Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time ±4 cm pan-and-tilt action. Robot-driven ±60° pivots of an integrated ±185° rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[¹⁸F] fluoro-2-deoxy-ᴅ-glucose (¹⁸F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less¹. In this article, we describe new radiation plans for the treatment of moving lung tumors.     

Human-cat relationship in an oceanic biosphere reserve: The case of La Palma Island,Canary archipelago

Removal of feral cats from island environments is a useful mechanism by which their ecological impact on endangered species can be reduced or ended. Nevertheless, because cats are anthropogenic in their origins, social perceptions of management practices play a large role in their implementation. Four-hundred questionnaires were delivered (386 were returned) with 100 going to each of the following: local residents; environmental workers; tourists; and, hunters. Questions explored respondents’ knowledge about island biodiversity and invasive species as well as attitudes towards cat population management methods. Habitat destruction and introduction of invasive species were considered the main threats for the conservation of island biodiversity. Most respondents considered cats to have a negative impact on biodiversity and sterilization campaigns were considered most appropriate for cat population control. Several free sterilization campaigns have been conducted in La Palma Island Biosphere Reserve in order to reduce free-ranging cats and were well received by local people. This research, which combined concepts of management, ecology and social sciences, provides valuable insights which may to be applicable on several other islands where cats and people are present and in conflict with conservation priorities.     

Increased abundance of native and non-native spiders with habitat fragmentation

Habitat fragmentation and invasive species often contribute to the decline of native taxa. Since the penetration of non‐native species into natural habitat may be facilitated by habitat fragmentation, it is important to examine how these two factors interact. Previous research documented that, in contrast to most other arthropod taxa, spiders increased in density and morphospecies richness with decreasing fragment area and increasing fragment age (time since insularization) in urban habitat fragments in San Diego County, California, USA. We tested whether a specific mechanism, an increase in non‐native species with fragmentation, is responsible for this pattern. We found that both native and non‐native taxa contributed to the pattern. Abundance of native spiders per pitfall trap sample increased significantly with decreasing fragment size (i.e. a negative density–area relationship) and abundance of non‐natives increased significantly with increasing fragment age. The proportion of non‐native individuals also increased significantly with age. One non‐native species, Oecobius navus, comprised the majority of non‐native individuals (82.2%) and a significant proportion of total individuals (25.1%). Richness of spider families per sample (family density) increased with fragment age due to an increase in the occurrence of non‐natives in older fragments, however, native family richness did not vary with age or area. Due to increasing dominance by non‐native and some native families, family evenness declined with decreasing fragment size and increasing fragment age. Native and non‐native abundance covaried positively arguing against strong negative interactions between the two groups. O. navus had a strong positive association with another common non‐native arthropod, the Argentine ant (Linepitheme humile), suggesting a possible direct interaction. In contrast, abundance of native spiders was negatively correlated with Argentine ant abundance. We hypothesize that fragmentation in this semiarid habitat increases productivity in smaller and older fragments enhancing the density of both native and non‐native taxa.     

Structure–activity relationships (SAR) and structure–kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists III: The role of a hydrogen-bond acceptor in long receptor residence times

The correct positioning and orientation of an hydrogen bond acceptor (HBA) in the tail portion of the biaryl series of CRTh2 antagonists is a requirement for long receptor residence time. The HBA in combination with a small steric substituent in the core section (R^core ≠ H) gives access to compounds with dissociation half-lives of ⩾24 h.     

Proteins in Tumor-Derived Plasma Extracellular Vesicles Indicate Tumor Origin

Cancer-derived extracellular vesicles (EVs) promote tumorigenesis, premetastatic niche formation, and metastasis via their protein cargo. However, the proteins packaged by patient tumors into EVs cannot be determined in vivo because of the presence of EVs derived from other tissues. We therefore developed a cross-species proteomic method to quantify the human tumor-derived proteome of plasma EVs produced by patient-derived xenografts of four cancer types. Proteomic profiling revealed individualized packaging of novel protein cargo, and machine learning accurately classified the type of the underlying tumor.     

Can altered muscle synergies control unimpaired gait?

Recent studies have postulated that the human motor control system recruits groups of muscles through low-dimensional motor commands, or muscle synergies. This scheme simplifies the neural control problem associated with the high-dimensional structure of the neuromuscular system. Several lines of evidence have suggested that neurological injuries, such as stroke or cerebral palsy, may reduce the dimensions that are available to the motor control system, and these altered dimensions or synergies are thought to contribute to impaired walking patterns. However, no study has investigated whether impaired low-dimensional control spaces necessarily lead to impaired walking patterns. In this study, using a two-dimensional model of walking, we developed a synergy-based control framework that can simulate the dynamics of walking. The simulation analysis showed that a synergy-based control scheme can produce well-coordinated movements of walking matching unimpaired gait. However, when the dimensions available to the controller were reduced, the simplified emergent pattern deviated from unimpaired gait. A system with two synergies, similar to those seen after neurological injury, could not produce an unimpaired walking pattern. These findings provide further evidence that altered muscle synergies can contribute to impaired gait patterns and may need to be directly addressed to improve gait after neurological injury.     

Meloidogyne incognita Surface Antigen Epitopes in Infected Arabidopsis Roots

Surface-coat epitopes of Meloidogyne incognita were detected in root tissues of Arabidopsis thaliana during migration and feeding site formation. A whole-mount root technique was used for immunolocalization of surface coat epitopes in A. thaliana, with the aid of a monoclonal antibody raised specifically against the outer surface of infective juveniles of M. incognita. The antibody, which was Meloidogyne-specific, recognized a fucosyl-bearing glycoprotein in the surface coat. During migration in host tissues the surface coat was shed, initially accumulating in the intercellular spaces next to the juvenile and later at cell junctions farther from the nematode. Upon induction of giant cell formation, the antibody bound to proximally located companion cells and sieve elements of the phloem.     

Global patterns of diversity among the specialist birds of riverine landscapes

1. Despite the growing view that biodiversity provides a unifying theme in river ecology, global perspectives on richness in riverine landscapes are limited. As a result, there is little theory or quantitative data on features that might have influenced global patterns in riverine richness, nor are there clear indications of which riverine landscapes are important to conservation at the global scale. As conspicuous elements of the vertebrate fauna of riverine landscapes, we mapped the global distributions of all of the world's specialist riverine birds and assessed their richness in relation to latitude, altitude, primary productivity and geomorphological complexity (surface configuration). 2. Specialist riverine birds, typical of high‐energy riverine landscapes and dependent wholly or partly on production from river ecosystems, occur in 16 families. They are represented by an estimated 60 species divided equally between the passerines and non‐passerines. Major radiation has occurred among different families on different continents, indicating that birds have evolved several times into the niches provided by riverine landscapes. 3. Continental richness varies from four species in Europe to 28 in Asia, with richness on the latter continent disproportionately larger than would be expected from a random distribution with respect to land area. Richness is greatest in mountainous regions at latitudes of 20–40°N in the riverine landscapes of the Himalayan mountains, where 13 species overlap in range. 4. Family, genus and species richness in specialist riverine birds all increase significantly with productivity and surface configuration (i.e. relief). However, family richness was the best single predictor of the numbers of species or genera. In keeping with the effect of surface configuration, river‐bird richness peaks globally at 1300–1400 m altitude, and most species occur typically on small, fast rivers where they feed predominantly on invertebrates. Increased lengths of such streams in areas of high relief and rainfall might have been responsible for species–area effects. 5. We propose the hypothesis that the diversity in channel forms and habitats in riverine landscapes, in addition to high temperature and primary productivity, have been prerequisites to the development of global patterns in the richness of specialist riverine organisms. We advocate tests of this hypothesis in other taxonomic groups. We draw attention, however, to the challenges of categorically defining riverine organisms in such tests because (i) rivers grade into many other habitat types across several different ecotones and (ii) `terrestrialisation' processes in riverine landscapes means that they offer habitat for organisms whose evolutionary origins are not exclusively riverine.     

Optimization and biological evaluation of celastrol derivatives as Hsp90–Cdc37 interaction disruptors with improved druglike properties

Heat shock protein 90 (Hsp90) as a molecular target for oncology therapeutics has attracted much attention in the last decade. The Hsp90 multichaperone complex has important roles in the growth and/or survival of cancer cells. Cdc37, as a cochaperone, associates kinase clients to Hsp90 and promotes the development of malignant tumors. Disrupting the Hsp90–Cdc37 interaction provides an alternative strategy to inhibit the function of Hsp90 for cancer therapy. Celastrol, as a natural product, can disrupt the Hsp90–Cdc37 interaction and induce degradation of kinase clients. The study conducted here attempted to elucidate the structure–activity relationship of celastrol derivatives as Hsp90–Cdc37 disruptors and to improve the druglike properties. 23 celastrol derivatives were designed, synthesized, and the biological activities and physicochemical properties were determined. The derivative CEL20 showed improved Hsp90–Cdc37 disruption activity, anti-proliferative activities as well as druglike properties. Additionally, CEL20 induced clients degradation, cell cycle arrest and apoptosis in Panc-1 cells. This study can provide reference for the discovery of novel Hsp90–Cdc37 disruptors.     

Vertical and horizontal distribution patterns of the giant sea anemone Heteractis crispa with symbiotic anemonefish on a fringing coral reef

The distribution patterns of the leathery sea anemone, Heteractis crispa, which contains an algal endosymbiont (zooxanthellae) and anemonefish, were investigated in relation to size distribution on a shallow fringing reef (3.2 ha, 0–4 m depth) in Okinawa, Japan. Individual growth and movements were also examined. Large individuals (>1,000 cm²) inhabited reef edges up to a depth of 4 m, while small anemone (<500 cm²) inhabited shallow reefs including inner reef flats. Individuals rarely moved, and their sizes were significantly correlated with their water depths. Growth of small anemones was negatively correlated with their distance from the reef edge, suggesting that reef edges provide more prey and lower levels of physiological stress. This study suggested that deep reef edges are suitable habitats for H. crispa. Large anemones were inhabited by large Amphiprion perideraion or large Amphiprion clarkii, both of which are effective defenders against anemone predators. Anemones that settle in deep reef edges may enjoy a higher survival rate and attain a large size because of their symbiotic relationship with anemonefish. However, early settlers do not harbor anemonefish. Their mortality rate would be higher in the deep edges than in shallow edges, the complicated topography of which provides refuge.