Modulation of insect Cav channels by peptidic spider toxins

Insects have a much smaller repertoire of voltage-gated calcium (Ca-v) channels than vertebrates. Drosophila melanogaster harbors only a single ortholog of each of the vertebrate Ca(v)1, Ca(v)2, and Ca(v)3 subtypes, although its basal inventory is expanded by alternative splicing and editing of Ca-v channel transcripts. Nevertheless, there appears to be little functional plasticity within this limited panel of insect Ca-v channels, since severe loss-of-function mutations in genes encoding the pore-forming a, subunits in Drosophila are embryonic lethal. Since the primary role of spider venom is to paralyze or kill insect prey, it is not surprising that most, if not all, spider venoms contain peptides that potently modify the activity of these functionally critical insect Ca-v channels. Unfortunately, it has proven difficult to determine the precise ion channel subtypes recognized by these peptide toxins since insect Ca-v channels have significantly different pharmacology to their vertebrate counterparts, and cloned insect Ca-v channels are not available for electrophysiological studies. However, biochemical and genetic studies indicate that some of these spider toxins might ultimately become the defining pharmacology for certain subtypes of insect Ca-v channels. This review focuses on peptidic spider toxins that specifically target insect Ca-v channels. In addition to providing novel molecular tools for ion channel characterization, some of these toxins are being used as leads to develop new methods for controlling insect pests. (c) 2006 Elsevier Ltd. All rights reserved.

Salume arricchito in acidi grassi polinsaturi omega-3: controllo delle caratteristiche sensoriali in relazione ad un possibile incremento di ossidabilità della frazione lipidica durante la shelf-life.

Questa relazione finale è stata frutto di un lavoro sperimentale svolto in collaborazione con un’azienda del territorio ed ha avuto come obiettivo principale quello di verificare i parametri qualitativi e compositivi di una nuova tipologia di salume in fase di studio. L’azienda sta studiando una nuova tipologia di “prodotto funzionale” addizionando componenti ad attività nutraceutica al salame ottenuto da sole parti magre di suino. L’intenzione dell’azienda è di arricchire il proprio prodotto con acidi grassi polinsaturi della serie omega-3 (da olio di semi di lino), noti per gli effetti benefici che possono esercitare sulla salute umana. A questo scopo, sul prodotto di nuova formulazione (ed in parallelo sul prodotto a formulazione classica e su un prodotto del tutto simile commercializzato da un’altra azienda) sono state effettuate sia la determinazione della percentuale lipidica, al fine di individuare il quantitativo totale di grasso, che una caratterizzazione gascromatografica del profilo quali-quantitativo in acidi grassi, analsi fondamentale per verificare la conformità con i requisiti indicati dal Reg. 1924/06, e successive modifiche, previsti per le indicazioni da inserire in etichetta (claims). Inoltre, è stato importante controllare che la concentrazione voluta di acido alfa-linolenico si mantenga tale durante tutto il periodo di shelf-life del prodotto (45 gg), perciò per soddisfare quest’ultima finalità, le analisi sono state eseguite sia all’inizio (T0) che alla fine (T1) della vita commerciale del prodotto. E’ apparso poi fondamentale monitorare un possibile decadimento/modifica della qualità organolettica del prodotto di nuova formulazione, a causa del possibile aumento di ossidabilità della frazione lipidica causata da una maggiore presenza di acidi grassi polinsaturi; ed infine, con l’intento di verificare se la nuova formulazione potesse comportare una variazione significativa delle caratteristiche sensoriali del prodotto, sono stati condotti un test descrittivo quantitativo (QDA), in grado di descrivere il profilo sensoriale del prodotto ed un test discriminante qualitativo (metodo triangolare) capace di valutare l’eventuale comparsa di cambiamenti in seguito alle modifiche apportate al prodotto; per ultimo è stato poi eseguito un test affettivo quantitativo (test di preferenza, condotto su scala di laboratorio) in grado fornire informazioni sul gradimento e di evidenziare i principali vettori che guidano le scelte dei consumatori. I risultati delle analisi chimiche e sensoriali, eseguite per soddisfare tali richieste, hanno evidenziato come il salume presenti un quantitativo di tali acidi grassi polinsaturi in linea con il claim “Alimento fonte di acidi grassi omega-3”, (requisiti indicati dal Reg. 1924/06 e successive modifiche), risultato confermato sia all’inizio che al termine della vita commerciale del prodotto (pari a circa 45 giorni). Inoltre, esso risulta essere piuttosto interessante dal punto di vista nutrizionale, poiché caratterizzato da un contenuto di grasso per la categoria dei salumi, relativamente limitato, pari a circa il 15%, con percentuali più favorevoli in acidi grassi insaturi. L’analisi del profilo sensoriale condotta ad inizio shelf-life ha invece evidenziato come questa tipologia di prodotto sia caratterizzata sia al gusto che all’olfatto da note più sapide e speziate , oltre ad una maggiore consistenza della fetta, rispetto agli altri campioni analizzati, mentre i risultati relativi al termine della shelf-life hanno evidenziato come esso tenda ad essere soggetto ad alterazioni sensoriali rilevabili proprio al termine della fase di conservazione dovute nello specifico alla formazione di composti responsabili dell’odore di rancido. I test discriminanti, condotti con giudici non allenati, non hanno invece fatto registrare differenze sensoriali significative tra il prodotto con formulazione classica e quello di nuova formulazione, confrontati ad inizio e a fine shelf-life. Riassumendo, dai risultati ottenuti da questo lavoro sperimentale, il prodotto di nuova formulazione, arricchito in acidi grassi polinsaturi della serie omega-3, risulta essere in linea con il claim “Alimento fonte di acidi grassi omega-3”, presenta in generale un contenuto di grasso totale inferiore a quello di altre tipologie di salumi ed un rapporto più favorevole tra acidi grassi insaturi e saturi, per questo può essere considerato un prodotto interessante dal punto di vista della salute e della nutrizione. Proprio per la sua formulazione più ricca in acidi grassi polinsaturi, tende però a fine shelf-life a presentare una leggera nota di rancido, riconducibile ad una maggiore ossidabilità della frazione lipidica. Tale variazione sensoriale è risultata comunque percepita solo da un panel allenato, mentre un test di tipo discriminante, condotto con giudici non allenati, non ha messo in luce differenze significative tra il salume di nuova formulazione e quello con formulazione classica né all’inizio, né al termine della vita commerciale del prodotto.

Salume arricchito in acidi grassi polinsaturi omega-3: controllo di parametri chimici qualitativi e compositivi in relazione ad un possibile incremento di ossidabilita’ della frazione lipidica durante la shelf-life

Questa relazione finale è incentrata sul lavoro sperimentale richiesto dalla collaborazione con l’azienda Natural Salumi ed ha come obiettivo principale quello di verifica dei parametri qualitativi e compositivi di una nuova tipologia di salume in fase di studio. L’azienda ha infatti messo a punto un nuovo “prodotto funzionale” addizionando componenti aventi attività nutraceutica al salame ottenuto da sole parti magre di suino (tipo NaturalFetta) e si propone di arricchire il proprio prodotto con acidi grassi polinsaturi della serie omega-3 (da olio di semi di lino), noti per gli effetti benefici esercitati sulla salute umana. Sul prodotto di nuova formulazione si effettueranno sia la determinazione della percentuale lipidica mediante metodo ufficiale Soxhlet ed automatizzato Soxtec, al fine di individuare il quantitativo totale della parte grassa, che una caratterizzazione del profilo quali-quantitativo in acidi grassi, fondamentale per verificare la conformità con i requisiti indicati dal Reg. 1924/06 (e successivi come il Reg. UE 432/2012) previsti per le indicazioni da inserire in etichetta (claims) per i prodotti arricchiti con acidi grassi polinsaturi (PUFA). La determinazione del profilo in acidi grassi e, nello specifico, del contenuto in acido -linolenico, sarà realizzata mediante gascromatografia previa estrazione della frazione lipidica dei salumi con metodo di Folch modificato, che prevede un'estrazione solido-liquido. La concentrazione di acido alfa-linolenico sarà inoltre monitorata durante tutto il periodo di shelf-life del prodotto (45 gg) al fine di valutare eventuali variazioni durante la conservazione. Per soddisfare quest’ultima finalità, le analisi saranno eseguite sia all’inizio (T0) che alla fine (T1) della vita commerciale del prodotto. Le stesse analisi verranno inoltre condotte sia sul prodotto a formulazione classica che su un prodotto del tutto simile, commercializzato da un’altra azienda e considerato come leader di mercato. In relazione ad un possibile aumento di ossidabilità della frazione lipidica, sarà realizzato un controllo dei parametri chimici, qualitativi e compositivi, con particolare riferimento ai prodotti di ossidazione del colesterolo (date le loro implicazioni in ambito biomedico). La maggiore presenza in formulazione di acidi grassi polinsaturi potrebbe infatti favorire un incremento dei COPs (Cholesterol Oxidation Products), che saranno separati, identificati e quantificati mediante la procedura SPE/GC-MS (estrazione e purificazione in fase solida accoppiata ad analisi gascromatografica con rivelazione mediante spettrometria di massa).

Omega-3 polyunsaturated fatty acids in the treatment of kidney disease

After more than 25 years of published investigation, including randomized controlled trials, the role of omega-3 polyunsaturated fatty acids in the treatment of kidney disease remains unclear. In vitro and in vivo experimental studies support the efficacy of omega-3 polyunsaturated fatty acids on inflammatory pathways involved with the progression of kidney disease. Clinical investigations have focused predominantly on immunoglobulin A (IgA) nephropathy. More recently, lupus nephritis, polycystic kidney disease, and other glomerular diseases have been investigated. Clinical trials have shown conflicting results for the efficacy of omega-3 polyunsaturated fatty acids in IgA nephropathy, which may relate to varying doses, proportions of eicosapentaenoic acid and docosahexaenoic acid, duration of therapy, and sample size of the study populations. Meta-analyses of clinical trials using omega-3 polyunsaturated fatty acids in IgA nephropathy have been limited by the quality of available studies. However, guidelines suggest that omega-3 polyunsaturated fatty acids should be considered in progressive IgA nephropathy. Omega-3 polyunsaturated fatty acids decrease blood pressure, a known accelerant of kidney disease progression. Well-designed, adequately powered, randomized, controlled clinical trials are required to further investigate the potential benefits of omega-3 polyunsaturated fatty acids on the progression of kidney disease and patient survival.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

Can social resilience inform SA/SIA for adaptive planning for climate change in vulnerable regions?

Social resilience concepts are gaining momentum in environmental planning through an emerging understanding of the socio-ecological nature of biophysical systems. There is a disconnect, however, between these concepts and the sociological and psychological literature related to social resilience. Further still, both schools of thought are not well connected to the concepts of social assessment (SA) and social impact assessment (SIA) that are the more standard tools supporting planning and decision-making. This raises questions as to how emerging social resilience concepts can translate into improved SA/SIA practices to inform regional-scale adaptation. Through a review of the literature, this paper suggests that more cross-disciplinary integration is needed if social resilience concepts are to have a genuine impact in helping vulnerable regions tackle climate change.

Intravenous injection of leconotide, an omega conotoxin : synergistic antihyperalgesic effects with morphine in a rat model of bone cancer pain

Objective.  Leconotide (CVID, AM336, CNSB004) is an omega conopeptide similar to ziconotide, which blocks voltage sensitive calcium channels. However, unlike ziconotide, which must be administered intrathecally, leconotide can be given intravenously because it is less toxic. This study investigated the antihyperalgesic potency of leconotide given intravenously alone and in combinations with morphine-administered intraperitoneally, in a rat model of bone cancer pain. Design.  Syngeneic rat prostate cancer cells AT3B-1 were injected into one tibia of male Wistar rats. The tumor expanded within the bone causing hyperalgesia to heat applied to the ipsilateral hind paw. Measurements were made of the maximum dose (MD) of morphine and leconotide given alone and in combinations that caused no effect in an open-field activity monitor, rotarod, and blood pressure and heart rate measurements. Paw withdrawal thresholds from noxious heat were measured. Dose response curves for morphine (0.312–5.0 mg/kg intraperitoneal) and leconotide (0.002–200 µg/kg intravenous) given alone were plotted and responses compared with those caused by morphine and leconotide in combinations. Results.  Leconotide caused minimal antihyperalgesic effects when administered alone. Morphine given alone intraperitoneally caused dose-related antihyperalgesic effects (ED50 = 2.40 ± 1.24 mg/kg), which were increased by coadministration of leconotide 20 µg/kg (morphine ED50 = 0.16 ± 1.30 mg/kg); 0.2 µg/kg (morphine ED50 = 0.39 ± 1.27 mg/kg); and 0.02 µg/kg (morphine ED50 = 1.24 ± 1.30 mg/kg). Conclusions.  Leconotide caused a significant increase in reversal by morphine of the bone cancer-induced hyperalgesia without increasing the side effect profile of either drug. Clinical Implication.  Translation into clinical practice of the method of analgesia described here will improve the quantity and quality of analgesia in patients with bone metastases. The use of an ordinary parenteral route for administration of the calcium channel blocker (leconotide) at low dose opens up the technique to large numbers of patients who could not have an intrathecal catheter for drug administration. Furthermore, the potentiating synergistic effect with morphine on hyperalgesia without increased side effects will lead to greater analgesia with improved quality of life.

Reflection on the SIA Ltd professional project and the body of knowledge

In the last five years the Safety Institute of Australia Limited (SIA) has developed and implemented a number of strategies to gain professional recognition for the ‘generalist occupational health and safety (OHS) professional’ in Australia and internationally. Despite a considerable amount of work by the SIA aimed at gaining professional status, there does not appear to have been any published debate or reflection about how the drive for professionalism (the ‘professional project’) will contribute to the prevention of occupational disease and injury. Professionalisation has been promoted as a sign of maturity for the SIA and as an unquestionably good outcome, as it has been assumed that professionalisation will provide unmitigated benefits for workplace health and safety. The aim of this paper is to critically reflect on the processes of professionalisation (the professional project) and discuss the ways in which this project may shape the field of occupational health and safety.

Can social resilience inform SA/SIA for adaptive planning for climate change in vulnerable regions?

This book represents a landmark effort to probe and analyze the theory and empirics of designing water disaster management policies. It consists of seven chapters that examine, in-depth and comprehensively, issues that are central to crafting effective policies for water disaster management. The authors use historical surveys, institutional analysis, econometric investigations, empirical case studies, and conceptual-theoretical discussions to clarify and illuminate the complex policy process. The specific topics studied in this book include a review and analysis of key policy areas and research priority areas associated with water disaster management, community participation in disaster risk reduction, the economics and politics of ‘green’ flood control, probabilistic flood forecasting for flood risk management, polycentric governance and flood risk management, drought management with the aid of dynamic inter-generational preferences, and how social resilience can inform SA/SIA for adaptive planning for climate change in vulnerable areas. A unique feature of this book is its analysis of the causes and consequences of water disasters and efforts to address them successfully through policy-rich, cross-disciplinary and transnational papers. This book is designed to help enrich the sparse discourse on water disaster management policies and galvanize water professionals to craft creative solutions to tackle water disasters efficiently, equitably, and sustainably. This book should also be of considerable use to disaster management professionals, in general, and natural resource policy analysts.

Owning omega-3: Monsanto and the invention of meat

In August of 2010, Anna Salleh of the Science Unit of the Australian Broadcasting Corporation broke a story about Monsanto seeking to patent the enhancement of meat, including omega-3 fatty acids: ‘Enhanced port is sparking debate over the ethics of placing patents on food. Patent applications covering the enhancement of meat, including pork with omega-3 fatty acids, are stimulating debate over the ethics and legalities of claiming intellectual property over food. Monsanto has filed patents that cover the feeding of animals soybeans, which have been genetically modified by the company to contain stearidonic acid (SDA), a plant-derived omega-3 fatty acid... Omega-3s have been linked to improved cardiovascular health and there are many companies engineering them into foodstuffs. But the new patent applications have touched a raw nerve among those who see them as an attempt by the company to exert control over the food chain.’ This article providers a critical evaluation of the controversy of Monsanto’s patent applications, and the larger issues over patenting food. It first considers the patent portfolio of Monsanto; the nature of the patent claims; and the examination of the claims by patent examiners. Second, it examines the withdrawal and revision of the patent claims by Monsanto in the wake of criticism by patent authorities and the public disquiet over the controversial application. Third, this article considers the larger policy issues raised by Monsanto’s patent applications – including the patenting of plants, animals, and foodstuffs. There is also a consideration of the impact of patents upon the administration of health-care, competition, and research.

Comparative analysis and distribution of Omega-3 lcPUFA Biosynthesis genes in marine molluscs

Recent research has identified marine molluscs as an excellent source of omega-3 long-chain polyunsaturated fatty acids (lcPUFAs), based on their potential for endogenous synthesis of lcPUFAs. In this study we generated a representative list of fatty acyl desaturase (Fad) and elongation of very long-chain fatty acid (Elovl) genes from major orders of Phylum Mollusca, through the interrogation of transcriptome and genome sequences, and various publicly available databases. We have identified novel and uncharacterised Fad and Elovl sequences in the following species: Anadara trapezia, Nerita albicilla, Nerita melanotragus, Crassostrea gigas, Lottia gigantea, Aplysia californica, Loligo pealeii and Chlamys farreri. Based on alignments of translated protein sequences of Fad and Elovl genes, the haeme binding motif and histidine boxes of Fad proteins, and the histidine box and seventeen important amino acids in Elovl proteins, were highly conserved. Phylogenetic analysis of aligned reference sequences was used to reconstruct the evolutionary relationships for Fad and Elovl genes separately. Multiple, well resolved clades for both the Fad and Elovl sequences were observed, suggesting that repeated rounds of gene duplication best explain the distribution of Fad and Elovl proteins across the major orders of molluscs. For Elovl sequences, one clade contained the functionally characterised Elovl5 proteins, while another clade contained proteins hypothesised to have Elovl4 function. Additional well resolved clades consisted only of uncharacterised Elovl sequences. One clade from the Fad phylogeny contained only uncharacterised proteins, while the other clade contained functionally characterised delta-5 desaturase proteins. The discovery of an uncharacterised Fad clade is particularly interesting as these divergent proteins may have novel functions. Overall, this paper presents a number of novel Fad and Elovl genes suggesting that many mollusc groups possess most of the required enzymes for the synthesis of lcPUFAs.

Omega-Hydroxylation of acyclic monoterpene alcohols by rat lung microsomes

Rat lung microsomes were shown to �-hydroxylate acyclic monoterpene alcohols in the presence of NADPH and O2. NADH could neither support hydroxylation efficiently nor did it show synergistic effect. The hydroxylase activity was greater in microsomes prepared from β-naphthoflavone (BNF)-treated rats than from phenobarbital (PB)-treated or control microsomal preparations. Hydroxylation was specific to the C-8 position in geraniol and has a pH optimum of 7.8. The inhibition of the hydroxylase activity by SKF-525A, CO, N-ethylmaleimide, ellipticine, α-naphthoflavone, cyt. Image and p-CMB indicated the involvement of the cyt. P-450 system. However, NaN3 stimulated the hydroxylase activity to a significant level. Rat kidney microsomes were also capable of �-hydroxylating geraniol although the activity was lower than that observed with lungs.

Omega-hydroxylation of acyclic monoterpene alcohols by rat lung microsomes

Rat lung microsomes were shown to ω-hydroxylate acyclic monoterpene alcohols in the presence of NADPH and O2. NADH could neither support hydroxylation efficiently nor did it show synergistic effect. The hydroxylase activity was greater in microsomes prepared from β-naphthoflavone (BNF)-treated rats than from phenobarbital (PB)-treated or control microsomal preparations. Hydroxylation was specific to the C-8 position in geraniol and has a pH optimum of 7.8. The inhibition of the hydroxylase activity by SKF-525A, CO, N-ethylmaleimide, ellipticine, α-naphthoflavone, cyt. Image and p-CMB indicated the involvement of the cyt. P-450 system. However, NaN3 stimulated the hydroxylase activity to a significant level. Rat kidney microsomes were also capable of ω-hydroxylating geraniol although the activity was lower than that observed with lungs.

Stereochemistry of peptides and polypeptides containing omega amino acids

The omega amino acids have a larger degree of conformational variability than the alpha amino acids, leading to a greater diversity of backbone structures in peptides and polypeptides. The synthetic accessibility of chiral beta-amino acids and the recent observation of novel helical folds in oligomers of cyclic beta-amino acids has led to renewed interest in the stereochemistry of omega-amino acid containing peptides. This review focuses on the conformational characteristics of the polymethylene chain in omega-amino acid segments and surveys structural features in peptides established by X-ray diffraction. The literature on polymers of achiral omega-amino acids (nylon derivatives) and chiral, substituted derivatives derived from trifunctional alpha-amino acids, reveals that while sheet-like, intermolecular hydrogen bonded structures are formed by the former, folded helices appear favoured by the latter. omega-Amino acids promise to expand the repertoire of peptide folds.