Progress and prospects: nuclear import of nonviral vectors.

UNLABELLED: The nuclear envelope represents a key barrier to successful nonviral transfection and gene therapy both in vitro and in vivo. Although the main purpose of the nuclear envelope is to partition the cell to maintain cytoplasmic components in the cytoplasm and nuclear components, most notably genomic DNA, in the nucleus, this function poses a problem for transfections in which exogenous DNA is delivered into the cytoplasm. After delivery to the cytoplasm, nucleic acids rapidly become complexed with cellular proteins that mediate interactions with the cellular machinery for trafficking. Thus, it is these proteins that, in essence, control the nuclear import of DNA, and we must also understand their activities in cells. In this review, we will discuss the principles of nuclear import of proteins and DNA-protein complexes, as well as the various approaches that investigators have used to improve nuclear targeting of plasmids. These approaches include complexation of plasmids with peptides, native and engineered proteins, ligands and polymers, as well as the inclusion of transcription factor-binding sites for general and cell-specific delivery. KEYWORDS: nonviral gene transfermid R:plasmidmid R:nuclear pore complexmid R:importinmid R:nuclear localization signalmid R:karyopherin.

Effects of Acute Aerobic Exercise on Response Inhibition in Adult Patients with ADHD.

Previous studies suggest beneficial effects of aerobic exercise on executive functions, which are a core deficit in ADHD. The aim of the present fMRI study was to investigate acute effects of aerobic exercise on inhibitory control and related brain activation in adult patients with ADHD. 23 patients and 23 matched healthy controls performed on a Go/No-go task in an MRI scanner, following both, an exercise condition involving 30 min of cycling at moderate intensity, and a control condition. ADHD patients compared to healthy controls showed increased brain activation during successful inhibition in the exercise compared to the control condition in parietal, temporal, and occipital regions. Exercise did not improve behavioral performance in either group, but in ADHD patients, exercise-related increases in brain activation and behavioral task performance (i.e., correct inhibition rate) negatively correlated with correct inhibition rate in the control condition. Thus, patients with worse inhibition performance showed stronger exercise-related enhancements, indicating that the lack of improvements on the behavioral level for the whole patient group could be due to ceiling effects. Our findings might be an important step in understanding the neural basis of exercise effects and could, in the long term, help in developing alternative treatment approaches for ADHD.

Help seeking by immigrant Indochinese psychiatric patients in Sydney, Australia.

To better understand factors contributing to underutilization of mental health treatment services by Asian immigrants in English-speaking countries, the authors compared the pathways to treatment of 30 psychiatric patients born in Indochina who currently resided in Australia and 30 Australian-born patients. A semistructured interview was used to gather data on time between onset of psychiatric symptoms and treatment in the first and most recent illness episodes. Indochinese patients took longer to receive psychiatric treatment for their first episode and tended to receive initial help from family members or traditional healers. This effect had disappeared by the time of the patient's current episode. The results suggest the need for culturally relevant psychiatric services for recent immigrants.

Epidemiology, prevention, and early detection of breast cancer.

Globally, breast cancer is the third most common form of cancer and the most common among women. The age-adjusted incidence rates of breast cancer are 176% higher in developed than in developing nations. Male breast cancer is rare, but important studies provided risk factor information for comparison with studies of female breast cancer. There has been considerable interest in a possible role of organochlorines and polychlorinated biphenyls in the etiology of breast cancer, but the results of several null studies indicate the likelihood of such associations is extremely remote, providing reassuring news for the public. Prophylactic mastectomy was observed to significantly reduce a woman's chances of developing breast cancer, but it does not lower the risk to zero. Tamoxifen was found to be an effective chemopreventive agent in the Breast Cancer Prevention Trial, but this result was not replicated in two randomized trials in Europe. Striking reductions in the risk for breast cancer were observed for raloxifene in a randomized, placebo-controlled trial that had been designed for the prevention of osteoporosis. A large-scale, randomized trial of tamoxifen-verus-raloxifene among women at increased risk for developing breast cancer is now underway.