Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells

Metastatic competence of cancer cells is influenced by many factors including metabolic alterations and changes in mitochondrial biogenesis and protein homeostasis. While it is generally accepted that mitochondria play important roles in tumorigenesis, the respective molecular events that regulate aberrant cancer cell proliferation remain to be clarified. Therefore, understanding the mechanisms underlying the role of mitochondria in cancer progression has potential implications in the development of new therapeutic strategies. We show that low expression of mitochondrial quality control protease OMA1 correlates with poor overall survival in breast cancer patients. Silencing OMA1 in vitro in patientderived metastatic breast cancer cells isolated from the metastatic pleural effusion and atypical ductal hyperplasia mammary tumor specimens (21MT-1 and 21PT) enhances the formation of filopodia, increases cell proliferation (Ki67 expression), and induces epithelial-mesenchymal transition (EMT). Mechanistically, loss of OMA1 results in alterations in the mitochondrial protein homeostasis, as reflected by enhanced expression of canonic mitochondrial unfolded protein response genes. These changes significantly increase migratory properties in metastatic breast cancer cells, indicating that OMA1 plays a critical role in suppressing metastatic competence of breast tumors. Interestingly, these results were not observed in OMA1-depleted non-tumorigenic MCF10A mammary epithelial cells. This newly identified reduced activity/levels of OMA1 provides insights into the mechanisms leading to breast cancer development, promoting malignant progression of cancer cells and unfavorable clinical outcomes, which may represent possible prognostic markers and therapeutic targets for breast cancer treatment

Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells

Metastatic competence of cancer cells is influenced by many factors including metabolic alterations and changes in mitochondrial biogenesis and protein homeostasis. While it is generally accepted that mitochondria play important roles in tumorigenesis, the respective molecular events that regulate aberrant cancer cell proliferation remain to be clarified. Therefore, understanding the mechanisms underlying the role of mitochondria in cancer progression has potential implications in the development of new therapeutic strategies. We show that low expression of mitochondrial quality control protease OMA1 correlates with poor overall survival in breast cancer patients. Silencing OMA1 in vitro in patientderived metastatic breast cancer cells isolated from the metastatic pleural effusion and atypical ductal hyperplasia mammary tumor specimens (21MT-1 and 21PT) enhances the formation of filopodia, increases cell proliferation (Ki67 expression), and induces epithelial-mesenchymal transition (EMT). Mechanistically, loss of OMA1 results in alterations in the mitochondrial protein homeostasis, as reflected by enhanced expression of canonic mitochondrial unfolded protein response genes. These changes significantly increase migratory properties in metastatic breast cancer cells, indicating that OMA1 plays a critical role in suppressing metastatic competence of breast tumors. Interestingly, these results were not observed in OMA1-depleted non-tumorigenic MCF10A mammary epithelial cells. This newly identified reduced activity/levels of OMA1 provides insights into the mechanisms leading to breast cancer development, promoting malignant progression of cancer cells and unfavorable clinical outcomes, which may represent possible prognostic markers and therapeutic targets for breast cancer treatment

Control of sexuality by the \u3cem\u3esk1\u3c/em\u3e-encoded UDP-glycosyltransferase of maize

Sex determination in maize involves the production of staminate and pistillate florets from an initially bisexual floral meristem. Pistil elimination in staminate florets requires jasmonic acid signaling, and functional pistils are protected by the action of the silkless 1 (sk1) gene. The sk1 gene was identified and found to encode a previously uncharacterized family 1 uridine diphosphate glycosyltransferase that localized to the plant peroxisomes. Constitutive expression of an sk1 transgene protected all pistils in the plant, causing complete feminization, a gain-of-function phenotype that operates by blocking the accumulation of jasmonates. The segregation of an sk1 transgene was used to effectively control the production of pistillate and staminate inflorescences in maize plants

An ALMA survey of submillimetre galaxies in the COSMOS field: The extent of the radio-emitting region revealed by 3 GHz imaging with the Very Large Array

We determine the radio size distribution of a large sample of 152 SMGs in COSMOS that were detected with ALMA at 1.3 mm. For this purpose, we used the observations taken by the VLA-COSMOS 3 GHz Large Project. One hundred and fifteen of the 152 target SMGs were found to have a 3 GHz counterpart. The median value of the major axis FWHM at 3 GHz is derived to be $4.6\pm0.4$ kpc. The radio sizes show no evolutionary trend with redshift, or difference between different galaxy morphologies. We also derived the spectral indices between 1.4 and 3 GHz, and 3 GHz brightness temperatures for the sources, and the median values were found to be $\alpha=-0.67$ and $T_{\rm B}=12.6\pm2$ K. Three of the target SMGs, which are also detected with the VLBA, show clearly higher brightness temperatures than the typical values. Although the observed radio emission appears to be predominantly powered by star formation and supernova activity, our results provide a strong indication of the presence of an AGN in the VLBA and X-ray-detected SMG AzTEC/C61. The median radio-emitting size we have derived is 1.5-3 times larger than the typical FIR dust-emitting sizes of SMGs, but similar to that of the SMGs' molecular gas component traced through mid-$J$ line emission of CO. The physical conditions of SMGs probably render the diffusion of cosmic-ray electrons inefficient, and hence an unlikely process to lead to the observed extended radio sizes. Instead, our results point towards a scenario where SMGs are driven by galaxy interactions and mergers. Besides triggering vigorous starbursts, galaxy collisions can also pull out the magnetised fluids from the interacting disks, and give rise to a taffy-like synchrotron-emitting bridge. This provides an explanation for the spatially extended radio emission of SMGs, and can also cause a deviation from the well-known IR-radio correlation.Comment: 32 pages (incl. 5 appendices), 17 figures, 7 tables; accepted for publication in A&A; abstract abridged for arXi

Planets Around Low-Mass Stars (PALMS). V. Age-Dating Low-Mass Companions to Members and Interlopers of Young Moving Groups

Copyright © 2015. The American Astronomical Society. All rights reserved.We present optical and near-infrared adaptive optics (AO) imaging and spectroscopy of 13 ultracool (>M6) companions to late-type stars (K7-M4.5), most of which have recently been identified as candidate members of nearby young moving groups (YMGs; 8-120 Myr) in the literature. The inferred masses of the companions (~10-100 Mjup) are highly sensitive to the ages of the primary stars so we critically examine the kinematic and spectroscopic properties of each system to distinguish bona fide YMG members from old field interlopers. 2MASS J02155892-0929121 C is a new M7 substellar companion (40-60 Mjup) with clear spectroscopic signs of low gravity and hence youth. The primary, possibly a member of the ~40 Myr Tuc-Hor moving group, is visually resolved into three components, making it a young low-mass quadruple system in a compact (1 Gyr) tidally-locked spectroscopic binaries without convincing kinematic associations with any known moving group. The high rate of false positives in the form of old active stars with YMG-like kinematics underscores the importance of radial velocity and parallax measurements to validate candidate young stars identified via proper motion and activity selection alone. Finally, we spectroscopically confirm the cool temperature and substellar nature of HD 23514 B, a recently discovered M8 benchmark brown dwarf orbiting the dustiest-known member of the Pleiades.NASANSFMt. Cuba Astronomical FoundationSamuel OschinAlfred P. Sloan Foundatio

Attentional Prioritization of Infant Faces Is Limited to Own-Race Infants

Background: Recent evidence indicates that infant faces capture attention automatically, presumably to elicit caregiving behavior from adults and leading to greater probability of progeny survival. Elsewhere, evidence demonstrates that people show deficiencies in the processing of other-race relative to own-race faces. We ask whether this other-race effect impacts on attentional attraction to infant faces. Using a dot-probe task to reveal the spatial allocation of attention, we investigate whether other-race infants capture attention. Principal Findings: South Asian and White participants (young adults aged 18–23 years) responded to a probe shape appearing in a location previously occupied by either an infant face or an adult face; across trials, the race (South Asian/ White) of the faces was manipulated. Results indicated that participants were faster to respond to probes that appeared in the same location as infant faces than adult faces, but only on own-race trials. Conclusions/Significance: Own-race infant faces attract attention, but other-race infant faces do not. Sensitivity to facespecific care-seeking cues in other-race kindenschema may be constrained by interracial contact and experience

High Quality Care and Ethical Pay-for-Performance: A Society of General Internal Medicine Policy Analysis

BACKGROUND: Pay-for-performance is proliferating, yet its impact on key stakeholders remains uncertain. OBJECTIVE: The Society of General Internal Medicine systematically evaluated ethical issues raised by performance-based physician compensation. RESULTS: We conclude that current arrangements are based on fundamentally acceptable ethical principles, but are guided by an incomplete understanding of health-care quality. Furthermore, their implementation without evidence of safety and efficacy is ethically precarious because of potential risks to stakeholders, especially vulnerable patients. CONCLUSION: We propose four major strategies to transition from risky pay-for-performance systems to ethical performance-based physician compensation and high quality care. These include implementing safeguards within current pay-for-performance systems, reaching consensus regarding the obligations of key stakeholders in improving health-care quality, developing valid and comprehensive measures of health-care quality, and utilizing a cautious evaluative approach in creating the next generation of compensation systems that reward genuine quality

Aligning the Goals of Learning Analytics with its Research Scholarship: An Open Peer Commentary Approach

To promote cross-community dialogue on matters of significance within the field of learning analytics], we as editors-in- chief of the Journal of Learning Analytics have introduced a section for papers that are open to peer commentary. The first of these papers, “A LAK of Direction: Misalignment Between the Goals of Learning Analytics and its Research Scholarship” by Motz et al. (2023), appeared in the journal’s early access section in March 2023, a few days before the start of the 13th International Learning Analytics and Knowledge Conference (LAK ’23). “A LAK of Direction” takes as its starting point the definition of learning analytics used in the call for papers of the first LAK conference (LAK ’11) and used since then by the Society for Learning Analytics Research (SoLAR): “Learning analytics is the measurement, collection, analysis and reporting of data about learners and their contexts, for purposes of understanding and optimizing learning and the environments in which it occurs” (Long & Siemens, 2011, p. 24). Following the conference, an invitation to submit proposals for commentaries on the paper was released, and 12 of these proposals were accepted. This paper brings those commentaries togethe