From little things big things grow: enhancement of an acoustic telemetry network to monitor broad-scale movements of marine species along Australia's east coast.

BACKGROUND: Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain. METHODS: Since 2007, the Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters. RESULTS: The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore "redundancy" is a critical consideration when designing this type of array. CONCLUSION: Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species.

A new species of Saropogon Loew, 1847 (Diptera, Asilidae) from Arizona, with a review of the Nearctic species north of Mexico.

The Nearctic species of Saropogon Loew, 1847 north of Mexico are reviewed, with 19 species recognized and one described as new: Saropogonpyrodes sp. nov. from Arizona. This previously recognized new species has awaited description since its first collection in 1964. Only after a community scientist posted photographs taken in nature to an online database did its description become a priority. All species of Saropogon occurring in the Nearctic Region north of the Mexican border have been reexamined. Photographs and diagnoses of all species are provided with a distribution map of the included specimens studied. An updated key to the Nearctic species north of Mexico is provided. Finally, the need for a review of the diverse Mexican fauna is expressed.

Relative influence of environmental factors on the timing and occurrence of multi-species coral reef fish aggregations.

Reef configuration and hydrodynamics were identified as the principle physical drivers behind coral reef fish aggregations on a mid-shelf patch reef in the northern section of the Great Barrier Reef (-16.845°, 146.23°). The study was carried out over a six-year period at a large reef pass on the oceanic margin of the northern Great Barrier Reef. Over this period (February 2006 -December 2012) tidal state, moon phase and surface seawater temperature were monitored. The timing of sampling was organised to assess variation in physical environment at daily, monthly, seasonal and annual time scales. Over these time scales, temporal patterns of occurrence of 10 species of coral reef fish from 5 families representing 5 defined trophic groups were monitored. The study incorporated 1,357 underwater visual census counts involving 402,370 fish and these estimates were collated with data on tidal state, water temperature, lunar and seasonal periodicity. Aggregated boosted regression trees analysed the univariate responses of fish abundance and species richness to the variation in the physical environment of the reef pass. Flood tides or when water flows from open water through the pass and into the Moore Reef lagoon had 2.3 times as many fish and 1.75 times as many species compared to counts made on ebb tides. Fish abundance was highest in late winter and spring months (Austral calendar), but notably when water temperatures were below the long-term mean of 27°C. Multivariate regression trees and Dufrêne-Legendre indicator predicted 4 out of 10 times the occurrence of all 10 species at any temporal scale ranging from hours to years. Flood tides were the principle driver underlying the occurrence of all 10 species regardless of their trophic classification and produced distinct seasonal assemblages, indicative of fishes aggregating to forage and reproduce.

Comprehensive inventory of true flies (Diptera) at a tropical site.

Estimations of tropical insect diversity generally suffer from lack of known groups or faunas against which extrapolations can be made, and have seriously underestimated the diversity of some taxa. Here we report the intensive inventory of a four-hectare tropical cloud forest in Costa Rica for one year, which yielded 4332 species of Diptera, providing the first verifiable basis for diversity of a major group of insects at a single site in the tropics. In total 73 families were present, all of which were studied to the species level, providing potentially complete coverage of all families of the order likely to be present at the site. Even so, extrapolations based on our data indicate that with further sampling, the actual total for the site could be closer to 8000 species. Efforts to completely sample a site, although resource-intensive and time-consuming, are needed to better ground estimations of world biodiversity based on limited sampling.

Remarkable fly (Diptera) diversity in a patch of Costa Rican cloud forest: Why inventory is a vital science.

Study of all flies (Diptera) collected for one year from a four-hectare (150 x 266 meter) patch of cloud forest at 1,600 meters above sea level at Zurquí de Moravia, San José Province, Costa Rica (hereafter referred to as Zurquí), revealed an astounding 4,332 species. This amounts to more than half the number of named species of flies for all of Central America. Specimens were collected with two Malaise traps running continuously and with a wide array of supplementary collecting methods for three days of each month. All morphospecies from all 73 families recorded were fully curated by technicians before submission to an international team of 59 taxonomic experts for identification.        Overall, a Malaise trap on the forest edge captured 1,988 species or 51% of all collected dipteran taxa (other than of Phoridae, subsampled only from this and one other Malaise trap). A Malaise trap in the forest sampled 906 species. Of other sampling methods, the combination of four other Malaise traps and an intercept trap, aerial/hand collecting, 10 emergence traps, and four CDC light traps added the greatest number of species to our inventory. This complement of sampling methods was an effective combination for retrieving substantial numbers of species of Diptera. Comparison of select sampling methods (considering 3,487 species of non-phorid Diptera) provided further details regarding how many species were sampled by various methods.        Comparison of species numbers from each of two permanent Malaise traps from Zurquí with those of single Malaise traps at each of Tapantí and Las Alturas, 40 and 180 km distant from Zurquí respectively, suggested significant species turnover. Comparison of the greater number of species collected in all traps from Zurquí did not markedly change the degree of similarity between the three sites, although the actual number of species shared did increase.        Comparisons of the total number of named and unnamed species of Diptera from four hectares at Zurquí is equivalent to 51% of all flies named from Central America, greater than all the named fly fauna of Colombia, equivalent to 14% of named Neotropical species and equal to about 2.7% of all named Diptera worldwide. Clearly the number of species of Diptera in tropical regions has been severely underestimated and the actual number may surpass the number of species of Coleoptera.        Various published extrapolations from limited data to estimate total numbers of species of larger taxonomic categories (e.g., Hexapoda, Arthropoda, Eukaryota, etc.) are highly questionable, and certainly will remain uncertain until we have more exhaustive surveys of all and diverse taxa (like Diptera) from multiple tropical sites.        Morphological characterization of species in inventories provides identifications placed in the context of taxonomy, phylogeny, form, and ecology. DNA barcoding species is a valuable tool to estimate species numbers but used alone fails to provide a broader context for the species identified.

Hoarseness in Adults.

Hoarseness is a common presentation in primary care practices. Combined with other voice-related changes, it falls under the umbrella diagnosis of dysphonia. Hoarseness has a number of causes, ranging from simple inflammatory processes to less common psychiatric disorders to more serious systemic, neurologic, or cancerous conditions. Medication-induced hoarseness is common and should be considered. The initial evaluation begins with a targeted history and physical examination, while also looking for signs of potential systemic etiologies. Treatment should begin with voice rest, especially avoidance of whispering, and conservative management directed toward a presumptive cause. For example, proton pump inhibitors are appropriate for hoarseness due to reflux, and proper vocal hygiene is recommended for vocal abuse-related indications. In the absence of a clear indication, antibiotics, oral corticosteroids, and proton pump inhibitors should not be used for the empiric treatment of hoarseness. Direct visualization of the larynx and vocal folds, commonly mislabeled as vocal cords, should be performed within three months if an etiology has not been determined or if conservative management has been ineffective. Patients who experience symptoms lasting longer than two weeks and who have risk factors for dysplasia (e.g., tobacco use, heavy alcohol use, hemoptysis) may require earlier laryngoscopic evaluation. Voice therapy is effective for improving voice quality in patients with dysphonia if conservative measures are unsuccessful, and it can also be helpful for prophylaxis in high-risk individuals (e.g., vocalists, public speakers). Surgical management is indicated for laryngeal or vocal fold dysplasia or malignancy, airway obstruction, or benign pathology resistant to conservative treatment.

Change of name for the Oriental robber fly Nyssomyia Hull, 1962 (Diptera: Asilidae, Asilinae), nec Nyssomyia Barretto, 1962 (Diptera: Psychodidae, Phlebotominae).

A new name for the Oriental genus Nyssomyia Hull, 1962 (Diptera: Asilidae) is proposed. Homonymy exists between this Oriental robber fly genus and the more senior Neotropical phlebotomine sand fly genus Nyssomyia Barretto, 1962 (sensu Galati 2003) (Diptera: Psychodidae), and the following replacement name is proposed: Ekkentronomyia nom. nov. for Nyssomyia Hull (nec Barretto 1962). Accordingly, a new combination is herein proposed for the only species currently included in this genus: Ekkentronomyia ochracea (Hull, 1962) comb. nov.

Two new species of Martintella Artigas, 1996 (Diptera, Asilidae, Asilinae) from Costa Rica.

Two new species of Martintella Artigas, 1996, Martintella aurata sp. nov. and Martintella fernandoi sp. nov., from Costa Rica are described and illustrations of species of the genus are provided.

Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion.

Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein (LDL) in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation (ERAD) by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regulated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autophagy and postprandial activation of the unfolded protein response (UPR) may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.

Four new species of Oidardis Hermann, 1912 (Diptera, Asilidae, Laphriinae, Atomosiini) from two major faunistic surveys in the Atlantic Rainforest.

Two recent faunistic surveys in the Brazilian Atlantic Forests region, the PROFAUPAR and the Biota/FAPESP Program, have provided important material for the discovery of new taxa from Brazil. We describe herein four new species of robber-flies of the genus Oidardis (O. falcimystax sp. n., O. fontenellei sp. n., O. maculiseta sp. n. and O. marinonii sp. n.), including illustrations and details on male hypopygia and female genitalia. A distribution map and a key to the species of Oidardis from the Brazilian Atlantic Forests region, including O. triangularis (Hermann), 1912, are also provided.

Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor.

High throughput screening to identify inhibitors of the mTOR kinase revealed sulfonyl-morpholino-pyrimidine 1 as an attractive start point. The compound displayed good physicochemical properties and selectivity over related kinases such as PI3Kα. Library preparation of related analogs allowed the establishment of additional SAR understanding and in particular the requirement for a key hydrogen bond donor motif at the 4-position of the phenyl ring in compounds such as indole 19. Isosteric replacement of the indole functionality led to the identification of urea compounds such as 32 that show good levels of mTOR inhibition in both enzyme and cellular assays.

Vertex centralities in input-output networks reveal the structure of modern economies.

Input-output tables describe the flows of goods and services between the sectors of an economy. These tables can be interpreted as weighted directed networks. At the usual level of aggregation, they contain nodes with strong self-loops and are almost completely connected. We derive two measures of node centrality that are well suited for such networks. Both are based on random walks and have interpretations as the propagation of supply shocks through the economy. Random walk centrality reveals the vertices most immediately affected by a shock. Counting betweenness identifies the nodes where a shock lingers longest. The two measures differ in how they treat self-loops. We apply both to data from a wide set of countries and uncover salient characteristics of the structures of these national economies. We further validate our indices by clustering according to sectors' centralities. This analysis reveals geographical proximity and similar developmental status.

Ubiquitination regulates the assembly of VLDL in HepG2 cells and is the committing step of the apoB-100 ERAD pathway.

Apolipoprotein B-100 (apoB-100) is degraded by endoplasmic reticulum-associated degradation (ERAD) when lipid availability limits assembly of VLDLs. The ubiquitin ligase gp78 and the AAA-ATPase p97 have been implicated in the proteasomal degradation of apoB-100. To study the relationship between ERAD and VLDL assembly, we used small interfering RNA (siRNA) to reduce gp78 expression in HepG2 cells. Reduction of gp78 decreased apoB-100 ubiquitination and cytosolic apoB-ubiquitin conjugates. Radiolabeling studies revealed that gp78 knockdown increased secretion of newly synthesized apoB-100 and, unexpectedly, enhanced VLDL assembly, as the shift in apoB-100 density in gp78-reduced cells was accompanied by increased triacylglycerol (TG) secretion. To explore the mechanisms by which gp78 reduction might enhance VLDL assembly, we compared the effects of gp78 knockdown with those of U0126, a mitogen-activated protein kinase/ERK kinase1/2 inhibitor that enhances apoB-100 secretion in HepG2 cells. U0126 treatment increased secretion of both apoB100 and TG and decreased the ubiquitination and cellular accumu-lation of apoB-100. Furthermore, p97 knockdown caused apoB-100 to accumulate in the cell, but if gp78 was concomitantly reduced or assembly was enhanced by U0126 treatment, cellular apoB-100 returned toward baseline. This indicates that ubiquitination commits apoB-100 to p97-mediated retrotranslocation during ERAD. Thus, decreasing ubiquitination of apoB-100 enhances VLDL assembly, whereas improving apoB-100 lipidation decreases its ubiquitination, suggesting that ubiquitination has a regulatory role in VLDL assembly.

Imidazoles: SAR and development of a potent class of cyclin-dependent kinase inhibitors.

An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been developed. Protein inhibitor structure determination has provided an understanding of the emerging structure activity trends for the imidazole series. The introduction of a methyl sulfone at the aniline terminus led to a more orally bioavailable CDK inhibitor that was progressed into clinical development.

Imidazole piperazines: SAR and development of a potent class of cyclin-dependent kinase inhibitors with a novel binding mode.

A piperazine series of cyclin-dependent kinase (CDK) inhibitors have been identified. The compounds exhibit excellent physiochemical properties and a novel binding mode, whereby a bridging interaction via a water molecule with Asp 86 of CDK2, leads to selectivity for the CDK family of enzymes over other kinases. Piperazines 2e and 2i were subsequently shown to inhibit tumour growth when dosed orally in a nude mouse xenograft study. Additional chemical series that exploit this unexpected interaction with Asp 86 are also described.

The AAA-ATPase p97 facilitates degradation of apolipoprotein B by the ubiquitin-proteasome pathway.

The ATPase associated with various cellular activities (AAA-ATPase) p97 (p97) has been implicated in the retrotranslocation of target proteins for delivery to the cytosolic proteasome during endoplasmic reticulum-associated degradation (ERAD). Apolipoprotein B-100 (apoB-100) is an ERAD substrate in liver cells, including the human hepatoma, HepG2. We studied the potential role of p97 in the ERAD of apoB-100 in HepG2 cells using cell permeabilization, coimmunoprecipitation, and gene silencing. Degradation was abolished when HepG2 cytosol was removed by digitonin permeabilization, and treatment of intact cells with the proteasome inhibitor MG132 caused accumulation of ubiquitinated apoB protein in the cytosol. Cross-linking of intact cells with the thiol-cleavable agent dithiobis(succinimidylpropionate) (DSP), as well as nondenaturing immunoprecipitation, demonstrated an interaction between p97 and intracellular apoB. Small interfering ribonucleic acid (siRNA)-mediated reduction of p97 protein increased the intracellular levels of newly synthesized apoB-100, predominantly because of a decrease in the turnover of newly synthesized apoB-100 protein. However, although the posttranslational degradation of newly synthesized apoB-100 was delayed by p97 knockdown, secretion of apoB-100 was not affected. Knockdown of p97 also impaired the release of apoB-100 and polyubiquitinated apoB into the cytosol. In summary, our results suggest that retrotranslocation and proteasomal degradation of apoB-100 can be dissociated in HepG2 cells, and that the AAA-ATPase p97 is involved in the removal of full-length apoB from the biosynthetic pathway to the cytosolic proteasome.

Missense mutations in APOB within the betaalpha1 domain of human APOB-100 result in impaired secretion of ApoB and ApoB-containing lipoproteins in familial hypobetalipoproteinemia.

Familial hypobetalipoproteinemia (FHBL) is associated with mutations in the APOB gene. We reported the first missense APOB mutation, R463W, in an FHBL kindred (Burnett, J. R., Shan, J., Miskie, B. A., Whitfield, A. J., Yuan, J., Tran, K., Mc-Knight, C. J., Hegele, R. A., and Yao, Z. (2003) J. Biol. Chem. 278, 13442-13452). Here we identified a second nonsynonymous APOB mutation, L343V, in another FHBL kindred. Heterozygotes for L343V (n = 10) had a mean plasma apoB at 0.31 g/liter as compared with 0.80 g/liter in unaffected family members (n = 22). The L343V mutation impaired secretion of apoB-100 and very low density lipoproteins. The secretion efficiency was 20% for B100wt and 10% for B100LV and B100RW. Decreased secretion of mutant apoB-100 was associated with increased endoplasmic reticulum retention and increased binding to microsomal triglyceride transfer protein and BiP. Reduced secretion efficiency was also observed with B48LV and B17LV. Biochemical and biophysical analyses of apoB domain constructs showed that L343V and R463W altered folding of the alpha-helical domain within the N terminus of apoB. Thus, proper folding of the alpha-helical domain of apoB-100 is essential for efficient secretion.