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J Mandler

Publications and source records attributed to J Mandler.

17 recordsLinked to original sources

Rigorous decimation-based construction of ground pure states for spin-glass models on random lattices.

A constructive scheme for determining pure states at very low temperature in the 3-spins glass model on a random lattice is provided, in full agreement with Parisi's one step replica symmetry breaking (RSB) scheme. Proof is based on the analysis of a partial decimation procedure and of the statistical properties of its output, i.e., a reduced Hamiltonian acting on a subset of the initial spins. The number of ground states (GS) in each state, the number of states, and the distances between GS are calculated and correspond to RSB predictions.

Journal Article↗

A reassortant H1N1 influenza A virus caused fatal epizootics among camels in Mongolia.

In the autumn of 1979 a severe influenza epizootic started among camels in Mongolia (Lvov et al., 1982; Viprosi Virusol. 27, 401-405.) Between 1980 and 1983 13 independent isolates of H1N1 viruses were obtained from diseased camels, which were virtually indistinguishable from the human A/USSR/90/77 strain by serological means. Two hundred and seventy-one samples of camel sera collected between 1978 and 1983 contained antibodies against the human A/USSR/90/77 isolate. After experimental infection of camels with some of these isolates, the animals developed similar symptoms as those found during natural infection: coughing, bronchitis, fever, discharge from nose and eyes. A genetic sequence analysis revealed that among the eight segments (genes) the PB1, HA, and NA genes were almost identical with allelic genes of the USSR/77 strain, and the PB2, PA, NP, M, and NS genes were almost identical with those of the A/PR/8/34 strain.

Animals↗

Detection of antibodies to HCV: comparison of a c100-3 EIA and the 2nd generation EIA.

The reactivity of 558 serum specimens in Abbott 1st and 2nd generation EIAs was compared. A significant increase in HCV seropositivity was especially found in high risk groups such as hemophiliacs (57.7 vs. 73.1%), IVDA (54.5 vs. 61.8%), HIV positives (21.8 vs. 25.5%) or patients on dialysis (15.7 vs. 16.9%). Reactivity of all sera which only reacted in the 2nd generation EIA was 'confirmed' by using supplemental research assays. In contrast, sera which were highly reactive in the c100-3 assay but could not be confirmed by Neutralization Assay were weakly positive or negative in the 2nd generation test.

Hemophilia A↗

Evolution of pig influenza viruses.

There is evidence that the nucleoprotein (NP) gene of the classical swine virus (A/Swine/1976/31) clusters with the early human strains at the nucleotide sequence level, while at the level of the amino acid sequence, as defined by consensus amino acids and in functional tests, its NP is clearly "avian like." Therefore it was suggested that the Sw/31 NP had been recently under strong selection pressure, possibly caused by reassortment with other avian influenza genes, whose gene products have to cooperate intimately with NP (Gammelin et al., 1989. Virology 170, 71-80). This suggestion has been investigated by sequencing the genes of internal and nonstructural proteins of Sw/31. The data on these sequences and on the phylogenetic trees are not in accordance with that suggestion: all these genes cluster with the early human strains at the nucleotide level while, at the level of the amino acid sequence, most of them are more closely related to the avian strains, thus resembling NP in this respect. This indicates that these genes rather evolved concomitantly with the NP gene. Our data are in agreement with the suggestion that, at about the time of the Spanish Flu (1918/19), a human influenza A (H1N1) virus entered the pig population. Furthermore, it is known that the NP of the human influenza A viruses--in contrast to that of the avian and swine strains--has been under strong selection pressure to change (Gammelin et al., 1990. Mol. Biol. Evol. 7, 194-200. Gorman et al., 1990a. J. Virol. 64, 1487-1497). Thus, after transfer of a human strain into pigs, the selection pressure might be released, enabling the NP and the other genes of the swine virus to evolve back to the optimal avian sequences, especially at the functionally important consensus positions. The swine influenza viruses circulating since 1979 in Northern Europe--represented by A/Swine/Germany/2/81 (H1N1)--have all genes, so far examined, derived from an avian influenza virus pool and are different from the classical swine viruses.

Animals↗

Mutants and revertants of an avian influenza A virus with temperature-sensitive defects in the nucleoprotein and PB2.

ts19 is a temperature-sensitive (ts) mutant of the influenza A fowl plague virus with a defect in the nucleoprotein (NP). In ts19-infected chicken embryo cells all viral components are synthesized in normal yields at the nonpermissive temperature, but infectious virus is not formed. Under these conditions the migration of the NP and M of ts19 from the cell nucleus to the cytoplasm is affected. This ts defect is due to a single amino acid replacement (R162K) in a completely conserved region of the NP. Another mutant with a different defect in the NP is ts81. After infection with ts81 at 40 degrees no vRNA is being synthesized. By backcross of a revertant derived from ts81 many isolates with a ts defect in the PB2 protein were obtained. This ts defect seems to extragenically suppress the ts defect in the NP gene and to be dominant in a wild-type background.

Amino Acid Sequence↗

Phylogenetic relationship of the nonstructural (NS) genes of influenza A viruses.

Phylogenetic trees were constructed using 38 sequences of the A group and 10 sequences of the B group of the NS gene of influenza A viruses. Within the A group we found avian as well as mammalian influenza a viruses, while within the B group exclusively avian strains were found. The avian and human NS genes of the A group were derived from a common ancestor existing at about 1912. At 13 positions of the amino acid sequences of the NS1 protein two subtypes of the A group can be differentiated, a human and a non-human subtype. Starting at the time of the introduction of an avian PB1 gene into human strains during the antigenic shift at 1957 the NS1 protein of the human strains came under an enhanced selection pressure which might indicate a cooperation of the NS1 protein with and adaptation of the NS1 protein on the newly introduced PB1 gene. Such a selection pressure on the NS2 protein is completely missing. Comparison of all sequences of the NS1 protein revealed four highly conserved regions within the amino-terminal half of the molecule. One of this regions seems to contain the nuclear migration signal. The carboxy-terminal half is completely variable and seems to be dispensable.

Amino Acid Sequence↗

Derivation of the nucleoproteins (NP) of influenza A viruses isolated from marine mammals.

The nucleoprotein (NP) genes of influenza viruses were sequenced from a variety of virus isolates derived from marine mammals: whales from the Pacific and Atlantic oceans, seal and gull from the Western Atlantic, and a tern from the Caspian Sea. In comparison to published NP sequences, we found pairs of NPs derived from avian and marine mammal isolates to be closely related, e.g., the gull-whale and mallard-seal pairs from the Atlantic Coast of the USA and the tern-Pacific Ocean whale pair of the Eastern Hemisphere. Our analysis suggests that influenza viruses have been independently introduced into marine mammals from avian sources for each of our three examples. Furthermore, the closeness of the relationship in these avian-mammalian NP pairs indicates that the introductions are relatively recent. The sequences of these marine mammal NPs are avian-like and can be clearly distinguished from human NPs. Our results provide further support of interspecies transmission of influenza A viruses from the avian host reservoir directly to mammalian hosts.

Amino Acid Sequence↗

Two subtypes of nucleoproteins (NP) of influenza A viruses.

The nucleoprotein (NP) genes of nine influenza A virus strains isolated from different species have been sequenced and the deduced amino acid sequences have been compared to published NP sequences and sequences in press. Two "subtypes" of NPs can clearly be defined, one "subtype" comprises the NPs found with all tested human and one porcine strain, and another "subtype" comprises the NPs found with all tested avian and equine, and some porcine strains and a mink virus. There are no significant differences between these two groups concerning secondary structure predictions. Pig viruses were the only ones whose NP can belong to the one or the other "subtype." Therefore, pigs can be regarded as "mixing vessels," where the two independently evolving reservoirs of influenza A viruses can meet for the creation of new pandemic strains by reassortment.

Amino Acid Sequence↗

Localisation of the temperature-sensitive defect in the nucleoprotein of an influenza A/FPV/Rostock/34 virus.

The nucleotide sequences of the nucleoprotein (NP) genes of fowl plague virus (FPV) and of a temperature-sensitive (ts) mutant (ts81) derived therefrom have been determined. The ts81-NP nucleotide sequence possesses a single nucleotide substitution in comparison to the wild type. This causes an amino acid exchange at position 332 of the NP. An alanine in the wild type-NP is substituted by a threonine in ts81-NP. This substitution leads to a significant difference in the secondary structure prediction. Although this mutation is located within the karyophilic region of the NP, the accumulation of the NP in ts81-infected cells is not significantly affected at 40 degrees C. Therefore, we assume that the cooperation with one of the polymerase proteins (P) is interfered with at 40 degrees C, leading to the loss of viral vRNA or replicative cRNA synthesis. The comparison of the FPV-NP nucleotide sequence to a previously published sequence of the same strain (Tomley and Roditi, 1984) highlights ten nucleotide differences, four of them leading to amino acid substitutions.

Amino Acid Sequence↗

Regulation of cardiac output during upright exercise in patients with aortic regurgitation.

The change in cardiac output during upright exercise in patients with aortic regurgitation (AR) is not well known. We measured left ventricular (LV) ejection fraction (EF) and volume, regurgitant fraction (RF), total cardiac output and forward cardiac output at rest, and peak upright exercise by means of radionuclide angiography in ten normal subjects and 15 patients with AR. In the normal subjects, there was no significant change in the end-diastolic volume but there was a significant decrease in the end-systolic volume (p = 0.0001) and a significant increase in EF (p = 0.0001). The increase in cardiac output during exercise was due to increases in both stroke volume and heart rate. In patients with AR, there was a significant decrease during exercise in RF (53 +/- 15% at rest, and 45 +/- 15% during exercise; p = 0.03), and in end-diastolic and end-systolic volume (p = 0.02, and p = 0.003, respectively). The EF increased during exercise (p = 0.003). The total stroke volume did not change (68 +/- 19 ml/m2 at rest, and 67 +/- 14 ml/m2 during exercise; p, NS). Thus, in patients with AR, individual changes in EF, RF, and volume are quite variable, but as a group a decrease in RF and an increase in heart rate contribute to the increase in forward flow. The total stroke volume may not increase during exercise, despite an increase in EF and a decrease in end-systolic volume because of a concomitant decrease in end-diastolic volume.

Adolescent↗