Exploring Fold Space Preferences of New-born and Ancient Protein Superfamilies

The evolution of proteins is one of the fundamental processes that has delivered the diversity and complexity of life we see around ourselves today. While we tend to define protein evolution in terms of sequence level mutations, insertions and deletions, it is hard to translate these processes to a more complete picture incorporating a polypeptide's structure and function. By considering how protein structures change over time we can gain an entirely new appreciation of their long-term evolutionary dynamics. In this work we seek to identify how populations of proteins at different stages of evolution explore their possible structure space. We use an annotation of superfamily age to this space and explore the relationship between these ages and a diverse set of properties pertaining to a superfamily's sequence, structure and function. We note several marked differences between the populations of newly evolved and ancient structures, such as in their length distributions, secondary structure content and tertiary packing arrangements. In particular, many of these differences suggest a less elaborate structure for newly evolved superfamilies when compared with their ancient counterparts. We show that the structural preferences we report are not a residual effect of a more fundamental relationship with function. Furthermore, we demonstrate the robustness of our results, using significant variation in the algorithm used to estimate the ages. We present these age estimates as a useful tool to analyse protein populations. In particularly, we apply this in a comparison of domains containing greek key or jelly roll motifs

Equal fitness paradigm explained by a trade-off between generation time and energy production rate

Most plant, animal and microbial species of widely varying body size and lifestyle are nearly equally fit as evidenced by their coexistence and persistence through millions of years. All organisms compete for a limited supply of organic chemical energy, derived mostly from photosynthesis, to invest in the two components of fitness: survival and production. All organisms are mortal because molecular and cellular damage accumulates over the lifetime; life persists only because parents produce offspring. We call this the equal fitness paradigm. The equal fitness paradigm occurs because: (1) there is a trade-off between generation time and productive power, which have equal-but-opposite scalings with body size and temperature; smaller and warmer organisms have shorter lifespans but produce biomass at higher rates than larger and colder organisms; (2) the energy content of biomass is essentially constant, ~22.4 kJ g−1 dry body weight; and (3) the fraction of biomass production incorporated into surviving offspring is also roughly constant, ~10–50%. As organisms transmit approximately the same quantity of energy per gram to offspring in the next generation, no species has an inherent lasting advantage in the struggle for existence. The equal fitness paradigm emphasizes the central importance of energy, biological scaling relations and power–time trade-offs in life history, ecology and evolution

A randomized clinical trial comparing hydrocolloid, phenytoin and simple dressings for the treatment of pressure ulcers [ISRCTN33429693]

BACKGROUND: Pressure sores are important and common complications of spinal cord injury. Many preventive and therapeutic approaches have been tried and new trials are evolving. One relatively recent method is application of a hydrocolloid dressing (HD). In this study we compared the therapeutic effects of HD on pressure ulcer healing with two other topical applications, phenytoin cream (PC) and simple dressing (SD). METHODS: Ninety-one stage I and stage II pressure ulcers of 83 paraplegic male victims of the Iran-Iraq war were randomly allocated to three treatment groups. Mean age and weight of the participants were 36.64 ± 6.04 years and 61.12 ± 5.08 kg, respectively. All the patients were managed in long term care units or in their homes for 8 weeks by a team of general practitioners and nurses, and the ulcer status was recorded as "Complete healing", "Partial healing", "Without improvement" and "Worsening". RESULTS: Complete healing of ulcers, regardless of location and stage, was better in the HD group than the PC [23/31(74.19%) vs 12/30(40%); difference: 34.19%, 95% CI = 10.85–57.52, (P < 0.01)] or the SD [23/31(74.19%) vs 8/30(26.66%); difference: 47.53%, 95% CI = 25.45–69.61, (P < 0.005)] groups. Complete healing of stage I ulcers in the HD group [11/13(85%)] was better than in the SD [5/11(45%); difference: 40%, 95% CI = 4.7–75.22, (P < 0.05)] or PC [2/9 (22%); difference: 63%, 95% CI = 29.69–96.3, (P < 0.005)] groups. Complete healing of stage II ulcer in the HD group [12/18 (67%)] was better than in the SD group [3/19(16%); difference: 51%, 95% CI = 23.73–78.26, (P < 0.005)], but not significantly different from the PC group [10/21 (48%); difference: 19%, 95% CI = -11.47–49.47, (P > 0.05)]. We performed a second analysis considering only one ulcer per patient (i.e. 83 ulcers in 83 patients). This "per patient" analysis showed that complete ulcer healing in the HD group was better than in the PC [20/28(71.4%) vs 11/28 (39.3%); difference: 32.1%, 95% CI = 7.4–56.7, (P < 0.01)] or SD [20/28(71.4%) vs 8/27 (29.6%); difference: 41.8%, 95% CI = 17.7–65.8, (P < 0.005)] groups. CONCLUSION: We deduced that HD is the most effective method investigated for treating stage I and II pressure ulcers in young paraplegic men

Sheldon Spectrum and the Plankton Paradox: Two Sides of the Same Coin : A trait-based plankton size-spectrum model

The Sheldon spectrum describes a remarkable regularity in aquatic ecosystems: the biomass density as a function of logarithmic body mass is approximately constant over many orders of magnitude. While size-spectrum models have explained this phenomenon for assemblages of multicellular organisms, this paper introduces a species-resolved size-spectrum model to explain the phenomenon in unicellular plankton. A Sheldon spectrum spanning the cell-size range of unicellular plankton necessarily consists of a large number of coexisting species covering a wide range of characteristic sizes. The coexistence of many phytoplankton species feeding on a small number of resources is known as the Paradox of the Plankton. Our model resolves the paradox by showing that coexistence is facilitated by the allometric scaling of four physiological rates. Two of the allometries have empirical support, the remaining two emerge from predator-prey interactions exactly when the abundances follow a Sheldon spectrum. Our plankton model is a scale-invariant trait-based size-spectrum model: it describes the abundance of phyto- and zooplankton cells as a function of both size and species trait (the maximal size before cell division). It incorporates growth due to resource consumption and predation on smaller cells, death due to predation, and a flexible cell division process. We give analytic solutions at steady state for both the within-species size distributions and the relative abundances across species

Genomewide Expression Analysis in Zebrafish mind bomb Alleles with Pancreas Defects of Different Severity Identifies Putative Notch Responsive Genes

10.1371/journal.pone.0001479PLoS ONE3