Why Do Protein Folding Rates Correlate with Metrics of Native Topology?

For almost 15 years, the experimental correlation between protein folding rates and the contact order parameter has been under scrutiny. Here, we use a simple simulation model combined with a native-centric interaction potential to investigate the physical roots of this empirical observation. We simulate a large set of circular permutants, thus eliminating dependencies of the folding rate on other protein properties (e.g. stability). We show that the rate-contact order correlation is a consequence of the fact that, in high contact order structures, the contact order of the transition state ensemble closely mirrors the contact order of the native state. This happens because, in these structures, the native topology is represented in the transition state through the formation of a network of tertiary interactions that are distinctively long-ranged.     

Rates of predation on mammals by gombe chimpanzees, 1972–1975

Rates of chimpanzee predation on mammals are calculated using data on 75 kills recorded during focal observation in Gombe National Park, Tanzania, from January 1972 to April 1975. The chimpanzees were members of two study communities (Kanyawara, or Northern, and Kahama, or Southern, community), and were observed as focal individuals for 14,583 hr by more than 30 researchers and field assistants working in pairs. The rate of predation by females was too low to allow reasonable estimates. For males, the mean rate of killing during the study period was 0.31 kills per male per 100 hr (N=17 males), or 4.65 kills per 100 hr in the two communities. In contrast to results from Mahale Mountains, there was no difference in predation rate between wet and dry seasons. However, predation rates varied over time, increasing by four times between the first three and last four seasons of the sample period. In an average year the 15 adult and subadult male chimpanzees are calculated to have killed 204 prey per year in an area of 16 km², varying between 99 and 420 prey per year in periods of low and high predation rate. Red colobus were the most frequent prey, followed by bushpig and bushbuck. Predation rates varied greatly on different prey species, and were not related to either the proportion of time spent within 200 m of male chimpanzees, or to their population densities. In relation to encounter rates and population density, baboons, blue monkeys, and redtail monkeys were killed at a fraction of the rate of red colobus monkeys, which suffered severe mortality from chimpanzee predation. Predation on bushpig and bushbuck also appears to have been high in relation to population density. The amount of food provided by predation is estimated to have averaged 600 kg per year for chimpanzees in the two communities (totalling 14–17 adult or subadult males, 18–20 adult of subadult females, and about 19 infants or juveniles). This suggests that adult males consumed around 25 kg of meat per year, although any average figure undoubtedly masks considerable individual variation. Present data suggest that chimpanzees in Gombe and Tai National Park, Ivory Coast, prey on mammals at rates higher than other populations.     

Can Reptile Embryos Influence Their Own Rates of Heating and Cooling?

Previous investigations have assumed that embryos lack the capacity of physiological thermoregulation until they are large enough for their own metabolic heat production to influence nest temperatures. Contrary to intuition, reptile embryos may be capable of physiological thermoregulation. In our experiments, egg-sized objects (dead or infertile eggs, water-filled balloons, glass jars) cooled down more rapidly than they heated up, whereas live snake eggs heated more rapidly than they cooled. In a nest with diel thermal fluctuations, that hysteresis could increase the embryo’s effective incubation temperature. The mechanisms for controlling rates of thermal exchange are unclear, but may involve facultative adjustment of blood flow. Heart rates of snake embryos were higher during cooling than during heating, the opposite pattern to that seen in adult reptiles. Our data challenge the view of reptile eggs as thermally passive, and suggest that embryos of reptile species with large eggs can influence their own rates of heating and cooling.     

Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed?

Background

Metachromatic leukodystrophy (MLD) is a severe neurometabolic disease caused mainly by deficiency of arylsulfatase A encoded by the ARSA gene. Based on epidemiological surveys the incidence of MLD per 100 000 live births varied from 0.6 to 2.5. Our purpose was to estimate the birth prevalence of MLD in Poland by determining population frequency of the common pathogenic ARSA gene mutations and to compare this estimate with epidemiological data.

Methodology

We studied two independently ascertained cohorts from the Polish background population (N∼3000 each) and determined carrier rates of common ARSA gene mutations: c.459+1G>A, p.P426L, p.I179S (cohort 1) and c.459+1G>A, p.I179S (cohort 2).

Principal Findings

Taking into account ARSA gene mutation distribution among 60 Polish patients, the expected MLD birth prevalence in the general population (assuming no selection against homozygous fetuses) was estimated as 4.0/100 000 and 4.1/100 000, respectively for the 1^st and the 2^nd cohort with a pooled estimate of 4.1/100 000 (CI: 1.8–9.4) which was higher than the estimate of 0.38 per 100 000 live births based on diagnosed cases. The p.I179S mutation was relatively more prevalent among controls than patients (OR = 3.6, P = 0.0082, for a comparison of p.I179S frequency relative to c.459+1G>A between controls vs. patients).

Conclusions/Significance

The observed discrepancy between the measured incidence of metachromatic leukodystrophy and the predicted carriage rates suggests that MLD is substantially underdiagnosed in the Polish population. The underdiagnosis rate may be particularly high among patients with p.I179S mutation whose disease is characterized mainly by psychotic symptoms.     

High Rates of O’Nyong Nyong and Chikungunya Virus Transmission in Coastal Kenya

BackgroundChikungunya virus (CHIKV) and o’nyong nyong virus (ONNV) are mosquito-borne alphaviruses endemic in East Africa that cause acute febrile illness and arthritis. The objectives of this study were to measure the seroprevalence of CHIKV and ONNV in coastal Kenya and link it to demographics and other risk factors.MethodologyDemographic and exposure questionnaires were administered to 1,848 participants recruited from two village clusters (Milalani-Nganja and Vuga) in 2009. Sera were tested for alphavirus exposure using standardized CHIKV IgG ELISA protocols and confirmed with plaque reduction neutralization tests (PRNT). Logistic regression models were used to determine the variables associated with seropositivity. Weighted K test for global clustering of houses with alphavirus positive participants was performed for distance ranges of 50–1,000 meters, and G* statistic and kernel density mapping were used to identify locations of higher seroprevalence.Conclusions/SignificanceAlphavirus exposure, particularly ONNV exposure, is common in coastal Kenya with ongoing interepidemic transmission of both ONNV and CHIKV. Women and adults were more likely to be seropositive. Household location may be a defining factor for the ecology of alphaviral transmission in this region.     

Rates of chilling to 0°C: implications for the survival of microorganisms and relationship with membrane fluidity modifications

The effects of slow chilling (2°C min⁻¹) and rapid chilling (2,000°C min⁻¹) were investigated on the survival and membrane fluidity of Escherichia coli, of Bacillus subtilis, and of Saccharomyces cerevisiae. Cell death was found to be dependent on the physiological state of cell cultures and on the rate of temperature downshift. Slow temperature decrease allowed cell stabilization, whereas the rapid chilling induced an immediate loss of viability of up to more than 90 and 70% for the exponentially growing cells of E. coli and B. subtilis, respectively. To relate the results of viability with changes in membrane physical state, membrane anisotropy variation was monitored during thermal stress using the fluorescence probe 1,6-diphenyl-1,3,5-hexatriene. No variation in the membrane fluidity of all the three microorganisms was found after the slow chilling. It is interesting to note that fluorescence measurements showed an irreversible rigidification of the membrane of exponentially growing cells of E. coli and B. subtilis after the instantaneous cold shock, which was not observed with S. cerevisiae. This irreversible effect of the rapid cold shock on the membrane correlated well with high rates of cell inactivation. Thus, membrane alteration seems to be the principal cause of the cold shock injury.     

Biogeochemical Budgets in a Mediterranean Catchment with High Rates of Atmospheric N Deposition – Importance of Scale and Temporal Asynchrony

In this study biogeochemical export in a set of catchments that vary from 6 ha to almost 1500 ha is investigated. Studying catchments across this large range of scales enables us to investigate the scale dependence and fundamental processes controlling catchment biogeochemical export that would not have been possible with a more limited data set. The Devil Canyon catchment, in the San Bernardino Mountains, California, has some of the highest atmospheric N deposition rates in the world (40–90 kg ha⁻¹year⁻¹ at the crest of the catchment). These high rates of deposition have translated into consistently high levels of NO⁻in 3 some streams of the San Bernardino Mountains. However, the streams of the Devil Canyon catchment have widely varying dissolved inorganic nitrogen (DIN) concentrations and export. These differences are also, to a more limited extent, present for dissolved organic carbon (DOC) but not in other dissolved species (Cl⁻, SO²⁻₄,Ca²⁺ and other weathering products). As catchment size increases DIN and DOC concentrations first increase until catchment area is ∼150 ha but then decrease as catchment scale increases beyond that size. The scale dependence of DIN export implies that catchments at different spatial scales are at different degrees of N saturation. The reason for this scale effect appears to be the dominance of flushing of DIN out of soil at small scales due to the temporal asynchrony between nutrient availability and biological N demand, the groundwater exfiltration of this flushed DIN at intermediate scales and the removal of this DIN from streamflow through in-stream processes and groundwater–surface water interaction at larger scales. While the particular scale effect observed here may not occur over the same range in catchment area in other ecosystems, it is likely that other ecosystems have similar scale dependant export for DIN and DOC.     

Jensen’s Inequality and the Impact of Short-Term Environmental Variability on Long-Term Population Growth Rates

It is well established in theory that short-term environmental fluctuations could affect the long-term growth rates of wildlife populations, but this theory has rarely been tested and there remains little empirical evidence that the effect is actually important in practice. Here we develop models to quantify the effects of daily, seasonal, and yearly temperature fluctuations on the average population growth rates, and we apply them to long-term data on the endangered Black-faced Spoonbill (Platalea minor); an endothermic species whose population growth rates follow a concave relationship with temperature. We demonstrate for the first time that the current levels of temperature variability, particularly seasonal variability, are already large enough to substantially reduce long-term population growth rates. As the climate changes, our results highlight the importance of considering the ecological effects of climate variability and not just average conditions.     

An Analysis of the Evaluations of Coulomb Logarithm and Electron–Ion Relaxation Rates in Deuterium Plasmas Across Coupling Regimes

Plasma Physics Reports - The evaluation of the Coulomb logarithm (CL) for different coupled plasma regimes is examined using generalized CL, effective CL, and conventional CL models. To find out...     

Differences in the Metabolic Rates of Exploited and Unexploited Fish Populations: A Signature of Recreational Fisheries Induced Evolution?

Non-random mortality associated with commercial and recreational fisheries have the potential to cause evolutionary changes in fish populations. Inland recreational fisheries offer unique opportunities for the study of fisheries induced evolution due to the ability to replicate study systems, limited gene flow among populations, and the existence of unexploited reference populations. Experimental research has demonstrated that angling vulnerability is heritable in Largemouth Bass Micropterus salmoides, and is correlated with elevated resting metabolic rates (RMR) and higher fitness. However, whether such differences are present in wild populations is unclear. This study sought to quantify differences in RMR among replicated exploited and unexploited populations of Largemouth Bass. We collected age-0 Largemouth Bass from two Connecticut drinking water reservoirs unexploited by anglers for almost a century, and two exploited lakes, then transported and reared them in the same pond. Field RMR of individuals from each population was quantified using intermittent-flow respirometry. Individuals from unexploited reservoirs had a significantly higher mean RMR (6%) than individuals from exploited populations. These findings are consistent with expectations derived from artificial selection by angling on Largemouth Bass, suggesting that recreational angling may act as an evolutionary force influencing the metabolic rates of fishes in the wild. Reduced RMR as a result of fisheries induced evolution may have ecosystem level effects on energy demand, and be common in exploited recreational populations globally.     

Does Bioavailability Limit Biodegradation? A Comparison of Hydrocarbon Biodegradation and Desorption Rates in Aged Soils

In order to determine whether bioavailability limits the biodegradability of petroleum hydrocarbons in aged soils, both the biodegradation and abiotic desorption rates of PAHs and n-alkanes were measured at various time points in six different aged soils undergoing slurry bioremediation treatment. Alkane biodegradation rates were always much greater than the respective desorption rates, indicating that these saturated hydrocarbons apparently do not need to be dissolved into the aqueous phase prior to metabolism by soil microorganisms. The biodegradation of PAHs was generally not mass-transfer rate limited during the initial phase, while it often became so at the end of the treatment period when biodegradation rates equaled abiotic desorption rates. However, in all cases where PAH biodegradation was not observed or PAH removal temporarily stalled, bioavailability limitations were not deemed responsible for this recalcitrance since these PAHs desorbed rapidly from the soil into the aqueous phase. Consequently, aged PAHs that are often thought to be recalcitrant due to bioavailability limitations may not be so and therefore may pose a greater risk to environmental receptors than previously thought.     

Does Global Warming Increase Establishment Rates of Invasive Alien Species? A Centurial Time Series Analysis

Background

The establishment rate of invasive alien insect species has been increasing worldwide during the past century. This trend has been widely attributed to increased rates of international trade and associated species introductions, but rarely linked to environmental change. To better understand and manage the bioinvasion process, it is crucial to understand the relationship between global warming and establishment rate of invasive alien species, especially for poikilothermic invaders such as insects.

Methodology/Principal Findings

We present data that demonstrate a significant positive relationship between the change in average annual surface air temperature and the establishment rate of invasive alien insects in mainland China during 1900–2005. This relationship was modeled by regression analysis, and indicated that a 1°C increase in average annual surface temperature in mainland China was associated with an increase in the establishment rate of invasive alien insects of about 0.5 species year⁻¹. The relationship between rising surface air temperature and increasing establishment rate remained significant even after accounting for increases in international trade during the period 1950–2005. Moreover, similar relationships were detected using additional data from the United Kingdom and the contiguous United States.

Conclusions/Significance

These findings suggest that the perceived increase in establishments of invasive alien insects can be explained only in part by an increase in introduction rate or propagule pressure. Besides increasing propagule pressure, global warming is another driver that could favor worldwide bioinvasions. Our study highlights the need to consider global warming when designing strategies and policies to deal with bioinvasions.     

The Rates of Hydrolysis of Thymidyl-3′, 5′-Thymidine-H-Phosphonate: The Possible Role of Nucleic Acids Linked by Diesters of Phosphorous Acid in the Origins of Life

Thymidyl-3,5-thymidine H-phosphonate undergoes acid, base, and water-catalyzed hydrolysis. The products were 3-thymidine H-phosphonate, 5-thymidine H-phosphonate, and thymidine in a ratio of 1:1:2. The rate constants are 1.8 × 10^-3 M^-1 sec^-1, 7.2 × 10³ M^-1 sec^-1, and 1.5 × 10^-6 sec^-1 for acid, base and water catalysis, respectively. These values are comparable with previous reports for the rates of hydrolysis of simple dialkyl esters of phosphorous acids. The Arrhenius activation energy for the base-catalyzed reaction is 20 kcal/mol. and the enthalpy and entropy of activation are 19 kcal/mol and –14 eu., respectively. The Gibbs free energy of activation is 23 kcal/mol. The rate constants suggest that nucleic acids linked by diesters of phosphorous acid hydrolyze too rapidly in aqueous solution to have accumulated in useful amounts on the primitive Earth.     

High Turnover Rates in Remnant Populations of the Harlequin Frog Atelopus cruciger (Bufonidae): Low Risk of Extinction?

Atelopus is among the most threatened of all amphibian genera. Most species of harlequin frogs disappeared more than two decades ago and only a few still exist. From ten critically endangered Atelopus species endemic to Venezuela, Atelopus cruciger is the only one that can be located at present. To assess the status of remnant populations of A. cruciger and to provide the demographic data for designing in situ management programs, we estimated: (1) the population size; (2) the apparent survival; and (3) the recruitment rates of one remnant population using mark‐recapture data. The adult population size varied (69–117), and this variation was not related to that of abundance indices based on visual counts at the river margins. Thus, caution is recommended when using visual counts as an index of abundance in Atelopus, because capture rates differ significantly among months and between seasons. Despite the observed variations, this population appears to be stable. Previous reports suggest that species of Atelopus are long‐lived. For populations of long‐lived species to remain approximately constant, recruitment must be low. Our mark‐recapture study, however, showed that adults tend to remain in the population for approximately 15 mo, but an average of 165 new frogs are recruited every year. Although immigration and emigration are possibilities, the site fidelity and the absence of nearby streams suggests that movement in and out of the study area is less important than births and deaths. Under the proposed hypothesis of a short life expectancy/high recruitment, the risk of extinction must be lower than previously thought.     

Low Rates of Repeat HIV Testing Despite Increased Availability of Antiretroviral Therapy in Rural Tanzania: Findings from 2003–2010

Background

HIV counselling and testing (HCT) services can play an important role in HIV prevention by encouraging safe sexual behaviours and linking HIV-infected clients to antiretroviral therapy (ART). However, regular repeat testing by high-risk HIV-negative individuals is important for timely initiation of ART as part of the ‘treatment as prevention’ approach.

Aim

To investigate HCT use during a round of HIV serological surveillance in northwest Tanzania in 2010, and to explore rates of repeat testing between 2003 and 2010.

Methods

HCT services were provided during the fourth, fifth and sixth rounds of serological surveillance in 2003–2004 (Sero-4), 2006–2007 (Sero-5) and 2010 (Sero-6). HCT services have also been available at a government-run health centre and at other clinics in the study area since 2005. Questionnaires administered during sero-surveys collected information on socio-demographic characteristics, sexual behaviour and reported previous use of HCT services.

Results

The proportion of participants using HCT increased from 9.4% at Sero-4 to 16.6% at Sero-5 and 25.5% at Sero-6. Among participants attending all three sero-survey rounds (n = 2,010), the proportions using HCT twice or more were low, with 11.1% using the HCT service offered at sero-surveys twice or more, and 25.3% having tested twice or more if reported use of HCT outside of sero-surveys was taken into account. In multivariable analyses, individuals testing HIV-positive were less likely to repeat test than individuals testing HIV-negative (aOR 0.17, 95% CI 0.006–0.52).

Discussion/Conclusions

Although HCT service use increased over time, it was disappointing that the proportions ever testing and ever repeat-testing were not even larger, considering the increasing availability of HCT and ART in the study area. There was some evidence that HIV-negative people with higher risk sexual behaviours were most likely to repeat test, which was encouraging in terms of the potential to pick-up those at greatest risk of HIV-infection.     

Influence of Protein – Micelle Ratios and Cysteine Residues on the Kinetic Stability and Unfolding Rates of Human Mitochondrial VDAC-2

Delineating the kinetic and thermodynamic factors which contribute to the stability of transmembrane β-barrels is critical to gain an in-depth understanding of membrane protein behavior. Human mitochondrial voltage-dependent anion channel isoform 2 (hVDAC-2), one of the key anti-apoptotic eukaryotic β-barrel proteins, is of paramount importance, owing to its indispensable role in cell survival. We demonstrate here that the stability of hVDAC-2 bears a strong kinetic contribution that is dependent on the absolute micellar concentration used for barrel folding. The refolding efficiency and ensuing stability is sensitive to the lipid-to-protein (LPR) ratio, and displays a non-linear relationship, with both low and high micellar amounts being detrimental to hVDAC-2 structure. Unfolding and aggregation process are sequential events and show strong temperature dependence. We demonstrate that an optimal lipid-to-protein ratio of 2600∶1 – 13000∶1 offers the highest protection against thermal denaturation. Activation energies derived only for lower LPRs are ∼17 kcal mol⁻¹ for full-length hVDAC-2 and ∼23 kcal mol⁻¹ for the Cys-less mutant, suggesting that the nine cysteine residues of hVDAC-2 impart additional malleability to the barrel scaffold. Our studies reveal that cysteine residues play a key role in the kinetic stability of the protein, determine barrel rigidity and thereby give rise to strong micellar association of hVDAC-2. Non-linearity of the Arrhenius plot at high LPRs coupled with observation of protein aggregation upon thermal denaturation indicates that contributions from both kinetic and thermodynamic components stabilize the 19-stranded β-barrel. Lipid-protein interaction and the linked kinetic contribution to free energy of the folded protein are together expected to play a key role in hVDAC-2 recycling and the functional switch at the onset of apoptosis.     

The Relative Rates of Thiol–Thioester Exchange and Hydrolysis for Alkyl and Aryl Thioalkanoates in Water

This article reports rate constants for thiol–thioester exchange (k _ex), and for acid-mediated (k _a), base-mediated (k _b), and pH-independent (k _w) hydrolysis of S-methyl thioacetate and S-phenyl 5-dimethylamino-5-oxo-thiopentanoate—model alkyl and aryl thioalkanoates, respectively—in water. Reactions such as thiol–thioester exchange or aminolysis could have generated molecular complexity on early Earth, but for thioesters to have played important roles in the origin of life, constructive reactions would have needed to compete effectively with hydrolysis under prebiotic conditions. Knowledge of the kinetics of competition between exchange and hydrolysis is also useful in the optimization of systems where exchange is used in applications such as self-assembly or reversible binding. For the alkyl thioester S-methyl thioacetate, which has been synthesized in simulated prebiotic hydrothermal vents, k _a = 1.5 × 10⁻⁵ M⁻¹ s⁻¹, k _b = 1.6 × 10⁻¹ M⁻¹ s⁻¹, and k _w = 3.6 × 10⁻⁸ s⁻¹. At pH 7 and 23°C, the half-life for hydrolysis is 155 days. The second-order rate constant for thiol–thioester exchange between S-methyl thioacetate and 2-sulfonatoethanethiolate is k _ex = 1.7 M⁻¹ s⁻¹. At pH 7 and 23°C, with [R″S(H)] = 1 mM, the half-life of the exchange reaction is 38 h. These results confirm that conditions (pH, temperature, pK _a of the thiol) exist where prebiotically relevant thioesters can survive hydrolysis in water for long periods of time and rates of thiol–thioester exchange exceed those of hydrolysis by several orders of magnitude.     

Is Quality and Completeness of Reporting of Systematic Reviews and Meta-Analyses Published in High Impact Radiology Journals Associated with Citation Rates?

Purpose

The purpose of this study is to determine whether study quality and completeness of reporting of systematic reviews (SR) and meta-analyses (MA) published in high impact factor (IF) radiology journals is associated with citation rates.

Methods

All SR and MA published in English between Jan 2007–Dec 2011, in radiology journals with an IF >2.75, were identified on Ovid MEDLINE. The Assessing the Methodologic Quality of Systematic Reviews (AMSTAR) checklist for study quality, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for study completeness, was applied to each SR & MA. Each SR & MA was then searched in Google Scholar to yield a citation rate. Spearman correlation coefficients were used to assess the relationship between AMSTAR and PRISMA results with citation rate. Multivariate analyses were performed to account for the effect of journal IF and journal 5-year IF on correlation with citation rate. Values were reported as medians with interquartile range (IQR) provided.

Results

129 studies from 11 journals were included (50 SR and 79 MA). Median AMSTAR result was 8.0/11 (IQR: 5–9) and median PRISMA result was 23.0/27 (IQR: 21–25). The median citation rate for SR & MA was 0.73 citations/month post-publication (IQR: 0.40–1.17). There was a positive correlation between both AMSTAR and PRISMA results and SR & MA citation rate; ρ=0.323 (P=0.0002) and ρ=0.327 (P=0.0002) respectively. Positive correlation persisted for AMSTAR and PRISMA results after journal IF was partialed out; ρ=0.243 (P=0.006) and ρ=0.256 (P=0.004), and after journal 5-year IF was partialed out; ρ=0.235 (P=0.008) and ρ=0.243 (P=0.006) respectively.

Conclusion

There is a positive correlation between the quality and the completeness of a reported SR or MA with citation rate which persists when adjusted for journal IF and journal 5-year IF.