The Inferior Temporal Numeral Area distinguishes numerals from other character categories during passive viewing: A representational similarity analysis

A region in the posterior inferior temporal gyrus (pITG) is thought to be specialized for processing Arabic numerals, but fMRI studies that compared passive viewing of numerals to other character types (e.g., letters and novel characters) have not found evidence of numeral preference in the pITG. However, recent studies showed that the engagement of the pITG is modulated by attention and task contexts, suggesting that passive viewing paradigms may be ill-suited for examining numeral specialization in the pITG. It is possible, however, that even if the strengths of responses to different category types are similar, the distributed response patterns (i.e., neural representations) in a candidate numeral-preferring pITG region ( pITG-numerals ) may reveal categorical distinctions, even during passive viewing. Using representational similarity analyses with three datasets that share the same task paradigm and stimulus sets (total N = 88), we tested whether the neural representations of digits, letters, and novel characters in pITG-numerals were organized according to visual form and/or conceptual categories (e.g., familiar versus novel, numbers versus others). Small-scale frequentist and Bayesian meta-analyses of our dataset-specific findings revealed that the organization of neural representations in pITG-numerals is unlikely to be described by differences in abstract shape, but can be described by a categorical digits versus letters distinction, or even a digits versus others distinction (suggesting greater numeral sensitivity). Evidence of greater numeral sensitivity during passive viewing suggest that pITG-numerals is likely part of a neural pathway that has been developed for automatic processing of objects with potential numerical relevance. Given that numerals and letters do not differ categorically in terms of shape, categorical distinction in pITG-numerals during passive viewing must reflect ontogenetic differentiation of symbol set representations based on repeated usage of numbers and letters in differing task contexts

Economic and Environmental Impacts of Harmful Non-Indigenous Species in Southeast Asia

Harmful non-indigenous species (NIS) impose great economic and environmental impacts globally, but little is known about their impacts in Southeast Asia. Lack of knowledge of the magnitude of the problem hinders the allocation of appropriate resources for NIS prevention and management. We used benefit-cost analysis embedded in a Monte-Carlo simulation model and analysed economic and environmental impacts of NIS in the region to estimate the total burden of NIS in Southeast Asia. The total annual loss caused by NIS to agriculture, human health and the environment in Southeast Asia is estimated to be US$33.5 billion (5th and 95th percentile US$25.8–39.8 billion). Losses and costs to the agricultural sector are estimated to be nearly 90% of the total (US$23.4–33.9 billion), while the annual costs associated with human health and the environment are US$1.85 billion (US$1.4–2.5 billion) and US$2.1 billion (US$0.9–3.3 billion), respectively, although these estimates are based on conservative assumptions. We demonstrate that the economic and environmental impacts of NIS in low and middle-income regions can be considerable and that further measures, such as the adoption of regional risk assessment protocols to inform decisions on prevention and control of NIS in Southeast Asia, could be beneficial

Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study

Objective: Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs. Design: Prospective animal study. Setting: Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children’s Research Institute, Melbourne, Australia. Subjects: Four weaned Border-Leicester/Suffolk lambs at 5 months of age. Interventions: Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go® or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure. Measurements and Main Results: Both the HYDRA and AeroNeb Go® produced palivizumab aerosols in the 1–5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 μm, range = 0.54–5.41μm) and the AeroNeb Go® (3.07 ± 1.56 μm, range = 0.86–10 μm). Aerosolized palivizumab was delivered to the lungs at 88.79–94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung. Conclusions: Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections

Novel HTS Strategy Identifies TRAIL-Sensitizing Compounds Acting Specifically Through the Caspase-8 Apoptotic Axis

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is potentially a very important therapeutic as it shows selectivity for inducing apoptosis in cancer cells whilst normal cells are refractory. TRAIL binding to its cognate receptors, Death Receptors-4 and -5, leads to recruitment of caspase-8 and classical activation of downstream effector caspases, leading to apoptosis. As with many drugs however, TRAIL's usefulness is limited by resistance, either innate or acquired. We describe here the development of a novel 384-well high-throughput screening (HTS) strategy for identifying potential TRAIL-sensitizing agents that act solely in a caspase-8 dependent manner. By utilizing a TRAIL resistant cell line lacking caspase-8 (NB7) compared to the same cells reconstituted with the wild-type protein, or with a catalytically inactive point mutant of caspase-8, we are able to identify compounds that act specifically through the caspase-8 axis, rather than through general toxicity. In addition, false positive hits can easily be “weeded out” in this assay due to their activity in cells lacking caspase-8-inducible activity. Screening of the library of pharmacologically active compounds (LOPAC) was performed as both proof-of-concept and to discover potential unknown TRAIL sensitizers whose mechanism is caspase-8 mediated. We identified known TRAIL sensitizers from the library and identified new compounds that appear to sensitize specifically through caspase-8. In sum, we demonstrate proof-of-concept and discovery of novel compounds with a screening strategy optimized for the detection of caspase-8 pathway-specific TRAIL sensitizers. This screen was performed in the 384-well format, but could easily be further miniaturized, allows easy identification of artifactual false positives, and is highly scalable to accommodate diverse libraries

Economic and Environmental Impacts of Harmful Non-Indigenous Species in Southeast Asia

10.1371/journal.pone.0071255PLoS ONE88-POLN