Seagrass can mitigate negative ocean acidification effects on calcifying algae

The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm structure and experimental assistance.info:eu-repo/semantics/publishedVersio

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

Paradoxical roles of antioxidant enzymes:Basic mechanisms and health implications

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate “paradoxical” outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of “antioxidant” nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that “paradoxical” roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways

Intra-Organ Variation in Age-Related Mutation Accumulation in the Mouse

Using a transgenic mouse model harboring chromosomally integrated lacZ mutational target genes, we previously demonstrated that mutations accumulate with age much more rapidly in the small intestine than in the brain. Here it is shown that in the small intestine point mutations preferentially accumulate in epithelial cells of the mucosa scraped off the underlying serosa. The mucosal cells are the differentiated villus cells that have undergone multiple cell divisions. A smaller age-related increase, also involving genome rearrangements, was observed in the serosa, which consists mainly of the remaining crypts and non-dividing smooth muscle cells. In the brain we observed an accumulation of only point mutations in no other areas than hypothalamus and hippocampus. To directly test for cell division as the determining factor in the generation of point mutations we compared mutation induction between mitotically active and quiescent embryonic fibroblasts from the same lacZ mice, treated with either UV (a point mutagen) or hydrogen peroxide (a clastogen). The results indicate that while point mutations are highly replication-dependent, genome rearrangements are as easily induced in non-dividing cells as in mitotically active ones. This strongly suggests that the point mutations found to have accumulated in the mucosal part of the small intestine are the consequence of replication errors. The same is likely true for point mutations accumulating in hippocampus and hypothalamus of the brain since neurogenesis in these two areas continues throughout life. The observed intra-organ variation in mutation susceptibility as well as the variation in replication dependency of different types of mutations indicates the need to not only extend observations made on whole organs to their sub-structures but also take the type of mutations and mitotic activity of the cells into consideration. This should help elucidating the impact of genome instability and its consequences on aging and disease

Distinct Binding and Immunogenic Properties of the Gonococcal Homologue of Meningococcal Factor H Binding Protein

Neisseria meningitidis is a leading cause of sepsis and meningitis. The bacterium recruits factor H (fH), a negative regulator of the complement system, to its surface via fH binding protein (fHbp), providing a mechanism to avoid complement-mediated killing. fHbp is an important antigen that elicits protective immunity against the meningococcus and has been divided into three different variant groups, V1, V2 and V3, or families A and B. However, immunisation with fHbp V1 does not result in cross-protection against V2 and V3 and vice versa. Furthermore, high affinity binding of fH could impair immune responses against fHbp. Here, we investigate a homologue of fHbp in Neisseria gonorrhoeae, designated as Gonococcal homologue of fHbp (Ghfp) which we show is a promising vaccine candidate for N. meningitidis. We demonstrate that Gfhp is not expressed on the surface of the gonococcus and, despite its high level of identity with fHbp, does not bind fH. Substitution of only two amino acids in Ghfp is sufficient to confer fH binding, while the corresponding residues in V3 fHbp are essential for high affinity fH binding. Furthermore, immune responses against Ghfp recognise V1, V2 and V3 fHbps expressed by a range of clinical isolates, and have serum bactericidal activity against N. meningitidis expressing fHbps from all variant groups

Neural Correlate of Filtering of Irrelevant Information from Visual Working Memory

In a dynamic environment stimulus task relevancy could be altered through time and it is not always possible to dissociate relevant and irrelevant objects from the very first moment they come to our sight. In such conditions, subjects need to retain maximum possible information in their WM until it is clear which items should be eliminated from WM to free attention and memory resources. Here, we examined the neural basis of irrelevant information filtering from WM by recording human ERP during a visual change detection task in which the stimulus irrelevancy was revealed in a later stage of the task forcing the subjects to keep all of the information in WM until test object set was presented. Assessing subjects' behaviour we found that subjects' RT was highly correlated with the number of irrelevant objects and not the relevant one, pointing to the notion that filtering, and not selection, process was used to handle the distracting effect of irrelevant objects. In addition we found that frontal N150 and parietal N200 peak latencies increased systematically as the amount of irrelevancy load increased. Interestingly, the peak latency of parietal N200, and not frontal N150, better correlated with subjects' RT. The difference between frontal N150 and parietal N200 peak latencies varied with the amount of irrelevancy load suggesting that functional connectivity between modules underlying fronto-parietal potentials vary concomitant with the irrelevancy load. These findings suggest the existence of two neural modules, responsible for irrelevant objects elimination, whose activity latency and functional connectivity depend on the number of irrelevant object

Structure–properties relationships in fibre drawing of bioactive phosphate glasses

New bioactive phosphate glasses suitable for continuous fibre production are investigated in this work. The structure of both bulk and fibres from Na2O–CaO–MgO–P2O5 glasses has been studied by means of Raman and 31P and 23Na nuclear magnetic resonance spectroscopies, and the structural results have been correlated with the mechanical properties of the fibres and the dissolution rate of the bulk glasses. It has been observed that the mechanical properties of the phosphate glass fibres are influenced by the glass network connectivity, while the dissolution rates are governed by the Qi speciation of the PO4 units. As seen in previous studies, molar volume seems to play an important role in the fragility behaviour of phosphate glasses. Here, a lower molar volume resulting from the increase in the oxygen packing density hinders the cooperative flow of the PO4 units throughout the glass network and, therefore, causes a reduction in the kinetic fragility

Patient organization involvement and the challenge of securing access to treatments for rare diseases:Report of a policy engagement workshop

Plain English summary Patients with rare diseases often help to develop new treatments for their conditions. But once developed, those treatments are sometimes priced too high for many patients to access them. We became aware that this is a problem in the course of a social science research project that examines the place of rare diseases in health policy. We therefore organized a two-day workshop to try and understand why this problem occurs and what might be done about it. The people who participated in our workshop were: representatives of rare disease patient organizations, experts in matters of drug regulation and assessment of new health technologies, consultants involved with companies producing treatments for rare diseases, and social scientists researching related issues. The main conclusions to emerge from the discussions were as follows: Problems of access to treatments for rare diseases are not just due to high prices; procedures for regulating, assessing and delivering new treatments also need to be better organized. Patients and patient organizations have much to contribute to this process. However, their resources are often very limited. Consequently, more needs to be done to help them use those resources as effectively as possible. In particular, regulators and healthcare providers need to ensure that their procedures are clear and efficiently managed, so as not to waste patient organizations’ time and money. Clearer guidance is needed on what patient organizations can do to provide evidence of the effectiveness of new drugs. Insights gained in tackling rare diseases might also be applicable to common disorders. Finally, the consequences of Brexit for UK policies on rare diseases urgently need to be assessed. Abstract Since the enactment of orphan drug legislation in the USA, Europe and several other countries, an increasing number of treatments for rare diseases have been developed and many of them been approved for marketing. However, such treatments tend to be priced very high, and access to effective treatments remains a major challenge for patients with rare diseases – despite active involvement of patients and their support organizations in various stages of basic and applied research and commercial development. In order to allow patients to benefit from treatments proved effective for their diseases, we need to better understand why this challenge persists, and what steps might be taken to address it. To that end, we organized a policy-engagement workshop, bringing together individuals and organizations with direct experience of trying to secure access to a treatment for a rare disease along with individuals with relevant expertise in regulatory and commissioning processes for new medicines. With additional input from social scientists who offered different perspectives on the value of patient involvement, the workshop aimed to initiate a dialogue among the participants about how to address the challenge in a sustainable manner. Discussions at the workshop stressed that active involvement of patients is as valuable in the regulatory and commissioning processes as in the research and development of new medicines. However, it also highlighted certain risks and costs associated with such involvement. These include the costs of adjusting to abrupt changes in regulatory and commissioning processes, and the risk of being perceived as too close to commercial interests. To optimize use of scarce resources and ensure continuing active involvement, such risks and costs need to be better managed. Participants also noted that, owing to advances in genomic technologies, common diseases are also becoming divided into rare sub-categories, which are equally eligible for orphan drug designation. Consequently, involvement of wider patient communities beyond rare disease communities will be critical for continuing discussions about patients’ involvement in regulatory and commissioning processes, and to consider how patients and their support organizations can best work with other stakeholders – including companies, regulators and policymakers – to ensure access to effective medicines

Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010

PURPOSE: Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, have been shown in randomized clinical trials to reduce the risk of developing primary invasive breast cancer (IBC) in high-risk women. In 1998, the U.S. Food and Drug Administration (FDA) used these studies as a basis for approving tamoxifen for primary breast chemoprevention in both premenopausal and postmenopausal women at high risk. In 2007, the FDA approved raloxifene for primary breast cancer chemoprevention for postmenopausal women. METHODS: Data from the year 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of tamoxifen and raloxifene use for chemoprevention of primary breast cancers among U.S. women. RESULTS: Prevalence of use of chemopreventive agents for primary tumors was 20,598 (95% CI, 518–114,864) for U.S. women aged 35 to 79 for tamoxifen. Prevalence was 96,890 (95% CI, 41,277–192,391) for U.S. women aged 50 to79 for raloxifene. CONCLUSION: Use of tamoxifen and raloxifene for prevention of primary breast cancers continues to be low. In 2010, women reporting medication use for breast cancer chemoprevention were primarily using the more recently FDA-approved drug raloxifene. Multiple possible explanations for the low use exist, including lack of awareness and/or concern about side effects among primary care physicians and patients