Dim-Light Vision Gene RH1 in Bats (Order: Chiroptera)

Rhodopsin, encoded by the gene Rhodopsin (RH1), is extremely sensitive to light, and is responsible for dim-light vision. Bats are nocturnal mammals that inhabit poor light environments. Megabats (Old-World fruit bats) generally have well-developed eyes, while microbats (insectivorous bats) have developed echolocation and in general their eyes were degraded, however, dramatic differences in the eyes, and their reliance on vision, exist in this group. In this study, we examined the rod opsin gene (RH1), and compared its evolution to that of two cone opsin genes (SWS1 and M/LWS). While phylogenetic reconstruction with the cone opsin genes SWS1 and M/LWS generated a species tree in accord with expectations, the RH1 gene tree united Pteropodidae (Old-World fruit bats) and Yangochiroptera, with very high bootstrap values, suggesting the possibility of convergent evolution. The hypothesis of convergent evolution was further supported when nonsynonymous sites or amino acid sequences were used to construct phylogenies. Reconstructed RH1 sequences at internal nodes of the bat species phylogeny showed that: (1) Old-World fruit bats share an amino acid change (S270G) with the tomb bat; (2) Miniopterus share two amino acid changes (V104I, M183L) with Rhinolophoidea; (3) the amino acid replacement I123V occurred independently on four branches, and the replacements L99M, L266V and I286V occurred each on two branches. The multiple parallel amino acid replacements that occurred in the evolution of bat RH1 suggest the possibility of multiple convergences of their ecological specialization (i.e., various photic environments) during adaptation for the nocturnal lifestyle, and suggest that further attention is needed on the study of the ecology and behavior of bats.

Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina), a primate species susceptible to Human Immunodeficiency Virus type 1 infection

Background: The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We have previously reported that the TRIM5-Cyclophilin A (TRIMCyp) fusion in pig-tailed macaques (Macaca n

Mandibular morphometric variation among Chinese cercopithecoids and the unique structure of the snub-nosed monkey (Rhinopithecus) mandible

In order to understand how mandibular structure differs among the Chinese cercopithecoids (Rhinopithecus, Trachypithecus and Macaca), particularly the uniqueness of the snub-nosed monkeys (Rhinopithecus), we analysed ten mandibular measurements by principal components analysis (PCA), and examined scaling patterns. The results provided by the PCA illustrated differences due to size among the cercopithecoids and the relationship between colobines (Trachypithecus and Rhinopithecus) and cercopithecines, in which macaques (Macaca) are included. Allometric analysis indicated that, biomechanically, there is not a marked difference between macaques and leaf-eating monkeys. This may be associated with the fact that both share some similar ecology and niches in south and southwest China. The snub-nosed monkeys exhibit a significantly more robust mandible, evident in the symphysis, corpus, condyle, and masticatory momentum arm. This supports the hypothesis, based on the study of dental structure, that Rhinopithecus is a unique group in Asian Old World monkeys (OWMs) and has developed some unique characteristics in order to adapt to the tough food available in the severe cold climate of the Plateaux of Qinghai-Tibet, Yun-Gui and Qingling in China.