New Insights into the Chloroplast Outer Membrane Proteome and Associated Targeting Pathways

Plastids are a dynamic class of organelle in plant cells that arose from an ancient cyanobacterial endosymbiont. Over the course of evolution, most genes encoding plastid proteins were transferred to the nuclear genome. In parallel, eukaryotic cells evolved a series of targeting pathways and complex proteinaceous machinery at the plastid surface to direct these proteins back to their target organelle. Chloroplasts are the most well-characterized plastids, responsible for photosynthesis and other important metabolic functions. The biogenesis and function of chloroplasts rely heavily on the fidelity of intracellular protein trafficking pathways. Therefore, understanding these pathways and their regulation is essential. Furthermore, the chloroplast outer membrane proteome remains relatively uncharted territory in our understanding of protein targeting. Many key players in the cytosol, receptors at the organelle surface, and insertases that facilitate insertion into the chloroplast outer membrane remain elusive for this group of proteins. In this review, we summarize recent advances in the understanding of well-characterized chloroplast outer membrane protein targeting pathways as well as provide new insights into novel targeting signals and pathways more recently identified using a bioinformatic approach. As a result of our analyses, we expand the known number of chloroplast outer membrane proteins from 117 to 138.     

Iron oxide-loaded polymer scaffolds for non-invasive hyperthermic treatment of infiltrated cells

Focal therapies such as hyperthermia have been successfully used to treat solid localized tumors; however, they are not easily applied to cancers that may present in a disseminated form such as ovarian cancer. To address this need, iron oxide (IO) particles were incorporated into microporous poly(caprolactone) scaffolds previously shown to recruit disseminating cancer cells. Under an alternating magnetic field, IO-loaded scaffolds exhibited heating and killed ID8 ovarian cancer cells in vitro. After implantation in the intraperitoneal cavity of mice, IO-loaded scaffolds became infiltrated with tissue after 6–7 weeks, and infiltrated cells were successfully treated ex vivo. Finally, IO-loaded scaffolds noninvasively killed infiltrated cells in vivo as evidenced by decreases in number of nuclei. These studies demonstrate the promising use of IO-loaded scaffolds as a tool for noninvasive hyperthermia, which could be an innovative modality for treatment of disseminated cancers.     

Trauma exposure, mental health, and service utilization rates among immigrant and United States-born Hispanic youth: Results from the Hispanic family study.

Although the largest immigrant group in the United States is Hispanic, little is known about their rates of traumatic experiences and psychiatric disorders, particularly for youth. Findings with adults suggest that recent immigrants have lower rates of mental illness than long-time residents or U.S.-born Hispanics, but use health-related services less often. The present study examined this relationship in a convenience sample of 131 foreign-born (64.5%) and 72 U.S.-born (35.5%) Hispanic youth, ages 8–17 years and a subset of their caregivers (n = 110). Findings from youth interview data suggest that immigrant and U.S.-born youth did not differ significantly in experiences of potentially traumatizing events or psychiatric disorders. However, findings from caregiver interview data suggest that there were significant disparities between the two groups in health service utilization for doctors and other medical professionals, with caregivers reporting that foreign-born youth utilize these health services at lower rates than U.S.-born youth. Results are discussed in the context of prior findings and recommendations offered for increasing service utilization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vaccine delivery: Nanopatch‐Targeted Skin Vaccination against West Nile Virus and Chikungunya Virus in Mice (Small 16/2010)

The ‘Nanopatch’ (NP) comprises arrays of densely packed projections with a defined geometry and distribution designed to physically target vaccines directly to thousands of epidermal and dermal antigen presenting cells (APCs). These miniaturized arrays are two orders of magnitude smaller than standard needles—which deliver most vaccines—and are also much smaller than current microneedle arrays. The NP is dry‐coated with antigen, adjuvant, and/or DNA payloads. After the NP was pressed onto mouse skin, a protein payload co‐localized with 91.4 ± 4.1 APC mm⁻² (or 2925 in total) representing 52% of the delivery sites within the NP contact area, agreeing well with a probability‐based model used to guide the device design; it then substantially increases as the antigen diffuses in the skin to many more cells. APC co‐localizing with protein payloads rapidly disappears from the application area, suggesting APC migration. The NP also delivers DNA payloads leading to cutaneous expression of encoded proteins within 24 h. The efficiency of NP immunization is demonstrated using an inactivated whole chikungunya virus vaccine and a DNA‐delivered attenuated West Nile virus vaccine. The NP thus offers a needle‐free, versatile, highly effective vaccine delivery system that is potentially inexpensive and simple to use.     

Differential Actions of Muscarinic Receptor Subtypes in Gastric,Pancreatic, and Colon Cancer

Cancers arising from gastrointestinal epithelial cells are common, aggressive, and difficult to treat. Progress in this area resulted from recognizing that the biological behavior of these cancers is highly dependent on bioactive molecules released by neurocrine, paracrine, and autocrine mechanisms within the tumor microenvironment. For many decades after its discovery as a neurotransmitter, acetylcholine was thought to be synthesized and released uniquely from neurons and considered the sole physiological ligand for muscarinic receptor subtypes, which were believed to have similar or redundant actions. In the intervening years, we learned this former dogma is not tenable. (1) Acetylcholine is not produced and released only by neurons. The cellular machinery required to synthesize and release acetylcholine is present in immune, cancer, and other cells, as well as in lower organisms (e.g., bacteria) that inhabit the gut. (2) Acetylcholine is not the sole physiological activator of muscarinic receptors. For example, selected bile acids can modulate muscarinic receptor function. (3) Muscarinic receptor subtypes anticipated to have overlapping functions based on similar G protein coupling and downstream signaling may have unexpectedly diverse actions. Here, we review the relevant research findings supporting these conclusions and discuss how the complexity of muscarinic receptor biology impacts health and disease, focusing on their role in the initiation and progression of gastric, pancreatic, and colon cancers.     

Best practices for modeling structural boundary conditions due to a localized fire

Recent studies suggest the assumption of uniform heating that is used in current structural fire design cannot be assumed conservative, especially if the fire is expected to burn locally. Aside from design equations, which have limited applicability, a common approach to simulating structural members subjected to a localized fire is modeling the fire-structure interaction using a coupled computational fluid dynamics (CFD)-finite element (FE) model. In the existing literature, a wide range of methods and parameters are used when determining the boundary conditions at the fire-structure interface, specifically regarding the representation of net heat flux, heat transfer coefficient, and surface emissivity of steel. The purpose of this study is to investigate various methods for representing the boundary conditions in terms of accuracy and computational efficiency and then identify best practices. In conclusion, our study found that net heat flux predicted by adiabatic surface temperature, a nonconstant heat transfer coefficient, and a surface emissivity of 0.9 for steel was the most reliable thermal boundary condition in a coupled CFD-FE model of a localized fire. These recommendations are based on the two cases studied here, and caution should be used when applying these results to future studies.     

Discovering Hidden Material Properties of MgCl2 at Atomic Resolution with Structured Temporal Electron Illumination of Picosecond Time Resolution

A combination of atomic resolution phase contrast electron microscopy and pulsed electron beams reveals pristine properties of MgCl₂ at 1.7 Å resolution that were previously masked by air and beam damage. Both the inter‐ and intra‐layer bonding in pristine MgCl₂ are weak, which leads to uncommonly large local orientation variations that characterize this Ziegler–Natta catalyst support. By delivering electrons with 1–10 ps pulses and ≈160 ps delay times, phonons induced by the electron irradiation in the material are allowed to dissipate before the subsequent delivery of the next electron packet, thus mitigating phonon accumulations. As a result, the total electron dose can be extended by a factor of 80–100 to study genuine material properties at atomic resolution without causing object alterations, which is more effective than reducing the sample temperature. In conditions of minimal damage, beam currents approach femtoamperes with dose rates around 1 eÅ^?2 s^?1. Generally, the utilization of pulsed electron beams is introduced herein to access genuine material properties while minimizing beam damage.     

Effect of Water and Solvent Selection on the SAFA Purification Times for Metallic Nitride Fullerenes

This paper addresses two key parameters in the SAFA purification method for isolating endohedral metallofullerenes. The percent water content in the reactive aminosilica significantly affects the time needed to isolate Sc₃N@I_h -C₈₀ metallic nitride fullerene (MNF). The role of solvent selection in the SAFA process is also discussed. The SAFA purification time needed for isolating Sc₃N@I_h -C₈₀ metallofullerene is influenced by the identity of the electron donating/accepting group on the aromatic solvent.