Exploring the dihydrodipicolinate synthase tetramer: How resilient is the dimer-dimer interface?

Dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) is a tetrameric enzyme that catalyses the first committed step of the lysine biosynthetic pathway. Dimeric variants of DHDPS have impaired catalytic activity due to aberrant protein motions within the dimer unit. Thus, it is thought that the tetrameric structure functions to restrict these motions and optimise enzyme dynamics for catalysis. Despite the importance of dimer-dimer association, the interface between subunits of each dimer is small, accounting for only 4.3% of the total monomer surface area, and the structure of the interface is not conserved across species. We have probed the tolerance of dimer-dimer association to mutation by introducing amino acid substitutions within the interface. All point mutations resulted in destabilisation of the ‘dimer of dimers’ tetrameric structure. Both the position of the mutation in the interface and the physico-chemical nature of the substitution appeared to effect tetramerisation. Despite only weak destabilisation of the tetramer by some mutations, catalytic activity was reduced to ∼10-15% of the wild-type in all cases, suggesting that the dimer-dimer interface is finely tuned to optimise function.     

How general is the nucleation–condensation mechanism?

We investigate the structures of the major folding transition states of nine proteins by correlation of published Phi-values with inter-residue contact maps. Combined with previous studies on six proteins, the analysis suggests that at least 10 of the 15 small globular proteins fold via a nucleation-condensation mechanism with a concurrent build-up of secondary and tertiary structure contacts, but a structural consolidation that is clearly nonuniformly distributed over the molecule and most intense in a single structural region suggesting the occurrence of a single folding nucleus. However, on average helix- and sheet-forming residues show somewhat larger Phi-values in the major transition state, suggesting that secondary structure formation is one important driving force in the nucleation-condensation in many proteins and that secondary-structure forming residues tend to be more prominent in folding nuclei. We synthesize the combined information on these 10 of 15 proteins into a unified nucleation-condensation mechanism which also accounts for effects described by the framework, hydrophobic collapse, zipper, and funnel models.     

How is a seita fitted to the body?

A seita is a carrier frame for backpacking used in Nishiki-cho, Yamaguchi Prefecture, Japan. In this mountainous district, people make their living by agriculture and forestry and carry everything on their backs with seita. In this study, we investigated the relationships between the sizes of a body and the dimensions of a seita. This survey was conducted on 30 subjects (mean +/- SD; 68.1 +/- 9.0 years old) at three mountain villages. We measured some anthropometric sizes and seita dimensions and found that the correlation between height and sum of shoulder-lumbar-nuki distance (back length of a seita) and shoulder strap length is significant. In additional surveys, we took photographs with some markers on iliocristale, trochanterion, and so on, when the subjects carried seita in two load conditions. The photographs indicate that the load-supporting points in 16 of 23 subjects were between the iliocristale and trochanterion (i.e., on the sacrum). It is important to note that nobody showed that point above the iliocristale (i.e., on the lumbar vertebra). These data lead to the conclusion that when people in Nishik-icho carry loads with seita, they support loads not on the lumbar vertebrae but on the sacrum, and that they adjust the perimeter consisting of the back part and shoulder strap of the seita.     

How are tree species distributed in climatic space? A simple and general pattern

Aim Although many factors undoubtedly affect species geographic distributions, can a single, simple model nonetheless capture most of the spatial variation in the probability of presence/absence in a large set of species? For 482 North American tree species that occur east of the Rocky Mountains, we investigated the shape(s) of the relationship between the probability of occupancy of a given location and macroclimate, and its consistency among species and regions. Location North America. Methods Using Little's tree range maps, we tested four hypothetical shapes of response relating occupancy to climate: (1) high occupancy of all suitable climates; (2) threshold response (i.e. unsuitable climates exclude species, but within the thresholds, species presence is independent of climate); (3) occupancy is a bivariate normal function of annual temperature and precipitation; and (4) asymmetric limitation (i.e. abiotic factors set abrupt range limits in stressful climates only). Finally, we compared observed climatic niches with the occupancy of similar climates on off‐shore islands as well as west of the Rockies. Results (a) Species' distributions in climatic space do not have strong thresholds, nor are they systematically skewed towards less stressful climates. (b) Occupancy can generally be described by a bivariate normal function of temperature and precipitation, with little or no interaction between the two variables. This model, averaged over all species, accounts for 82% of the spatial variation in the probability of occupancy of a given area. (c) Occupied geographic ranges are typically ringed by unoccupied, but climatically suitable areas. (d) Observed climatic niche positions are largely conserved between regions. Main conclusions We conclude that, despite the complexities of species histories and biologies, to a first approximation most of the variation in their geographic distributions relates to climate, in similar ways for nearly all species.     

Geriatric dentistry: is rethinking still required? A community‐based survey in Indian population

Gerodontology 2012; doi: 10.1111/j.1741‐2358.2012.00667.x Geriatric dentistry: is rethinking still required? A community‐based survey in Indian population Background: India has a large geriatric population (60 years and above) of 77 million; comprising 7.7% of its total population. Poor oral health and loss of teeth not only adversely affect the dietary intake and nutritional status and thereby compromise general health, but can also deny them the pleasure of eating food of their choice. Objective: To assess the level of edentulousness, denture wearing and denture needs of the elderly in the community and to study the correlation between oral health parameters and sociodemographic variables which would help us to define better treatment modalities, counselling and thus improve the oral health of our geriatric patients. Materials and Methods: Subjects who were 60 years and above were considered for this study and were randomly selected. Of the 1360 elderly who were enrolled in the study, 780 (57.35%) were males and 580 (42.64%) were female. This sample size is in proportion to the total population for the pilot study. They were given an oral examination and a questionnaire. Results: Fifty seven percent (57%) of the elderly were not satisfied with their oral health status and function. Conclusion: Complete edentulousness of both the arches was highest in the middle socio‐economic group, and was the lowest in the low socio‐economic group. Less than 50% of edentulous elderly and only 10% of partially edentulous elderly were wearing dentures.     

How to lift a model for individual behaviour to the population level?

The quick answer to the title question is: by bookkeeping; introduce as p(opulation)-state a measure telling how the individuals are distributed over their common i(ndividual)-state space, and track how the various i-processes change this measure. Unfortunately, this answer leads to a mathematical theory that is technically complicated as well as immature. Alternatively, one may describe a population in terms of the history of the population birth rate together with the history of any environmental variables affecting i-state changes, reproduction and survival. Thus, a population model leads to delay equations. This delay formulation corresponds to a restriction of the p-dynamics to a forward invariant attracting set, so that no information is lost that is relevant for long-term dynamics. For such equations there exists a well-developed theory. In particular, numerical bifurcation tools work essentially the same as for ordinary differential equations. However, the available tools still need considerable adaptation before they can be practically applied to the dynamic energy budget (DEB) model. For the time being we recommend simplifying the i-dynamics before embarking on a systematic mathematical exploration of the associated p-behaviour. The long-term aim is to extend the tools, with the DEB model as a relevant goal post.     

How useful is DNA extracted from the legs of archived insects for microsatellite-based population genetic analyses?

DNA obtained from museum specimens provides a historical perspective on levels of genetic diversity. Archived samples are irreplaceable so it is desirable that only parts of the specimens are used, which constrains the amount of DNA obtained from small taxa. However, at present there are no quantitative data on yields of DNA from such samples. In this paper we determine the amount of DNA that may be extracted from the legs of museum-archived specimens of the damselfly Coenagrion mercuriale (Charpentier) and the suitability of this DNA for PCR-amplification of nuclear genetic loci (microsatellites). We find that (i) the yield of DNA correlates with the genotyping success rate and (ii) the amount of DNA obtained from the legs decreases with time since sample collection until 1954, before which no DNA could be detected (although DNA may be present in very low quantities). This cut-off point for successful DNA extraction corresponds with the date until reliable genotypes could be obtained by routine PCR. Thus, air-dried insect legs more than 50 years old appear to have limited usefulness for studies that seek to amplify many nuclear loci without the use of other techniques that may be used to increase the possible low-quantities of template DNA present.     

Do physicians assess lifestyle health risks during general medical examinations? A survey of general practitioners and obstetrician-gynecologists in Quebec

BACKGROUND: In Canada several guidelines have been published for the screening of lifestyle health risks during general medical examinations. The authors sought to examine the extent to which such screening practices have been integrated into medical practice, to measure physicians'' perceived level of difficulty in assessing these risks and to document physicians'' evaluation of their formal medical training in lifestyle risk assessment. METHODS: An anonymous mail survey was conducted in 1995 in Quebec with a stratified random sample of 1086 general practitioners (GPs) and with all 241 obstetrician-gynecologists (Ob-Gyns). The authors evaluated the proportion of physicians who reported routine assessment (with 90% or more of their patients) of substance use, family violence and sexual history during general medical examinations of adult and adolescent patients; the proportion of those who find inquiring about these issues difficult; and the proportion of those who evaluated their medical training in lifestyle risk assessment as adequate or excellent. RESULTS: The overall response rate was 72.6%. Among adult patients, 82.2% of the GPs reported routinely assessing tobacco use, 67.2% alcohol consumption, 34.2% illicit drug use and 3.2% family violence; the corresponding proportions for assessment among adolescent patients were 77.1%, 61.8%, 52.9% and 5.6%. Comparatively fewer Ob-Gyns reported routinely assessing these issues (56.1%, 28.6%, 20.4% and 1.3% respectively among adults and 62.7%, 35.2%, 26.8% and 2.8% respectively among adolescents). In the area of sexual history, condom use was routinely assessed by more Ob-Gyns than GPs (47.0% v. 28.2%); however, the proportion of Ob-Gyns and GPs was equally low for assessing number of partners (24.8% and 23.1%), sexual orientation (18.8% and 16.9%) and STD risk (26.2% and 21.2%). The vast majority of GPs and Ob-Gyns reported finding it difficult to assess family violence (86.5% and 93.0%) and sexual abuse (92.7% and 92.4% respectively). Over 80% of the physicians felt that they had had adequate or excellent medical training in assessing risk behaviours for heart disease and STD risk. The proportion who felt this way about their training in screening for illicit drug use, family violence and sexual abuse ranged between 12.7% and 31.6%. INTERPRETATION: Although morbidity and mortality associated with smoking, alcohol consumption, illicit drug use, unsafe sexual practices, family violence and sexual abuse have been well documented, routine screening for these risk factors during general medical examinations has yet to be integrated into medical practice.     

What happens to the DNA vaccine in fish? A review of current knowledge

The primary function of DNA vaccines, a bacterial plasmid DNA containing a construct for a given protective antigen, is to establish specific and long-lasting protective immunity against diseases where conventional vaccines fail to induce protection. It is acknowledged that less effort has been made to study the fate, in terms of cellular uptake, persistence and degradation, of DNA vaccines after in vivo administration. However, during the last year some papers have given new insights into the fate of DNA vaccines in fish. By comparing the newly acquired information in fish with similar knowledge from studies in mammals, similarities with regard to transport, blood clearance, cellular uptake and degradation of DNA vaccines have been found. But the amount of DNA vaccine redistributed from the administration site after intramuscular administration seems to differ between fish and mammals. This review presents up-to-date and in-depth knowledge concerning the fate of DNA vaccines with emphasis on tissue distribution, cellular uptake and uptake mechanism(s) before finally describing the intracellular hurdles that DNA vaccines need to overcome in order to produce their gene product.     

How important is it to consider lineage diversification heterogeneity in macroevolutionary studies? Lessons from the lizard family Liolaemidae

Macroevolutionary and biogeographical studies commonly apply multiple models to test state-dependent diversification. These models track the association between states of interest along a phylogeny, although many of them do not consider whether different clades might be evolving under different evolutionary drivers. Yet, they are still commonly applied to empirical studies without careful consideration of possible lineage diversification heterogeneity along the phylogenetic tree. A recent biogeographic study has suggested that orogenic uplift of the southern Andes has acted as a species pump, driving diversification of the lizard family Liolaemidae (307 described species), native to temperate southern South America. Here, we argue against the Andean uplift as main driver of evolution in this group. We show that there is a clear pattern of heterogeneous diversification in the Liolaemidae, which biases state- and environment-dependent analyses in, respectively, the GeoSSE and RPANDA programs. We show here that there are two shifts to accelerated speciation rates involving two clades that have both been classified as having “Andean” distributions. We incorporated the Geographic Hidden-State Speciation and Extinction model (GeoHiSSE) to accommodate unrelated diversification shifts, and also re-analyzed the data in RPANDA program after splitting biologically distinct clades for separate analyses, as well as including a more appropriate set of models. We demonstrate that the “Andean uplift” hypothesis is not supported when the heterogeneous diversification histories among these lizards is considered. We use the Liolaemidae as an ideal system to demonstrate potential risks of ignoring clade-specific differences in diversification patterns in macroevolutionary studies. We also implemented simulations to show that, in agreement with previous findings, the HiSSE approach can effectively and substantially reduce the level of distribution-dependent models receiving the highest AIC weights in such scenarios. However, we still find a relatively high rate (15%) of distribution-dependent models receiving the highest AIC weights, and provide recommendations related to the set of models included in the analyses that reduce these rates by half. Finally, we demonstrate that trees including clades following different dependent-drivers affect RPANDA analyses by producing different outcomes, ranging from partially correct models to completely misleading results. We provide recommendations for the implementation of both programs.