Origin of the Koreans: a population genetic study.

A population genetic study was undertaken to investigate the origin of Koreans. Thirteen polymorphic and 7 monomorphic blood genetic markers (serum proteins and red cell enzymes) were studied in a group of 437 Koreans. Genetic distance analyses by both cluster and principal components models were performed between Koreans and eight other populations (Koreans in China, Japanese, Han Chinese, Mongolians, Zhuangs, Malays, Javanese, and Soviet Asians) on the basis of 47 alleles controlled by 15 polymorphic loci. A more detailed analysis using 65 alleles at 19 polymorphic loci was performed on six populations. Both analyses demonstrated genetic evidence of the origin of Koreans from the central Asian Mongolians. Further, the Koreans are more closely related to the Japanese and quite distant from the Chinese. The above evidence of the origin of Koreans fits well with the ethnohistoric account of the origin of Koreans and the Korean language. The minority Koreans in China also maintained their genetic identity.     

Interplay between hydrophobic cluster and loop propensity in beta-hairpin formation: a mechanistic study

We investigated the structural determinants of the stability of a designed beta-hairpin containing a natural hydrophobic cluster from the protein GB1 and a D-Pro-Gly turn forming sequence. The results of our simulations shed light on the factors leading to an ordered secondary structure in a model peptide: in particular, the importance of the so-called diagonal interactions in forming a stable hydrophobic nucleus in the beta-hairpin, together with the more obvious lateral interactions, is examined. With the use of long timescale MD simulations in explicit water, we show the role of diagonal interactions in driving the peptide to the correct folded structure (formation of the hydrophobic core with Trp 2, Tyr 4, and Phe 9 in the first stages of refolding) and in keeping it in the ensemble of folded conformations. The combination of the stabilizing effects of the D-Pro-Gly turn sequence and of the hydrophobic nucleus formation thus favors the attainment of an ordered secondary structure compatible with the one determined experimentally. Moreover, our data underline the importance of the juxtapositions of the side chains of amino acids not directly facing each other in the three-dimensional structure. The combination of these interactions forces the peptide to sample a nonrandom portion of the conformational space, as can be seen in the rapid collapse to an ordered structure in the refolding simulation, and shows that the unfolded state can be closely correlated to the folded ensemble of structures, at least in the case of small model peptides.     

Nature vs nurture: Interplay between the genetic control of telomere length and environmental factors

Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic chromosomes, thus protecting their stability and integrity. They play important roles in DNA replication and repair and are central to our understanding of aging and cancer development. In rapidly dividing cells, telomere length is maintained by the activity of telomerase. About 400 TLM (telomere length maintenance) genes have been identified in yeast, as participants of an intricate homeostasis network that keeps telomere length constant. Two papers have recently shown that despite this extremely complex control, telomere length can be manipulated by external stimuli. These results have profound implications for our understanding of cellular homeostatic systems in general and of telomere length maintenance in particular. In addition, they point to the possibility of developing aging and cancer therapies based on telomere length manipulation.     

Sibling rivalry between seeds within a fruit: Some population genetic models

Competition between seeds within a fruit for parental resources is described using one-locus-two-allele models. While a “normal” allele leads to an equitable distribution of resources between seeds (a situation which also corresponds to the parental optimum), the “selfish” allele is assumed to cause the seed carrying it to usurp a higher proportion of the resources. The outcome of competition between “selfish” alleles is also assumed to lead to an asymmetric distribution of resources, the “winner” being chosen randomly. Conditions for the spread of an initially rare selfish allele and the optimal resource allocation corresponding to the evolutionarily stable strategy, derived for species with n-seeded fruits, are in accordance with expectations based on Hamilton’s inclusive fitness criteria. Competition between seeds is seen to be most intense when there are only two seeds, and decreases with increasing number of seeds, suggesting that two-seeded fruits would be rarer than one-seeded or many-seeded ones. Available data from a large number of plant species are consistent with this prediction of the model. Based on a talk given at the Haldane Centenary Symposium held on 6 November 1992 at Ahmedabad as part of the 58th Annual Meeting of the Indian Academy of Sciences.     

黑线毛足鼠年龄和种群密度与肝毛细线虫感染率的关系

2004—2005年,在内蒙古锡林郭勒盟阿巴嘎旗和东乌珠穆沁旗研究了肝毛细线虫病对黑线毛足鼠种群感染情况,分析肝毛细线虫对黑线毛足鼠的感染率与鼠体年龄以及种群密度的关系。结果表明,黑线毛足鼠达到一定的年龄(或体质量)才可感染肝毛细线虫病,最低感染个体体质量为14.6g。肝毛细线虫对低龄鼠的感染检出率比较低,而对成体鼠感染检出率较高,其感染率和感染度均随着个体年龄的增长而增高(感染率与年龄:r=0.97,P<0.05;感染度与年龄:r=0.93,P<0.05)。此外,黑线毛足鼠体质量与肝毛细线虫感染率和感染度也存在显著的相关关系(感染率与体质量:r=0.99,P<0.05;感染度与体质量:r=0.95,P<0.05),黑线毛足鼠的种群密度则对肝毛细线虫的感染率(r=0.27,P>0.05)和平均感染度(r=0.41,P>0.05)没有明显的影响,其感染率可能与地区不同有关。     

The genetic pattern of population threat and loss: a case study of butterflies

Recent decreases in biodiversity in Europe are commonly thought to be due to land use and climate change. However, the genetic diversity of populations is also seen as one essential factor for their fitness. Genetic diversity in species across the continent of Europe has been recognized as being in part a consequence of ice age isolation in southern refugia and postglacial colonization northwards, and these phylogeographical patterns may themselves affect the adaptability of populations. Recent work on butterfly species with different refugia, colonization paths and genetic structures allows this idea to be examined. The 'chalk-hill blue' pattern is one of decreasing genetic diversity from south to north, whereas the 'woodland ringlet' pattern shows greater genetic diversity in eastern than in western lineages. Comparison of population demographic trends in species with these biogeographical patterns reveals higher rates of decrease with lower genetic diversity. This indicates reduced adaptability due to genetic impoverishment as a result of glacial and postglacial range changes. Analysis of phylogeographical pattern may be a useful guide to interpreting demographic trends and in conservation planning.     

On a simple epidemic model with a heterogeneous infective population

This paper is concerned with a generalization of the simple epidemic model in which the infective population is partitioned intom classes, each of specific infectiousness. Attention is restricted, however, to the case where all the meeting rates between two individuals are equal to each other. Both deterministic and stochastic versions are examined. In either case the development in time of the epidemic process is investigated by exploiting a connection with the standard simple epidemic model. Finally, it is shown that the technique used also applies to a similar model for the spread of information.     

Spatiotemporal relationship between adult census size and genetic population size across a wide population size gradient

Adult census population size (N) and effective number of breeders (N_b) are highly relevant for designing effective conservation strategies. Both parameters are often challenging to quantify, however, making it of interest to determine whether one parameter can be generalized from the other. Yet, the spatiotemporal relationship between N and N_b has not been well characterized empirically in many taxa. We analysed this relationship for 5–7 consecutive years in twelve brook trout populations varying greatly in N (49‐10032) and N_b (3‐567) and identified major environmental variables affecting the two parameters. N or habitat size alone explained 47–57% of the variance in N_b, and N_b was strongly correlated with effective population size. The ratio N_b/N ranged from 0.01 to 0.45 and increased at small N or following an annual decrease in N, suggesting density‐dependent constraints on N_b. We found no evidence for a consistent, directional difference between variability in N_b and/or N_b/N among small and large populations; however, small populations had more varying temporal variability in N_b/N ratios than large populations. Finally, N_b and N_b/N were 2.5‐ and 2.3‐fold more variable among populations than temporally within populations. Our results demonstrate a clear linkage between demographic and evolutionary parameters, suggesting that N_b could be used to approximate N (or vice versa) in natural populations. Nevertheless, using one variable to infer the other to monitor trends within populations is less recommended, perhaps even less so in small populations given their less predictable N_b vs. N dynamics.     

Interplay between inflammation and cancer

Tumor-promoting inflammation is one of the hallmarks of cancer. It has been shown that cancer development is strongly influenced by both chronic and acute inflammation process. Progress in research on inflammation revealed a connection between inflammatory processes and neoplastic transformation, the progression of tumour, and the development of metastases and recurrences. Moreover, the tumour invasive procedures (both surgery and biopsy) affect the remaining tumour cells by increasing their survival, proliferation and migration. One of the concepts explaining this phenomena is an induction of a wound healing response. While in normal tissue it is necessary for tissue repair, in tumour tissue, induction of adaptive and innate immune response related to wound healing, stimulates tumour cell survival, angiogenesis and extravasation of circulating tumour cells. It has become evident that certain types of immune response and immune cells can promote tumour progression more than others. In this review, we focus on current knowledge on carcinogenesis and promotion of cancer growth induced by inflammatory processes.     

Interplay between Endometriosis and Pregnancy in a Mouse Model

Objectives

To evaluate the effect of endometriosis on fertility and the levels of the IL-2 and IFN-γ in the peritoneal fluid in a mouse model; to evaluate the effect of pregnancy on endometriotic lesion growth, apoptosis and cell proliferation.

Study Design

Two month old C57BL/6 female mice underwent either a surgical procedure to induce endometriosis or a sham surgery. Four weeks after surgery mice were mated and sacrificed at day 18 of pregnancy. Number of implantation sites, fetuses and fetal weight were recorded. Endometriotic lesions were counted, measured, excised and fixed. Apoptosis and cell proliferation were evaluated in lesions by TUNEL and immunohistochemistry for PCNA respectively. Levels of IL-2 and IFN-γ were assessed by ELISA in the peritoneal fluid.

Results

Pregnancy rate (i.e. pregnant mice/N) decreased in mice with endometriosis. However there were no significant differences in resorption rate, litter size and pup weight between groups. IFN-γ augmented in endometriosis mice independently of pregnancy outcome. Additionally IFN-γ increased in pregnant endometriosis mice compared to pregnant sham animals. While IFN-γ increased in non pregnant versus pregnant mice in the sham group, IL-2 was increased in non pregnant mice in the endometriosis group. The size of endometriotic lesions increased in pregnant mice while apoptosis increased in the stroma and cell proliferation decreased in the epithelium of these lesions. Additionally, leukocyte infiltration, necrosis and decidualization were increased in the same lesions.

Conclusions

Pregnancy rate is reduced in this mouse model of endometriosis. Levels of IL-2 are increased in the peritoneal fluid of mice with endometriosis suggesting a role of this cytokine in infertility related to this disease. The size of endometriotic lesions is increased in pregnant mice; however pregnancy has a beneficial effect on lesions by decreasing cell proliferation and by increasing apoptosis, decidualization and necrosis.     

Natural genetic exchanges between vaccine and wild poliovirus strains in humans

In a previous study of poliovirus vaccine-derived strains isolated from patients with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that a high proportion (over 50%) of viruses had a recombinant genome. Most were intertypic vaccine/vaccine recombinants. However, some had restriction fragment length polymorphism (RFLP) profiles different from those of poliovirus vaccine strains. We demonstrate here that five such recombinants, of 88 VAPP strains examined, carried sequences of wild (nonvaccine) origin. To identify the parental wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one case was the donor identified, and it was a wild type 1 poliovirus. For the other four vaccine/wild recombinants, the wild parent could not be identified. The possibility that the wild sequences were of a non-poliovirus-enterovirus origin could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine-derived sequences in the 3' moiety of their genome. All these results suggest that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus enteroviruses, are also a natural means of evolution for poliovirus vaccine strains.     

The ancient Yakuts: a population genetic enigma

This study is part of an ongoing project aiming at determining the ethnogenesis of an eastern Siberian ethnic group, the Yakuts, on the basis of archaeological excavations carried out over a period of 10 years in three regions of Yakutia: Central Yakutia, the Vilyuy River basin and the Verkhoyansk area. In this study, genetic analyses were carried out on skeletal remains from 130 individuals of unknown ancestry dated mainly from the fifteenth to the nineteenth century AD. Kinship studies were conducted using sets of commercially available autosomal and Y-chromosomal short tandem repeats (STRs) along with hypervariable region I sequences of the mitochondrial DNA. An unexpected and intriguing finding of this work was that the uniparental marker systems did not always corroborate results from autosomal DNA analyses; in some cases, false-positive relationships were observed. These discrepancies revealed that 15 autosomal STR loci are not sufficient to discriminate between first degree relatives and more distantly related individuals in our ancient Yakut sample. The Y-STR analyses led to similar conclusions, because the current Y-STR panels provided the limited resolution of the paternal lineages.     

Chromosome 17 markers and von Recklinghausen neurofibromatosis: A genetic linkage study in a British population

A genetic linkage study of the RFLPs identified by nine DNA probes localized to the pericentromeric region and long arm of chromosome 17 has been undertaken in 16 families with von Recklinghausen neurofibromatosis (NF1). Close linkage has been shown with the markers CRI-L946 (D17S36), CRI-L581 (D17S37), p17H8 (D17Z1), and pA10-41 (D17S71). The ERBA1 and COL1A1 loci may also be closely linked, but the data are limited. The results for HOX2 and NGFR suggest only loose linkage with the NF1 gene, while no linkage was found between NF1 and the growth hormone locus. No suggestion of nonallelic heterogeneity of NF1 was found in this study.     

The association between physical health and delusional-like experiences: a general population study

Objective

Delusional-like experiences (DLE) are prevalent in the community. Recent community based studies have found that DLE are more common in those with depression and anxiety disorders, and in those with subclinical symptoms of depression and anxiety. Chronic physical disorders are associated with comorbid depression and anxiety; however, there is a lack of evidence about the association of DLE with common physical conditions. The aim of this study was to explore associations between the common physical disorders and DLE using a large population sample.

Methods

Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007, a national household survey of 8841 residents aged between 16 and 85 years. The presence of DLE, selected common physical disorders and symptoms were assessed using a modified World Mental Health Composite International Diagnostic Interview (CIDI) schedule. We examined the relationship between DLE, and physical health-related variables using logistic regression, with adjustments for potential confounding factors.

Results

Of the 8771, 776 (8.4%) subjects positively endorsed one or more DLE. Of the six physical disorders examined, only diabetes and arthritis were significantly associated with the endorsement of DLE. Of the seven broad physical symptoms explored, only hearing problems were consistently associated with DLE.

Conclusion

Delusional-like experiences are common in the Australian community, and are associated with selected chronic physical disorders and with impaired hearing. The direction of causality between these variables warrants closer research scrutiny.     

Translational genetic approaches to substance use disorders: bridging the gap between mice and humans

While substance abuse disorders only occur in humans, mice and other model organisms can make valuable contributions to genetic studies of these disorders. In this review, we consider a few specific examples of how model organisms have been used in conjunction with studies in humans to study the role of genetic factors in substance use disorders. In some examples genes that were first discovered in mice were subsequently studied in humans. In other examples genes or specific polymorphisms in genes were first studied in humans and then modeled in mice. Using anatomically and temporally specific genetic, pharmacological and other environmental manipulations in conjunction with histological analyses, mechanistic insights that would be difficult to obtain in humans have been obtained in mice. We hope these examples illustrate how novel biological insights about the effect of genes on substance use disorders can be obtained when mouse and human genetic studies are successfully integrated.     

Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model

Summary: The discovery of a new class of cytosolic receptors recognizing viral RNA, called the RIG-like receptors (RLRs), has revolutionized our understanding of the interplay between viruses and host cells. A tremendous amount of work has been accumulating to decipher the RNA moieties required for an RLR agonist, the signal transduction pathway leading to activation of the innate immunity orchestrated by type I interferon (IFN), the cellular and viral regulators of this pathway, and the viral inhibitors of the innate immune response. Previous reviews have focused on the RLR signaling pathway and on the negative regulation of the interferon response by viral proteins. The focus of this review is to put this knowledge in the context of the virus replication cycle within a cell. Likewise, there has been an expansion of knowledge about the role of innate immunity in the pathophysiology of viral infection. As a consequence, some discrepancies have arisen between the current models of cell-intrinsic innate immunity and current knowledge of virus biology. This holds particularly true for the nonsegmented negative-strand viruses (Mononegavirales), which paradoxically have been largely used to build presently available models. The aim of this review is to bridge the gap between the virology and innate immunity to favor the rational building of a relevant model(s) describing the interplay between Mononegavirales and the innate immune system.