A comprehensive phylogeny helps clarify the evolutionary history of host breadth and lure response in the Australian Dacini fruit flies (Diptera: Tephritidae).

The tribe Dacini (Diptera: Tephritidae) contains over 930 recognised species and has been widely studied due to the economic importance of some taxa, such as the Oriental fruit fly Bactrocera dorsalis. Despite the attention this group has received, very few phylogenetic reconstructions have comprehensively sampled taxa from a single biogeographic region, thereby limiting our capacity to address more targeted evolutionary questions. To study the evolution of diet breadth and male lure response, two key traits fundamental to understanding dacine diversity and the biology of pest taxa, we analysed 273 individuals representing 144 described species from Australia (80% continental coverage), the Pacific, and select close relatives from South-east Asia to estimate a dated molecular phylogenetic reconstruction of the Dacini. We utilised seven loci with a combined total of 4,332 nucleotides, to estimate both Bayesian and Maximum Likelihood phylogenies of the tribe. Consistent with other molecular phylogenies of the tribe, there was a high level of disagreement between the placement of species in the phylogeny and their current subgeneric and species-complex level taxonomies. The Australian fauna exhibit high levels of endemism, with radiations of both exclusively Australian clades, and clades that originate elsewhere (e.g. the Bactrocera dorsalis species group). Bidirectional movement of species has occurred between Papua New Guinea and Australia, with evidence for multiple incursions over evolutionary time. The Bactrocera aglaiae species group emerged sister to all other Bactrocera species examined. Divergence time estimates were âˆ¼ 30 my younger than previously reported for this group, with the tribe diverging from its most recent common ancestor âˆ¼ 43 mya. Ancestral trait reconstruction and tests for trait phylogenetic signal revealed a strong signal for the evolution of male lure response across the tree, with cue-lure/raspberry ketone lure response the ancestral trait. Methyl eugenol response has arisen on multiple, independent occasions. The evolution of host breadth exhibited a weaker signal; yet, basal groups were more likely to be host specialists. Both the evolution of lure response and host fruit use provide predictive information for the outbreak management of understudied pest fruit flies for which direct inference of these features may be lacking. Our results, which parallel those of earlier research into the closely-related African Dacus spp., demonstrate how geographically focussed taxon coverage allows Dacini phylogenetics to more explicitly test evolutionary hypotheses, thereby progressing our understanding of the evolution of this highly diverse and recently-radiated group of flies.

Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder.

Alcohol use disorder (AUD) is a common and chronic disorder with substantial effects on personal and public health. The underlying pathophysiology is poorly understood but strong evidence suggests significant roles of both genetic and epigenetic components. Given that alcohol affects many organ systems, we performed a cross-tissue and cross-phenotypic analysis of genome-wide methylomic variation in AUD using samples from 3 discovery, 4 replication, and 2 translational cohorts. We identified a differentially methylated region in the promoter of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes. Biological validation showed that PCSK9 promoter methylation is conserved across tissues and positively correlated with expression. Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of AUD showed that alcohol exposure leads to PCSK9 downregulation. PCSK9 is primarily expressed in the liver and regulates low-density lipoprotein cholesterol (LDL-C). Our finding of alcohol-induced epigenetic regulation of PCSK9 represents one of the underlying mechanisms between the well-known effects of alcohol on lipid metabolism and cardiovascular risk, with light alcohol use generally being protective while chronic heavy use has detrimental health outcomes.

Vulnerabilities in aquatic animal production.

The role of aquatic animals in global food and nutrition security is increasingly recognised. The global demand for fish is increasing, leading to a need to significantly increase its supply. Securing future fish supplies through sustainable production is a challenge as major resources such as fresh water and land are becoming limited worldwide. Aquaculture and capture fisheries face various threats from both human-mediated and natural environmental change, including climate change. Aquaculture systems and practices are vulnerable to such changes. Moreover, aquatic animal diseases are currently considered one of the most important constraints to sustainable global fish production. The need to increase global production, combined with climate change, may increase losses due to diseases. This paper examines key vulnerabilities, their impacts and management to achieve increased and sustainable global fish production. The authors focus on the need to apply international standards, and to develop biosecurity and capacity in aquatic animal health to improve global fish health. Research needed to underpin the development of improved detection and control of fish diseases is also discussed.

L'importance des animaux aquatiques pour la sécurité alimentaire et nutritionnelle mondiale est désormais reconnue. La demande mondiale en aliments issus d'animaux aquatiques ne cessant d'augmenter, il est devenu impératif de renforcer significativement l'offre du secteur. La sécurisation future de cette offre grâce à la mise en place d'une production durable constitue un défi de taille en raison de la raréfaction de certaines ressources cruciales, dont l'eau douce et les terres. L'aquaculture et la pêche de capture font face à plusieurs menaces induites par les transformations tant naturelles qu'anthropiques subies par l'environnement, y compris le changement climatique. Les systèmes et les pratiques de l'aquaculture présentent des vulnérabilités à ces changements. De plus, on considère aujourd'hui que les maladies des animaux aquatiques constituent l'une des principales entraves à une production aquacole durable au niveau mondial. Les pertes dues aux maladies vont probablement augmenter par l'effet conjoint du changement climatique et de la nécessité d'accroître les quantités produites dans le monde. Les auteurs examinent les principales vulnérabilités à l'œuvre ainsi que leur impact et les manières d'y faire face en vue d'une production aquacole mondiale accrue et durable. Ils mettent l'accent sur la nécessité de se conformer aux normes internationales et de renforcer la biosécurité et les capacités du secteur de la santé des animaux aquatiques afin d'améliorer le statut sanitaire de ces animaux à l'échelle mondiale. Ils font également le point sur les travaux de recherche qu'il convient de mener afin de mettre au point de meilleures méthodes de détection et de contrôle des maladies des animaux aquatiques.

Cada vez está más clara la función de los animales acuáticos en relación con la seguridad alimentaria y nutricional del mundo. La demanda planetaria de alimentos derivados de animales acuáticos va en aumento, lo que obliga a incrementar sustancialmente el suministro. El objetivo de asegurar el abastecimiento de animales acuáticos en el futuro gracias a una producción sostenible plantea no pocas dificultades, en la medida en que recursos importantes, como el agua dulce o las tierras, empiezan a escasear en todo el mundo. La acuicultura y la pesca de captura afrontan una serie de amenazas derivadas de los cambios ambientales, ya sean de origen natural o antrópico, en particular el cambio climático. Las praxis y los sistemas acuícolas son vulnerables a esos cambios. Están además las enfermedades de los animales acuáticos, consideradas actualmente uno de los principales frenos a la producción sostenible del sector en el mundo. La necesidad de elevar la producción mundial, combinada con el cambio climático, puede acrecentar el volumen de pérdidas debidas a enfermedades. Los autores examinan las principales fragilidades del sistema, sus consecuencias y la forma de gestionarlas para lograr una producción acuícola mundial más cuantiosa y sostenible, centrándose en la necesidad de aplicar normas internacionales y de desarrollar tanto la seguridad biológica como la capacidad en materia de sanidad de los animales acuáticos para mejorar el estado de salud de estos animales a escala mundial. También se refieren a las investigaciones necesarias para fundamentar sistemas más eficaces de detección y control de las enfermedades de los animales acuáticos.

Overexpression of Fibrinogen-Like Protein 2 Promotes Tolerance in a Fully Mismatched Murine Model of Heart Transplantation.

Fibrinogen-like protein 2 (FGL2) is an immunomodulatory protein that is expressed by regulatory T cells (Tregs). The objective of this study was to determine if recombinant FGL2 (rFGL2) treatment or constitutive FGL2 overexpression could promote transplant tolerance in mice. Although rFGL2 treatment prevented rejection of fully mismatched cardiac allografts, all grafts were rejected after stopping treatment. Next, we generated FGL2 transgenic mice (fgl2(Tg) ) that ubiquitously overexpressed FGL2. These mice developed normally and had no evidence of the autoimmune glomerulonephritis seen in fgl2(-/-) mice. Immune characterization showed fgl2(Tg) T cells were hypoproliferative to stimulation with alloantigens or anti-CD3 and anti-CD28 stimulation, and fgl2(Tg) Tregs had increased immunosuppressive activity compared with fgl2(+/+) Tregs. To determine if FGL2 overexpression can promote tolerance, we transplanted fully mismatched cardiac allografts into fgl2(Tg) recipients. Fifty percent of cardiac grafts were accepted indefinitely in fgl2(Tg) recipients without any immunosuppression. Tolerant fgl2(Tg) grafts had increased numbers and proportions of Tregs and tolerant fgl2(Tg) mice had reduced proliferation to donor but not third party antigens. These data show that tolerance in fgl2(Tg) recipients involves changes in Treg and T cell activity that contribute to a higher intragraft Treg-to-T cell ratio and acceptance of fully mismatched allografts.

Meeting the food and nutrition needs of the poor: the role of fish and the opportunities and challenges emerging from the rise of aquaculture.

People who are food and nutrition insecure largely reside in Asia and Sub-Saharan Africa and for many, fish represents a rich source of protein, micronutrients and essential fatty acids. The contribution of fish to household food and nutrition security depends upon availability, access and cultural and personal preferences. Access is largely determined by location, seasonality and price but at the individual level it also depends upon a person's physiological and health status and how fish is prepared, cooked and shared among household members. The sustained and rapid expansion of aquaculture over the past 30 years has resulted in >40% of all fish now consumed being derived from farming. While aquaculture produce increasingly features in the diets of many Asians, it is much less apparent among those living in Sub-Saharan Africa. Here, per capita fish consumption has grown little and despite the apparently strong markets and adequate biophysical conditions, aquaculture has yet to develop. The contribution of aquaculture to food and nutrition security is not only just an issue of where aquaculture occurs but also of what is being produced and how and whether the produce is as accessible as that from capture fisheries. The range of fish species produced by an increasingly globalized aquaculture industry differs from that derived from capture fisheries. Farmed fishes are also different in terms of their nutrient content, a result of the species being grown and of rearing methods. Farmed fish price affects access by poor consumers while the size at which fish is harvested influences both access and use. This paper explores these issues with particular reference to Asia and Africa and the technical and policy innovations needed to ensure that fish farming is able to fulfil its potential to meet the global population's food and nutrition needs.

The evolutionary history of the extinct ratite moa and New Zealand Neogene paleogeography.

The ratite moa (Aves: Dinornithiformes) were a speciose group of massive graviportal avian herbivores that dominated the New Zealand (NZ) ecosystem until their extinction approximately 600 years ago. The phylogeny and evolutionary history of this morphologically diverse order has remained controversial since their initial description in 1839. We synthesize mitochondrial phylogenetic information from 263 subfossil moa specimens from across NZ with morphological, ecological, and new geological data to create the first comprehensive phylogeny, taxonomy, and evolutionary timeframe for all of the species of an extinct order. We also present an important new geological/paleogeographical model of late Cenozoic NZ, which suggests that terrestrial biota on the North and South Island landmasses were isolated for most of the past 20-30 Ma. The data reveal that the patterns of genetic diversity within and between different moa clades reflect a complex history following a major marine transgression in the Oligocene, affected by marine barriers, tectonic activity, and glacial cycles. Surprisingly, the remarkable morphological radiation of moa appears to have occurred much more recently than previous early Miocene (ca. 15 Ma) estimates, and was coincident with the accelerated uplift of the Southern Alps just ca. 5-8.5 Ma. Together with recent fossil evidence, these data suggest that the recent evolutionary history of nearly all of the iconic NZ terrestrial biota occurred principally on just the South Island.

The prothrombinase activity of FGL2 contributes to the pathogenesis of experimental arthritis.

OBJECTIVE: Fibrin deposition is integral to the pathogenesis of collagen-induced arthritis (CIA), an experimental model of rheumatoid arthritis (RA). Membrane-associated fibrinogen-like protein 2 (mFGL2), a novel inducible prothrombinase, generates fibrin by an alternate pathway and has been reported to be involved in the pathogenesis of a number of immune-mediated diseases. We hypothesized that expression of mFGL2 in inflamed synovium contributes to the fibrin deposition and subsequent inflammation in arthritis. METHODS: DBA/1 mice were immunized with 100 µg bovine collagen type II (CII) emulsified in complete Freund's adjuvant (CFA) followed by lipopolysaccharide (LPS) injection. Expression of mFGL2 prothrombinase in association with fibrin deposition was examined in mice with CIA and CD200-treated mice following induction of CIA. To directly assess the contribution of mFGL2, fgl2(-/-) mice were injected with antibody to CII (anti-CII). RESULTS: Levels of fgl2 mRNA transcripts and mFGL2 protein were markedly up-regulated in joints of mice that developed CIA. Fibrin deposition was prominent within the synovial lining and articular joint space associated with expression of mFGL2. Inhibition of CIA by the immunosuppressant CD200 was associated with decreased expression of fgl2 mRNA and mFGL2 protein and absence of fibrin deposition. Following injection of anti-CII, all fgl2(+/+) mice developed severe arthritis with clinical and histological manifestations characteristic of RA, whereas fgl2(-/-) mice failed to develop any clinical manifestation or histological evidence of arthritis. CONCLUSIONS: This study demonstrates that the prothrombinase activity of mFGL2 contributes to the pathogenesis of experimental arthritis. These studies may have therapeutic implications for patients with RA.

Stimulus specificity of the generation of leukotrienes by dog mastocytoma cells.

Isolated dog mastocytoma cells sensitized with dog anti-ragweed IgE and challenged with ragweed antigen or incubated with ionophore A23187 or the carboxy-terminal dodecapeptide of platelet factor 4, PF4(59-70), release histamine and concurrently generate leukotrienes B4, C4, and D4. In contrast, the exposure of mastocytoma cells to 0.1-3 micrograms/ml of 15-hydroxyeicosatetraenoic acid (15-HETE) stimulates selectively the generation of leukotrienes, in the absence of histamine release, while 0.1-1 micrograms/ml of compound 48/80 releases histamine without enhancing the generation of leukotrienes. That natural stimuli are capable of selectively activating one synthetic or secretory compartment of mast cells suggests that separate subsets of receptors as well as different biochemical events may serve to mobilize each class of mediators.

Monoclonal antiprothrombinase (3D4.3) prevents mortality from murine hepatitis virus (MHV-3) infection.

The induction of monocyte/macrophage procoagulant activity (PCA) has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3) infection and disease. Previously, we have shown that induction of PCA by MHV-3 correlated with resistance/susceptibility to infection in different mouse strains. In this study, all BALB/cJ mice that were infected with 10(3) plaque-forming units of MHV-3 developed severe liver disease and died within 96-120 h. Examination of the livers of these animals showed marked hepatic necrosis, deposition of fibrin, and cellular expression of PCA by direct immunofluorescence staining in areas of necrosis as well as in hepatic sinusoids. Splenic mononuclear cells recovered from these mice expressed high concentrations of PCA with time after infection. Infusion into mice of a high-titered monoclonal antibody that neutralized PCA (3D4.3) attenuated the development of hepatic necrosis and enhanced survival in a dose-dependent manner. All of the animals receiving 100 micrograms, and 44% and 22% of the animals that received 50 and 25 micrograms per day, respectively, survived for 10 d and made a full recovery. Administration of the antibody resulted in a dose-dependent reduction in fibrin deposition, PCA expression as detected by direct immunofluorescence staining and by a functional assay. In animals treated with high concentrations of antibody, titers of antibody to PCA fell from 87 +/- 15 micrograms/ml to 100 +/- 7 ng/ml during the active phase of the disease, consistent with sequestration due to binding of the immunoglobulin to cells expressing PCA. Surviving animals, when rechallenged with MHV-3, had a 40% mortality, consistent with the known rates of metabolism of immunoglobulin. This further suggested that protection was by a passive mechanism. The results reported here demonstrate that a neutralizing antibody to PCA protects animals from fulminant hepatitis and death associated with MHV-3 infection, and supports the notion that PCA is a potent inflammatory mediator that plays a pivotal role in the pathogenesis of liver injury resulting from MHV-3 infection.

Measuring airway dimensions during bronchoscopy using anatomical optical coherence tomography.

Airway dimensions are difficult to quantify bronchoscopically because of optical distortion and a limited ability to gauge depth. Anatomical optical coherence tomography (aOCT), a novel imaging technique, may overcome these limitations. This study evaluated the accuracy of aOCT against existing techniques in phantom, excised pig and in vivo human airways. Three comparative studies were performed: 1) micrometer-derived area measurements in 10 plastic tubes were compared with aOCT-derived area; 2) aOCT-derived airway compliance curves from excised pig airways were compared with curves derived using an endoscopic technique; and 3) airway dimensions from the trachea to subsegmental bronchi were measured using aOCT in four anaesthetised patients during bronchoscopy and compared with computed tomography (CT) measurements. Measurements in plastic tubes revealed aOCT to be accurate and reliable. In pig airways, aOCT-derived compliance measurements compared closely with endoscopic data. In human airways, dimensions measured with aOCT and CT correlated closely. Bland-Altman plots showed that aOCT diameter and area measurements were higher than CT measurements by 7.6% and 15.1%, respectively. Airway measurements using aOCT are accurate, reliable and compare favourably with existing imaging techniques. Using aOCT with conventional bronchoscopy allows real-time measurement of airway dimensions and could be useful clinically in settings where knowledge of airway calibre is required.

Managing obstruction of the central airways.

Lung cancer is the most common cause of cancer death in Australia, Europe and the USA. Up to 20-30% of these cancers eventually affect the central airways and result in reduced quality of life, dyspnoea, haemoptysis, post-obstructive pneumonia and ultimately death. Non-malignant processes may also lead to central airway obstruction and can have similar symptoms. With the development of newer technologies, the last 20 years have seen the emergence of the field of interventional pulmonology to deal specifically with the diagnosis and management of thoracic malignancy, including obstruction of the central airways. This review discusses the pathology, pre-procedure work-up and management options for obstructing central airway lesions. Several treatment modalities exist for dealing with endobronchial pathology with local availability and expertise guiding choice of treatment. While the literature lacks large, multicentre, randomized studies defining the optimal management strategy for a given problem, there is growing evidence from numerous case studies of improved physiology, of quality of life and possibly of survival with modern interventional techniques.

Quantifying tracheobronchial tree dimensions: methods, limitations and emerging techniques.

The ability to measure airway dimensions is important for clinicians, interventional bronchoscopists and researchers in order to accurately quantify structural abnormalities and track their changes over time or in response to treatment. Most quantitative airway measurements are based on X-ray computed tomography and, more recently, on multidetector computed tomography. Quantitative bronchoscopic techniques have also been developed, although these are less widely employed. Emerging techniques, including magnetic resonance imaging, endoscopic optical coherence tomography, endobronchial ultrasound and confocal endomicroscopy, provide new research tools with potential clinical applications. An understanding of issues related to the acquisition, processing and analysis of images, and how such issues impact on imaging the tracheobronchial tree, is essential in order to assess measurement accuracy and to make effective use of the newer methods. This article contributes to this understanding by providing a comprehensive review of current and emerging techniques for quantifying airway dimensions.

Motility of bile canaliculi in the living animal: implications for bile flow.

Modern fluorescence microscopic techniques were used to image the bile canalicular system in the intact rat liver, in vivo. By combining the use of sodium fluorescein secretion into bile, with digitally enhanced fluorescence microscopy and time-lapse video, it was possible to capture and record the canalicular motility events that accompany the secretion of bile in life. Active bile canalicular contractions were found predominantly in zone 1 (periportal) hepatocytes of the liver. The contractile movements were repetitive, forceful, and appeared unidirectional moving bile in a direction towards the portal bile ducts. Contractions were not seen in the network of canaliculi on the surface of the liver. Cytochalasin B administration resulted in reduced canalicular motility, progressive dilation of zone 1 canaliculi, and impairment of bile flow. Canalicular dilations invariably involved the branch points of the canalicular network. The findings add substantively to previous in vitro studies using couplets, and suggest that canalicular contractions contribute physiologically to bile flow in the liver.

Effects of cytochalasin B on membrane-associated microfilaments in a cell-free system.

The mode of action of cytochalasin B was examined in vitro using bile canaliculus-enriched plasma membrane fractions isolated from rat liver. The pericanalicular microfilaments, which are mainly actin filaments and which are normally attached to the canalicular membranes, were dissociated from the membranes by cytochalasin B treatment. A microfilamentous network was found in the supernate of the cytochalasin B treatment. A microfilamentous network was found in the supernate of the cytochalasin-treated specimens and a number of polypeptides, of which a polypeptide corresponding in molecular weight to actin was a notable member. These results suggest that actin filaments become detached from the canaliculus membranes by cytochalasin B.

Contractility of bile canaliculi: implications for liver function.

Dynamic contractions of bile canaliculi were observed in groups of cultured hepatocytes by time-lapse cinephotomicrography during the early stages of monolayer formation. The contractions, which were forceful and appeared to have a pumping action, may facilitate the flow of bile in the liver's canalicular system.

Cellular transplantation in the treatment of experimental hepatic failure.

The survival of Lewis rats with D-galactosamine-induced fulminant hepatic failure was prolonged if they were given intraperitoneal injections of single-cell suspensions of liver or bone marrow cells from normal rats. Suspensions of liver cells were also effective in prolonging the survival of rats with ischemia-induced hepatic necrosis. The liver cells did not act by repopulating the recipient liver.

Farm-level plans and husbandry measures for aquatic animal disease emergencies.

Disease is one of the gravest threats to the sustainability of the aquaculture industry. A good understanding of biosecurity and disease causation is essential for developing and implementing farm-level plans and husbandry measures to respond to disease emergencies. Using epidemiological approaches, it is possible to identify pond- and farm-level risk factors for disease outbreaks and develop intervention strategies. Better management practices (BMPs) should be simple, science-based, cost-effective and appropriate to their context if farmers are to adopt and implement them. As part of a regional initiative by the Network of Aquaculture Centres in Asia-Pacific (NACA) to control aquatic animal diseases, effective extension approaches to promote the widespread adoption of BMPs have been developed in India, Indonesia, Vietnam and Thailand, and have proved their worth. A highly successful programme, which addresses rising concerns about the effect of disease on the sustainability of shrimp farming in India, is now in its seventh year. In this paper, the authors present a brief insight into the details of the programme, its outcomes and impact, the lessons learned and the way forward.

Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.

Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene.

We report the chromosomal localization, mutant gene identification, ophthalmic appearance, histology, and functional analysis of two new hereditary mouse models of retinal degeneration not having the Pde6brd1("r", "rd", or "rodless") mutation. One strain harbors an autosomal recessive mutation that maps to mouse chromosome 5. Sequence analysis showed that the retinal degeneration is caused by a missense point mutation in exon 13 of the beta-subunit of the rod cGMP phosphodiesterase (beta-PDE) gene (Pde6b). The gene symbol for this strain was set as Pde6brd10, abbreviated rd10 hereafter. Mice homozygous for the rd10 mutation showed histological changes at postnatal day 16 (P16) of age and sclerotic retinal vessels at four weeks of age, consistent with retinal degeneration. Retinal sections were highly positive for TUNEL and activated caspase-3 immunoreactivity, specifically in the outer nuclear layer (ONL). ERGs were never normal, but rod and cone ERG a- and b-waves were easily measured at P18 and steadily declined over 90% by two months of age. Protein extracts from rd10 retinas were positive for beta-PDE immunoreactivity starting at about the same time as wild-type (P10), though signal averaged less than 40% of wild-type. Interestingly, rearing rd10 mice in total darkness delayed degeneration for at least a week, after which morphological and functional loss progressed irregularly. With the second strain, a complementation test with rd1 mice revealed that the retinal degeneration phenotype observed represents a possible new allele of Pde6b. Sequencing demonstrated a missense point mutation in exon 16 of the beta-subunit of rod phosphodiesterase gene, different from the point mutations in rd1 and rd10. The gene symbol for this strain was set as Pde6bnmf137, abbreviated nmf137 hereafter. Mice homozygous for this mutation showed retinal degeneration with a mottled retina and white retinal vessels at three weeks of age. The exon 13 missense mutation (rd10) is the first known occurrence of a second mutant allele spontaneously arising in the Pde6b gene in mice and may provide a model for studying the pathogenesis of autosomal recessive retinitis pigmentosa (arRP) in humans. It may also provide a better model for experimental pharmaceutical-based therapy for RP because of its later onset and milder retinal degeneration than rd1 and nmf137.

Communication and networking in a regional organisation.

Access to accurate information and technical expertise is a pre-requisite for informed decision making. The Network of Aquaculture Centres in Asia-Pacific (NACA), an intergovernmental organization of 17 governments in Asia-Pacific, works on the principle of cooperation and collaboration with the intention of sharing regional resources amongst the stakeholders within the network: governments, institutions and individuals. Networking, communication and project implementation coordinated by NACA in collaboration with partner organizations and donor agencies has been instrumental in facilitating the flow of science and provision of technical assistance to relevant stakeholders in Member Countries. Development and adoption of the FAO/NACA's Asia regional technical guidelines (TG) for the responsible movement of live aquatic animals by 21 Asia-Pacific governments is a major outcome of networking and communication that had been facilitated by the NACA, from 1999 to 2001. Since then, the implementation of key elements of the TG has remained the focus of NACA's regional aquatic animal health programme. The present paper provides some examples of past and ongoing activities that highlight the role of networking and communication in a regional organization in strengthening aquatic animal health capacity and biosecurity in the Asia-Pacific region.