Evolution of sexual segregation in mammalian herbivores: kangaroos as marsupial models

Sexual segregation is best known in sexually dimorphic ungulates. Many hypotheses have been proposed to explain the evolution of sexual segregation in ungulates, but all are reducible to the influence of two factors: body size and sex-specific reproductive strategy. Definitive tests of these hypotheses are lacking in ungulates because these factors are confounded, all males being somewhat larger than females. Kangaroos represent a parallel radiation of terrestrial herbivores, but their populations are composed of a spectrum of adult body sizes, ranging from small males the same size as females to large males more than twice the size. We exploited this heteromorphism to assess the independent influences of size and sex in these ungulate analogues. We conducted a preliminary study of western grey kangaroos (Macropus fuliginosus) in north-western Victoria, Australia. Adult males predominately occupied grassland habitat, whereas females occurred mostly in lakebed, woodland and shrubland. Single-sex groups occurred more often than expected during the non-mating season. The diet of large males had the highest proportion of grass, and females had the least. These initial results indicate that both size and sex influence segregation in this species, confirming the worth of kangaroos as marsupial models for research into the evolution of sexual segregation.

Soluble NSF attachment protein receptor molecular mimicry by a Legionella pneumophila Dot/Icm effector

Upon infection, Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate effector proteins from the Legionella-containing vacuole (LCV) into the host cell cytoplasm. The effectors target a wide array of host cellular processes that aid LCV biogenesis, including the manipulation of membrane trafficking. In this study, we used a hidden Markov model screen to identify two novel, non-eukaryotic soluble NSF attachment protein receptor (SNARE) homologs: the bacterial Legionella SNARE effector A (LseA) and viral SNARE homolog A proteins. We characterized LseA as a Dot/Icm effector of L. pneumophila, which has close homology to the Qc-SNARE subfamily. The lseA gene was present in multiple sequenced L. pneumophila strains including Corby and was well distributed among L. pneumophila clinical and environmental isolates. Employing a variety of biochemical, cell biological and microbiological techniques, we found that farnesylated LseA localized to membranes associated with the Golgi complex in mammalian cells and LseA interacted with a subset of Qa-, Qb- and R-SNAREs in host cells. Our results suggested that LseA acts as a SNARE protein and has the potential to regulate or mediate membrane fusion events in Golgi-associated pathways.

Mechanistic details of the membrane perforation and passive translocation of TAT peptides

The trans-activator of transcription (TAT) peptide is regarded as the “gold standard” for cell-penetrating peptides, capable of traversing a mammalian membrane passively into the cytosolic space. This characteristic has been exploited through conjugation of TAT for applications such as drug delivery. However, the process by which TAT achieves membrane penetration remains ambiguous and unresolved. Mechanistic details of TAT peptide action are revealed herein by using three complementary methods: quartz crystal microbalance with dissipation (QCM-D), scanning electrochemical microscopy (SECM) and atomic force microscopy (AFM). When combined, these three scales of measurement define that the membrane uptake of the TAT peptide is by trans-membrane insertion using a “worm-hole” pore that leads to ion permeability across the membrane layer. AFM data provided nanometre-scale visualisation of TAT punctuation using a mammalian-mimetic membrane bilayer. The TAT peptide does not show the same specificity towards a bacterial mimetic membrane and QCM-D and SECM showed that the TAT peptide demonstrates a disruptive action towards these membranes. This investigation supports the energy-independent uptake of the cationic TAT peptide and provides empirical data that clarify the mechanism by which the TAT peptide achieves its membrane activity. The novel use of these three biophysical techniques provides valuable insight into the mechanism for TAT peptide translocation, which is essential for improvements in the cellular delivery of TAT-conjugated cargoes including therapeutic agents required to target specific intracellular locations.

The Why, What, and How of Global Biodiversity Indicators Beyond the 2010 Target

The 2010 biodiversity target agreed by signatories to the Convention on Biological Diversity directed the attention of conservation professionals toward the development of indicators with which to measure changes in biological diversity at the global scale. We considered why global biodiversity indicators are needed, what characteristics successful global indicators have, and how existing indicators perform. Because monitoring could absorb a large proportion of funds available for conservation, we believe indicators should be linked explicitly to monitoring objectives and decisions about which monitoring schemes deserve funding should be informed by predictions of the value of such schemes to decision making. We suggest that raising awareness among the public and policy makers, auditing management actions, and informing policy choices are the most important global monitoring objectives. Using four well-developed indicators of biological diversity (extent of forests, coverage of protected areas, Living Planet Index, Red List Index) as examples, we analyzed the characteristics needed for indicators to meet these objectives. We recommend that conservation professionals improve on existing indicators by eliminating spatial biases in data availability, fill gaps in information about ecosystems other than forests, and improve understanding of the way indicators respond to policy changes. Monitoring is not an end in itself, and we believe it is vital that the ultimate objectives of global monitoring of biological diversity inform development of new indicators. ©2010 Society for Conservation Biology.

A Mammalian Circadian Clock Model Incorporating Daytime Expression Elements

Models of the mammalian clock have traditionally been based around two feedback loops-the self-repression of Per/Cry by interfering with activation by BMAL/CLOCK, and the repression of Bmal/Clock by the REV-ERB proteins. Recent experimental evidence suggests that the D-box, a transcription factor binding site associated with daytime expression, plays a larger role in clock function than has previously been understood. We present a simplified clock model that highlights the role of the D-box and illustrate an approach for finding maximum-entropy ensembles of model parameters, given experimentally imposed constraints. Parameter variability can be mitigated using prior probability distributions derived from genome-wide studies of cellular kinetics. Our model reproduces predictions concerning the dual regulation of Cry1 by the D-box and Rev-ErbA/ROR response element (RRE) promoter elements and allows for ensemble-based predictions of phase response curves (PRCs). Nonphotic signals such as Neuropeptide Y (NPY) may act by promoting Cry1 expression, whereas photic signals likely act by stimulating expression from the E/E' box. Ensemble generation with parameter probability restraints reveals more about a model's behavior than a single optimal parameter set.

Microtubulin binding sites as target for developing anticancer agents

Microtubules (MTs) play important and diverse roles in eukaryotic cells. Their function and biophysical properties have made α−and β−tubulin, the main components of MTs, the subject of intense study. Interfering with normal MT dynamics, for example, by the addition of tubulin ligands, can cause the cell great distress and affect MT stability and functions, including mitosis, cell motion and intracellular organelle transport. It has been shown in the literature that tubulin is an important target molecule for developing anticancer drugs. Tubulin binding molecules have generated considerable interest after the successful introduction of the taxanes into clinical oncology and the widespread use of the vinca alkaloids vincristine and vinblastine. These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization into the MTs. This mode of action is also shared with other natural agents eg colchicine and podophyllotoxin. However various tubulin isotypes have shown resistance to taxanes and other MT agents. Therefore, there is a strong need to design and develop new natural analogs as antimitotic agents to interact with tubulin at sites different from those of vinca alkaloids and taxanes. This minireview provides SAR on several classes of antimitotic agents reported in the literature. The structures and data given are essential to the scientists who are involved in drug design and development in the field of anticancer drugs.

In the Solanaceae, a hierarchy of bHLHs confer distinct target specificity to the anthocyanin regulatory complex

The anthocyanin biosynthetic pathway is regulated by a transcription factor complex consisting of an R2R3 MYB, a bHLH, and a WD40. Although R2R3 MYBs belonging to the anthocyanin-activating class have been identified in many plants, and their role well elucidated, the subgroups of bHLH implicated in anthocyanin regulation seem to be more complex. It is not clear whether these potential bHLH partners are biologically interchangeable with redundant functions, or even if heterodimers are involved. In this study, AcMYB110, an R2R3 MYB isolated from kiwifruit (Actinidia sp.) showing a strong activation of the anthocyanin pathway in tobacco (Nicotiana tabacum) was used to examine the function of interacting endogenous bHLH partners. Constitutive expression of AcMYB110 in tobacco leaves revealed different roles for two bHLHs, NtAN1 and NtJAF13. A hierarchical mechanism is shown to control the regulation of transcription factors and consequently of the anthocyanin biosynthetic pathway. Here, a model is proposed for the regulation of the anthocyanin pathway in Solanaceous plants in which AN1 is directly involved in the activation of the biosynthetic genes, whereas JAF13 is involved in the regulation of AN1 transcription.

Room-temperature tilted-target sputtering deposition of highly transparent and low sheet resistance Al doped ZnO electrodes

Target-tilted room temperature sputtering of aluminium doped zinc oxide (AZO) provides transparent conducting electrodes with sheet resistances of <10 Ω □-1 and average transmittance in the visible region of up to 84%. The properties of the AZO electrode are found to be strongly dependent on the target-tilting angle and film thickness. The AZO electrodes showed comparable performance to commercial indium tin oxide (ITO) electrodes in organic photovoltaic (OPV) devices. OPV devices containing a bulk heterojunction active layer comprised of poly(3-n-hexylthiophene) (P3HT):phenyl-C61-butyric acid methyl ester (PCBM) and an AZO transparent conducting electrode had a power conversion efficiency (PCE) of up to 2.5% with those containing ITO giving a PCE of 2.6%. These results demonstrate that AZO films are a good alternative to ITO for transparent conducting electrodes.

Target acquired: Progress and promise of targeted therapeutics in the treatment of prostate cancer

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient’s disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

Studies on the target conditioning for deposition of $LiCoO_{2}$ films

Deposition of good quality thin films of Lithium Cobalt Oxide (LiCoO2), by sputtering is preceded by target conditioning, which dictates the surface composition, morphology and electrochemical performance of the deposited film. Sputtering from a Virgin target surface, results in films with excess of the more reactive elements. The concentration of these reactive elements in the films decreases until the system reaches a steady state after sufficient sputtering from the target. This paper discusses the deposition kinetics in terms of target conditioning of LiCoO2. The composition, morphology and texturing of deposited film during various hours of sputtering were analyzed using X-ray photoelectron Spectroscopy (XPS) and Field Emission Scanning electron microscopy (FESEM). The compositional stability is not observed in the films formed during the initial hours or Sputtering from the fresh target, which becomes stable after several hours of sputtering. The Li and Co concentration in the Films deposited subsequently is found to be varying and possible causes are discussed. After the compositional stability is reached, electrochemical analysis of LiCoO2 thin films was performed, which shows a discharge capacity of 129 mu Ah/cm(2).

targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis

Background: Tuberculosis still remains one of the largest killer infectious diseases, warranting the identification of newer targets and drugs. Identification and validation of appropriate targets for designing drugs are critical steps in drug discovery, which are at present major bottle-necks. A majority of drugs in current clinical use for many diseases have been designed without the knowledge of the targets, perhaps because standard methodologies to identify such targets in a high-throughput fashion do not really exist. With different kinds of 'omics' data that are now available, computational approaches can be powerful means of obtaining short-lists of possible targets for further experimental validation. Results: We report a comprehensive in silico target identification pipeline, targetTB, for Mycobacterium tuberculosis. The pipeline incorporates a network analysis of the protein-protein interactome, a flux balance analysis of the reactome, experimentally derived phenotype essentiality data, sequence analyses and a structural assessment of targetability, using novel algorithms recently developed by us. Using flux balance analysis and network analysis, proteins critical for survival of M. tuberculosis are first identified, followed by comparative genomics with the host, finally incorporating a novel structural analysis of the binding sites to assess the feasibility of a protein as a target. Further analyses include correlation with expression data and non-similarity to gut flora proteins as well as 'anti-targets' in the host, leading to the identification of 451 high-confidence targets. Through phylogenetic profiling against 228 pathogen genomes, shortlisted targets have been further explored to identify broad-spectrum antibiotic targets, while also identifying those specific to tuberculosis. Targets that address mycobacterial persistence and drug resistance mechanisms are also analysed. Conclusion: The pipeline developed provides rational schema for drug target identification that are likely to have high rates of success, which is expected to save enormous amounts of money, resources and time in the drug discovery process. A thorough comparison with previously suggested targets in the literature demonstrates the usefulness of the integrated approach used in our study, highlighting the importance of systems-level analyses in particular. The method has the potential to be used as a general strategy for target identification and validation and hence significantly impact most drug discovery programmes.

An Algorithm for Tracking a Maneuvering Target in Clutter

We consider the problem of tracking a maneuvering target in clutter. In such an environment, missed detections and false alarms make it impossible to decide, with certainty, the origin of received echoes. Processing radar returns in cluttered environments consists of three functions: 1) target detection and plot formation, 2) plot-to-track association, and 3) track updating. Two inadequacies of the present approaches are 1) Optimization of detection characteristics have not been considered and 2) features that can be used in the plot-to-track correlation process are restricted to a specific class. This paper presents a new approach to overcome these limitations. This approach facilitates tracking of a maneuvering target in clutter and improves tracking performance for weak targets.

Effect of the Queensland Shark Control Program on non target species : whale, dugong, turtle and dolphin : a review

The Queensland Shark Control Program (QSCP) aims to protect swimmers at ten beach areas on the east coast of Queensland between Cairns (17°S) and the Gold coast (28°S). Since its inception in 1962 it has deployed shark nets and baited drumlines in a `mixed gear strategy' that adapts the type of gear to the characteristics of a site (e .g . extreme tidal range, high energy wave action, or proximity of turtle breeding areas) . The policy has provided swimmer protection, and the incidental capture of non-target species has been lower than that resulting from deployment of nets alone (Dudley 1997; Gribble et al. 1998b). The QSCP is the only major public-safety shark-control program to routinely use mixed gear. Both the New South Wales (Holt 1998) and KwaZulu-Natal (Dudley 1998) programs use nets exclusively, although the KwaZulu-Natal program has recently tested drumlines on an experimental basis (Dudley 1998; Dudley, personal communication).

The suitability of non-target native mangroves for the survival and development of the lantana bug Aconophora compressa, an introduced weed biological control agent

Aconophora compressa (Hemiptera: Membracidae), a biological control agent introduced against the weed Lantana camara (Verbenaceae) in Australia, has since been observed on several non-target plant species, including native mangrove Avicennia marina (Acanthaceae). In this study we evaluated the suitability of two native mangroves, A. marina and Aegiceras corniculatum (Myrsinaceae), for the survival and development of A. compressa through no-choice field cage studies. The longevity of females was significantly higher on L. camara (57.7 ± 3.8 days) than on A. marina (43.3 ± 3.3 days) and A. corniculatum (45.7 ± 3.8 days). The proportion of females laying eggs was highest on L. camara (72%) followed by A. marina (36%) and A. corniculatum (17%). More egg batches per female were laid on L. camara than on A. marina and A. corniculatum. Though more nymphs per shoot emerged on L. camara (29.9 ± 2.8) than on A. marina (13 ± 4.8) and A. corniculatum (10 ± 5.3), the number of nymphs that developed through to adults was not significantly different. The duration of nymphal development was longer on A. marina (67 ± 5.8 days) than on L. camara (48 ± 4 days) and A. corniculatum (43 ± 4.6 days). The results, which are in contrast to those from previous glasshouse and quarantine trials, provide evidence that A. compressa adults can survive, lay eggs and complete nymphal development on the two non-target native mangroves in the field under no-choice condition.

Temporal patterns in incidence and abundance of Aconophora compressa (Hemiptera: Membracidae), a biological control agent for Lantana camara, on target and nontarget plants

The membracid Aconophora compressa Walker, a biological control agent released in 1995 to control Lantana camara (Verbenaceae) in Australia, has since been collected on several nontarget plant species. Our survey suggests that sustained populations of A. compressa are found only on the introduced nontarget ornamental Citharexylum spinosum (Verbenaceae) and the target weed L. camara. It is found on other nontarget plant species only when populations on C. spinosum and L. camara are high, suggesting that the presence of populations on nontarget species may be a spill-over effect. Some of the incidence and abundance on nontarget plants could have been anticipated from host specificity studies done on this agent before release, whereas others could not. This raises important issues about predicting risks posed by weed biological control agents and the need for long-term postintroduction monitoring on nontarget species.