Impact of apolipoprotein E genetic polymorphisms on liver disease: An essential review.

Cirrhosis is an advanced stage of liver disease, compromising liver function with systemic health implications and poor quality of life. Hepatitis C virus (HCV) infection and alcoholic liver disease are the main causes of this pathology. However, since genetic factors may play a large role in the progression and severity of liver disease, and as apolipoprotein E (apoE) has been recognised to be mainly synthesised in the liver, apoE polymorphism studies are important to better understand the causal mechanisms in liver diseases. In this review, we summarise up-to-date studies addressing how apoE polymorphisms influence liver cirrhosis and liver transplantation outcomes and potential protective mechanisms. Although more clinical studies are needed to support these findings, the apoE ɛ4 allele seems to be protective against the progression of liver cirrhosis in the majority of aetiologies and the postoperative serum apoE phenotype of the transplanted subject receptors was converted to that of the donor, indicating that >90% of apoE in plasma is synthesised in the hepatic system.

Differences in timing of migration and response to sexual signalling drive asymmetric hybridization across a migratory divide.

Ecological traits and sexual signals may both contribute to the process of ecological speciation. Here we investigate the roles of an ecological trait, seasonal migratory behaviour and a sexual trait, song, in restricting or directing gene flow across a migratory divide in the Swainson's thrush (Catharus ustulatus). We show that short-distance migratory ecotypes wintering in Central America arrive earlier at the breeding grounds than long-distance migratory ecotypes wintering primarily in South America, providing the potential for some premating isolation. Playback experiments suggest that early- and late-arriving forms recognize each other as competitors, but that the early-arriving form responds more aggressively to a broader spectrum of stimuli. Genetic analysis suggests that hybridization occurs more often between males of the early-arriving ecotype and females of the late-arriving ecotype. Together our results suggest that differences in arrival times may reduce the temporal coincidence of mate choice, but asymmetry in response to heterotypic song may hinder complete divergence. These data provide further insight into the roles of ecological traits and sexual signals during the incipient stages of speciation.

The effect of thymidine on the duration of G1 in Chinese hamster cells.

The generation time of a Chinese hamster cell line was varied by the use of different lots of sera in the culture media. Analysis of the division waves following thymidine synchronization showed that lengthening of the generation time was a result of an increase in duration of the G(1) phase and that thymidine treatment reduced the duration of G(1) back to its minimum value.

A differential screen for ligand-regulated genes: identification of HoxA10 as a target of vitamin D3 induction in myeloid leukemic cells.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the hormonal ligand for vitamin D3, is a potent inducer of myeloid-leukemic-cell differentiation. Such cells differentiate exclusively into monocytes/macrophages in response to this ligand. Since 1,25(OH)2D3 transduces its hormone signal through the vitamin D3 receptor (VDR), a ligand-modulated transcription factor and member of the nuclear hormone receptor superfamily, we sought to identify direct VDR target genes induced during this differentiation process. To do so, we applied a modified differential screen with a nascent-RNA purification strategy using biases for immediate-early-response genes induced by 1,25(OH)2D3 in the myelomonocytic cell line U937. Using this screen, we had previously identified p21Waf1/Cip1 as a gene transcriptionally induced by 1,25(OH)2D3 and demonstrated that this induction facilitates the differentiation of U937 cells into monocytes/macrophages (24). Here, we describe in detail our differential screen strategy and the identification and isolation of 20 1,25(OH)2D3-inducible genes or unknown cDNAs by means of this screen. One gene newly identified as a target of VDR regulation in myeloid cells is the homeobox HoxA10 gene. HoxA10 protein may act as a general regulator of cell growth, since overexpression of HoxA10 facilitated the differentiation of U937 cells into monocytes/macrophages independent of 1,25(OH)2D3 and acted to strongly inhibit the growth of the breast cancer cell line MCF-7 by arresting these cells in G1.

A model-based method for identifying species hybrids using multilocus genetic data.

We present a statistical method for identifying species hybrids using data on multiple, unlinked markers. The method does not require that allele frequencies be known in the parental species nor that separate, pure samples of the parental species be available. The method is suitable for both markers with fixed allelic differences between the species and markers without fixed differences. The probability model used is one in which parentals and various classes of hybrids (F(1)'s, F(2)'s, and various backcrosses) form a mixture from which the sample is drawn. Using the framework of Bayesian model-based clustering allows us to compute, by Markov chain Monte Carlo, the posterior probability that each individual belongs to each of the distinct hybrid classes. We demonstrate the method on allozyme data from two species of hybridizing trout, as well as on two simulated data sets.

Monte Carlo evaluation of the likelihood for N(e) from temporally spaced samples.

A population's effective size is an important quantity for conservation and management. The effective size may be estimated from the change of allele frequencies observed in temporally spaced genetic samples taken from the population. Though moment-based estimators exist, recently Williamson and Slatkin demonstrated the advantages of a maximum-likelihood approach that they applied to data on diallelic genetic markers. Their computational methods, however, do not extend to data on multiallelic markers, because in such cases exact evaluation of the likelihood is impossible, requiring an intractable sum over latent variables. We present a Monte Carlo approach to compute the likelihood with data on multiallelic markers. So as to be computationally efficient, our approach relies on an importance-sampling distribution constructed by a forward-backward method. We describe the Monte Carlo formulation and the importance-sampling function and then demonstrate their use on both simulated and real datasets.

Vertebral artery trauma: transcatheter embolization.

Injuries of the vertebral arteries in four patients were treated by transcatheter embolization. Embolotherapy was performed after incomplete or unsuccessful surgery in three of the patients and as a preventive measure in lieu of surgery in the fourth patient. All procedures were successful and without complications. An injured vertebral artery is usually extremely difficult to approach surgically, but because of extensive collateral blood supply it is usually expendable; therefore, it becomes an inviting target for management by interventional angiographic techniques. Embolotherapy of an injured vertebral artery is easier, faster, and safer than its surgical ligation and, therefore, decidedly superior. With few exceptions, embolotherapy should be considered the preferred method in the management of vertebral artery trauma.

Morbillivirus infections in wildlife (in relation to their population biology and disease control in domestic animals).

The three members of the morbillivirus genus that infect wildlife in ecosystems where domestic animals occur are rinderpest, peste des petits ruminants (PPR) and canine distemper. Data on the relative susceptibility of species of the Order Artiodactyla for rinderpest have been obtained from historical records of outbreaks. Rinderpest in wildlife has only occurred in equatorial and eastern Africa since the great pandemic of 1889-1897. The distributions, densities and population dynamics of susceptible species in this region are described. There has only been one recorded outbreak of PPR in wildlife but the possibility of its occurrence in the future now that it is present in many parts of west and eastern Africa is discussed. Wild carnivora are not likely to be important maintenance hosts for canine distemper but the disease is of significance in free-ranging carnivores and particularly in small populations of endangered susceptible wildlife species. It is also of great significance in zoo populations.

Observations on the pathogenicity for sheep and goats and the transmissibility of the strain of virus isolated during the rinderpest outbreak in Sri Lanka in 1987.

The pathogenicity for sheep and goats of the virus strain that caused acute rinderpest in cattle and domestic buffalo in Sri Lanka after an interval of over 40 years has been examined. The results show that it can cause overt clinical disease in goats, but only mild or unapparent infection in sheep. The disease was transmitted from infected sheep to in-contact susceptible sheep and calves.

African swine fever virus infection of the bushpig (Potamochoerus porcus) and its significance in the epidemiology of the disease.

Warthog (Phacochoerus aethiopicus), giant forest hog (Hylochoerus meinertzhageni) and bushpig (Potamochoerus porcus) are known to be susceptible to infection with African swine fever (ASF) virus. Little however, is known about the ecology of the disease in the bushpig. This study has shown that the bushpig remains viraemic for between 35 and 91 days following infection during which time it is able to infect the tick vector O. moubata. These ticks were able to transmit the disease to pigs. The virus persists in the lymphatic tissues for less than 34 weeks. Bushpigs infected with LIL 20/l virus but not VIC T90/l virus transmitted infection to in-contact pigs. Infected domestic pigs did not transmit the infection to in-contact bushpigs. ASF virus was able to replicate in in vitro cultures of bushpig leucocytes and endothelial cells. Recovered bushpigs could be reinfected with some strains of virus but not others. While it has been demonstrated that bushpigs remain carriers of ASFV following infection a complete understanding of their significance in the epidemiology of the disease awaits further investigations of their association with O. moubata.

Variation in foot-and-mouth disease virus isolates in Kenya: an examination of field isolates by T1 oligonucleotide fingerprinting.

Ribonuclease T1 oligonucleotide maps of strains of 4 of the endemic serotypes of foot-and-mouth disease virus isolated in Kenya between 1964 and 1982 have been compared with data obtained in complement-fixation and neutralization tests. There was a continual change in the oligonucleotide maps obtained for all the serotypes examined. This genetic heterogeneity was generally associated with antigenic variation. Viruses isolated during the 12-month course of an epidemic of the SAT 1 serotype showed few changes in their oligonucleotide fingerprints, and were serologically related. These maps form a data base that will be useful in future epidemiological studies on the maintenance and spread of foot-and-mouth disease virus in this region.

The foot-and-mouth disease risk posed by African buffalo within wildlife conservancies to the cattle industry of Zimbabwe.

Quantification of the risk that African buffalo (Syncerus caffer) (isolated within wildlife conservancies in Zimbabwe by a double fencing system) would infect cattle outside the conservancies with foot-and-mouth disease (FMD) virus was assessed by scenario-pathway analysis. Of the five scenarios considered, the greatest annual risk (1:5000) for cattle would be from antelope jumping over the outer perimeter fence of the conservancy and infecting cattle on the outside. The other transmission scenarios (including air-borne transmission) had a FMD risk that was low to very low. Risk management would include means to prevent the escape of antelope from the conservancies and restriction of cattle density in the proximity of the perimeter fence.

Susceptibility and carrier status of impala, sable, and tsessebe for Cowdria ruminantium infection (heartwater).

Three species of wild African ruminants, impala (Aepyceros melampus), sable (Hippotragus equinus), and tsessebe (Damaliscus lunatus), were experimentally inoculated with in vitro culture-derived Cowdria ruminantium organisms, the tick-borne causative agent of heartwater in domestic ruminants, to determine their susceptibility to infection. No clinical disease was observed in any of the ruminants. However, C. ruminantium was detected in the sable by the transmission of heartwater to susceptible sheep, through the tick vector Amblyomma hebraeum, at 10 and 37 days postinfection (PI). Attempts to detect infection in the impala and tsessebe by tick transmission at 54 days PI failed. The impala and tsessebe were reinoculated with C. ruminantium organisms at 146 days after the first inoculation; however, a tick transmission attempt at 66 days after the reinoculation also failed. Seroconversion, as detected by immunoblotting, was demonstrated in the sable and the tsessebe but not in the impala. The results demonstrate that sable can be carriers of C. ruminantium. The susceptibility of tsessebe and impala, however, remains undetermined.

Potential for the transmission of foot-and-mouth disease virus from African buffalo (Syncerus caffer) to cattle.

Foot-and-mouth disease viruses of types SAT 1 and SAT 2 isolated from diseased cattle and carrier buffalo, either on the same farm or in the same ecological area within a short time of each other, were compared by T1 oligonucleotide mapping. No similarity was observed between the maps obtained, indicating that the different populations of virus were unique to each species and that no interspecies transmission had occurred.

Arachidonic acid metabolites in the pathophysiology of thrombocytopenia and haemorrhage in acute African swine fever.

Changes in the production of proaggregatory (thromboxane A2 and prostaglandin E2) and antiaggregatory (prostacyclin) prostaglandins by blood platelets, macrophages and endothelial cells during acute African swine fever caused by both a highly virulent virus and a less virulent virus were studied. No impairment in thromboxane A2 release by either platelets or macrophages could be detected but prostacyclin production by the endothelium was impaired. There was also a significant increase in prostaglandin E2 release by macrophages at the time when thrombocytopenia was most marked. However, the early event that causes primary aggregation remains obscure.

An investigation into the source and spread of foot and mouth disease virus from a wildlife conservancy in Zimbabwe.

African buffalo were introduced into a wildlife conservancy in the southeast of Zimbabwe in an effortto increase the conservancy's economic viability, which is primarily based on eco-tourism. The buffalo were infected with SAT serotypes (SAT-1, SAT-2 and SAT-3) of foot and mouth disease (FMD) virus, and in order to isolate the conservancy and prevent the transmission of FMD to adjacent populations of domestic livestock, the conservancy was surrounded by a double-fence system, 1.8 m in height. The intention was to prevent the movement of both wildlife and domestic animals across the perimeter. However, two years after the buffalo were introduced, FMD occurred in cattle farmed just outside of the conservancy. Using serological and molecular diagnostic tests, epidemiological investigations showed that it was most likely that antelope (impala or kudu), infected through contact with the buffalo herd within the conservancy, had jumped over the fence and transmitted the virus to the cattle.

Outer membrane protein profiling to distinguish between Haemophilus aegyptius and non-capsulate Haemophilus influenzae biotype III.

Outer membrane protein profiling was used to assist in determining the identity of an isolate of Haemophilus spp. that was presumptively identified as non-capsulate Haemophilus influenzae biotype III. The possibility that this strain was in fact Haemophilus aegyptius was queried because of clinical information and the source of the isolate. Sodium dodecyl-sulphate polyacrylamide gel electrophoresis was used to establish the identity of the isolate as non-capsulate H. influenzae biotype III and no H. aegyptius. Generally, protein profiling compared very favourably with other standard tests for identifying H. aegyptius: the method was easily and rapidly performed and gave an unequivocal result.

Typing of pestiviruses from eland in Zimbabwe.

Pestiviruses were isolated from three eland (Taurotragus oryx) in Zimbabwe. The viruses were characterised by typing with monoclonal antibodies and by partial genetic sequencing. All were similar to bovine viral diarrhea viruses commonly isolated from cattle. This suggests that bovine viral diarrhea virus can spread from cattle to eland.

The pathogenicity of bovine strains of foot and mouth disease virus for impala and wildebeest.

Impala (Aepyceros melampus) and wildebeest (Connochaetes taurinus) were infected with bovine strains of foot and mouth disease virus by intradermolingual inoculation. No clinical signs developed in the impala but mild atypical lesions developed in the tongues of the wildebeest with generalized spread to one foot in two of the eight animals exposed. All the impala but only some of the wildebeest developed viraemia. No virus could be isolated from any tissues in either species after the 7th day following virus inoculation. Immune response occurred in both species. A field survey revealed few animals of either species with significant antibody titers and no virus 'carriers' were found.