Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages.

Bacteriophages infecting pathogenic hosts play an important role in medical research, not only as potential treatments for antibiotic-resistant infections but also offering novel insights into pathogen genetics and evolution. A prominent example is cluster K mycobacteriophages infecting Mycobacterium tuberculosis, a causative agent of tuberculosis in humans. However, as handling M. tuberculosis as well as other pathogens in a laboratory remains challenging, alternative nonpathogenic relatives, such as Mycobacterium smegmatis, are frequently used as surrogates to discover therapeutically relevant bacteriophages in a safer environment. Consequently, the individual host ranges of the majority of cluster K mycobacteriophages identified to date remain poorly understood. Here, we characterized the complete genome of Stinson, a temperate subcluster K1 mycobacteriophage with a siphoviral morphology. A series of comparative genomic analyses revealed strong similarities with other cluster K mycobacteriophages, including the conservation of an immunity repressor gene and a toxin/antitoxin gene pair. Patterns of codon usage bias across the cluster offered important insights into putative host ranges in nature, highlighting that although all cluster K mycobacteriophages are able to infect M. tuberculosis, they are less likely to have shared an evolutionary infection history with Mycobacterium leprae (underlying leprosy) compared to the rest of the genus' host species. Moreover, subcluster K1 mycobacteriophages are able to integrate into the genomes of Mycobacterium abscessus and Mycobacterium marinum-two bacteria causing pulmonary and cutaneous infections which are often difficult to treat due to their drug resistance.

Complete Genome Sequence of Microbacterium Bacteriophage Erla.

We characterized the complete genome sequence of Siphoviridae bacteriophage Erla, an obligatory lytic subcluster EA1 bacteriophage infecting Microbacterium foliorum NRRL B-24224, with a capsid width of 65 nm and a tail length of 112 nm. The 41.5-kb genome, encompassing 62 predicted protein-coding genes, is highly similar (99.52% identity) to that of bacteriophage Calix.

Urological involvement in renal transplantation.

Historically, urologists were the primary surgeons in renal transplantation. Specialization and increased complexity of the field of transplantation, coupled with a de-emphasis of vascular surgical training in urology, has created a situation where many renal transplants are carried out by surgeons with a general surgery background. Because of its genitourinary nature, however, urological input in renal transplantation is still vital. For living donors, a urologist should be involved to help evaluate and prepare certain patients for eventual donation. This could involve both medical and surgical intervention. Additionally, urologists who carry out living donor nephrectomy maintain a sense of ownership in the renal transplant process and provide a unique opportunity to the trainees of that particular program. For renal transplant recipients, preoperative evaluation of voiding dysfunction and other genitourinary anomalies might be necessary before the transplant. Also, occasional surgical intervention to prepare a patient for renal transplant might be necessary, such as in a patient with a small renal mass that is detected by a screening pretransplant ultrasound. Intraoperatively, for patients with complex urological reconstructions that might be related to the etiology of the renal failure (urinary diversion, bladder augmentation), a urologist who is familiar with the anatomy should be available. Postoperatively, urological evaluation and intervention might be necessary for patients who had a pre-existing urological condition or who might have developed something de novo after the transplant. Although renal transplant programs could consult an on-call urologist for particular issues on an as-needed basis, having a urologist, who has repeated exposure to the particular issues and procedures that are involved with renal transplantation, and who is part of a dedicated multidisciplinary renal transplant team, provides optimal quality of care to these complex patients.

Enhanced transrectal ultrasound modalities in the diagnosis of prostate cancer.

Standard grayscale transrectal ultrasound has a poor sensitivity for detection of prostate cancer. Saturation biopsy schemes have improved prostate cancer detection rates over standard template biopsy schemes, but carry additional morbidity and cost. Enhanced ultrasound modalities (EUM), including color and power Doppler, contrast-enhancement, harmonic and flash replenishment imaging, and elastography have demonstrated improved prostate cancer detection. EUM targeting areas with increased or abnormal vascularity or firmness for biopsy offer improved prostate cancer detection. EUM, detect prostate cancer more efficiently than standard ultrasound guided biopsies. These emerging technologies may potentially augment standard prostate biopsy in clinical practice.

Ingenuity network-assisted transcription profiling: Identification of a new pharmacologic mechanism for MK886.

The small molecular inhibitor MK886 is known to block 5-lipoxygenase-activating protein ALOX5AP and shows antitumor activity in multiple human cell lines. The broad antitumor therapeutic window reported in vivo for MK886 in rodents supports further consideration of this structural class. Better understanding of the mode of action of the drug is important for application in humans to take place. Affymetrix microarray study was conducted to explore MK886 pharmacologic mechanism. Ingenuity Pathway Analysis software was applied to validate the results at the transcriptional level by putting them in the context of an experimental proteomic network. Genes most affected by MK886 included actin B and focal adhesion components. A subsequent National Cancer Institute-60 panel study, RT-PCR validation followed by confocal microscopy, and Western blotting also pointed to actin B down-regulation, filamentous actin loss, and disorganization of the transcription machinery. In agreement with these observations, MK886 was found to enhance the effect of UV radiation in H720 lung cancer cell line. In light of the modification of cytoskeleton and cell motility by lipid phosphoinositide 3-kinase products, MK886 interaction with actin B might be biologically important. The low toxicity of MK886 in vivo was modeled and explained by binding and transport by dietary lipids. The rate of lipid absorbance is generally higher for tumors, suggesting a promise of a targeted liposome-based delivery system for this drug. These results suggest a novel antitumor pharmacologic mechanism.