Immunotherapy for Alzheimer's disease: will vaccination work?

Active or passive immunization against the beta-amyloid peptide (Abeta) has been proposed as a method for preventing and/or treating Alzheimer's disease (AD). In addition to lowering brain Abeta and amyloid burden in transgenic mouse models of AD, a beneficial effect of immunization on previously characterized memory impairment(s) has also been reported in these mice. Whether these preclinical data will predict efficacy in AD patients remains to be seen. A clinical trial of active immunization (vaccination) was halted, owing to a serious adverse event (meningoencephalitis), raising questions about the safety of this approach. Two recent reports suggest that immunotherapy-based approaches to treating and preventing AD will require careful antigen and antibody selection, to maximize efficacy and minimize serious adverse events. However, given the potential efficacy of this approach, we believe that immunotherapy for AD should not be prematurely abandoned.     

Genome-wide association mapping of quantitative resistance to sudden death syndrome in soybean

Background

Sudden death syndrome (SDS) is a serious threat to soybean production that can be managed with host plant resistance. To dissect the genetic architecture of quantitative resistance to the disease in soybean, two independent association panels of elite soybean cultivars, consisting of 392 and 300 unique accessions, respectively, were evaluated for SDS resistance in multiple environments and years. The two association panels were genotyped with 52,041 and 5,361 single nucleotide polymorphisms (SNPs), respectively. Genome-wide association mapping was carried out using a mixed linear model that accounted for population structure and cryptic relatedness.

Result

A total of 20 loci underlying SDS resistance were identified in the two independent studies, including 7 loci localized in previously mapped QTL intervals and 13 novel loci. One strong peak of association on chromosome 18, associated with all disease assessment criteria across the two panels, spanned a physical region of 1.2 Mb around a previously cloned SDS resistance gene (GmRLK18-1) in locus Rfs2. An additional variant independently associated with SDS resistance was also found in this genomic region. Other peaks were within, or close to, sequences annotated as homologous to genes previously shown to be involved in plant disease resistance. The identified loci explained an average of 54.5% of the phenotypic variance measured by different disease assessment criteria.

Conclusions

This study identified multiple novel loci and refined the map locations of known loci related to SDS resistance. These insights into the genetic basis of SDS resistance can now be used to further enhance durable resistance to SDS in soybean. Additionally, the associations identified here provide a basis for further efforts to pinpoint causal variants and to clarify how the implicated genes affect SDS resistance in soybean.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-809) contains supplementary material, which is available to authorized users.     

低温对植物叶片中超氧物歧化酶、过氧化氢酶和过氧化氢水平的影响

番茄和鸡蛋果叶片中可提取的SOD活性不受低温的影响。在电泳谱带上SOD主同工酶带被氰化物而不被低温抑制,次同工酶带在低温下不稳定,且活性很低,它的变化不影响总的SOD活性。一些冷敏感植物叶片中CAT活性被低温抑制,而H_2O_3水平在低温下稳定或有增加,这可能使毒性更强的羟基离子(OH·)易于形成。     

Involvement of a Caspase-3-Like Cysteine Protease in 1-Methyl-4-Phenylpyridinium-Mediated Apoptosis of Cultured Cerebellar Granule Neurons

Abstract: Exposure of various neuronal cells or cell lines to high concentrations of 1-methyl-4-phenylpyridinium (MPP⁺), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), results in cell death. Recently, it has been reported that low concentrations of MPP⁺ induce apoptosis in susceptible neurons. We have further characterized MPP⁺-mediated toxicity of cultured cerebellar granule neurons (CGNs) and found that exposure of CGNs to relatively low concentrations of MPP⁺ results in apoptosis, whereas higher concentrations result in necrosis. Cotreatment of CGNs with MPP⁺ and the tetrapeptide inhibitor of caspase-3-like proteases, acetyl-DEVD-CHO, markedly attenuates apoptotic but not necrotic death of these neurons. The more specific inhibitor of caspase-1-like proteases, acetyl-YVAD-CHO, however, was ineffective against MPP⁺ neurotoxicity. Moreover, cytoplasmic extracts prepared from MPP⁺-treated CGNs contain markedly increased protease activity that cleaves the caspase-3 substrate acetyl-DEVD- p -nitroaniline. Finally, the cytoplasmic concentration of the apoptogenic protein cytochrome c was increased in a time-dependent fashion in MPP⁺-treated CGNs before the onset of apoptosis. Our data confirm that the neurotoxicity of MPP⁺ is due to both necrosis and apoptosis and suggest that the latter is mediated by activation of a caspase-3-like protease.     

Intragenic duplication and divergence in the spectrin superfamily of proteins

Many structural, signaling, and adhesion molecules contain tandemly repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin superfamily of F-actin-crosslinking proteins contains an array of triple alpha-helical motifs (spectrin repeats). We present here the complete sequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H). The sequence of beta H supports the origin of alpha- and beta-spectrins from a common ancestor, and we present a novel model for the origin of the spectrins from a homodimeric actin-crosslinking precursor. The pattern of similarity between the spectrin repeat units indicates that they have evolved by a series of nested, nonuniform duplications. Furthermore, the spectrins and dystrophins clearly have common ancestry, yet the repeat unit is of a different length in each family. Together, these observations suggest a dynamic period of increase in repeat number accompanied by homogenization within each array by concerted evolution. However, today, there is greater similarity of homologous repeats between species than there is across repeats within species, suggesting that concerted evolution ceased some time before the arthropod/vertebrate split. We propose a two-phase model for the evolution of the spectrin repeat arrays in which an initial phase of concerted evolution is subsequently retarded as each new protein becomes constrained to a specific length and the repeats diverge at the DNA level. This evolutionary model has general applicability to the origins of the many other proteins that have tandemly repeated motifs.      

Induction of Salivary Proteins Modifies Measures of Both Orosensory and Postingestive Feedback during Exposure to a Tannic Acid Diet

There are hundreds of proteins in saliva. Although it has long been hypothesized that these proteins modulate taste by interacting with taste receptors or taste stimuli, the functional impact of these proteins on feeding remains relatively unexplored. We have developed a new technique for saliva collection that does not interfere with daily behavioral testing and allows us to explore the relationship between feeding behavior and salivary protein expression. First, we monitored the alterations in salivary protein expression while simultaneously monitoring the animals'' feeding behavior and meal patterns on a custom control diet or on the same diet mixed with 3% tannic acid. We demonstrated that six protein bands increased in density with dietary tannic acid exposure. Several of these bands were significantly correlated with behaviors thought to represent both orosensory and postingestive signaling. In a follow-up experiment, unconditioned licking to 0.01–3% tannic acid solutions was measured during a brief-access taste test before and after exposure to the tannic acid diet. In this experiment, rats with salivary proteins upregulated found the tannin solution less aversive (i.e., licked more) than those in the control condition. These data suggest a role for salivary proteins in mediating changes in both orosensory and postingestive feedback.     

Developmental experiences and the oxytocin receptor system

The long-term effects of developmental experiences on social behavior, and the neuropeptide systems such as oxytocin which subserve the behavior, are still little understood. In this article, we review various types of early experience, including normal development, knockout models, pharmacological exposures, and early social experiences. We consider the processes by which experience can affect oxytocin receptor binding, and what is known about the directionality of experience effects on oxytocin receptors. Finally, we attempt to synthesize the literature into a predictive model as to the direction of early experience effects on oxytocin receptor binding potential, and whether these changes have functional significance. These predictions are relevant to current human health practice, given proposals to use chronic intranasal oxytocin to treat developmental disorders including autism and schizophrenia. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.