Forest structure and composition alleviate human thermal stress.

Current climate change aggravates human health hazards posed by heat stress. Forests can locally mitigate this by acting as strong thermal buffers, yet potential mediation by forest ecological characteristics remains underexplored. We report over 14 months of hourly microclimate data from 131 forest plots across four European countries and compare these to open-field controls using physiologically equivalent temperature (PET) to reflect human thermal perception. Forests slightly tempered cold extremes, but the strongest buffering occurred under very hot conditions (PET >35°C), where forests reduced strong to extreme heat stress day occurrence by 84.1%. Mature forests cooled the microclimate by 12.1 to 14.5°C PET under, respectively, strong and extreme heat stress conditions. Even young plantations reduced those conditions by 10°C PET. Forest structure strongly modulated the buffering capacity, which was enhanced by increasing stand density, canopy height and canopy closure. Tree species composition had a more modest yet significant influence: that is, strongly shade-casting, small-leaved evergreen species amplified cooling. Tree diversity had little direct influences, though indirect effects through stand structure remain possible. Forests in general, both young and mature, are thus strong thermal stress reducers, but their cooling potential can be even further amplified, given targeted (urban) forest management that considers these new insights.

How 'hot' is too hot? Evaluating acceptable outdoor thermal comfort ranges in an equatorial urban park.

Urban green spaces offer vital ecosystem services such as regulating elevated temperatures in cities. Less information exists, however, on how urban green spaces influence outdoor thermal comfort (OTC), which is dependent on people's perceptions of the complex interactions amongst ambient humidity, wind and both air and radiant temperatures. In this study, we analysed an existing OTC dataset compiled within a large Singapore urban park and calibrated OTC thresholds for physiological equivalent temperatures (PET) by analysing PET against thermal perception survey responses from the park visitors (n = 1508). We examined OTC according to (i) neutral, (ii) acceptable and (iii) preferred temperatures, where respondents felt 'comfortable' outdoors in the park. We estimated that neutral temperature, when all respondents experience neither heat nor cold stress, is 26.2 °C; acceptable temperatures, when only slight heat or cold stress is experienced, range between 21.6 and 31.6 °C; and preferred ('ideal') temperature for all respondents is 24.2 °C. Respondents residing for more than 6 months in Singapore achieved thermal neutrality, suggesting that a greater degree of thermal adaptation likely developed during acclimatisation to local climate through a combination of physiological, behavioural and psychological circumstances. Comparisons with other OTC studies showed differences in synoptic climates are linked to variations in the magnitude and ranges of perceived PET. Lastly, respondents in this study perceived lower neutral and preferred temperatures compared to respondents surveyed over a variety of urban land use categories in another local study. The differences in neutral and preferred temperatures between studies suggest that lower park temperatures and different environmental attitudes influence perceived OTC.

Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity.

Tropane-containing small molecules like scopolamine are a promising class of psychoplastogens. However, their potent antagonism of all muscarinic receptor subtypes presents the potential for undesirable anticholinergic side effects. In an effort to decouple their neuroplasticity-promoting effects from their muscarinic activity, we performed phenotypic structure-activity relationship studies across a variety of structurally distinct subclasses of tropanes. We discovered several novel tropanes capable of significantly increasing cortical neuronal growth while exhibiting drastically reduced activity at all muscarinic receptor subtypes compared to scopolamine.

Rapid Synthesis of Psychoplastogenic Tropane Alkaloids.

Tropane alkaloids are an important class of biologically active small molecules characterized by their 8-azabicyclo[3.2.1]octane core. Because of their numerous medicinal applications, microbial biosynthesis and a variety of chemical syntheses have been designed for individual family members. However, current approaches are not amenable to late-stage structural diversification at N8, C3, C6, or C7, positions that are critical for modulating the biological properties of these molecules. Here, we describe a general approach to the synthesis of tropane alkaloids and their analogues that relies on the construction of the 8-azabicyclo[3.2.1]octane core through aziridination of a cycloheptadiene intermediate, followed by vinyl aziridine rearrangement. Using this strategy, we synthesized six tropane alkaloids and several analogues in only 5-7 steps. Given that the tropane alkaloid scopolamine has been reported to promote structural neuroplasticity and produce antidepressant effects, we tested five tropane-containing compounds for their ability to promote dendritic spine growth in cultured cortical neurons. We found that the orientation of the C3 substituent may play a role in the psychoplastogenic effects of tropane alkaloids. Our work provides a robust platform for producing tropane analogs for future structure-activity relationship studies.

5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines.

Psychedelic compounds have displayed antidepressant potential in both humans and rodents. Despite their promise, psychedelics can induce undesired effects that pose safety concerns and limit their clinical scalability. The rational development of optimized psychedelic-related medicines will require a full mechanistic understanding of how these molecules produce therapeutic effects. While the hallucinogenic properties of psychedelics are generally attributed to activation of serotonin 2A receptors (5-HT2ARs), it is currently unclear if these receptors also mediate their antidepressant effects as several nonhallucinogenic analogues of psychedelics with antidepressant-like properties have been developed. Moreover, many psychedelics exhibit promiscuous pharmacology, making it challenging to identify their primary therapeutic target(s). Here, we use a combination of pharmacological and genetic tools to demonstrate that activation of 5-HT2A receptors is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. Our results suggest that psychedelic tryptamines can induce hallucinogenic and therapeutic effects through activation of the same receptor.

Synthesis of Tertiary Amines through Extrusive Alkylation of Carbamates.

Basic amines are key elements of many biologically active natural products and pharmaceuticals. Given their inherent reactivity, it is often necessary to protect basic amines during target-directed synthesis, which results in wasteful protection/deprotection sequences. We report a step-economical approach enabling the protection of secondary amines as carbamates prior to their conversion to tertiary amines via the formal extrusion of CO2. This method is applied to the synthesis of iboga alkaloids (±)-conodusine A and (±)-conodusine B.

Patterns of land change and their potential impacts on land surface temperature change in Yangon, Myanmar.

This study used remote sensing imagery to characterize land use/cover patterns and to derive land surface temperature (LST) of Greater Yangon, the largest urban agglomeration in Myanmar, to provide insights into the association between land use/cover and seasonal, daytime, and nighttime LST change. Analysis of Landsat images from 1987 to 2015 showed urban expansion radiating from the city center and along prominent rivers, with major increases in built-up land (6.4%) and grassland (10.1%) and consequent decline in agricultural land (17%). Examination of MODIS LST showed that agricultural land was warmer than the city core during daytime in hot seasons, while in cold seasons, the city core was warmer than its rural surroundings during both daytime and nighttime. Correlation analysis revealed stronger association between built-up land and nighttime LST from 2000 to 2015, suggesting an increased surface urban heat island effect. Furthermore, this study highlighted two main differences from prior work on the influences of land use/cover on LST. First, the predominant land use/cover type that had great overall impact on LST was agricultural land, marked by its statistically significant correlation coefficients across all time periods of analysis. Such finding emphasized the influence of agriculture and related practices on the atmosphere and climate system. Second, the temporal analysis of LST highlighted a stronger and more complicated role water played because of its negative correlations with daytime LST and positive correlations with nighttime LST. The findings of this study underscored more complex effects of land use/cover on the spatial and temporal variations of LST in Yangon, compared to prior work that generally reported high LST in the urban areas. These insights improve the understanding of the land change consequences on the temporal dynamics of LST and can support sustainable land use planning for the better well-being of the inhabitants in Greater Yangon.

Long-term safety and clinical effectiveness of controlled-release metoclopramide in cancer-associated dyspepsia syndrome: a multicentre evaluation.

Patients with cancer frequently report gastrointestinal symptoms such as anorexia, early satiety, nausea, vomiting, and bloating. A reduction of the severity of some of these symptoms would benefit the patient by enhancing quality of life and improving their treatment. Forty-eight patients (25 female and 23 male; mean age 63 +/- 11 years) with a minimum two-week history of cancer-associated gastrointestinal symptoms were assigned to a single, open-label treatment group and received controlled-release metoclopramide 20 mg-80 mg q12h for a maximum period of 12 weeks (mean 46 +/- 35 days). There was a 40%-60% decrease in the severity of nausea over the first two weeks of treatment, and an approximate 50% reduction in severity of vomiting over the first four weeks of treatment. Appetite and bloating also improved, although smaller and less consistent changes were observed. Patient ratings of overall clinical effectiveness with respect to relief from symptoms and tolerability of side effects indicated that controlled-release metoclopramide was highly and moderately effective in 36% and 30% of the patients, respectively. Controlled-release metoclopramide is a useful treatment for the management of gastrointestinal symptoms associated with the cancer-associated dyspepsia syndrome including nausea, vomiting, loss of appetite, and bloating.