Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner.

Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem cell and tissue population dynamics. We show that healthy cells induce clonal extinction in weak tissues, targeting both stem and differentiated cells for elimination. We also find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization. Finally, we show that winner cell proliferation is fueled by the JAK-STAT ligand Unpaired-3, produced by Minute(-/+) cells in response to chronic JNK stress signaling.This work was supported by a Cancer Research UK Programme Grant (E.P. and G.K. A12460), a Royal Society University Research fellowship to E.P. (UF090580), an EMBO Long-Term Fellowship (ALTF 1476-2012), NWO Rubicon grant (825.12.027) and a Dutch Cancer Society Fellowship (BUIT-2013-5847) to S.J.E.S, a Wellcome Trust PhD studentships to IK and Core grant funding from the Wellcome Trust Core (092096) and CRUK (C6946/A14492).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.devcel.2015.06.01

Analysis of spatial relationships in three dimensions: tools for the study of nerve cell patterning

<p>Abstract</p> <p>Background</p> <p>Multiple technologies have been brought to bear on understanding the three-dimensional morphology of individual neurons and glia within the brain, but little progress has been made on understanding the rules controlling cellular patterning. We describe new matlab-based software tools, now available to the scientific community, permitting the calculation of spatial statistics associated with 3D point patterns. The analyses are largely derived from the Delaunay tessellation of the field, including the nearest neighbor and Voronoi domain analyses, and from the spatial autocorrelogram.</p> <p>Results</p> <p>Our tools enable the analysis of the spatial relationship between neurons within the central nervous system in 3D, and permit the modeling of these fields based on lattice-like simulations, and on simulations of minimal-distance spacing rules. Here we demonstrate the utility of our analysis methods to discriminate between two different simulated neuronal populations.</p> <p>Conclusion</p> <p>Together, these tools can be used to reveal the presence of nerve cell patterning and to model its foundation, in turn informing on the potential developmental mechanisms that govern its establishment. Furthermore, in conjunction with analyses of dendritic morphology, they can be used to determine the degree of dendritic coverage within a volume of tissue exhibited by mature nerve cells.</p

Anatomical and biomechanical evaluation of the tension band technique in patellar fractures

Tension band wiring for patellar fractures is common, but some recent reports refer to disadvantages of this approach. Our anatomical and biomechanical study focused on use of tension band techniques in patellar fractures. The anatomy of the patella and tendon insertion was examined with knee magnetic resonance imaging (MRI) and correlated with the technical requirements of the tension band. Tension band wiring over tendinous tissue was simulated and calculated with a cyclic biomechanical test on cow patellae. According to tension band templating on the MRI section, Kirschner wire insertion was needed for the tension band to turn over the tendinous tissue. The tension band became more stable while turning over less tendinous tissue and more adjacent bone surface. Nevertheless, cyclic loading tests indicate that all tension band applications in this study lose their initial stability. Excessive initial compression by the tension band resulted in bending of the Kirschner wire and thus reduction failure. For optimum stabilisation, tension force transfer should be done directly on bone or at least material that protects the tendon would be useful

A composite axion from a supersymmetric product group

A global $U(1)_\text{PQ}$ symmetry is protected from gravitational effects in the s-confining $SU(N)^k$ product group theory with $A+4Q +N\overline{Q}$ matter. If the $SU(4)$ family symmetry is gauged and an appropriate tree-level superpotential is added, then the dynamically generated superpotential spontaneously breaks $SU(4)\times U(1)_\text{PQ} \rightarrow SU(3)_c$ and produces a QCD axion. Small values of the $CP$-violating $\theta$ parameter are then possible without any fine-tuning, as long as the product group is suitably large. By introducing a second copy of the s-confining $SU(N)$ product group also coupled to the gauged $SU(4)$, we find that values as small as $N=7$ are consistent with $\bar\theta<10^{-10}$, even under the pessimistic assumption that the dominant contribution to the axion quality is at tree level.Comment: 16 pages, 3 figures, 4 tables, 2 appendice

Elastin is Localised to the Interfascicular Matrix of Energy Storing Tendons and Becomes Increasingly Disorganised With Ageing

Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone. Recent data indicates enrichment of elastin within the IFM, but this has yet to be quantified. We hypothesised that elastin is more prevalent in energy storing than positional tendons, and is mainly localised to the IFM. Further, we hypothesised that elastin becomes disorganised and fragmented, and decreases in amount with ageing, especially in energy storing tendons. Biochemical analyses and immunohistochemical techniques were used to determine elastin content and organisation, in young and old equine energy storing and positional tendons. Supporting the hypothesis, elastin localises to the IFM of energy storing tendons, reducing in quantity and becoming more disorganised with ageing. These changes may contribute to the increased injury risk in aged energy storing tendons. Full understanding of the processes leading to loss of elastin and its disorganisation with ageing may aid in the development of treatments to prevent age related tendinopathy

Increased insolation threshold for runaway greenhouse processes on Earth like planets

Because the solar luminosity increases over geological timescales, Earth climate is expected to warm, increasing water evaporation which, in turn, enhances the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can "runaway" until all the oceans are evaporated. Through increases in stratospheric humidity, warming may also cause oceans to escape to space before the runaway greenhouse occurs. The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated with unidimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of Earth's climate. Here we use a 3D global climate model to show that the threshold for the runaway greenhouse is about 375 W/m$^2$, significantly higher than previously thought. Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback on the long term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to defer the runaway greenhouse limit to higher insolation than inferred from 1D models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains cold and dry enough to hamper atmospheric water escape, even at large fluxes. This has strong implications for Venus early water history and extends the size of the habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013. Accepted version before journal editing and with Supplementary Informatio

Mechanisms of Esophago-Pharyngeal Acid Regurgitation in Human Subjects

Esophago-pharyngeal regurgitation is implicated in various otolaryngologic and respiratory disorders. The pathophysiological mechanisms causing regurgitation are still largely unknown

Strength is in engagement The rise of an online scientific community during the COVID‐19 pandemic

Many scientists, confined to home office by COVID-19, have been gathering in online communities, which could become viable alternatives to physical meetings and conferences

Tendinopathy—from basic science to treatment

Chronic tendon pathology (tendinopathy), although common, is difficult to treat. Tendons possess a highly organized fibrillar matrix, consisting of type I collagen and various 'minor' collagens, proteoglycans and glycoproteins. The tendon matrix is maintained by the resident tenocytes, and there is evidence of a continuous process of matrix remodeling, although the rate of turnover varies at different sites. A change in remodeling activity is associated with the onset of tendinopathy. Major molecular changes include increased expression of type III collagen, fibronectin, tenascin C, aggrecan and biglycan. These changes are consistent with repair, but they might also be an adaptive response to changes in mechanical loading. Repeated minor strain is thought to be the major precipitating factor in tendinopathy, although further work is required to determine whether it is mechanical overstimulation or understimulation that leads to the change in tenocyte activity. Metalloproteinase enzymes have an important role in the tendon matrix, being responsible for the degradation of collagen and proteoglycan in both healthy patients and those with disease. Metalloproteinases that show increased expression in painful tendinopathy include ADAM (a disintegrin and metalloproteinase)-12 and MMP (matrix metalloproteinase)-23. The role of these enzymes in tendon pathology is unknown, and further work is required to identify novel and specific molecular targets for therapy