In this issue

Location, location, location According to real estate agents, the value of a house is driven by primarily one thing: Location. Those of us in California know what that means – existing homes in good neighborhoods are often torn down to build houses that match the value of the location, driving prices ever higher, until the bubble bursts. Pampaloni et al. examined the effect of the neighborhood on the proteome of MDCK cells on various 2‐ and 3‐D culture supports: uncoated plastic (2P), thin collagen coat on plastic (2C), and a relatively thick collagen gel which allows differentiation into 3‐D cyst structures (3C). Pairwise proteome comparisons between the various supports revealed significant differences. In 2C versus 3C, upregulated 2C species were characteristic of tumor cells. Cells cultured under 3C conditions exhibited consistent upregulation of SOD1 and proteins involved in the remodeling of the cytoskeleton. In short, culture conditions have strong effects on cell physiology. pp. 3394–3413Hot time means no kids, pups, lambs, or calves In land mammals, the scrotum is where it is for reason. And the testes hang out in the scrotum for a good reason—it's air conditioned and they work better. It has been demonstrated that warming testicles for a short period for several consecutive days reversibly inhibits spermatogenesis for several weeks. The next logical questions: what protein(s) is/are the target for this effect? Is there a potential opportunity for male birth control here? Zhu et al. pursued these questions by applying proteomic technology (2‐DE, MALDI‐TOF/TOF, MS/MS, Western blots) to mouse testes’ samples before and after heating. Of particular interest was the protein Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1), which showed upregulation and was involved in a number of cell functions, including apoptosis, cell proliferation and survival. pp. 3480–3493When is a digital test not digital? Drum roll, please. And the answer is.... when it's a rectal prostate examination (RPE). The RPE combined with the prostate specific antigen (PSA) test is currently about as good as it gets for detecting what is probably the most common cancer of men. Rare is the man who dies without signs of prostate cancer, although it's not the most frequent killer. The challenge is discriminating between benign and aggressive cancers. Although thousands of potential biomarkers have been proposed, few are developing at a reasonable pace. Yocum et al. address the discrimination problem by creating a multiplexed mix of markers: AMACR for localized tumors with some aggressive character, EZH2 for aggressive forms, PSA for historic compatibility, and isotopically labeled markers for quantitative references (SID‐SRM‐MS). Although the assay is still in a preliminary state, it looks very promising, exhibiting appropriate quantitative shifts depending on the degree of progression in vivo . pp. 3506–3514