The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism

The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans

Lifelong socioeconomic position and physical performance in midlife: results from the British 1946 birth cohort

Socioeconomic position (SEP) across life is found to be related to adult physical performance, but the underlying pathways are not well characterized. Using a British birth cohort (N = 2956), the associations of SEP from childhood into midlife with objective physical performance measures in midlife were examined, adjusting for possible confounders or mediators, including indicators of muscle development and central nervous system function. Childhood and adulthood SEP were positively related to standing balance and chair rise performance, but not to grip strength after basic adjustments. When both father’s occupation and mother’s education were included in the same model, having a mother with low education was associated with 0.6 standard deviations (SD) (95% confidence interval (CI: 0.3, 0.8)) poorer standing balance time compared with having a mother with the highest educational level, and having a father in the lowest occupational group was associated with a 0.3 SD (95% CI: 0.1, 0.6) lower chair rise score compared with having a father in the highest occupational group. These associations were maintained, albeit attenuated, after adjustment. In contrast, the associations of own education and adult occupation with physical performance were generally not maintained after adjustment. SEP across life impacts on midlife physical performance, and thereby the ageing process

Observing convective aggregation

Convective self-aggregation, the spontaneous organization of initially scattered convection into isolated convective clusters despite spatially homogeneous boundary conditions and forcing, was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad a distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network

Detection of the Temporal Variation of the Sun's Cosmic Ray Shadow with the IceCube Detector

We report on the observation of a deficit in the cosmic ray flux from the directions of the Moon and Sun with five years of data taken by the IceCube Neutrino Observatory. Between 2010 May and 2011 May the IceCube detector operated with 79 strings deployed in the glacial ice at the South Pole, and with 86 strings between 2011 May and 2015 May. A binned analysis is used to measure the relative deficit and significance of the cosmic ray shadows. Both the cosmic ray Moon and Sun shadows are detected with high statistical significance (>10σ) for each year. The results for the Moon shadow are consistent with previous analyses and verify the stability of the IceCube detector over time. This work represents the first observation of the Sun shadow with the IceCube detector. We show that the cosmic ray shadow of the Sun varies with time. These results make it possible to study cosmic ray transport near the Sun with future data from IceCube

Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers.

OPINION STATEMENT: Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes

Search for transient optical counterparts to high-energy IceCube neutrinos with Pan-STARRS1

In order to identify the sources of the observed diffuse high-energy neutrino flux, it is crucial to discover their electromagnetic counterparts. To increase the sensitivity of detecting counterparts of transient or variable sources by telescopes with a limited field of view, IceCube began releasing alerts for single high-energy (E-v > 60 TeV) neutrino detections with sky localisation regions of order 1 degrees radius in 2016. We used Pan-STARRS1 to follow-up five of these alerts during 2016-2017 to search for any optical transients that may be related to the neutrinos. Typically 10-20 faint m(ip1) less than or similar to 22.5 mag) extragalactic transients are found within the Pan-STARRS1 footprints and are generally consistent with being unrelated field supernovae (SNe) and AGN. We looked for unusual properties of the detected transients, such as temporal coincidence of explosion epoch with the IceCube timestamp, or other peculiar light curve and physical properties. We found only one transient that had properties worthy of a specific follow-up. In the Pan-STARRS1 imaging for IceCube-160427A (probability to be of astrophysical origin of similar to 50%), we found a SN PS16cgx, located at 10.0' from the nominal IceCube direction. Spectroscopic observations of PS16cgx showed that it was an H-poor SN at redshift z = 0.2895 +/- 0.0001. The spectra and light curve resemble some high-energy Type Ic SNe, raising the possibility of a jet driven SN with an explosion epoch temporally coincident with the neutrino detection. However, distinguishing Type Ia and Type Ic SNe at this redshift is notoriously difficult. Based on all available data we conclude that the transient is more likely to be a Type Ia with relatively weak Sin absorption and a fairly normal rest-frame r-band light curve. If, as predicted, there is no high-energy neutrino emission from Type Ia SNe, then PS16cgx must be a random coincidence, and unrelated to the IceCube-160427A. We find no other plausible optical transient for any of the five IceCube events observed down to a 5 sigma limiting magnitude of mip1 approximate to 22 mag, between 1 day and 25 days after detection

Establishing the role of cytokine therapy in advanced renal cell carcinoma.

Item does not contain fulltextTribute to Professor Pieter De Mulder, from Martin Gore. Pieter and I were often pitted against each other in debates at international meetings on the role of cytokine therapy. The truth is that there was little disagreement between us, but we both thought such set pieces were a good way to highlight the issues surrounding the use of cytokines. He wanted our true joint view to be put on record, and the result is this article. Pieter himself suffered from kidney cancer for many years and he died in April as we were putting the finishing touches to this manuscript. Pieter was a remarkable man in so many ways. He was a physician of great compassion, immense intellect, utter integrity and unshakeable scientific rigor. These qualities meant that his perspective on many clinical controversies was in great demand internationally. The European oncology community has lost one of its giants and I, a dear friend. This manuscript is dedicated to the memory of Professor Pieter de Mulder

Diagnosis and management of haemochromatosis since the discovery of the HFE gene: A European experience

Articles free to read on publisher website Hereditary haemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism common in populations of north-west European ancestry. The term haemochromatosis was first used by von Recklinghausen (1889) to describe his post-mortem findings in patients who had died from ‘bronzed diabetes’. The condition was first suggested to be familial by Sheldon (1935), although it was as late as 1975 before the genetic nature of the condition was proven, when Simon et al (1975 ) demonstrated association with the HLA-A3 allele in the major histocompatibility complex (MHC) on chromosome 6..