A Blue Spectral Shift of the Hemoglobin Soret Band Correlates with the Age (Time Since Deposition) of Dried Bloodstains

The ability to determine the time since deposition of a bloodstain found at a crime scene could prove invaluable to law enforcement investigators, defining the time frame in which the individual depositing the evidence was present. Although various methods of accomplishing this have been proposed, none has gained widespread use due to poor time resolution and weak age correlation. We have developed a method for the estimation of the time since deposition (TSD) of dried bloodstains using UV-VIS spectrophotometric analysis of hemoglobin (Hb) that is based upon its characteristic oxidation chemistry. A detailed study of the Hb Soret band (λmax = 412 nm) in aged bloodstains revealed a blue shift (shift to shorter wavelength) as the age of the stain increases. The extent of this shift permits, for the first time, a distinction to be made between bloodstains that were deposited minutes, hours, days and weeks prior to recovery and analysis. The extent of the blue shift was found to be a function of ambient relative humidity and temperature. The method is extremely sensitive, requiring as little as a 1 µl dried bloodstain for analysis. We demonstrate that it might be possible to perform TSD measurements at the crime scene using a portable low-sample-volume spectrophotometer

Nutrient Enrichment and Food Web Composition Affect Ecosystem Metabolism in an Experimental Seagrass Habitat

Food web composition and resource levels can influence ecosystem properties such as productivity and elemental cycles. In particular, herbivores occupy a central place in food webs as the species richness and composition of this trophic level may simultaneously influence the transmission of resource and predator effects to higher and lower trophic levels, respectively. Yet, these interactions are poorly understood.Using an experimental seagrass mesocosm system, we factorially manipulated water column nutrient concentrations, food chain length, and diversity of crustacean grazers to address two questions: (1) Does food web composition modulate the effects of nutrient enrichment on plant and grazer biomasses and stoichiometry? (2) Do ecosystem fluxes of dissolved oxygen and nutrients more closely reflect above-ground biomass and community structure or sediment processes? Nutrient enrichment and grazer presence generally had strong effects on biomass accumulation, stoichiometry, and ecosystem fluxes, whereas predator effects were weaker or absent. Nutrient enrichment had little effect on producer biomass or net ecosystem production but strongly increased seagrass nutrient content, ecosystem flux rates, and grazer secondary production, suggesting that enhanced production was efficiently transferred from producers to herbivores. Gross ecosystem production (oxygen evolution) correlated positively with above-ground plant biomass, whereas inorganic nutrient fluxes were unrelated to plant or grazer biomasses, suggesting dominance by sediment microbial processes. Finally, grazer richness significantly stabilized ecosystem processes, as predators decreased ecosystem production and respiration only in the zero- and one- species grazer treatments.Overall, our results indicate that consumer presence and species composition strongly influence ecosystem responses to nutrient enrichment, and that increasing herbivore diversity can stabilize ecosystem flux rates in the face of perturbations

A systematic variation of the stellar initial mass function in early-type galaxies

Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars. It depends on the stellar initial mass function (IMF) describing the distribution of stellar masses when the population formed. Consequently knowledge of the IMF is critical to virtually every aspect of galaxy evolution. More than half a century after the first IMF determination, no consensus has emerged on whether it is universal in different galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot be both universal, but they could not break the degeneracy between the two effects. Only recently indications were found that massive elliptical galaxies may not have the same IMF as our Milky Way. Here we report unambiguous evidence for a strong systematic variation of the IMF in early-type galaxies as a function of their stellar mass-to-light ratio, producing differences up to a factor of three in mass. This was inferred from detailed dynamical models of the two-dimensional stellar kinematics for the large Atlas3D representative sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass. Our finding indicates that the IMF depends intimately on a galaxy's formation history.Comment: 4 pages, 2 figures, LaTeX. Accepted for publication as a Nature Letter. More information about our Atlas3D project is available at http://purl.org/atlas3

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan Africa, <it>Plasmodium falciparum </it>malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance of the different types of malaria diagnosis as well as risk factors associated with malaria infection at delivery were investigated.</p> <p>Method</p> <p>In a cross-sectional survey, 306 women reporting for delivery in the Mutenegene maternity clinic, Fako division, South West province, Cameroon were screened for <it>P. falciparum </it>in peripheral blood, placental blood and placental tissue sections by microscopy. Information relating to the use of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine, history of fever attack, infant birth weights and maternal anaemia were recorded.</p> <p>Results</p> <p>Among these women, <it>P. falciparum </it>infection was detected in 5.6%, 25.5% and 60.5% of the cases in peripheral blood, placental blood and placental histological sections respectively. Placental histology was more sensitive (97.4%) than placental blood film (41.5%) and peripheral blood (8.0%) microscopy. In multivariate analysis, age (≤ 20 years old) (OR = 4.61, 95% CI = 1.47 – 14.70), history of fever attack (OR = 2.98, 95% CI = 1.58 – 5.73) were significant risk factors associated with microscopically detected parasitaemia. The use of ≥ 2 SP doses (OR = 0.18, 95% CI = 0.06 – 0.52) was associated with a significant reduction in the prevalence of microscopic parasitaemia at delivery. Age (>20 years) (OR = 0.34, 95% CI = 0.15 – 0.75) was the only significant risk factor associated with parasitaemia diagnosed by histology only in univariate analysis. Microscopic parasitaemia (OR = 2.74, 95% CI = 1.33–5.62) was a significant risk factor for maternal anaemia at delivery, but neither infection detected by histology only, nor past infection were associated with increased risk of anaemia.</p> <p>Conclusion</p> <p>Placenta histological examination was the most sensitive indicator of malaria infection at delivery. Microscopically detected parasitaemia was associated with increased risk of maternal anaemia at delivery, but not low-grade parasitaemia detected by placental histology only.</p

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Evidence for a novel Kit adhesion domain mediating human mast cell adhesion to structural airway cells

Background: Human lung mast cells (HLMCs) infiltrate the airway epithelium and airway smooth muscle (ASM) in asthmatic airways. The mechanism of HLMC adhesion to both cell types is only partly defined, and adhesion is not inhibited by function-blocking anti-Kit and anti-stem cell factor (SCF) antibodies. Our aim was to identify adhesion molecules expressed by human mast cells that mediate adhesion to human ASM cells (HASMCs) and human airway epithelial cells. Methods: We used phage-display to isolate single chain Fv (scFv) antibodies with adhesion-blocking properties from rabbits immunised with HLMC and HMC-1 membrane proteins. Results: Post-immune rabbit serum labelled HLMCs in flow cytometry and inhibited their adhesion to human BEAS-2B epithelial cells. Mast cell-specific scFvs were identified which labelled mast cells but not Jurkat cells by flow cytometry. Of these, one scFv (A1) consistently inhibited mast cell adhesion to HASMCs and BEAS-2B epithelial cells by about 30 %. A1 immunoprecipitated Kit (CD117) from HMC-1 lysates and bound to a human Kit-expressing mouse mast cell line, but did not interfere with SCF-dependent Kit signalling. Conclusion: Kit contributes to human mast cell adhesion to human airway epithelial cells and HASMCs, but may utilise a previously unidentified adhesion domain that lies outside the SCF binding site. Targeting this adhesion pathway might offer a novel approach for the inhibition of mast cell interactions with structural airway cells, without detrimental effects on Kit signalling in other tissues

Protocol of a randomized controlled trial of the Tobacco Tactics website for operating engineers

<p>Abstract</p> <p>Background</p> <p>Recent research indicates that 35 percent of blue-collar workers in the US currently smoke while only 20 percent of white-collar workers smoke. Over the last year, we have been working with heavy equipment operators, specifically the Local 324 Training Center of the International Union of Operating Engineers, to study the epidemiology of smoking, which is 29% compared to 21% among the general population. For the current study funded by the National Cancer Institute (1R21CA152247-01A1), we have developed the Tobacco Tactics website which will be compared to the state supported 1-800-QUIT-NOW telephone line. Outcome evaluation will compare those randomized to the Tobacco Tactics web-based intervention to those randomized to the 1-800-QUIT-NOW control condition on: a) 30-day and 6-month quit rates; b) cotinine levels; c) cigarettes smoked/day; d) number of quit attempts; and e) nicotine addiction. Process evaluation will compare the two groups on the: a) contacts with intervention; b) medications used; c) helpfulness of the nurse/coach; and d) willingness to recommend the intervention to others.</p> <p>Methods/Design</p> <p>This will be a randomized controlled trial (N = 184). Both interventions will be offered during regularly scheduled safety training at Local 324 Training Center of the International Union of Operating Engineers and both will include optional provision of over-the-counter nicotine replacement therapy and the same number of telephone contacts. However, the Tobacco Tactics website has graphics tailored to Operating Engineers, tailored cessation feedback from the website, and follow up nurse counseling offered by multimedia options including phone and/or email, and/or e-community. Primary Analysis of Aim 1 will be conducted by using logistic regression to compare smoking habits (e.g., quit rates) of those in the intervention arm to those in the control arm. Primary analyses for Aim 2 will compare process measures (e.g., medications used) between the two groups by linear, logistic, and Poisson regression.</p> <p>Discussion</p> <p>Dissemination of an efficacious work-site, web-based smoking cessation intervention has the potential to substantially impact cancer rates among this population. Based on the outcome of this smaller study, wider scale testing in conjunction with the International Environment Technology Testing Center which services Operating Engineers across North America (including US, Mexico, and Canada) will be conducted.</p> <p>Trial registration</p> <p>NCT01124110</p

Potassium Dependent Regulation of Astrocyte Water Permeability Is Mediated by cAMP Signaling

Astrocytes express potassium and water channels to support dynamic regulation of potassium homeostasis. Potassium kinetics can be modulated by aquaporin-4 (AQP4), the essential water channel for astrocyte water permeability regulation. We investigated whether extracellular potassium ([K+]o) can regulate astrocyte water permeability and the mechanisms of such an effect. Studies were performed on rat primary astrocytes and a rat astrocyte cell line transfected with AQP4. We found that 10mM [K+]o caused an immediate, more than 40%, increase in astrocyte water permeability which was sustained in 5min. The water channel AQP4 was a target for this regulation. Potassium induced a significant increase in intracellular cAMP as measured with a FRET based method and with enzyme immunoassay. We found that protein kinase A (PKA) could phosphorylate AQP4 in vitro. Further elevation of [K+]o to 35mM induced a global intracellular calcium response and a transient water permeability increase that was abolished in 5min. When inwardly rectifying potassium (Kir)-channels were blocked, 10mM [K+]o also induced a calcium increase and the water permeability increase no longer persisted. In conclusion, we find that elevation of extracellular potassium regulates AQP4 and astrocyte water permeability via intracellular signaling involving cAMP. A prolonged increase of astrocyte water permeability is Kir-channel dependent and this response can be impeded by intracellular calcium signaling. Our results support the concept of coupling between AQP4 and potassium handling in astrocytes

Molecular characteristics of screen-detected vs symptomatic breast cancers and their impact on survival

BACKGROUND: Several recent studies have shown that screen detection remains an independent prognostic factor after adjusting for disease stage at presentation. This study compares the molecular characteristics of screen-detected with symptomatic breast cancers to identify if differences in tumour biology may explain some of the survival benefit conferred by screen detection. METHODS: A total of 1379 women (aged 50-70 years) with invasive breast cancer from a large population-based case-control study were included in the analysis. Individual patient data included tumour size, grade, lymph node status, adjuvant therapy, mammographic screening status and mortality. Immunohistochemistry was performed on tumour samples using 11 primary antibodies to define five molecular subtypes. The effect of screen detection compared with symptomatic diagnosis on survival was estimated after adjustment for grade, nodal status, Nottingham Prognostic Index (NPI) and the molecular markers. RESULTS: Fifty-six per cent of the survival benefit associated with screen-detected breast cancer was accounted for by a shift in the NPI, a further 3-10% was explained by the biological variables and more than 30% of the effect remained unexplained. CONCLUSION: Currently known biomarkers remain limited in their ability to explain the heterogeneity of breast cancer fully. A more complete understanding of the biological profile of breast tumours will be necessary to assess the true impact of tumour biology on the improvement in survival seen with screen detection