Putting it all together: intrinsic and extrinsic mechanisms governing proteasome biogenesis

Background The 26S proteasome is at the heart of the ubiquitin-proteasome system, which is the key cellular pathway for the regulated degradation of proteins and enforcement of protein quality control. The 26S proteasome is an unusually large and complicated protease comprising a 28-subunit core particle (CP) capped by one or two 19-subunit regulatory particles (RP). Multiple activities within the RP process incoming ubiquitinated substrates for eventual degradation by the barrel-shaped CP. The large size and elaborate architecture of the proteasome have made it an exceptional model for understanding mechanistic themes in macromolecular assembly. Objective In the present work, we highlight the most recent mechanistic insights into proteasome assembly, with particular emphasis on intrinsic and extrinsic factors regulating proteasome biogenesis. We also describe new and exciting questions arising about how proteasome assembly is regulated and deregulated in normal and diseased cells. Methods A comprehensive literature search using the PubMed search engine was performed, and key findings yielding mechanistic insight into proteasome assembly were included in this review. Results Key recent studies have revealed that proteasome biogenesis is dependent upon intrinsic features of the subunits themselves as well as extrinsic factors, many of which function as dedicated chaperones. Conclusion Cells rely on a diverse set of mechanistic strategies to ensure the rapid, efficient, and faithful assembly of proteasomes from their cognate subunits. Importantly, physiological as well as pathological changes to proteasome assembly are emerging as exciting paradigms to alter protein degradation in vivo

Realization of the Einstein-Podolsky-Rosen Paradox Using Momentum- and Position-Entangled Photons from Spontaneous Parametric Down Conversion

We report on a momentum-position realization of the EPR paradox using direct detection in the near and far fields of the photons emitted by collinear type-II phase-matched parametric down conversion. Using this approach we achieved a measured two-photon momentum-position variance product of 0.01ℏ2, which dramatically violates the bounds for the EPR and separability criteria

Quantum and Classical Coincidence Imaging

Coincidence, or ghost, imaging is a technique that uses two correlated optical fields to form an image of an object. In this work we identify aspects of coincidence imaging which can be performed with classically correlated light sources and aspects which require quantum entanglement. We find that entangled photons allow high-contrast, high-resolution imaging to be performed at any distance from the light source. We demonstrate this fact by forming ghost images in the near and far fields of an entangled photon source, noting that the product of the resolutions of these images is a factor of 3 better than that which is allowed by classical diffraction theory

Discriminating Orthogonal Single-Photon Images

We can encode an image from an orthogonal basis set onto a single photon from a downconverted pair via the use of an amplitude mask. We can then discriminate the image imprinted on the photon from other images in the set using holographic-matched filtering techniques. We demonstrate this procedure experimentally for an image space of two objects, and we discuss the possibility of applying this method to a much larger image space. This process could have important implications for the manipulation of images at the quantum level

Molecular evidence for gender differences in the migratory behaviour of a small seabird

Molecular sexing revealed an unexpectedly strong female bias in the sex ratio of pre-breeding European Storm Petrels (Hydrobates pelagicus), attracted to playback of conspecific calls during their northwards migration past SW Europe. This bias was consistent across seven years, ranging from 80.8% to 89.7% female (mean annual sex ratio ± SD = 85.5% female ±4.1%). The sex ratio did not differ significantly from unity (i.e., 50% female) among (i) Storm Petrel chicks at a breeding colony in NW France, (ii) adults found dead on beaches in Southern Portugal, (iii) breeding birds attending nest burrows in the UK, captured by hand, and (iv) adults captured near a breeding colony in the UK using copies of the same sound recordings as used in Southern Europe, indicating that females are not inherently more strongly attracted to playback calls than males. A morphological discriminant function analysis failed to provide a good separation of the sexes, showing the importance of molecular sexing for this species. We found no sex difference in the seasonal or nocturnal timing of migration past Southern Europe, but there was a significant tendency for birds to be caught in sex-specific aggregations. The preponderance of females captured in Southern Europe suggests that the sexes may differ in migration route or in their colony-prospecting behaviour during migration, at sites far away from their natal colonies. Such differences in migration behaviour between males and females are poorly understood but have implications for the vulnerability of seabirds to pollution and environmental change at sea during the non-breeding season

LiDAR, UAV or compass-clinometer? Accuracy, coverage and the effects on structural models

This study was carried out as part of a University of Aberdeen provided PhD supported by The NERC Centre for Doctoral Training in Oil & Gas, (grant reference: NE/M00578X/1). Thanks to Magda Chmielewska for her training and help with LiDAR processing, without which this study could not have been undertaken. Midland Valley Exploration is thanked for academic use of Move 2016 software. We gratefully acknowledge the detailed and constructive reviews by Mike James and an anonymous reviewer, and thanks to Bill Dunne for careful and thorough editorial comments, all of which greatly improved the manuscript.Peer reviewedPublisher PD

Juror Perceptions of Trial Testimony as a Function of the Method of Presentation: A Comparison of Live, Color Video, Black-and-White Video, Audio, and Transcript Presentations

Summary of Contents I. Introduction A. Uses of videotape in the litigation process 1. Prelitigation videotape uses 2. Videotaped depositions 3. Electronic trial records 4. Electronic presentation of evidence B. A review of the research literature II. The Research Design: Rationale and Description A. The need to assess the impact of videotape in the litigation process B. The live trial as a standard of comparison C. Description of the research design 1. The stimulus trial 2. The trial participants 3. The physical setting 4. A description of the different trial procedures 5. The questionnaire III. Research Results A. Juror perceptions of the trial participants as rated on the bipolar adjective scales 1. Competency 2. Honesty 3. Friendliness 4. Appearance 5. Objectivity 6. Additional adjective pairs B. The amount of compensation awarded the landowner C. The relationship of the dollar awards to juror ratings of trial participants D. Juror preferences for the trial participants E. Juror reactions to the trials IV. Discussion of the Results A. Comparative merits of deposition presentation methods 1. Read transcript 2. Audiotape 3. Black-and-white videotape 4. Color videotape 5. Conclusion B. An evaluation of the use of videotape to present all testimony at trial C. Recommendations for future researc

Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor

The Notch receptor signalling pathway plays an important role in breast development, regulation of stem cells and differentiation of luminal progenitor cells. The pathway also plays a significant role in breast cancer development and progression. However, which of the Notch receptors that regulate breast cancer stem cells is unknown. We assessed stem cell activity in breast cancer cell lines and nine primary human tumour samples. In vitro and in vivo breast cancer stem cell activity was enriched using selection of anoikis resistant cells or cells expressing the membrane phenotype ESA(+)/CD44(+)/CD24(low). We compared the activation of Notch receptors in the breast cancer stem cell-enriched population to luminally differentiated cells and studied the effects of pathway inhibition, both in vitro and in vivo. We find that Notch4 signalling activity is 8-fold higher in the breast cancer stem cell-enriched cells compared to the differentiated cells while Notch1 activation is 4-fold lower in breast cancer stem cells. Furthermore, pharmacological or genetic Notch inhibition markedly reduced breast cancer stem cell activity in vitro, and significantly reduced tumour formation in vivo. Importantly, cells with Notch4 knock-down using specific shRNA formed fewer mammosphere colonies than Notch1 knock-down cells. In vivo Notch1 knock-down, like pharmacological inhibition, reduced the number and size of tumours but Notch4 knock-down suppressed tumour initiation completely. Our findings indicate that Notch4-targeted therapies will be more effective than targeting Notch1 in suppressing breast cancer recurrence initiated by breast cancer stem cells

Juror Perceptions of Trial Testimony as a Function of the Method of Presentation: A Comparison of Live, Color Video, Black-and-White Video, Audio, and Transcript Presentations

Summary of Contents I. Introduction A. Uses of videotape in the litigation process 1. Prelitigation videotape uses 2. Videotaped depositions 3. Electronic trial records 4. Electronic presentation of evidence B. A review of the research literature II. The Research Design: Rationale and Description A. The need to assess the impact of videotape in the litigation process B. The live trial as a standard of comparison C. Description of the research design 1. The stimulus trial 2. The trial participants 3. The physical setting 4. A description of the different trial procedures 5. The questionnaire III. Research Results A. Juror perceptions of the trial participants as rated on the bipolar adjective scales 1. Competency 2. Honesty 3. Friendliness 4. Appearance 5. Objectivity 6. Additional adjective pairs B. The amount of compensation awarded the landowner C. The relationship of the dollar awards to juror ratings of trial participants D. Juror preferences for the trial participants E. Juror reactions to the trials IV. Discussion of the Results A. Comparative merits of deposition presentation methods 1. Read transcript 2. Audiotape 3. Black-and-white videotape 4. Color videotape 5. Conclusion B. An evaluation of the use of videotape to present all testimony at trial C. Recommendations for future researc