Ecological genomics of tropical trees: how local population size and allelic diversity of resistance genes relate to immune responses, cosusceptibility to pathogens, and negative density dependence.

In tropical forests, rarer species show increased sensitivity to species-specific soil pathogens and more negative effects of conspecific density on seedling survival (NDD). These patterns suggest a connection between ecology and immunity, perhaps because small population size disproportionately reduces genetic diversity of hyperdiverse loci such as immunity genes. In an experiment examining seedling roots from six species in one tropical tree community, we found that smaller populations have reduced amino acid diversity in pathogen resistance (R) genes but not the transcriptome in general. Normalized R gene amino acid diversity varied with local abundance and prior measures of differences in sensitivity to conspecific soil and NDD. After exposure to live soil, species with lower R gene diversity had reduced defence gene induction, more cosusceptibility of maternal cohorts to colonization by potentially pathogenic fungi, reduced root growth arrest (an R gene-mediated response) and their root-associated fungi showed lower induction of self-defence (antioxidants). Local abundance was not related to the ability to induce immune responses when pathogen recognition was bypassed by application of salicylic acid, a phytohormone that activates defence responses downstream of R gene signalling. These initial results support the hypothesis that smaller local tree populations have reduced R gene diversity and recognition-dependent immune responses, along with greater cosusceptibility to species-specific pathogens that may facilitate disease transmission and NDD. Locally rare species may be less able to increase their equilibrium abundance without genetic boosts to defence via immigration of novel R gene alleles from a larger and more diverse regional population.

The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli.

Complex gene regulation networks are made of simple recurring gene circuits called network motifs. One of the most common network motifs is the incoherent type-1 feed-forward loop (I1-FFL), in which a transcription activator activates a gene directly, and also activates a repressor of the gene. Mathematical modeling suggested that the I1-FFL can show two dynamical features: a transient pulse of gene expression, and acceleration of the dynamics of the target gene. It is important to experimentally study the dynamics of this motif in living cells, to test whether it carries out these functions even when embedded within additional interactions in the cell. Here, we address this using a system with incoherent feed-forward loop connectivity, the galactose (gal) system of Escherichia coli. We measured the dynamics of this system in response to inducing signals at high temporal resolution and accuracy by means of green fluorescent protein reporters. We show that the galactose system displays accelerated turn-on dynamics. The acceleration is abolished in strains and conditions that disrupt the I1-FFL. The I1-FFL motif in the gal system works as theoretically predicted despite being embedded in several additional feedback loops. Response acceleration may be performed by the incoherent feed-forward loop modules that are found in diverse systems from bacteria to humans.

Aortic calcification.

OBJECTIVES: Vascular calcification is a complicating factor observed in advanced atherosclerosis. This review summarises the present knowledge regarding abdominal aortic calcification. DESIGN: Literature review. METHODS: A literature review was carried using MEDLINE and PUBMED with the search terms 'abdominal', 'aortic' and 'calcification'. Articles were assessed for data regarding mechanisms, measurement, risk factors and outcomes of aortic calcification. RESULTS: Thirty relevant studies were identified. These demonstrated a positive correlation between abdominal aortic calcification and the following factors: older age, hypertension, and smoking. Further studies are required to critically assess other risk factors such as gender, diabetes mellitus and renal failure. Calcification of the abdominal aorta is associated with an increased risk of mortality, coronary heart disease and stroke. CONCLUSION: Aortic calcification predicts an increased incidence of cardiovascular events, however, the reasons for this association requires further investigation. Accurate measurement of aortic calcification is likely to be increasingly used to determine the risk of cardiovascular events.

The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks.

Recent analysis of the structure of transcription regulation networks revealed several "network motifs": regulatory circuit patterns that occur much more frequently than in randomized networks. It is important to understand whether these network motifs have specific functions. One of the most significant network motifs is the coherent feedforward loop, in which transcription factor X regulates transcription factor Y, and both jointly regulate gene Z. On the basis of mathematical modeling and simulations, it was suggested that the coherent feedforward loop could serve as a sign-sensitive delay element: a circuit that responds rapidly to step-like stimuli in one direction (e.g. ON to OFF), and at a delay to steps in the opposite direction (OFF to ON). Is this function actually carried out by feedforward loops in living cells? Here, we address this experimentally, using a system with feedforward loop connectivity, the L-arabinose utilization system of Escherichia coli. We measured responses to step-like cAMP stimuli at high temporal resolution and accuracy by means of green fluorescent protein reporters. We show that the arabinose system displays sign-sensitive delay kinetics. This type of kinetics is important for making decisions based on noisy inputs by filtering out fluctuations in input stimuli, yet allowing rapid response. This information-processing function may be performed by the feedforward loop regulation modules that are found in diverse systems from bacteria to humans.

Structure and function of the feed-forward loop network motif.

Engineered systems are often built of recurring circuit modules that carry out key functions. Transcription networks that regulate the responses of living cells were recently found to obey similar principles: they contain several biochemical wiring patterns, termed network motifs, which recur throughout the network. One of these motifs is the feed-forward loop (FFL). The FFL, a three-gene pattern, is composed of two input transcription factors, one of which regulates the other, both jointly regulating a target gene. The FFL has eight possible structural types, because each of the three interactions in the FFL can be activating or repressing. Here, we theoretically analyze the functions of these eight structural types. We find that four of the FFL types, termed incoherent FFLs, act as sign-sensitive accelerators: they speed up the response time of the target gene expression following stimulus steps in one direction (e.g., off to on) but not in the other direction (on to off). The other four types, coherent FFLs, act as sign-sensitive delays. We find that some FFL types appear in transcription network databases much more frequently than others. In some cases, the rare FFL types have reduced functionality (responding to only one of their two input stimuli), which may partially explain why they are selected against. Additional features, such as pulse generation and cooperativity, are discussed. This study defines the function of one of the most significant recurring circuit elements in transcription networks.

Fleas (siphonaptera) collected from small mammals in Southern Viet Nam in 1997-1998.

We report on fleas collected from small mammals in two forests, a lowland semideciduous dipterocarp forest and a highland evergreen forest, in southern Viet Nam. In the lowland forest, only one species of flea (Xenopsylla vexabilis Jordan) infested a single species of rodent [Berylmys berdmorei (Blyth)]. In the highland forest, seven species of fleas were collected from eight species of small mammals. Three species of fleas, Lentistivalius insolli (Traub), Lentistivalius occidentayunnanus Li, Xie & Gong, and Gryphopsylla jacobsoni (Jordan & Rothschild), collected from mammals in the highland forest represent new records for Viet Nam.

Increased prevalence of abnormal Papanicolaou smears in urban adolescents.

OBJECTIVE: To determine the secular trend in the prevalence of cervical dysplasia as evidenced by abnormal Papanicolaou smear results in sexually active adolescents. DESIGN: Descriptive case series. SETTING: Outpatient department of an urban public hospital. PARTICIPANTS: All sexually active adolescents with Papanicolaou smear results recorded during 2 periods: January 1, 1982, through December 31, 1983 (n = 577), and January 1, 1992, through December 31, 1993 (n = 871). MEASUREMENTS: Age, ethnicity, patient care location in which the Papanicolaou smear preparation was performed, and Papanicolaou smear results were obtained for each patient. For patients with more than 1 Papanicolaou smear result during the specified period, only the first result was included in this study. Papanicolaou smear results were classified according to the Bethesda system as within normal limits, benign cellular change, atypical squamous cells of undetermined significance, lowgrade squamous intraepithelial lesion, or high-grade squamous intraepithelial lesion. Any Papanicolaou smear classified as atypical squamous cells of undetermined significance or low- or high-grade squamous intraepithelial lesion was defined as abnormal. RESULTS: The prevalence of abnormal Papanicolaou smear results was 2.8% in 1982 through 1983 vs 11.7% in 1992 through 1993; prevalence odds ratio was 4.7 (95% confidence interval, 2.7-8.3). The higher rate of abnormal Papanicolaou smear results in 1992 through 1993 persisted after controlling for age, patient care location, and ethnicity in a logistic regression model (adjusted prevalence odds ratio, 5.0; 95% confidence interval, 2.8-8.9). The prevalence of benign cellular change was 8.7% in 1982 through 1983 vs 20.1% in 1992 through 1993; prevalence odds ratio was 2.7 (95% confidence interval, 1.9-3.8). CONCLUSIONS: The prevalence of abnormal Papanicolaou smear results has significantly increased in the last decade in sexually active adolescents seen at a city hospital clinic. The results of this study emphasize the importance of routine Papanicolaou smear screening for all sexually active female adolescents.