News and ISN

• Journal of Neurochemistry announces the move to Online Only publication as of January 2014 (issue 128‐1), with the recent release of the new App for iPad. Versions for iPhone and Android will follow soon.
• The App can be downloaded from https://itunes.apple.com/us/app/journal-neurochemistry-for/id655612235

• Special Issues have been published on:
  • 150 Years of Friedreich Ataxia Research
  • Virtual Issue on Molecular Imaging
  • Mini article series featuring Model systems for Neurodegenerative Diseases (yeast, drosophila, zebrafish) with an accompanying Editorial Highlight
• In addition to the Society for Neuroscience (SfN) and the Federation of European Neuroscience Societies (FENS), the ISN has become a member of the global advocacy initiative recently launched by International Brain Research Organization (IBRO) , with a first panel discussion and poster presentation held at SfN in San Diego this November.
• The ISN council has decided to launch two new exciting ventures:
  • A joint ISN‐JNeurochem Flagship School envisioned to be a recurring school that focuses on high impact research, to be launched in celebration of ISN's 50th anniversary celebration
  • A junior investigator committee to provide a voice for our junior researchers in society and biennial meeting issues.

     

News & ISN

• The 2014 Nobel Prize in Chemistry has been awarded to Stefan W. Hell, Eric Betzig and William E. Moerner for the development of a superresolution imaging technique, STED (stimulated emission depletion). The technique opens up new possibilities in imaging nanostructures, and has been featured in a review article in the Journal of Neurochemistry, entitled “STED microscopy of living cells ‐ new frontiers in membrane and neurobiology” by Christian Eggeling, Kathrin I. Willig and Francisco J. Barrantes: http://onlinelibrary.wiley.com/doi/10.1111/jnc.12243/abstract
• A Virtual Issue on Neuroinflammation in Nervous System Disorders: Diversity in Insults and Outcomes, edited by Deputy Chief Editor Tammy Kielian ( http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1471-4159/homepage/virtual_issues.htm#neuroinflammation ), will shortly be followed by a Special Issue on neuroinflammation.
• The Journal of Neurochemistry now has a new page for special Article Series and/or reviews solicited at ISN meetings such as the 5th Special ISN Conference 2012 .
• The Committee for Aid and Education in Neurochemistry ( CAEN ) provides funds for travelling to another laboratory to develop new technical or conceptual expertise, purchasing research supplies, attending workshops/training courses/satellite meetings or organizing a workshop/small school. The ISN‐CAEN application deadlines for this year are on April 30, August 31 and December 31.

     

Virus diseases of lupins

• I. INTRODUCTION
• II. APHID-TRANSMITTED VIRUSES

• (a) Potyvirus group

• (i) Bean yellow mosaic virus
• (ii) Clover yellow vein virus
• (iii) Bean common mosaic virus
• (iv) Peanut mottle virus
• (v) Bidens mottle virus

• (b) Cucumovirus group

• (i) Cucumber mosaic virus
• (ii) Peanut stunt virus

• (c) Alfalfa mosaic virus
• (d) Fabavirus group: broad bean wilt virus
• (e) Pea enation mosaic virus
• (f) Luteovirus group: soybean dwarf virus
• (g) Rhabdovirus group: lettuce necrotic yellows virus

• III. THRIPS-TRANSMITTED VIRUSES
• Tomato spotted wilt virus

• IV. NEMATODE-TRANSMITTED VIRUSES

• (a) Tobravirus group: pea early browning virus
• (b) Nepovirus group: tomato black ring virus

• V. VIRUS-LIKE DISEASES

• (a) Lupin leaf curl ‘virus’
• (b) ‘Lupin witches’ broom disease

• VI. CONTROL VII. CONCLUSIONS
• VII. CONCLUSIONS

     

Subcellular distribution of aromatic amino acid transaminases in rat brain

Abstract— The subcellular distributions of tyrosine transaminase, DOPA transaminase, tryptophan transaminase and 5-hydroxytryptophan (5-HTP) transaminase were studied in rat brain.

• 1 For all of these transaminases 60-81 per cent of the total activities were found in the crude mitochondrial fraction. Tyrosine transaminase was the most active enzyme.

• 2 Tyrosine transaminase and DOPA transaminase had very similar distributions in all fractions, but the distribution of tryptophan transaminase and 5-HTP transaminase differed in the microsomal (Mic) and synaptic vesicle (M₂) fractions. Only 5-HTP transaminase was highly concentrated in the M₂ fraction.

• 3 DOPA transaminase was inhibited by dopamine and 5-HT, but these compounds had no effect on 5-HTP transaminase. Both enzymes were completely inhibited by m-hydroxybenzoyloxyamine.

     

On the Evolutionary Relationship in the Family Brassicaceae

• 1 The study gives the evaluation of the dissepimentum and gynophore for the establishment of the evolutionary relationship in the family Brassicaceae.

• 2 The genus Macropodium R. Br. represents an organizational degree. Different, divergently going younger evolutionary lines, developed from evolutionary lines leading to both present species.

     

THE COMPARTMENTATION OF GLUTAMATE AND ITS METABOLITES IN FRACTIONS OF NEURON CELL BODIES AND NEUROPIL; STUDIED BY INTRAVENTRICULAR INJECTION OF [U-14C]GLUTAMATE

Abstract—

• 1 The in vivo metabolism of glutamate in rat neuron cell bodies and neuropil was studied after intraventricular injection of (U-¹⁴C)glutamic acid followed by separation of the tissue into neuronal and neuropil fractions.

• 2 The losses of amino acid and of radioactivity during the fractionation were equivalent. Recoveries were: glutamate, 32; glutamine, 15; aspartate, 25; GABA, 41; alanine, 30 per cent. In the washed cell fractions glutamine was 45 per cent and alanine 132 per cent higher in the neuronal fraction, glutamate was 62, GABA 77 and aspartate 95 per cent of neuropil levels. This contrasted with results obtained previously for in vitro incorporation. Calculation from these results indicated that 28 per cent of the original cell suspension was neuronal, 72 per cent neuropil. In the final cell preparations, 29 per cent of the neuron cell bodies and 26 per cent of the neuropil were recovered.

• 3 Specific activity of glutamate in the neuronal fraction 15 min after injection was higher than in the original suspension, but had declined to 30 per cent of its initial value by 2 h. In the neuropil, specific activity of glutamate was below that of the cell suspension at 15 min, but at later times rose above it by up to 40 per cent.

• 4 Radioactivity was detected in aspartate and glutamine 15 min after injection and GABA by 60 min after injection. In the original cell suspension the specific activity of glutamine was higher than that of glutamate at all times (the Waelsch effect) but aspartate and GABA were lower than glutamate.

• 5 In the neuronal fraction the specific activity of glutamine was below that of glutamate at all times, indicating a precursor-product relationship. In the neuropil fraction, glutamine specific activity remained above glutamate for the first hour.

• 6 These results are discussed in relation to the interpretation of the Waelsch effect in terms of metabolic compartmentation.

     

TOXIC EFFECTS OF OXYGEN ON CEREBRAL METABOLISM

Abstract— The effect of 100% O₂ at one atmosphere on carbohydrate metabolism in cell-free homogenates of rat brain was studied under different experimental conditions. The principal findings were the following:

• 1 Compared to 10% O₂-90% N₂, oxygen at one atmosphere inhibited metabolism of α-oxoglutarate and depressed the net synthesis of ATP. With glucose as substrate, accumulation of ATP was also markedly inhibited but substrate utilization was only slightly affected.

• 2 Glycolysis in brain was relatively resistant to oxygen toxicity, except in the presence of added Cu²⁺.

• 3 With α-oxoglutarate as the substrate, inhibition of the formation of ATP occurred earlier than inhibition of substrate utilization, indicating the particular sensitivity of oxidative phosphorylation to inactivation by oxygen in vitro.

• 4 Cu²⁺ and Fe²⁺ accentuated oxygen toxicity but appeared to act by different mechanisms. Co²⁺ exerted a protective effect.

• 5 The sulphydryl compounds, dithiothreitol and reduced glutathione, strongly diminished the toxic effect of oxygen.

     

Global Proteome and Ubiquitinome Changes in the Soluble and Insoluble Fractions of Q175 Huntington Mice Brains

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Highlights

• •Quantitative changes in global proteome and ubiquitinome in Huntington's disease.
• •Differential ubiquitination of wild-type and mutant Htt in mice brain.
• •Enriched pathways include vesicle transport and mRNA processing.
• •Correlation between protein and diGly site fold changes.

     

EFFECT OF THYROID HORMONE ON THE BIOCHEMICAL MATURATION OF RAT BRAIN: CONVERSION OF GLUCOSE-CARBON INTO AMINO ACIDS

• 1 The rapid and extensive conversion of glucose-carbon into amino acids is an index of the final coordination of the mechanisms underlying energy metabolism in the adult brain. This phenomenon develops in the rat during a short period extending from 10 to about 19 days after birth. The underlying factors have been analysed.

• 2 The development of the pattern of distribution of glucose-carbon characteristic of the adult brain was markedly influenced by the thyroid state of the animals. The age-curve for the conversion of glucose-carbon into brain amino acids was displaced to the left after treatment with thyroid hormone (T₃) in infancy thus indicating an accelerated maturation. Conversely, neonatal thyroidectomy resulted in a significant retardation in the conversion of glucose-carbon into amino acids.

• 3 The specific radioactivity of glutamate increased five-fold in the brain of normal rats from the 10th to the 19th day of age. The values (as a percentage of those for littermate controls) were 220 in the case of the 10 day-old thyroid treated rats and about 30 for the 19 day-old thyroid deficient animals. At the age of 10 days neither treatment affected the concentration of glutamate which was also only slightly less than the control values in the brain of 19 day-old thyroid deficient animals (–17 per cent).

• 4 Specific pool(s) of glutamate associated with the formation of GABA can be demonstrated in the brain of 19 day-old rats after administration of [U-¹⁴C]glucose as a result of anoxia post mortem. These pools did not develop in the brain of 10 day-old animals. Neonatal thyroidectomy retarded the development of these glutamate pools.

• 5 Evidence is summarized which indicates that the development of the rapid conversion of glucose-carbon into amino acids reflects the enlargement, during maturation, of the metabolic compartments which are associated with neuronal processes.

     

Island biogeography and landscape ecology of mammals inhabiting fragmented, temperate rain forests

• 1 We expanded the island biogeography paradigm to test whether mammalian communities of the heavily fragmented temperate rain forests of the Olympic Peninsula were influenced by local environmental conditions, biogeographic factors (fragment area and isolation) and characteristics of the surrounding landscape.
  • 2 We used live‐trapping, sign surveys and infra‐red triggered cameras to compare distributions of non‐volant mammals among fragments and between fragments and other principal landscape components (continuous old‐growth, riparian corridors, second‐growth forest and clearcuts).
    • 3 Of the 24 species of non‐volant mammals detected during our studies, 18 occurred in at least one fragment.
      • 4 Species richness of old‐growth mammals was not significantly correlated with fragment area or isolation, per se, but was significantly and positively correlated with the amount of old‐growth fragments and old second‐growth (41–159 years) in the surrounding landscape (r² = 0.95, P < 0.005).
        • 5 Distributions of three old‐growth dependent species [shrew‐mole (Neurotrichus gibbsii), Douglas squirrel (Tamiasciurus douglasii) and Trowbridge shew (Sorex trowbridgii)] were significantly associated with local environmental conditions within the fragment, with geographical isolation from continuous old‐growth and riparian corridors, and with the amount of old‐growth and old second growth in the adjacent matrix.

     

CHANGES IN POLYSOMES OF THE DEVELOPING RAT BRAIN

Abstract— Rat brain polysomes were prepared from a deoxycholate-treated postmito-chondrial supernatant in the presence of 2% bentonite and 1 mg/ml of yeast RNA to prevent partial degradation during preparation.

• 1 The polysomal preparations had an absorption maximum at 260 mμ and an absorption minimum at 235 mμ. The ratio of absorption maximum to minimum and the RNA to protein ratio were 1·58 and 1·06 respectively in 6-day-old rat brain polysomes. The sedimentation patterns showed six distinct peaks with sedimentation coefficients of 235S, 185S, 173S, 135S, 100S and 80S, indicating that these preparations have the characteristics of pure heavy polysomes.

• 2 The rate of [¹⁴C]phenylalanine incorporation into brain polysomal protein was maximal at approximately 10 days of age and decreased thereafter. A similar progressive reduction with increasing age was found in the stimulation of phenylalanine incorporation by the addition of 60 μg/tube of polyuridylic acid. However, the incorporation of phenylalanine into young rat brain polysomes was usually greater even with the addition of polyuridylic acid than in the older animals.

• 3 The comparative studies on sucrose density gradient centrifugation of polysomes between young and adult rat brains showed a considerable decrease of heavy polysomes in the older animals.

• 4 The effect of various factors on the stability of brain polysomes from both ages has been studied. The rates of RNA, protein and acid-soluble phosphorus release from polysomes of the adult rat brains were usually greater in the presence of high salt concentration, ethylenediaminetetra-acetic acid and urea than those from the corresponding preparations of younger animals. On the basis of evidence obtained from the above results it suggested that the adult brain polysomes were more unstable than those of younger animals.

• 5 The amount of polysomal RNA linearly increased up to the first 20 days after birth and then levelled off. The ratio of G + C/A + U of polysomal RNA was less in the young rat brains, falling to 1·30 as compared to 1·50 in older animals. The differences were statistically significant at less than a 1% level of confidence.

• 6 Polysomal preparations also contained RNase, phosphomonoesterase, phospho-diesterase and 5′-nucleotidase activities which cannot be washed off. The specific activities of these enzymes were generally higher in young rat brains than those in the adult.

     

Reproductive ecology of the carnivorous plant Pinguicula moranensis (Lentibulariaceae)

• The interaction of plants with pollinators can be a determinant of their reproductive fitness. However, information about the pollination biology of carnivorous plants is scarce. To increase knowledge of reproductive ecology of carnivorous plants we focused on Pinguicula moranensis. Specifically, based on the presence of large, zygomorphic and spurred flowers, we predicted higher reproductive fitness in cross‐pollinated than in self‐pollinated flowers.
• Within a plot of 51 m² we characterised the reproductive phenology, including flower lifespan and stigmatic receptivity. We identified pollinators and their movement patterns within the plot. Breeding system was experimentally evaluated using hand‐pollination (i.e. autonomous, self‐ and cross‐pollination).
• Flowers of P. moranensis were visited by long‐tongued pollinators, mainly members of the Lepidoptera. Hand‐pollination experiments confirmed our prediction and suggest that flower traits might favour cross‐pollination.
• We mainly discuss the implications of the patchy distribution of plants and behaviour of pollinators on gene movement in this plant species, as pollination between genetically related individuals could be occurring.

     

Physically modeling operative temperatures and evaporation rates in amphibians

• (1)We designed a physical model that simulates the thermal and evaporative properties of live Western toads (Bufo boreas).
• (2)In controlled tests, the model tracked the body temperature of live toads with an average error of 0.3±0.03 °C (test range=4–30 °C).
• (3)It estimated the evaporative water loss of live toads with an average error of 0.35–0.65  g/h, or about 14% (test range=0.7–9 g/h).
• (4)Data collected with this physical model should provide an effective way for biologists to better understand habitat selection in toads and other amphibians

     

Dormancy cycles in buried seeds of three perennial Xyris (Xyridaceae) species from the Brazilian campo rupestre

• Dormancy cycles are an important mechanism for avoiding seed germination under unfavourable periods for seedling establishment. This mechanism has been scarcely studied in tropical species. Here, we studied three tropical and perennial species of Xyris, X. asperula, X. subsetigera and X. trachyphylla, to investigate in situ longevity and the existence of seasonal seed dormancy cycles.
• Seeds of three species of Xyris were buried in their natural habitat, with samples exhumed bimonthly for 18 months. Germination of exhumed seeds was assessed under a 12‐h photoperiod over a broad range of temperatures. Seeds of X. trachyphylla were also subjected to treatments to overcome secondary dormancy.
• Seeds of all species are able to form a persistent seed bank and exhibit seasonal changes in germinability. Secondary dormancy was acquired during the rainy summer and was overcome during the subsequent dry season (autumn/winter). Desiccation partially overcomes secondary dormancy in X. trachyphylla seeds.
• Soil seed bank persistence and synchronisation of seed germination under favourable conditions for seedling establishment contribute to the persistence and regeneration of X. asperula, X. subsetigera and X. trachyphylla in their natural environment.

     

ILSI/HESI maternal toxicity workshop summary: maternal toxicity and its impact on study design and data interpretation

Workshops on maternal toxicity were held at the annual Society of Toxicology, Teratology Society, and European Teratology Society meetings in 2009. Speakers presented background information prior to a general discussion on this topic. The following recommendations/options are based on the outcome of the discussions at the workshops:

• 1. A comprehensive evaluation of all available data from general toxicity studies, range‐finding Developmental and Reproductive Toxicology (DART) studies, class effects, structure–activity relationships, exposure studies, etc. is essential for appropriate dose selection for definitive DART studies. The intent is to avoid marked maternal toxicity leading to mortality or decreased body weight gains of greater than 20% for prolonged periods.

• (a) Evaluate alternative endpoints for dose selection and data interpretation (e.g., target tissue effects and pharmacology) for biotherapeutics.
• (B) Evaluate additional maternal parameters based on effects and/or target organs observed in short‐term (e.g., 2‐ or 4‐week) general toxicity studies.

• 2. Evaluate all available data to determine a cause–effect relationship for developmental toxicity.

• (a) Conduct a pair‐feeding/pair‐watering study as a follow‐up.
• (b) Evaluate individual data demonstrating maternal toxicity in the mother with adverse embryo–fetal outcomes in the litter associated with the affected mother.
• (c) Conduct single‐dose studies at increasing doses as a complement to conventional embryo–fetal toxicity studies for certain classes of compounds that affect the hERG channel.

• 3. Support statements that embryo–fetal effects are caused by maternal toxicity and/or exaggerated pharmacology, especially for malformations.

• (a) Provide mechanistic or other supporting data.
• (b) Establish the relevance of the DART findings in animals for human exposures. Birth Defects Res (Part B) 92:36–51, 2010. © 2011 Wiley‐Liss, Inc.

     

Gene therapy in Alzheimer’s disease – potential for disease modification

• ? Introduction
• ? Targets and ongoing research
  • ‐ NGF
    • ‐ Neurotrophic function of NGF
    • ‐ Levels of NGF in AD
    • ‐ Role of NGF in AD
    • ‐ NGF as a therapeutic agent
    • ‐ Development of NGF gene therapy
    • ‐ In vivo gene delivery of NGF
  • ‐ BDNF
    • ‐ Neurotrophic function of BDNF
    • ‐ BDNF levels in AD
    • ‐ BDNF function in AD
    • ? Towards BDNF gene therapy
  • ‐ Neprilysin
    • ‐ Role of neprilysin in AD
    • ‐ Neprilysin levels in AD
    • ‐ Gene delivery of neprilysin in AD animal models
• ? Potential gene therapy target candidates
  • ‐ APOE
  • ‐ ECE
  • ‐ Cathepsin B
  • ‐ Other Aβ degrading enzymes
• ? Down‐regulation of AD‐associated proteins by siRNA
  • ‐ BACE1
  • ‐ APP
• ? Concluding remarks

Alzheimer’s disease (AD) is the major cause of dementia in the elderly, leading to memory loss and cognitive decline. The mechanism underlying onset of the disease has not been fully elucidated. However, characteristic pathological manifestations include extracellular accumulation and aggregation of the amyloid β‐peptide (Aβ) into plaques and intracellular accumulation and aggregation of hyperphosphorylated tau, forming neurofibrillary tangles. Despite extensive research worldwide, no disease modifying treatment is yet available. In this review, we focus on gene therapy as a potential treatment for AD, and summarize recent work in the field, ranging from proof‐of‐concept studies in animal models to clinical trials. The multifactorial causes of AD offer a variety of possible targets for gene therapy, including two neurotrophic growth factors, nerve growth factor and brain‐derived neurotrophic factor, Aβ‐degrading enzymes, such as neprilysin, endothelin‐converting enzyme and cathepsin B, and AD associated apolipoprotein E. This review also discusses advantages and drawbacks of various rapidly developing virus‐mediated gene delivery techniques for gene therapy. Finally, approaches aiming at down‐regulating amyloid precursor protein (APP) and β‐site APP cleaving enzyme 1 levels by means of siRNA‐mediated knockdown are briefly summarized. Overall, the prospects appear hopeful that gene therapy has the potential to be a disease modifying treatment for AD.     

News and ISN

• Did you know Journal of Neurochemistry offers authors the option to publish Open Access ? ISN members receive a reduced fee ($1,000 USD compared to the regular fee of $3,000 USD, less than most other journals charge).
• Download the new JNeurochem App for free: https:// itunes.apple.com/us/app/journal-neurochemistry-for/id655612235
• A virtual issue on Neuroinflammation in nervous system disorders, edited by Tammy Kielian, is now available: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1471-4159/homepage/virtual_issues.htm#neuroinflammation

     

Ultrastructural and metabolic disorders induced by short‐term cadmium exposure in Avicennia schaueriana plants and its excretion through leaf salt glands

• Environmental cadmium (Cd) sources have increased in mangrove sediments in recent decades, inducing cellular damage to many plants. Avicennia schaueriana is abundant in mangrove sites and has been subject to Cd contamination. The possible effects of Cd toxicity and the structural and physiological disturbances to this plant were studied. Can this plant express early cellular tolerance mechanisms to such metal contamination?
• Seedlings of A. schaueriana were collected from sites of their natural occurrence, placed in plastic pots containing nutrient solution for 60 days, and subsequently exposed to increasing Cd concentrations for 5 days under experimental conditions. The anatomical, ultrastructural and physiological changes induced by Cd were analysed.
• Cd accumulated mainly in the root system and in pneumatophores, stems and leaves, induced differential accumulation of mineral nutrients, but did not induce necrosis or changes in leaf anatomy. However, there was a decrease in starch grains and an increase in deposited electron‐dense material in the cortex and vascular bundles. Cd induced both increases in calcium (Ca) content in shoots and Ca oxalate crystal precipitation in leaf mesophyll and was detected in crystals and in the secretion of salt glands.
• Our observations and experimental results provide evidence of Cd tolerance in A. schaueriana. As a new feature, despite the clear cellular physiological disorders, this plant is able to eliminate Cd through leaf salt glands and immobilise it in Ca crystals, representing fast mechanisms for Cd exclusion and complexation in leaves in heavy metal coastal polluted marine ecosystems.