Lineage analysis of the olfactory epithelium using a replication-incompetent retrovirus

We have analysed the lineage of olfactory receptor neurons usinga replication-incompetent retrovirus injected beneath the olfactoryepithelium of young rats. There are two major types of clustersof infected cells seen at 5–40 days after infection: (i)horizontal basal cells (HBCs); (ii) variable numbers of globosebasal cells (GBCs), and immature and mature sensory neurons.Olfactory nerve lesion increased the frequency of the globose/sensoryneuron clusters, as well as the number of cells/cluster, butdid not change the number of HBC clusters or cells/cluster.No clusters contained sustentacular cells. These data indicatethat, at least in young rats: (i) HBCs are not precursors ofolfactory neurons; (ii) there is a lineage path from GBCs tomature neurons; and (iii) sustentacular cells arise from a separatelineage.     

Acanthocephaloides cyrusi n. sp. (Acanthocephala: Arhythmacanthidae) from southeast African teleost fishes

A new species,Acanthocephaloides cyrusi, is described from the fishesSolea bleekeri andPomadasys commersoni from Lake St. Lucia, Natal, South Africa. It is distinguished from the other species in the genus by the more marked sexual dimorphism in length, the arrangement of hooks, the proboscis with the longest hooks at the anterior-most extremity and the greater size of the proboscis hooks and body spines. An acanthella, which may represent this species, was found in the tanaidApseudes digitalis.     

Disparity in Physician Perception of Patients' Adherence to Medications by Obesity Status

Physician perception of medication adherence may alter prescribing patterns. Perception of patients has been linked to readily observable factors, such as race and age. Obesity shares a similar stigma to these factors in society. We hypothesized that physicians would perceive patients with a higher BMI as nonadherent to medication. Data were collected from the baseline visit of a randomized clinical trial of patient–physician communication (240 patients and 40 physicians). Physician perception of patient medication adherence was measured on a Likert scale and dichotomized as fully adherent or not fully adherent. BMI was the predictor of interest. We performed Poisson regression analyses with robust variance estimates, adjusting for clustering of patients within physicians, to examine the association between BMI and physician perception of medication adherence. The mean (s.d.) BMI was 32.6 (7.7) kg/m². Forty‐five percent of patients were perceived as nonadherent to medications by their physicians. Higher BMI was significantly and negatively associated with being perceived as adherent to medication (prevalence ratio (PrR) 0.76, 95% confidence interval (CI): 0.64–0.90; P = 0.002; per 10 kg/m² increase in BMI). BMI remained significantly and negatively associated with physician perception of medication adherence after adjustment for patient and physician characteristics (PrR 0.80, 95% CI: 0.66–0.96; P = 0.020). In this study, patients with higher BMI were less likely to be perceived as adherent to medications by their providers. Physician perception of medication adherence has been shown to affect prescribing patterns in other studies. More work is needed to understand how this perception may affect the care of patients with obesity.     

Nuclear envelope‐associated dynein drives prophase centrosome separation and enables Eg5‐independent bipolar spindle formation

The microtubule motor protein kinesin‐5 (Eg5) provides an outward force on centrosomes, which drives bipolar spindle assembly. Acute inhibition of Eg5 blocks centrosome separation and causes mitotic arrest in human cells, making Eg5 an attractive target for anti‐cancer therapy. Using in vitro directed evolution, we show that human cells treated with Eg5 inhibitors can rapidly acquire the ability to divide in the complete absence of Eg5 activity. We have used these Eg5‐independent cells to study alternative mechanisms of centrosome separation. We uncovered a pathway involving nuclear envelope (NE)‐associated dynein that drives centrosome separation in prophase. This NE‐dynein pathway is essential for bipolar spindle assembly in the absence of Eg5, but also functions in the presence of full Eg5 activity, where it pulls individual centrosomes along the NE and acts in concert with Eg5‐dependent outward pushing forces to coordinate prophase centrosome separation. Together, these results reveal how the forces are produced to drive prophase centrosome separation and identify a novel mechanism of resistance to kinesin‐5 inhibitors.     

A physiological analogy of the niche for projecting the potential distribution of plants

Aim  To develop a physiologically based model of the plant niche for use in species distribution modelling. Location  Europe. Methods  We link the Thornley transport resistance (TTR) model with functions which describe how the TTR’s model parameters are influenced by abiotic environmental factors. The TTR model considers how carbon and nutrient uptake, and the allocation of these assimilates, influence growth. We use indirect statistical methods to estimate the model parameters from a high resolution data set on tree distribution for 22 European tree species. Results  We infer, from distribution data and abiotic forcing data, the physiological niche dimensions of 22 European tree species. We found that the model fits were reasonable (AUC: 0.79–0.964). The projected distributions were characterized by a false positive rate of 0.19 and a false negative rate 0.12. The fitted models are used to generate projections of the environmental factors that limit the range boundaries of the study species. Main conclusions  We show that physiological models can be used to derive physiological niche dimensions from species distribution data. Future work should focus on including prior information on physiological rates into the parameter estimation process. Application of the TTR model to species distribution modelling suggests new avenues for establishing explicit links between distribution and physiology, and for generating hypotheses about how ecophysiological processes influence the distribution of plants.     

Short hairpin RNAs against eotaxin or interleukin‐5 decrease airway eosinophilia and hyper‐responsiveness in a murine model of asthma

Background

Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up‐regulation of eotaxin, which, together with interleukin (IL)‐5, is important for differentiation, chemo‐attraction, degranulation, and survival of eosinophils in local tissue. In a previous study, we found that administration of lentivirus‐delivered short hairpin RNA (shRNA) to suppress the expression of IL‐5 inhibited airway inflammation. The present study aimed to investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and IL‐5 shRNAs on airway inflammation in an ovalbumin (OVA)‐induced murine model of asthma.

Methods

Lentivirus‐delivered shRNAs were used to suppress the expression of eotaxin and/or IL‐5 in local tissue in an OVA‐induced murine asthma model.

Results

Intra‐tracheal administration of lentivirus containing eotaxin shRNA expressing cassette (eoSEC3.3) efficiently moderated the characteristics of asthma, including airway hyper‐responsiveness, cellular infiltration of lung tissues, and eotaxin and IL‐5 levels in bronchio‐alveolar lavage fluid. Administration of lentiviruses expressing IL‐5 or eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model.

Conclusions

Local delivery of lentiviruses expressing IL‐5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia. Copyright © 2008 John Wiley & Sons, Ltd.     

Absence of functional and structural homology of natural and recombinant human leukocyte interferon (IFN-α) with human α-ACTH and β-endorphin

A comparison of the amino acid sequence of one human recombinant IFN-α (IFLrA) with either human β-endorphin or ACTH reveals only a minimal and insignificant degree of homology. Also, synthetic ACTH, β-endorphin and β-endorphin-(1–15) have no antiviral protective effects on human fibroblasts and cannot inhibit the neutralization of the antiviral effects of natural IFN-α by an antiserum directed against the interferon. Anti ACTH and Anti β-endorphin do not neutralize the antiviral effects of IFLrA, and radioimmunoassays of partially purified natural IFN-α and pure IFLrA do not reveal any evidence of α-MSH or β-endorphin-like material in the interferons. These results demonstrate an absence of functional and structural homology of natural and recombinant IFN-α with ACTH and β-endorphin.     

How Can the Eco‐efficiency of a Region be Measured and Monitored?

The concept of eco-efficiency is commonly referred to as a business link to sustainable development. In this article, ecoefficiency is examined at a regional level as an approach to promoting the competitiveness of economic activities in the Finnish Kymenlaakso region and mitigating their harmful impacts on the environment. The aim is to develop appropriate indicators for monitoring changes in the eco-efficiency of the region. A starting point is to produce indicators for the environmental and economic dimensions of regional development and use them for measuring regional eco-efficiency. The environmental impact indicators are based on a life-cycle assessment method, producing different types of environmental impact indicators: pressure indicators (e.g., emissions of CO₂), impact category indicators (e.g., CO₂ equivalents in the case of climate change), and a total impact indicator (aggregating different impact category indicator results into a single value). Environmental impact indicators based on direct material input, total material input, and total material requirement of the Kymenlaakso region are also assessed. The economic indicators used are the gross domestic product, the value added, and the output of the main economic sectors of Kymenlaakso. In the eco-efficiency assessment, the economic and environmental impact indicators are monitored in the same graph. In a few cases eco-efficiency ratios can also be calculated (the economic indicators are divided by the environmental indicators). Output (= value added + intermediate consumption) is used as an economic indicator related to the environmental impact indicators, which also cover the upstream processes of the region's activities. In the article, we also discuss the strengths and weaknesses of using the different environmental impact indicators.