Map-based analysis of genetic loci on chromosome 2D that affect glume tenacity and threshability,components of the free-threshing habit in common wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

During the domestication of bread wheat (Triticum aestivum L.), evolutionary modifications that took place in seed dispersal mechanisms enhanced its suitability for agricultural production. One of these modifications involved the evolution of the free-threshing or hulless characteristic. In this study, we studied quantitative trait loci (QTL) affecting components of the free-threshing habit (threshability and glume tenacity) on chromosome 2D in a recombinant inbred line (RIL) population developed by the International Triticeae Mapping Initiative (ITMI) as well as the tenacious glumes 1 (Tg1) gene in F₂ progeny (CS/CS2D F₂) of a cross between Chinese Spring and the 2D2 substitution line [Chinese Spring (Ae. tauschii 2D)]. In the ITMI population, two QTL affected threshability (QFt.orst-2D.1 and QFt.orst-2D.2) and their location coincided with QTL affecting glume tenacity (QGt.orst-2D.1 and QGt.orst-2D.2). In the CS/CS2D F₂ population, the location of QTL that affected glume tenacity (QGt.orst-2D.1), the size of a glume base scar after detachment (QGba.orst-2D), and Tg1 (12-cM interval between Xwmc112 and Xbarc168) also coincided. Map comparisons suggest that QFt-orst-2D.1, QGt.orst-2D.1, and QGba.orst-2D correspond to Tg1 whereas QFt.orst-2D.2 and QGt.orst-2D.2 appear to represent separate loci. The observation of coincident QTL for threshability and glume tenacity suggests that threshability is a function of glume adherence. In addition, the observation of the coincident locations of Tg1 and QTL for the force required to detach a glume and the size of a glume base scar after detachment suggests that Tg1’s effect on both glume tenacity and threshability resides on its ability to alter the level of physical attachment of glumes to the rachilla of a spikelet.     

Simvastatin treatment prevents oxidative damage to DNA in whole blood leukocytes of dyslipidemic type 2 diabetic patients

Type 2 diabetes (T2D) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products. Since reactive oxygen species (ROS) can cause damage to biological macromolecules including DNA, this study investigated oxidative damage to DNA using the alkaline (pH > 13) comet assay in peripheral whole blood leukocytes sampled from 15 dyslipidemic T2D patients treated with simvastatin (20 mg/day), 15 dyslipidemic T2D patients not treated with simvastatin, 20 non‐dyslipidemic T2D patients, and 20 healthy individuals (controls). Our results showed a greater DNA migration in terms of damage index (DI) (p < 0.01) in the dyslipidemic T2D patients not treated with statin (DI = 67.70 ± 10.89) when compared to the dyslipidemic T2D patients under statin treatment (DI = 47.56 ± 7.02), non‐dyslipidemic T2D patients (DI = 52.25 ± 9.14), and controls (DI = 13.20 ± 6.40). Plasma malondialdehyde (MDA) and C‐reactive protein (CRP) levels were also increased and total antioxidant reactivity (TAR) and paraoxonase activity (PON1) decreased in non‐dyslipidemic T2D patients and dyslipidemic T2D non‐treated with simvastatin. We also found that DI was inversely correlated with TAR (r = ?0.61, p < 0.05) and PON1 (r = ?0.67, p < 0.01). In addition, there was a significant positive correlation between DI and CRP (r = 0.80, p < 0.01). Our results therefore indicate that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients. Copyright © 2010 John Wiley & Sons, Ltd.     

Association of eNOS and MCP-1 Genetic Variants with Type 2 Diabetes and Diabetic Nephropathy Susceptibility: A Case–Control and Meta-Analysis Study

Type 2 diabetes (T2D) and its secondary complications result from the complex interplay of genetic and environmental factors. To understand the role of these factors on disease susceptibility, the present study was conducted to assess the association of eNOS and MCP-1 variants with T2D and diabetic nephropathy (DN) in two ethnically and geographically different cohorts from North India. A total of 1313 subjects from two cohorts were genotyped for eNOS (rs2070744, rs869109213 and rs1799983) and MCP-1 (rs1024611 and rs3917887) variants. Cohort-I (Punjab) comprised 461 T2D cases (204 T2D with DN and 257 T2D without DN) and 315 healthy controls. Cohort-II (Jammu and Kashmir) included 337 T2D (150 T2D with DN and 187 T2D without DN) and 200 controls. Allele, genotype and haplotype frequencies were compared among the studied participants, and phenotype–genotype interactions were determined. Meta-analysis was performed to investigate the association between the selected variants and disease susceptibility. All three eNOS variants were associated with 1.5–4.0-fold risk of DN in both cohorts. MCP-1 rs1024611 conferred twofold risk towards DN progression in cohort-II, while rs3917887 provided twofold risk for both T2D and DN in both cohorts. eNOS and MCP-1 haplotypes conferred risk for T2D and DN susceptibility. Phenotype–genotype interactions showed significant associations between the studied variants and anthropometric and biochemical parameters. In meta-analysis, all eNOS variants conferred risk towards DN progression, whereas no significant association was observed for MCP-1 rs1024611. We show evidences for an association of eNOS and MCP-1 variants with T2D and DN susceptibility.

     

Role of Neostriatal Dopamine D1 and D2 Receptors in the Organization of Neuronal Activity in the Entopeduncular Nucleus

In chronic experiments on cats, we studied the effects of selective blockade of the dopamine D1 and D2 receptors in the nucleus caudatus (NC) against the background neuronal activity (BA) in the entopeduncular nucleus (ENT) and on the responses of these neurons evoked by stimulation of the subthalamic nucleus (STN). A blocker of D1 receptors, SCH 23390, and sulpiride, a blocker of D2 receptors, when injected into the NC head, led to changes in the BA frequency. The direction of these effects was different: blockade of the D2 receptors evoked a significant decrease in the BA frequency of ENT neurons, but when the D2 receptors were blocked, a trend toward an increase in this frequency was observed. Some of the ENT cells demonstrated similar changes in the temporal organization of their impulse activity with blockade of the D1 and D2 receptors. Namely, besides single action potentials (AP), high-frequency burst discharges began to be generated. Blockade of both D1 and D2 receptors prolonged the responses of ENT neurons to STN stimulation due to the appearance of similar AP bursts, while control animals demonstrated reactions consisting of solely single AP. The question on a dual (synergic and antagonistic) involvement of the neostriatal D1 and D2 receptors in the dopaminergic regulation of the basal ganglia is under discussion.     

Ala45Thr polymorphism of the NEUROD1 gene and diabetes susceptibility: a meta-analysis

A meta-analysis assessed whether the Ala45Thr polymorphism of the neurogenic differentiation 1 (NEUROD1) gene is associated with increased risk of diabetes mellitus type 1 (T1D) or type 2 (T2D). Fourteen case-control studies were analyzed, including genotype data on 3,057 patients with diabetes (T1D n=1,213, T2D n=1,844) and 2,446 controls. Overall and race-specific summary odds ratios (ORs) were obtained with fixed and random effects models. The Thr allele did not significantly increase the overall risk for T1D (OR 1.27 [0.94–1.71], P=0.12) or T2D (OR 1.07 [0.90–1.28], P=0.46). The Thr allele conferred increased susceptibility in subjects of Asian racial descent to T1D (OR 1.88 [1.10–3.21], P=0.020), but not to T2D (OR 1.08 [0.74–1.56], P=0.70). There was no association in subjects of European descent (OR 0.97 [0.76–1.23], P=0.80 for T1D; OR 1.03 [0.88–1.21], P=0.68 for T2D). Larger studies seemed to show more conservative estimates for the association with T1D (P=0.083). The Ala45Thr polymorphism of the NEUROD1 gene has no effect on susceptibility to T2D. It may however be a risk factor for susceptibility to T1D, in particular for subjects of Asian descent, although bias cannot be totally excluded.     

Simenoside A,a New Triterpenoid Saponin from Gypsophila simonii Hub.‐Mor.

Saponins are amphiphilic glycoconjugates which give soap‐like foams in H₂O. A new triterpenoid saponin, simenoside A ( 1 ), based on gypsogenin aglycone, and the known saponin 2 were isolated from Gypsophila simonii Hub.‐Mor. The structure of the new saponin was elucidated as 3‐O‐β‐D ‐galactopyranosyl‐(1→2)‐[β‐D ‐xylopyranosyl‐(1→3)]‐β‐D ‐glucuronopyranosylgypsogenin 28‐O‐β‐D ‐glucopyranosyl‐(1→3)‐[β‐D ‐glucopyranosyl‐(1→2)‐β‐D ‐xylopyranosyl‐(1→4)]‐α‐L ‐rhamnopyranosyl‐(1→2)‐β‐D ‐fucopyranosyl ester on the basis of extensive spectral analyses and chemical evidence. Saponins 1 and 2 were isolated from G. simonii for the first time.     

Multiple blood pressure QTL on rat Chromosome 2 defined by congenic Dahl rats

Linkage analysis previously demonstrated a blood pressure quantitative trait locus (QTL) on rat Chromosome 2 (Chr 2) in crosses utilizing Dahl salt-sensitive (S) rats. The present work dissects this QTL by using congenic strains in which segments of Chr 2 from Wistar Kyoto rats (WKY) are placed on the S genetic background. Two distinct QTLs were found where one QTL was anticipated. These each accounted for a blood pressure of 15–20 mm Hg in rats fed 2% NaCl diet for 24 days. One QTL was in the <9-cM interval between D2Rat35 and D2Wox18 (Fgg), and the other was in the <7-cM interval between D2Wox18 (Fgg) and D2Mgh10. A third tentative QTL was suggested, but not clearly established, in the <3-cM interval between D2Mgh10 and D2Rat259. Received: 26 July 2001 / Accepted 6 September 2001     

Mapping murine loci for seizure response to kainic acid

Mature DBA/2J (D2) mice are very sensitive to seizures induced by various chemical and physical stimuli, whereas C57BL/6J (B6) mice are relatively seizure resistant. We have conducted a genome-wide search for quantitative trait loci (QTLs) influencing the differential sensitivity of these strains to kainic acid (KA)-induced seizures by studying an F₂ intercross population. Parental, F₁, and F₂ mice (8–10 weeks of age) were injected subcutaneously with 25 mg/kg of KA and observed for 3 h. Latencies to focal and generalized seizures and status epilepticus were recorded and used to calculate an overall seizure score. Results of seizure testing indicated that the difference in susceptibility to KA-induced seizures between D2 and B6 mice is a polygenic phenomenon with at least 65% of the variance due to genetic factors. First-pass genome screening (10-cM marker intervals) in F₂ progeny (n = 257) documented a QTL of moderate effect on Chromosome (Chr) 1 with a peak LOD score of 5.5 (17% of genetic variance explained) localized between D1Mit30 and D1Mit16. Provisional QTLs of small effect were detected on Chr 11 (D11Mit224–D11Mit14), 15 (D15Mit6–D15Mit46) and 18 (D18Mit9–D18Mit144). Multiple locus models generally confirmed the Mapmaker/QTL results and also provided evidence for another QTL on Chr 4 (D4Mit9). Multilocus analysis of seizure severity suggested that additional loci on Chrs 5 (D5Mit11), 7 (D7Mit66), and 15 (D15Nds2) might also contribute to KA-induced seizure response. Overall, our results document a complex genetic determinism for KA-induced seizures in these mouse strains with contributions from as many as eight QTLs. Received: 16 April 1996 / Accepted: 21 October 1996     

Triterpene Glucosides from the Leaves of Aralia elata and Their Cytotoxic Activities

Three new triterpene glucosides, named congmuyenosides C–E ( 1 – 3 , resp.), along with four known ones, were isolated from an EtOH extract of Aralia elata (Miq .) Seem . leaves. The structures of the new compounds were identified as 3‐O‐{β‐D ‐glucopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐(1→3)‐[β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐glucopyranosyl}caulophyllogenin ( 1 ), 3‐O‐{β‐D ‐glucopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐(1→3)‐[β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐glucopyranosyl}hederagenin 28‐O‐β‐D ‐glucopyranosyl ester ( 2 ), 3‐O‐{β‐D ‐glucopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐(1→3)‐[β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐glucopyranosyl}echinocystic acid 28‐O‐β‐D ‐glucopyranosyl ester ( 3 ) on the basis of spectral analyses, including MS, ¹H‐NMR, ¹³C‐NMR, DEPT, HSQC, HMBC, NOESY, and HSQC‐TOCSY experiments. All isolates obtained were evaluated for their cytotoxic activities against three human tumor cell lines (HepG2, SKOV3, and A549). Compound 3 showed significant cytotoxicity against A549 cell line (IC₅₀ 9.9±1.5 μM ).     

Inhibition of NO Production by Grindelia argentina and Isolation of Three New Cytotoxic Saponins

A bioassay‐guided phytochemical analysis of the ethanolic extract of Grindelia argentina Deble & Oliveira ‐Deble (Asteraceae) allowed the isolation of a known flavone, hispidulin, and three new oleanane‐type saponins, 3‐O‐β‐D ‐xylopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐2β,3β,16α,23‐tetrahydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D ‐xylopyranosyl‐(1→2)‐β‐D ‐apiofuranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→3)‐α‐L ‐rhamnopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl ester ( 2 ), 3‐O‐β‐D ‐glucopyranosyl‐2β,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D ‐xylopyranosyl‐(1→2)‐β‐D ‐apiofuranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→3)‐α‐L ‐rhamnopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl ester, ( 3 ) and 3‐O‐β‐D ‐xylopyranosyl‐(1→3)‐β‐D ‐glucopyranosyl‐2β,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D ‐xylopyranosyl‐(1→2)‐β‐D ‐apiofuranosyl‐(1→3)‐β‐D ‐xylopyranosyl‐(1→3)‐α‐L ‐rhamnopyranosyl‐(1→2)‐α‐L ‐arabinopyranosyl ester ( 4 ), named grindeliosides A–C, respectively. Their structures were determined by extensive 1D‐ and 2D‐NMR experiments along with mass spectrometry and chemical evidence. The isolated compounds were evaluated for their inhibitory activities against LPS/IFN‐γ‐induced NO production in RAW 264.7 macrophages and for their cytotoxic activities against the human leukemic cell line CCRF‐CEM and MRC‐5 lung fibroblasts. Hispidulin markedly reduced LPS/IFN‐γ‐induced NO production (IC₅₀ 51.4 μM ), while grindeliosides A–C were found to be cytotoxic, with grindelioside C being the most active against both CCRF‐CEM (IC₅₀ 4.2±0.1 μM ) and MRC‐5 (IC₅₀ 4.5±0.1 μM ) cell lines.     

Genomic and Yeast Artificial Chromosome Long-Range Regular Article Linking Six Loci in 10q11.2 and Spanning the Multiple Endocrine Neoplasia Type 2A (MEN2A) Region

Multiple endocrine neoplasia types 2A and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma (FMTC) are dominantly inherited cancers that have in common the clinical feature of medullary thyroid carcinoma (MTC). We have performed both genomic long-range restriction mapping and yeast artificial chromosome (YAC) contig assembly and restriction mapping to establish physical linkage, order, and distances between six loci in 10q11.2 near the genes responsible for these hereditary cancers. RET, D10S94, D10S182, and D10S102 have been mapped in genomic DNA. RET, D10S94, D10S182, D10F3853, and the 10q11.2 sequences detected by DNA marker DM124 are encompassed by a 1-Mb YAC contig. Six physically linked loci are within 1.4 Mb and have an order and orientation of 10cen, D10F38S3, DM124, RET, D10S94, D10S182, D10S102, 10qter. Mutations in the RET proto-oncogene have recently been demonstrated to be associated with MEN 2A and FMTC. RET is located within a genetically defined MEN2A candidate interval between D10S141 and D10S94; MEN2B has been mapped to a larger, overlapping region between D10S141 and a more distal locus, RBP3. Both our genomic physical map and our YAC contig span the entire MEN2A candidate region and overlap with that of MEN2B . These maps will facilitate the identification of genes that can be considered candidates for MEN2B and the identification of tumor-specific alterations important in sporadic MTC.     

Enantioselectivity of bunitrolol 4‐hydroxylation is reversed by the change of an amino acid residue from valine to methionine at position 374 of cytochrome P450‐2D6

The enantioselectivity of 4‐hydroxylation of bunitrolol (BTL), a β‐adrenoceptor blocking drug, was studied in microsomes from human liver, human hepatoma (Hep G2) cells expressing CYP2D6, and lymphoblastoid cells expressing CYP2D6. Kinetics in human liver microsomes showed that the Vmax value for (+)‐BTL was 2.1‐fold that of (−)‐BTL, and that the Km value for (+)‐BTL was lower than that for the (−)‐antipode, resulting in the intrinsic clearance (Vmax/Km) of (+)‐BTL being 2.1‐fold over its (−)‐antipode. CYP2D6 (CYP2D6‐met) expressed in Hep G2 cells had a methionine residue at position 373 of the amino acid sequence and a rat‐type N‐terminal peptide (MELLNGTGLWSM) instead of the human‐type (MGLEALVPLAVIV), and showed enantioselectivity of [(+)‐BTL < (−)‐BTL] for the rate of BTL 4‐hydroxylation. In contrast, enantioselectivity [(+)‐BTL > (−)‐BTL] for Hep G2‐CYP2D6 (CYP2D6‐val) with a human‐type N‐terminal peptide that had a valine residue at 374, which corresponds to the methionine of the CYP2D6‐met variant, was the same as that for human liver microsomes. We further confirmed that CYP2D6‐met and CYP2D6‐val expressed in human lymphoblastoid cells, both of which have methionine and valine, respectively, at position 374 and a human‐type N‐terminal peptide, exhibited the same enantioselectivities as those obtained from CYP2D6‐met and CYP2D6‐val expressed in the Hep G2 cell system. These results indicate that the amino acid at 374 of CYP2D6 is one of the key factors influencing the enantioselectivity of BTL 4‐hydroxylation. Chirality 11:1–9, 1999. © 1999 Wiley‐Liss, Inc.     

Retrotransposon-induced ectopic expression of the Om(2D) gene causes the eye-specific Om(M) phenotype in Drosophila ananassae

Optic morphology (Om) mutations in Drosophila ananassae map to at least 22 loci, which are scattered throughout the genome. Om mutations are all semidominant, neomorphic, nonpleiotropic, and associated with the insertion of a retrotransposon, tom. We have found that the Om(2D) gene encodes a novel protein containing histidine/proline repeats, and is ubiquitously expressed during embryogenesis. The Om(2D) RNA is not detected in wild-type eye imaginal discs, but is abundantly found in the center of the eye discs of Om(2D) mutants, where excessive cell death occurs. D. melanogaster flies transformed with the Om(2D) cDNA under control of the hsp70 promoter display abnormal eye morphology when heat-shocked at the third larval instar stage. These results suggest that the Om(2D) gene is not normally expressed in the eye imaginal discs, but its ectopic expression, induced by the tom element, in the eye disc of third instar larvae results in defects in adult eye morphology.     

Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses

Chondrodysplastic dwarfism in Miniature horses appeared to be a recessive genetic trait based on the occurrence of affected offspring by normal parents. Dwarf phenotypes vary and range from abnormal abortuses to viable offspring with evidence of skeletal dysplasia. A genome‐wide association study implicated a region of ECA1 with dwarfism in Miniature horses. Aggrecan (ACAN) was a candidate gene in that region, and exons were sequenced to compare DNA sequences for dwarf and non‐dwarf horses. Sequencing led to the discovery of variants in exons 2, 6, 7 and 15 associated with dwarfism. The four variants are identified with reference to Ecab 3.0 (GCF_002863925.1) as g.95291270del (rs1095048841), g.95284530C>T (ERP107353), g.95282140C>G (rs1095048823) and g.95257480_95257500del (rs1095048839) and designated here as D1, D2, D3* and D4 respectively. A previous study at another laboratory reported dwarfism associated with homozygosity for D3*. Homozygotes for those variants and compound heterozygotes for any combination of those variants always expressed a dwarfism phenotype. However, eight additional horses with dwarfism were found, seven of which were heterozygotes for D2, D3* or D4, suggesting the existence of additional ACAN alleles causing dwarfism. Among Miniature horses, the combined frequency of D1, D2, D3* and D4 was 0.163, suggesting a carrier rate of 26.2% for alleles causing chondrodysplastic dwarfism.     

Phylogenetic analysis of ITS2 sequences suggests the taxonomic re‐structuring of Dunaliella viridis (Chlorophyceae,Dunaliellales)

We analyzed the ITS2 primary and secondary structure (including Compensatory Base Changes (CBCs)) of 17 new Dunaliella strains (11 D. viridis, two D. tertiolecta, and four Dunaliella sp.), and compared these with other Dunaliella sequences available from the ITS2 database to circumscribe their taxonomic position. The ITS2 primary and secondary structure analysis positioned the majority of D. viridis strains in four main clades, showing that D. viridis is polyphyletic. The detection of at least one CBC among these clades strongly suggests that they could correspond to different biological species. Unexpectedly, while D. viridis var. euchlora (CCAP19/21) was positioned within the subgenus Dunaliella, D. viridis var. palmelloides (CCAP11/34) was positioned clearly outside this subgenus, suggesting that this taxon may not be properly placed in Dunaliella. Furthermore, the detection of at least three compensatory base changes (CBCs) between D. viridis var. palmelloides (CCAP11/34) and the other strains analyzed, confirm that this strain is a different species. For these reasons we propose re‐naming D. viridis var. palmelloides (CCAP11/34) to incertae sedis, and D. viridis var. euchlora (CCAP19/21) to Dunaliella sp. Therefore, the ITS2 primary and secondary structure data suggest a taxonomic re‐structuring of D. viridis.     

The effectiveness of commercial antimicrobial compounds against saccharolytic microorganisms isolated from a beet sugar production line

The antimicrobial activities of five commercial disinfectants containing quaternary ammonium compound-isopropanol (D1), sodium methyl dithiocarbamate (D2), sodium thiocarbamate (D3), sodium dimethyl dithiocarbamate (D4) and formaldehyde (D5) were studied against three main saccharolytic indigenous isolates (Bacillus cereus, Lactobacillus plantarum and Leuconostoc mesenteroides) from a beet sugar extraction line. Preliminary studies suggested that although all the disinfectants were effective against those isolates, the high economic cost in combination with large amounts of the disinfectants D2, D3 and D4 weaken their possibility for industrial use. Therefore, the minimum inhibitory concentration (MIC) of the other two examined disinfectants D1 and D5 was determined and survivor curves were obtained, for a period of 7 days. Bacterial counts against time (h) suggested that D1 was more effective than D5 against the microbial population. In particular, D1 was bacteriolytic above 7 mg/l for B. cereus and bactericidal above 80 mg/l for Lc. mesenteroides and above 100 mg/l for L. plantarum. The disinfectant D5 was bacteriolytic above 25 mg/l for B. cereus and bactericidal above 500 mg/l for Lc. mesenteroides and L. plantarum. Taking into consideration both features, i.e. high concentration and very low cost, the use of D5 (formaldehyde) appeared more suitable to the concerned beet sugar processor. This revised version was published online in August 2006 with corrections to the Cover Date.     

Genetic control of murine hemagglutinin formation to H-2.5

When B10.D2 (H-2^d) mice are immunized with lymphoid cells from C57B1/10 (H-2 ^d ) and their antisera tested against B10.A (H-2 ^a ) target cells, only antibodies to H-2.5 are measured. The same is true for immunization of DBA/2 (H-2 ^d ) mice when their antisera are absorbed with B10.D2 cells prior to testing. Irrespective of the dose of immunogen administered, the primary hemagglutinin response of B10.D2 mice is significantly lower than that of DBA/2 mice and (B10.D2 × DBA/2)F₁ hybrids, but the secondary responses are similar. The low responsiveness of B10.D2 mice appears to be determined by a single dominant gene with incomplete penetrance; the gene is not linked to eitherH- 2, Hc, or the immunoglobulin allotype loci. In addition, the H-2.5 hemagglutinin response is susceptible to nongenetic influences. When antisera from B10.D2, devoid of H-2.5 hemagglutinins, were assayed in a complement-mediated cytotoxic test, they contained almost as much anti-H-2.5 activity as did the antisera from DBA/2 mice or (B10.D2 × DBA/2)F₁ hybrids. The possibility is discussed that the locus responsible for the deficient primary hemagglutinin response of B 10.D2 may not be determinant-specific but may affect hemagglutinin responses in general.     

Lack of association of glutathione-S-transferase omega 1(A140D) and omega 2 (N142D) gene polymorphisms with urinary arsenic profile and oxidative stress status in arsenic-exposed population

Individual variability in arsenic metabolism is suggested to be associated with the effects of chronic arsenic exposure on health. Glutathione-S-transferase omega (GSTO) 1 and 2 are known to have the activity of monomethyl arsenate [MMA(V)] reductase, which is the rate-limiting enzyme for the biotransformation of inorganic arsenic. This study was conducted to investigate the relationship between polymorphisms in the GSTO1 and GSTO2 genes and arsenic metabolism and oxidative stress status in Chinese populations chronically exposed to different levels of arsenic in drinking water. Two polymorphisms (GSTO1*A140D and GSTO2*N142D) with relatively higher mutation frequencies in the Chinese population were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The allele frequencies of 140D and 142D in the entire study population were 0.17 and 0.25, respectively. There were no significant differences in the urinary arsenic profile, the blood reduced glutathione (GSH) levels, the blood superoxide dismutase (SOD) activity, or the urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels between the study subjects with different genotypes of GSTO1*A140D or GSTO2*N142D. Multivariate analysis revealed that there was no association between the urinary profile or oxidative stress status and the polymorphism of GSTO1*A140D or GSTO2*N142D. Collectively, polymorphisms in GSTO1 or GSTO2 do not appear to contribute to the large individual variability in arsenic metabolism or susceptibility to arsenicosis.     

A genetic locus susceptible to the overt proteinuria in BUF/Mna rat

The BUF/Mna (BUF) strain is a high-proteinuria line of rats, and virtually all rats develop overt proteinuria by the age of 20 weeks. Genetic analysis revealed that proteinuria susceptibility was determined principally by two autosomal recessive genes. These findings prompted us to perform genetic mapping of the genes. (BUF/Mna × WKY/NCrj) F₁× BUF/Mna backcross rats were raised and maintained for 40–60 weeks to detect proteinuria. DNAs were extracted from ears of these rats and were examined by linkage study with polymerase chain reaction (PCR) with 132 microsatellite markers. Fifty-three out of 167 rats developed proteinuria. DNAs of 51 out of these 53 rats showed homozygous BUF/BUF genotype in the D13Mgh4 and D13N1 markers located on Chromosome (Chr) 13. The D13Rat1, D13Mgh2, D13Rat13, D13Mgh3, Syt2, Ren, D13Rat25, D13Mit2, D13Mgh5, and D13N2 markers located on the chromosome also showed statistically significant linkage to the development of proteinuria, whereas the other 110 markers showed no linkage. Here we report that a proteinuria-susceptible gene, Pur1, resides on a region flanked by the loci D13Mgh3 and D13Mgh4 on Chr 13. Received: 28 May 1998 / Accepted: 22 July 1998