The Geography of the Stationary Gene Migration Rate in the Human Population of Northern Eurasia

Approximation of the empirical distribution of gene frequencies by a theoretical steady-state distribution was used to obtain a geographical distribution of the limiting gene migration rates in the Northern Eurasian population. The rate averaged over the map was = 0.0432 ± 0.0003. A geographical map of ²values, which reflect the local nonstationarity character of genetic processes and intensity of selection on the distribution of gene frequencies, is presented. Over 90.1% of Northern Eurasia, the ²values satisfy the goodness-of-fit test at a significance level of = 0.1. The geographical distribution that characterizes the ratio between the stepping-stone and island properties of the population migration structure has been obtained. Combined analysis of the spatial characteristics of population migration structure demonstrated that the Pacific coast of Eurasia has played a special role in population genetic processes. This is most likely related to populating the Far East by humans in the remote past and, probably, their more recent expansion to North America through Beringia. The Caucasian region is shown to be extremely stable in terms of the stationarity of migration processes, which agrees with the general view on traditional Caucasian isolates.     

Style morph frequencies in Minnesota populations of Lythrum (Lythraceae)

Style morph frequencies (shortmidlong) were determined for a total of n = 11 918 plants in 16 Minnesota populations of Lythrum salicaria L. Nine populations were in the establishment phase, with population sizes ranging from n = 56 to n = 2 192. Most of these populations exceeded previously reported population sizes in the native European habitat. A nonparametric statistical test, the chi-square (²), can be used to determine if populations are at isoplethic equilibrium (111, shortmidlong); a ² value >5.99 is significant at the 5% level. Only one established population (White Bear Lake, n = 1991, ² = 3.0) fitted the null hypothesis for isoplethy, although all established populations contained all three style morphs. Pooled values for these populations indicated an excess of mids and longs, with shorts being deficient. Colonizing populations had a higher percentage of mids (54%) when compared to established populations (33.7%). Short styles were almost nonexistent (8%) in colonizing populations. Five out of the seven populations lacked at least one style morph. A review of the literature reporting style morph frequencies in tristylous L. salicaria revealed that no statistical analysis for isoplethy has been performed. Darwin originally assumed that all populations would be isoplethic, possessing equal numbers of all three style morphs, but concluded, without statistical analysis, that, instead, populations were anisoplethic. Since tests for statistical deviations from the expected frequencies (111) have not been used, ² analysis was performed. Several of these populations were at isoplethic equilibrium (Nadder su2 = 1.7, Blelham ² = 1.69, Potsdam ² = 1.5, Vestfold ² = 0.4, Buskerud ² = 5.62, Kilchberg ² = 0.35, Lausanne ² = 3.32, Canberra ² = 5.29, Massachusetts ² = 3.13), suggesting that the general conclusion of anisoplethy in tristylous L. salicaria is inappropriate.This is Scientific Journal Series Paper Number 19 128 of the Minnesota Agricultural Experiment Station     

Analysis of local conformation of membrane-bound and polycrystalline peptides by two-dimensional slow-spinning rotor-synchronized MAS exchange spectroscopy

2D slow-spinning, rotor-synchronized MAS exchange spectroscopy (SSRS-MASE) was applied to study local secondary structure of three structurally different peptides, two of which were membrane-bound. Each peptide was ¹³C carbonyl labeled at two adjacent residues in the peptide backbone. In general, this methodology is attractive for membrane-bound peptides because of its lenient spinning, decoupling, and RF homogeneity requirements.For a single set of raw SSRS-MASE data, two linearly independent methods exist for obtaining a 2D spectrum and each spectrum can be fit to obtain conformational constraints. An approach is described for combining the results of these two fits and this method is shown to work for spectra with both resolved and unresolved labeled site resonances. A spectrum is often fit well to a few different conformations which have somewhat different values of the fitting parameter ². A simple statistical theory is developed which relates the ² difference between a local minimum and the global minimum ² to the likelihood that the local minimum conformation is the correct structure. Because uncertainty in the simulated data can also contribute to the overall fitting uncertainty, an empirical method is described for incorporating the simulation uncertainty into the ² analysis.These data analysis methods were tested on polycrystalline Ala-Gly-Gly and then applied to the membrane-bound melittin and HIV-1 fusion peptides. Melittin gave a best-fit helical structure at Ala-4 while the fusion peptide gave a good-fit strand structure at Phe-8. The melittin analysis is in agreement with the known overall structure of this peptide.     

Genetic Determinants of Predisposition to Bronchial Asthma

The ratio between the normal (+) and null (0) alleles of the genes encoding glutatione S-transferases M1 (GSTM1) and T1 (GSTT1) were studied in normal individuals from northwestern Russia (control group) and in patients with bronchial asthma (BA). The frequency of the GSTM1 0/0 genotype in the population sample was statistically significantly lower (37.8%) than in the BA patients (82.1%; ² = 16.8;P< 0.001; _W² = 15.7; = 0.01). For the GSTT1 gene, similar data were obtained. The frequency of the GSTT1 0/0 genotype in healthy donors was statistically significantly higher (16.3%) than in the BA patients (73.7%; ² = 28.5;P < 0.001; _W² = 23.22; = 0.01). A significant preponderance of the compound homozygotes for the GSTM1 and GSTT1 null alleles among the BA patients was observed. The frequency of the GSTM1 0/0, GSTT10/0 individuals among the patients was 57.9%, while it was only 4.7% among the controls (² = 27.4; P < 0.001).     

Einfluß von Bromuracil auf die Mutationsauslösung und Inaktivierung durch UV und Röntgenstrahlen beim Phagen χ

Zusammenfassung Durch Anreicherung in BUdR- und FUdR-haltigem Medium wurde in die DNS des Serratiaphagen Bromuracil (BU) eingebaut. Im CsCl-Gradienten zeigte die Dichte der BU--Partikel einen Ersatz des Thymins durch BU von 25 bis 30% an. Die Häufigkeit zweier Plaquetypmutanten (c und b) war in der BU--Population signifikant (durchschnittlich 1,4 bzw. 2,4), die des dritten Typs (e) nur insignifikant über die in BU-freien Phagen erhöht. Im Vergleich zu letzterem betrug die absolute Häufigkeit der zusätzlichen c- und b-Mutanten in BU- 2,2 × 10^–4 bzw. 1,1 × 10^–4.Die UV-Inaktivierung von BU- war etwa um den Faktor 1,40 höher als die des normalen . Die Inaktivierung durch Röntgenstrahlen war dagegen nur um das 1,14fache erhöht. Die Häufigkeit der durch Röntgenstrahlen induzierten Plaquemutationen wurde durch den BU-Einbau nicht merklich beeinflußt. Dagegen war die UV-Induktion der Mutationen sehr viel mehr verstärkt als die UV-Inaktivierung. Die Sensibilisierungsfaktoren der drei Mutantentypen waren verschieden und am höchsten bei niederen UV-Dosen (3,4, 5,0 und 22 für c, b bzw. e). Das bedeutet eine Annäherung der Dosiskurven an linearen Verlauf. Die zur Auslösung von Mutationen erforderliche Trefferzahl wird somit durch BU-Einbau vermindert. Für -normal entsprachen die Kurven der UV-Mutationsinduktion dem 2-Treffertyp. Es wird geschlossen, daß die Hemmung der Dunkelreaktivierung (HCR) der Letalläsionen und Prämutationen in BU-DNA nicht die einzige Ursache für die Unterschiede in den UV-Sensibilitäten ist, sondern daß die Bildung anderer UV-Produkte als in der normalen DNA ebenfalls eine Rolle spielt.

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Summary Bromouracil (BU) was incorporated into the DNA of theSerratiaphage by means of culture in a medium with BUdR and FUdR. The density of BU-x particles in the CsCl-gradient indicated a replacement of about 24 to 32 % of the thymine by BU. The frequency of two types of plaquemutants (c and b) in the BU--population was increased significantly above the frequencies in BU-free phage by average factors of 1.4 and 2.4, resp. A third mutant type (e) was increased less. The absolut frequencies of additional c- and b-mutants in BU- compared with normal were about 2.10^–4 and 1.10^–4, resp.The UV-inactivation of BU- was higher by a factor of about 1.40 than that of normal , the inactivation by X-rays was only 1.14 times higher. The X-ray induced plaquemutation frequencies were not remarkably influenced by incorporated BU, but UV-mutation-induetion was increased much stronger than UV-inactivation. The sensitization factors were different for the three mutation types and highest at low UV-doses (3.4, 5.0 and 22 for c, b and e resp.). The UV-dose curves of mutation induction in normal are of the 2 hit type, but for BU- they were significantly less curved indicating the participation of 1-hit-processes in premutation production. It is concluded that inhibition of dark repair (HCR) of lethal lesions and premutations in BU-DNA is not the only reason for the differences in UV-sensitivities but that production of other species of UV-products in BU-DNA than in normal DNA plays also a role.

     

Measuring the chi 1 torsion angle in protein by CH-CH cross-correlated relaxation: a new resolution-optimised experiment

Here we introduce an experiment with high sensitivity and resolution for the measurement of CH-CH dipolar-dipolar cross-correlated relaxation rates (CCRR) in protein side-chains. The new methodology aims to the determination of structural and dynamical parameters around the torsion angle ₁ by measuring CH-CH cross-correlated relaxation rates. The method is validated on the protein ubiquitin: the ₁ angles determined from the CCRR data are compared with the ₁ angles of a previously determined NMR structure. The agreement between the two data sets is excellent for most residues. The few discrepancies that were found between the CCR-derived ₁ angles and the angles of the previously determined NMR structure could be explained by taking internal motion into account. The new methodology represents a very powerful tool to determine both structure and dynamics of protein side-chains in only one experiment.     

Polymorphism of the Tumor Necrosis Factor α Gene in Patients with Infiltrative Tuberculosis from the Bashkortostan Populations

The polymorphism at position –308 of the TNF- gene promoter was analyzed in three ethnic groups and in patients with infiltrative pulmonary tuberculosis from Bashkortostan. No interethnic difference in allele or genotype frequency distribution was observed. The frequency of allele TNF2 in tuberculosis patients was significantly higher than in controls (² = 11.69, p = 0.001), suggesting association of this allele with higher risk of pulmonary tuberculosis or with markedly disturbed immune response.     

A Trp in chi space

Our aim is to identify and synthesise a family of tryptophan mimetics which thoroughly explore chi space and then incorporate them into selected ligands for biological receptors e.g. Tachykinin NK₁. This project is considered important as only the - angles have previously been explored; obtaining a greater understanding of the spacial orientation of the side chain in chi space (₁-₂) should prove invaluable to the future design of peptidomimetics. The amino acid tryptophan was selected as it has proved pivotal in many pharmaceutic drug programmes.     

ABO blood groups,leprosy, and serum proteins

Summary In 683 leprosy patients from Chiang Mai, Thailand, the associations between ABO blood groups, type and clinical features of leprosy, and electrophoretically identifiable serumprotein fractions (albumins: ₁-, ₂-, - and -globulins) were examined. Besides, the blood group frequencies in 388 leprosy patients were compared with suitable controls. Blood groups A and AB turned out to be somewhat more frequent in patients than in controls. Combined analysis with 31 series from literature reports gave X=1.0776; ²=1)=12.232. In comparisons within our group of patients which contained almost exclusively lepromatous and dimorphous patients a certain tendency towards more severe involvement of blood group A was observed within the lepromatous group and a higher frequency of eye involvement in group A was (weakly) significant (²=1)=6.188).As to serum proteins ₁- and ₂-globulins were decreased (weakly) significantly in blood group A patients who were at least 40 years old. Furthermore, a number of relationships of serum protein fractions with age, sex, and state of the infection, most of which are known from the literature, could be confirmed.     

Human class III alcohol dehydrogenase/glutathione-dependent formaldehyde dehydrogenase

The class III human liver alcohol dehydrogenase, identical to glutathione-dependent formaldehyde dehydrogenase, separates electrophoretically into a major anodic form (₁) of known structure, and at least one minor, also anodic but a slightly faster migrating form (₂). The primary structure of the minor form isolated by ion-exchange chromatography has now been determined. Results reveal an amino acid sequence identical to that of the major form, suggesting that the two derive from the same translation product, with the minor form modified chemically in a manner not detectable by sequence analysis. This pattern resembles that for the classical alcohol dehydrogenase (class I). Hence, the ₁/₂ multiplicity does not add further primary forms to the complex alcohol dehydrogenase system but shows the presence of modified forms also in class III.     

Allele Polymorphism of the Serotonin Transporter Gene and Clinical Heterogeneity of Depressions

Depression disorders are a clinically heterogeneous disease group. Their development is to a substantial extent underlain by dysfunction of the serotonin system, in particular, disturbed serotonin transport. The heterogeneity of depressions is associated, among other factors, with the age at disease onset. Allele polymorphism of the serotonin transporter (5-HTT) gene was tested for association with age at disease onset, clinical signs, and anxiety-related traits of depression patients. A sample included 77 patients (mean age 61.2 ± 8.8 years) with late-onset depression (LOD, mean age at onset 56.58 ± 9.7 years) and 74 patients (mean age 31.0 ± 11.8 years) with early-onset depression (EOD, mean age at onset 23.9 ± 7.4 years). In genotype frequency distribution of two 5-HTT gene polymorphisms, the LOD and EOD groups did not differ from each other (² = 0.33, P = 0.85 for VNTR; ² = 3.33, P = 0.19 for HTTLPR) and from a control group (² = 0.34,P = 0.84 for VNTR; ² = 2.1, P= 0.35 for HTTLPR). In either group, patients differing in VNTR and HTTLPR genotypes did not differ in psychological traits and, in particular, in anxiety-related traits. In the case of the HTTLPR polymorphism, LOD patients with genotype sstended to display less severe neuroticism (t= 2.03, P = 0.0507) and scored significantly less on the Hamilton depression scale (t = 2.19, P = 0.039). Thus, the 5-HTT gene polymorphisms do not affect the risk of depression but is possibly associated with specific clinical signs of the disease, at least in elderly patients.     

Pulse schemes for the measurement of3 JC′Cγ and3 JNCγ scalar couplings in 15N,13C uniformly labeled proteins

Pulse sequences are presented for the measurement of³J_CC and³J_NC scalar couplings for allC containing residues in¹⁵N,¹³C uniformly labeled proteins. The methodsdescribed are based on quantitative J correlation spectroscopy pioneered byBax and co-workers [Bax et al. (1994) Methods Enzymol., 239, 79–105].The combination of ³J_CC and³J_NC scalar coupling constants allows theassignment of discrete rotameric states about the ₁ torsion angle in cases where such states exist or, alternatively,facilitates the establishment of noncanonical ₁conformations or the presence of rotameric averaging. The methods areapplied to a 1.5 mM sample of staphylococcal nuclease.     

Theoretical studies on the necessary number of components in mixtures

Summary Theoretical studies on the optimal numbers of components in mixtures (for example multiclonal varieties or mixtures of lines) have been performed according to phenotypic yield stability (measured by the parameter variance). For each component i, i = 1, 2,..., n, a parameter u_i with 0 u_i 1 has been introduced reflecting the different survival and yielding ability of the components. For the stochastic analysis the mean of each u_i is denoted by u ₁ and its variance by _i ² For the character total yield the phenotypic variance V can be explicitly expressed dependent on 1) the number n of components in the mixture, 2) the mean of the _i ² 3) the variance of the _i ² 4) the ratio and 5) the ratio _i ² /² where denotes the mean of the u _i and _u ² is the variance of the u _j. According to the dependence of the phenotypic stability on these factors some conclusions can be easily derived from this V-formula. Furthermore, two different approaches for a calculation of necessary or optimal numbers of components using the phenotypic variance V are discussed: A. Determination of optimal numbers in the sense that a continued increase of the number of components brings about no further significant effect according to stability. B. A reduction of b % of the number of components but nevertheless an unchanged stability can be realized by an increase of the mean of the u _i by 1% (with and _u ² assumed to be unchanged). Numerical results on n (from A) and 1 (from B) are given. Computing the coefficient of variation v for the character total yield and solving for the number n of components one obtains an explicit expression for n dependent on v and the factors 2.-5. mentioned above. In the special case of equal variances, _i ² = _o ² for each i, the number n depends on v, x = (₀/)² and y = (_u/)². Detailed numerical results for n = n (v, x, y) are given. For x 1 and y 1 one obtains n = 9, 20 and 79 for v = 0.30, 0.20 and 0.10, respectively while for x 1 and arbitrary y-values the results are n = 11, 24 and 95.This publication is an extended version of a lecture given at the 1984-EUCARPIA meeting (Section Biometrics in Plant Breeding) in Stuttgart-Hohenheim (Federal Republic of Germany)     

Analysis of the Pectin Methylesterase Activity in a Segregating Population of a Tobacco Transgenic Plant using Callus Tissue

With the aim to develop a callus-based tool to study the activity of transgenes, we induced callus from a segregating population of a tobacco transgenic plant expressing a single copy of a transgene designed to overexpress a pectin methylesterase isoenzyme (pmeu1). Pectin methylesterase (PME) activity in the whole plant showed 4-fold induction whereas in callus tissue we found up to 20-fold induction. Furthermore, determination of PME activity of 38 segregating transgenic calluses showed the presence of four groups: calluses with activity like control (calluses-c), calluses with 5-fold induction (calluses-5); calluses with 10-fold induction (calluses-10) and calluses with 20-fold induction (calluses-20) of PME activity. Based on the expected Mendelian segregation of azygous:hemizygous:homozygous, we placed calluses-c, calluses-10 and calluses-20 as azygous, hemizygous and homozygous, respectively. This is a behavior that can be explained by the gene-dosage phenomena. Chi-square statistics was used to test whether the calluses-5 are azygous (²= 4.24) or either homozygous or heterozygous (²= 0.034). The Chi-square critical value is ² _{(=0.05, 1 df)}= 3.84 which allowed to conclude that calluses-5 are either homozygous or heterozygous. Next, we tested whether calluses-5 are either hemizygous (²= 6.36) or homozygous (²= 0.314). The critical value of ² _{(=0.05, 2 df)}= 5.99 was highly significant for concluding that calluses-5 are homozygous for the transgene. This is a behavior that can be explained by the co-silencing phenomena. It is concluded that the use of callus tissue can allowed to find changes in expression of transgenes that are difficult to observe in the whole plant.     

HYPER: A hierarchical algorithm for automatic determination of protein dihedral-angle constraints and stereospecific CβH2 resonance assignments from NMR data

A new computer program, HYPER, has been developed for automated analysis of protein dihedral angle values and CH₂ stereospecific assignments from NMR data. HYPER uses a hierarchical grid-search algorithm to determine allowed values of , , and ₁ dihedral angles and CH₂ stereospecific assignments based on a set of NMR-derived distance and/or scalar-coupling constraints. Dihedral-angle constraints are valuable for restricting conformational space and improving convergence in three-dimensional structure calculations. HYPER computes the set of , , and ₁dihedral angles and CH₂ stereospecific assignments that are consistent with up to nine intraresidue and sequential distance bounds, two pairs of relative distance bounds, thirteen homo- and heteronuclear scalar coupling bounds, and two pairs of relative scalar coupling constant bounds. The program is designed to be very flexible, and provides for simple user modification of Karplus equations and standard polypeptide geometries, allowing it to accommodate recent and future improved calibrations of Karplus curves. The C code has been optimized to execute rapidly (0.3–1.5 CPU-sec residue^–1 using a 5° grid) on Silicon Graphics R8000, R10000 and Intel Pentium CPUs, making it useful for interactive evaluation of inconsistent experimental constraints. The HYPER program has been tested for internal consistency and reliability using both simulated and real protein NMR data sets.     

Effect of bacterial chemotaxis on dynamics of microbial competition

Although the dynamic behavior of microbial populations in nonmixed systems is a central aspect of many problems in biochemical engineering and microbiology, the factors that govern this behavior are not well understood. In particular, the effects of bacterial chemotaxis (biased migration of cells in the direction of chemical concentration gradients) have been the subject of much speculation but very little quantitative investigation. In this paper, we provide the first theoretical analysis of the effects of bacterial chemotaxis on the dynamics of competition between two microbial populations for a single rate-limiting nutrient in a confined nonmixed system. We use a simple unstructured model for cell growth and death, and the most soundly based current model for cell population migration. Using numerical finite element techniques, we examine both transient and steady-state behavior of the competing populations, focusing primarily on the influence of the cell random motility coefficient,, and the cell chemotaxis coefficient, . We find that, in general, there are four possible steady-state outcomes: both populations die out, population 1 exists alone, population 2 exists alone, and the two populations coexist. We find that, in contrast to well-mixed systems, the slower-growing population can coexist and even exist alone if it possesses sufficiently superior motility and chemotaxis properties. Our results allow estimation of the value of necessary to allow coexistence and predominance for reasonable values of growth and random motility parameters in common systems. An especially intriguing finding is that there is a minimum value of necessary for a chemotactic population to have a competitive advantage over an immotile population in a confined nonmixed system. Further, for typical system parameter values, this minimum value of is the range of values that can be estimated from independent experimental assays for chemotaxis.Thus, in typical nonmixed systems, cell motility and chemotaxis properties can be the determining factors in governing population dynamics.     

Resonance assignment of methionine methyl groups and χ3angular information from long-range proton—carbon and carbon—carbon J correlation in a calmodulin—peptide complex

Summary Several simple 3D experiments are used to provide J correlations between methionine C methyl carbons and either the CH₂ protons or C and C. The intensity of the J correlations provides information on the size of the three-bond J couplings and thereby on the ³ torsion angle. In addition, a simple 3D version of the HMBC experiment provides a sensitive link between the CH₃ methyl protons and C. The methods are demonstrated for a 20 kDa complex between calmodulin and a 26-residue peptide fragment of skeletal muscle myosin light chain kinase.     

Characteristics and distribution of β thalassemia haplotypes in South China

Summary Eleven restriction site polymorphisms in the -globin gene cluster were determined in 48 Chinese with homozygous -thalassemia and their parents. Seven haplotypes were identified as associated with the ^thal chromosome and 25 with the ^A chromosome. The distribution of the various ^thal haplotypes in different regions of South China was mapped and discussed in relation to prenatal diagnosis and migration of the Chinese people.     

Optimal growth of Streptococcus cremoris HP in milk is related to β- and ϰ-casein degradation

Summary Initiation of growth and the growth rate of Streptococcus cremoris HP in a complete synthetic medium supplemented with an enzymatic digest of casein appeared to be inhibited by (di)hydrogen phosphate. The inhibitory effect of the inorganic phosphate fraction was counteracted by -glycerophosphate.Growth experiments involving different caseins or combinations of caseins as the only source of nitrogen (and essential amino acids) were performed in an adapted medium in which optimal growth was expected to depend only on the type of nitrogen source. Maximal growth occurred on a combination of -casein and a relatively low concentration of . It approximated the growth on milk added to the medium. These results and those showing the capacity of the organism to grow on milk-derived fractions suggest that in milk it is mainly the soluble (-) casein fraction together with the easily accessible hydrophilic part of micellar , which maintain optimal growth.