Modeling Tumor Phenotypes In Vitro with Three-Dimensional Bioprinting

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Regionalization in LCA: current status in concepts,software and databases—69th LCA forum,Swiss Federal Institute of Technology,Zurich, 13 September, 2018

The International Journal of Life Cycle Assessment -     

Deubiquitinating c-Myc: USP36 steps up in the nucleolus

Ubiquitination plays a key and complex role in the regulation of c-Myc stability, transactivation, and oncogenic activity. c-Myc is ubiquitinated by a number of ubiquitin ligases (E3s), such as SCF^Fbw7 and SCF^Skp2. Depending on the E3s, ubiquitination can either positively or negatively regulate c-Myc levels and activity. Meanwhile, c-Myc ubiquitination can be reversed by deubiquitination. An early study showed that USP28 deubiquitinates c-Myc via interacting with Fbw7α whereas a recent study reveals that USP37 deubiquitinates c-Myc independently of Fbw7 and c-Myc phosphorylation. Consequently, both USP28 and USP37 stabilize c-Myc and enhance its activity. We recently found the nucleolar USP36 as a novel c-Myc deubiquitinase that controls the end-point of c-Myc degradation pathway in the nucleolus. Here we briefly review the current understanding of ubiquitination and deubiquitination regulation of c-Myc and further discuss the USP36-c-Myc regulatory pathway.     

Storm impacts on alpine lakes: Antecedent weather conditions matter more than the event intensity

Extreme weather events may be just as important as gradual trends for the long‐term trajectories of ecosystems. For alpine lakes, which are exposed to both exacerbated atmospheric warming and intense episodic weather events, future conditions might not be appropriately forecast by only climate change trends, i.e. warming, if extreme events have the potential to deflect their thermal and metabolic states from their seasonal ranges. We used high‐frequency monitoring data over three open‐water seasons with a one‐dimensional hydrodynamic model of the high‐altitude Lake Muzelle (France) to show that rainstorms or windstorms, notwithstanding their intensity, did not trigger long‐lasting consequences to the lake characteristics when light penetration into the lake was not modified. In contrast, storms associated with high turbidity input from the watershed (“turbid storms”) strongly modified the lacustrine hydrodynamics and metabolism for the rest of the open‐water season through reduced light penetration. The long‐lasting effects of turbid storms were related to the inputs and in‐lake persistence of very light glacial suspensoids from the watershed. The occurrence of the observed turbid storms was not related to the wind or rain intensities during the events. Instead, the turbid storms occurred after dry and atypically warm spells, i.e. meteorological conditions expected to be more frequent in this alpine region in the upcoming decades. Consequently, storm events, notwithstanding their intensity, are expected to strongly imprint the future ecological status of alpine lakes under climate warming.     

Collagen XVIII/endostatin is essential for vision and retinal pigment epithelial function

Age-related macular degeneration (ARMD) with abnormal deposit formation under the retinal pigment epithelium (RPE) is the major cause of blindness in the Western world. basal laminar deposits are found in early ARMD and are composed of excess basement membrane material produced by the RPE. Here, we demonstrate that mice lacking the basement membrane component collagen XVIII/endostatin have massive accumulation of sub-RPE deposits with striking similarities to basal laminar deposits, abnormal RPE, and age-dependent loss of vision. The progressive attenuation of visual function results from decreased retinal rhodopsin content as a consequence of abnormal vitamin A metabolism in the RPE. In addition, aged mutant mice show photoreceptor abnormalities and increased expression of glial fibrillary acidic protein in the neural retina. Our data demonstrate that collagen XVIII/endostatin is essential for RPE function, and suggest an important role of this collagen in Bruch's membrane. Consistent with such a role, the ultrastructural organization of collagen XVIII/endostatin in basement membranes, including Bruch's membrane, shows that it is part of basement membrane molecular networks.     

A spatially explicit data-driven approach to assess the effect of agricultural land occupation on species groups

Purpose

Change of vegetation cover and increased land use intensity, particularly for agricultural use, can affect species richness. Within life cycle impact assessment, methods to assess impacts of land use on a global scale are still in need of development. In this work, we present a spatially explicit data-driven approach to characterize the effect of agricultural land occupation on different species groups.

Methods

We derived characterization factors for the direct impact of agricultural land occupation on relative species richness. Our method identifies potential differences in impacts for cultivation of different crop types, on different species groups, and in different world regions. Using empirical species richness data gathered via an extensive literature search, characterization factors were calculated for four crop groups (oil palm, low crops, Pooideae, and Panicoideae), four species groups (arthropods, birds, mammals, and vascular plants), and six biomes.

Results and discussion

Analysis of the collected data showed that vascular plant richness is more sensitive than the species richness of arthropods to agricultural land occupation. Regarding the differences between world regions, the impact of agricultural land use was lower in boreal forests/taiga than in temperate and tropical regions. The impact of oil palm plantations was found to be larger than that of Pooideae croplands, although we cannot rule out that this difference is influenced by the spatial difference between the oil palm- and Pooideae-growing regions as well. Analysis of a subset of data showed that the impact of conventional farming was larger than the impact of low-input farming.

Conclusions

The impact of land occupation on relative species richness depends on the taxonomic groups considered, the climatic region, and farm management. The influence of crop type, however, was found to be of less importance.     

Prestin Regulation and Function in Residual Outer Hair Cells after Noise-Induced Hearing Loss

The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. Tecta^C1509G transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9–12 kHz region), where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30–40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9–12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32–58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in order to maintain stable auditory thresholds and frequency discrimination.     

Independence of the Sodium and Potassium Conductance Channels: A Kinetic Argument

Tightly coupled models for the sodium and potassium conductance changes, in which the potassium “on” process is intimately related to the sodium “on” and “off” processes, are studied. It is shown that such coupled models are incapable of simultaneously showing the observed effects of conditioning potentials on sodium inactivation and on the translation of the potassium conductance in time. It is concluded that the primary mechanisms for the sodium and potassium channels are probably independent.