Response to commentary by Woinarski (Critical‐weight‐range marsupials in northern Australia are declining: a commentary on Fisher et al. (2014) ‘The current decline of tropical marsupials in Australia: is history repeating?’)

The recent commentary by Woinarski (2014, Global Ecology and Biogeography, doi: 10.1111/geb.12165) disagreed with our conclusions on the correlates of decline in the marsupials of tropical Australia (Fisher et al., 2014, Global Ecology and Biogeography, 23 , 181–190). We compared traits of species that were associated with range decline in southern and northern Australia. We found that habitat structure, climate and body size were correlated with range decline. In the north, declines of marsupials were most severe in savanna with moderate rainfall. In the south, the ranges of species in open habitat with very low rainfall have declined most. Also, the association between range decline and body mass differed between north and south: this is the main concern of Woinarski, who further disagreed with our choice of the Tropic of Capricorn as a boundary between north and south, our omission of rodents, how to treat timing of extinctions, and our inference that cats are major drivers of decline. We address these concerns in this response.     

Role of α2‐macroglobulin in regulating amyloid β‐protein neurotoxicity: protective or detrimental factor?

alpha2-Macroglobulin (alpha2M) has been identified as a carrier protein for beta-amyloid (Abeta) decreasing fibril formation and affecting the neurotoxicity of this peptide. The alpha2-macroglobulin receptor/low density lipoprotein receptor related protein (LRP) is involved in the internalization and degradation of the alpha2M/Abeta complexes and its impairment has been reported to occur in Alzheimer's disease. Previous studies have shown alpha2M to determine an enhancement or a reduction of Abeta toxicity in different culture systems. In order to clarify the role of alpha2M in Abeta neurotoxicity, we challenged human neuroblastoma cell lines with activated alpha2M in combination with Abeta. Our results show that in neuroblastoma cells expressing high levels of LRP, the administration of activated alpha2M protects the cells from Abeta neurotoxicity. Conversely, when this receptor is not present alpha2M determines an increase in Abeta toxicity as evaluated by MTT and TUNEL assays. In LRP-negative cells transfected with the full-length human LRP, the addition of activated alpha2M resulted to be protective against Abeta-induced neurotoxicity. By means of recombinant proteins we ascribed the neurotoxic activity of alpha2M to its FP3 fragment which has been previously shown to bind and neutralize transforming growth factor-beta. These studies provide evidence for both a neuroprotective and neurotoxic role of alpha2M regulated by the expression of its receptor LRP.     

The α‐sheet: A missing‐in‐action secondary structure?

The α-sheet has been speculated to play a role as a toxic conformer in amyloid diseases. However, except for relatively short fragments, its detection has remained elusive. Here, we present molecular dynamics simulations that support the existence of the α-sheet as a stable, metastable, or long-lived secondary structure in polyglutamine and, to a lesser extent, in polyasparagine aggregates.     

Extended π‐Bridge in Organic Dye‐Sensitized Solar Cells: the Longer,the Better?

The elongation of π‐conjugated bridges between the donor (D) and the acceptor (A) represents a feasible strategy towards enhancement of light‐harvesting in both breadth and depth of organic D‐π‐A dyes suitable for nanocrystalline TiO₂‐based dye‐sensitized solar cells (DSSCs). Here, a series of organic dyes with elongating conjugated bridges is synthesized and characterized. DSSC devices employing a cobalt (II/III) redox electrolyte are fabricated using these dyes as light‐harvesting sensitizers. Compared to a dye with the 3,4‐ethylenedioxythiophene (EDOT) linker ( G188 ), the three counterparts with further extended π‐bridges present gradually red‐shifted electronic absorption spectra and a persistent decrease in oxidation potential. The photocurrent action spectra show that the extension of π‐conjugated bridges decreases the open‐circuit photovoltage. The best performance is shown in G268 with a short‐circuit photocurrent density (J_sc) of 16.27 mA cm², an open‐circuit photovoltage (V_oc) of 0.83 V, and a fill factor (FF) of 0.67, corresponding to an overall conversion efficiency of 9.24%. Unexpectedly, G270, which has with the longest π‐bridge , showed the lowest J_sc, V_oc, and efficiency.     

Who Is the King? The α‐Hydroxy‐β‐oxo‐α,β‐enone Moiety or the Catechol B Ring: Relationship between the Structure of Quercetin Derivatives and Their Pro‐Oxidative Abilities

Quercetin and other flavonoids have been reported to exhibit both antioxidant and pro‐oxidant properties. Most studies about the pro‐oxidative ability were conducted in the presence of metal ions, and the essential functional moiety of quercetin responsible for the pro‐oxidative effect is still unclear. In this study, we evaluated the pro‐oxidative abilities in the absence of metal ions of two quercetin derivatives, i.e., quercetin‐3′‐O‐β‐D ‐glucoside ( 1 ) and quercetin‐3‐O‐β‐D ‐glucoside ( 2 ), by assessing DNA cleavage and HO^.‐radical production. The binding mode between these compounds and DNA was studied by fluorescence and viscometric titrations. The results showed that 1 can efficiently induce oxidative damage to plasmid DNA, while 2 shows poor activity. Both 1 and 2 bind to DNA via groove‐binding. These results proved that the α‐hydroxy‐β‐oxo‐α,β‐enone moiety contributes to the pro‐oxidative activity of quercetin.     

Lipopolysaccharide‐induced increase in signalling in hippocampus is abrogated by IL‐10 – a role for IL‐1β?

Parenterally administered lipopolysaccharide (LPS) increases the concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the rat hippocampus and evidence suggests that this effect plays a significant role in inhibiting long-term potentiation (LTP). The anti-inflammatory cytokine IL-10, antagonizes certain effects of IL-1beta, so if the effects of LPS are mediated through an increase in IL-1beta, it might be predicted that IL-10 would also abrogate the effect of LPS. Here, we report that IL-10 reversed the inhibitory effect of LPS on LTP and the data couple this with an inhibitory effect on the LPS-induced increase in IL-1beta. LPS treatment increased hippocampal expression of IL-1 receptor Type I protein. Consistent with the LPS-induced increases in IL-1beta concentration and receptor expression, were downstream changes which included enhanced phosphorylation of IRAK and the stress-activated kinases, JNK and p38; these LPS-induced changes were reversed by IL-10, which concurs with the idea that these events are triggered by increased activation of IL-1RI by IL-1beta. We provide evidence which indicates that LPS treatment leads to evidence of cell death and this was reversed in hippocampus prepared from LPS-treated rats which received IL-10. The evidence is therefore consistent with the idea that IL-10 acts to protect neuronal tissue from the detrimental effects induced by LPS.     

What stabilizes the 314‐helix in β3‐peptides? A conformational analysis using molecular simulation

β‐Peptides are analogs of natural α‐peptides and form a variety of remarkably stable structures. Having an additional carbon atom in the backbone of each residue, their folded conformation is not only influenced by the side‐chain sequence but also and foremost by their substitution pattern. The precise mechanism by which the side chains interact with the backbone is, however, hitherto not completely known. To unravel the various effects by which the side chains influence the backbone conformation, we quantify to which extent the dihedral angles of a β³‐substited peptide with an additional methyl group on the central C_α‐atom can be regarded as independent degrees of freedom and analyze the distributions of these dihedral angles. We also selectively capture the steric effect of substituents on the C_α‐ and C_β‐atoms of the central residue by alchemically changing them into dummy atoms, which have no nonbonded interactions. We find that the folded state of the β³‐peptide is primarily stabilized by a steric exclusion of large parts of the unfolded state (entropic effect) and only subsequently by mutual dependence of the ψ‐dihedral angles (enthalpic effect). The folded state of β‐peptides is stabilized by a different mechanism than that of α‐peptides. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

Is (9Z)‐“meso”‐zeaxanthin optically active?

The question raised in the title was answered. (3R, 3'S)-meso-Zeaxanthin was submitted to iodine catalyzed photochemical stereoisomerisation. The enantiomeric (9Z) and (9'Z) geometrical isomers were isolated by semipreparative HPLC and separated as diastereomeric dicarbamates on a chiral column only. Cleavage of the carbamate could not be effected. CD-Spectra of (1"S, 1"S)- and (1"R, 1"R)-dicarbamates of geometrical isomers of (3R, 3'R)- and (3R, 3'S)-meso-zeaxanthin were systematically studied and the contribution from the carbamate moieties revealed. It was concluded that (9Z, 3R, 3'S)-"meso"-zeaxanthin, in spite of having no symmetry elements, is optically inactive. The result has been rationalised in line with the current hypothesis on the origin of carotenoid CD spectra.     

Can the combination of electrochemical regeneration of NAD+, selectivity of L‐α‐amino‐acid dehydrogenase,and reductive amination of α‐keto‐acid be applied to the inversion of configuration of a L‐α‐amino‐acid?

The inversion of configuration of L‐alanine can be carried out by combining its selective oxidation in the presence of NAD⁺ and L‐alanine dehydrogenase, electrochemical regeneration of the NAD⁺ at a carbon felt anode, and reductive amination of pyruvate, i.e., reduction of its imino derivative at a mercury cathode, the reaction mixture being buffered with concentrated ammonium/ammonia (1.28M / 1.28M). The dehydrogenase exhibits astonishing activity and stability under such extreme conditions of pH and ionic strength. The main drawback of the process is its slowness. At best, the complete inversion of a 10 mM solution of L‐alanine requires 140 h. A careful and detailed quantitative analysis of each of the key steps involved shows that the enzyme catalyzed oxidation is so thermodynamically uphill that it can be driven efficiently to completion only when both the coenzyme regeneration and the pyruvate reduction are very effective. The first condition is easily fulfilled. Under the best conditions, it is the rate of the chemical reaction producing the imine which controls the whole process kinetically. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 101–107, 1999.     

SIRT1 longevity factor suppresses NF‐κB ‐driven immune responses: regulation of aging via NF‐κB acetylation?

The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF-kappaB signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF-kappaB system in aging and immune responses. Adler et al showed that the NF-kappaB binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al studying HIV-1 infection and subsequent immune deficiency process demonstrated that HIV-1 Tat protein binds to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT1-mediated deacetylation of the p65 component of the NF-kappaB complex. As a consequence, the transactivation efficiency of the NF-kappaB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF-kappaB transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF-kappaB signaling, the major outcome of which is inflamm-aging via proinflammatory responses.     

Étienne Geoffroy St.‐Hilaire: father of “evo‐devo”?

SUMMARY In the early decades of the nineteenth century, the most important disagreement among comparative anatomists was not evolution versus "special creation" but between advocates of "transcendental morphology" and those of teleological anatomy—form versus function. In France this dichotomy was represented by the 1830–1832 public debate between Geoffroy St.-Hilaire (form) and Cuvier (function). Geoffroy's aim was to establish links of homology (known to him as "analogies") between the four "embranchements" into which Cuvier had divided the animal kingdom. Despite the fanciful nature of some of his homologies, Geoffroy, who was guided by his " principe de connections ," set in motion a school of morphology, some of whose conclusions, notably the homology of the dorsal surface of segmented invertebrates with the ventral surface of vertebrates, has been corroborated by recent studies in developmental genetics.     

Poisoning for production: how effective is fox baiting in south‐eastern Australia?

• 1 The European red fox Vulpes vulpes represents a continuing threat to both livestock and native vertebrates in Australia, and is commonly managed by setting ground‐level baits impregnated with 1080 (sodium fluoroacetate) poison. However, the long‐term effectiveness of such control campaigns is likely to be limited due to the ability of foxes to disperse over considerable distances and to swiftly recolonize areas from where they had been removed.
• 2 To investigate the effectiveness of fox baiting in a production landscape, we assessed the potential for foxes to reinvade baited farm property areas within the jurisdiction of the Molong Rural Lands Protection Board (RLPB), an area of 815 000 ha on the central tablelands of New South Wales, Australia. The spatial distribution and timing of fox baiting campaigns between 1998 and 2002 was estimated from RLPB records and mapped using Geographical Information System software. The effectiveness of the control campaign was assessed on the basis of the likely immigration of foxes from non‐baited farms using immigration distances calculated from published relationships between dispersal distance and home range size.
• 3 Few landholders undertook baiting campaigns in any given year, and the area baited was always so small that no baited property would have been sufficiently far from an unbaited property to have been immune from immigrating individuals. It is likely, therefore, that immigration onto farms negated any long‐term effects of baiting operations. This study highlights some of the key deficiencies in current baiting practices in south‐eastern Australia and suggests that pest management programmes should be monitored using such methods to ensure they achieve their goals.