Mitochondrial mutations in adenoid cystic carcinoma of the salivary glands.

BACKGROUND: The MitoChip v2.0 resequencing array is an array-based technique allowing for accurate and complete sequencing of the mitochondrial genome. No studies have investigated mitochondrial mutation in salivary gland adenoid cystic carcinomas. METHODOLOGY: The entire mitochondrial genome of 22 salivary gland adenoid cystic carcinomas (ACC) of salivary glands and matched leukocyte DNA was sequenced to determine the frequency and distribution of mitochondrial mutations in ACC tumors. PRINCIPAL FINDINGS: Seventeen of 22 ACCs (77%) carried mitochondrial mutations, ranging in number from 1 to 37 mutations. A disproportionate number of mutations occurred in the D-loop. Twelve of 17 tumors (70.6%) carried mutations resulting in amino acid changes of translated proteins. Nine of 17 tumors (52.9%) with a mutation carried an amino acid changing mutation in the nicotinamide adenine dinucleotide dehydrogenase (NADH) complex. CONCLUSIONS/SIGNIFICANCE: Mitochondrial mutation is frequent in salivary ACCs. The high incidence of amino acid changing mutations implicates alterations in aerobic respiration in ACC carcinogenesis. D-loop mutations are of unclear significance, but may be associated with alterations in transcription or replication.

Deformation of stem cell nuclei by nanotopographical cues.

Cells sense cues in their surrounding microenvironment. These cues are converted into intracellular signals and transduced to the nucleus in order for the cell to respond and adapt its function. Within the nucleus, structural changes occur that ultimately lead to changes in the gene expression. In this study, we explore the structural changes of the nucleus of human mesenchymal stem cells as an effect of topographical cues. We use a controlled nanotopography to drive shape changes to the cell nucleus, and measure the changes with both fluorescence microscopy and a novel light scattering technique. The nucleus changes shape dramatically in response to the nanotopography, and in a manner dependent on the mechanical properties of the substrate. The kinetics of the nuclear deformation follows an unexpected trajectory. As opposed to a gradual shape change in response to the topography, once the cytoskeleton attains an aligned and elongation morphology on the time scale of several hours, the nucleus changes shape rapidly and intensely.

Simultaneous two-wavelength transmission quantitative phase microscopy with a color camera.

We present a quantitative phase microscopy method that uses a Bayer mosaic color camera to simultaneously acquire off-axis interferograms in transmission mode at two distinct wavelengths. Wrapped phase information is processed using a two-wavelength algorithm to extend the range of the optical path delay measurements that can be detected using a single temporal acquisition. We experimentally demonstrate this technique by acquiring the phase profiles of optically clear microstructures without 2pi ambiguities. In addition, the phase noise contribution arising from spectral channel crosstalk on the color camera is quantified.

Separating the scattering and absorption coefficients using the real and imaginary parts of the refractive index with low-coherence interferometry.

We present an analytical method that yields the real and imaginary parts of the refractive index (RI) from low-coherence interferometry measurements, leading to the separation of the scattering and absorption coefficients of turbid samples. The imaginary RI is measured using time-frequency analysis, with the real part obtained by analyzing the nonlinear phase induced by a sample. A derivation relating the real part of the RI to the nonlinear phase term of the signal is presented, along with measurements from scattering and nonscattering samples that exhibit absorption due to hemoglobin.

Measuring morphological features using light-scattering spectroscopy and Fourier-domain low-coherence interferometry.

We present measurements of morphological features in a thick turbid sample using light-scattering spectroscopy (LSS) and Fourier-domain low-coherence interferometry (fLCI) by processing with the dual-window (DW) method. A parallel frequency domain optical coherence tomography (OCT) system with a white-light source is used to image a two-layer phantom containing polystyrene beads of diameters 4.00 and 6.98 mum on the top and bottom layers, respectively. The DW method decomposes each OCT A-scan into a time-frequency distribution with simultaneously high spectral and spatial resolution. The spectral information from localized regions in the sample is used to determine scatterer structure. The results show that the two scatterer populations can be differentiated using LSS and fLCI.

Fiber-optic interferometric two-dimensional scattering-measurement system.

We present a fiber-optic interferometric system for measuring depth-resolved scattering in two angular dimensions using Fourier-domain low-coherence interferometry. The system is a unique hybrid of the Michelson and Sagnac interferometer topologies. The collection arm of the interferometer is scanned in two dimensions to detect angular scattering from the sample, which can then be analyzed to determine the structure of the scatterers. A key feature of the system is the full control of polarization of both the illumination and the collection fields, allowing for polarization-sensitive detection, which is essential for two-dimensional angular measurements. System performance is demonstrated using a double-layer microsphere phantom. Experimental data from samples with different sizes and acquired with different polarizations show excellent agreement with Mie theory, producing structural measurements with subwavelength accuracy.

Decoding an olfactory mechanism of kin recognition and inbreeding avoidance in a primate.

BACKGROUND: Like other vertebrates, primates recognize their relatives, primarily to minimize inbreeding, but also to facilitate nepotism. Although associative, social learning is typically credited for discrimination of familiar kin, discrimination of unfamiliar kin remains unexplained. As sex-biased dispersal in long-lived species cannot consistently prevent encounters between unfamiliar kin, inbreeding remains a threat and mechanisms to avoid it beg explanation. Using a molecular approach that combined analyses of biochemical and microsatellite markers in 17 female and 19 male ring-tailed lemurs (Lemur catta), we describe odor-gene covariance to establish the feasibility of olfactory-mediated kin recognition. RESULTS: Despite derivation from different genital glands, labial and scrotal secretions shared about 170 of their respective 338 and 203 semiochemicals. In addition, these semiochemicals encoded information about genetic relatedness within and between the sexes. Although the sexes showed opposite seasonal patterns in signal complexity, the odor profiles of related individuals (whether same-sex or mixed-sex dyads) converged most strongly in the competitive breeding season. Thus, a strong, mutual olfactory signal of genetic relatedness appeared specifically when such information would be crucial for preventing inbreeding. That weaker signals of genetic relatedness might exist year round could provide a mechanism to explain nepotism between unfamiliar kin. CONCLUSION: We suggest that signal convergence between the sexes may reflect strong selective pressures on kin recognition, whereas signal convergence within the sexes may arise as its by-product or function independently to prevent competition between unfamiliar relatives. The link between an individual's genome and its olfactory signals could be mediated by biosynthetic pathways producing polymorphic semiochemicals or by carrier proteins modifying the individual bouquet of olfactory cues. In conclusion, we unveil a possible olfactory mechanism of kin recognition that has specific relevance to understanding inbreeding avoidance and nepotistic behavior observed in free-ranging primates, and broader relevance to understanding the mechanisms of vertebrate olfactory communication.

Mix it and fix it: functions of composite olfactory signals in ring-tailed lemurs.

Animals communicating via scent often deposit composite signals that incorporate odorants from multiple sources; however, the function of mixing chemical signals remains understudied. We tested both a 'multiple-messages' and a 'fixative' hypothesis of composite olfactory signalling, which, respectively, posit that mixing scents functions to increase information content or prolong signal longevity. Our subjects-adult, male ring-tailed lemurs (Lemur catta)-have a complex scent-marking repertoire, involving volatile antebrachial (A) secretions, deposited pure or after being mixed with a squalene-rich paste exuded from brachial (B) glands. Using behavioural bioassays, we examined recipient responses to odorants collected from conspecific strangers. We concurrently presented pure A, pure B and mixed A + B secretions, in fresh or decayed conditions. Lemurs preferentially responded to mixed over pure secretions, their interest increasing and shifting over time, from sniffing and countermarking fresh mixtures, to licking and countermarking decayed mixtures. Substituting synthetic squalene (S)-a well-known fixative-for B secretions did not replicate prior results: B secretions, which contain additional chemicals that probably encode salient information, were preferred over pure S. Whereas support for the 'multiple-messages' hypothesis underscores the unique contribution from each of an animal's various secretions, support for the 'fixative' hypothesis highlights the synergistic benefits of composite signals.