Heat induces multiomic and phenotypic stress propagation in zebrafish embryos

Heat alters biology from molecular to ecological levels, but may also have unknown indirect effects. This includes the novel concept that animals exposed to abiotic stress can induce stress in naive receivers. Here, we provide a comprehensive picture of the molecularsignatures of this process, by integrating multiomic and phenotypic data. In individual zebrafish embryos, repeated heat peakselicited both a molecular response and a burst of accelerated growth followed by a growth slowdown in concert with reducedresponses to novel stimuli. Metabolomes of the media of heat treated vs. untreated embryos revealed candidate stress metabolitesincluding sulfur-containing compounds and lipids. These stress metabolites elicited transcriptomic changes in naive receivers related to immune response, extracellular signaling, glycosaminoglycan/keratan sulfate, and lipid metabolism. Consequently, non–heatexposed receivers (exposed to stress metabolites only) experienced accelerated catch-up growth in concert with reduced swimming performance. The combination of heat and stress metabolites accelerated development the most, mediated by apelin signaling. Our results prove the concept of indirect heat-induced stress propagation toward naive receivers, inducing phenotypes comparable with those resulting from direct heat exposure, but utilizing distinct molecular pathways. Group-exposing a nonlaboratory zebrafish line, we independently confirm that the glycosaminoglycan biosynthesis–related gene chs1 and the mucus glycoprotein gene prg4a, functionally connected to the candidate stress metabolite classes sugars and phosphocholine, are differentially expressed in receivers. This hints at the production of Schreckstoff-like cues in receivers, leading to further stress propagation within groups, which may have ecological and animal welfare implications for aquatic populations in a changing climate

Inhibition of Hsp90 Leads to Cell Cycle Arrest and Apoptosis in Human Malignant Pleural Mesothelioma

IntroductionHeat shock protein 90 (Hsp90) is an abundant molecular chaperone that mediates the maturation and stability of a variety of proteins associated with the promotion of cell growth and survival. Inhibition of Hsp90 function leads to proteasomal degradation of its mis-folded client proteins. Recently, Hsp90 has emerged as being of prime importance to the growth and survival of cancer cells and its inhibitors have already been used in phase I and II clinical trials.MethodsWe investigated how 17-allylamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is implicated in human malignant pleural mesothelioma (MM).ResultsWe found that 17-AAG led to significant G1 or G2/M cell cycle arrest, inhibition of cell proliferation, and decrease of AKT, AKT1, and survivin expression in all human malignant pleural mesothelioma cell lines examined. We also observed significant apoptosis induction in all MM cell lines treated with 17-AAG. Furthermore, 17-AAG induced apoptosis in freshly cultured primary MM cells and caused signaling changes identical to those in 17-AAG treated MM cell lines.ConclusionThese results suggest that Hsp90 is strongly associated with the growth and survival of MM and that inhibition of Hsp90 may have therapeutic potential in the treatment of MM

Evans Committee Statement on Pioneer

Letter from University of Denver faculty and alumni on the university\u27s use of the \u27Pioneer\u27 moniker

Next Generation Very Large Array Memo No. 6, Science Working Group 1: The Cradle of Life

This paper discusses compelling science cases for a future long-baseline interferometer operating at millimeter and centimeter wavelengths, like the proposed Next Generation Vary Large Array (ngVLA). We report on the activities of the Cradle of Life science working group, which focused on the formation of low- and high-mass stars, the formation of planets and evolution of protoplanetary disks, the physical and compositional study of Solar System bodies, and the possible detection of radio signals from extraterrestrial civilizations. We propose 19 scientific projects based on the current specification of the ngVLA. Five of them are highlighted as possible Key Science Projects: (1) Resolving the density structure and dynamics of the youngest HII regions and high-mass protostellar jets, (2) Unveiling binary/multiple protostars at higher resolution, (3) Mapping planet formation regions in nearby disks on scales down to 1 AU, (4) Studying the formation of complex molecules, and (5) Deep atmospheric mapping of giant planets in the Solar System. For each of these projects, we discuss the scientific importance and feasibility. The results presented here should be considered as the beginning of a more in-depth analysis of the science enabled by such a facility, and are by no means complete or exhaustive.Comment: 51 pages, 12 figures, 1 table. For more information visit https://science.nrao.edu/futures/ngvl

Functional genomics of abiotic environmental adaptation in lacertid lizards and other vertebrates

Understanding the genomic basis of adaptation to different abiotic environments is important in the context of climate change and resulting short-term environmental fluctuations. Using functional and comparative genomics approaches, we here investigated whether signatures of genomic adaptation to a set of environmental parameters are concentrated in specific subsets of genes and functions in lacertid lizards and other vertebrates. We first identify 200 genes with signatures of positive diversifying selection from transcriptomes of 24 species of lacertid lizards and demonstrate their involvement in physiological and morphological adaptations to climate. To understand how functionally similar these genes are to previously predicted candidate functions for climate adaptation and to compare them with other vertebrate species, we then performed a meta-analysis of 1,100 genes under selection obtained from -omics studies in vertebrate species adapted to different abiotic factors. We found that the vertebrate gene set formed a tightly connected interactome, which was to 23% enriched in previously predicted functions of adaptation to climate, and to a large part (18%) involved in organismal stress response. We found a much higher degree of identical genes being repeatedly selected among different animal groups (43.6%), and of functional similarity and post-translational modifications than expected by chance, and no clear functional division between genes used for ectotherm and endotherm physiological strategies. In total, 171 out of 200 genes of Lacertidae were part of this network. These results highlight an important role of a comparatively small set of genes and their functions in environmental adaptation and narrow the set of candidate pathways and markers to be used in future research on adaptation and stress response related to climate change

John Evans Study Committee Recommendations

With the completion of this report the University of Denver is presented with an opportunity to reflect on our institutional origins, history, and legacy. We have an opportunity to provide a model of transparency, accountability, and transformation for institutions that have directly profited or indirectly benefited from the displacement of the indigenous communities whose lands and histories they occupy. This moment invites us to bend the arc of history away from the clamor of old apologetics that have caused deep wounds for those whose voices have been silenced and toward justice, healing, and peace. This likewise holds for those whose privilege and power has been upheld by historical noise, silence, and intentional omission. This is truly a new horizon and DU should be a change leader illuminating a new path forward: a path of unity, collaboration, and healing for all communities

Top ten accelerating cosmological models

Recent astronomical observations indicate that the Universe is presently almost flat and undergoing a period of accelerated expansion. Basing on Einstein's general relativity all these observations can be explained by the hypothesis of a dark energy component in addition to cold dark matter (CDM). Because the nature of this dark energy is unknown, it was proposed some alternative scenario to explain the current accelerating Universe. The key point of this scenario is to modify the standard FRW equation instead of mysterious dark energy component. The standard approach to constrain model parameters, based on the likelihood method, gives a best-fit model and confidence ranges for those parameters. We always arbitrary choose the set of parameters which define a model which we compare with observational data. Because in the generic case, the introducing of new parameters improves a fit to the data set, there appears the problem of elimination of model parameters which can play an insufficient role. The Bayesian information criteria of model selection (the AIC and BIC) are dedicated to promotion a set of parameters which should be incorporated to the model. We divide class of all accelerating cosmological models into two groups according to the two types of explanation acceleration of the Universe. Then the Bayesian framework of model selection is used to determine the set of parameters which gives preferred fit to the SNIa data. We find a few of flat cosmological models which can be recommend by both the Bayes factor and Akaike information criterion.Comment: RevTeX4, 11 pages, 7 figures; v2 some clarifications, bibliography additions, new figure (comparisons with respect to LambdaCDM

The benefit of sequentiality in social networks *

Abstract This paper examines the benefit of sequentiality in the social networks. We adopt the elegant theoretical framework proposed by We then examine the structure of optimal mechanism and allow for arbitrary sequence of players' moves. We show that starting from any fixed sequence, the aggregate contribution always goes up while making simultaneous-moving players move sequentially. This suggests a robust rule of thumbs -any local modification towards the sequential-move game is beneficial. Pushing this idea to the extreme, the optimal sequence turns out to be a chain structure, i.e., players should move one by one. Our results continue to hold when either players exhibit strategic substitutes instead or the network designer's goal is to maximize the players' aggregate payoff rather than the aggregate contribution