Publications

BACKGROUND

Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences.

RESULTS

We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly.

CONCLUSIONS

This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.

INTRODUCTION

HIV voluntary counseling and testing (VCT) comprise an effective preventive measure and an entry point to care and support services. We sought to assess VCT uptake and HIV-related knowledge and perceived risk among female sex workers (FSWs) in five provinces of the Mekong Delta region.

METHODS

A cross-sectional survey was carried out in 1998 FSWs, including both street-based sex workers (SSWs) and entertainment-based sex workers (ESWs).

RESULTS

High proportions of FSWs were aware that using condoms (94.6%), and clean needles (34.1%) are preventive measures that reduce the risk of HIV transmission. Some FSWs reported avoiding public toilet use (8.6%), physical contacts (16.1%), or sharing meals (10.9%) with people living with HIV/AIDS, and preventing mosquito bites (20.8%). Twenty-nine percent (29.0%) of FSWs perceived themselves as being at risk of HIV infection. Only 32.7% had ever tested for HIV, of whom 54% were voluntary for testing. FSWs who ever injected drugs (OR = 0.03, p=0.05), had drug-injecting clients (OR = 0.07, p<0.01), and had inconsistent condom use with husbands or lovers (OR = 0.10, p=0.01) were less likely to have a voluntary test. Inconsistent condom use with clients (OR = 13.86, p<0.01), and receiving HIV information from radio (OR = 13.28, p<0.05) and communication campaigns (OR = 6.69, p<0.05), increased the likelihood of VCT uptake.

CONCLUSION

Inadequate knowledge and some misconceptions about HIV transmission routes and preventive measures, low perceived risk of HIV infection, and low VCT uptake were observed among FSWs in the Mekong Delta region. Interventions to improve their knowledge and self-efficacy, reduce risky behaviors, and encourage VCT uptake and early access to health care services are necessary to prevent HIV transmission in this region.

BACKGROUND

Patellar fractures are debilitating injuries that compromise the knee extensor mechanism and are frequently associated with poor outcomes. The purpose of this study was to quantify the functional outcomes of operative treatment of patellar fractures.

METHODS

Functional outcome data on thirty patients with an isolated unilateral patellar fracture were prospectively obtained at three, six, and twelve months postoperatively.

RESULTS

All fractures healed. There were two complications (7%) related to the surgery (wound dehiscence and refracture), and eleven patients (37%) underwent removal of symptomatic implants. The tibial plateau-patella angle demonstrated patella baja in seventeen (57%) of the patients. Anterior knee pain during activities of daily living was experienced by twenty-four (80%) of the patients. Clinical improvement occurred over the first six months. However, functional impairment persisted at twelve months, with objective testing demonstrating that the knee extensor mechanism on the injured side had deficits in strength (-41%), power (-47%), and endurance (-34%) as compared with the uninjured side.

CONCLUSIONS

Despite advances in surgical protocols and acceptable radiographic outcomes, functional impairment remains common after treatment of patellar fractures. Rehabilitation strategies following surgical stabilization of these injuries will be a fruitful area for future clinical research.