Response of Phytoplankton Photophysiology to Varying Environmental Conditions in the Sub-Antarctic and Polar Frontal Zone

Climate-driven changes are expected to alter the hydrography of the Sub-Antarctic Zone (SAZ) and Polar Frontal Zone (PFZ) south of Australia, in which distinct regional environments are believed to be responsible for the differences in phytoplankton biomass in these regions. Here, we report how the dynamic influences of light, iron and temperature, which are responsible for the photophysiological differences between phytoplankton in the SAZ and PFZ, contribute to the biomass differences in these regions. High effective photochemical efficiency of photosystem II (F 0 q/F 0 mw0.4), maximum photosynthesis rate (PB max), light-saturation intensity (Ek), maximum rate of photosynthetic electron transport (1/tPSII), and low photoprotective pigment concentrations observed in the SAZ correspond to high chlorophyll a and iron concentrations. In contrast, phytoplankton in the PFZ exhibits low F 0 q/F 0 m (* 0.2) and high concentrations of photoprotective pigments under low light environment. Strong negative relationships between iron, temperature, and photoprotective pigments demonstrate that cells were producing more photoprotective pigments under low temperature and iron conditions, and are responsible for the low biomass and low productivity measured in the PFZ. As warming and enhanced iron input is expected in this region, this could probably increase phytoplankton photosynthesis in this region. However, complex interactions between the biogeochemical processes (e.g. stratification caused by warming could prevent mixing of nutrients), which control phytoplankton biomass and productivity, remain uncertain

Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Vascular dysfunction is one of the major causes of cardiovascular (CV) mortality and increases with age. Epidemiological studies suggest that Mediterranean diets and high nut consumption reduce CV disease risk and mortality while increasing plasma α-tocopherol. Therefore, we have investigated whether almond supplementation can improve oxidative stress markers and CV risk factors over 4 weeks in young and middle-aged men. Healthy middle-aged men (56 ± 5.8 years), healthy young men (22.1 ± 2.9 years) and young men with two or more CV risk factors (27.3 ± 5 years) consumed 50 g almond/day for 4 weeks. A control group maintained habitual diets over the same period. Plasma α-tocopherol/cholesterol ratios were not different between groups at baseline and were significantly elevated by almond intervention with 50 g almond/day for 4 weeks (p < 0.05). Plasma protein oxidation and nitrite levels were not different between groups whereas, total-, HDL- and LDL-cholesterols and triglycerides were significantly higher in healthy middle-aged and young men with CV risk factors but were not affected by intake. In the almond-consuming groups, flow-mediated dilatation (FMD) improved and systolic blood pressure reduced significantly after 50 g almonds/day for 4 weeks, but diastolic blood pressure reduced only in healthy men. In conclusion, a short-term almond-enriched diet can increase plasma α-tocopherol and improve vascular function in asymptomatic healthy men aged between 20 and 70 years without any effect on plasma lipids or markers of oxidative stress. © 2014 Informa UK, Ltd

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Gaining insight into the Clinical Practice Guideline development processes: qualitative study in a workshop to implement the GRADE proposal in Spain

BACKGROUND: The GRADE method represents a new approach to grading the quality of evidence and strength of recommendations in the preparation of Clinical Practice Guidelines (CPG). In the context of a pilot study to assess the implementability of the system in Spain, we considered it relevant to gain an insight into the significance of the perceptions and attitudes expressed by the actual experts participating in the system try-out. METHODS: Qualitative research with an ethnographic approach, through non-participant observation and focus groups within the context of a consensus workshop in which 19 CPG experts participated to evaluate the GRADE proposal using 12 evidence tables taken from hypertension, asthma and arthritis CPGs. The interventions were recorded, under a guarantee of confidentiality. The transcriptions and field notes were analyzed, based on a sociological discourse analysis model, and the provisional findings were re-sent to participants in order to improve their validity. RESULTS: 1) Certain problems over procedure and terminology hindered the acceptance of this new method as a common reference system for the preparation of CPGs. 2). A greater closeness to clinical practice was accompanied by concerns over value judgments and subjectivity, with a demand for greater explicitness in the consensus process. 3). The type of "evidence" on which the guidelines are based, how and by whom the evidence is prepared, and what the role of the different actors should be, all constitute unresolved concerns in the CPG preparation and implementation processes. 4). The grading process is not neutral: professional background, prior experience and the degree of leadership all condition the participants' input and interactions. CONCLUSION: The findings obtained allow the quantitative evaluation to be better interpreted and, in turn, go beyond the particularities of the GRADE method. Adaptation to the complexities of clinical practice, the need for carefully designed multi-disciplinary work and the reflexivity present in the CPG preparation process, all represent lines of debate that are necessary to improve the CPG quality in the Spanish health care sector

MicroRNA Expression Profiling of the Porcine Developing Brain

BACKGROUND: MicroRNAs are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level and play an important role in the control of developmental and physiological processes. In particular, the developing brain contains an impressive diversity of microRNAs. Most microRNA expression profiling studies have been performed in human or rodents and relatively limited knowledge exists in other mammalian species. The domestic pig is considered to be an excellent, alternate, large mammal model for human-related neurological studies, due to its similarity in both brain development and the growth curve when compared to humans. Considering these similarities, studies examining microRNA expression during porcine brain development could potentially be used to predict the expression profile and role of microRNAs in the human brain. METHODOLOGY/PRINCIPAL FINDINGS: MicroRNA expression profiling by use of microRNA microarrays and qPCR was performed on the porcine developing brain. Our results show that microRNA expression is regulated in a developmentally stage-specific, as well as a tissue-specific manner. Numerous developmental stage or tissue-specific microRNAs including, miR-17, miR-18a, miR-29c, miR-106a, miR-135a and b, miR-221 and miR-222 were found by microarray analysis. Expression profiles of selected candidates were confirmed by qPCR. CONCLUSIONS/SIGNIFICANCE: The differential expression of specific microRNAs in fetal versus postnatal samples suggests that they likely play an important role in the regulation of developmental and physiological processes during brain development. The data presented here supports the notion that microRNAs act as post-transcriptional switches which may regulate gene expression when required

Physical activity inversely associated with the presence of depression among urban adolescents in regional China

<p>Abstract</p> <p>Background</p> <p>An inverse relationship between physical activity (PA) and depression among adolescents has been reported in developed communities without consideration of sedentary behaviors (SB, including sitting for course study, viewing TV, and sleeping). We explored the association between recreational PA time (hr/wk) and depression after adjustment with SB and other possible confounders among Chinese adolescents.</p> <p>Methods</p> <p>A population-based cross-sectional study was conducted in Nanjing municipality of China in 2004 using a multi-stage cluster sampling approach. A total of 72 classes were randomly selected from 24 urban junior high schools and all students completed the structured questionnaire. Adolescent depression was examined by the Children's Depression Inventory (CDI) of Chinese version with cutoff point value of 20 or above as the presence of depression. Recreational PA time was measured by a question on weekly hours of PA outside of school. Descriptive statistics, multivariate logistic and linear regression models were used in analysis.</p> <p>Results</p> <p>The overall prevalence of depression was 15.7% (95%CI: 14.3%, 17.1%) among 2,444 eligible participants. It was found that physical activity was negatively associated with depression. After adjustment for sedentary behaviors and other potential confounders, participants who spent 1–7 hr/wk, 8–14 hr/wk and 15+ hr/wk for recreational PA, respectively, had odds ratios of 0.70 (95% CI = 0.57, 0.86), 0.68 (95% CI = 0.53, 0.88) and 0.66 (95% CI = 0.50, 0.87) for likelihood of being depressive, compared to their counterparts who spent 0–0.9 hr/wk for PA. This inverse relationship between PA time and depression remained statistically significant by gender and grade.</p> <p>Conclusion</p> <p>This study, conducted among Chinese adolescents, strengthened the evidence that physical activity was inversely associated with depression. Our study has important implications for health officers and public health professionals to pay much attention to the relationship between physical activity and depression in Mainland China.</p