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The incidence rate of cervical cancer (CC) is three times greater in Southeast Asia (SEA), where screening tests are less common than in Northern America, underlining a need for convenient self-diagnostic methods. The expression pattern of microRNAs (miRNAs) has been considered a molecular tool for non-invasive cancer diagnosis and prognosis. This study aimed at the development of the first miRNA biomarker panel for early detection of CC in Thai women. Genome-wide miRNA expression profiling was performed on cervical tissue and discharge samples from high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS) subjects. Machine learning was used for handling imbalanced data and feature selection before differential expression analysis to identify significantly dysregulated miRNA panels. Pathway analysis was conducted to provide the cellular functions involved in CC progression. The study identified a shared 18-miRNA panel for both tissue and discharge, with which the prediction model distinguished HSIL and AIS from normal samples with an accuracy of 90.9%. Three dysregulated miRNAs comprised of miR-125b-1-3p, miR-487b-3p, and miR-1180-3p in CC were first described. Most of the miRNAs in the panel were down-regulated, whereas merely miR-142-3p was significantly up-regulated in HSIL and AIS, suggesting a convenient biomarker for detecting precancerous conditions. Moreover, our miRNA panel highlighted important roles played by the cell-cell interaction pathways in CC. Together, our miRNA panel hold promise as a biomarker for the early detection of cervical cancer with cervical discharge, offering the possibility for developing non-invasive diagnostic tools. [ABSTRACT FROM AUTHOR]

Silicibacter sp. TM1040 is a member of the marine Roseobacter clade of Alphaproteobacteria that forms symbioses with unicellular eukaryotic phytoplankton, such as dinoflagellates. The symbiosis is complex and involves a series of steps that physiologically change highly motile bacteria into cells that readily form biofilms on the surface of the host. The initial phases of symbiosis require bacterial motility and chemotaxis that drive the swimming bacteria toward their planktonic host. Cells lacking wild-type motility fail to establish biofilms on host cells and do not produce effetive symbioses, emphasizing the importance of understanding the molecular mechanisms controlling flagellar biosynthesis and the biphasic 'swim-or-stick' switch. In the present study, we used a combination of bioinformatic and genetic approaches to identify the genes critical for swimming of Silicibacter sp. TM1040. More than 40 open reading frames with homology to known flagellar structural and regulatory genes were identified, most of which are organized into approximately eight operons comprising a 35.4-kb locus, with surprising similarity to the fla2 locus of Rhodobacter sphaeroides. The genome has homologs of CckA, CtrA, FlbT, and FlaF, proteins that in Caulobacter crescentus regulate flagellum biosynthesis. In addition, we uncovered three novel genes, flaB, flaC, and flaD, which encode flagellar regulatory proteins whose functions are likely to involve regulation of motor function (FlaD) and modulation of the swim-or-stick switch (FlaC). The data support the conclusion that Silicibacter sp. TM1040 uses components found in other Alphaproteobacteria, as well as novel molecular mechanisms, to regulate the expression of the genes required for motility and biofilm formation. These unique molecular mechanisms may enhance the symbiosis and survival of Roseobacter clade bacteria in the marine environment.

Proteus mirabilis is a urinary tract pathogen that differentiates from a short swimmer cell to an elongated, highly flagellated swarmer cell. Swarmer cell differentiation parallels an increased expression of several virulence factors, suggesting that both processes are controlled by the same signal. The molecular nature of this signal is not known but is hypothesized to involve the inhibition of flagellar rotation. In this study, data are presented supporting the idea that conditions inhibiting flagellar rotation induce swarmer cell differentiation and implicating a rotating flagellar filament as critical to the sensing mechanism. Mutations in three genes, fliL, fliF, and fliG, encoding components of the flagellar basal body, result in the inappropriate development of swarmer cells in noninducing liquid media or hyperelongated swarmer cells on agar media. The fliL mutation was studied in detail. Fli[L.sup.-] mutants are nonmotile and fail to synthesize flagellin, while complementation of fliL restores wild-type cell elongation but not motility. Overexpression of fli[L.sup.+] in wild-type cells prevents swarmer cell differentiation and motility, a result also observed when P. mirabilis fli[L.sup.+] was expressed in Escherichia coli. These results suggest that FliL plays a role in swarmer cell differentiation and implicate FliL as critical to transduction of the signal inducing swarmer cell differentiation and virulence gene expression. In concert with this idea, defects in fliL up-regulate the expression of two virulence genes, zapA and hpmB. These results support the hypothesis that P. mirabilis ascertains its location in the environment or host by assessing the status of its flagellar motors, which in turn control swarmer cell gene expressions.