Effectiveness of a Novel Porphyrin Exhibiting Dark Toxicity against the Model Organism Mycobacterium smegmatis

Antimicrobial photodynamic therapy (PDT) utilizing porphyrins has emerged as a possible ancillary treatment against antibiotic resistant bacteria. Porphyrins, such a novel zinc containing porphyrin designated ZnP, create reactive oxygen species that are toxic to bacterial cells utilizing light by a mechanism that is not yet fully understood. Previous experiments have shown ZnP to be able to kill microorganisms in the dark which is unique to few porphyrins. The aim of this research is to understand the effect ZnP has on Mycobacterium smegmatis, a model organism for the pathogenic bacterium Mycobacterium tuburculosis which causes the lung infection tuberculosis. Further experimentation is to include understanding the effects of ZnP on M. smegmatis biofilm formation and disruption as well as antibiotic uptake in formerly antibiotic resistant cells

Basic Communication Course Students’ Perceptions of the Purpose and Their Role in the Peer Feedback Process

Students enrolled in the basic communication course often engage in peer feedback workshops to enhance presentational speaking competence. As such, peer feedback workshops in the basic communication course provide an opportunity for students to provide and receive feedback on speech form, structure, and delivery (Broeckelman-Post & Hosek, 2014). The present study qualitatively examined data from 110 students enrolled in a basic communication course to determine their perceptions of the peer feedback process and what role(s), if any, they believed they had in the peer feedback process. Our thematic analysis revealed that students’ perceive peer feedback as a form of agency, influence, and skill building and perceive their role as a content editor, audience/body, and performance evaluator. Limitations and future research directions are also discussed

Sortilin regulates sorting and secretion of Sonic hedgehog

Sonic Hedgehog (Shh) is a secreted morphogen that is an essential regulator of patterning and growth. The Shh full-length protein undergoes autocleavage in the ER to generate the biologically active amino-terminal ShhN fragment, which is destined for secretion. Few receptors have been identified that control the trafficking of this morphogen through the secretory pathway. We identified Sortilin (Sort1), a member of the VPS10P domain receptor family, as a novel Shh trafficking receptor. We demonstrate that Sort/Shh interact using co-IP and proximity ligation in transfected cells and that they co-localize to the Golgi. Sort1 overexpression causes re-distribution of ShhN, and to a lesser extent ShhFL, to the Golgi and reduces Shh secretion. We show loss of Sort1 can partially rescue Hedgehog-associated patterning defects in a mouse model of deficient Shh processing and that Sort1 levels negatively regulate anterograde Shh transport in axons in vitro and Hh-dependent axon-glial interactions in vivo Taken together, we conclude that Shh and Sort1 can interact at the level of the Golgi and that Sort1 directs Shh away from the pathways that promote its secretion

Effects of being uninsured or underinsured and living in high poverty neighborhoods on colon cancer care and survival in California: historical cohort analysis, 1996—2011

Background: We examined the mediating effects of health insurance on poverty-colon cancer care and survival relationships and the moderating effects of poverty on health insurance-colon cancer care and survival relationships among women and men in California. Methods: We analyzed registry data for 3,291 women and 3,009 men diagnosed with colon cancer between 1996 and 2000 and followed until 2011 on lymph node investigation, stage at diagnosis, surgery, chemotherapy, wait times and survival. We obtained socioeconomic data for individual residences from the 2000 census to categorize the following neighborhoods: high poverty (30% or more poor), middle poverty (5-29% poor) and low poverty (less than 5% poor). Primary health insurers were Medicaid, Medicare, private or none. Results: Evidence of mediation was observed for women, but not for men. For women, the apparent effect of poverty disappeared in the presence of payer, and the effects of all forms of health insurance seemed strengthened. All were advantaged on 6-year survival compared to the uninsured: Medicaid (RR = 1.83), Medicare (RR = 1.92) and private (RR = 1.83). Evidence of moderation was also only observed for women. The effects of all forms of health insurance were stronger for women in low poverty neighborhoods: Medicaid (RR = 2.90), Medicare (RR = 2.91) and private (RR = 2.60). For men, only main effects of poverty and payers were observed, the advantaging effect of private insurance being largest. Across colon cancer care processes, Medicare seemed most instrumental for women, private payers for men. Conclusions: Health insurance substantially mediates the quality of colon cancer care and poverty seems to make the effects of being uninsured or underinsured even worse, especially among women in the United States. These findings are consistent with the theory that more facilitative social and economic capital is available in more affluent neighborhoods, where women with colon cancer may be better able to absorb the indirect and direct, but uncovered, costs of care

Better Colon Cancer Care for Extremely Poor Canadian Women Compared with American Women

Extremely poor Canadian women were recently observed to be largely advantaged on most aspects of breast cancer care as compared with similarly poor, but much less adequately insured, women in the United States. This historical study systematically replicated the protective effects of single- versus multipayer health care by comparing colon cancer care among cohorts of extremely poor women in California and Ontario between 1996 and 2011. The Canadian women were again observed to have been largely advantaged. They were more likely to have received indicated surgery and chemotherapy, and their wait times for care were significantly shorter. Consequently, the Canadian women were much more likely to experience longer survival times. Regression analyses indicated that health insurance nearly completely explained the Canadian advantages. Implications for contemporary and future reforms of U.S. health care are discussed

Utilizing Computational Machine Learning Tools to Understand Immunogenic Breadth in the Context of a CD8 T-Cell Mediated HIV Response

Predictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals within a population and consideration of sequence diversity in the context of an individual's CD8 T-cell immune repertoire to assess the HIV proteome for defined regions of immunogenicity. Using this approach, analysis of HLA adaptation and functional immunogenicity data enabled the identification of regions within the proteome that offer significant conservation, HLA recognition within a population, low prevalence of HLA adaptation and demonstrated immunogenicity. We believe this unique and novel approach to vaccine design as a supplement to vitro functional assays, offers a bespoke pipeline for expedited and rational CD8 T-cell vaccine design for HIV and potentially other pathogens with the potential for both global and local coverage.Fil: McGowan, Ed. Imperial College London; Reino UnidoFil: Rosenthal, Rachel. Francis Crick Institute; Reino UnidoFil: Fiore Gartland, Andrew. Fred Hutchinson Cancer Research Cente; Estados UnidosFil: Macharia, Gladys. Imperial College London; Reino UnidoFil: Balinda, Sheila. Uganda Virus Research Institute; UgandaFil: Kapaata, Anne. Uganda Virus Research Institute; UgandaFil: Umviligihozo, Gisele. Center for Family Health Research; RuandaFil: Muok, Erick. Center for Family Health Research; RuandaFil: Dalel, Jama. Imperial College London; Reino UnidoFil: Streatfield, Claire L.. Imperial College London; Reino UnidoFil: Coutinho, Helen. Imperial College London; Reino UnidoFil: Dilernia, Dario. University of Emory; Estados UnidosFil: Monaco, Daniela C.. University of Emory; Estados UnidosFil: Morrison, David. South Walsham; Reino UnidoFil: Yue, Ling. University of Emory; Estados UnidosFil: Hunter, Eric. University of Emory; Estados UnidosFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gilmour, Jill. Imperial College London; Reino UnidoFil: Hare, Jonathan. International Aids Vaccine Initiative; Estados Unido

Public perceptions and attitudes toward thalassaemia: Influencing factors in a multi-racial population

<p>Abstract</p> <p>Background</p> <p>Thalassaemia is a common public health problem in Malaysia and about 4.5 to 6% of the Malays and Chinese are carriers of this genetic disorder. The major forms of thalassaemia result in death <it>in utero </it>of affected foetuses (α-thalassaemia) or life-long blood transfusions for survival in β-thalassaemia. This study, the first nationwide population based survey of thalassaemia in Malaysia, aimed to determine differences in public awareness, perceptions and attitudes toward thalassaemia in the multi-racial population in Malaysia.</p> <p>Methods</p> <p>A cross-sectional computer-assisted telephone interview survey of a representative sample of multi-racial Malaysians aged 18 years and above was conducted between July and December 2009.</p> <p>Results</p> <p>Of a total of 3723 responding households, 2846 (76.4%) have heard of thalassaemia. Mean knowledge score was 11.85 (SD ± 4.03), out of a maximum of 21, with higher scores indicating better knowledge. Statistically significant differences (<it>P </it>< 0.05) in total knowledge score by age groups, education attainment, employment status, and average household income were observed. Although the majority expressed very positive attitudes toward screening for thalassaemia, only 13.6% of married participants interviewed have been screened for thalassaemia. The majority (63.4%) were unsupportive of selective termination of foetuses diagnosed with thalassaemia major.</p> <p>Conclusion</p> <p>Study shows that carrier and premarital screening programs for thalassaemia may be more effective and culturally acceptable in the reduction of pregnancies with thalassaemia major. The findings provide insights into culturally congruent educational interventions to reach out diverse socio-demographic and ethnic communities to increase knowledge and cultivate positive attitudes toward prevention of thalassaemia.</p

Fast-Response Calmodulin-Based Fluorescent Indicators Reveal Rapid Intracellular Calcium Dynamics

Faithful reporting of temporal patterns of intracellular Ca 2 + dynamics requires the working range of indicators to match the signals. Current genetically encoded calmodulin-based fluorescent indicators are likely to distort fast Ca 2 + signals by apparent saturation and integration due to their limiting fluorescence rise and decay kinetics. A series of probes was engineered with a range of Ca 2 + affinities and accelerated kinetics by weakening the Ca 2 + -calmodulin-peptide interactions. At 37 °C, the GCaMP3-derived probe termed GCaMP3 fast is 40-fold faster than GCaMP3 with Ca 2 + decay and rise times, t 1/2 , of 3.3 ms and 0.9 ms, respectively, making it the fastest to-date. GCaMP3 fast revealed discreet transients with significantly faster Ca 2 + dynamics in neonatal cardiac myocytes than GCaMP6f. With 5-fold increased two-photon fluorescence cross-section for Ca 2 + at 940 nm, GCaMP3 fast is suitable for deep tissue studies. The green fluorescent protein serves as a reporter providing important novel insights into the kinetic mechanism of target recognition by calmodulin. Our strategy to match the probe to the signal by tuning the affinity and hence the Ca 2 + kinetics of the indicator is applicable to the emerging new generations of calmodulin-based probe