Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics

Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 h exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 h of environmental exposure to Florida red tide aerosols for up to 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period.     

Impulsivity, risk taking, and timing

This study examined the relations among measures of impulsivity and timing. Impulsivity was assessed using delay and probability discounting, and self-report impulsivity (as measured by the Barratt Impulsiveness Scale; BIS-11). Timing was assessed using temporal perception as measured on a temporal bisection task and time perspective (as measured by the Zimbardo Time Perspective Inventory). One hundred and forty three college students completed these measures in a computer laboratory. The degree of delay discounting was positively correlated with the mean and range of the temporal bisection procedure. The degree of delay and probability discounting were also positively correlated. Self-reported motor impulsiveness on the BIS-11 was positively correlated with present hedonism and negatively correlated with future orientation on the ZTPI. Self-reported non-planning on the BIS-11 was positively correlated with fatalism on the ZTPI. These results show that people who overestimate the passage of time (perceive time as passing more quickly) hold less value in delayed rewards. They also confirm previous results regarding the relation between delay and probability discounting, as well as highlight similarities in self-report measures of impulsivity and time perspective.     

Functional significance of glycogen synthase kinase-3 regulation by serotonin

Serotonin modulates brain physiology and behavior and has major roles in brain diseases involving abnormal mood and cognition. Enhancing brain serotonin has been found to regulate glycogen synthase Kinase-3 (GSK3), but the signaling mechanism and functional significance of this regulation remain to be determined. In this study, we tested the signaling mechanism mediating 5-HT1A receptor-regulated GSK3 in the hippocampus. Using mutant GSK3 knock-in mice, we also tested the role of GSK3 in the behavioral effects of 5-HT1A receptors and the serotonin reuptake inhibitor fluoxetine. The results showed that activation of 5-HT1A receptors by 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) increased phosphorylation of the N-terminal serine of both GSK3α and GSK3β in several areas of the hippocampus. The effect of 8-OH-DPAT was accompanied by an increase in the active phosphorylation of Akt, and was blocked by LY294002, an inhibitor of phosphoinositide 3-kinases (PI3K). Phosphorylation of GSK3β, but not GSK3α, was necessary for 5-HT1A receptors to suppress the hippocampus-associated contextual fear learning. Furthermore, acute fluoxetine treatment up-regulated both phospho-Ser21-GSK3α and phospho-Ser9-GSK3β in the hippocampus. Blocking phosphorylation of GSK3α and GSK3β diminished the anti-immobility effect of fluoxetine treatment in the forced swim test, wherein the effect of GSK3β was more prominent. These results together suggest that PI3K/Akt is a signaling mechanism mediating the GSK3-regulating effect of 5-HT1A receptors in the hippocampus, and regulation of GSK3 is an important intermediate signaling process in the behavioral functions of 5-HT1A receptors and fluoxetine.     

Enhanced expression of human β-defensin 2 in peripheral lungs of patients with chronic obstructive pulmonary disease

Human β-defensin 2 (hBD-2) has antimicrobial activity and may play a role in airway mucosal defense, but studies have not yet examined its expression in lung tissue of patients with chronic obstructive pulmonary disease (COPD). Here we investigated hBD-2 levels in lung tissues of COPD patients and analyzed their correlations with IL-8, IL-1β, cigarette smoking and lung function in order to see whether the protein may be involved in pathogenesis of the disease. Peripheral lung tissue specimens were obtained from 51 patients who underwent lung resection for peripheral lung cancer: healthy non-smokers (n = 8), healthy current smokers (n = 7), non-smokers with COPD (n = 11), and current smokers with COPD (n = 25). RT-PCR and immunohistochemical staining were used to detect expression levels of hBD-2, IL-8 and IL-1β. Expression of hBD-2 mRNA was significantly higher in COPD patients than in healthy controls, and significantly higher in current smokers than in non-smokers (p < 0.05). Among healthy controls, hBD-2 mRNA levels were similar between current smokers and non-smokers. Immunohistochemistry showed hBD-2 protein to be expressed mainly in epithelia of distal bronchioles and its expression pattern among our patient groups mirrored that of the mRNA. IL-8 mRNA levels were significantly higher in COPD patients than in healthy controls (p < 0.05), while IL-1β mRNA levels did not differ significantly among the groups. Levels of hBD-2 mRNA positively correlated with levels of IL-8 mRNA (r = 0.545, p = 0.002), and negatively correlated with FEV1/FVC ratios and with predicted FEV1% values (r = −0.406, p = 0.011). Our results indicate that hBD-2 expression is elevated in distal airways of COPD patients and that it may be involved in pathogenesis of the disease. Our data implicate cigarette smoking as a factor that may elevate hBD-2 levels in lung tissues of COPD patients.     

Systemic expression of inflammatory mediators in patients with chronic rhinosinusitis and nasal polyps with and without Aspirin Exacerbated Respiratory Disease

BackgroundSystemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD.MethodsPatients with nasal polyposis and asthma with AERD (n = 20) and without (n = 18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6 h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F₂, and leukotriene E₄ (uLTE₄) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges.ResultsAERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE₄ and percentage of CD4⁺CD25⁺CD127^pos and CD4⁺CD45RA⁻CD45RO⁺ but decreased levels of TGF-β₁ and number of CD4⁺CD25⁺CD127^neg cells. Aspirin challenge induced the release of uLTE₄, IL-6 and increased the number of CD4⁺CD45RA⁻CD45RO⁺ memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD₂₀ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal).ConclusionsAERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.     

A simple DNA handle attachment method for single molecule mechanical manipulation experiments

Manipulating single molecules and systems of molecules with mechanical force is a powerful technique to examine their physical properties. Applying force requires attachment of the target molecule to larger objects using some sort of molecular tether, such as a strand of DNA. DNA handle attachment often requires difficult manipulations of the target molecule, which can preclude attachment to unstable, hard to obtain, and/or large, complex targets. Here we describe a method for covalent DNA handle attachment to proteins that simply requires the addition of a preprepared reagent to the protein and a short incubation. The handle attachment method developed here provides a facile approach for studying the biomechanics of biological systems.     

Altered gene expression in hippocampus and depressive‐like behavior in young adult female mice by early protein malnutrition

Perinatal development represents a critical period in the life of an individual. A common cause of poor development is that which comes from undernutrition or malnutrition. In particular, protein deprivation during development has been shown to have deep deleterious effects on brain's growth and plasticity. Early‐life stress has also been linked with an increased risk to develop different psychopathologies later in life. We have previously shown that perinatal protein malnutrition in mice leads to the appearance of anxiety‐related behaviors in the adulthood. We also found evidence that the female offspring was more susceptible to the development of depression‐related behaviors. In the present work, we further investigated this behavior together with its molecular bases. We focused our study on the hippocampus, as it is a structure involved in coping with stressful situations. We found an increase in immobility time in the forced swimming test in perinatally malnourished females, and an alteration in the expression of genes related with neuroplasticity, early growth response 1, calcineurin and c‐fos. We also found that perinatal malnutrition causes a reduction in the number of neurons in the hippocampus. This reduction, together with altered gene expression, could be related to the increment in immobility time observed in the forced swimming test.     

Scientific and Islamic perspectives in relation to the Halal status of cultured meat

Cultured meat is meat produced from stem cell biopsies of cattle. Stem cells were cultured in a bioreactor in the presence of serum to grow the flesh to maturity. Cultured meat technology originated from regenerative medical technology; however, it has been given a new lease of life to produce cultured meat as an innovative food source in the future without involving cattle breeding. This technology can reduce the negative environmental impacts of global warming, water use, soil, and unethical handling of animals. In the excitement of accepting this new technology, the halal status of cultured meat is in question, as it can be produced from embryonic stem cells and myosatellite cells, each of which can be disputed for their halal status. Additionally, the process of culturing and maturation of stem cells involves the use of an impure medium derived from animal blood. Thus, cultured meat is acceptable to Muslims only if the stem cells, medium and scaffold biomaterials used to manufacture it are from Halal sources and shall be in line with the six principles discussed in this study. The discussion is based on Halal and haram animals; Animal slaughtering; Not derived from a source of najs (impurity); Istihalah tammah (perfect substance change); Maslahah (public interest or benefit) and mafsadah (damage); and Darurat (exigency) of cultured meat)).     

The effects of linear perspective on relative size discrimination in chimpanzees (Pan troglodytes) and humans (Homo sapiens)

In this study, we tested the corridor illusion in three chimpanzees and five humans, applying a relative size discrimination task to assess pictorial depth perception using linear perspective. The subjects were required to choose the physically larger cylinder of two on a background containing drawn linear perspective cues. We manipulated both background and cylinder size in each trial. Our findings suggest that chimpanzees, like humans, exhibit the corridor illusion.     

Environmental Implications of Resource Use:Environmental Input-Output Analyses for Germany

In a German case study, environmental input-output analyses (eIOA) combined with NAMEA-type tables were conducted for eleven selected environmental pressure variables. (NAMEA is an acronym for national accounts matrix including environmental accounts.) The analyses were conducted to derive the production-cycle-wide resource use and environmental impact potentials of final-demand product groups. The methodology permits identification and preliminary ranking of 10 product chains along which about two-thirds of German production-born environmental pressures arise. The most relevant product groups are construction work, food, motor vehicles, basic metals, and electricity. The ten product groups are characterized by both high resource requirements and high residual outputs (air emissions, wastes). The EU policy areas of integrated product policy and sustainable use of natural resources may address these product chains as a priority in order to identify and explore the possibility of reducing the environmental impacts from products throughout their life cycles and to decouple environmental impacts from resource use.