Are communities saturated? On the relationship between α, β and γ diversity

A popular way to suggest a regional influence on local species diversity has been to plot local versus regional diversity. The form of these curves has been interpreted as evidence for or against "community saturation" due to species interactions. This interpretation, however, is unwarranted. Using the concepts of α, β and γ diversity, I show that local–regional richness curves are determined by the way total diversity is partitioned between its α and β components, which itself is a matter of scale. Changing the scale of the local community amounts to changing the scale at which the heterogeneity of the interactions between organisms and their environment manifests itself, and hence the balance between α and β diversity. Community saturation may occur because of physical limitations, but there are no theoretical grounds for the belief that species interactions set an absolute upper limit to diversity at any scale. A distinction between different meanings of the concept of "saturation" is proposed to clarify this issue. I argue that the challenge now is to understand the relationship between α and β diversity at multiple scales, and the processes that determine it.     

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.     

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.     

How and why does β‐actin mRNA target?

beta-Actin mRNA is localized near the leading edge in several cell types where actin polymerization is actively promoting forward protrusion. The localization of the beta-actin mRNA near the leading edge is facilitated by a short sequence in the 3'UTR (untranslated region), the 'zipcode'. Localization of the mRNA at this region is important physiologically. Treatment of chicken embryo fibroblasts with antisense oligonucleotides complementary to the localization sequence (zipcode) in the 3'UTR leads to delocalization of beta-actin mRNA, alteration of cell phenotype and a decrease in cell motility. The dynamic image analysis system (DIAS) used to quantify movement of cells in the presence of sense and antisense oligonucleotides to the zipcode showed that net pathlength and average speed of antisense-treated cells were significantly lower than in sense-treated cells. This suggests that a decrease in persistence of direction of movement and not in velocity results from treatment of cells with zipcode-directed antisense oligonucleotides. We postulate that delocalization of beta-actin mRNA results in delocalization of nucleation sites and beta-actin protein from the leading edge followed by loss of cell polarity and directional movement. Hence the physiological consequences of beta-actin mRNA delocalization affect the stability of the cell phenotype.     

Is the binding of β-amyloid protein to antichymotrypsin in Alzheimer plaques mediated by a β-strand insertion?

A growing body of experimental evidence demonstrates that the serpin antichymotrypsin plays a regulatory role in Alzheimer plaque physiology by interacting with the 42 residue β-amyloid protein, and we have used molecular modeling and energy minimization techniques to study this interaction. Based on the unique plasticity of β-sheet elements in antichymotrypsin (as well as other serpins), we conclude that the interaction of the two proteins is mediated by insertion of the N-terminus of β-amyloid into β-sheet C of antichymotrypsin as a pseudo-strand s1C. This β-strand insertion requires the displacement of native antichymotrypsin strand s1C, which is known to occur partially or completely at different stages of serpin function. Thus, the association of the two proteins in vivo may be facilitated by a particular functional state of the serpin, e.g., the native or protease-complexed state. © 1996 Wiley-Liss, Inc.     

Do commonly used indices of β‐diversity measure species turnover?

Abstract. Indices of β‐diversity are of two major types, (1) those that measure among‐plot variability in species composition independently of the position of individual plots on spatial or environmental gradients, and (2) those that measure the extent of change in species composition along predefined gradients, i.e. species turnover. Failure to recognize this distinction can lead to the inappropriate use of some β‐diversity indices to measure species turnover. Several commonly‐used indices of β‐diversity are based on Whittaker's β_W (β_W = γ/α, where γ is the number of species in an entire study area and α is the number of species per plot within the study area). It is demonstrated that these indices do not take into account the distribution of species on spatial or environmental gradients, and should therefore not be used to measure species turnover. The terms ‘β‐diversity’ and ‘species turnover’ should not be used interchangeably. Species turnover can be measured using matrices of compositional similarity and physical or environmental distances among pairs of study plots. The use of indices of β‐diversity and similarity‐distance curves is demonstrated using simulated data sets.     

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.     

Beyond taxonomic diversity patterns: how do α, β and γ components of bird functional and phylogenetic diversity respond to environmental gradients across France?

Aim To test how far can macroecological hypotheses relating diversity to environmental factors be extrapolated to functional and phylogenetic diversities, i.e. to the extent to which functional traits and evolutionary backgrounds vary among species in a community or region. We use a spatial partitioning of diversity where regional or γ‐diversity is calculated by aggregating information on local communities, local or α‐diversity corresponds to diversity in one locality, and turnover or β‐diversity corresponds to the average turnover between localities and the region. Location France. Methods We used the Rao quadratic entropy decomposition of diversity to calculate local, regional and turnover diversity for each of three diversity facets (taxonomic, phylogenetic and functional) in breeding bird communities of France. Spatial autoregressive models and partial regression analyses were used to analyse the relationships between each diversity facet and environmental gradients (climate and land use). Results Changes in γ‐diversity are driven by changes in both α‐ and β‐diversity. Low levels of human impact generally favour all three facets of regional diversity and heterogeneous landscapes usually harbour higher β‐diversity in the three facets of diversity, although functional and phylogenetic turnover show some relationships in the opposite direction. Spatial and environmental factors explain a large percentage of the variation in the three diversity facets (>60%), and this is especially true for phylogenetic diversity. In all cases, spatial structure plays a preponderant role in explaining diversity gradients, suggesting an important role for dispersal limitations in structuring diversity at different spatial scales. Main conclusions Our results generally support the idea that hypotheses that have previously been applied to taxonomic diversity, both at local and regional scales, can be extended to phylogenetic and functional diversity. Specifically, changes in regional diversity are the result of changes in both local and turnover diversity, some environmental conditions such as human development have a great impact on diversity levels, and heterogeneous landscapes tend to have higher diversity levels. Interestingly, differences between diversity facets could potentially provide further insights into how large‐ and small‐scale ecological processes interact at the onset of macroecological patterns.     

The Wnt/β‐catenin pathway: master regulator of liver zonation?

The liver contains two systems for the removal of ammonia - the urea cycle and the enzyme glutamine synthetase. These systems are expressed in a complementary fashion in two distinct populations of hepatocytes, referred to as periportal and perivenous cells. One of the unresolved problems in hepatology has been to elucidate the molecular mechanisms responsible for induction and maintenance of the cellular heterogeneity for ammonia detoxification. There is now a potential molecular explanation for the zonation of the urea cycle and glutamine synthetase based on the Wnt/beta-catenin pathway.     

β‐Amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?

The steady-state level of amyloid beta-peptide (Abeta) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the beta- and gamma-secretases and its catabolism by a variety of proteolytic enzymes. Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself degrades both Abeta(1-40) and Abeta(1-42) in vitro and in vivo, and this metabolism is prevented by NEP inhibitors. Other NEP family members, for example endothelin-converting enzyme, may contribute to amyloid catabolism and may also play a role in neuroprotection. Another metalloproteinase, insulysin (insulin-degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may contribute more generally to metabolism of amyloid-forming peptides. Other candidate enzymes proposed include angiotensin-converting enzyme, some matrix metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase-24.15). This review critically evaluates the evidence relating to proteinases implicated in amyloid catabolism. Therapeutic strategies aimed at promoting A,beta degradation may provide a novel approach to the therapy of Alzheimer's disease.     

Interleukin‐1β: a bridge between inflammation and excitotoxicity?

Interleukin-1 (IL-1) is a proinflammatory cytokine released by many cell types that acts in both an autocrine and/or paracrine fashion. While IL-1 is best described as an important mediator of the peripheral immune response during infection and inflammation, increasing evidence implicates IL-1 signaling in the pathogenesis of several neurological disorders. The biochemical pathway(s) by which this cytokine contributes to brain injury remain(s) largely unidentified. Herein, we review the evidence that demonstrates the contribution of IL-1β to the pathogenesis of both acute and chronic neurological disorders. Further, we highlight data that leads us to propose IL-1β as the missing mechanistic link between a potential beneficial inflammatory response and detrimental glutamate excitotoxicity.     

A gene for speed? The evolution and function of α‐actinin‐3

The alpha-actinins are an ancient family of actin-binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. alpha-actinin-3 is the most-highly specialised of the four mammalian alpha-actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion ( approximately 18%) of the human population is totally deficient in alpha-actinin-3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other alpha-actinin family members. The alpha-actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution.     

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.     

Phylogeny of γ‐proteobacteria: resolution of one branch of the universal tree?

The reconstruction of bacterial evolutionary relationships has proven to be a daunting task because variable mutation rates and horizontal gene transfer (HGT) among species can cause grave incongruities between phylogenetic trees based on single genes. Recently, a highly robust phylogenetic tree was constructed for 13 gamma-proteobacteria using the combined alignments of 205 conserved orthologous proteins.1 Only two proteins had incongruent tree topologies, which were attributed to HGT between Pseudomonas species and Vibrio cholerae or enterics. While the evolutionary relationships among these species appears to be resolved, further analysis suggests that HGT events with other bacterial partners likely occurred; this alters the implicit assumption of gamma-proteobacteria monophyly. Thus, any thorough reconstruction of bacterial evolution must not only choose a suitable set of molecular markers but also strive to reduce potential bias in the selection of species.     

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.     

青弋江鱼类分类群和功能群的α和β多样性纵向梯度格局

确定溪流鱼类多样性的时空分布格局可为鱼类多样性保护与管理提供科学基础。尽管溪流鱼类分类群多样性的纵向梯度格局已有大量报道, 但以鱼类生物学特征为基础的功能多样性研究较少。本文基于2009-2010年4个季度对青弋江1-5级溪流共15个样点的调查数据, 利用形态特征数据和食性构建了鱼类复合功能群, 研究了不同级别溪流间鱼类分类群和功能群组成及多样性的异同, 着重探讨了鱼类分类群和功能群的α和β多样性沿溪流纵向梯度的变化规律。采集到的56种鱼类可分为4个营养功能群和5个运动功能群, 共计14个“营养-运动”复合功能群。双因素交互相似性分析结果显示, 鱼类分类群和功能群组成都随河流级别显著变化, 但季节动态不显著; 双因素方差分析后发现, 鱼类分类群和功能群α、β多样性都随河流级别显著变化, 但受季节影响不显著。经回归分析, 分类群和功能群α多样性与河流级别大小呈显著的线性正相关, 但最大分类群α多样性出现于4级河流, 最大功能群α多样性在4级和5级河流间一致; 分类群和功能群β多样性与河流级别大小呈显著的二项式关系, 呈U型分布。分类群β多样性的空间变化主要取决于物种周转, 而功能群β多样性主要由嵌套所驱动。本研究表明, 沿着“上游-下游”的纵向梯度, 河流鱼类的α和β多样性的空间变化规律不同, 分类群和功能群α多样性的空间格局基本一致, 但分类群(主要是物种周转)和功能群β多样性(主要是功能嵌套)的空间变化过程的驱动机制不同。     

Glycogen synthase kinase‐3β, or a link between amyloid and tau pathology?

Phosphorylation is the most common post-translational modification of cellular proteins, essential for most physiological functions. Deregulation of phosphorylation has been invoked in disease mechanisms, and the case of Alzheimer's disease (AD) is no exception: both in the amyloid pathology and in the tauopathy are kinases deeply implicated. The glycogen synthase kinase-3 (GSK-3) isozymes participate in diverse cellular processes and important signalling pathways and have been implicitly linked to diverse medical problems, i.e. from diabetes and cancer to mood disorders and schizophrenia, and in the neurodegeneration of AD. Here, we review specific aspects of GSK-3 isozymes in the framework of recent data that we obtained in novel transgenic mouse models that robustly recapitulate the pathology and mechanistical problems of AD.