Theoretical biology - Comparing models of species abundance

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62867/1/nature04826.pd

Hematological Changes in Women and Infants Exposed to an AZT-Containing Regimen for Prevention of Mother-to-child-transmission of HIV in Tanzania.

Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants. A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12. For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2. AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Attentional Processing in C57BL/6J Mice Exposed to Developmental Vitamin D Deficiency

Epidemiological evidence suggests that Developmental Vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in mice is associated with altered behaviour, however there has been no detailed investigation of cognitive behaviours in DVD-deficient mice. The aim of this study was to determine the effect of DVD deficiency on a range of cognitive tasks assessing attentional processing in C57BL/6J mice. DVD deficiency was established by feeding female C57BL/6J mice a vitamin D-deficient diet from four weeks of age. After six weeks on the diet, vitamin D-deficient and control females were mated with vitamin D-normal males and upon birth of the pups, all dams were returned to a diet containing vitamin D. The adult offspring were tested on a range of cognitive behavioural tests, including the five-choice serial reaction task (5C-SRT) and five-choice continuous performance test (5C-CPT), as well as latent inhibition using a fear conditioning paradigm. DVD deficiency was not associated with altered attentional performance on the 5C-SRT. In the 5C-CPT DVD-deficient male mice exhibited an impairment in inhibiting repetitive responses by making more perseverative responses, with no changes in premature or false alarm responding. DVD deficiency did not affect the acquisition or retention of cued fear conditioning, nor did it affect the expression of latent inhibition using a fear conditioning paradigm. DVD-deficient mice exhibited no major impairments in any of the cognitive domains tested. However, impairments in perseverative responding in DVD-deficient mice may indicate that these animals have specific alterations in systems governing compulsive or reward-seeking behaviour

Being young in a changing world: how temperature and salinity changes interactively modify the performance of larval stages of the barnacle Amphibalanus improvisus

The fate of key species, such as the barnacle Amphibalanus improvisus, in the course of global change is of particular interest since any change in their abundance and/or performance may entail community-wide effects. In the fluctuating Western Baltic, species typically experience a broad range of environmental conditions, which may preselect them to better cope with climate change. In this study, we examined the sensitivity of two crucial ontogenetic phases (naupliar, cypris) of the barnacle toward a range of temperature (12, 20, and 28°C) and salinity (5, 15, and 30 psu) combinations. Under all salinity treatments, nauplii developed faster at intermediate and high temperatures. Cyprid metamorphosis success, in contrast, was interactively impacted by temperature and salinity. Survival of nauplii decreased with increasing salinity under all temperature treatments. Highest settlement rates occurred at the intermediate temperature and salinity combination, i.e., 20°C and 15 psu. Settlement success of “naive” cyprids, i.e., when nauplii were raised in the absence of stress (20°C/15 psu), was less impacted by stressful temperature/salinity combinations than that of cyprids with a stress history. Here, settlement success was highest at 30 psu particularly at low and high temperatures. Surprisingly, larval survival was not highest under the conditions typical for the Kiel Fjord at the season of peak settlement (20°C/15 psu). The proportion of nauplii that ultimately transformed to attached juveniles was, however, highest under these “home” conditions. Overall, only particularly stressful combinations of temperature and salinity substantially reduced larval performance and development. Given more time for adaptation, the relatively smooth climate shifts predicted will probably not dramatically affect this species

Hedgehog Signaling in Tumor Cells Facilitates Osteoblast-Enhanced Osteolytic Metastases

The remodeling process in bone yields numerous cytokines and chemokines that mediate crosstalk between osteoblasts and osteoclasts and also serve to attract and support metastatic tumor cells. The metastatic tumor cells disturb the equilibrium in bone that manifests as skeletal complications. The Hedgehog (Hh) pathway plays an important role in skeletogenesis. We hypothesized that the Hh pathway mediates an interaction between tumor cells and osteoblasts and influences osteoblast differentiation in response to tumor cells. We have determined that breast tumor cells have an activated Hh pathway characterized by upregulation of the ligand, IHH and transcription factor GLI1. Breast cancer cells interact with osteoblasts and cause an enhanced differentiation of pre-osteoblasts to osteoblasts that express increased levels of the osteoclastogenesis factors, RANKL and PTHrP. There is sustained expression of osteoclast-promoting factors, RANKL and PTHrP, even after the osteoblast differentiation ceases and apoptosis sets in. Moreover, tumor cells that are deficient in Hh signaling are compromised in their ability to induce osteoblast differentiation and consequently are inefficient in causing osteolysis. The stimulation of osteoblast differentiation sets the stage for osteoclast differentiation and overall promotes osteolysis. Thus, in the process of developing newer therapeutic strategies against breast cancer metastasis to bone it would worthwhile to keep in mind the role of the Hh pathway in osteoblast differentiation in an otherwise predominant osteolytic phenomenon

Strong Neutral Spatial Effects Shape Tree Species Distributions across Life Stages at Multiple Scales

Traditionally, ecologists use lattice (regional summary) count data to simulate tree species distributions to explore species coexistence. However, no previous study has explicitly compared the difference between using lattice count and basal area data and analyzed species distributions at both individual species and community levels while simultaneously considering the combined scenarios of life stage and scale. In this study, we hypothesized that basal area data are more closely related to environmental variables than are count data because of strong environmental filtering effects. We also address the contribution of niche and the neutral (i.e., solely dependent on distance) factors to species distributions. Specifically, we separately modeled count data and basal area data while considering life stage and scale effects at the two levels with simultaneous autoregressive models and variation partitioning. A principal coordinates of neighbor matrix (PCNM) was used to model neutral spatial effects at the community level. The explained variations of species distribution data did not differ significantly between the two types of data at either the individual species level or the community level, indicating that the two types of data can be used nearly identically to model species distributions. Neutral spatial effects represented by spatial autoregressive parameters and the PCNM eigenfunctions drove species distributions on multiple scales, different life stages and individual species and community levels in this plot. We concluded that strong neutral spatial effects are the principal mechanisms underlying the species distributions and thus shape biodiversity spatial patterns

The impact of psychological factors on recovery from injury: a multicentre cohort study

Purpose Unintentional injuries have a significant long-term health impact in working age adults. Depression, anxiety and post-traumatic stress disorder are common post-injury, but their impact on self-reported recovery has not been investigated in general injury populations. This study investigated the role of psychological predictors 1 month post-injury in subsequent self-reported recovery from injury in working-aged adults. Methods A multicentre cohort study was conducted of 668 unintentionally injured adults admitted to five UK hospitals followed up at 1, 2, 4 and 12 months post-injury. Logistic regression explored relationships between psychological morbidity 1 month post-injury and self-reported recovery 12 months post-injury, adjusting for health, demographic, injury and socio-legal factors. Multiple imputations were used to impute missing values. Results A total of 668 adults participated at baseline, 77% followed up at 1 month and 63% at 12 months, of whom 383 (57%) were included in the main analysis. Multiple imputation analysis included all 668 participants. Increasing levels of depression scores and increasing levels of pain at 1 month and an increasing number of nights in hospital were associated with significantly reduced odds of recovery at 12 months, adjusting for age, sex, centre, employment and deprivation. The findings were similar in the multiple imputation analysis, except that pain had borderline statistical significance. Conclusions Depression 1 month post-injury is an important predictor of recovery, but other factors, especially pain and nights spent in hospital, also predict recovery. Identifying and managing depression and providing adequate pain control are essential in clinical care post-injury