Benzothiophene Carboxamide Derivatives as Novel Antimalarials

Bromo-benzothiophene carboxamide derivatives have been shown in the preceding article to inhibit Plasmodium falciparum Enoyl-ACP reductase. Here, we report bromo-benzothiophene carboxamide derivatives as potent inhibitors of Plasmodium asexual blood-stages in vitro as well as in vivo in the mouse model. These compounds specifically impair the development of metabolically active trophozoite stage of intraerythrocytic cycle and the intravenous administration of 3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide (compound 6) enhances the longevity of P. berghei infected mice by 2 weeks compared to disease control animals thereby preventing the onset of ataxia and convulsions in treated mice. These compounds thus hold promise for the development of potent antimalarials.(C) 2011 IUBMB IUBMB Life, 63(12): 1111-1115, 2011

Skeletal Muscle Degeneration and Regeneration in Mice and Flies

Many aspects of skeletal muscle biology are remarkably similar between mammals and tiny insects, and experimental models of mice and flies (Drosophila) provide powerful tools to understand factors controlling the growth, maintenance, degeneration (atrophy and necrosis), and regeneration of normal and diseased muscles, with potential applications to the human condition. This review compares the limb muscles of mice and the indirect flight muscles of flies, with respect to the mechanisms of adult myofiber formation, homeostasis, atrophy, hypertrophy, and the response to muscle degeneration, with some comment on myogenic precursor cells and common gene regulatory pathways. There is a striking similarity between the species for events related to muscle atrophy and hypertrophy, without contribution of any myoblast fusion. Since the flight muscles of adult flies lack a population of reserve myogenic cells (equivalent to satellite cells), this indicates that such cells are not required for maintenance of normal muscle function. However, since satellite cells are essential in postnatal mammals for myogenesis and regeneration in response to myofiber necrosis, the extent to which such regeneration might be possible in flight muscles of adult flies remains unclear. Common cellular and molecular pathways for both species are outlined related to neuromuscular disorders and to age-related loss of skeletal muscle mass and function (sarcopenia). The commonality of events related to skeletal muscles in these disparate species (with vast differences in size, growth duration, longevity, and muscle activities) emphasizes the combined value and power of these experimental animal models.

Parasites exert conflicting selection pressures to affect reproductive asynchrony of their host plant in an obligate pollination mutualism

1. Plant reproductive phenology is generally viewed as an individual's strategy to maximize gamete exchange and propagule dispersal and is often considered largely dependent on patterns of floral initiation. Reproductive phenology, however, can be affected by proximate responses to pollinators, parasites and herbivores which could influence floral longevity or fruit development time. 2. We examined the influence of insect interactants on within-plant reproductive phenology in the fig-fig wasp nursery pollination mutualism in Ficus racemosa (Moraceae). Most figs support a wasp community comprised of a mutualistic pollinator, with several host-plant-specific non-pollinating herbivorous gallers and parasitoids. These wasps reproduce within enclosed inflorescences called syconia, which develop into fruit after pollination. While different wasp species oviposit into syconia at varying times during its ontogeny, all wasp progeny are constrained to exit syconia simultaneously just prior to fruit ripening. Developing larvae of early-ovipositing wasps may hasten syconium ontogeny through formation of earlier and larger nutrient sinks, whereas larvae of late-arriving parasites may lengthen syconium ontogeny to complete their development successfully. Seeds are also important nutrient sinks. The number of seeds and the type and number of developing wasps may therefore be expected to influence syconium development times, thereby affecting the reproductive synchrony of syconia on a plant. 3. Observations on naturally pollinated and parasitized syconia indicated that their seed and wasp content affected syconium development time. Experimental manipulations of syconia to produce only seeds or various combinations of wasps confirmed this finding. Early-ovipositing galler progeny reduced syconium development times, while gallers ovipositing concurrently with pollinators had no effect on syconium development. Late-ovipositing parasitoid progeny, the presence of only seeds within the syconium, or delayed pollination increased syconium development time. The differential development of syconia, which was influenced by mutualistic or parasitic progeny, accordingly contributed to within-tree reproductive asynchrony. 4. Synthesis. Individual reproductive units in fig trees called syconia, which also function as brood sites for pollinating and parasitic fig wasps, have plastic development durations dependent on pollination timing and species of wasps developing within them. Syconium development times are a likely compromise between conflicting demands from developing seeds and different wasp species.

Skeletal Muscle Degeneration and Regeneration in Mice and Flies

Many aspects of skeletal muscle biology are remarkably similar between mammals and tiny insects, and experimental models of mice and flies (Drosophila) provide powerful tools to understand factors controlling the growth, maintenance, degeneration (atrophy and necrosis), and regeneration of normal and diseased muscles, with potential applications to the human condition. This review compares the limb muscles of mice and the indirect flight muscles of flies, with respect to the mechanisms of adult myofiber formation, homeostasis, atrophy, hypertrophy, and the response to muscle degeneration, with some comment on myogenic precursor cells and common gene regulatory pathways. There is a striking similarity between the species for events related to muscle atrophy and hypertrophy, without contribution of any myoblast fusion. Since the flight muscles of adult flies lack a population of reserve myogenic cells (equivalent to satellite cells), this indicates that such cells are not required for maintenance of normal muscle function. However, since satellite cells are essential in postnatal mammals for myogenesis and regeneration in response to myofiber necrosis, the extent to which such regeneration might be possible in flight muscles of adult flies remains unclear. Common cellular and molecular pathways for both species are outlined related to neuromuscular disorders and to age-related loss of skeletal muscle mass and function (sarcopenia). The commonality of events related to skeletal muscles in these disparate species (with vast differences in size, growth duration, longevity, and muscle activities) emphasizes the combined value and power of these experimental animal models.

Modeling Ultrasonic NDE and Guided Wave based Structural Health Monitoring

Structural Health Monitoring (SHM) systems require integration of non-destructive technologies into structural design and operational processes. Modeling and simulation of complex NDE inspection processes are important aspects in the development and deployment of SHM technologies. Ray tracing techniques are vital simulation tools to visualize the wave path inside a material. These techniques also help in optimizing the location of transducers and their orientation with respect to the zone of interrogation. It helps in increasing the chances of detection and identification of a flaw in that zone. While current state-of-the-art techniques such as ray tracing based on geometric principle help in such visualization, other information such as signal losses due to spherical or cylindrical shape of wave front are rarely taken into consideration. The problem becomes a little more complicated in the case of dispersive guided wave propagation and near-field defect scattering. We review the existing models and tools to perform ultrasonic NDE simulation in structural components. As an initial step, we develop a ray-tracing approach, where phase and spectral information are preserved. This enables one to study wave scattering beyond simple time of flight calculation of rays. Challenges in terms of theory and modelling of defects of various kinds are discussed. Various additional considerations such as signal decay and physics of scattering are reviewed and challenges involved in realistic computational implementation are discussed. Potential application of this approach to SHM system design is highlighted and by applying this to complex structural components such as airframe structures, SHM is demonstrated to provide additional value in terms of lighter weight and/or longevity enhancement resulting from an extension of the damage tolerance design principle not compromising safety and reliability.

Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.

Assessment of cobia, Rachycentron canadum, in the waters of the U.S. Gulf of Mexico

This assessment applies to cobia (Rachycentron canadum) located in the territorial waters of the U.S. Gulf of Mexico. Separation of the Gulf of Mexico and Atlantic Ocean is defined by the seaward extension of the Dade/Monroe county line in south Florida. Mixing of fish between the Atlantic and Gulf of Mexico occurs in the Florida Keys during winter months. Cobia annually migrate north in early spring in the Gulf to spawning grounds in the northern Gulf of Mexico, returning to the Florida Keys by winter. Catches of cobia in the Gulf of Mexico are dominated by recreational landings, accounting for nearly 90% of the total. Since 1980, the landings of cobia in the recreational fishery have remained fairly stable at around 400-600 mt with a slight peak of 1,014 mt in 1997. The recreational fishery was estimated to have landed 471 mt in 2000. The landings from the commercial fishery have shown a steady increase from 45 mt in 1980 to a peak of 120 mt in 1994, followed by a decline to 62 mt in 2000. The previous assessment of cobia occurred in 1996 using a virtual population analysis (VPA) model. For this analysis a surplus-production model (ASPIC) and a forward-projecting, age-structured population model programmed in the AD Model Builder (ADMB) software were applied to cobia data from the Gulf of Mexico. The primary data consisted of four catch-per-unit-effort (CPUE) indices derived from the Marine Recreational Fisheries Statistics Survey (MRFSS) (1981-1999), Southeast region headboat survey (1986-1999), Texas creel survey (1983-1999), and shrimp bycatch estimates (1980-1999). Length samples were available from the commercial (1983-2000) and recreational (1981-2000) fisheries. The ASPIC model applied to the cobia data provided unsatisfactory results. The ADMB model fit described the observed length composition data and fishery landings fairly well based on graphical examination of model residuals. The CPUE indices indicated some disagreement for various years, but the model fit an overall increasing trend from 1992-1997 for the MRFSS, headboat, and Texas creel indices. The shrimp bycatch CPUE was treated as a recruitment index in the model. The fit to these data followed an upward trend in recruitment from 1988-1997, but did not fit the 1994-1997 data points very well. This was likely the result of conflicting information from other data sources. Natural mortality (M) for cobia is unknown. As a result, a range of values for M from 0.2-0.4, based on longevity and growth parameters, were selected for use in the age-structured model. The choice of natural mortality appears to greatly influence the perceived status of the population. Population status as measured by spawning stock biomass in the last year relative to the value at maximum sustainable yield (SSB2000/SSBMSY), spawning stock biomass in the last year relative to virgin spawning stock biomass (SSB2000/S0), and static spawning stock biomass per recruit (SSBR) all indicate the population is either depleted, near MSY, or well above MSY depending on the choice of M. The variance estimates for these benchmarks are very large and in most cases ranges from depleted to very healthy status. The only statement that can be made with any degree of certainty about cobia in the Gulf of Mexico is that the population has increased since the 1980s. (PDF contains 61 pages)

Some aspects of the ecology of the leatherback turtle Dermochelys coriacea at Laguna Jalova, Costa Rica

The ecology and reproductive biology of the leatherback turtle (Dennochelys coriacea) was studied on a high-energy nesting beach near Laguna Jalova, Costa Rica, between 28 March and 8 June 1985. The peak of nesting was between 15 April and 21 May. Leatherbacks here measured an average 146.6 cm straightline standard carapace length and laid an average 81.57 eggs. The eggs measured a mean 52.12 mm diameter and weighed an average of 85.01 g. Significant positive relationships were found between the carapace lengths of nesters and their clutch sizes and average diameter and weight of eggs. The total clutch weighed between 4.02 and 13.39 kg, and yolkless eggs accounted for an average 12.4% of this weight. The majority of nesters dug shallow (<24 cm) body pits and spent an average 81 minutes at the nest site. A significant number of c1utcbes were laid below the berm crest. In a hatchery 42.2% of the eggs hatched, while in natural nests 70.2% hatched. The average hatchling carapace length was 59.8 mm and weight was 44.6 g. The longevity of leatherback tracks and nests on the beach was affected by weather. One nester was recaptured about one year later off the coast of Mississippi, U.S.A. Egg poaching was intense on some sections of the Costa Rican coast. Four aerial surveys in four different months provided the basis for comparing density of nesting on seven sectors of the Caribbean coast of Costa Rica. The beach at Jalova is heavily used by green turtles (Chelonia mydJJs) after the leatherback nesting season. The role of the Parque Nacional Tortuguero in conserving the leatherback and green turtle is discussed.(PDF file contains 20 pages.)

Age and growth of Mugil cephalus (Linnaeus, 1758) (Perciformes: Mugilidae) in Bonny Estuary

The age and growth of Mugil cephalus was investigated in Bonny Estuary, Nigeria, from January, 1995 to December, 1996. Length-weight relationships were isometric with length exponents of 2.84 (males), 2.90 (females) and 2.88 (overall). Modal length at age were 12.0cm, 20.9cm, 25.0cm, 28.4cm and 30.2cm TL for ages 0+, 1+, 2+, 3+ and 4+ respectively. Corresponding total weights were 20.01g, 78.93g, 173.12g, 217.61g and 247.50g, respectively. Asymptotic length (Lo) was estimated 33.2cm TL, asymptotic weight (W sub(o)) was 484g, growth coefficient K=0.55847 super(-1) and hypothetical age at zero length To = 0.152yr. Longevity, Tmax, was 5.0yr, length and weight growth performance indices were Q super(1)=2.79 and Q = 1.44, respectively. Total mortality, natural mortality and fishing mortality were z = 1.02yr super(-1), M=0.607yr super(-1) and F=O. 3129yr super(-1), respectively. The exploitation ratio E was 0.4048 and exploitation rate U = 0.2302yr super(-1)

Using space geodesy to constrain variations in seismogenic behavior on subduction megathrusts

The concept of seismogenic asperities and aseismic barriers has become a useful paradigm within which to understand the seismogenic behavior of major faults. Since asperities and barriers can be thought of as defining the potential rupture area of large megathrust earthquakes, it is thus important to identify their respective spatial extents, constrain their temporal longevity, and to develop a physical understanding for their behavior. Space geodesy is making critical contributions to the identification of slip asperities and barriers but progress in many geographical regions depends on improving the accuracy and precision of the basic measurements. This thesis begins with technical developments aimed at improving satellite radar interferometric measurements of ground deformation whereby we introduce an empirical correction algorithm for unwanted effects due to interferometric path delays that are due to spatially and temporally variable radar wave propagation speeds in the atmosphere. In chapter 2, I combine geodetic datasets with complementary spatio-temporal resolutions to improve our understanding of the spatial distribution of crustal deformation sources and their associated temporal evolution – here we use observations from Long Valley Caldera (California) as our test bed. In the third chapter I apply the tools developed in the first two chapters to analyze postseismic deformation associated with the 2010 Mw=8.8 Maule (Chile) earthquake. The result delimits patches where afterslip occurs, explores their relationship to coseismic rupture, quantifies frictional properties associated with inferred patches of afterslip, and discusses the relationship of asperities and barriers to long-term topography. The final chapter investigates interseismic deformation of the eastern Makran subduction zone by using satellite radar interferometry only, and demonstrates that with state-of-art techniques it is possible to quantify tectonic signals with small amplitude and long wavelength. Portions of the eastern Makran for which we estimate low fault coupling correspond to areas where bathymetric features on the downgoing plate are presently subducting, whereas the region of the 1945 M=8.1 earthquake appears to be more highly coupled.

Acumulação de compostos organoclorados (PCBs, DDTs e HCB) em tecido hepático de delfinídeos (Cetacea, Mammalia) do Estado do Rio de Janeiro

No decorrer das últimas décadas a pesquisa relacionada à contaminação de organismos marinhos por compostos organoclorados (OCs) se intensificou aliada à utilização de algumas espécies como sentinelas da qualidade ambiental quanto aos poluentes orgânicos. Dentre essas espécies, podem-se destacar os cetáceos, animais que entre outras características possuem grande longevidade, alta porcentagem lipídica em seus tecidos e são predadores de topo de cadeia trófica, tendendo assim a acumular altos níveis de OCs em seus tecidos. O presente estudo teve por objetivo determinar as concentrações de OCs de origem industrial e agrícola (PCBs, HCB e DDTs) em tecido hepático de oito diferentes espécies de cetáceos delfinídeos pertencentes a três distintas áreas oceânicas do Estado do Rio de Janeiro, são elas a região costeira, a plataforma continental e a região oceânica. A determinação foi realizada em cromatógrafo a gás (GC - Agilent 6890) conectado a um espectrômetro de massa (MS - Agilent 5973). Os valores de DDTs (1263617272 ng.g -1 lip.) e PCBs (7648877288 ng.g -1 lip.) aqui encontrados estão entre os mais altos já reportados para o táxon. Em todas as áreas observou-se uma predominância do ΣPCB, seguida do ΣDDT e HCB, em níveis que refletem o caráter fortemente industrial da região analisada. Entre os PCBs, a maior contribuição advém dos hexabifenis, seguida dos hepta e pentabifenis, sendo os congêneres 153, 138 e 180 os principais em todas as áreas. A razão p,pDDE/ΣDp,pDDT foi alta em todas as regiões (0,9), refletindo um input antigo do poluente na área. Foram realizadas correlações entre as concentrações de OCs e os parâmetros biológicos das espécies, como idade, sexo e comprimento total. A transferência placentária de OCs foi analisada em dois pares de fêmea-feto de Sotalia guianensis, mostrando uma maior transferência dos compostos com menor log Kow. Como esperado, foi encontrada uma diferença significativa no perfil de contaminação entre as espécies das diferentes regiões, relacionada à proximidade da fonte, características espécie-específicas e ao arranjo trófico das espécies.

The bullhead Cottus gobio , a versatile and successful fish

A series of studies on the ecology of the bullhead, Cottus gobio is described. Habitat choice, growth rate and longevity, population density, biomass and production, reproduction, life history and feeding is compared at 8 sites in England and 1 site in Wales. Evidence suggests that in Cottus gobio the prevailing environmental conditions result in considerable modifications in longevity, growth rate and egg production. It also indicates that the advantages of fast growth and high reproductive effort in favourable habitats are offset, at least partially by increases in mortality.

Uso do espaço do marsupial Caluromys philander (Didelphimorphia, Didelphidae) no Parque Nacional da Serra dos Órgãos - Rio de Janeiro, Brasil

Uso do espaço é um padrão bem estudado em ecologia. Entretanto, formação de área de vida e posição relativa dos abrigos com área de uso são pouco estudados, principalmente para marsupiais didelfídeos. Dentre estes animais, podemos destacar Caluromys philander, devido ao seu baixo registro em armadilhas na Mata Atlântica e características peculiares dentro do grupo, como seu desenvolvimento, longevidade e hábito alimentar. Neste estudo foram investigadas as formações das áreas de uso destes animais através da comparação com seus movimentos diários, e a posição dos seus abrigos dentro das suas áreas de uso. Para isso foram monitorados seis indivíduos de C. philander através de colares rádio transmissores. Estes indivíduos se deslocaram em média 534 153 m por noite. Além disso, apresentaram área diária de 9548 3591 m e área de vida de 2,8 0,4 ha. Noventa e sete por cento das áreas diárias apresentaram sobreposição entre si, com média de 19,4% de sobreposição. Não houve diferença nos locais dos abrigos dos indivíduos monitorados, dentro dos seus Mínimos Polígonos Convexos. Entretanto, estes mesmos abrigos não estiveram localizados nas áreas de maior intensidade de uso. A média de abrigos utilizados por indivíduo foi de 6,3 (3-10) com utilização média de 2,9 (1-17) vezes em cada abrigo, sendo que 48% das vezes os animais só possuíram um registro em cada abrigo, demonstrando baixa fidelidade. Entretanto, dois indivíduos apresentaram diferença de utilização entre seus abrigos, com três destes sendo mais utilizados que os outros. O trabalho sugere que os indivíduos de C. philander monitorados apresentam área de vida propriamente dita (restrita), onde ocorrem as sobreposições entre suas áreas diárias. C. philander utilizam mais de um abrigo em suas vidas, trocando com frequência de abrigos, apesar de alguns destes abrigos poderem ser mais utilizados que outros. Além disso, os abrigos destes animais não são localizados nas suas áreas de maior intensidade de uso.

The effects of stress on benthic algal communities

The effects of stress on both microalgal and macroalgal communities are considered. On one hand the contrasting approaches of studies of these two communities reflect intrinsic differences in plant size, longevity and ease of handling. On the other hand they reveal that biological monitoring of the potentially deleterious effects of man's activities has focused largely on freshwater environments in which macroalgae only occasionally dominate. Large conspicuous plants can be readily investigated as individuals, whereas it is virtually impossible to trace effects of stress on an individual cell of a vegetatively-reproducing microalga; a population approach is almost inevitably necessary. However, rapid turnover rates, a spectrum of ecological characteristics distributed between many taxa, and the potential for statistical analysis, have facilitated the use of microalgae in environmental impact studies. Failure to extend such investigations into marine systems rests as much on man's ability to ignore environmental deterioration until it affects his quality of life as on the visual dominance of seaweeds around our coasts. However, large gaps remain in our knowledge of both large and small algae; some reported community changes over time are suspect, and the causes of even blatant changes are not always apparent.

From the individual to the community and beyond: water quality, stress indicators and key species in coastal waters

This review examines water quality and stress indicators at levels of organisation from the individual to the community and beyond by means of three case studies concentrating on rocky shores within the north-east Atlantic. Responses of dogwhelks (Nucella) to tributyltin pollution from antifouling paints is examined as the main case study. There are effects at the individual level (development of male sexual characteristics in the female leading to effective sterility) and population level (reduction in juveniles, few females and eventual population disappearance of dogwhelks in badly contaminated areas) but information on community level effects of dogwhelk demise is sparse. Such effects were simulated by dogwhelk removal experiments on well studied, moderately exposed ledges on shores on the Isle of Man. The removal of dogwhelks reduced the size and longevity of newly established Fucus clumps that had escaped grazing. Removal of dogwhelks also increased the likelihood of algal escapes. In a factorial experiment dogwhelks were shown to be less important than limpets \{Patella) in structuring communities but still had a significant modifying effect by increasing the probability of algal escapes. Community level responses to stress on rocky shores are then explored by reference to catastrophic impacts such as oil spills, using the Torrey Canyon as a case study. Recovery of the system in response to this major perturbation took between 10-15 years through a series of damped oscillations. The final case study is that of indicators of ecosystem level change in response to climate fluctuations, using ratios of northern \{Semibalanus balanoides) and southern (Chthamalus spp.) barnacles. Indices derived from counts on the shore show good correlations with inshore sea-water temperatures after a 2-year lag phase. The use of barnacles to measure offshore changes is reviewed. The discussion considers the use of bioindicators at various levels of organisation.