Loose Linkage Research Articles

Asymptotic sampling distributions made easy: loose linkage in the ancestral recombination graph

Asymptotic sampling distributions made easy: loose linkage in the ancestral recombination graph

Early clinical exposure in medical education: the experience from Debre Tabor University

BackgroundThe idea of early clinical exposure in Ethiopian medical schools is a young concept. Old and newly established universities across the nation are shifting towards incorporation of early clinical exposure (ECE) in their curricula. Debre Tabor University introduced ECE in undergraduate medical education from inception. This study generated evidence on students’ experience and academic leaders’ reflection on early clinical exposure implementation.ObjectiveThis study was carried out to investigate medical students’ perception towards early clinical exposure and its implementation process by instructors in undergraduate medical education at Debre Tabor University.MethodA cross-sectional survey design that combines quantitative and qualitative methods was conducted in 2021. We asked fifth year medical students (42) to complete a self-administered questionnaire on 5-point Likert scale. The data were supplemented by semi-structured interview with 6 purposively selected academic leaders on the factors that facilitate or impede early clinical exposure implementation. The quantitative data were entered and analyzed using SPSS 20 to compute frequency, median and interquartile range. The qualitative data were analyzed thematically.ResultsThe study findings suggest that early clinical exposure (ECE) has a positive impact on the development of students’ professional knowledge, problem-solving skills, motivation, active learning, and community orientation. Specifically, 64.3% of the surveyed students believed that ECE was effective in constructing their professional knowledge, while 52.4% felt that it improved their problem-solving skills and facilitated constructive/active learning. Additionally, 57.1% of students reported that ECE improved their motivation and 50% noted that it facilitated community orientation. The study also identified several barriers to the implementation of ECE, with the heavy workload being the most commonly mentioned (78.6%). Other challenges included a loose linkage between academic and healthcare institutions (59.5%) and a lack of orientation on the implementation process (35.7%). Academic leaders reflected that ECE was beneficial in familiarizing students with the clinical environment, but staff commitment was crucial for its successful implementation. The study also found that heavy workload, lack of assessment dedicated to ECE on the curriculum, and poorly oriented staff about the program impeded its implementation.Conclusion and recommendationsThe findings of this study suggest that early clinical exposure was beneficial learning method. Teachers’ commitment to their roles with adequate preparation, and the contribution of curriculum in providing the learning objective and cases for each session were factors that facilitate effective implementation of ECE. Heavy workload and poor orientation about the program could impede ECE implementation.

The Role of Researchers and Farmers Linkage in Agricultural Innovation System: Challenges and Intervention Options in Ethiopia

Agriculture is the backbone of Ethiopian economy. Conventional approaches to agricultural development in Ethiopia have tended to regard innovation as the result of research, and see its dissemination as linear technique limited to researchers, extension staff and farmers. This does not result in increasing agricultural production and productivity and resulted in food insecurity. However, Ethiopian agriculture is characterized by smallholders farming whose access to modern technology and basic education is very limited. This is due to many factors that are limiting sustainable agricultural development coming from loose linkage of researchers with farmers, weak institutional and technical innovation. Therefore, the main objective is to reviewed different challenges that are hindered researchers’ and farmers’ linkages and proposed alternative interventions that are improving the effectiveness linkage between different relevant agricultural actors in agricultural innovations system in Ethiopia. These linkage inhibiting factors knocked active participation of both farmers and researcher in research to bring social learning and innovation. Based on finding results of different literature reviews, six critical dimension factors that are hindering farmers participation from AIS to improve food security of household in Ethiopia. Those dimension challenge includes are researchers’ characteristics, farmers’ characteristics, researchers’ and farmers’ interaction, type of research project, research approach, and researchers’ and farmers’ benefit from interaction. Thus, policy framework that synergizes the relevant actors’ linkage in a sustainable manner should be in place to bring the intended growth and transformation in agriculture through technology and innovation as well as the agricultural extension system of the country should be revised and participating the farmers in all developmental research process. Keywords: Researchers, Farmers, Linkage, Agricultural Innovation system, Challenges, Intervention Options, Ethiopia: DOI: 10.7176/RJFA/13-9-01 Publication date: May 31 st 2022

The effectiveness of pseudomagic traits in promoting divergence and enhancing local adaptation.

"Magic traits," in which the same trait is both under divergent ecological selection and forms the basis of assortative mating, have been sought after due to their supposed unique ability to promote divergence with gene flow. Here, we ask how unique magic traits are, by exploring whether a tightly linked complex of a locus under divergent selection and a locus that acts as a mating cue can mimic a magic trait in its divergence. We find that these "pseudomagic traits" can be very effective in promoting divergence; with tight linkage they are essentially as effective as a magic trait and with loose linkage, and even no linkage, divergence can still be enhanced. Distinguishing between magic and pseudomagic traits in empirical cases may thus not be important when inferring their role in divergence. The ability of divergence in the mating trait to drive divergence in the ecological trait by lowering the effective migration rate, which occurs somewhat even without linkage, is particularly striking; magic traits are typically considered to have the other direction of causality. Our results thus suggest that divergence in a mating trait can at least modestly increase local adaption by allowing more ecological divergence, particularly with tighter linkage.

Introducing WikiPathways as a Data-Source to Support Adverse Outcome Pathways for Regulatory Risk Assessment of Chemicals and Nanomaterials.

A paradigm shift is taking place in risk assessment to replace animal models, reduce the number of economic resources, and refine the methodologies to test the growing number of chemicals and nanomaterials. Therefore, approaches such as transcriptomics, proteomics, and metabolomics have become valuable tools in toxicological research, and are finding their way into regulatory toxicity. One promising framework to bridge the gap between the molecular-level measurements and risk assessment is the concept of adverse outcome pathways (AOPs). These pathways comprise mechanistic knowledge and connect biological events from a molecular level toward an adverse effect outcome after exposure to a chemical. However, the implementation of omics-based approaches in the AOPs and their acceptance by the risk assessment community is still a challenge. Because the existing modules in the main repository for AOPs, the AOP Knowledge Base (AOP-KB), do not currently allow the integration of omics technologies, additional tools are required for omics-based data analysis and visualization. Here we show how WikiPathways can serve as a supportive tool to make omics data interoperable with the AOP-Wiki, part of the AOP-KB. Manual matching of key events (KEs) indicated that 67% could be linked with molecular pathways. Automatic connection through linkage of identifiers between the databases showed that only 30% of AOP-Wiki chemicals were found on WikiPathways. More loose linkage through gene names in KE and Key Event Relationships descriptions gave an overlap of 70 and 71%, respectively. This shows many opportunities to create more direct connections, for example with extended ontology annotations, improving its interoperability. This interoperability allows the needed integration of omics data linked to the molecular pathways with AOPs. A new AOP Portal on WikiPathways is presented to allow the community of AOP developers to collaborate and populate the molecular pathways that underlie the KEs of AOP-Wiki. We conclude that the integration of WikiPathways and AOP-Wiki will improve risk assessment because omics data will be linked directly to KEs and therefore allow the comprehensive understanding and description of AOPs. To make this assessment reproducible and valid, major changes are needed in both WikiPathways and AOP-Wiki.

Clines on the seashore: The genomic architecture underlying rapid divergence in the face of gene flow.

Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g., outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e., focuses on spatial patterns of allele frequency change) with system‐specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome‐wide SNP set from an ideally suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non‐neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non‐neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasizes that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.

A pivotal role for a conserved bulky residue at the α1-helix of the αI integrin domain in ligand binding

The ligand-binding βI and αI domains of integrin are the best-studied von Willebrand factor A domains undergoing significant conformational changes for affinity regulation. In both βI and αI domains, the α1- and α7-helixes work in concert to shift the metal-ion-dependent adhesion site between the resting and active states. An absolutely conserved Gly in the middle of the α1-helix of βI helps maintain the resting βI conformation, whereas the homologous position in the αI α1-helix contains a conserved Phe. A functional role of this Phe is structurally unpredictable. Using αLβ2 integrin as a model, we found that the residue volume at the Phe position in the α1-helix is critical for αLβ2 activation because trimming the Phe by small amino acid substitutions abolished αLβ2 binding with soluble and immobilized intercellular cell adhesion molecule 1. Similar results were obtained for αMβ2 integrin. Our experimental and molecular dynamics simulation data suggested that the bulky Phe acts as a pawl that stabilizes the downward ratchet-like movement of β6-α7 loop and α7-helix, required for high-affinity ligand binding. This mechanism may apply to other von Willebrand factor A domains undergoing large conformational changes. We further demonstrated that the conformational cross-talk between αL αI and β2 βI could be uncoupled because the β2 extension and headpiece opening could occur independently of the αI activation. Reciprocally, the αI activation does not inevitably lead to the conformational changes of the β2 subunit. Such loose linkage between the αI and βI is attributed to the αI flexibility and could accommodate the αLβ2-mediated rolling adhesion of leukocytes.

Alternative packing of EGFR transmembrane domain suggests that protein–lipid interactions underlie signal conduction across membrane

The human epidermal growth factor receptor (EGFR) of HER/ErbB receptor tyrosine kinase family mediates a broad spectrum of cellular responses transducing biochemical signals via lateral dimerization in plasma membrane, while inactive receptors can exist in both monomeric and dimeric forms. Recently, the dimeric conformation of the helical single-span transmembrane domains of HER/ErbB employing the relatively polar N-terminal motifs in a fashion permitting proper kinase activation was experimentally determined. Here we describe the EGFR transmembrane domain dimerization via an alternative weakly polar C-terminal motif A661xxxG665 presumably corresponding to the inactive receptor state. During association, the EGFR transmembrane helices undergo a structural adjustment with adaptation of inter-molecular polar and hydrophobic interactions depending upon the surrounding membrane properties that directly affect the transmembrane helix packing. This might imply that signal transduction through membrane and allosteric regulation are inclusively mediated by coupled protein–protein and protein–lipid interactions, elucidating paradoxically loose linkage between ligand binding and kinase activation.

Evaluation of QTLs for Shoot Fly (Atherigona soccata) Resistance Component Traits of Seedling Leaf Blade Glossiness and Trichome Density on Sorghum (Sorghum bicolor) Chromosome SBI-10L

Shoot fly is a major insect pest of sorghum damaging early crop growth, establishment and productivity. Host plant resistance is an efficient approach to minimize yield losses due to shoot fly infestation. Seedling leaf blade glossiness and trichome density are morphological traits associated with shoot fly resistance. Our objective was to identify and evaluate QTLs for glossiness and trichome density using- i) 1894 F2s, ii) a sub-set of 369 F2-recombinants, and iii) their derived 369 F2:3 progenies, from a cross involving introgression lines RSG04008-6 (susceptible) × J2614-11 (resistant). The QTLs were mapped to a 37–72 centimorgan (cM) or 5–15 Mb interval on the long arm of sorghum chromosome 10 (SBI-10L) with flanking markers Xgap001 and Xtxp141. One QTL each for glossiness (QGls10) and trichome density (QTd10) were mapped in marker interval Xgap001-Xnhsbm1044 and Xisep0630-Xtxp141, confirming their loose linkage, for which phenotypic variation accounted for ranged from 2.29 to 11.37 % and LOD values ranged from 2.03 to 24.13, respectively. Average physical map positions for glossiness and trichome density QTLs on SBI-10 from earlier studies were 4 and 2 Mb, which in the present study were reduced to 2 Mb and 800 kb, respectively. Candidate genes Glossy15 (Sb10g025053) and ethylene zinc finger protein (Sb10g027550) falling in support intervals for glossiness and trichome density QTLs, respectively, are discussed. Also we identified a sub-set of recombinant population that will facilitate further fine mapping of the leaf blade glossiness and trichome density QTLs on SBI-10.

Application of in silico bulked segregant analysis for rapid development of markers linked to Bean common mosaic virus resistance in common bean.

BackgroundCommon bean was one of the first crops that benefited from the development and utilization of molecular marker-assisted selection (MAS) for major disease resistance genes. Efficiency of MAS for breeding common bean is still hampered, however, due to the dominance, linkage phase, and loose linkage of previously developed markers. Here we applied in silico bulked segregant analysis (BSA) to the BeanCAP diversity panel, composed of over 500 lines and genotyped with the BARCBEAN_3 6K SNP BeadChip, to develop codominant and tightly linked markers to the I gene controlling resistance to Bean common mosaic virus (BCMV).ResultsWe physically mapped the genomic region underlying the I gene. This locus, in the distal arm of chromosome Pv02, contains seven putative NBS-LRR-type disease resistance genes. Two contrasting bulks, containing BCMV host differentials and ten BeanCAP lines with known disease reaction to BCMV, were subjected to in silico BSA for targeting the I gene and flanking sequences. Two distinct haplotypes, containing a cluster of six single nucleotide polymorphisms (SNP), were associated with resistance or susceptibility to BCMV. One-hundred and twenty-two lines, including 115 of the BeanCAP panel, were screened for BCMV resistance in the greenhouse, and all of the resistant or susceptible plants displayed distinct SNP haplotypes as those found in the two bulks. The resistant/susceptible haplotypes were validated in 98 recombinant inbred lines segregating for BCMV resistance. The closest SNP (~25-32 kb) to the distal NBS-LRR gene model for the I gene locus was targeted for conversion to codominant KASP (Kompetitive Allele Specific PCR) and CAPS (Cleaved Amplified Polymorphic Sequence) markers. Both marker systems accurately predicted the disease reaction to BCMV conferred by the I gene in all screened lines of this study.ConclusionsWe demonstrated the utility of the in silico BSA approach using genetically diverse germplasm, genotyped with a high-density SNP chip array, to discover SNP variation at a specific targeted genomic region. In common bean, many disease resistance genes are mapped and their physical genomic position can now be determined, thus the application of this approach will facilitate further development of codominant and tightly linked markers for use in MAS.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-903) contains supplementary material, which is available to authorized users.

The role of thromboxane A2 receptor gene promoter polymorphism in acute cerebral infarction

To investigate the association between thromboxane A2 receptor (TXA2R) gene promoter rs2271875, rs768963 polymorphism and acute cerebral infarction in Chinese Han population. A prospective study was conducted. From October 2009 to May 2013, 223 patients with cerebral infarction (cerebral infarction group) and 142 cohorts with normal physical examination results (control group) from Taizhou City Central Hospital in Zhejiang Province were enrolled. Triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined by enzymatic colorimetry, whereas blood glucose was determined with hexokinase. The genotypes of rs2271875 and rs768963 polymorphism in TXA2R gene were detected by the polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. Differences in gender, age, serum TG, TC, HDL-C, LDL-C, concentration of blood glucose, and blood pressure (systolic pressure, diastolic pressure) between cerebral infarction group and control group were compared as well as TXA2R promoter rs2271875, rs768963 genotype and allele frequencies distribution. The significant differences in males (147 cases vs. 57 cases, χ(2)=23.385, P=0.000), serum TG (2.02±1.14 mmol/L vs. 1.56±0.79 mmol/L, t=4.663, P=0.000), blood glucose (6.40±2.50 mmol/L vs. 5.28±0.92 mmol/L, t=6.084, P=0.000), systolic pressure (146.64±21.34 mmHg vs. 135.73±18.09 mmHg, t=5.234, P=0.000), diastolic blood pressure (86.29±11.79 mmHg vs. 80.74±11.23 mmHg, t=4.468, P=0.000) between cerebral infarction patients and controls were found. The results from multi-logistic regression analysis suggested that male was an independent risk factor for cerebral infarction [odds ratio (OR) 3.300, 95% confidence interval (95%CI) 1.905-5.175, P=0.000]. There were statistically significant differences between infarction group and the control group both in aspects of genotype (TT: 0.112 vs. 0.183, TC: 0.498 vs. 0.535, CC: 0.390 vs. 0.282, χ(2)=6.298, P=0.043) and the allele frequency distribution (T: 0.361 vs. 0.451, C: 0.639 vs. 0.549, χ(2)=5.839, P=0.016) of TXA2R gene rs768963. No statistical significant difference was found in rs2271875 in respect of genotype (GG: 0.336 vs. 0.352, GA: 0.480 vs. 0.451, AA: 0.184 vs. 0.197, χ (2)=0.302, P=0.859) and the allele frequency distribution (G: 0.576 vs. 0.577, A: 0.424 vs. 0.423, χ(2)=0.001, P=0.974). Coefficient of both linkage disequilibrium (D') of rs2271875 and rs768963 was 0.684. When the pair was haplotype AT, the frequency in the infarction group was significantly lower than that in the control group (0.034 vs. 0.081, χ(2)=7.883, P=0.005). rs768963 gene mutation, but not that of the rs2271875, showed significant correlation with the occurrence of cerebral infarction. There was a loose linkage disequilibrium between rs2271875 and rs768963 of TXA2R. Haplotype AT reduces the risk of cerebral infarction.

Economics of Intellectual Property in the Context of a Shifting Innovation Paradigm: A Review from the Perspective of Developing Countries

This paper discusses how the evolving nature of innovation has affected the way Intellectual Property Right (IPR) regime has affected economic growth in developing countries. Focusing more on utilization rather than protection of IPs for human society, it argues that the linkages from protection of knowledge to innovation incentives should be given more priority at the later stage of economic development when developing countries reach a certain level of technological capabilities. Despite the loose or open linkage between IP protection and economic growth, strong IP enforcement can still seriously decrease the catching-up probability of latecomer firms, especially small and medium-sized enterprises (SMEs). The lawsuits by patent trolls may be more damaging because cross-licensing or patent pooling strategy is not available at all as a settlement option. Thus, latecomer firms are facing heavier challenges than before, especially the SMEs with limited financial and human resources. In such circumstance, there can be a case for the active role of public policies and interventions.

Learning experiences and gains from continuing professional education and their applicability to work for Japanese government officials

This study aims to understand the perceived learning experiences and gains for Japanese government officials from US and Japanese graduate and professional schools, and how applicable their continuing professional education (CPE) is to professional performance. Interview participants were drawn from long-term overseas and domestic fellowship programs within the government's National Personnel Authority. Human capital theory and Ottoson's situated evaluation framework were applied for the analysis of 30 purposefully selected interviews. The officials from the overseas program reported more diverse and positive outcomes in cognitive, social, and affective domains as well as networking opportunities from their experiences than those from the domestic program. The interviews, however, revealed a loose linkage between CPE participants' outcomes and their subsequent work.

Estimation of recombination frequency in bi-parental genetic populations

Summary Linkage analysis plays an important role in genetic studies. In linkage analysis, accurate estimation of recombination frequency is essential. Many bi-parental populations have been used, and determining an appropriate population is of great importance in precise recombination frequency. In this study, we investigated the estimation efficiency of recombination frequency in 12 bi-parental populations. The criteria that we used for comparison were LOD score in testing linkage relationship, deviation between estimated and real recombination frequency, standard error (SE) of estimates and the least theoretical population size (PS) required to observe at least one recombinant and to declare the statistically significant linkage relationship. Theoretical and simulation results indicated that larger PS and smaller recombination frequency resulted in higher LOD score and smaller deviation. Lower LOD score, higher deviation and higher SE for estimating the recombination frequency in the advanced backcrossing and selfing populations are larger than those in backcross and F2 populations, respectively. For advanced backcrossing and selfing populations, larger populations were needed in order to observe at least one recombinant and to declare significant linkage. In comparison, in F2 and F3 populations higher LOD score, lower deviation and SE were observed for co-dominant markers. A much larger population was needed to observe at least one recombinant and to detect loose linkage for dominant and recessive markers. Therefore, advanced backcrossing and selfing populations had lower precision in estimating the recombination frequency. F2 and F3 populations together with co-dominant markers represent the ideal situation for linkage analysis and linkage map construction.

Structural Evidence for Loose Linkage between Ligand Binding and Kinase Activation in the Epidermal Growth Factor Receptor

The mechanisms by which signals are transmitted across the plasma membrane to regulate signaling are largely unknown for receptors with single-pass transmembrane domains such as the epidermal growth factor receptor (EGFR). A crystal structure of the extracellular domain of EGFR dimerized by epidermal growth factor (EGF) reveals the extended, rod-like domain IV and a small, hydrophobic domain IV interface compatible with flexibility. The crystal structure and disulfide cross-linking suggest that the 7-residue linker between the extracellular and transmembrane domains is flexible. Disulfide cross-linking of the transmembrane domain shows that EGF stimulates only moderate association in the first two α-helical turns, in contrast to association throughout the membrane over five α-helical turns in glycophorin A and integrin. Furthermore, systematic mutagenesis to leucine and phenylalanine suggests that no specific transmembrane interfaces are required for EGFR kinase activation. These results suggest that linkage between ligand-induced dimerization and tyrosine kinase activation is much looser than was previously envisioned.

Experience report

The Ada language has been architected to provide a strong foundation for building software at the heart of safety critical, real-time, and long-maintained programs. The benefits of Ada in such environments have led to its use in a wide range of systems where correctness and predictability are critical. The current trend in our industry is to loosely tie systems together to share data that previously required manual re-entry, simply was not available, or worse could have been inconsistent between systems. This trend is resulting in a need to connect previously closed systems over in-house and external networks to perform that loose linkage. The FAA has embraced this technology and has been developing an architecture, code framework, and standards for sharing data across their entire spectrum of Air Traffic Control systems and consumers. The FAA's overall umbrella for this is termed SWIM (System Wide Information Management), and programs participating in the architecture are called "SWIM implementing programs". The ERAM (EnRoute Automation Modernization) program I work on and previously presented at SIG Ada 2009 is one of the first SWIM implementing programs. ERAM has recently entered the test phase of the first increment of SWIM functionality. ERAM SWIM faced many of the same hurdles as other legacy Ada systems around the globe. The new interfaces are built on standard web protocols and need to provide secure reliable information flow to both other internal FAA systems, and external customers such as the major commercial air carriers. In an effort to use best industry practices Lockheed Martin and the FAA chose Java and other web-standard technologies to implement much of the new SWIM interface. Java has gained a strong foothold in the internet environment and the classrooms for a variety of reasons. The result is that Java enjoys a large amount of FOSS and commercial support that makes it a natural choice for such a web interface, even in a high stakes environment such as ATC. ERAM SWIM development has encountered several issues with bridging the gap between Ada and Java and the quickly evolving world of FOSS/COTS SW. Performance issues and command and control issues have dominated our internal discussions and been the focus of much of our effort to achieve test readiness. Efficient data representation, baseline control (remember much of it is FOSS), and debugging have also received a lot of attention. We had a lot of prior experience with mixed languages having several hundred thousand lines of C and C++ and considered ourselves prepared. However, integrating with Java is completely unlike integrating with those others, and we have had to adapt across the board to this new challenge. My talk will focus on the challenges we have encountered, and the lessons we have learned about the strengths and weaknesses of the various languages and other technology elements we have used implementing ERAM SWIM.

Relational analysis among fibrinogenic Bβ-chain gene polymorphisms and its functional expression and obesity

Recently, there have been a few studies showing the association between obesity and fibrinogen (Fg) gene polymorphisms, but the reasons still do not clear completely. In this research, we studied the relationship among overweight, obesity and -854G/A, -455G/A, -249C/T, -148C/T, 448G/A, Bcl-1G/A gene polymorphisms of Fg β-chain and its functional expression such as plasma Fg concentration and molecule conglomerate function. 1391 subjects of retired aged employees from Kailuan Group were enrolled with medical examination and questionnaire survey, and which were divided into normal weight group (597 cases), overweight group (609 cases), obese group (185 cases) based on body mass index (BMI). Plasma Fg concentration, fibrin monomer polymerized velocity (FMPV), absorbance maximum (Amax) and FMPV/Amax were measured in all subjects. The gene polymorphisms at six sites of Fg β-chain were detected by polymerase chain reaction-restriction fragment length polymorphism. We found that only the frequencies of Bcl-1A allele and its mutated genotypes in overweight group were significantly higher than ones in normal weight group (P < 0.01). The loose linkage disequilibrium was evident between FgβBcl-1G/A and -455G/A, -148C/T polymorphisms. Fg concentration, FMPV, FMPV/Amax of subjects only with β-854 mutated genotype were significantly higher those with wild genotype in three groups (P < 0.01), and FMPV/Amax of subjects with β-455 mutated genotypes and FMPV of ones with β-249 mutated genotypes were yet higher than those with wild genotype in overweight group (P < 0.05). In conclusion, the Fg β-854 site is an important locus regulating plasma Fg concentration and conglomerate functional expression. Only the people with FgβBcl-1 mutated genotype is the genetic susceptible population of overweight with obvious stable phase. This overweight people can enhance plasma fibrinogenic molecular activity expression by activating mutated genotypes of Fgβ-455 and -249. There are different genetic basis and genetic susceptible population between the overweight patients with obvious stable phase and the patients of progressive development to obesity without obvious overweight stable phase.:

Reconstructing Race in Science and Society: Biology Textbooks, 1952–2002

How has growing knowledge about human genetics affected how American textbooks present race? This article analyzes 80 biology textbooks published from 1952 to 2002 to reveal that U.S. biology texts have pursued the topic of race with renewed vigor in recent years. Moreover, textbooks have redefined race as genetic without furnishing empirical evidence for this framing. The textbooks' transformation sheds light on the broader relationship between race and science in the United States, where claims about racial difference have not only drawn instrumentally and selectively from empirical research, but at times forgo scientific grounding altogether. As the textbooks show, both the tight and the loose linkage of race to science can preserve the cultural authority of the race concept. The texts also make clear that race is not a one-time construct or a relic of centuries past. Instead, it is continually remade -- and is being reworked today -- suggesting its dynamic adaptation for ongoing use as a fundamental tool of social stratification.

The origin of mammalian endothermy: a paradigm for the evolution of complex biological structure

Several mutually incompatible theories exist about how and why endothermy evolved in mammals and birds. Some take the primary function to have been thermoregulation, selected for one adaptive purpose or another. Others take the high aerobic metabolic rate to have been primary. None of these theories is incontrovertibly supported by evidence, either from the fossil record of the synapsid amniotes or from observations and experiments on modern organisms. Furthermore, all are underpinned by the tacit assumption that endothermy must have evolved in a stepwise pattern, with an initial adaptive function followed only later by the addition of further functions. It is argued that this assumption is unrealistic and that the evolution of endothermy can be explained by the correlated progression model. Each structure and function associated with endothermy evolved a small increment at a time, in loose linkage with all the others evolving similarly. The result is that the sequence of organisms maintained functional integration throughout, and no one of the functions of endothermy was ever paramount over the others. The correlated progression model is tested by the nature of the integration between the parts as seen in living mammals, by computer simulations of the evolution of complex, multifunctional, multifactorial biological systems, and by reference to the synapsid fossil record, which is fully compatible with the model. There are several potentially important implications to be drawn from this example concerning the study of the evolution of complex structure and the new higher taxa that manifest it.

Identification and mapping of microsatellite markers linked to a root-knot nematode resistance gene (rkn1) in Acala NemX cotton (Gossypium hirsutum L.)

Host-plant resistance is the most economic and effective strategy for root-knot nematode (RKN) Meloidogyne incognita control in cotton (Gossypium hirsutum L.). Molecular markers linked to resistance are important for incorporating resistance genes into elite cultivars. To screen for microsatellite markers (SSR) closely linked to RKN resistance in G. hirsutum cv. Acala NemX, F1, F2, BC1F1, and F2:7 recombinant inbred lines (RILs) from intraspecific crosses and an F2 from an interspecific cross with G. barbadense cv. Pima S-7 were used. Screening of 284 SSR markers, which cover all the known identified chromosomes and most linkage groups of cotton, was performed by bulked segregant analysis, revealing informative SSRs. The informative SSRs were then mapped on the above populations. One co-dominant SSR marker CIR316 was identified tightly linked to a major resistance gene (designated as rkn1), producing amplified DNA fragments of approximately 221 bp (CIR316a) and 210 bp (CIR316c) in Acala NemX and susceptible Acala SJ-2, respectively. The linkage between CIR316a marker and resistance gene rkn1 in Acala NemX had an estimated distance of 2.1-3.3 cM depending on the population used. Additional markers, including BNL1231 with loose linkage to rkn1 (map distance 25.1-27.4 cM), BNL1066, and CIR003 allowed the rkn1 gene to be mapped to cotton linkage group A03. This is the first report in cotton with a closely linked major gene locus determining nematode resistance, and informative SSRs may be used for marker-assisted selection.