Differential inhibition of postnatal brain, spinal cord and body growth by a growth hormone antagonist

BACKGROUND: Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH. RESULTS: Before 50 days of postnatal age, GHA reduces spinal cord weight more than brain weight, but less than body weight. Thereafter, GHA ceases to inhibit the increase in body weight, which approaches control levels by day 150. In contrast, GHA continues to act on the CNS after day 50, reducing spinal cord growth to a greater extent and for a longer duration than brain growth. CONCLUSIONS: Judging from its inhibition by GHA, GH differentially affects the magnitude, velocity and duration of postnatal growth of the brain, spinal cord and body. GH promotes body enlargement more than CNS growth early in postnatal life. Later, its CNS effects are most obvious in the spinal cord, which continues to exhibit GH dependence well into adulthood. As normal CNS growth slows, so does its inhibition by GHA, suggesting that reduced trophic effects of GH contribute to the postnatal slowing of CNS growth. GHA is a highly useful tool for studying the role of endogenous GH on organ-specific growth during aging

New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice

Calcium is the most abundant mineral in the human body and is central to many physiological processes, including immune system activation and maintenance. Studies continue to reveal the intricacies of calcium signalling within the immune system. Perhaps the most well-understood mechanism of calcium influx into cells is store-operated calcium entry (SOCE), which occurs via calcium release-activated channels (CRACs). SOCE is central to the activation of immune system cells; however, more recent studies have demonstrated the crucial role of other calcium channels, including transient receptor potential (TRP) channels. In this review, we describe the expression and function of TRP channels within the immune system and outline associations with murine models of disease and human conditions. Therefore, highlighting the importance of TRP channels in disease and reviewing potential. The TRP channel family is significant, and its members have a continually growing number of cellular processes. Within the immune system, TRP channels are involved in a diverse range of functions including T and B cell receptor signalling and activation, antigen presentation by dendritic cells, neutrophil and macrophage bactericidal activity, and mast cell degranulation. Not surprisingly, these channels have been linked to many pathological conditions such as inflammatory bowel disease, chronic fatigue syndrome and myalgic encephalomyelitis, atherosclerosis, hypertension and atopy

The effect of thermal variance on the phenotype of marine turtle offspring.

PublishedJournal ArticleTemperature can have a profound effect on the phenotype of reptilian offspring, yet the bulk of current research considers the effects of constant incubation temperatures on offspring morphology, with few studies examining the natural thermal variance that occurs in the wild. Over two consecutive nesting seasons, we placed temperature data loggers in 57 naturally incubating clutches of loggerhead sea turtles Caretta caretta and found that greater diel thermal variance during incubation significantly reduced offspring mass, potentially reducing survival of hatchlings during their journey from the nest to offshore waters and beyond. With predicted scenarios of climate change, behavioral plasticity in nest site selection may be key for the survival of ectothermic species, particularly those with temperature-dependent sex determination.We thank all the volunteers of the Marine Turtle Conservation Project (northern Cyprus) who aided in data collection during the 2011/2012 nesting seasons. This work would not have been possible without the Society for the Protection of Turtles (SPOT) and the Department for Environmental Protection. For their continued support we thank the British Chelonia Group, the British High Commission, the British Resident’s Society, Ektam Kıbrıs, Erwin Warth Foundation, Friends of SPOT, Gemini Dataloggers (UK), and Kuzey Kıbrıs Turkcell

Body mass and hibernation microclimate may predict bat susceptibility to white-nose syndrome

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Electron quantum metamaterials in van der Waals heterostructures

In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed

Plasmatic and urinary glycosaminoglycans characterization in mucopolysaccharidosis II Patient treated with enzyme-replacement therapy with Idursulfase

We report the structural characterization of plasmatic and urinary GAGs in a Patient affected by MPS II (Hunter syndrome) before and during the first ten months of enzyme-replacement therapy (ERT). Plasmatic GAGs before ERT were rich in pathological DS consisting of iduronic acid (IdoA) and composed of ~90% \uf044Di4s and trace amounts of disulfated disaccharides. DS was also characterized as the main (~90%) urinary GAG mainly composed of ~90% \uf044Di4s with minor percentages of monosulfated and disulfated disaccharides, in particular \u394Di2,4dis. After 300 days of ERT, plasmatic DS strongly decreased but ~14% of IdoA-rich \uf044Di4s was still detected. Similarly, urinary galactosaminoglycans were mainly composed of 78% \uf044Di4s, ~11% \uf044Di6s and ~4% \uf044Di0s with the persistence of \u394Di2,4dis (~4%). About 40% of IdoA-formed \uf044Di4s were also calculated thus confirming that pathological DS is still present in excreted urinary GAGs during ERT. By considering the % of IdoA, we observed rather similar kinetics of excretion in fluids from the beginning of the treatment. Immediately after the first enzyme infusion, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and this process lasts for about two weeks. After this, the percentage of IdoA-rich material present in biological fluids remains fairly constant over the following nine months of treatment. To date, these are the first data regarding plasmatic and urinary kinetics directly measured on products released by the activity of the recombinant enzyme Idursulfase, iduronate-2-sulfatase, evaluated using specific and sensitive analytical procedures

Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

<p>Abstract</p> <p>Purpose</p> <p>Hypofractionated, stereotactic body radiotherapy (SBRT) is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT.</p> <p>Method and Materials</p> <p>Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method) and RTOG toxicity outcomes were assessed.</p> <p>Results</p> <p>At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%). Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation.</p> <p>Conclusion</p> <p>Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.</p

Domestication Syndrome in Caimito (Chrysophyllum cainito L.): Fruit and Seed Characteristics

Domestication Syndrome in Caimito (Chrysophyllum cainitoL.): Fruit and Seed Characteristics: The process of domestication is understudied and poorly known for many tropical fruit tree crops. The star apple or caimito tree (Chrysophyllum cainito L., Sapotaceae) is cultivated throughout the New World tropics for its edible fruits. We studied this species in central Panama, where it grows wild in tropical moist forests and is also commonly cultivated in backyard gardens. Using fruits collected over two harvest seasons, we tested the hypothesis that cultivated individuals of C. cainito show distinctive fruit and seed characteristics associated with domestication relative to wild types. We found that cultivated fruits were significantly and substantially larger and allocated more to pulp and less to exocarp than wild fruits. The pulp of cultivated fruits was less acidic; also, the pulp had lower concentrations of phenolics and higher concentrations of sugar. The seeds were larger and more numerous and were less defended with phenolics in cultivated than in wild fruits. Discriminant Analysis showed that, among the many significant differences, fruit size and sugar concentration drove the great majority of the variance distinguishing wild from cultivated classes. Variance of pulp phenolics among individuals was significantly higher among wild trees than among cultivated trees, while variance of fruit mass and seed number was significantly higher among cultivated trees. Most traits showed strong correlations between years. Overall, we found a clear signature of a domestication syndrome in the fruits of cultivated caimito in Panama

Estimation of health effects of prenatal methylmercury exposure using structural equation models

BACKGROUND: Observational studies in epidemiology always involve concerns regarding validity, especially measurement error, confounding, missing data, and other problems that may affect the study outcomes. Widely used standard statistical techniques, such as multiple regression analysis, may to some extent adjust for these shortcomings. However, structural equations may incorporate most of these considerations, thereby providing overall adjusted estimations of associations. This approach was used in a large epidemiological data set from a prospective study of developmental methyl-mercury toxicity. RESULTS: Structural equation models were developed for assessment of the association between biomarkers of prenatal mercury exposure and neuropsychological test scores in 7 year old children. Eleven neurobehavioral outcomes were grouped into motor function and verbally mediated function. Adjustment for local dependence and item bias was necessary for a satisfactory fit of the model, but had little impact on the estimated mercury effects. The mercury effect on the two latent neurobehavioral functions was similar to the strongest effects seen for individual test scores of motor function and verbal skills. Adjustment for contaminant exposure to poly chlorinated biphenyls (PCBs) changed the estimates only marginally, but the mercury effect could be reduced to non-significance by assuming a large measurement error for the PCB biomarker. CONCLUSIONS: The structural equation analysis allows correction for measurement error in exposure variables, incorporation of multiple outcomes and incomplete cases. This approach therefore deserves to be applied more frequently in the analysis of complex epidemiological data sets