Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia

NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis

Autofluorescence spectroscopy of malpighian epithelial cells, as a new tool for analysis of cervical cancer precursors

A spectroscopic analysis of autofluorescence was investigated within the cell cytoplasm from cervical malpighian epithelia prepared on Thin-Prep smears. Autofluorescence emission spectra from 22 cervix were analyzed by microspectrofluorometry under a 363 nm laser excitation. Among the analyzed cervix, 6 were in normal limits, 6 in inflammatory limits, 5 were evocative of Low-Grade Squamous Intraepithelial Lesions (LGSILs) and 5 were evocative of High-Grade Squamous Intraepithelial Lesions (HGSILs). Cytoplasmic emission intensities at 450 nm of cells from inflammatory, LGSIL and HGSIL cervix were equivalent and were 3-fold higher than from normal cervix. All smears presented a two-fold lower autofluorescence emission in the cytoplasm than in the nucleus. The spectral profile analysis allows the discrimination of cells from inflammatory, LGSIL and HGSIL cervix. The 525/425 nm emission ratios were 0.75±0.1, 0.96±0.04 and 1.2±0.1 for inflammatory, LGSIL and HGSIL, respectively. We suggest that smears of normal, inflammatory, LGSIL and HGSIL cervix could be discriminated by the analysis of the 450 nm emission intensity and 525/425 nm emission ratios from cells of malpighian epithelia

A simple experimental method for measuring the thermal sensitivity of single-mode fibers

We present a simple technique to experimentally determine the optical-path length change with temperature for optical single-mode fibers. Standard single-mode fibers act as natural low-finesse cavities, with the Fresnel reflection of the straight cleaved surfaces being ∼3%, for the laser light coupled to them. By measuring the intensity variations due to interference of light reflected from the fiber front and end surfaces, while ramping the ambient temperature, the thermal sensitivity of the optical-path length of the fiber can be derived. Light was generated by a narrow linewidth, low drift laser. With our fairly short test fibers, we found that it was possible to reach a relative precision of the temperature sensitivity, compared to a reference fiber, on the 0.4%-2% scale and an absolute precision of 2%-5%, with the potential to improve both by an order of magnitude. The results for single-acrylate, dual-acrylate, and copper- and aluminum-coated fibers are presented. Values are compared with analytic models and results from a finite element method simulation. With the aid of these measurements, a simple fiber-interferometer, which is insensitive to thermal drifts, could be constructed