Identification of a Classical Bipartite Nuclear Localization Signal in the Drosophila TEA/ATTS Protein Scalloped

Drosophila melanogaster wing development has been shown to rely on the activity of a complex of two proteins, Scalloped (Sd) and Vestigial (Vg). Within this complex, Sd is known to provide DNA binding though its TEA/ATTS domain, while Vg modulates this binding and provides transcriptional activation through N- and C-terminal activation domains. There is also evidence that Sd is required for the nuclear translocation of Vg. Indeed, a candidate sequence which shows consensus to the bipartite family of nuclear localization signals (NLSs) has been identified within Sd previously, though it is not known if it is functional, or if additional unpredicted signals that mediate nuclear transport exist within the protein. By expressing various enhanced green fluorescent protein (eGFP) tagged constructs within Drosophila S2 cells, we demonstrate that this NLS is indeed functional and necessary for the proper nuclear localization of Sd. Additionally, the region containing the NLS is critical for the wildtype function of ectopically expressed Sd, in the context of wing development. Using site-directed mutagenesis, we have identified a group of five amino acids within this NLS which is critical for its function, as well as another group of two which is of lesser importance. Together with data that suggests that this sequence mediates interactions with Importin-α3, we conclude that the identified NLS is likely a classical bipartite signal. Further dissection of Sd has also revealed that a large portion of the C-terminal domain of the protein is required its proper nuclear localization. Finally, a Leptomycin B (LB) sensitive signal which appears to facilitate nuclear export is identified, raising the possibility that Sd also contains a nuclear export signal (NES)

Promotoras as Mental Health Practitioners in Primary Care: A Multi-Method Study of an Intervention to Address Contextual Sources of Depression

We assessed the role of promotoras—briefly trained community health workers—in depression care at community health centers. The intervention focused on four contextual sources of depression in underserved, low-income communities: underemployment, inadequate housing, food insecurity, and violence. A multi-method design included quantitative and ethnographic techniques to study predictors of depression and the intervention’s impact. After a structured training program, primary care practitioners (PCPs) and promotoras collaboratively followed a clinical algorithm in which PCPs prescribed medications and/or arranged consultations by mental health professionals and promotoras addressed the contextual sources of depression. Based on an intake interview with 464 randomly recruited patients, 120 patients with depression were randomized to enhanced care plus the promotora contextual intervention, or to enhanced care alone. All four contextual problems emerged as strong predictors of depression (chi square, p < .05); logistic regression revealed housing and food insecurity as the most important predictors (odds ratios both 2.40, p < .05). Unexpected challenges arose in the intervention’s implementation, involving infrastructure at the health centers, boundaries of the promotoras’ roles, and “turf” issues with medical assistants. In the quantitative assessment, the intervention did not lead to statistically significant improvements in depression (odds ratio 4.33, confidence interval overlapping 1). Ethnographic research demonstrated a predominantly positive response to the intervention among stakeholders, including patients, promotoras, PCPs, non-professional staff workers, administrators, and community advisory board members. Due to continuing unmet mental health needs, we favor further assessment of innovative roles for community health workers

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591

Tomato-aphid-hoverfly: A tritrophic interaction incompatible for pest management

peer reviewedTrichome-based tomato resistance offers the potential to reduce pesticide use, but its compatibility with biological control remains poorly understood. We evaluated Episyrphus balteatus De Geer (Diptera, Syrphidae), an efficient aphidophagous predator, as a potential biological control agent of Myzus persicae Sulzer (Hemiptera, Aphididae) on trichome-bearing tomato cultivars. Episyrphus balteatus’ foraging and oviposition behavior, as well as larval mobility and aphid accessibility, were compared between two tomato cultivars (Lycopersicon esculentum Mill. ‘Moneymaker’ and ‘Roma’) and two other crop plants; broad bean (Vicia faba L.) and potato (Solanum tuberosum L.). Hoverfly adults landed and laid more eggs on broad beans than on three species of Solanaceae. Hoverfly larval movement was drastically reduced on tomato, and a high proportion of hoverfly larvae fell from the plant before reaching aphid prey. After quantifying trichome abundance on each of these four plants, we suggest that proprieties of the plant surface, specifically trichomes, are a key factor contributing to reduced efficacy of E. balteatus as a biological agent for aphid control on tomatoes

Toward the Development of Virtual Surgical Tools to Aid Orthopaedic FE Analyses

Computational models of joint anatomy and function provide a means for biomechanists, physicians, and physical therapists to understand the effects of repetitive motion, acute injury, and degenerative diseases. Finite element models, for example, may be used to predict the outcome of a surgical intervention or to improve the design of prosthetic implants. Countless models have been developed over the years to address a myriad of orthopaedic procedures. Unfortunately, few studies have incorporated patient-specific models. Historically, baseline anatomic models have been used due to the demands associated with model development. Moreover, surgical simulations impose additional modeling challenges. Current meshing practices do not readily accommodate the inclusion of implants. Our goal is to develop a suite of tools (virtual instruments and guides) which enable surgical procedures to be readily simulated and to facilitate the development of all-hexahedral finite element mesh definitions