The effects of climate change and land‐use change on demographic rates and population viability

Understanding the processes that lead to species extinctions is vital for lessening pressures on biodiversity. While species diversity, presence and abundance are most commonly used to measure the effects of human pressures, demographic responses give a more proximal indication of how pressures affect population viability and contribute to extinction risk. We reviewed how demographic rates are affected by the major anthropogenic pressures, changed landscape condition caused by human land use, and climate change. We synthesized the results of 147 empirical studies to compare the relative effect size of climate and landscape condition on birth, death, immigration and emigration rates in plant and animal populations. While changed landscape condition is recognized as the major driver of species declines and losses worldwide, we found that, on average, climate variables had equally strong effects on demographic rates in plant and animal populations. This is significant given that the pressures of climate change will continue to intensify in coming decades. The effects of climate change on some populations may be underestimated because changes in climate conditions during critical windows of species life cycles may have disproportionate effects on demographic rates. The combined pressures of land‐use change and climate change may result in species declines and extinctions occurring faster than otherwise predicted, particularly if their effects are multiplicative.     

Design and synthesis of long acting inhaled corticosteroids for the treatment of asthma

In this Letter we present data for a novel series of ICS for the treatment of asthma. 'Inhalation by design' principles have been applied to a series of highly potent steroidal GR agonists, with a focus on optimising the potential therapeutic index in human. Pharmacokinetic properties were tuned with high intrinsic clearance and low oral bioavailability in mind, to minimise systemic exposure and reduce systemically driven adverse events. High CYP mediated clearance as well as glucuronidation were targeted to achieve high intrinsic clearance coupled with multiple routes of clearance to minimise drug-drug interactions. Furthermore, pharmaceutical properties such as stability, crystallinity and solubility were considered to ensure compatibility with a dry powder inhaler. This work culminated in the identification of the clinical candidate 15, which demonstrates preclinically the desired efficacy and safety profiles confirming its potential as an inhaled agent for the treatment of asthma.     

Functional ultrasound imaging of the brain

We present functional ultrasound (fUS), a method for imaging transient changes in blood volume in the whole brain at better spatiotemporal resolution than with other functional brain imaging modalities. fUS uses plane-wave illumination at high frame rate and can measure blood volumes in smaller vessels than previous ultrasound methods. fUS identifies regions of brain activation and was used to image whisker-evoked cortical and thalamic responses and the propagation of epileptiform seizures in the rat brain.     

‘Ecologically complex carbon’– linking biodiversity values,carbon storage and habitat structure in some austral temperate forests

Aim We assessed how avian biodiversity and above‐ground carbon storage were related in different forest age‐classes, including mature stands (> 100 years), in a managed, mixed‐species eucalypt forest. Location Gippsland, south‐eastern Australia. Methods In 50 2‐ha stands ranging in age from ≤ 5 years to mature stands > 100 years, we undertook repeated avian surveys, performed detailed habitat measurements and estimated amounts of above‐ground carbon. Extensive wildfire reduced the number of sites to 28 (seven in each of four age classes) upon which analyses and inferences were made. We also analysed data on carbon storage and some bird responses from previously published studies. Results Mature vegetation (> 100 years) had the greatest richness, abundance and biomass of birds. Key ecological resources, such as tree‐hollows for nesting, generally occurred mostly in stands > 60 years. Avian richness per unit of above‐ground carbon storage was relatively low for stands of 20–60 years. While above‐ground carbon storage appeared to increase in a monotonic fashion as stands age and mature, there were quantum increases in all measures of avian biodiversity in mature stands (> 100 years). Main conclusions Our results suggest that carbon is organized in a different way, with substantially greater biodiversity benefits, in very old stands. Mature vegetation simultaneously maximizes both avian biodiversity and above‐ground carbon storage. These results bolster arguments for allocating highest priorities to the preservation of old‐growth forest stands rather than alternative investments (e.g. reafforestation for carbon sequestration).     

Module-based multiscale simulation of angiogenesis in skeletal muscle

Background  

Mathematical modeling of angiogenesis has been gaining momentum as a means to shed new light on the biological complexity underlying blood vessel growth. A variety of computational models have been developed, each focusing on different aspects of the angiogenesis process and occurring at different biological scales, ranging from the molecular to the tissue levels. Integration of models at different scales is a challenging and currently unsolved problem.     

Integrifolin,a guaianolide from Andryala integrifolia

Integrifolin, the major constituent of Andryala integrifolia, has been isolated and characterized as 3β,8β-dihydroxy-4(15),10(14),11(13)-trien-(1αH), (5αH) guaian-6,12-olide (8-epi-desacylcynaropicrin).     

Effects of 6-methoxy-2-benzoxazolinone on the germination and alpha-amylase activity in lettuce seeds

Germination of lettuce seeds was inhibited by 6-methoxy-2-benzoxazolinone (MBOA) at concentrations greater than 0.03 mmol/L. MBOA also inhibited the induction of alpha-amylase activity in the lettuce seeds at concentrations greater than 0.03 mmol/L. These two concentration-response curves for the germination and alpha-amylase indicate that the percentage of the germination was positively correlated with the activity of alpha-amylase in the seeds. Lettuce seeds germinated around 18h after incubation and inhibition of alpha-amylase by MBOA occurred within 6h after seed incubation. These results show that MBOA may inhibit the germination of lettuce seeds by inhibiting the induction of alpha-amylase activity.     

Discovery that a melanocortin regulates sexual functions in male and female humans

Melanocortins (MCs) are multifunctional peptide hormones that regulate a diversity of physiological functions. MCs have been implicated in sexual function in animals. We document here that a MC analog, Melanotan II (MTII), can enhance sexual function in human males (erectile activity) and females (increased levels of sexual desire and genital arousal). Unlike other sexual-enhancement drugs, MTII works at the level of the brain, thus eliciting a rather natural sexual response with minimal or no undesirable side effects. The actions of the peptide were discovered accidentally while studying the effects of the peptide and related analogs on human skin pigmentation (tanning).     

Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis

Morphine analgesic properties and side effects such as tolerance are mediated by the mu opioid receptor (MOR) whose endocytosis is considered of primary importance for opioid pharmacological effects. Here, we show that p38 mitogen-activated protein kinase (MAPK) activation is required for MOR endocytosis and sufficient to trigger its constitutive internalization in the absence of agonist. Further studies established a functional link between p38 MAPK and the small GTPase Rab5, a key regulator of endocytosis. Expression of an activated mutant of Rab5 stimulated endocytosis of MOR ligand-independently in wild-type but not in p38alpha-/- cells. We found that p38alpha can phosphorylate the Rab5 effectors EEA1 and Rabenosyn-5 on Thr-1392 and Ser-215, respectively, and these phosphorylation events regulate the recruitment of EEA1 and Rabenosyn-5 to membranes. Moreover, phosphomimetic mutation of Thr-1392 in EEA1 can bypass the requirement for p38alpha in MOR endocytosis. Our results highlight a novel mechanism whereby p38 MAPK regulates receptor endocytosis under physiological conditions via phosphorylation of Rab5 effectors.     

Cu(II) complexes with a sulfonamide derived from benzoguanamine. Oxidative cleavage of DNA in the presence of H2O2 and ascorbate

Reaction between benzoguanamine (2,4-diamino-6-phenyl-1,3,5-triazine) and 2-mesitylenesulfonyl chloride leads to formation of a sulfonamide able to form two mononuclear Cu(II) complexes with a CuL(2) stoichiometry. The local environment of the metal cation is a distorted octahedron, with two ligands and two solvent molecules; both complexes crystallize in the monoclinic structure, space group P2(1), with Z=2. In the presence of ascorbate/H(2)O(2,) the two complexes significantly cleavage double-strand pUC18 DNA plasmid. Both complexes exhibit more nuclease efficiency that the copper phenantroline complex. From scavenging reactive oxygen studies we conclude that the hydroxyl radical and a singlet oxygen-like entity, such a peroxide copper complex, are the radical species involved in the DNA damage.