Analysis of the mobilities of band 3 populations associated with ankyrin protein and junctional complexes in intact murine erythrocytes

Current models of the erythrocyte membrane depict three populations of band 3: (i) a population tethered to spectrin via ankyrin, (ii) a fraction attached to the spectrin-actin junctional complex via adducin, and (iii) a freely diffusing population. Because many studies of band 3 diffusion also distinguish three populations of the polypeptide, it has been speculated that the three populations envisioned in membrane models correspond to the three fractions observed in diffusion analyses. To test this hypothesis, we characterized band 3 diffusion by single-particle tracking in wild-type and ankyrin- and adducin-deficient erythrocytes. We report that ～40% of total band 3 in wild-type murine erythrocytes is attached to ankyrin, whereas ～33% is immobilized by adducin, and ～27% is not attached to any cytoskeletal anchor. More detailed analyses reveal that mobilities of individual ankyrin- and adducin-tethered band 3 molecules are heterogeneous, varying by nearly 2 orders of magnitude and that there is considerable overlap in diffusion coefficients for adducin and ankyrin-tethered populations. Taken together, the data suggest that although the ankyrin- and adducin-immobilized band 3 can be monitored separately, significant heterogeneity still exists within each population, suggesting that structural and compositional properties likely vary considerably within each band 3 complex.     

Family history of cancer and non-malignant diseases and risk of childhood acute lymphoblastic leukemia: a Children's Oncology Group Study

Background: Studies of family history of cancer and non-malignant diseases in childhood acute lymphoblastic leukemia (ALL) show inconsistent findings. Most studies show no increased risk with family history of cancer. Non-malignant diseases such as allergic diseases, autoimmune diseases, birth defects and thyroid diseases have been reported to be associated with ALL. Methods: We conducted a case-control study of family history of cancer and selected non-malignant conditions (allergic diseases, autoimmune diseases, birth defects, and thyroid diseases). ALL cases were obtained from Children's Cancer Group institutions from January 1989 to June 1993. Controls were recruited via random digit dialing. Family history for first degree relatives and grandparents of ALL cases and controls was collected by structured telephone questionnaires. Conditional logistical regression was used to calculate odds ratios adjusting for potential confounders. Results: We found a borderline association of ALL and having a family member with a history of cancer in cases (n = 1842) compared to controls (n = 1986) (OR = 0.98, 95%CI = 0.93, 1.00) and an inverse association for esophageal cancer based on small numbers. Family history of food and drug allergies demonstrated a modestly reduced risk (OR = 0.83, 95%CI = 0.73, 0.95) as did family history of rheumatoid arthritis (OR = 0.79, 95%CI = 0.65, 0.96). There were no associations with family history of any autoimmune diseases, immunodeficiencies, birth defects, thyroid diseases and risk of childhood ALL. Conclusions: These results show no association of overall family history of cancer with childhood ALL, while providing additional evidence for an inverse association with family history of allergic disease. Two potentially new associations of ALL with family history of esophageal cancer and rheumatoid arthritis require confirmation in other studies and validation with medical records.     

Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study

Introduction

Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [¹⁸F]FDG and [¹¹C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [¹⁸F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference.

Methods

In a stepwise approach different PET tracers were investigated. First, whole body [¹⁸F]FDG and [¹¹C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [¹⁸F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data.

Results

No increased [¹⁸F]FDG and [¹¹C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [¹⁸F]Fluoride PET-CT, [¹⁸F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [¹⁸F]FDG depicted only three lesions, with an uptake of five times lower compared to [¹⁸F]Fluoride, and again no [¹¹C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [¹⁸F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [¹⁸F]Fluoride PET positive lesions.

Conclusions

Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [¹⁸F]Fluoride. In contrast to active RA, inflammation tracers [¹⁸F]FDG and [¹¹C](R)PK11195 appeared to be less useful for AS imaging.     

Distribution of Influenza-Like Illness (ILI) by Occupation in Washington State,September 2009–August 2010

Objectives

: We aim to estimate the prevalence of influenza-like illness (ILI) by occupation and to identify occupations associated with increased ILI prevalence.

Methods

Between September 2009 and August 2010, the Centers for Disease Control (CDC) included questions on ILI symptoms on the Behavioral Risk Factor Surveillance System (BRFSS). Washington State collects the occupation of all employed BRFSS respondents. ILI prevalence and prevalence ratios (PR) were calculated by occupational group.

Results

There were 8,758 adult, currently employed, non-military respondents to the Washington BRFSS during the study period. The ILI prevalence for all employed respondents was 6.8% (95% Confidence Interval (95% CI) = 6.1, 7.6). PRs indicated a lower prevalence of ILI in Technicians (PR = 0.4, 95% CI = 0.2, 0.9) and Truck Drivers (PR = 0.2, 95% CI = 0.1, 0.7) and higher prevalence in Janitors and Cleaners (PR = 2.5, 95% CI = 1.3, 4.7) and Secretaries (PR = 2.4, 95% CI = 1.1, 5.4).

Conclusions

Some occupations appear to have higher prevalence of ILI than others. These occupational differences may be explained, in part, by differing levels of social contact with the public or contact with contaminated surfaces at work, or by other occupational factors such as stress or access to health care resources.     

Chromatin dynamics and gene positioning

The mammalian cell nucleus provides a landscape where genes are regulated through their organization and association with freely diffusing proteins and nuclear domains. In many cases, specific genes are highly dynamic, and the principles governing their movements and interchromosomal interactions are currently under intensive study. Recent investigations have implicated actin and myosin in chromatin dynamics and gene expression. Here, we discuss our current understanding of the dynamics of the interphase genome and how it impacts nuclear organization and gene activity.     

Identification of PLCL1 gene for hip bone size variation in females in a genome-wide association study

Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating approximately 380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72x10(-7). The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62x10(-3) and 2.44x10(-3), respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values<10(-5) in the two samples. The PLCL1 gene's relevance to HF was also observed in a Chinese sample containing 403 females, including 266 with HF and 177 control subjects. A SNP of the PLCL1 gene, rs3771362 that is only approximately 0.6 kb apart from the most significant SNP detected in our GWAS (rs7595412), achieved a p value of 7.66x10(-3) (odds ratio = 0.26) for association with HF. Additional biological support for the role of PLCL1 in BS comes from previous demonstrations that the PLCL1 protein inhibits IP3 (inositol 1,4,5-trisphosphate)-mediated calcium signaling, an important pathway regulating mechanical sensing of bone cells. Our findings suggest that PLCL1 is a novel gene associated with variation in hip BS, and provide new insights into the pathogenesis of HF.     

Effects of Degradation and Replacement of Southern Brazilian Coastal Sandy Vegetation on the Dung Beetles (Coleoptera: Scarabaeidae)

In this paper we address the effects of anthropogenic disturbance and replacement of Brazilian Coastal sandy vegetation (restingas) on dung beetles communities. We sampled dung beetles in the four main vegetative physiognomies of Guriri Island, Espírito Santo State: forest restinga, restinga Clusia, disturbed restinga (from burning events), and pastures. We placed four sets of two pitfall traps (baited with horse and human dung) in four independent areas of each vegetation type, and collected 14,534 individuals of 13 dung beetle species. Neither log₁₀ of individuals nor log₁₀ of species richness were good predictors of restinga disturbance. However, a significant amount of variation in dung beetle abundance and richness could be explained by bait type. Ordination of these sites using hybrid multidimensional scaling revealed a gradient of habitat disturbance from undisturbed restinga samples to pasture. Dung beetle communities along this gradient demonstrated a complete turnover in species composition, from restinga‐specialists to invasive and generalists species respectively. This complete turnover signals the local extirpation of forest‐adapted species in disturbed and converted areas. Only a single dung beetle species in preserved restingas is protected by Brazilian law (Dichotomius schiffleri). Given the extent of the clearing of restinga habitat, the conservation status of dung beetles associated with restinga forest gives cause for concern.