A Pivotal Role for β-Aminoisobutyric Acid and Oxidative Stress in Dihydropyrimidine Dehydrogenase Deficiency?

Dihydropyrimidine dehydrogenase (DPD) constitutes the first step of the pyrimidine degradation pathway in which the pyrimidine bases uracil and thymine are catabolised to β-alanine and β-aminoisobutyric acid (β-AIB), respectively. The mean concentration of β-AIB was approximately 5- to 8-fold lower in urine of patients with a DPD deficiency, when compared to age-matched controls. Comparable levels of 8-hydroxydeoxyguanosine (8-OHdG) were present in urine from controls and DPD patients at the age <2 year. In contrast, slightly elevated levels of 8-OHdG were detected in urine from DPD patients with an age >2 year, suggesting the presence of increased oxidative stress.     

Extracellular DNA: A Relevant Plant Damage-Associated Molecular Pattern (DAMP) for Crop Protection Against Pests—A Review

Journal of Plant Growth Regulation - The immune response against pathogens, both in plants and animals, relies on a complex recognition system of danger signs. This system is based on the...     

Evidence for Hysteretic Substrate Channeling in the Proline Dehydrogenase and Δ1-Pyrroline-5-carboxylate Dehydrogenase Coupled Reaction of Proline Utilization A (PutA)

PutA (proline utilization A) is a large bifunctional flavoenzyme with proline dehydrogenase (PRODH) and Δ¹-pyrroline-5-carboxylate dehydrogenase (P5CDH) domains that catalyze the oxidation of l-proline to l-glutamate in two successive reactions. In the PRODH active site, proline undergoes a two-electron oxidation to Δ¹-pyrroline-5-carboxlylate, and the FAD cofactor is reduced. In the P5CDH active site, l-glutamate-γ-semialdehyde (the hydrolyzed form of Δ¹-pyrroline-5-carboxylate) undergoes a two-electron oxidation in which a hydride is transferred to NAD⁺-producing NADH and glutamate. Here we report the first kinetic model for the overall PRODH-P5CDH reaction of a PutA enzyme. Global analysis of steady-state and transient kinetic data for the PRODH, P5CDH, and coupled PRODH-P5CDH reactions was used to test various models describing the conversion of proline to glutamate by Escherichia coli PutA. The coupled PRODH-P5CDH activity of PutA is best described by a mechanism in which the intermediate is not released into the bulk medium, i.e., substrate channeling. Unexpectedly, single-turnover kinetic experiments of the coupled PRODH-P5CDH reaction revealed that the rate of NADH formation is 20-fold slower than the steady-state turnover number for the overall reaction, implying that catalytic cycling speeds up throughput. We show that the limiting rate constant observed for NADH formation in the first turnover increases by almost 40-fold after multiple turnovers, achieving half of the steady-state value after 15 turnovers. These results suggest that EcPutA achieves an activated channeling state during the approach to steady state and is thus a new example of a hysteretic enzyme. Potential underlying causes of activation of channeling are discussed.     

Zoo Playgrounds: A Source of Enrichment or Stress for a Group of Nearby Cockatoos? A Case Study

There is increasing evidence that in some circumstances, zoo visitors may be aversive stimuli to nonhuman animals housed in zoos. Yet, most previous research has focused on primates with little attention given to numerous other species who are housed in zoos. The focus animal of this project was the cockatoo, a species who has received minimal attention in zoo-based research. Furthermore, although the influence of the zoo setting has become increasingly important in visitor effect studies, this is the 1st study to quantify the effect of activity at a children's playground on zoo animals. There was an investigation on the effect of a zoo playground on the behavior of citron-crested and Moluccan cockatoos (Cacatua sulphurea citrinocristata and Cacatua moluccensis), as well as the effect of children standing in front of the birds' aviaries. The results showed that in some circumstances, the Moluccan cockatoos retreated from visitors, while the citron-crested cockatoos did not retreat from visitors and became more social in the presence of visitors. These findings highlight the importance of careful selection of species and individual animals to be housed near zoo playgrounds.     

A method for improving Centre for Environmental Studies (CML) characterisation factors for metal (eco)toxicity — the case of zinc gutters and downpipes

Background, aim and scope  

The environmental impact of building products made from heavy metals has been a topic of discussion for some years. This was fuelled by results of life cycle assessments (LCAs), where the emission of heavy metals strongly effected the results. An issue was that the characterisation factors of the Centre for Environmental Studies (CML) 2000 life cycle impact assessment (LCIA) methodology put too much emphasis on the impact of metal emissions. We adjusted Zn characterisation factors according to the most recent insights in the ecotoxicity of zinc and applied them in an LCA using zinc gutters and downpipes as an example.     

Open-Loop Audio-Visual Stimulation (AVS): A Useful Tool for Management of Insomnia?

Audio Visual Stimulation (AVS), a form of neurofeedback, is a non-pharmacological intervention that has been used for both performance enhancement and symptom management. We review the history of AVS, its two sub-types (close- and open-loop), and discuss its clinical implications. We also describe a promising new application of AVS to improve sleep, and potentially decrease pain. AVS research can be traced back to the late 1800s. AVS’s efficacy has been demonstrated for both performance enhancement and symptom management. Although AVS is commonly used in clinical settings, there is limited literature evaluating clinical outcomes and mechanisms of action. One of the challenges to AVS research is the lack of standardized terms, which makes systematic review and literature consolidation difficult. Future studies using AVS as an intervention should; (1) use operational definitions that are consistent with the existing literature, such as AVS, Audio-visual Entrainment, or Light and Sound Stimulation, (2) provide a clear rationale for the chosen training frequency modality, (3) use a randomized controlled design, and (4) follow the Consolidated Standards of Reporting Trials and/or related guidelines when disseminating results.     

Peptide nucleic acid (PNA): A model structure for the primordial genetic material?

It is proposed that the primordial genetic material could have been peptide nucleic aicds,i.e., DNA analogues having a peptide backbone. PNA momomers based on the amino acid, , -diaminobutyric acid or ornithine are suggested as compounds that could have been formed in the prebiotic soup. Finally, the possibility of a PNA/RNA world is presented, in which PNA constitutes the stable genetic material, while RNA which may be polymerized using the PNA as template accounts for enzymatic activities including PNA replication.     

Does Invasion Success Reflect Superior Cognitive Ability? A Case Study of Two Congeneric Lizard Species (Lampropholis,Scincidae)

A species'' intelligence may reliably predict its invasive potential. If this is true, then we might expect invasive species to be better at learning novel tasks than non-invasive congeners. To test this hypothesis, we exposed two sympatric species of Australian scincid lizards, Lampropholis delicata (invasive) and L. guichenoti (non-invasive) to standardized maze-learning tasks. Both species rapidly decreased the time they needed to find a food reward, but latencies were always higher for L. delicata than L. guichenoti. More detailed analysis showed that neither species actually learned the position of the food reward; they were as likely to turn the wrong way at the end of the study as at the beginning. Instead, their times decreased because they spent less time immobile in later trials; and L. guichenoti arrived at the reward sooner because they exhibited “freezing” (immobility) less than L. delicata. Hence, our data confirm that the species differ in their performance in this standardized test, but neither the decreasing time to find the reward, nor the interspecific disparity in those times, are reflective of cognitive abilities. Behavioural differences may well explain why one species is invasive and one is not, but those differences do not necessarily involve cognitive ability.     

Programmed cell death protein 4 (pdcd4): A novel target for antineoplastic therapy?

Pdcd4 is a novel gene first identified as a differentially expressed protein during apoptosis. In the meantime not only the impact of Pdcd4 in programmed cell death but also an implication in transformation suppression by inhibition of protein translation is discussed. These features implicate a potential value of Pdcd4 as a molecular target in cancer therapy. This review summarizes the current knowledge about expression, structure and function of Pdcd4.     

Ecological genetics of the Bromus tectorum (Poaceae)-Ustilago bullata (Ustilaginaceae) pathosystem: A role for frequency-dependent selection?

? Premise of the study: Evolutionary processes that maintain genetic diversity in plants are likely to include selection imposed by pathogens. Negative frequency-dependent selection is a mechanism for maintenance of resistance polymorphism in plant-pathogen interactions. We explored whether such selection operates in the Bromus tectorum-Ustilago bullata pathosystem. Gene-for-gene relationships between resistance and avirulence loci have been demonstrated for this pathosystem. ? Methods: We used molecular markers and cross-inoculation trials to learn whether the SSR genotypes of the host exhibited resistance to co-occurring pathogen races, whether host genotypes within a population had equal disease probability, and whether a common resistance locus and its corresponding avirulence locus exhibited predicted allele frequency changes during an epidemic. ? Key results: Five of six putative resistance loci that conferred resistance to co-occurring pathogen races occurred in common host SSR genotypes. Some common genotypes within populations were more likely to be diseased than others, and genotype frequencies sometimes changed across years in patterns consistent with frequency-dependent selection. Observed changes in frequency of resistance and virulence alleles during an epidemic provided further support, but evidence was inconclusive. ? Conclusions: Frequency-dependent selection may operate at endemic disease levels in this pathosystem, but is difficult to detect because many susceptible plants escape infection. Most pathogen isolates were virulent on most host genotypes, minimizing the apparent importance of frequency-dependent selection even during epidemics.     

The Next Direction for Primatology? A Commentary on Setchell (2013)

Primatologists were asked to submit their “ideas for the Big Questions that remain unanswered in Primatology” and, from this, Setchell (2013) grouped the 170 responses into 11 broad themes. This exercise created a valuable tool that can help primatologists identify both the “missing gaps” and current broad overarching themes within our field. In this commentary, we offer our perspective on the methodology and results of this survey. By considering the 11 themes more holistically, primatologists can more easily address a broader range of questions, methods, and outcomes for their research endeavors and conservation efforts. Ultimately, the results of this survey should enable researchers and policymakers to recognize gaps in our knowledge and plan how to proceed with new research initiatives and funding applications. The identified themes should also provide a reference point for new avenues of investigation, and we are hopeful that this list can encourage interdisciplinary research if primatologists consider the overlaps across the themes. However, as Setchell noted, as some key areas of research were omitted from the list, the 11 themes should be used as a tool for guidance in expanding our research horizons and not as a template for the minimum of what is required.     

New karyotype for Mesomys stimulax (Rodentia,Echimyidae) from the Brazilian Amazon: A case for species complex?

Mesomys Wagner, 1845 (Rodentia, Echimyidae, Eumysopinae) currently has four recognized species, three of which occur in Brazil: Mesomys hispidus (probably a species complex), M. occultus, and M. stimulax. Mesomys leniceps is found in montane forests of northern Peru. Mesomys stimulax, the focus of the present study, has a distribution that is restricted to the central and eastern Amazonia south of the Amazon River, extending from the left bank of the Tapajós River to the right bank of the Tocantins River, and south to the southeast portion of Pará State. The genus presents karyotypes with diploid number 2n = 60 and Fundamental Number (FN) = 116 for M. hispidus and M. stimulax, and 2n = 42, FN = 54 for M. occultus. We studied the karyotype of a female specimen of M. stimulax collected from the Tapirapé‐Aquiri National Forest, Marabá, Pará, Brazil, in the Xingu/Tocantins interfluvium. The obtained karyotype (2n = 60 and FN = 110) differs from that described in the literature for both M. stimulax and M. hispidus by exhibiting more biarmed chromosomes, probably due to pericentric inversions and/or centromeric repositioning, and exhibiting differences in the amount and distribution of constitutive heterochromatin (CH). These results suggest that, similar to what has already been proposed for M. hispidus, M. stimulax may represent a species complex and/or cryptic species. The mechanisms of chromosomal diversification in Mesomys and the biogeographic implications are discussed reinforcing the need for broad systematic review for Mesomys.     

Protective Effects of Hesperidin Against Amyloid-β (Aβ) Induced Neurotoxicity Through the Voltage Dependent Anion Channel 1 (VDAC1)-Mediated Mitochondrial Apoptotic Pathway in PC12 Cells

Amyloid-β (Aβ) is known to exert cytotoxic effects by inducing mitochondrial dysfunction. Additionally, the mitochondrial voltage-dependent anion channel 1 (VDAC1), which is involved in the release of apoptotic proteins with possible relevance in Alzheimer’s disease (AD) neuropathology, plays an important role in maintaining mitochondrial function and integrity. However, the application of therapeutic drugs, especially natural products in (AD) therapy via VDAC1-regulated mitochondrial apoptotic pathway has not aroused extensive attention. In the present study, we investigated neuroprotective effects of hesperidin, a bioactive flavonoid compound, on Aβ_25–35-induced neurotoxicity in PC12 cells and also examined the potential cellular signalling mechanism. Our results showed that treatment with hesperidin significantly inhibited Aβ_25–35-induced apoptosis by reversing Aβ-induced mitochondrial dysfunction, including the mitochondrial permeability transition pore opening, intracellular free calcium increase and reactive oxygen species production. Further study indicated that hesperidin can increase the level of VDAC1 phosphorylation through enhancing the activity of the glycogen synthasekinase-3β and decrease the level of hexokinaseI in mitochondrial, resulting in mitochondrial release of cytochrome c. Furthermore, hesperidin inhibited mitochondria-dependent downstream caspase-mediated apoptotic pathway, such as that involving caspase-9 and caspase-3. These results demonstrate that hesperidin can protect Aβ-induced neurotoxicity via VDAC1-regulated mitochondrial apoptotic pathway, and they raise the possibility that hesperidin could be developed into a clinically valuable treatment for AD and other neuronal degenerative diseases associated with mitochondrial dysfunction.     

Back to Gondwanaland: can ancient vicariance explain (some) Indian Ocean disjunct plant distributions?

Oceans, or other wide expanses of inhospitable environment, interrupt present day distributions of many plant groups. Using molecular dating techniques, generally incorporating fossil evidence, we can estimate when such distributions originated. Numerous dating analyses have recently precipitated a paradigm shift in the general explanations for the phenomenon, away from older geological causes, such as continental drift, in favour of more recent, long-distance dispersal (LDD). For example, the ‘Gondwanan vicariance’ scenario has been dismissed in various studies of Indian Ocean disjunct distributions. We used the gentian tribe Exaceae to reassess this scenario using molecular dating with minimum (fossil), maximum (geological), secondary (from wider analyses) and hypothesis-driven age constraints. Our results indicate that ancient vicariance cannot be ruled out as an explanation for the early origins of Exaceae across Africa, Madagascar and the Indian subcontinent unless a strong assumption is made about the maximum age of Gentianales. However, both the Gondwanan scenario and the available evidence suggest that there were also several, more recent, intercontinental dispersals during the diversification of the group.