A unique role for Stat5 in recovery from acute anemia

The precise role of erythropoietin receptor–activated (EpoR-activated) Stat5 in the regulation of erythropoiesis remains unclear. In this issue of the JCI, Menon and colleagues present new experimental data that indicate a distinct role for Stat5 in the regulation of stress-induced erythropoiesis, such as during acute anemic states. A critical function for Stat5 is to promote cell survival, possibly through transcriptional induction of the antiapoptotic protein Bcl-x. In the present experimental system, erythropoietin-Stat5 signals did not induce Bcl-x expression but did induce oncostatin-M. Moreover, oncostatin-M was found to enhance survival of erythroid progenitors. This work differentiates between steady-state (or homeostatic) erythropoiesis and stress-induced erythropoiesis at the level of EpoR signaling

Identifying Contaminated K-band Globular Cluster RR Lyrae Photometry

Acquiring near-infrared K-band (2.2 um) photometry for RR Lyrae variables in globular clusters and nearby galaxies is advantageous since the resulting distances are less impacted by reddening and metallicity. However, K-band photometry for RR Lyrae variables in M5, Reticulum, M92, omega Cen, and M15 display clustercentric trends. HST ACS data imply that multiple stars in close proximity to RR Lyrae variables located near the cluster core, where the stellar density increases markedly, are generally unresolved in ground-based images. RR Lyrae variables near the cluster cores appear to suffer from photometric contamination, thereby yielding underestimated cluster distances and biased ages. The impact is particularly pernicious since the contamination propagates a systematic uncertainty into the distance scale, and hinders the quest for precision cosmology. The clustercentric trends are probably unassociated with variations in chemical composition since an empirical K-band period-magnitude relation inferred from Araucaria/VLT data for RR Lyrae variables in the Sculptor dSph exhibits a negligible metallicity dependence: (0.059+-0.095)[Fe/H], a finding that supports prior observational results. A future multi-epoch high-resolution near-infrared survey, analogous to the optical HST ACS Galactic Globular Cluster Survey, may be employed to establish K-band photometry for the contaminating stars discussed here.Comment: To appear in PAS

Daylighting: appraisal at the early design stages

For a building design team concerned with the quality of the internal environment of buildings the percentage area of glazing on a building facade is one of the most useful criteria for judging the building envelope as a modifier of climate at early design stages since it is at the window that the various environmental parameters (heat, light and sound) remain only minimally modified. The percentage area of glazing can be used to relate the numerous and often conflicting functions of the window such as the provision of daylight, summer time teperatures, sound insulation, energy efficiency and view satisfaction

Tracing the Conversion of Gas into Stars in Young Massive Cluster Progenitors

Whilst young massive clusters (YMCs; $M$ $\gtrsim$ 10$^{4}$ M$_{\odot}$, age $\lesssim$ 100 Myr) have been identified in significant numbers, their progenitor gas clouds have eluded detection. Recently, four extreme molecular clouds residing within 200 pc of the Galactic centre have been identified as having the properties thought necessary to form YMCs. Here we utilise far-IR continuum data from the Herschel Infrared Galactic Plane Survey (HiGAL) and millimetre spectral line data from the Millimetre Astronomy Legacy Team 90 GHz Survey (MALT90) to determine their global physical and kinematic structure. We derive their masses, dust temperatures and radii and use virial analysis to conclude that they are all likely gravitationally bound -- confirming that they are likely YMC progenitors. We then compare the density profiles of these clouds to those of the gas and stellar components of the Sagittarius B2 Main and North proto-clusters and the stellar distribution of the Arches YMC. We find that even in these clouds -- the most massive and dense quiescent clouds in the Galaxy -- the gas is not compact enough to form an Arches-like ($M$ = 2x10$^{4}$ M$_{\odot}$, R$_{eff}$ = 0.4 pc) stellar distribution. Further dynamical processes would be required to condense the resultant population, indicating that the mass becomes more centrally concentrated as the (proto)-cluster evolves. These results suggest that YMC formation may proceed hierarchically rather than through monolithic collapse.Comment: 12 pages, 8 figures, 1 table. Accepted by MNRA

LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer

Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed and markedly activated before initiation of self-renewal. Moreover, TAZ, SNAIL, CHK1/2, and Aurora-A were expressed in hierarchical, oscillating patterns during sphere formation, suggesting that the process consists of four sequential steps. Our results indicate that LATS1/2 trigger self-renewal of CSCs by regulating the Hippo pathway, the EMT, and cell division

Rho1 regulates adherens junction remodeling by promoting recycling endosome formation through activation of myosin II

Once adherens junctions (AJs) are formed between polarized epithelial cells they must be maintained because AJs are constantly remodeled in dynamic epithelia. AJ maintenance involves endocytosis and subsequent recycling of E-cadherin to a precise location along the basolateral membrane. In the Drosophila pupal eye epithelium, Rho1 GTPase regulates AJ remodeling through Drosophila E-cadherin (DE-cadherin) endocytosis by limiting Cdc42/Par6/aPKC complex activity. We demonstrate that Rho1 also influences AJ remodeling by regulating the formation of DE-cadherin–containing, Rab11-positive recycling endosomes in Drosophila postmitotic pupal eye epithelia. This effect of Rho1 is mediated through Rok-dependent, but not MLCK-dependent, stimulation of myosin II activity yet independent of its effects upon actin remodeling. Both Rho1 and pMLC localize on endosomal vesicles, suggesting that Rho1 might regulate the formation of recycling endosomes through localized myosin II activation. This work identifies spatially distinct functions for Rho1 in the regulation of DE-cadherin–containing vesicular trafficking during AJ remodeling in live epithelia

DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs

Biomechanical changes in the tumor microenvironment influence tumor progression and metastases. Collagen content and fiber organization within the tumor stroma are major contributors to biomechanical changes (e., tumor stiffness) and correlated with tumor aggressiveness and outcome. What signals and in what cells control collagen organization within the tumors, and how, is not fully understood. We show in mouse breast tumors that the action of the collagen receptor DDR2 in CAFs controls tumor stiffness by reorganizing collagen fibers specifically at the tumor-stromal boundary. These changes were associated with lung metastases. The action of DDR2 in mouse and human CAFs, and tumors in vivo, was found to influence mechanotransduction by controlling full collagen-binding integrin activation via Rap1-mediated Talin1 and Kindlin2 recruitment. The action of DDR2 in tumor CAFs is thus critical for remodeling collagen fibers at the tumor-stromal boundary to generate a physically permissive tumor microenvironment for tumor cell invasion and metastases

Micro‐cultures of Conflict: Couple‐level Perspectives on Reasons for and Causes of Intimate Partner Violence in Young Adulthood

Objective To highlight the development of young adult couples\u27 shared understandings about reasons for conflict in their relationships, views about why some disagreements included the use of aggression ( causes ), and gendered perspectives on these relationship dynamics. Background Feminist theories have centered on relationship dynamics associated with intimate partner violence (IPV), but have focused primarily on men\u27s concerns (e.g., jealousy) and use of violence as a means of control over female partners. The current analysis drew on symbolic interaction theory as a framework for exploring couple-level concerns, and ways in which dyadic communication contributes to these understandings, or what can be considered “micro-cultures” of conflict. Method The study relied on in-depth interviews with a heterogeneous sample of IPV-experienced young adults who had participated in a larger longitudinal study (Toledo Adolescent Relationships Study [TARS]) and separate interviews with their partners (n = 90). Results Analyses revealed that women\u27s concerns about men\u27s actions (e.g., infidelity) were frequently cited as reasons for serious conflicts, and showed significant concordance in partners\u27 reports. Shared understandings sometimes extended to views on the role of more distal causes (e.g., family background) and the meaning(s) of each partner\u27s use of aggression. Gendered dynamics included men\u27s tendency to minimize women\u27s concerns, and both partners\u27 more open discussions of women\u27s perpetration. Conclusions Theories of IPV and associated programmatic efforts should include attention to the social construction of these micro-cultures, as these shared meanings affect behavior, are potentially malleable, and add to the more intuitive focus on one-sided forces of control and constraint