Genetic heterogeneity in five Italian regions: analysis of PAH mutations and minihaplotypes

Molecular analysis of 289 chromosomes has been performed in a cohort of phenylketonuria (PKU) patients whose ancestors lived in five Italian regions, Calabria, Campania, Piemonte, Puglia/Basilicata and Sicilia. Phenylalaninehydroxylase (PAH) gene mutations and minihaplotypes (combinations of PAH gene STR and VNTR systems) have been determined for 78.5 and 64%, respectively, of the chromosomes studied. 21 different minihaplotypes and 24 PKU mutations were found. Heterogeneity tests carried out for the frequencies of mutations and minihaplotypes show that the distribution of eight mutations and four minihaplotypes is statistically heterogeneous in the five Italian regions. Although the evolutionary rate of microsatellites or the age of these mutations is difficult to estimate with accuracy, our findings taken together show a genetic stratification of the Italian population. These results rule out allelic homogeneity of PKU at the molecular level between regions of Italy, yet minihaplotype data may be of practical use for a multistep approach to PAH gene genotyping.     

Detecting substitution-rate heterogeneity among regions of a nucleotide sequence

Likelihood-ratio statistics are proposed to test for heterogeneity in nucleotide substitution rate among regions of a DNA sequence. The tests examine three-sequence phylogenies, and two specific tests are proposed: a test to detect rate heterogeneity among genic regions within a sequence, over all evolutionary lineages; and a test to detect rate heterogeneity among regions in a specific evolutionary lineage. Simulations examine the ability of tests to detect a single region that varies in nucleotide substitution rate relative to the remainder of the sequence. A 50-bp region with a fivefold substitution-rate increase can be detected > or = 90% of the time when it is found in all three lineages of the phylogeny, and a 50-bp region of fivefold rate increase can be detected with approximately 70% power when it is found in only one evolutionary lineage. Simulation also examines the effect of transition- and transversion-rate differences. The tests are applied to published DNA sequences. While the tests are powerful, significant results can be difficult to interpret biologically.      

孕妇肥胖与死产关系的Meta分析

目的:探讨孕妇超重或肥胖与死产的关系。方法:采用RevMan4.2.10版本软件中的Meta分析,检索Pubmed文献数据库中1980年～2008年有关死产的孕妇超重或肥胖因素文献,并进行定量综合分析。结果:经检索、筛选后纳入的有关死产的孕妇超重或肥胖因素文献11篇;经异质性检验,采用固定效应模型、随机效应模型进行定量综合分析。综合结果表明孕妇超重、孕妇肥胖对死产的影响OR值分别为1.21(95%CI:1.05-1.40)、1.69(95%CI:1.51-1.90)。结论:孕妇因超重或肥胖的死产率明显高于正常体重孕妇。     

Maternal age and risk of stillbirth: a systematic review

Background

The number of women who delay childbirth to their late 30s and beyond has increased significantly over the past several decades. Studies regarding the relation between older maternal age and the risk of stillbirth have yielded inconsistent conclusions. In this systematic review we explored whether older maternal age is associated with an increased risk of stillbirth.

Methods

We searched MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews for all relevant articles (original studies and systematic reviews) published up to Dec. 31, 2006. We included all cohort and case–control studies that measured the association between maternal age and risk of stillbirth. Two reviewers independently abstracted data from all included studies using a standardized data abstraction form. Methodologic and statistical heterogeneities were reviewed and tested.

Results

We identified 913 unique citations, of which 31 retrospective cohort and 6 case–control studies met our inclusion criteria. In 24 (77%) of the 31 cohort studies and all 6 of the case–control studies, we found that greater maternal age was significantly associated with an increased risk of stillbirth; relative risks varied from 1.20 to 4.53 for older versus younger women. In the 14 studies that presented adjusted relative risk, we found no extensive change in the direction or magnitude of the relative risk after adjustment. We did not calculate a pooled relative risk because of the extreme methodologic heterogeneity among the individual studies.

Interpretation

Women with advanced maternal age have an increased risk of stillbirth. However, the magnitude and mechanisms of the increased risk are not clear, and prospective studies are warranted.Over the past several decades, economic, technologic and social changes in the developed world have significantly increased the number of women who delay childbirth to their late 30s and beyond. Between 1980 and 1993 in the European Union, the mean maternal age at first birth rose by 1.5 years, from 27.1 to 28.6 years.¹ Between 1991 and 2001 in the United States, the percentage of first births for women 35–39 years of age increased by 36% and that for women 40–44 years of age increased by 70%.^2,3 This huge demographic shift has become an important public health issue, since numerous studies have indicated that increased maternal age (35 years of age or older) is associated with an increased risk of maternal morbidity, obstetric interventions and adverse pregnancy outcomes.^4–11The intention to conceive and the timing of conception are complex issues influenced by many factors. Understanding the potential outcomes of pregnancy at an advanced maternal age may constitute one of these factors. Stillbirth, or late fetal death, is one of the adverse pregnancy outcomes of most concern, but studies on the relation between increased maternal age and stillbirth risk have led to inconsistent conclusions. We therefore conducted a systematic review of observational studies to explore the association between advanced maternal age and the risk of stillbirth.     

Trends in triplet stillbirth rates in Japan, 1975-1998.

Stillbirth rates of triplet births in the whole of Japan were analyzed using vital statistics from 1975 to 1998. Stillbirths were registered at 12 weeks gestation or later. The stillbirth rate was significantly higher in like- than in unlike-sex triplets for 1975-1998. During the 23-year period the stillbirth rate decreased from 342 to 49 per 1000 total births for like-sex and from 195 to 54 for unlike-sex triplets. The decrease in the stillbirth rate in the 23- year period was greater in both like- and unlike-sex triplets than in singleton and twin births. Risk factors for stillbirth in triplets were like-sex, youngest or oldest maternal age groups, shorter gestational age and lower birthweight. It is recommended that the optimum period to give birth for triplet pregnancies is 34-35 weeks of gestation for Japanese women.     

Genetic heterogeneity among isolates of Ross River virus from different geographical regions.

The RNase T1 maps of 80 isolates of Ross River virus from different regions of mainland Australia and the Pacific Islands were compared. Four different clusters of isolates with greater than an estimated 5 to 6% diversity at the nucleotide level were found. There was a pattern of differences between eastern and western Australian strains; however, the pattern was disturbed by overlaps and incursants. Pacific Islands isolates belonged to the eastern Australian topotype. Our findings suggest that certain genetic types of Ross River virus predominate in different geographical regions. In contrast, populations of other important Australian arboviruses (Murray Valley encephalitis, Kunjin, and Sindbis viruses) are distributed across the Australian continent as minor variants of one strain. Our data also show that in one region, strains of Ross River virus with identical RNase T1 maps circulate during both years when epidemics occur and years when they do not. This finding suggests that Ross River virus epidemics are not dependent on the introduction or evolution of new strains of the virus. Two strains, belonging to the eastern Australian topotype, were isolated in Western Australia. It is likely that viremic humans or possibly domestic livestock travelling by aircraft were responsible for this movement.     

Changes in the calcium current among different transmural regions contributes to action potential heterogeneity in rat heart

To clarify the transmural heterogeneity of action potential (AP) time course, we examined the regulation of L-type Ca²⁺ current (I_Ca,L) by voltage and Ca²⁺-dependent mechanisms. Currents were recorded using patch clamp of single rat subepicardial (EPI) and subendocardial (ENDO) of left ventricular, right ventricular (RV) and septal (SEP) cardiomyocytes. Voltage clamp commands were derived from ENDO and EPI APs or rectangular voltage pulses.During rectangular pulses, peak I_Ca,L was significantly greater in EPI than in other cells. The inactivation of I_Ca,L by Ca²⁺-dependent mechanisms (suppressed by ryanodine and BAPTA) was present in all cells but greater in extent in ENDO and SEP cells. Activation and inactivation curves for all regions show subtle differences that are Ca²⁺ sensitive, with Ca²⁺ inactivation shifting the activation variables negative by ∼ 7 mV and inactivation variables positive by 2-7 mV (EPI being least, RV greatest). In AP-clamps, the peak I_Ca,L was significantly smaller in ENDO than in EPI cells, while the integrated current was significantly larger in ENDO than in EPI cells. The results are discussed with regard to the interplay of AP time course and net Ca²⁺ influx.     

Sow-level risk factors for stillbirth of piglets in organic sow herds

In Danish organic pig production, one-third of total born piglets die before weaning, and stillbirth has previously crudely been estimated to account for 27% of the total preweaning mortality. The objective of this study was to evaluate season, litter size, parity and body condition of the sow as risk factors for stillbirth in nine commercial Danish organic pig herds. The study was conducted over a 1-year period, and the data included registrations on 5170 farrowings with 82 906 total born piglets. The average number of total born piglets per litter was 16.0, and the number of stillborn piglets per litter was 1.1. A significant effect of season was seen with an odds ratio for stillbirth of 1.15 during summer (May to August) compared with the remaining part of the year. A non-linear effect of litter size was seen where an increase in litter size from 11 to 16 resulted in an odds ratio of stillbirth of 1.11. An increase in litter size from 16 to 21 resulted in an odds ratio of stillbirth of 1.45. A significant interaction between body condition and parity was present. In first parity sows, an increase in body condition score from 2 (thin) to 3 (moderate) and from 3 to 4 (fat) increased the probability of stillbirth with an odds ratio of 1.23 and 1.36, respectively. In sows with parity above 4, an increase in body condition score from 2 to 3 and from 3 to 4 decreases the probability of stillbirth with an odds ratio of 0.68 and 0.79, respectively. In conclusion, increasing litter size and being born during the summer months of May to August were found to be risk factors for stillbirth. Furthermore, an interaction between body condition and parity showed that thin sows with parity above 4 had a substantially increased risk of stillbirth compared with normal and fat sows with parity above 4. In contrast, for parity 1 sows risk of stillbirth was increased in fat sows.     

岩溶山区水分时空异质性及植物适应机理研究进展

西南岩溶地区虽然降水充沛,但因具有二元水文结构,地表水大量渗漏、地下水深埋,加上土层浅薄且分布不连续、土壤储水能力低,岩溶干旱严重,水分亏缺仍然是植被恢复重建的关键限制因子。如何有效地进行植被的恢复重建和实现水土资源的协调利用,是该地区石漠化综合治理面临的主要难题。由于地质背景的特殊性、地形地貌的复杂性和生境的高度异质性,岩溶山区水分运移过程与其他类型区显著不同,亟需综合考虑岩性、地形地貌、土壤与岩石分布、植被等因素的影响。在简要介绍岩溶山区土壤-岩石环境特征的基础上,综述了降雨入渗产流规律、水分时空异质性、植物水分来源及适应机理等几个方面的研究进展,探讨了当前研究中存在的问题,并对未来研究进行了展望。今后应以大气-植被-土壤-岩石系统为研究对象,将水分运移过程与植物的水分利用方式有机结合,综合运用土壤物理学、生态水文学、植物生理学、岩溶地质学等多学科研究手段,探讨表层岩溶带的水文调节功能及其主要影响因素,揭示坡面、小流域尺度植被与水文过程的相互作用机理,为西南岩溶山区水源涵养型植物群落的优化配置提供科学依据。     

Evolutionary rate heterogeneity in proteins with long disordered regions

The dominant view in protein science is that a three-dimensional (3-D) structure is a prerequisite for protein function. In contrast to this dominant view, there are many counterexample proteins that fail to fold into a 3-D structure, or that have local regions that fail to fold, and yet carry out function. Protein without fixed 3-D structure is called intrinsically disordered. Motivated by anecdotal accounts of higher rates of sequence evolution in disordered protein than in ordered protein we are exploring the molecular evolution of disordered proteins. To test whether disordered protein evolves more rapidly than ordered protein, pairwise genetic distances were compared between the ordered and the disordered regions of 26 protein families having at least one member with a structurally characterized region of disorder of 30 or more consecutive residues. For five families, there were no significant differences in pairwise genetic distances between ordered and disordered sequences. The disordered region evolved significantly more rapidly than the ordered region for 19 of the 26 families. The functions of these disordered regions are diverse, including binding sites for protein, DNA, or RNA and also including flexible linkers. The functions of some of these regions are unknown. The disordered regions evolved significantly more slowly than the ordered regions for the two remaining families. The functions of these more slowly evolving disordered regions include sites for DNA binding. More work is needed to understand the underlying causes of the variability in the evolutionary rates of intrinsically ordered and disordered protein.     

Urban faecal pollution and parasitic risk: the Italian skill

Owing to the recent emergency of urban faecal pollution it is important to point out new strategies in order to fight the problem starting with the knowledge of past experiences. A punctual chronography of the different approach (telluric, coprological--zoonotic and phenomenological) was attempted to furnish a scientific base for future, modern approach.     

Spectral heterogeneity in protein fluorescence of bacteriorhodopsin: evidence for intraprotein aqueous regions

By the use of derivative spectral analysis, the broad tryptophan (Trp) fluorescence emission from aqueous suspensions of bacteriorhodopsin in its native purple membrane may be resolved into contributions from buried, surface, and exposed residues. Addition of glycerol produces a progressive enhancement of the fluorescence yield to a limiting value at about 70% v/v glycerol. Glycerol enhancement of fluorescence is also observed for monomeric Trp, and a good correlation exists between this effect and literature estimates of the fractional degree of Trp exposure in nine globular proteins. The estimate of fractional Trp exposure in bacteriorhodopsin from this correlation (50 +/- 15%) is in agreement with the value obtained by spectral differentiation and also by modified Stern-Volmer curves for quenching by water-soluble acrylamide. The absence of significant quenching by Tb(III) or Eu(III) ions, which may be expected to bind to the purple membrane surface, shows that the exposed Trp residues are in contact with water in intraprotein regions of the membrane and may be the first direct evidence for a transmembrane aqueous channel by which protons are actively transported during the bacteriorhodopsin photochemical cycle.     

Soil nitrogen and carbon heterogeneity in woodlands and grasslands: contrasts between temperate and tropical regions

Aim  Soil resource heterogeneity is linked to several ecological processes including invasion of woody species into grasslands. Studies from the temperate zone have demonstrated greater soil heterogeneity beneath woody vegetation than beneath grasslands. Woody species have a more widespread and coarser root system than herbaceous species, and may have a competitive advantage in relatively heterogeneous soils. We tested the global generality of greater soil heterogeneity beneath woody vegetation.
Location  Global.
Methods  We used data from published literature for soil nitrogen and carbon heterogeneity from paired woodland and grassland sites around the world.
Results  Woodland and grassland soil heterogeneities from paired observations were strongly correlated. There was, however, significant geographical variability in the relationship. Soils were more heterogeneous in woodlands than grasslands in temperate areas, but the opposite was true for tropical habitats. Grassland soils were more heterogeneous at lower than higher latitudes. Woodland soil heterogeneity did not vary with latitude.
Main conclusions  The previously described high soil heterogeneity in woody vegetation compared to grasslands holds only for temperate regions. Consequently, the relationship between soil resource heterogeneity and vegetation type is dependent on the study region. Macroecological studies should test the generality of relationships between soil and vegetation at the global scale.     

Genomic heterogeneity in Chlorobium limicola: chromosomic and plasmidic differences among strains

Abstract The purpose of this study is to certify the importance of the fimbriae as an attachment factor of Actinobacillus actinomycetemcomitans , a human periodontopathic bacterium, and the significance of anti-fimbrial antibody function as an attachment inhibitor. Fimbrial antigen was prepared from the A. actinomycetemcomitans 310-a strain. Oligopeptides were synthesized according to the amino acid sequence of the fimbrial protein. The peptide antigen was conjugated with branched lysine polymer resin beads. The peptide antigen was suspended in PBS emulsified with incomplete Freund's adjuvant and used to immunize rabbits. A rabbit antiserum reacted with an approximately 54 kDa protein of the fimbriae protein from A. actinomycetemcomitans 310-a and with those of other fimbriated strains. This antiserum strongly inhibited the attachment of fimbriated A. actinomycetemcomitans strains to saliva-coated hydroxyapatite beads, buccal epithelial cells, and a fibroblast cell line, Gin-1. Such a synthetic fimbrial peptide antigen may be effective in inducing antibodies which inhibit adhesion and subsequent colonization by A. actinomycetemcomitans .     

Microsite heterogeneity in litterfall risk to seedlings

Abstract Litterfall is an important cause of damage and mortality to seedlings in many forest ecosystems. This study is the first to investigate the contribution of variable risk of litterfall damage to microsite heterogeneity. Two hundred artificial seedlings were ‘planted’ in the ground at 2‐m intervals along transects in each of two New Zealand forests, and all plant species with foliage directly above each artificial seedling were recorded. Additional artificial seedlings were planted on the ground underneath treeferns and on their trunks (epiphytically). The artificial seedlings were monitored monthly for damage over 2 years. Three overtopping species that cause litterfall damage, along with one species that impedes litterfall, produced different microsites with a hierarchy of litterfall damage risk to seedlings (2–30% per year). This risk differed significantly among microsites (P < 0.0005). Seedlings differ in resilience to litterfall and, therefore, microsites with different litterfall risks provided the potential for regeneration niche differentiation. More seedlings were damaged beneath Cyathea dealbata (Cyatheaceae), which drops whole fronds, than on its trunks. The reverse was found for Dicksonia fibrosa (Dicksoniaceae), which retains dead fronds as a ‘skirt’. We suggest that shedding whole fronds, or producing a skirt of fronds, are alternative ‘strategies’ that can reduce competition from terrestrial and epiphytic seedlings, respectively.     

Prevalence and risk factors of schistosomiasis among primary school children in four selected regions of The Gambia

BackgroundThe Gambia initiated a control programme for schistosomiasis in 2015. In light of this, recent and comprehensive data on schistosomiasis is required to effectively guide the control programme. This study aimed to evaluate the prevalence and associated risk factors of schistosomiasis among primary school children in The Gambia.MethodsWe utilised data from a previous study conducted in 2015 in 4 regions of The Gambia: North Bank Region (NBR), Lower River Region (LRR), Central River Region (CRR) and Upper River Region (URR). In the parent study, ten schools were selected randomly from each region. Urine and stool samples collected from 25 boys and 25 girls (7–14 years) in each school were examined for urinary schistosomiasis (Schistosoma haematobium infection) and intestinal schistosomiasis (Schistosoma mansoni infection) using urine filtration, dipstick and Kato-Katz methods.Principal findingsUrinary schistosomiasis had an overall prevalence of 10.2% while intestinal schistosomiasis had a prevalence of 0.3% among the sampled school children. Prevalence of urinary schistosomiasis was significantly different among regions (χ 2 = 279.958, df = 3, p < 0.001), with CRR (27.6%) being the most endemic region, followed by URR (12.0%), then LRR (0.6%), and NBR (0.0%). Prevalence of intestinal schistosomiasis was also significantly variable among regions, with 4 of the 5 positive cases detected in CRR and 1 case in URR. Every school sampled in CRR had at least one student infected with S. haematobium, 50% of schools in URR had S. haematobium infection, and just one school in LRR had S. haematobium infection. While S. haematobium infection was significantly higher in boys (χ 2 = 4.440, df = 1, p = 0.035), no significant difference in infection rate was observed among age groups (χ 2 = 0.882, df = 2, p = 0.643). Two of the 5 students infected with S. mansoni were boys and 3 were girls. Four of these 5 students were in the 10–12 years age group and 1 was in the 7–9 years age group. Macrohaematuria and microhaematuria were found to be statistically associated with presence of S. haematobium eggs in urine. Being a male was a risk factor of S. haematobium infection. Bathing, playing and swimming in water bodies were found to pose less risk for S. haematobium infection, indicating that the true water contact behaviour of children was possibly underrepresented.ConclusionThe findings of this study provide invaluable information on the prevalence of schistosomiasis in The Gambia. This was useful for the schistosomiasis control efforts of the country, as it guided mass drug administration campaigns in eligible districts in the study area. More studies on S. mansoni and its intermediate snail hosts are required to establish its true status in The Gambia. As children sometimes tend to provide responses that potentially please the research or their teacher, data collection frameworks and approaches that ensure true responses in studies involving children should be devised and used.     

Galactosialidosis: molecular heterogeneity among distinct clinical phenotypes.

The lysosomal storage disorder galactosialidosis has been recognized as a distinct genetic and biochemical entity, associated with a combined beta-galactosidase and neuraminidase deficiency that is due to the lack of a 32-kilodalton (kDa) glycoprotein. The molecular basis of different clinical variants of galactosialidosis has been investigated. In the early-infantile form, the synthesis of the 52-kDa precursor of the 32-kDa "protective protein" is markedly reduced and the absence of the latter protein explains the severe neuraminidase deficiency. In the juvenile-adult form, there is relatively more 52-kDa precursor but no 32-kDa protein can be detected. Cells from the late-infantile form have in comparison with controls, besides a small amount of the 32-kDa glycoprotein, an accumulation of the 52-kDa precursor. Apparently, this protein is genetically altered in such a way that its further processing is impaired. Furthermore, in this mutant, the residual neuraminidase activity is stimulated four- to sixfold upon leupeptin treatment together with an increase of the 32-kDa glycoprotein.