Characterisation of the bacterial and fungal communities associated with different lesion sizes of Dark Spot Syndrome occurring in the Coral Stephanocoenia intersepta

The number and prevalence of coral diseases/syndromes are increasing worldwide. Dark Spot Syndrome (DSS) afflicts numerous coral species and is widespread throughout the Caribbean, yet there are no known causal agents. In this study we aimed to characterise the microbial communities (bacteria and fungi) associated with DSS lesions affecting the coral Stephanocoenia intersepta using nonculture molecular techniques. Bacterial diversity of healthy tissues (H), those in advance of the lesion interface (apparently healthy AH), and three sizes of disease lesions (small, medium, and large) varied significantly (ANOSIM R = 0.052 p,0.001), apart from the medium and large lesions, which were similar in their community profile. Four bacteria fitted into the pattern expected from potential pathogens; namely absent from H, increasing in abundance within AH, and dominant in the lesions themselves. These included ribotypes related to Corynebacterium (KC190237), Acinetobacter (KC190251), Parvularculaceae (KC19027), and Oscillatoria (KC190271). Furthermore, two Vibrio species, a genus including many proposed coral pathogens, dominated the disease lesion and were absent from H and AH tissues, making them candidates as potential pathogens for DSS. In contrast, other members of bacteria from the same genus, such as V. harveyii were present throughout all sample types, supporting previous studies where potential coral pathogens exist in healthy tissues. Fungal diversity varied significantly as well, however the main difference between diseased and healthy tissues was the dominance of one ribotype, closely related to the plant pathogen, Rhytisma acerinum, a known causal agent of tar spot on tree leaves. As the corals’ symbiotic algae have been shown to turn to a darker pigmented state in DSS (giving rise to the syndromes name), the two most likely pathogens are R. acerinum and the bacterium Oscillatoria, which has been identified as the causal agent of the colouration in Black Band Disease, another widespread coral disease

Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential

Ajudes rebudes: Marie Curie Career Integration Grant; Dexeus Foundation for Women's Health Research; i Contratos Ramón y CajalCD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential

Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation

Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached

Phloroglucinol Inhibits the Bioactivities of Endothelial Progenitor Cells and Suppresses Tumor Angiogenesis in LLC-Tumor-Bearing Mice

Background: There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis. Methodology/Principal Findings: This is the first report on phloroglucinol’s ability to potentially inhibit the functional bioactivities of endothelial progenitor cells (EPCs) and thereby attenuate tumor growth and angiogenesis in the Lewis lung carcinoma (LLC)-tumor-bearing mouse model. Although Phloroglucinol did not affect their cell toxicity, it specifically inhibited vascular endothelial growth factor (VEGF) dependent migration and capillary-like tube formation of EPCs. Our matrigel plug assay clearly indicated that orally injected phloroglucinol effectively disrupts VEGF-induced neovessel formation. Moreover, we demonstrated that when phloroglucinol is orally administered, it significantly inhibits tumor growth and angiogenesis as well as CD45 2 /CD34 + progenitor mobilization into peripheral blood in vivo in the LLC-tumorbearing mouse model. Conclusions/Significance: These results suggest a novel role for phloroglucinol: Phloroglucinol might be a modulator of circulating EPC bioactivities, eventually suppressing tumorigenesis. Therefore, phloroglucinol might be a candidat

Environmental chemical stressors as epigenome modifiers:a new horizon in assessment of toxicological effects

In eukaryotic cells, chromatin transformation from euchromatin into heterochromatin as a means of controlling gene expression and replication has been known as the ?accessibility hypothesis?. The interplay of epigenetic changes including histone modifications, DNA methylation, RNA interference (RNAi) and other functional epigenetic components are intricate. It is believed that these changes are well-programmed, inherited and can be modified by environmental contaminant stressors. Environmentally-driven epigenetic alterations during development, e.g. embryonic, foetal or neonatal stage, may influence disease susceptibility in adulthood. Therefore, understanding how epigenome modifications develop in response to environmental chemicals and, how epigenetic-xenobiotic interactions influence human health will shed new insights into gene-environment interactions in the epidemiology of several diseases including cancer. In this review, we consider studies of chemical modifiers including nutritional and xenobiotic effects on epigenetic components in vitro or in vivo. By examining the most-studied epigenome modifications and how their respective roles are interlinked, we highlight the central role of xenbiotic-modified epigenetic mechanisms. A major requirement will be to study and understand effects following environmentally-relevant exposures. We suggest that the study of epigenetic toxicology will open up new opportunities to devise strategies for the prevention or treatment of at-risk populations

Adhesion Molecules Associated with Female Genital Tract Infection

Altres ajuts: Marie Curie Career Integration Grant i una beca Fundació Dexeus Salut de la DonaEfforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes

New Insights into the Mechanisms of Embryonic Stem Cell Self-Renewal under Hypoxia: A Multifactorial Analysis Approach

Previous reports have shown that culturing mouse embryonic stem (mES) cells at different oxygen tensions originated different cell proliferation patterns and commitment stages depending on which signaling pathways are activated or inhibited to support the pluripotency state. Herein we provide new insights into the mechanisms by which oxygen is influencing mES cell self-renewal and pluripotency. A multifactorial approach was developed to rationally evaluate the singular and interactive control of MEK/ERK pathway, GSK-3 inhibition, and LIF/STAT3 signaling at physiological and non-physiological oxygen tensions. Collectively, our methodology revealed a significant role of GSK-3-mediated signaling towards maintenance of mES cell pluripotency at lower O2 tensions. Given the central role of this signaling pathway, future studies will need to focus on the downstream mechanisms involved in ES cell self-renewal under such conditions, and ultimately how these findings impact human models of pluripotency

Challenges in multidisciplinary cancer care among general surgeons in Canada

<p>Abstract</p> <p>Background</p> <p>While many factors can influence the way that cancer care is delivered, including the way that evidence is packaged and disseminated, little research has evaluated how health care professionals who manage cancer patients seek and use this information to identify whether and how this could be supported. Through interviews we identified that general surgeons experience challenges in coordinating care for complex cancer patients whose management is not easily addressed by guidelines, and conducted a population-based survey of general surgeon information needs and information seeking practices to extend these findings.</p> <p>Methods</p> <p>General surgeons with privileges at acute care hospitals in Ontario, Canada were mailed a questionnaire to solicit information needs (task, importance), information seeking (source, frequency of and reasons for use), key challenges and suggested solutions. Non-responders received up to three reminder packages. Significant differences among sub-groups (age, setting) were examined statistically (Kruskal Wallis, Mann Whitney, Chi Square). Standard qualitative methods were used to thematically analyze open-ended responses.</p> <p>Results</p> <p>The response rate was 44.2% (170/385) representing all 14 health regions. System resource constraints (60.4%), comorbidities (56.4%) and physiologic factors (51.8%) were top-ranked issues creating information needs. Local surgical colleagues (84.6%), other local colleagues (82.2%) and the Internet (81.1%) were top-ranked sources of information, primarily due to familiarity and speed of access. No resources were considered to be highly applicable to patient care. Challenges were related to limitations in diagnostics and staging, operative resources, and systems to support multidisciplinary care, together accounting for 76.0% of all reported issues. Findings did not differ significantly by surgeon age or setting of care.</p> <p>Conclusion</p> <p>General surgeons appear to use a wide range of information resources but they may not address the complex needs of many cancer patients. Decision-making is challenged by informational and logistical issues related to the coordination of multidisciplinary care. This suggests that limitations in system capacity may, in part, contribute to variable guideline compliance. Further research is required to evaluate the appropriateness of information seeking, and both concurrent and consecutive mechanisms by which to achieve multidisciplinary care.</p

Relationship Contexts as Sources of Socialization: An Exploration of Intimate Partner Violence Experiences of Economically Disadvantaged African American Adolescents

Intimate partner violence (IPV) among African Americans is a serious public health concern. Research suggest that African Americans adolescents, particularly those from economically disadvantaged communities, are at heightened risk for experiencing and perpetrating dating violence compared to youth from other racial and ethnic groups. In the present study, we examined different relationship contexts that are sources of IPV socialization. Semi-structured interviews were conducted with 22 economically disadvantaged African American adolescents. Content analysis yielded five relationship contexts through which the participants witnessed, experienced, and perpetrated IPV: (a) adolescents’ own dating relationships (64%), (b) siblings and extended family members (e.g., cousins, aunts, uncles) (59%), (c) parent-partners (27%), (d) friends (23%), and (e) neighbors (18%). Adolescents also frequently described IPV in their own dating relationships and in parent-partner relationships as mutual. Moreover, they appeared to minimize the experience of IPV in their own relationships. Efforts to reduce rates of IPV among economically disadvantaged African American adolescents should consider these relational contexts through which adolescents are socialized with regards to IPV and adolescents’ beliefs about mutual violence in relationships. Results highlight the importance of culturally relevant prevention and intervention programs that consider these relationship contexts

Health-related physical fitness of adolescents and young adults with myelomeningocele

To assess components of health-related physical fitness in adolescents and young adults with myelomeningocele (MMC), and to study relations between aerobic capacity and other health-related physical fitness components. This cross-sectional study included 50 adolescents and young adults with MMC, aged 16–30 years (25 males). Aerobic capacity was quantified by measuring peak oxygen uptake (peakVO2) during a maximal exercise test on a cycle or arm ergometer depending on the main mode of ambulation. Muscle strength of upper and lower extremity muscles was assessed using a hand-held dynamometer. Regarding flexibility, we assessed mobility of hip, knee and ankle joints. Body composition was assessed by measuring thickness of four skin-folds. Relations were studied using linear regression analyses. Average peakVO2 was 1.48 ± 0.52 l/min, 61% of the participants had subnormal muscle strength, 61% had mobility restrictions in at least one joint and average sum of four skin-folds was 74.8 ± 38.8 mm. PeakVO2 was significantly related to gender, ambulatory status and muscle strength, explaining 55% of its variance. Adolescents and young adults with MMC have poor health-related physical fitness. Gender and ambulatory status are important determinants of peakVO2. In addition, we found a small, but significant relationship between peakVO2 and muscle strength