Consanguinity and susceptibility to infectious diseases in humans

Studies of animal populations suggest that low genetic heterozygosity is an important risk factor for infection by a diverse range of pathogens, but relatively little research has looked to see whether similar patterns exist in humans. We have used microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increases risk of infection. Our results indicate that inbred individuals are more common among our infected cases for TB and hepatitis, but only in populations where consanguineous marriages are common. No effect was found either for leprosy, which is thought to be oligogenic, or for hepatitis in Italy where consanguineous marriages are rare. Our results suggest that consanguinity is an important risk factor in susceptibility to infectious diseases in humans.     

Population genomics of the inbred Scandinavian wolf

The Scandinavian wolf population represents one of the genetically most well-characterized examples of a severely bottlenecked natural population (with only two founders), and of how the addition of new genetic material (one immigrant) can at least temporarily provide a 'genetic rescue'. However, inbreeding depression has been observed in this population and in the absence of additional immigrants, its long-term viability is questioned. To study the effects of inbreeding and selection on genomic diversity, we performed a genomic scan with approximately 250 microsatellite markers distributed across all autosomes and the X chromosome. We found linkage disequilibrium (LD) that extended up to distances of 50 Mb, exceeding that of most outbreeding species studied thus far. LD was particularly pronounced on the X chromosome. Overall levels of observed genomic heterozygosity did not deviate significantly from simulations based on known population history, giving no support for a general selection for heterozygotes. However, we found evidence supporting balancing selection at a number of loci and also evidence suggesting directional selection at other loci. For markers on chromosome 23, the signal of selection was particularly strong, indicating that purifying selection against deleterious alleles may have occurred even in this very small population. These data suggest that population genomics allows the exploration of the effects of neutral and non-neutral evolution on a finer scale than what has previously been possible.     

Alanine substitutions of noncysteine residues in the cysteine‐stabilized αβ motif

The protein scaffold is a peptide framework with a high tolerance of residue modifications. The cysteine‐stabilized αβ motif (CSαβ) consists of an α‐helix and an antiparallel triple‐stranded β‐sheet connected by two disulfide bridges. Proteins containing this motif share low sequence identity but high structural similarity and has been suggested as a good scaffold for protein engineering. The Vigna radiate defensin 1 (VrD1), a plant defensin, serves here as a model protein to probe the amino acid tolerance of CSαβ motif. A systematic alanine substitution is performed on the VrD1. The key residues governing the inhibitory function and structure stability are monitored. Thirty‐two of 46 residue positions of VrD1 are altered by site‐directed mutagenesis techniques. The circular dichroism spectrum, intrinsic fluorescence spectrum, and chemical denaturation are used to analyze the conformation and structural stability of proteins. The secondary structures were highly tolerant to the amino acid substitutions; however, the protein stabilities were varied for each mutant. Many mutants, although they maintained their conformations, altered their inhibitory function significantly. In this study, we reported the first alanine scan on the plant defensin containing the CSαβ motif. The information is valuable to the scaffold with the CSαβ motif and protein engineering.     

A novel solid phase approach to Aia‐containing peptides

A strategy was developed to directly assemble 4‐amino‐1,2,4,5‐tetrahydro‐indolo[2,3‐c]‐azepin‐3‐ones on solid‐phase‐supported peptide sequences. Fmoc‐ and Boc‐based strategies were investigated. The Fmoc‐strategy approach strongly depends on the peptide sequence being synthesized while the Boc‐based synthesis leads to excellent results for all the selected peptide analogs. The method was applied to prepare Aia‐analogs of several bioactive peptides containing one or more Trp‐residues which were shown to be important for biological recognition. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.     

脑梗死后智能障碍影响因素分析

目的 探讨影响脑梗死后智能障碍的因素。方法 应用长谷川痴呆量表对249例经CT证实的脑梗死患者进行智能测评,评分0～21．5为智能障碍组,22～32．5为正常组,探讨智能障碍的发生与性别、年龄、文化程度、卒中主要危险因素(高血压和糖尿病)、梗死灶数量及体积,以及脑萎缩和脑白质疏松之间的相互关系．结果 249例脑梗死患者中有106例(42．6％)出现智能障碍．并发现年龄、性别、文化程度、高血压病、糖尿病与智能障碍的发生有关;梗死灶的数量越多、体积越大其智能障碍发生率越高;脑萎缩及脑白质疏松与智能障碍关系密切．结论 脑梗死后智能障碍是多因素相互作用的结果,与梗死灶数量、体积、脑萎缩及脑白质疏松等多种因素有关．     

Scintigraphie de perfusion cérébrale positionnelle : résultats physiologiques et applications cliniques

To assess the impact of standing on brain perfusion, 125 brain perfusion scans in the upright and supine position were performed, including 108 patients. Perfusion values were compared using a relative quantitative approach and a segmentation of vascular territories with the help of an atlas of brain perfusion. We found a change in the distribution of the perfusion in favor of the vertebro-basilar system in the upright position. We discuss the case of a patient whose symptoms could be explained with the help of the comparison of brain perfusion scans in the upright and supine position. Atheromatous and post-dissection stenosis and their influence on perfusion are also discussed.     

A single-nucleotide polymorphism in tumor necrosis factor-α (− 308 G/A) as a biomarker in chronic pancreatitis

Objective

Chronic pancreatitis is a gradual, long-term inflammation of the pancreas that results in alteration of its normal structure and function. The study aims to investigate the role of − 308 (G/A) polymorphism of TNF-α gene in chronic pancreatitis.

Material and methods

A total of 200 subjects were included in this case–control study. A total of 100 in patients admitted in the Gastroenterology Unit of Gandhi Hospital and Osmania General Hospital, Hyderabad were included in the present study. An equal number of healthy control subjects were randomly selected for the study. The genotyping of TNF-α gene was carried out by tetra-primer ARMS PCR followed by gel electrophoresis. The TNF-α levels were assayed by enzyme-linked immunosorbent assay.

Results

A significant variation with respect to the genotypic and allelic distribution in the disease group when compared to control subjects [OR = 2.001 (1.33–3.005), p < 0.0001**] was observed. Subjects homozygous for the A allele had higher TNF-α levels compared to G allele.

Conclusion

The present study revealed a significant association of the TNF-α gene promoter polymorphism with chronic pancreatitis. Thus, TNF-α genotype can be considered as one of the biological markers in the etiology of chronic pancreatitis.     

A heterogeneous thermal environment enables remarkable behavioral thermoregulation in Uta stansburiana

Ectotherms can attain preferred body temperatures by selecting specific temperature microhabitats within a varied thermal environment. The side‐blotched lizard, Uta stansburiana may employ microhabitat selection to thermoregulate behaviorally. It is unknown to what degree habitat structural complexity provides thermal microhabitats for thermoregulation. Thermal microhabitat structure, lizard temperature, and substrate preference were simultaneously evaluated using thermal imaging. A broad range of microhabitat temperatures was available (mean range of 11°C within 1–2 m²) while mean lizard temperature was between 36°C and 38°C. Lizards selected sites that differed significantly from the mean environmental temperature, indicating behavioral thermoregulation, and maintained a temperature significantly above that of their perch (mean difference of 2.6°C). Uta's thermoregulatory potential within a complex thermal microhabitat structure suggests that a warming trend may prove advantageous, rather than detrimental for this population.     

Outlier SNP markers reveal fine‐scale genetic structuring across European hake populations (Merluccius merluccius)

Shallow population structure is generally reported for most marine fish and explained as a consequence of high dispersal, connectivity and large population size. Targeted gene analyses and more recently genome‐wide studies have challenged such view, suggesting that adaptive divergence might occur even when neutral markers provide genetic homogeneity across populations. Here, 381 SNPs located in transcribed regions were used to assess large‐ and fine‐scale population structure in the European hake (Merluccius merluccius), a widely distributed demersal species of high priority for the European fishery. Analysis of 850 individuals from 19 locations across the entire distribution range showed evidence for several outlier loci, with significantly higher resolving power. While 299 putatively neutral SNPs confirmed the genetic break between basins (F_CT = 0.016) and weak differentiation within basins, outlier loci revealed a dramatic divergence between Atlantic and Mediterranean populations (F_CT range 0.275–0.705) and fine‐scale significant population structure. Outlier loci separated North Sea and Northern Portugal populations from all other Atlantic samples and revealed a strong differentiation among Western, Central and Eastern Mediterranean geographical samples. Significant correlation of allele frequencies at outlier loci with seawater surface temperature and salinity supported the hypothesis that populations might be adapted to local conditions. Such evidence highlights the importance of integrating information from neutral and adaptive evolutionary patterns towards a better assessment of genetic diversity. Accordingly, the generated outlier SNP data could be used for tackling illegal practices in hake fishing and commercialization as well as to develop explicit spatial models for defining management units and stock boundaries.