The Fibrinogen Molecule: Its Size, Shape, and Mode of Polymerization

Improved electron micrographs of the shadow-cast bovine fibrinogen molecule have been obtained establishing its general morphology and dimensions in the dry state. It consists of a linear array of 3 nodules held together by a very thin thread which is estimated to have a diameter of from 8 to 15 A, though it is not clearly resolved. The two end nodules are alike but the center one is slightly smaller. Measurements of shadow lengths indicate that nodule diameters are in the range 50 to 70 A. The length of the dried molecule is 475 ± 25 A. Adopting the molecular volume from previous physical chemical data and the general morphological features and length from electron microscopy, we calculate the diameters of the end nodules to be 65 A and the center one as 50 A. The model of the molecule so obtained is consistent with the electron microscopical observations and the data from physical chemistry. The intermediate polymers formed when fibrinogen is activated with thrombin were also examined and found to be end-to-end aggregates of altered fibrinogen molecules which shrink in length during the process. Intermediate polymer lengths are from 1000 to 5000 A. The nodular nature of fibrinogen, its shrinkage and end-to-end aggregation on polymerization permits us to deduce an explanation for the system of cross-bands previously observed in stained fibrin fibrils.     

Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development

An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p?=?10(-20)) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p?=?10(-23)). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p?=?0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p?=?0.01), and earlier AR (-4.72% (-5.81, -3.63), p?=?10(-17)), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.     

The relation between the specific absorption rate and electromagnetic field intensity for heterogeneous exposure conditions at mobile communications frequencies

The relation between the incident electromagnetic field strength and both the whole‐body and the local specific absorption rate (SAR) was investigated for typical heterogeneous exposure scenarios for frequencies relevant for mobile communication. The results were compared to results from plane wave exposure. Heterogeneous exposure arises from multiple path propagation of the electromagnetic waves to the location of interest. It is shown that plane wave exposure does not represent worst‐case exposure conditions. When the electric field strength arising at plane wave exposure is compared to the electric field strength averaged over the volume of the human body occurring during multipath exposure, 12% of all heterogeneous cases examined represent worse exposure conditions than plane wave exposure for whole‐body exposure at 946 MHz, 15% at 1840 MHz, and 22% at 2140 MHz. The deviation between plane wave and heterogeneous whole‐body SAR ranges from ?54% to 54%. For partial‐body SAR averaged over 10 g of tissue, a range from ?93% to 209% was found when comparing multiple wave exposure to single incoming plane waves. The investigations performed using the Visible Human as phantom showed that the basic restrictions are met as long as the reference levels are not exceeded. However, this must not be necessarily the case when different phantoms are used to perform similar investigations because recent studies demonstrated that reference levels might not be conservative when phantoms of children are used. Therefore, the results of this work indicate the need to extend the investigations to numerical simulations with additional human phantoms representing parts of the human population having different anatomy and morphology compared to the phantom used within the frame of this project. This also applies to phantoms of children. Bioelectromagnetics 30:651–662, 2009. © 2009 Wiley‐Liss, Inc.     

Structure-based de novo design of ligands using a three-dimensional model of the insulin receptor

For the first time, a three-dimensional model of the insulin receptor is used in the de novo design of novel ligands that potentially mimic interactions of insulin at its receptor. Compound 4 competed with insulin as seen in autophosphorylation assays and inhibited up to 68% of IR autophosphorylation at 300 microM of 4 in 3T3IR cells induced by 1 nM insulin. This model provides a basis for the design of potent insulin receptor ligands.     

Mycoplasmosis in free-ranging desert tortoises in Utah and Arizona

Upper respiratory tract disease (URTD) has been associated with major losses of free-ranging desert tortoises (Gopherus agassizii) in the southwestern United States. This prompted a clinical examination of 63 free-ranging desert tortoises for signs of URTD and sampling for Mycoplasma agassizii, the causative agent of URTD. Tortoises were sampled from three sites in the eastern Mojave Desert (1992-93), and from three sites in the Sonoran Desert (1992-94). Plasma samples were tested for antibodies to M. agassizii using an enzyme-linked immunosorbent assay (ELISA). Nasal aspirate samples from 12 Sonoran tortoises were tested using polymerase chain reaction (PCR) test directed at the 16S rRNA gene of M. agassizii. Nasal aspirate samples from all tortoises were cultured for M. agassizii. In the Mojave Desert, nine tortoises had clinical signs of URTD and eight were seropositive for M. agassizii. In the Sonoran Desert, there were no clinical signs of URTD, but two tortoises were seropositive, and two tortoises had positive PCR results.     

Striped bass survival in Lake Blackshear,Georgia during drought conditions: implications for restoration efforts in Gulf of Mexico drainages

Synopsis Endemic striped bass Morone saxatilis (Walbaum) populations in Gulf Coast rivers have declined dramatically since the 1940s as a result of anthropogenic activities that limited access to historical spawning areas and adversely affected cool-water springs. Efforts to restore these populations to self-sustaining levels have been under way since the 1950s and continue to the present. In 1998–1999, we fitted 27 adult Gulf-strain striped bass with radio transmitters and released them in Lake Blackshear, Georgia. We used data on their survival, habitat use, and movement patterns to assess the potential long-term survival of fingerling striped bass stocked in this lake since 1996. Overall, we re-located only 27% of tagged fish in cool-water springs, and all radio-tagged striped bass that remained in the lake died during summer. Drought conditions based on rainfall and groundwater withdrawals during the study caused some cool-water springs in Lake Blackshear to stop flowing. Lake temperatures >27°C for 13 consecutive weeks, die-offs of non-tagged fish, intermittent spring flows, and widespread mortality of tagged fish suggest that the long-term survival of stocked striped bass in Lake Blackshear probably will be poor. Successful re-introductions of Gulf-strain striped bass to rivers and reservoirs in their historic range will depend on the presence of cool-water springs. The persistence, abundance, and sizes of springs in this region are heavily dependent on the periodicity of droughts and the magnitude of groundwater use. Regional climatological data indicate that droughts occur about every 3years. Therefore, better management of groundwater withdrawals during drought periods will become increasingly important to maintain aquifer levels (and cool-water springs) needed for restoring native striped bass to Gulf Coast rivers.     

Human Papillomavirus (HPV) Vaccination and Adolescent Girls' Knowledge and Sexuality in Western Uganda: A Comparative Cross-Sectional Study

The purpose of the study was to investigate the influence of human papillomavirus (HPV) vaccination on adolescent girls’ knowledge of HPV and HPV vaccine, perception of sexual risk and intentions for sexual debut. This cross-sectional comparative study was conducted in Ibanda and Mbarara districts. Data was collected using a standardized self-administered questionnaire and analyzed using the Statistical Package for the Social Sciences computer software. Univariate, bivariate, and logistic regression analyses were conducted with significance level set at p < .05. Results showed that HPV vaccination was associated with being knowledgeable (Crude OR: 5.26, CI: 2.32–11.93; p = 0.000). Vaccination against HPV did not predict perception of sexual risk. Knowledge was low (only 87/385 or 22.6% of vaccinated girls were knowledgeable), but predicted perception of a high sexual risk (Adjusted OR: 3.12, CI: 1.37–3.63; p = 0.008). HPV vaccination, knowledge and perceived sexual risk did not predict sexual behaviour intentions. High parental communication was associated with adolescent attitudes that support postponement of sexual debut in both bivariate and multiple regression analyses. In conclusion, findings of this study suggest that HPV vaccination is not likely to encourage adolescent sexual activity. Influence of knowledge on sexual behaviour intentions was not definitively explained. Prospective cohort studies were proposed to address the emerging questions.     

Anti-Inflammatory Activity of Purine Nucleoside Analogs

Abstract

It is well known that adenosine plays an important role in inflammatory processes. A collection of adenosine analogs modified in the base and/or sugar functional moiety have been synthesized and submitted for biological testing. Each purine nucleoside analog was tested for inhibition of endothelial cell activation by various inflammatory stimuli. A number of analogs exhibited potent anti-inflammatory activity. Animal studies have been carried out on AMG002370 which was found to potently inhibit adjuvant induced arthritis in the Lewis rat.