Improved method for the identification of the fluoride-resistant plasmacholinesterase genotypes

This investigation was prompted by the findings that (1) dibucaine-resistant homozygotes and heterozygotes for plasmacholinesterase also exhibit resistance to fluoride inhibition, (2) the differentiation of dibucaine-resistant from the fluoride-resistant genotypes is ambiguous with the method of Harris and Whittaker, (3) the plasmacholinesterase inhibition by Na fluoride (FN) is markedly influenced by the temperature. Therefore, we modified their method by increasing (1) the temperature of the reaction from 25C to 37C and (2) the concentration of Na fluoride from 5.0×10^?5 m to 2.5×10^?4 m. With this method, genetically normal individuals have a mean FN±sd=77.0±3.22 while atypical dibucaine-resistant homozygotes have a mean FN±sd=43.0±10.0 and atypical dibucaine-resistant heterozygotes 67.0±5.37. Since a linear correlation was observed between DN and FN by our new method, a fluoride number 2 sd lower than the predicted FN from the DN can distinctly identify the fluoride-resistant plasmacholinesterase genotype E ₁ ^f .     

Genetic Analysis of the Relationship between Bone Mineral Density and Low-Density Lipoprotein Receptor-Related Protein 5 Gene Polymorphisms

Background

A number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.

Methods

Published literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.

Results

A total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02g/cm², 95% CI = 0.01-0.03, P < 10^-4; at femur neck (FN): WMD = 0.01g/cm², 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02g/cm², 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02g/cm², 95% CI = 0.02-0.03, P < 10^-5; WMD at FN = 0.01g/cm², 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03g/cm², 95% CI = 0.01-0.05, P = 0.005).

Conclusion

This meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.     

Modification,Biological Evaluation and SAR Studies of Novel 1H‐Pyrazol Derivatives Containing N,N′‐Disubstituted Urea Moiety as Potential Anti‐melanoma Agents

Malignant melanomas are amongst the most aggressive cancers. BRAF Inhibitors have exhibited therapeutic effects against BRAF‐mutant melanoma. In continuation of our earlier studies on anti‐melanoma agents based on 1H‐pyrazole skeleton, two sets of novel compounds that include 1H‐pyrazole‐4‐amines FA 1 – FA13 and corresponding urea derivatives FN 1 – FN13 have been synthesized and evaluated for their BRAF^V600E inhibitory and antiproliferation activities. Compound FN 10 displayed the most potent biological activity against BRAF^V600E (IC₅₀ = 0.066 μm ) and the A375 human melanoma cell line (GI₅₀ = 0.81 μm ), which was comparable to the positive control vemurafenib, and more potent than our previously reported 1H‐pyrazole‐3‐amines and their urea derivatives. The results of SAR studies and molecular docking can guide further optimization and may help to improve potency of these pyrazole‐based anti‐melanoma agents.     

Bark morphological and chemical features are differentially correlated with disease resistance and yield in hybrid poplar taxa

In the southeastern United States, the establishment of short-rotation intensively cultured plantations of hybrid poplar has been hindered by its susceptibility to stem cankers. We evaluated the tradeoffs between biomass yield and disease tolerance in hybrid poplar genotypes belonging to P. deltoides × P. maximowiczii (DM), P. deltoides × P. nigra (DN), P. trichocarpa × P. maximowiczii (TM), and P. deltoides × P. deltoides (DD) taxa. We hypothesized that canker resistant genotypes will have thicker bark but bark thickness and biomass yield will be negatively correlated. After two growing seasons, the DD genotypes developed thicker bark compared to the genotypes of other taxa and bark thickness was not correlated with biomass yield in the DD genotypes (R² = 0.002). However, in the TM, DM, and DN genotypes, bark thickness was negatively correlated with biomass yield (R² = 0.33–0.77). Disease incidence studies revealed that the DM genotypes were most susceptible to canker whereas no disease was detected in DD genotypes. Furthermore, bark analysis conducted by Fourier transform infrared spectroscopy coupled with multivariate analysis showed that that DD genotypes to be chemically separate from the three hybrid genotypes and that bark chemistry was correlated with canker disease incidence. Taken together, these results reveal that it is possible to generate hybrid poplar genotypes with thicker bark, disease resistance, and higher biomass yields. This insight should guide further efforts to develop genetically improved hybrid poplar genotypes, both in terms of biomass yield and disease tolerance, for cultivation in the southeastern United States. Hybrid poplar cultivation in southeastern United States is hindered by its susceptibility to stem cankers. We evaluated tradeoffs between yield and canker disease resistance in various hybrid poplar genotypes. After two growing seasons, the DD genotypes showed disease resistance and developed thicker bark that was chemically distinct from the other genotypes. Bark thickness was not correlated with yield in the DD genotypes but was negatively correlated with yield in the other genotypes. These results will guide the development of hybrid poplar genotypes that are both disease resistant and high yielding for cultivation in the southeastern United States.     

血清微小RNA-21水平与糖尿病肾病患者氧化应激的相关性研究

目的:探讨血清微小RNA-21(mi R-21)水平与糖尿病肾病(DN)患者氧化应激的相关性。方法:选择2015年1月到2017年5月我院就诊的169例DN患者作为研究对象,其中DN分期早期组95例,中晚期组74例。另选同期在我院接受健康体检者90例作为对照组,对比各组血清mi R-21水平和氧化应激指标,分析患者血清mi R-21水平与氧化应激指标的相关性。结果:各组血清mi R-21水平相比差异有统计学意义(P0.05),中晚期DN组及早期DN组血清mi R-21水平均明显低于对照组,且中晚期DN组又明显低于早期DN组,差异均有统计学意义(P0.05)。各组氧化应激指标相比差异有统计学意义(P0.05),中晚期DN组及早期DN组丙二醛(MDA)、超氧化物歧化酶(SOD)、晚期氧化蛋白产物(AOPP)及NADPH氧化酶4(NOX4)均明显高于对照组,且中晚期DN组又明显高于早期DN组;而血红素氧合酶1(HO-1)明显低于对照组,且中晚期DN组又明显低于早期DN组,差异均有统计学意义(P0.05)。依据Spearman法分析相关性发现,血清miR-21水平与MDA、SOD、AOPP及NOX4均呈负相关(P0.05),与HO-1呈正相关(P0.05)。结论:血清mi R-21水平与DN患者氧化应激指标均具有明显的相关性,临床上可尝试将miR-21纳入到DN患者病情监测的指标体系中,从而有助于疾病的诊治及患者的预后。     

Analysis of the association of the G-7A polymorphism of the matrix Gla protein gene with ischemic atherothrombotic stroke in humans with its different risk factors

The G-7A polymorphism (rs1800801) of the matrix Gla protein (MGP) gene was determined in 170 patients with ischemic atherothrombotic stroke (IATS) and 124 control persons. It was found that the distribution of the major allele homozygotes, heterozygotes, and minor allele homozygotes was 35.9, 48.8, and 15.3% in patients with IATS (in the control, 43.5, 50.0, and 6.5%; P = 0.051 by the χ² test). Significant differences in the distribution of genotypes were revealed only in women (P = 0.022). The odds ratio (OR) for minor allele homozygotes (A/A) vs. major allele carriers (G/A + G/G) was 2.618 (P = 0.023), while in women it was equal to 6.645 (P = 0.015). In patients with the A/A genotype, the values of the blood coagulation parameters (prothrombin time) indicated increased their predisposition to hypercoagulability. The results obtained prove that the A/A variant of the MGP gene is associated with an increased risk of IATS in females of the Ukrainian population and may be related to blood hypercoagulability and formation of thrombi.     

Tolerance to Zinc Deficiency in Rice Correlates with Zinc Uptake and Translocation

To study variation in zinc efficiency (ZE) among current Chinese rice genotypes, a pot experiment was conducted with 15 aerobic and 8 lowland rice genotypes. Aerobic rice is currently bred by crossing lowland with upland rice genotypes, for growth in an aerobic cultivation system, which is saving water and producing high yields. A Zn deficient clay soil was used in our screening. Zn deficiency resulted in a marked decrease in shoot dry matter production of most genotypes after 28 days of growth. Genotypes were ranked according to their tolerance to Zn deficiency based on ZE, expressed as the ratio of shoot dry weight at Zn deficiency over that at adequate Zn supply. Substantial genotypic variation in ZE (50–98%) was found among both lowland and aerobic genotypes. ZE correlated significantly (P < 0.05) with Zn uptake (R ² = 0.34), Zn translocation from root to shoot (R ² = 0.19) and shoot Zn concentration (R ² = 0.27). The correlation with seed Zn content was insignificant. In stepwise multiple regression analyses, variation in Zn uptake and Zn translocation explained 53% of variation in ZE. Variation in Zn uptake could be explained only for 32% by root surface area. These results indicate that Zn uptake may be an important determinant of ZE and that mechanisms other than root surface area are of major importance in determining Zn uptake by rice.     

Genetic control of avian scleroderma

The inheritance of avian scleroderma, a fibrotic autoimmune disease of chickens resembling human scleroderma, was investigated. Comb inflammations and lesions were used to determine the state of disease of 4-week-old chickens. All line 200 males and 60% of female line 200 chicks showed abnormalities. Crosses (F₄) between line 200 and eight partially inbred lines of chickens maintained at the University of California at Davis were all normal. Backcrosses of F, cocks to line 200 hens showed a higher incidence of scleroderma in males than in females for all lines. The incidence of affected birds varied between backcrosses from a low of 42% for backcross line 217 males derived from a New Hampshire line, to 88% for males of backcross line 213 derived from a partially inbred Leghorn line, demonstrating the presence of genes modifying the penetrance of presumed major genes causing the disease. Backcross genotypes segregating for haplotypes of the major histocompatibility complex (MHC) derived from inbred lines showed consistently lower penetrance of scleroderma than homozygotes carrying the line 200 haplotype. Thus B³ B^S (lines 211 and 215), B¹⁴Bu^s (line 217), and B¹⁵B^S (lines 212, 213, 216, and 218) all had fewer affected individuals than B^SB^S homozygotes from the same families.     

乙型肝炎病毒不同基因分型与淋巴细胞亚群分布、肝功能及脂代谢的关系

目的:探讨乙型肝炎病毒(HBV)不同基因分型与淋巴细胞亚群分布、肝功能及脂代谢的关系。方法:选择2016年10月-2017年12月在我院治疗的HBV患者130例,将患者进行HBV基因分型检查,根据不同基因分型将患者分为B型组(n=59)和C型组(n=71),采用实时荧光PCR法检测血清HBV-DNA载量,采用ADVIA2400全自动生化分析仪测定患者丙氨酸转氨酶(ALT)、白蛋白(ALB)、总胆红素(Tbil)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,采用美国ACL-TOP700血凝仪检测凝血酶原时间(PT)。采用流式细胞仪测定不同基因分型患者CD3~+、CD4~+、CD8~+及CD4~+/CD8~+水平。结果:两组患者HBV-DNA载量、PT比较差异无统计学意义(P0.05);B型组患者ALT、ALB、TbiL水平均低于C型组(P0.05)。B型组患者CD3~+、CD4~+、CD4~+/CD8~+水平均高于C型组,CD8~+水平低于C型组(P0.05)。两组患者TC、TG、HDL-C和LDL-C水平比较差异无统计学意义(P0.05)。结论:不同基因分型对HBV患者病毒复制能力及脂代谢无明显影响,但C型HBV对患者免疫功能及肝功能损伤更严重。     

Phenotypic and Genotypic Analysis of Rats with Cerebellar GABAA Receptors Composed from Mutant and Wild-Type α6 Subunits

Abstract: The alcohol-sensitive (ANT) rat line, developed for high behavioral sensitivity to ethanol, also exhibits enhanced sensitivity to benzodiazepines, such as diazepam. The rat line carries a point mutation in the cerebellum-specific γ-aminobutyric acid type A (GABA_A) receptor subunit α6, making their diazepam-insensitive (DIS) receptors sensitive to diazepam. We now report that phenotypes of individual ANT and alcohol-insensitive rats, classified on diazepam sensitivity of cerebellar [³H]Ro 15-4513 binding, correlated well with homozygous wild-type, homozygous mutant, and heterozygous genotypes, although some heterozygotes were biased toward the parental phenotypes. GABA down-modulated DIS [³H]Ro 15-4513 binding in mutant homozygotes but tended to up-modulate it in heterozygotes and wild-type homozygotes. Slopes for GABA inhibition of cerebellar t-butylbicyclophosphoro[³⁵S]thionate binding were larger in mutant than in wild-type homozygotes, with heterozygotes being intermediate. Diazepam displacement of [³H]Ro 15-4513 binding in heterozygotes revealed three components, with their affinities indistinguishable from those in combined wild-type and mutant homozygotes. This lack of interaction in DIS binding between wild-type and mutant α6 subunits was substantiated by experiments on recombinant receptors. The data suggest that the α6 subunit-containing GABA_A receptors in the heterozygotes are formed from individual mutant and wild-type subunits with their relative expression differing from animal to animal.     

WDTC1, the Ortholog of Drosophila Adipose Gene,Associates With Human Obesity,Modulated by MUFA Intake

Adipose (adp) is an obesity gene in Drosophila and mice with crucial functions in fat metabolism. We investigated the correlation between genetic variation of the WDTC1 locus, the ortholog of adp, and human obesity. Five WDTC1 single‐nucleotide polymorphisms (SNPs) were genotyped in 935 and 1,115 adults of two ethnically diverse US populations. In the Boston Puerto Rican population, we demonstrated that two WDTC1 SNPs strongly associated with obesity. Homozygote and heterozygote carriers of the major allele i22835A, representing ～96% of the population, had significantly higher mean BMI (31.5 and 31.0 kg/m², respectively) than noncarriers (28.6 kg/m²). Conversely, homozygotes of the minor allele i22835G were leaner and were 74% less likely to be overweight or obese (odds ratio (OR) = 0.26, P = 0.003) compared to homozygote carriers of the major allele. Haplotype analyses based on two SNPs further supported these findings. In addition, we found a strong interaction of monounsaturated fatty acid (MUFA) intake by genotype in this population. As dietary MUFA intake increased, minor allele carriers of SNP i22835A>G had higher BMIs, whereas major allele carriers had lower BMIs. A white population also exhibited a pattern of association between WDTC1 genotypes and obesity although of a different nature. Those WDTC1 variants which associated with obesity likely have experienced strong positive selection in human history, when food supply was unpredictable. Given the high frequency of the major alleles in both populations, we suggest that WDTC1 variation may be an important risk factor contributing to obesity in these populations.     

Developmental rates of heterozygous and homozygous rainbow trout reared at three temperatures

The hatching distributions of rainbow trout (Salmo gairdneri) with different genotypes at eight loci are compared in two experiments with the same strain. Embryos were incubated at temperatures colder (5 and 8°C) and warmer (12°C) than normally experienced by these fish (9.5°C). At hatching, embryos were separated into five hatching groups representing the chronological order of hatching. There is no significant correlation between multilocus heterozygosity and hatching time at any temperature in either experiment. Fish in the middle of the hatching distribution had the highest average heterozygosity. In both experiments, heterozygotes at the majority of loci examined tended to hatch relatively later within the hatching distribution at 12°C than at both 5 and 8°C. Fish with different genotypes atPgm2 andCk1 showed significant differences in hatching time that were consistent between experiments.Ck1 heterozygotes hatched sooner than homozygotes at 8°C but later at 12°C.Pgm2 heterozygotes hatched later than homozygotes at all temperatures and significantly later in four of five cases. At the other loci examined, however, the relative hatching distributions of fish with particular genotypes were not significantly different or repeatable between experiments.This research was supported by National Science Foundation Grant BSR-8300039 awarded to Dr. Fred W. Allendorf. Moira M. Ferguson was supported by a postgraduate scholarship from the Natural Sciences and Engineering Research Council of Canada.     

基于多光谱遥感影像的表层土壤有机质空间格局反演

利用多光谱LandSat TM遥感影像反演辽宁省阜新镇表层土壤有机质的空间格局,筛选出与土壤有机质分布相关的TM波段,分析并确定表层土壤有机质含量与TM1、TM2、TM3、TM4、TM5、TM6、TM7波段亮度值(digital number,DN)的相关关系,建立了土壤有机质含量的光谱预测模型.结果表明:研究区表层土壤有机质含量与TM4、TM5波段DN值呈极显著的负相关关系(r分别为-0.617和-0.623,P0.001),与TM3、TM5波段DN值之间满足负二次多项式回归关系(R2=0.9134,P0.001);基于TM3、TM5波段DN值的回归模型对研究区表层土壤有机质含量的预测结果可靠(R2=0.9151,P0.001).研究区表层土壤有机质含量10g·kg-1的农田主要分布在山地边缘地带,而平坦地区农田表层土壤有机质含量一般10g·kg-1,部分达到15～20g·kg-1.     

A resistin gene polymorphism is associated with body mass index in women

The potential association of resistin (RETN) gene variability with obesity-related phenotypes was investigated in 585 non-diabetic individuals of European descent. The polymorphism studied (–420 C>G) is located in the RETN gene 5-flanking region. A significant association between the polymorphism and body mass index and waist circumference was observed in the women subsample (n=356), where the G allele was somewhat less frequent in the overweight/obese group than in normal-weight individuals (0.25 vs. 0.32; p=0.040; OR=0.70 [0.50–0.98]). Female carriers of the G-allele presented a lower mean BMI than C/C homozygotes (25.5 vs. 26.8 kg/m²; p=0.010). Furthermore, when women were stratified by menopausal status, the association was restricted to premenopausal women (C/C homozygotes, mean BMI=26.3 kg/m²; G-carriers, 24.4 kg/m²; p=0.014). Our findings suggest that RETN gene variation has gender-specific effects on BMI and warrants further investigation of its implications for the development of obesity.     

Housing conditions and respiratory morbidity in Indigenous children in remote communities in Northwestern Ontario,Canada

Background:Rates of lower respiratory tract infection (LRTI) among First Nations (FN) children living in Canada are elevated. We aimed to quantify indoor environmental quality (IEQ) in the homes of FN children in isolated communities and evaluate any associations with respiratory morbidity.Methods:We performed a cross-sectional evaluation of 98 FN children (81 with complete data) aged 3 years or younger, living in 4 FN communities in the Sioux Lookout region of Northern Ontario. We performed medical chart reviews and administered questionnaires. We performed a housing inspection, including quantifying the interior surface area of mould (SAM). We monitored air quality for 5 days in each home and quantified the contaminant loading of settled floor dust, including endotoxin. We analyzed associations between IEQ variables and respiratory conditions using univariable and multivariable analyses.Results:Participants had a mean age of 1.6 years and 21% had been admitted to hospital for respiratory infections before age 2 years. Houses were generally crowded (mean occupancy 6.6 [standard deviation 2.6, range 3–17] people per house). Serious housing concerns were frequent, including a lack of functioning controlled ventilation. The mean SAM in the occupied space was 0.2 m². In multivariable modelling, there was evidence of an association of LRTI with log endotoxin (p = 0.07) and age (p = 0.02), and for upper respiratory tract infections, with SAM (p = 0.07) and age (p = 0.03). Wheeze with colds was associated with log endotoxin (p = 0.03) and age (p = 0.04).Interpretation:We observed poor housing conditions and an association between endotoxin and wheezing in young FN children living in Northern Ontario.

Young First Nations (FN) children in Canada have high rates of lower respiratory tract infections (LRTIs), including bronchiolitis and pneumonia, with 44 hospital admissions for LRTI per 1000 infants younger than 1 year living in the Sioux Lookout FN Health Authority (SLFNHA) region of northwestern Ontario, compared with 25 per 1000 in the general population, although rates are higher among Inuit infants in Nunavut (235 per 1000).^1,2Adverse respiratory health outcomes have been associated with poor indoor environmental quality (IEQ) worldwide.^3,4 Surveys have found that more than 24% of FN and Inuit housing is overcrowded or in need of major repairs or both, compared with 6% elsewhere in Canada.⁵ Issues related to IEQ are anecdotally reported to be common.^6,7 Few studies have quantified IEQ in FN housing, and most have focused on road-accessible communities.^8–11 We evaluated IEQ and respiratory morbidity in the homes of young children in 4 FN communities receiving health services from SLFNHA. Three communities were accessible only by air or winter road. We hypothesized that poor IEQ would be associated with respiratory morbidity in this population.     

Intrapopulation foraging niche variation between phenotypes and genotypes of Spirit bear populations

Foraging niche variation within a species can contribute to the maintenance of phenotypic diversity. The multiniche model posits that phenotypes occupying different niches can contribute to the maintenance of balanced polymorphisms. Using coastal populations of black bears (Ursus americanus kermodei) from British Columbia, Canada, we examined potential foraging niche divergence between phenotypes (black and white “Spirit” coat color) and between genotypes (black‐coated homozygote and heterozygous). We applied the Bayesian multivariate models, with biotracers of diet (δ¹³C and δ¹⁵N) together comprising the response variable, to draw inference about foraging niche variation. Variance–covariance matrices from multivariate linear mixed‐effect models were visualized as the Bayesian standard ellipses in δ¹³C and δ¹⁵N isotopic space to assess potential seasonal and annual niche variation between phenotypes and genotypes. We did not detect a difference in annual isotopic foraging niche area in comparisons between genotypes or phenotypes. Consistent with previous field experimental and isotopic analyses, however, we found that white phenotype Spirit bears were modestly more enriched in δ¹⁵N during the fall foraging season, though with our modest sample sizes these results were not significant. Although also not statistically significant, variation in isotopic niches between genotypes revealed that heterozygotes were moderately more enriched in δ¹³C along hair segments grown during fall foraging compared with black‐coated homozygotes. To the extent to which the pattern of elevated δ¹⁵N and δ¹³C may signal the consumption of salmon (Oncorhynchus spp.), as well as the influence of salmon consumption on reproductive fitness, these results suggest that black‐coated heterozygotes could have a minor selective advantage in the fall compared with black‐coated homozygotes. More broadly, our multivariate approach, coupled with knowledge of genetic variation underlying a polymorphic trait, provides new insight into the potential role of a multiniche mechanism in maintaining this rare morph of conservation priority in Canada''s Great Bear Rainforest and could offer new understanding into polymorphisms in other systems.     

Role of mannose binding lectin gene variants on its protein levels and macrophage phagocytosis with live Mycobacterium tuberculosis in pulmonary tuberculosis

Mannose-binding lectin (MBL) plays an important role in innate immunity. Functional mutant homozygotes of the MBL gene affect the serum MBL levels and have been correlated with disease susceptibility. We have studied the regulatory role of variant MBL genotypes on serum MBL level and macrophage phagocytosis with live Mycobacterium tuberculosis, and the lymphoproliferative response to M. tuberculosis culture filtrate antigen in pulmonary tuberculosis (PTB) patients (n = 48) and normal healthy subjects (NHS) (n = 58). The total serum MBL level was higher in PTB patients than in NHS (P = 0.0085). Patients and NHS with AA genotype (homozygotes of MBL - common alleles) showed a very high serum MBL level, and those with OO genotype (functional mutant homozygotes of MBL - less frequent alleles) showed a very low MBL level (AA vs. OO: NHS, P = 3.3 x 10(-9); PTB, P = 3.1 x 10(-9)). A significantly lower phagocytosis was observed in NHS with AA genotype than in NHS with AO (heterozygotes) genotype (P = 0.046). In PTB patients, no such difference was observed. A negative correlation of macrophage phagocytosis with MBL level was seen in patients and NHS (P = 0.019). Antigen-induced lymphoproliferative response was significantly decreased in PTB patients with AA genotype as compared with NHS with AA genotype (P = 0.036). The present study suggests that AA genotype with its associated higher serum MBL levels plays a regulatory role in immunity to tuberculosis than functional mutant homozygotes (OO genotype) with its associated lower level of MBL.     

Sprouting Resistance and Falling Number Values in Introgressive Triticale/T. Monococcum Lines

The aim of this work was to evaluate how the Falling Number (FN) in introgressive triticale lines is influenced by introduced Triticum monococcum genes responsive for mature spikes sprouting resistance (SR). These lines were developed in two independent series (A and B) by incorporating of diploid wheat (T. monococcum) genes in two different strains of hexaploid triticale (LT 176/10 and LT 522/6) using the synthetic allotetraploid T. monococcum/Secale cereale (A^mA^mRR) as a bridging form. In three consecutive vegetation seasons the mature spikes response to artificial wetting was tested to assess SR. FN was evaluated in full milling of seeds to characterize the level of starch-protein matrix damage in 57 introgressive triticale lines. The obtained results showed twofold higher coefficients of variation of the SR than FN. SR-FN correlation was generally significant in a B-series of lines and statistically insignificant in an A-series showing dependence on the triticale recipient parent and year. In opposite to SR, in both series there was not a line having FN comparable with that of diploid wheat parent. This demonstrates that genetic background of the FN is more complicated in relation to inheritance of SR. This revised version was published online in July 2006 with corrections to the Cover Date.     

The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case–control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p < 0.05). Leu/Met and Met/Met type 2 diabetics had significantly lower AER and Scr levels and higher eGFR level than Leu/Leu type 2 diabetics (all p < 0.001). The GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.