Nucleotide polymorphism at the alcohol dehydrogenase locus of pocket gophers, genus Geomys

Using the strictly neutral model as a null hypothesis, we tested for deviations from expected levels of nucleotide polymorphism at the alcohol dehydrogenase locus (Adh-1) within and among four species of pocket gophers (Geomys bursarius major, G. knoxjonesi, G. texensis llanensis, and G. attwateri). The complete protein-encoding region was examined, and 10 unique alleles, representing both electromorphic and cryptic alleles, were used to test hypotheses (e.g., the neutral model) concerning the maintenance of genetic variation. Nineteen variable sites were identified among the 10 alleles examined, including 9 segregating sites occurring in synonymous positions and 10 that were nonsynonymous. Several statistical methods, including those that test for within-species variation as well as those that examine variation within and among species, failed to reject the null hypothesis that variation (both within and between species of Geomys) at the Adh locus is consistent with the neutral theory. However, there was significant heterogeneity in the ratio of polymorphism to divergence across the gene, with polymorphisms clustered in the first half of the coding region and fixed differences clustered in the second half of the gene. Two alternative hypotheses are discussed as possible explanations for this heterogeneity: an old balanced polymorphism in the first half of the gene or a recent selective sweep in the second half of the gene.      

EGF-stimulation activates the nuclear localization signal of SHP-1

Protein tyrosine phosphatase SHP-1 plays a critical role in the regulation of a variety of intracellular signaling pathways. SHP-1 is predominantly expressed in the cells of hematopoietic origin, and is recognized as a negative regulator of lymphocyte development and activation. SHP-1 consists of two Src homology 2 (SH2) domains and one protein tyrosine phosphatase (PTP) domain followed by a highly basic C-terminal tail containing tyrosyl phosphorylation sites. It is unclear how the C-terminal tail regulates SHP-1 function. We report the examination of the subcellular localization of a variety of truncated or mutated SHP-1 proteins fused with enhanced green fluorescent protein (EGFP) protein at either the N-terminal or the C-terminal end in different cell lines. Our data demonstrate that a nuclear localization signal (NLS) is located in the C-terminal tail of SHP-1 and the signal is primarily defined by three amino-acid residues (KRK) at the C-terminus. This signal is generally blocked in the native protein and can be exposed by fusing EGFP at the appropriate position or by domain truncation. We have also revealed that this NLS of SHP-1 is triggered by epidermal growth factor (EGF) stimulation and mediates translocation of SHP-1 from the cytosol to the nucleus in COS7 cell lines. These results not only demonstrate the importance of the C-terminal tail of SHP-1 in the regulation of nuclear localization, but also provide insights into its role in SHP-1-involved signal transduction pathways.     

The use of zootherapeutics in folk veterinary medicine in the district of Cubati, Paraíba State, Brazil

Background

Viewed through the micro focus of an interpretive lens, medical anthropology remains mystified because interpretivist explanations seriously downplay the given context in which individual health seeking-behaviours occur. This paper draws upon both the interpretivist and political economy perspectives to reflect on the ethno medical practices within the Korean-Australian community in Sydney.

Methods

We draw on research data collected between 1995 and 1997 for an earlier study of the use of biomedical and traditional medicine by Korean-Australians in Sydney. A total of 120 interviews were conducted with a range of participants, including biomedical doctors, traditional health professionals, Korean community leaders and Korean migrants representing a range of socio-economic backgrounds and migration patterns.

Results and Discussion

First, the paper highlights the extent to which the social location of migrants in a host society alters or restructures their initial cultural practices they bring with them. Second, taking hanbang medicine in the Korean-Australian community as an illustrative case, the paper explores the transformation of the dominant biomedicine in Australia as a result of the influx of ethnomedicine in the era of global capitalism and global movement.

Conclusion

In seeking to explain the popularity and supply of alternative health care, it is important to go beyond the culture of each kind of health care itself and to take into consideration the changes occurring at societal, national and global levels as well as consequential individual response to the changes. New social conditions influence the choice of health care methods, including herbal/alternative medicine, health foods and what are often called New Age therapies.     

Segregation Analysis of Body Mass Index in an Unselected French-Canadian Sample: The Québec Family Study

Interest in a single gene etiology for obesity, as assessed by the body mass index (BMI), has been spurred recently by reports of a putative recessive major gene for extreme values, which accounts for as much as 40% of the variance. The major gene hypothesis was evaluated here in the Québec Family Study, a random sample of 375 French-Canadian volunteer families. This report represents one component in a more complete investigation of obesity in these families. In contrast to the recent studies, a major gene hypothesis for BMI was not verified here. Although there was a major effect, it did not conform to a Mendelian pattern of transmission. A multifactorial component (i.e., polygenic and/or common environmental factors) accounted for 42% of the phenotypic variance. In addition, evidence of heterogeneity between the generations was found. The heterogeneity was traced to the major non-Mendelian component (which accounted for 0.01% of the variance in parents and over 40% in offspring) rather than to the multifactorial one. These results would suggest that a simple recessive gene mixed model may not be sufficient to explain the familial distribution of the BMI. Several factors which may have contributed to these results include temporal trends and surrogate effects such as those related to variation in body composition and energy balance components. (OBESITY RESEARCH 1993; 1:288–294)     

Bias Assessment of General Chemistry Analytes using Commutable Samples

Harmonisation of reference intervals for routine general chemistry analytes has been a goal for many years. Analytical bias may prevent this harmonisation. To determine if analytical bias is present when comparing methods, the use of commutable samples, or samples that have the same properties as the clinical samples routinely analysed, should be used as reference samples to eliminate the possibility of matrix effect. The use of commutable samples has improved the identification of unacceptable analytical performance in the Netherlands and Spain. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has undertaken a pilot study using commutable samples in an attempt to determine not only country specific reference intervals but to make them comparable between countries. Australia and New Zealand, through the Australasian Association of Clinical Biochemists (AACB), have also undertaken an assessment of analytical bias using commutable samples and determined that of the 27 general chemistry analytes studied, 19 showed sufficiently small between method biases as to not prevent harmonisation of reference intervals. Application of evidence based approaches including the determination of analytical bias using commutable material is necessary when seeking to harmonise reference intervals.     

The cervical microbiome over 7 years and a comparison of methodologies for its characterization

Background

The rapidly expanding field of microbiome studies offers investigators a large choice of methods for each step in the process of determining the microorganisms in a sample. The human cervicovaginal microbiome affects female reproductive health, susceptibility to and natural history of many sexually transmitted infections, including human papillomavirus (HPV). At present, long-term behavior of the cervical microbiome in early sexual life is poorly understood.

Methods

The V6 and V6–V9 regions of the 16S ribosomal RNA gene were amplified from DNA isolated from exfoliated cervical cells. Specimens from 10 women participating in the Natural History Study of HPV in Guanacaste, Costa Rica were sampled successively over a period of 5–7 years. We sequenced amplicons using 3 different platforms (Sanger, Roche 454, and Illumina HiSeq 2000) and analyzed sequences using pipelines based on 3 different classification algorithms (usearch, RDP Classifier, and pplacer).

Results

Usearch and pplacer provided consistent microbiome classifications for all sequencing methods, whereas RDP Classifier deviated significantly when characterizing Illumina reads. Comparing across sequencing platforms indicated 7%–41% of the reads were reclassified, while comparing across software pipelines reclassified up to 32% of the reads. Variability in classification was shown not to be due to a difference in read lengths. Six cervical microbiome community types were observed and are characterized by a predominance of either G. vaginalis or Lactobacillus spp. Over the 5–7 year period, subjects displayed fluctuation between community types. A PERMANOVA analysis on pairwise Kantorovich-Rubinstein distances between the microbiota of all samples yielded an F-test ratio of 2.86 (p<0.01), indicating a significant difference comparing within and between subjects’ microbiota.

Conclusions

Amplification and sequencing methods affected the characterization of the microbiome more than classification algorithms. Pplacer and usearch performed consistently with all sequencing methods. The analyses identified 6 community types consistent with those previously reported. The long-term behavior of the cervical microbiome indicated that fluctuations were subject dependent.     

Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer

Background

Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer.

Methodology/Principal Findings

We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P _trend<0.0001), and RPS19 rs2305809 (P _trend=0.0007), respectively. Both SNPs were also associated with progression.

Conclusions/Significance

These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.     

A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement

Cells polarize their movement or growth toward external directional cues in many different contexts. For example, budding yeast cells grow toward potential mating partners in response to pheromone gradients. Directed growth is controlled by polarity factors that assemble into clusters at the cell membrane. The clusters assemble, disassemble, and move between different regions of the membrane before eventually forming a stable polarity site directed toward the pheromone source. Pathways that regulate clustering have been identified but the molecular mechanisms that regulate cluster mobility are not well understood. To gain insight into the contribution of chemical noise to cluster behavior we simulated clustering using the reaction-diffusion master equation (RDME) framework to account for molecular-level fluctuations. RDME simulations are a computationally efficient approximation, but their results can diverge from the underlying microscopic dynamics. We implemented novel concentration-dependent rate constants that improved the accuracy of RDME-based simulations, allowing us to efficiently investigate how cluster dynamics might be regulated. Molecular noise was effective in relocating clusters when the clusters contained low numbers of limiting polarity factors, and when Cdc42, the central polarity regulator, exhibited short dwell times at the polarity site. Cluster stabilization occurred when abundances or binding rates were altered to either lengthen dwell times or increase the number of polarity molecules in the cluster. We validated key results using full 3D particle-based simulations. Understanding the mechanisms cells use to regulate the dynamics of polarity clusters should provide insights into how cells dynamically track external directional cues.