The Natural History of Oxygen

The nuclear reactions occurring in the cores of stars which are believed to produce the element oxygen are first described. Evidence for the absence of free oxygen in the early atmosphere of the earth is reviewed. Mechanisms of creation of atmospheric oxygen by photochemical processes are then discussed in detail. Uncertainty regarding the rate of diffusion of water vapor through the cold trap at 70 km altitude in calculating the rate of the photochemical production of oxygen is avoided by using data for the concentration of hydrogen atoms at 90 km obtained from the Meinel OH absorption bands. It is estimated that the present atmospheric oxygen content could have been produced five to ten times during the earth's history. It is shown that the isotopic composition of atmospheric oxygen is not that of photosynthetic oxygen. The fractionation of oxygen isotopes by organic respiration and oxidation occurs in a direction to enhance the O¹⁸ content of the atmosphere and compensates for the O¹⁸ dilution resulting from photosynthetic oxygen. Thus, an oxygen isotope cycle exists in nature.     

The Natural History of Biocatalytic Mechanisms

Phylogenomic analysis of the occurrence and abundance of protein domains in proteomes has recently showed that the α/β architecture is probably the oldest fold design. This holds important implications for the origins of biochemistry. Here we explore structure-function relationships addressing the use of chemical mechanisms by ancestral enzymes. We test the hypothesis that the oldest folds used the most mechanisms. We start by tracing biocatalytic mechanisms operating in metabolic enzymes along a phylogenetic timeline of the first appearance of homologous superfamilies of protein domain structures from CATH. A total of 335 enzyme reactions were retrieved from MACiE and were mapped over fold age. We define a mechanistic step type as one of the 51 mechanistic annotations given in MACiE, and each step of each of the 335 mechanisms was described using one or more of these annotations. We find that the first two folds, the P-loop containing nucleotide triphosphate hydrolase and the NAD(P)-binding Rossmann-like homologous superfamilies, were α/β architectures responsible for introducing 35% (18/51) of the known mechanistic step types. We find that these two oldest structures in the phylogenomic analysis of protein domains introduced many mechanistic step types that were later combinatorially spread in catalytic history. The most common mechanistic step types included fundamental building blocks of enzyme chemistry: “Proton transfer,” “Bimolecular nucleophilic addition,” “Bimolecular nucleophilic substitution,” and “Unimolecular elimination by the conjugate base.” They were associated with the most ancestral fold structure typical of P-loop containing nucleotide triphosphate hydrolases. Over half of the mechanistic step types were introduced in the evolutionary timeline before the appearance of structures specific to diversified organisms, during a period of architectural diversification. The other half unfolded gradually after organismal diversification and during a period that spanned ∼2 billion years of evolutionary history.     

雌激素与女性缺血性脑卒中

雌激素具有广泛的生物学效应。大量研究表明,雌激素对缺血性脑损伤具有保护作用,其作用机制是多方面的。本文对雌激素的生物学特性和神经保护作用的可能机制以及雌激素替代治疗的现状做一综述。     

高原脑血管病的研究进展

3000m以上的高原因大气压及其氧分压低,气候干燥寒冷,昼夜温差大,太阳辐射线和紫外线照射量增多等因素而导致很多"高原病".其中,高原脑血管病是严重威胁高原人群健康的主要疾病之一.本文就高原脑血管病的危险因素及高原脑血管病的可能发病机制进行简要综述.     

The Natural History of Trachoma Infection and Disease in a Gambian Cohort with Frequent Follow-Up

Background

The natural history of ocular Chlamydia trachomatis infections in endemic communities has not been well characterised and is an important determinant of the effectiveness of different mass treatment strategies to prevent blindness due to trachoma.

Methodology/Principal Findings

A multistate hidden Markov model was fitted to data on infection and active disease from 256 untreated villagers in The Gambia who were examined every 2 weeks over a 6-month period. Parameters defining the natural history of trachoma were estimated, and associations between these parameters, demographic and baseline immune measurements examined. The median incubation period following infection was estimated at 17 days (95% confidence interval: 11–28). Disease persisted for longer than infection (median 21 (15–32) weeks) versus 17 (12–24) weeks), with an estimated median duration of post-infection inflammation of 5 (3–8) weeks. The duration of active disease showed a significant decline with age even after accounting for lower rates of re-infection and disease at older ages (p = 0.004). Measurements of levels of baseline IgA to epitopes in the major outer membrane protein of Chlamydia trachomatis were not significantly correlated with protection or more rapid clearance of infection.

Conclusions

The average duration of infection with Chlamydia trachomatis especially at younger ages is long. This contributes to the persistence and gradual return of trachoma after community-wide treatment with antibiotics.