The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges.

BACKGROUND: Hematophagous mosquitoes transmit many pathogens that cause human diseases. Pathogen acquisition and transmission occur when female mosquitoes blood feed to acquire nutrients for reproduction. The midgut epithelium of mosquitoes serves as the point of entry for transmissible viruses and parasites. RESULTS: We studied midgut epithelial dynamics in five major mosquito vector species by quantifying PH3-positive cells (indicative of mitotic proliferation), the incorporation of nucleotide analogs (indicative of DNA synthesis accompanying proliferation and/or endoreplication), and the ploidy (by flow cytometry) of cell populations in the posterior midgut epithelium of adult females. Our results show that the epithelial dynamics of post-emergence maturation and of mature sugar-fed guts were similar in members of the Aedes, Culex, and Anopheles genera. In the first three days post-emergence, ~ 20% of cells in the posterior midgut region of interest incorporated nucleotide analogs, concurrent with both proliferative activity and a broad shift toward higher ploidy. In mature mosquitoes maintained on sugar, an average of 3.5% of cells in the posterior midgut region of interest incorporated nucleotide analogs from five to eight days post-emergence, with a consistent presence of mitotic cells indicating constant cell turnover. Oral bacterial infection triggered a sharp increase in mitosis and nucleotide analog incorporation, suggesting that the mosquito midgut undergoes accelerated cellular turnover in response to damage. Finally, blood feeding resulted in an increase in cell proliferation, but the nature and intensity of the response varied by mosquito species and by blood source (human, bovine, avian or artificial). In An. gambiae, enterocytes appeared to reenter the cell cycle to increase ploidy after consuming blood from all sources except avian. CONCLUSIONS: We saw that epithelial proliferation, differentiation, and endoreplication reshape the blood-fed gut to increase ploidy, possibly to facilitate increased metabolic activity. Our results highlight the plasticity of the midgut epithelium in mosquitoes' physiological responses to distinct challenges.

Fourier transform spectrometer based on high-repetition-rate mid-infrared supercontinuum sources for trace gas detection.

We present a fast-scanning Fourier transform spectrometer (FTS) in combination with high-repetition-rate mid-infrared supercontinuum sources, covering a wavelength range of 2-10.5 µm. We demonstrate the performance of the spectrometer for trace gas detection and compare various detection methods: baseband detection with a single photodetector, baseband balanced detection, and synchronous demodulation at the repetition rate of the supercontinuum source. The FTS uses off-the-shelf optical components and provides a minimum spectral resolution of 750 MHz. It achieves a noise equivalent absorption sensitivity of ∼10-6 cm-1 Hz-1/2 per spectral element, by using a 31.2 m multipass absorption cell.

Identification of novel TMPRSS2:ERG mechanisms in prostate cancer metastasis: involvement of MMP9 and PLXNA2.

Prostate cancer (PCa) is one of the major public health problems in Western countries. Recently, the TMPRSS2:ERG gene fusion, which results in the aberrant expression of the transcription factor ERG, has been shown to be the most common gene rearrangement in PCa. Previous studies have determined the contributions of this fusion in PCa disease initiation and/or progression in vitro and in vivo. In this study on TMPRSS2:ERG regulation in PCa, we used an androgen receptor and TMPRSS2:ERG fusion double-negative PCa cell model: PC3c. In three cell clones with different TMPRSS2:ERG expression levels, ectopic expression of the fusion resulted in significant induction of cell migration and invasion in a dose-dependent manner. In agreement with this phenotype, high-throughput microarray analysis revealed that a set of genes, functionally associated with cell motility and invasiveness, were deregulated in a dose-dependent manner in TMPRSS2:ERG-expressing cells. Importantly, we identified increased MMP9 (Metalloproteinase 9) and PLXNA2 (Plexin A2) expression in TMPRSS2:ERG-positive PCa samples, and their expression levels were significantly correlated with ERG expression in a PCa cohort. In line with these findings, there was evidence that TMPRSS2:ERG directly and positively regulates MMP9 and PLXNA2 expression in PC3c cells. Moreover, PLXNA2 upregulation contributed to TMPRSS2:ERG-mediated enhancements of PC3c cell migration and invasion. Furthermore, and importantly, PLXNA2 expression was upregulated in metastatic PCa tumors compared with localized primary PCa tumors. This study provides novel insights into the role of the TMPRSS2:ERG fusion in PCa metastasis.

Great saphenous vein ablation with steam injection: results of a multicentre study.

OBJECTIVE: To assess the safety and efficiency of steam vein sclerosis (SVS) of the great saphenous vein (GSV) in a multicentre open prospective cohort study. DESIGN: 75 consecutive adult patients with GSV reflux, CEAP C2-C5 and vein diameter 4-13 mm. METHODS: Patients treated using an SVS™ generator delivering homogenous pulses of superheated steam were followed up at 8 days and 1, 3, 6 and 12 months (clinical, duplex ultrasound, quality of life [QoL] with SF12). RESULTS: 88 veins were treated in 75 patients. At 6 months, 72/75 (96%) veins were obliterated (95% CI: 89-99) and Kaplan-Meier analysis found an obliteration rate of 96.1% at 12 months. QoL increased at 6 months for both the physical and mental components (p = 0.049 and p < 0.001 respectively). SVS was well tolerated: no major complications were reported. Adverse events occurred mainly at day 8 and incidents amounted to ecchymosis (n = 60) and pain (n = 7). CONCLUSIONS: SVS achieved an obliteration rate similar to that of other thermal ablation techniques. It was well tolerated with minimal post-operative pain.

Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease.

The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n=945). Seventeen genes exhibited at least one polymorphism associated with AD risk, and following correction for multiple testing, we retained the interleukin (IL)-33 gene. We first confirmed that the IL-33 expression was decreased in the brain of AD cases compared with that of controls. Further genetic analysis led us to select three polymorphisms within this gene, which we analyzed in three independent case-control studies. These polymorphisms and a resulting protective haplotype were systematically associated with AD risk in non-APOE epsilon 4 carriers. Using a large prospective study, these associations were also detected when analyzing the prevalent and incident AD cases together or the incident AD cases alone. These polymorphisms were also associated with less cerebral amyloid angiopathy (CAA) in the brain of non-APOE epsilon 4 AD cases. Immunohistochemistry experiments finally indicated that the IL-33 expression was consistently restricted to vascular capillaries in the brain. Moreover, IL-33 overexpression in cellular models led to a specific decrease in secretion of the A beta(40) peptides, the main CAA component. In conclusion, our data suggest that genetic variants in IL-33 gene may be associated with a decrease in AD risk potentially in modulating CAA formation.

Reconstruction of the floor of the mouth following surgery for cancer.

The authors, members of a very active service of Head and Neck Surgery, tell of their experience with the reconstruction of the floor of the mouth following surgery for cancer. They feel that the simplest methods of reconstruction are the best.

[Radiotherapy following surgery of the larynx]. / Radiothérapie à la suite de chirurgie laryngée

A method of radiotherapy following total or partial surgery of the larynx is described. Criteria for the selection of patients and a technique of treatment are suggested. The results from 1966 to 1971 are reported.