In the social amoebae Dictyostelium discoideum, periodic synthesis and release of extracellular cyclic AMP (cAMP) guides cell aggregation and commitment to form fruiting bodies. It is unclear whether these oscillations represent an intrinsic property of individual cells or if they only exist as a population-level phenomenon. Here we show by live-cell imaging of intact cell populations that pulses originate from a discrete location despite constant exchange of cells to and from the region. In a perfusion chamber, both isolated single cells and cell populations switch from quiescence to rhythmic activity depending on the level of extracellular cAMP. A quantitative analysis shows that stochastic pulsing of individual cells below the threshold concentration of extracellular cAMP plays a critical role in the onset of collective behavior.

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The identification of cancer biomarkers is critical for target-linked cancer therapy. The overall level of phosphatidylcholine (PC) is elevated in colorectal cancer (CRC). To investigate which species of PC is overexpressed in colorectal cancer, an imaging mass spectrometry was performed using a panel of non-neoplastic mucosal and CRC tissues. In the present study, we identified a novel biomarker, PC(16:0 ⁄ 16:1), in CRC using imaging mass spectrometry. Specifically, elevated levels of PC(16:0 ⁄ 16:1) expression were observed in the more advanced stage of CRC. Our data further showed that PC(16:0 ⁄ 16:1) was specifically localized in the cancer region when examined using imaging mass spectrometry. Notably, because the ratio of PC(16:0 ⁄ 16:1) to lyso-PC(16:0) was higher in CRC, we postulated that lyso-PC acyltransferase (LPCAT) activity is elevated in CRC. In an in vitro analysis, we showed that LPCAT4 is involved in the deregulation of PC (16: (1) Previous studies have reported that CRC contains increased amounts of phospholipids as well as an altered phospholipid composition of the CRC cell membrane.(2,3) These changes in membrane phospholipid levels can affect cell proliferation, viability and tumor development.(2,4) Moreover, although phosphatidylcholine (PC) is the most dominant phospholipid in both non-neoplastic and cancer tissues,the amount of PC is highly increased in CRC cells.(2) In addition, the changes in membrane potential and the increased PC ⁄ phosphatidylethanolamine (PE) composition rate are related to the grade of CRC malignancy.(3) In higher eukaryotes, PC is synthesized via two pathways: (i) the triple methylation of PE; and (ii) the cytidine diphosphate (CDP)-choline pathway. (6) However, the steady-state composition of PC species is maintained by the remodeling cycle (Lands' cycle).(7) The precise and concerted deacylation by phospholipase A 2 (PLA 2 ) and reacylation by lyso-PC acyltransferase (LPCAT) are required for normal cell functioning. Notably, the elevated expression of LPCAT1 was associated with colon cancer growth. (8) LPCAT1 is a member of the LPCAT family (LPCAT1-4) and shows LPCAT activity, preferentially incorporating palmitate into PC.(8) However, the relationship between PC remodeling and the progression of cancer, as well as the class of LPCAT involved in this process, remains unclear.Direct mass spectrometry (MS) of biological tissue sections using matrix-assisted laser desorption ⁄ ionization (MALDI) can profile many molecules including phospholipid subtypes. (9) Furthermore, this approach can be extended to imaging MS, which can visualize the distribution of biomolecules in the tissue section.(10-13) Because specific antibodies against lipids and macromolecules are often difficult to obtain, MALDI imaging is a suitable option for detecting distinct species of these molecules directly in a tissue section. This technique has already been applied to various human cancers including prostate and gastric cancer. (14,15) Although this emerging analytical technique was initial...

In the catheter ablation for AF, we found no significant reduction in the 1-year incidence of recurrent atrial tachyarrhythmias by ATP-guided PVI compared with conventional PVI.