Extracts From New Zealand Undaria Pinnatifida Containing Fucoxanthin As Potential Functional Biomaterials Against Cancer in Vitro

This study tested extracts from New Zealand seaweed Undaria pinnatifida containing fucoxanthin, in parallel with pure fucoxanthin, in nine human cancer cell lines, for anticancer activity. Growth inhibition effects of extracts from Undaria pinnatifida were found in all types of cancer cell lines in dose- and time- dependent manners. Cytotoxicity of fucoxanthin in three human non-cancer cell lines was also tested. Compared with pure fucoxanthin, our extracts containing low level of fucoxanthin were found to be more effective in inhibiting the growth of lung carcinoma, colon adenocarcinoma and neuroblastoma. Our results suggest that fucoxanthin is a functional biomaterial that may be used as a chemopreventive phytochemical or in combination chemotherapy. Furthermore, we show for the first time that some unknown compounds with potential selective anti-cancer effects may exist in extracts of New Zealand Undaria pinnatifida, and New Zealand Undaria pinnatifida could be used as a source for either functional biomaterial extraction or production of functional food

Anti-proliferation Potential and Content of Fucoidan Extracted From Sporophyll of New Zealand Undaria Pinnatifida

Undaria pinnatifida is a species of brown seaweed known to contain rich amounts of fucoidan, a sulfated polysaccharide known to possess various biological activities. We isolated crude fucoidan (F0) from the sporophylls of U. pinnatifida grown in the Marlborough Sounds, New Zealand. Sulfate content, uronic acid content, and molecular weight of F0 were 15.02, 1.24, and >150 kDa, respectively. F0 was fractionated to yield three further fractions: F1, F2, and F3. Cytotoxicity of two major fractions was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The algal fucoidans specifically suppressed the proliferation of three cancer cell lines with less cytotoxicity against the normal cells. Selective cytotoxicity could relate to the distinctive structures of each fucoidan fraction. Results from this study provide evidence that fucoidan, especially from U. pinnatifida grown in New Zealand, possesses great potential to be used as a functional food to reduce cancer risk or supplement cancer treatment

The Natural Compound Fucoidan From New Zealand Undaria Pinnatifida Synergizes With the ERBB Inhibitor Lapatinib Enhancing Melanoma Growth Inhibition

Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U. pinnatifida is integrated into the treatment regimen. Fucoidan not only enhances tumor growth inhibition, it counteracts the morbidity associated with prolonged lapatinib treatment. Fucoidan doubles the cell killing capacity of lapatinib. These effects are associated with a further decrease in AKT and NFκB signaling, two key pathways involved in melanoma cell survival. Importantly, the enhancing cell killing effects of fucoidan can be recapitulated by inhibiting ERBB3 by either a specific shRNA or a novel, selective ERBB3 neutralizing antibody, reiterating the key roles played by this receptor in melanoma. We therefore propose the use of lapatinib or specific ERBB inhibitors, in combination with fucoidan as a new treatment of melanoma that potentiates the effects of the inhibitors while protecting from their potential side effects

Autonomous decision-making against induced seismicity in deep fluid injections

The rise in the frequency of anthropogenic earthquakes due to deep fluid injections is posing serious economic, societal, and legal challenges to geo-energy and waste-disposal projects. We propose an actuarial approach to mitigate this risk, first by defining an autonomous decision-making process based on an adaptive traffic light system (ATLS) to stop risky injections, and second by quantifying a "cost of public safety" based on the probability of an injection-well being abandoned. The ATLS underlying statistical model is first confirmed to be representative of injection-induced seismicity, with examples taken from past reservoir stimulation experiments (mostly from Enhanced Geothermal Systems, EGS). Then the decision strategy is formalized: Being integrable, the model yields a closed-form ATLS solution that maps a risk-based safety standard or norm to an earthquake magnitude not to exceed during stimulation. Finally, the EGS levelized cost of electricity (LCOE) is reformulated in terms of null expectation, with the cost of abandoned injection-well implemented. We find that the price increase to mitigate the increased seismic risk in populated areas can counterbalance the heat credit. However this "public safety cost" disappears if buildings are based on earthquake-resistant designs or if a more relaxed risk safety standard or norm is chosen.Comment: 8 pages, 4 figures, conference (International Symposium on Energy Geotechnics, 26-28 September 2018, Lausanne, Switzerland

Evidence for a Positive Cosmological Constant from Flows of Galaxies and Distant Supernovae

Recent observations of high-redshift supernovae seem to suggest that the global geometry of the Universe may be affected by a `cosmological constant', which acts to accelerate the expansion rate with time. But these data by themselves still permit an open universe of low mass density and no cosmological constant. Here we derive an independent constraint on the lower bound to the mass density, based on deviations of galaxy velocities from a smooth universal expansion. This constraint rules out a low-density open universe with a vanishing cosmological constant, and together the two favour a nearly flat universe in which the contributions from mass density and the cosmological constant are comparable. This type of universe, however, seems to require a degree of fine tuning of the initial conditions that is in apparent conflict with `common wisdom'.Comment: 8 pages, 1 figure. Slightly revised version. Letter to Natur

Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation

Low Spigelian hernia in a 6-year-old boy presenting as an incarcerated inguinal hernia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lower Spigelian hernia is a very rare entity. The clinical findings are similar to those of inguinal hernias and in many cases may be misdiagnosed. In the literature, only a few references to this entity have been reported in children. To the best of our knowledge, this is the first case report of a lower Spigelian hernia in a child who presented with an acute painful scrotum.</p> <p>Case presentation</p> <p>We discuss the case of a 6-year-old Greek boy who presented to our emergency department complaining of severe pain in the left inguinal area and scrotum. The acute painful swelling started suddenly, without any obvious cause. The initial diagnosis was incarcerated inguinal hernia which was reduced with difficulty. Five days later, the patient still experienced mild pain during palpation and he was operated on. During the operation, a large lower Spigelian hernia was revealed and reconstructed.</p> <p>Conclusion</p> <p>Although Spigelian hernias are rare in children and difficult to diagnose, physicians should be aware of them and include them in the differential diagnosis.</p

Reconstructing ‘the Alcoholic’: Recovering from Alcohol Addiction and the Stigma this Entails

Public perception of alcohol addiction is frequently negative, whilst an important part of recovery is the construction of a positive sense of self. In order to explore how this might be achieved, we investigated how those who self-identify as in recovery from alcohol problems view themselves and their difficulties with alcohol and how they make sense of others’ responses to their addiction. Semi-structured interviews with six individuals who had been in recovery between 5 and 35 years and in contact with Alcoholics Anonymous were analysed using Interpretative Phenomenological Analysis. The participants were acutely aware of stigmatising images of ‘alcoholics’ and described having struggled with a considerable dilemma in accepting this identity themselves. However, to some extent they were able to resist stigma by conceiving of an ‘aware alcoholic self’ which was divorced from their previously unaware self and formed the basis for a new more knowing and valued identity

Woodland Recovery after Suppression of Deer: Cascade effects for Small Mammals, Wood Mice (Apodemus sylvaticus) and Bank Voles (Myodes glareolus)

Over the past century, increases in both density and distribution of deer species in the Northern Hemisphere have resulted in major changes in ground flora and undergrowth vegetation of woodland habitats, and consequentially the animal communities that inhabit them. In this study, we tested whether recovery in the vegetative habitat of a woodland due to effective deer management (from a peak of 0.4–1.5 to <0.17 deer per ha) had translated to the small mammal community as an example of a higher order cascade effect. We compared deer-free exclosures with neighboring open woodland using capture-mark-recapture (CMR) methods to see if the significant difference in bank vole (Myodes glareolus) and wood mouse (Apodemus sylvaticus) numbers between these environments from 2001–2003 persisted in 2010. Using the multi-state Robust Design method in program MARK we found survival and abundance of both voles and mice to be equivalent between the open woodland and the experimental exclosures with no differences in various metrics of population structure (age structure, sex composition, reproductive activity) and individual fitness (weight), although the vole population showed variation both locally and temporally. This suggests that the vegetative habitat - having passed some threshold of complexity due to lowered deer density - has allowed recovery of the small mammal community, although patch dynamics associated with vegetation complexity still remain. We conclude that the response of small mammal communities to environmental disturbance such as intense browsing pressure can be rapidly reversed once the disturbing agent has been removed and the vegetative habitat is allowed to increase in density and complexity, although we encourage caution, as a source/sink dynamic may emerge between old growth patches and the recently disturbed habitat under harsh conditions