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The Saharo-Arabian desert is part of the largest near-continuous chain of drylands stretching from north-western Africa to the northern China. This harsh and often hyper-arid belt acts as a transition zone separating major biogeographic realms, including the Palearctic, Afrotropics and Indomalayan. This aridity is thought responsible for the creation of unique geographic endemism between Africa and Eurasia. However, there are no direct hydroclimate records from the Arabian hyper-arid interior before the mid-Pleistocene, leaving the terrestrial hydroclimate and the role of Arabia as a biogeographic crossroads or barrier largely unknown.We use desert speleothems preserved from the northern Arabian interior to identify past humid phases over the last 8 million years. These are particularly useful terrestrial climate archives as they act as underground rain gauges, requiring a minimum of ~300 mm a-1 precipitation, pedogenesis and vegetation cover to form. Moreover, they can be accurately and precisely dated and are subsequently a valuable tool in identifying past large-scale hydrological and vegetation changes in ancient drylands. Our data reveal evidence of multiple ‘windows of opportunity’ of climate amelioration, allowing biogeographic exchange and dispersals to occur across the Arabian hyper-arid zone. Further, the novel analyses of the isotopic composition (d18O and d2H) of speleothem fluid inclusion waters, representing ‘fossil rainwater’, reveal the diminishing influence of tropical rain-belt precipitation in Arabia across Earth’s transition from a largely ‘ice-free’ northern hemisphere to an ‘ice-age’ world. The extent of Arabian aridity may thus be important in controlling biogeographic dispersals through the Arabian corridor, becoming increasingly less favourable through time. This is supported by fossil evidence which suggest that exchange between biogeographic regions across the Old World Savannah Biome were favoured in the Late Miocene, but became increasingly latitudinally fragmented from the Pliocene onwards. These results have significant implications for understanding the drivers of dryland aridity in non-polar deserts globally.

The global development and modern distribution of arid zones in subtropical regions (drylands) are likely associated with the global cooling marking the dawn of the Quaternary (~2.6 Ma). This coincides with global shifts in ocean circulation patterns, the intensification of the Walker-Hadley circulation, declining atmospheric CO2, the initiation of glacial–interglacial cycles and the intensification of Northern Hemisphere glaciation, the combination of which has led to the current global distribution of non-polar deserts at ~30° latitude. Although modern drylands represent Earth’s largest terrestrial biome, covering ~46% of global land surfaces and supporting a global population of ~3 billion people, it is currently unclear how drylands will change under future climate change scenarios. Speleothems, preserved in arid-zone caves, are particularly useful terrestrial climate archives as they act as underground rain gauges, which require a minimum of ~300 mm a-1 precipitation, pedogenesis and vegetation cover to form. Moreover, they can be accurately and precisely dated and are subsequently a valuable tool in identifying past large-scale hydrological and vegetation changes in ancient drylands. Here, we present new data from speleothems during past ‘warm periods’ from the Arabian hyper-arid zone. We apply a novel technique of extracting speleothem fluid inclusions waters to reconstruct the isotopic composition (d18O and d2H) of ‘fossil rainwater’ preserved in the speleothem fabric pristinely over millions of years. Speleothem evidence suggests that during the last 7 million years, the Sahara-Arabian desert experienced numerous intermittent humid phases, typically occurring with periods of low global ice-volume and warmer global temperatures. We further explore tropical push-pull mechanisms driving heating of the deep tropics and subsequent expansion of the tropical zone and synchronicity of humid phases regionally. These results have significant implications for understanding the drivers of dryland aridity in non-polar deserts globally.

Dissolved silicon (DSi) is a key nutrient in the oceans, but there are few data available regarding Si isotopes in coastal aquifers. Here we investigate the Si isotopic composition of 12 fresh and 17 saline groundwater samples from Rottnest Island, Western Australia, which forms part of the world’s most extensive aeolianite deposit (the Tamala Limestone Formation). Two bedrock samples were also collected from Rottnest Island for Si isotope analysis. The δ30Si values of groundwaters ranged from −0.39 to +3.60 ‰ with an (average: +1.59 ‰) and the rock samples were −0.76 and −0.13 ‰. Due to the relatively low concentrations of DSi (64 to 196 μM) and clay-forming cations in fresh groundwaters, the correlation between δ30Si values and DSi concentrations (ρ = 0.59, p = 0.02) may be explained by Si adsorption onto Fe-Al (oxy)hydroxides present in the aquifer. An increase in groundwater δ30Si in association with the occurrence of water-rock interactions may explain the spatial pattern in δ30Si across the aquifer, and is consistent with the correlation between δ30Si and tritium activities when considering all groundwaters (ρ = −0.68, p = 0.0002). In the deeper aquifer, the inverse correlation between DSi and Cl concentrations (ρ = −0.79, p = 0.04) for the more saline groundwaters is attributed to groundwater mixing with local seawater that is depleted in DSi (

There is a lack of knowledge regarding in-vehicle concentrations of nitrogen dioxide (NO2) during transit through road tunnels in urban environments. Furthermore, previous studies have tended to involve a single vehicle and the range of in-vehicle NO2 concentrations that vehicle occupants may be exposed to is not well defined. This study describes simultaneous measurements of in-vehicle and outside-vehicle NO2 concentrations on a route through Sydney, Australia that included several major tunnels, minor tunnels and busy surface roads. Tests were conducted on nine passenger vehicles to assess how vehicle characteristics and ventilation settings affected in-vehicle NO2 concentrations and the in-vehicle-to-outside vehicle (I/O) concentration ratio. NO2 was measured directly using a cavity attenuated phase shift (CAPS) technique that gave a high temporal and spatial resolution. In the major tunnels, transit-average in-vehicle NO2 concentrations were lower than outside-vehicle concentrations for all vehicles with cabin air recirculation either on or off. However, markedly lower I/O ratios were obtained with recirculation on (0.08–0.36), suggesting that vehicle occupants can significantly lower their exposure to NO2 in tunnels by switching recirculation on. The highest mean I/O ratios for NO2 were measured in older vehicles (0.35–0.36), which is attributed to older vehicles having higher air exchange rates. The results from this study can be used to inform the design and operation of future road tunnels and modelling of personal exposure to NO2.

Conjugation of the phenol derived from rivastigmine with amphetamines gave access to novel carbamate cholinesterase inhibitors. All compounds possessed increased affinity and selectivity for AChE compared to rivastigmine and were orally bioavailable. Compound 4a, incorporating d-amphetamine, caused significant inhibition of cholinesterase in vivo at doses that were well tolerated. Release of amphetamine from 4a was demonstrated following in vitro and in vivo inhibition of cholinesterase. Compound 4a was also effective in alleviating scopolamine induced amnesia in a rat passive avoidance model.

Phosphodiesterases (PDEs) belonging to the PDE4 family control intracellular concentrations of cyclic adenosine monophosphate (cAMP) by catalyzing its hydrolysis. Four separate PDE4 genes (PDE4A, PDE4B, PDE4C, and PDE4D) have been identified. PDE4 has been reported to be involved in various central nervous system (CNS) functions including depression, memory, and schizophrenia, although the specific subtype mediating these effects remains unclear. To investigate the role of PDE4B in the CNS, PDE4B wild-type and knockout mice (C57BL/6N background) were assessed in a variety of well-characterized behavioral tasks, and their brains were assayed for monoamine content. Knockout mice showed a significant reduction in prepulse inhibition. Spontaneous locomotor activity was decreased (16%) in knockout mice. Furthermore, when challenged with amphetamine, both groups of mice responded similarly to a low dose of d-amphetamine (1.0 mg/kg), but knockout mice showed an enhanced response to a higher dose (1.78 mg/kg). Decreases in baseline levels of monoamines and their metabolites within the striatum of knockout mice were also observed. PDE4B knockout mice showed a modest decrease in immobility time in the forced swim test that approached significance. In several other tests, including the elevated plus maze, hot plate, passive avoidance, and Morris water maze, wild-type and knockout mice performed similarly. The present studies demonstrate decreased striatal DA and 5-HT activity in the PDE4B knockout mice associated with decreased prepulse inhibition, decreased baseline motor activity, and an exaggerated locomotor response to amphetamine. These data further support a role for PDE4B in psychiatric diseases and striatal function.

The phenotype of genetically modified animals is strongly influenced by both the genetic background of the animal as well as environmental factors. We have previously reported the behavioral and neurochemical characterization of PDE10A knockout mice maintained on a DBA1LacJ (PDE10A(DBA)) genetic background. The aim of the present studies was to assess the behavioral and neurochemical phenotype of PDE10A knockout mice on an alternative congenic C57BL/6N (PDE10A(C57)) genetic background. Consistent with our previous results, PDE10A(C57) knockout mice showed a decrease in exploratory locomotor activity and a delay in the acquisition of conditioned avoidance responding. Also consistent with previous studies, the elimination of PDE10A did not alter basal levels of striatal cGMP or cAMP or affect behavior in several other well-characterized behavioral assays. PDE10A(C57) knockout mice showed a blunted response to MK-801, although to a lesser degree than previously observed in the PDE10A(DBA) knockout mice, and no differences were observed following a PCP challenge. PDE10A(C57) knockout mice showed a significant change in striatal dopamine turnover, which was accompanied by an enhanced locomotor response to AMPH, These studies demonstrate that while many of the behavioral effects of the PDE10A gene deletion appear to be independent of genetic background, the impact of the deletion on behavior can vary in magnitude. Furthermore, the effects on the dopaminergic system appear to be background-dependent, with significant effects observed only in knockout mice on the C57BL6N genetic background.

Recent studies provide evidence for reduced phosphodiesterase-4B (PDE4B) as a genetic susceptibility factor as well as suggesting an association of several single nucleotide polymorphisms (SNPs) in PDE4B that are associated with an increased incidence of schizophrenia.The aim of the current study was to assess the activity of rolipram, a nonsubtype-selective PDE4 inhibitor, in several animal models predictive of antipsychotic-like efficacy and side-effect liability and to use PDE4B wild-type and knockout mice to begin to understand the subtypes involved in the activity of rolipram.In rats, rolipram antagonized both phencyclidine hydrochloride- and D-amphetamine-induced hyperactivity and inhibited conditioned avoidance responding (CAR). In PDE4B wild-type mice, rolipram dose-dependently suppressed CAR (ED(50) = 2.4 mg/kg); however, in knockout mice, their sensitivity to rolipram at the higher doses (1.0 and 3.2 mg/kg) was reduced, resulting in a threefold shift in the ED(50) (7.3 mg/kg), suggesting PDE4B is involved, at least in part, with the activity of rolipram. Only the highest dose of rolipram (3.2 mg/kg) produced a modest but significant degree of catalepsy.Rolipram has a pharmacologic profile similar to that of the atypical antipsychotics and has low extrapyramidal symptom liability. These results suggest that PDE4B mediates the antipsychotic effects of rolipram in CAR and that the PDE4B-regulated cyclic adenosine monophosphate signaling pathway may play a role in the pathophysiology and pharmacotherapy of psychosis.

Group 4 metal complexes Zr-1 to Zr-4, Ti-4 and Ti-4a that contain an (OSSO)-type tetradentate bis(phenolate) ligand were found to initiate the ring-opening polymerization of meso-, rac-, and L-lactides in toluene solution. The polymerizations were controlled with initiator efficiency values around one and gave polymers with low polydispersity (Mw/Mn < 1.2). The polylactides were atactic when rac-lactide was used as the monomer and heterotactic biased when meso-lactide was used. Kinetic measurements showed that meso-lactide was polymerized generally faster than rac- and L-lactide.