A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities

Profilin-1 (Pfn-1) is a ubiquitously expressed actin-binding protein that is essential for normal cell proliferation and migration. In breast cancer and several other adenocarcinomas, Pfn-1 expression is downregulated when compared to normal tissues. Previous studies from our laboratory have shown that genetically modulating Pfn-1 expression significantly impacts proliferation, migration, and invasion of breast cancer cells in vitro, and mammary tumor growth, dissemination, and metastatic colonization in vivo. Therefore, small molecules that can modulate Pfn-1 expression could have therapeutic potential in the treatment of metastatic breast cancer. The overall goal of this study was to perform a multiplexed phenotypic screen to identify compounds that inhibit cell motility through upregulation of Pfn-1. Screening of a test cassette of 1280 compounds with known biological activities on an Oris™ Pro 384 cell migration platform identified several agents that increased Pfn-1 expression greater than two-fold over vehicle controls and exerted anti-migratory effects in the absence of overt cytotoxicity in MDA-MB-231 human breast cancer cells. Concentration-response confirmation and orthogonal follow-up assays identified two bona fide inducers of Pfn-1, purvalanol and tyrphostin A9, that confirmed in single-cell motility assays and Western blot analyses. SiRNA-mediated knockdown of Pfn-1 abrogated the inhibitory effect of tyrphostin A9 on cell migration, suggesting Pfn-1 is mechanistically linked to tyrphostin A9's anti-migratory activity. The data illustrate the utility of the high-content cell motility assay to discover novel targeted anti-migratory agents by integrating functional phenotypic analyses with target-specific readouts in a single assay platform. © 2014 Joy et al

Angular sensitivity of blowfly photoreceptors: intracellular measurements and wave-optical predictions

The angular sensitivity of blowfly photoreceptors was measured in detail at wavelengths λ = 355, 494 and 588 nm. The measured curves often showed numerous sidebands, indicating the importance of diffraction by the facet lens. The shape of the angular sensitivity profile is dependent on wavelength. The main peak of the angular sensitivities at the shorter wavelengths was flattened. This phenomenon as well as the overall shape of the main peak can be quantitatively described by a wave-optical theory using realistic values for the optical parameters of the lens-photoreceptor system. At a constant response level of 6 mV (almost dark adapted), the visual acuity of the peripheral cells R1-6 is at longer wavelengths mainly diffraction limited, while at shorter wavelengths the visual acuity is limited by the waveguide properties of the rhabdomere. Closure of the pupil narrows the angular sensitivity profile at the shorter wavelengths. This effect can be fully described by assuming that the intracellular pupil progressively absorbs light from the higher order modes. In light-adapted cells R1-6 the visual acuity is mainly diffraction limited at all wavelengths.

Carotid axillary bypass in a patient with blocked subclavian stents: a case report

<p>Abstract</p> <p>Introduction</p> <p>Surgical treatment of symptomatic occlusive lesions of the proximal subclavian artery is infrequently necessary. Carotid subclavian bypass has gained popularity and is now considered standard treatment when stenting is not possible. Exposure of the subclavian artery and bypass grafting onto it is difficult, as the vessel is delicate, thin-walled and located deep in the supraclavicular fossa. The thoracic duct and brachial plexus are in close proximity to the left subclavian artery and are therefore susceptible to damage. Distal grafting to the axillary artery instead of the subclavian artery has the potential of avoiding some of these risks. Infraclavicular exposure of the axillary artery is more straightforward. The vessel wall is thicker and is easier to handle. In this case report, we describe a patient with a left proximal subclavian occlusion which was stented twice and blocked on both occasions. The patient underwent a carotid axillary bypass, as grafting onto the subclavian artery was impossible because of the two occluded metal stents.</p> <p>Case presentation</p> <p>A 56-year-old Caucasian woman, a heavy smoker, presented acutely with left arm numbness and pain and blood pressure discrepancies in both arms. A diagnosis of subclavian stenosis was confirmed on the basis of a computed tomographic scan and a magnetic resonance angiogram. The patient had undergone subclavian artery stenting twice, and unfortunately the stents blocked on both occasions. The patient underwent carotid axillary bypass surgery. She had an uneventful recovery and was able to return to a full, normal life.</p> <p>Conclusion</p> <p>Carotid axillary bypass appears to be a good alternative to carotid subclavian bypass in the treatment of symptomatic proximal stenosis or occlusion of the subclavian artery.</p

The role of receptivity in the courtship behavior of Podocnemis erythrocephala in captivity

The courtship behavior of Podocnemis erythrocephala (Red-headed Amazon River Turtle) in captivity was studied to examine female receptivity and male response to female rejection. We observed 20 females and 39 males in 150 sessions (3–6 h/day for a total of 450 h). In 36% of the trials, there was no interaction between males and females, and 20% of the trials resulted in copulations. All males introduced into tanks approached females, and eventually there was aggression among the males. In 48% of the experiments, females also searched for or approached males. When males initially approached females, they either accepted the male’s advances (14%), rejected the male passively (38%), or rejected the male aggressively (48%). In 86% of the cases where males were rejected, 4% attempted to approach females again, and in 51% they were ultimately successful

Controlling passively-quenched single photon detectors by bright light

Single photon detectors based on passively-quenched avalanche photodiodes can be temporarily blinded by relatively bright light, of intensity less than a nanowatt. I describe a bright-light regime suitable for attacking a quantum key distribution system containing such detectors. In this regime, all single photon detectors in the receiver Bob are uniformly blinded by continuous illumination coming from the eavesdropper Eve. When Eve needs a certain detector in Bob to produce a click, she modifies polarization (or other parameter used to encode quantum states) of the light she sends to Bob such that the target detector stops receiving light while the other detector(s) continue to be illuminated. The target detector regains single photon sensitivity and, when Eve modifies the polarization again, produces a single click. Thus, Eve has full control of Bob and can do a successful intercept-resend attack. To check the feasibility of the attack, 3 different models of passively-quenched detectors have been tested. In the experiment, I have simulated the intensity diagrams the detectors would receive in a real quantum key distribution system under attack. Control parameters and side effects are considered. It appears that the attack could be practically possible.Comment: Experimental results from a third detector model added. Minor corrections and edits made. 11 pages, 10 figure

Dynamic Thermal Structure of Imported Fire Ant Mounds

A study was undertaken to characterize surface temperatures of mounds of imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae) and S. richteri Forel, and their hybrid, as it relates to sun position and shape of the mounds, to better understand factors that affect absorption of solar radiation by the nest mound and to test feasibility of using thermal infrared imagery to remotely sense mounds. Mean mound surface temperature peaked shortly after solar noon and exceeded mean surface temperature of the surrounding surface. Temperature range for mounds and their surroundings peaked near solar noon, and the temperature range of the mound surface exceeded that of the surrounding area. The temperature difference between mounds and their surroundings peaked around solar noon and ranged from about 2 to 10°C. Quadratic trends relating temperature measurements to time of day (expressed as percentage of daylight hours from apparent sunrise to apparent sunset) explained 77 to 88% of the variation in the data. Mounds were asymmetrical, with the apex offset on average 81.5 ± 1.2 mm to the north of the average center. South facing aspects were about 20% larger than north facing aspects. Mound surface aspect and slope affected surface temperature; this affect was greatly influenced by time of day. Thermal infrared imagery was used to illustrate the effect of mound shape on surface temperature. These results indicate that the temperature differences between mounds and their surroundings are sufficient for detection using thermal infrared remote sensing, and predictable temporal changes in surface temperature may be useful for classifying mounds in images

Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD. METHODS: rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS) was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI) and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis was applied for the discrimination of the two subgroups at baseline. RESULTS: The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%–76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. CONCLUSION: A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD

Genes Suggest Ancestral Colour Polymorphisms Are Shared across Morphologically Cryptic Species in Arctic Bumblebees

email Suzanne orcd idCopyright: © 2015 Williams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited