Modification of telomeric DNA in Trypanosoma brucei; a role in antigenic variation?

Expression of surface antigen genes in Trypanosoma brucei occurs at expression sites located near telomeres. Since only one antigen is produced at a time, a mechanism must exist to prevent the simultaneous activity of multiple expression sites. Here we report that PstI and PvuII restriction sites in silent telomeric antigen genes are partially uncleavable , presumably as a consequence of DNA modification. The modification, which is absent in transcribed genes but returns after gene inactivation, may be specific for telomeric DNA because (1) it is not detected in non-telomeric genes; (2) modification is highest close to the telomere; (3) the level of modification in a telomeric gene is influenced by the size of the telomeric DNA segment downstream. Whether telomere modification is cause or consequence of antigen gene switch-off remains to be determined.     

Conservation genetic assessment of four plant species in a small replica of a steppe ecosystem >30 years after establishment

To counter species loss living ex situ collections in botanic gardens became important elements of robust conservation programs. Several limitations, problems, and risks associated with living ex situ collections have been reported such as appropriate cultivation management to maintain genetic diversity and stochastic effects in small isolated populations in artificial habitats. However, not all small and isolated populations exhibit these predicted genetic changes. In a multi-species in situ/ex situ comparison of sand dune steppe- and grassland vegetation >30 years after the ex situ population establishment, we compared four different species’ population genetic diversities (Alyssum montanum ssp. gmelinii, Gypsophila fastigiata, Helianthemum nummularium ssp. obscurum, Onosma arenaria) by means of ISSR. We observed different species-specific genetic responses to quite similar abiotic selective forces concerning different neutral genetic diversities of wild versus botanic garden populations. The genetic divergence was kept relatively low in two of the four investigated species between the model steppe plant community within the botanic garden where human interference was kept at a minimum and the wild population. However, the moderate genetic divergence of the two other species kept under the same conditions highlights the importance of species-specific intrinsic responses and stochastic effects to ecosystem changes and provides data on population genetic dynamics in small and isolated populations. This contributes to further improve recommendations on how to best conserve endangered plant species in ex situ environments (cultivation in near nature-like replicas of the original site with as little human inference as possible over only certain periods of time, >30 years).     

Climate change and outbreaks of amphibian chytridiomycosis in a montane area of Central Spain; is there a link?

Amphibian species are declining at an alarming rate on a global scale in large part owing to an infectious disease caused by the chytridiomycete fungus, Batrachochytrium dendrobatidis. This disease of amphibians has recently emerged within Europe, but knowledge of its effects on amphibian assemblages remains poor. Importantly, little is known about the environmental envelope that is associated with chytridiomycosis in Europe and the potential for climate change to drive future disease dynamics. Here, we use long-term observations on amphibian population dynamics in the Pe?alara Natural Park, Spain, to investigate the link between climate change and chytridiomycosis. Our analysis shows a significant association between change in local climatic variables and the occurrence of chytridiomycosis within this region. Specifically, we show that rising temperature is linked to the occurrence of chytrid-related disease, consistent with the chytrid-thermal-optimum hypothesis. We show that these local variables are driven by general circulation patterns, principally the North Atlantic Oscillation. Given that B. dendrobatidis is known to be broadly distributed across Europe, there is now an urgent need to assess the generality of our finding and determine whether climate-driven epidemics may be expected to impact on amphibian species across the wider region.     

The role of CS<Subscript>2</Subscript> in CS<Subscript>2</Subscript>/NMP mixed solvent in weakening the hydrogen bond of OH–N in coal: a DFT investigation

The interaction processes of trace amounts of N-methyl-2-pyrrolidinone (NMP), CS₂/NMP (1:1 by volume) and pure NMP solvent with the hydrogen bond of OH?N in coal were constructed and simulated by density functional theory methods. The distances and bond orders between the main related atoms, and the hydrogen bond energy of OH?N were calculated. The calculated results show that pure NMP solvent does not weaken the hydrogen bond of OH?N in coal. However, trace amounts of NMP and CS₂/NMP (1:1 by volume) have a strong capacity to weaken the hydrogen bond of OH?N in coal. The H2–N3 distances are elongated from 1.87 Å to 3.80 Å and 3.44 Å, the bond orders of H2–N3 all disappear, and the corresponding hydrogen bond energies of OH?N in coal decrease from 45.72 kJ mol^?1 to 7.06 and 11.24 kJ mol^?1, respectively. These results show that CS₂ added to pure NMP solvent plays an important role in releasing the original capacity of NMP to weaken the hydrogen bond of OH?N in coal, in agreement with experimental observations.     

Sources of variation in consumer-diet δ<Superscript>15</Superscript>N enrichment: a meta-analysis

Measurements of ¹⁵N of consumers are usually higher than those of their diet. This general pattern is widely used to make inferences about trophic relationships in ecological studies, although the underlying mechanisms causing the pattern are poorly understood. However, there can be substantial variation in consumer-diet ¹⁵N enrichment within this general pattern. We conducted an extensive literature review, which yielded 134 estimates from controlled studies of consumer-diet ¹⁵N enrichment, to test the significance of several potential sources of variation by means of meta-analyses. We found patterns related to processes of nitrogen assimilation and excretion. There was a significant effect of the main biochemical form of nitrogenous waste: ammonotelic organisms show lower ¹⁵N enrichment than ureotelic or uricotelic organisms. There were no significant differences between animals feeding on plant food, animal food, or manufactured mixtures, but detritivores yielded significantly lower estimates of enrichment. ¹⁵N enrichment was found to increase significantly with the C:N ratio of the diet, suggesting that a nitrogen-poor diet can have an effect similar to that already documented for fasting organisms. There were also differences among taxonomic classes: molluscs and crustaceans generally yielded lower ¹⁵N enrichment. The lower ¹⁵N enrichment might be related to the fact that molluscs and crustaceans excrete mainly ammonia, or to the fact that many were detritivores. Organisms inhabiting marine environments yielded significantly lower estimates of ¹⁵N enrichment than organisms inhabiting terrestrial or freshwater environments, a pattern that was influenced by the number of marine, ammonotelic, crustaceans and molluscs. Overall, our analyses point to several important sources of variation in ¹⁵N enrichment and suggest that the most important of them are the main biochemical form of nitrogen excretion and nutritional status. The variance of estimates of ¹⁵N enrichment, as well as the fact that enrichment may be different in certain groups of organisms should be taken into account in statistical approaches for studying diet and trophic relationships.     

Temporal variation of δ<Superscript>13</Superscript>C of larch leaves from a montane boreal forest in Mongolia

This paper reports the temporal variation (2002–2004) in foliar δ¹³C values, which are indicative of long-term integrated photosynthetic and water use characteristics, of Siberian larch (Larix sibirica Ledeb.) trees in a montane forest at Mongonmorit, NE Mongolia. At the stand, the δ¹³C value for understory shaded leaves was more negative by 2‰ on average than that for sunlit leaves sampled concurrently from open and sun-exposed environments in a forest gap. The δ¹³C value of both sunlit and shaded leaves showed pronounced intra- but relatively small inter-seasonal variations. The δ¹³C value was more positive for juvenile than mature leaves. We conjecture that juvenile leaves may derive carbon reserves in woody tissues (e.g., stems). Regardless of leaf habitats, the δ¹³C value was also affected by insect herbivores occurred in mid summer of 2003, being more negative in newly emerging leaves from the twigs after defoliation than in non-defoliated mature leaves. This pattern seems to contrast with that for the juvenile leaves in the early growing season. We surmise that the newly emerging leaves used stored organic carbon that was depleted due to fractionation during remobilization and translocation for leaf regrowth. There was also intra- and inter-seasonal variation in the foliar N concentrations and C:N ratios. A good positive (negative) correlation between the foliar δ¹³C values and N concentrations (C:N ratios) was also observed for both sunlit and shaded leaves, suggesting that the relationship between water and nitrogen use is a crucial factor affecting the plant carbon–water relationship in this mid latitude forest with a cold semiarid climate. Our isotopic data demonstrate that the larches in NE Mongolia exhibits relatively higher water use efficiency with a distinct within-season variability.     

H<Superscript>−</Superscript> ion density in the plasma of a low-voltage cesium-hydrogen discharge as a function of the cathode emission current

It was shown theoretically that the increase in the cathode emission current in a low-voltage cesium-hydrogen discharge to ≈10 A/cm² leads to an increase in the electron temperature in the anode plasma to T _e ≥ 1 eV. In this regime, the rate constant for the production of H^? ions via dissociative electron attachment to vibrationally excited H₂ molecules is close to its maximum value and the density of H^? ions is maximal (about 10¹³ cm^?3) in the anode plasma.     

The accumulation of deleterious genes in a population—Muller's Ratchet

A quantitative study of the operation of Muller's Ratchet for the accumulation of deleterious genes in an asexually reproducing population is made. For a population of size N, in which deleterious mutations occur at rate λ/genome/ generation, and the relative fitness of an individual with k mutants is (1 ? s)^k, the most important parameter is $\text{n}{}_0\text{= Ne}{}^{\mathrm{?\theta }}\text{,}\text{where}\text{θ =}\text{λ}\text{s}$. If n₀ is large (?25), deleterious mutations will accumulate very slowly, and independently of each other; if n₀ is small (<1), the rate of accumulation of deleterious mutations will be greater than a natural population could plausibly bear; an estimate of the speed of the Ratchet for intermediate values of n₀ is made. It is pointed out that the frequency distribution for the numbers of individuals carrying k mutants will retain its shape, but will move bodily to the right at the same average speed as the Ratchet. When favourable mutations also occur, the frequency distributions can move right of left; an estimate of the probability that any particular step is right or left is made, and it is shown that, for a given net rate of arrisal of deleterious mutations, the greater the rate of beneficial mutation, the greater the chance that beneficial mutations will accumulate.     

Establishment of a quasi-field trial in <Emphasis Type="Italic">Abies nordmanniana</Emphasis>—test of a new approach to forest tree breeding

This study used DNA markers to establish a quasi-field trial within a production Christmas tree stand produced from seed collected in an open-pollinated clonal seed orchard (CSO). A total of 660 offspring from the CSO, which comprised 99 clones of Abies nordmanniana, were genotyped with 12 microsatellites. Parentage was assigned successfully to 93% and 98% of the progeny at 95% and 80% confidence, respectively. The assignment rate declined only to 90% when the number of markers was reduced to 10. The distribution of parentage to the offspring among the CSO clones was highly skewed. The most successful clone was assigned as parent in 7% of the cases, and only 92 of the 119 potential parental genotypes were assigned as parents. The obtained pedigree was used to estimate breeding values for the CSO clones for five characters relevant for Christmas tree breeding. For high-heritability traits, such as flushing, accurate breeding values could be estimated for a considerable proportion of the clones. To estimate breeding values for low-heritability traits, such as Christmas tree quality score, more genotyped offspring will be required. The largest drawback of the method is the highly skewed distribution of parentage among the parents in the seed orchards, making it difficult to calculate breeding values for all clones. The approach seems well suited for tree breeding that puts more emphasis on pure selection of parental genotypes and less on estimating quantitative genetic parameters.     

Microgeographic variation in shell characters of Littorina saxatilis Olivi—a question mainly of size?

The question of whether there are shape differences between populations of Littorina saxatilis living in different environments is examined by multivariate analyses of 13 morphological characters. Principal component analysis reveals that morphologic differences between populations from habitats with contrasting degrees of wave exposure are mainly due to a general size factor, including shell thickness. Utilizing the group structure among the snails, canonical variate analysis discloses that the main character excluding size that influences subpopulation differentiation is pointedness.     

An example of de‐Tai‐isation? Longue durée ethnic change in a mountainous area of southern China

Inspired by Grant Evans’ work Tai‐ization: Ethnic Change in Northern Indo‐China, this article explores aspects of historical ethnic change in the Yunkai and Yunwu Mountain Ranges, a small upland region intersected by the boundary of Guangdong and Guangxi provinces in southern China over the period 600–1700 C.E. The discussion begins with some of the early linguistic evidence for populations of Tai speakers in the region and what is known of their political and cultural systems, then moves on to consider how Chinese military conquests of the eighth century coupled with the migration of Sinitic and Mien peoples from the eleventh century onwards altered the ethnic composition and political landscape of the region. This is followed by an examination of different exonyms used in Chinese texts for populations of southern China from the fifteenth century onwards and how these might have related to linguistic groupings and identities on the ground, demonstrating that historical usage of Chinese exonyms now connected with Tai or Mien speakers is not always a reliable indicator of a corresponding presence of historical Tai or Mien‐speaking populations. Further research drawing on a number of disciplines is required on a localised level in order to determine when Tai and Mien languages were abandoned in the region and how the inhabitants of the area shifted from the status of named Others to ordinary Chinese subjects.     

Bi‐parental vs. cooperative breeding in a passerine: fitness‐maximizing strategies of males in response to risk of extra‐pair paternity?

In socially monogamous species, males that risk cuckoldry more than others might gain inclusive fitness by yielding paternity to relatives. We tested this prediction in the Tibetan ground tit Pseudopodoces humilis , an unusual facultative cooperative breeder wherein most helpers (87% males) join a mated pair shortly before clutch completion. Extra-pair paternity among bi-parental broods occurred less often (26% of broods, 9% of young) compared with cooperative broods (68%, 25%). In the former, most extra-pair sires (88%) were pair breeders unrelated to the cuckolded males, whereas in the latter, sires (87%) were mainly helpers related to the dominant males. Brood productivity did not differ between the bi-parental and cooperative breeders, but helpers' partitioning over group paternity reduced the realized reproductive success of helped males. After taking inclusive fitness into account, however, there was no difference in success of dominant males between the two social systems. One possible explanation for the differences in the rates of cuckoldry in the two systems was body size, because pair-bond males in bi-parental situations were significantly larger than those in cooperative ones. We propose two alternative strategies for males to maximize fitness: breed as a pair if large to avoid cuckoldry from helpers, or breed cooperatively if small but compromise some paternity to relatives. Our results provide an unusual route to the incidence of cooperative groups, based on constraints imposed by low competitive ability of breeding males rather than some external ecological or demographic factors.     

Coexistence of competitors in metacommunities due to spatial variation in resource growth rates; does R * predict the outcome of competition?

Simple mathematical models are used to investigate the coexistence of two consumers using a single limiting resource that is distributed over distinct patches, and that has unequal growth rates in the different patches. Relatively low movement rates or high demographic rates of an inefficient resource exploiter allow it to coexist at a stable equilibrium with a more efficient species whose ratio of movement to demographic rates is lower. The range of conditions allowing coexistence depends on the between‐patch heterogeneity in resource growth rates, but this range can be quite broad. The between‐patch movement of the more efficient consumer turns patches with high resource growth rates into sources, while low‐growth‐rate patches effectively become sinks. A less efficient species can coexist with or even exclude the more efficient species from the global environment if it is better able to bias its spatial distribution towards the source patches. This can be accomplished with density independent dispersal if the less efficient species has a lower ratio of per capita between‐patch movement rate to demographic rates. Conditions that maximize the range of efficiencies allowing coexistence of two species are: a relatively high level of heterogeneity in resource growth conditions; high dispersal (or low demographic rates) of the superior competitor; and low dispersal (or high demographic rates) of the inferior competitor. Global exclusion of the more efficient competitor requires that the inferior competitor have sufficient movement to also produce a source‐sink environment.     

Ferritin—a mediator of apoptosis?

Previously we have demonstrated an apoptosis inducing activity for a rat hepatocyte conditioned medium (CM) presumably mediated by acidic isoferritins. Here, we present support for this assumption since isoferritins purified from different rat hepatocyte CM significantly enhanced the frequency of apoptotic cells in primary rat hepatocytes, an effect completely inhibited by a neutralizing anti-H-ferritin antibody. The apoptosis induction appears to be related to a 43 kDa ferritin subunit contained in the isoferritins released from primary hepatocytes, presumably representing a ferritin heavy/light chain heterodimer. In addition, these isoferritins immunologically crossreact with antibodies raised against placental isoferritin p43-PLF (which also contains a 43 kDa ferritin subunit) and melanoma-derived H-chain ferritin, representing ferritin isoforms which reveal immunomodulatory properties. Furthermore, p53 and FasL are upregulated upon isoferritin treatment in a time dependent mode, and apoptosis induction can be suppressed by neutralizing anti-FasL antibodies. Proapoptotic Bid is upregulated too and translocated into mitochondria in primary hepatocytes exposed to the isoferritins purified from the CM. Finally, epidermal growth factor (EGF) and dexamethasone (DEX), which counteract proapoptotic mitochondrial signalling, almost completely abolished the proapoptotic effect of the hepatocyte derived isoferritins. In conclusion, our findings demonstrate that acidic isoferritins with homology to immunomodulatory ferritin isoforms (p43-PLF, melanoma-derived-H-chain ferritin) are released from hepatocytes in vitro, and are able to stimulate upregulation of p53 and mediate apoptosis involving Fas (CD95) signalling as well as addressing the intrinsic mitochondrial proapoptotic pathway.     

Pharmacokinetic profile of a 24-hour controlled-release OROS<Superscript>®</Superscript> formulation of hydromorphone in the presence and absence of food

Background

The objective of this study was to compare the pharmacokinetic profile of a novel, once-daily, controlled-release formulation of hydromorphone (OROS^® hydromorphone) under fasting conditions with that immediately after a high-fat breakfast in healthy volunteers. The effect of the opioid antagonist naltrexone on fasting hydromorphone pharmacokinetics also was evaluated.

Methods

In an open-label, three-way, crossover study, 30 healthy volunteers were randomized to receive a single dose of 16 mg OROS^® hydromorphone under fasting conditions, 16 mg OROS^® hydromorphone under fed conditions, or 16 mg OROS^® hydromorphone under fasting conditions with a naltrexone 50-mg block. Plasma samples taken pre-dose and at regular intervals up to 48 hours post-dose were assayed for hydromorphone concentrations. Analysis of variance was performed on log-transformed data; for mean ratios of 0.8 to 1.2 (20%), differences were considered minimal. Bioequivalence was reached if 90% confidence intervals (CI) of treatment mean ratios were between 80% and 125%.

Results

The mean geometric ratios of the fed and fasting treatment groups for maximum plasma concentration (C_max) and area under the concentration-time curve (AUC_0-t; AUC_0-∞) were within 20%. Confidence intervals were within 80% to 125% for AUC_0-t and AUC_0-∞ but were slightly higher for C_max (105.9% and 133.3%, respectively). With naltrexone block, the hydromorphone C_max increased by 39% and the terminal half-life decreased by 4.5 hours. There was no significant change in T_max, AUC_0-t or AUC_0-∞.

Conclusion

Standard bioavailability measures show minimal effect of food on the bioavailability of hydromorphone from OROS^® hydromorphone. Naltrexone co-administration results in a slight increase in the rate of absorption but not the extent of absorption.

Trial Registration

Clinical Trials.gov NCT00399295

     

Generation and exploration of a dense genetic map in a region of a QTL affecting corpora lutea in a Meishan × Yorkshire cross

Previously genomic scans revealed quantitative trait loci (QTL) on porcine Chromosome 8 (SSC8) as significantly affecting the number of corpora lutea (CL) in swine. In one study, statistical evidence for the putative QTL was found in the chromosomal region defined by the microsatellites (MS) SW205, SW444, SW206, and SW29. A Yeast Artificial Chromosome library was screened by using the corresponding primers for clones containing these MS by PCR. From five positive YAC clones, 10 additional MS were isolated and mapped to SSC8 with the INRA-University of Minnesota porcine Radiation Hybrid (IMpRH) panel. The genetic map position of the QTL has been refined by addition of these 10 markers. The QTL evaluation included pedigrees of F₂-intercross Meishan × Yorkshire design, with phenotypic data of 108 F₂ female offspring and genotypic data for 29 MS markers on SSC8. The analysis was performed by using the least squares regression method. The calculated QTL effect for CL obtained by the multilocus least squares method showed a maximum test statistic (F value = 13.98) at position 99 cM between three MS derived from YACs containing SW205 and SW1843 spanning an interval of 7.1 cM. The point-wise (nominal) P-value was 5.21 × 10⁻⁶ corresponding to a genome-wide P-value of 0.009. The additive QTL effect explained 17.4% of the phenotypic variance. Received: 23 December 2000 / Accepted: 07 May 2001