Pore formation by GSDMD is the effector mechanism of pyroptosis

Pyroptosis is a unique, pro‐inflammatory form of lytic cell death that is initiated by the activation of inflammatory caspases. The caspase substrate gasdermin D (GSDMD) plays a critical function in pyroptosis, yet the precise mode of action of this molecule in cell death execution remained unclear. Several recent reports, including a The EMBO Journal article, show that the caspase‐matured N‐terminal fragment of GSDMD is recruited to lipid membranes to form pore‐like structures, which constitutes the key effector mechanism of pyroptotic cell death.     

Introducing an algal carbon‐concentrating mechanism into higher plants: location and incorporation of key components

Many eukaryotic green algae possess biophysical carbon‐concentrating mechanisms (CCMs) that enhance photosynthetic efficiency and thus permit high growth rates at low CO₂ concentrations. They are thus an attractive option for improving productivity in higher plants. In this study, the intracellular locations of ten CCM components in the unicellular green alga Chlamydomonas reinhardtii were confirmed. When expressed in tobacco, all of these components except chloroplastic carbonic anhydrases CAH3 and CAH6 had the same intracellular locations as in Chlamydomonas. CAH6 could be directed to the chloroplast by fusion to an Arabidopsis chloroplast transit peptide. Similarly, the putative inorganic carbon (Ci) transporter LCI1 was directed to the chloroplast from its native location on the plasma membrane. CCP1 and CCP2 proteins, putative Ci transporters previously reported to be in the chloroplast envelope, localized to mitochondria in both Chlamydomonas and tobacco, suggesting that the algal CCM model requires expansion to include a role for mitochondria. For the Ci transporters LCIA and HLA3, membrane location and Ci transport capacity were confirmed by heterologous expression and H¹⁴CO₃^‐ uptake assays in Xenopus oocytes. Both were expressed in Arabidopsis resulting in growth comparable with that of wild‐type plants. We conclude that CCM components from Chlamydomonas can be expressed both transiently (in tobacco) and stably (in Arabidopsis) and retargeted to appropriate locations in higher plant cells. As expression of individual Ci transporters did not enhance Arabidopsis growth, stacking of further CCM components will probably be required to achieve a significant increase in photosynthetic efficiency in this species.     

Inducible gene modification in the gastric epithelium of Tff1‐CreERT2, Tff2‐rtTA,Tff3‐luc mice

Temporal and spatial regulation of genes mediated by tissue‐specific promoters and conditional gene expression systems provide a powerful tool to study gene function in health, disease, and during development. Although transgenic mice expressing the Cre recombinase in the gastric epithelium have been reported, there is a lack of models that allow inducible and reversible gene modification in the stomach. Here, we exploited the gastrointestinal epithelium‐specific expression pattern of the three trefoil factor (Tff) genes and bacterial artificial chromosome transgenesis to generate a novel mouse strain that expresses the CreERT2 recombinase and the reverse tetracycline transactivator (rtTA). The Tg(Tff1‐CreERT2;Tff2‐rtTA;Tff3‐Luc) strain confers tamoxifen‐inducible irreversible somatic recombination and allows simultaneous doxycycline‐dependent reversible gene activation in the gastric epithelium of developing and adult mice. This strain also confers luciferase activity to the intestinal epithelium to enable in vivo bioluminescence imaging. Using fluorescent reporters as conditional alleles, we show Tff1‐CreERT2 and Tff2‐rtTA transgene activity in a partially overlapping subset of long‐term regenerating gastric stem/progenitor cells. Therefore, the Tg(Tff1‐CreERT2;Tff2‐rtTA;Tff3‐Luc) strain can confer intermittent transgene expression to gastric epithelial cells that have undergone previous gene modification, and may be suitable to genetically model therapeutic intervention during development, tumorigenesis, and other genetically tractable diseases. Birth Defects Research (Part A) 106:626–635, 2016. © 2016 Wiley Periodicals, Inc.     

A bootstrap-aggregated hybrid semi-parametric modeling framework for bioprocess development

Bioprocess and Biosystems Engineering - Hybrid semi-parametric modeling, combining mechanistic and machine-learning methods, has proven to be a powerful method for process development. This paper...     

Sequentially Deposited versus Conventional Nonfullerene Organic Solar Cells: Interfacial Trap States,Vertical Stratification,and Exciton Dissociation

Bulk heterojunction (BHJ) nonfullerene organic solar cells prepared from sequentially deposited donor and acceptor layers (sq‐BHJ) have recently been shown to be highly efficient, environmentally friendly, and compatible with large area and roll‐to‐roll fabrication. However, the related photophysics at donor‐acceptor interface and the vertical heterogeneity of donor‐acceptor distribution, critical for exciton dissociation and device performance, have been largely unexplored. Herein, steady‐state and time‐resolved optical and electrical techniques are employed to characterize the interfacial trap states. Correlating with the luminescent efficiency of interfacial states and its nonradiative recombination, interfacial trap states are characterized to be about 40% more populated in the sq‐BHJ devices than the as‐cast BHJ (c‐BHJ), which probably limits the device voltage output. Cross‐sectional energy‐dispersive X‐ray spectroscopy and ultraviolet photoemission spectroscopy depth profiling directly visualize the donor–acceptor vertical stratification with a precision of 1–2 nm. From the proposed “needle” model, the high exciton dissociation efficiency is rationalized. This study highlights the promise of sequential deposition to fabricate efficient solar cells, and points toward improving the voltage output and overall device performance via eliminating interfacial trap states.     

Methane yield and species diversity dynamics of perennial wild plant mixtures established alone,under cover crop maize (Zea mays L.), and after spring barley (Hordeum vulgare L.)

The cultivation of perennial wild plant mixtures (WPMs) in biogas cropping systems dominated by maize (Zea mays L.) restores numerous ecosystem functions and improves both spatial and temporal agrobiodiversity. In addition, the colorful appearance of WPM can help enhance landscape beauty. However, their methane yield per hectare (MYH) varies greatly and amounts to only about 50% that of maize. This study aimed at decreasing MYH variability and increasing accumulated MYH of WPM by optimizing the establishment method. A field trial was established in southwest Germany in 2014, and is still running. It tested the effects of three WPM establishment procedures (E1: alone [without maize, in May], E2: undersown in cover crop maize [in May], E3: WPM sown after whole‐crop harvest of spring barley [Hordeum vulgare L.] in June) on both MYH and species diversity of two WPMs [S1, S2]). Mono‐cropped maize and cup plant (Silphium perfoliatum L.) were used as reference crops. Of the WPM treatments tested, S2E2 achieved the highest (19,296 , 60.5% of maize) and S1E1 the lowest accumulated MYH (8,156 , 25.6% of maize) in the years 2014–2018. Cup plant yielded slightly higher than S2E2 (19,968 , 62.6% of maize). In 2014, the WPM sown under maize did not significantly affect the cover crop performance. From 2015 onward, E1 and E2 had comparable average annual MYH and average annual number of WPM species. With a similar accumulated MYH but significantly higher number of species (3.5–10.2), WPM S2E2 outperformed cup plant. Overall, the long‐term MYH performance of WPM cultivation for biogas production can be significantly improved by undersowing with maize as cover crop. This improved establishment method could help facilitate the implementation of WPM cultivation for biogas production and thus reduce the trade‐off between bioenergy and biodiversity.     

The highly diverged trypanosomal MICOS complex is organized in a nonessential integral membrane and an essential peripheral module

The mitochondrial contact site and cristae organization system (MICOS) mediates the formation of cristae, invaginations in the mitochondrial inner membrane. The highly diverged MICOS complex of the parasitic protist Trypanosoma brucei consists of nine subunits. Except for two Mic10‐like and a Mic60‐like protein, all subunits are specific for kinetoplastids. Here, we determined on a proteome‐wide scale how ablation of individual MICOS subunits affects the levels of the other subunits. The results reveal co‐regulation of TbMic10‐1, TbMic10‐2, TbMic16 and TbMic60, suggesting that these nonessential, integral inner membrane proteins form an interdependent network. Moreover, the ablation of TbMic34 and TbMic32 reveals another network consisting of the essential, intermembrane space‐localized TbMic20, TbMic32, TbMic34 and TbMic40, all of which are peripherally associated with the inner membrane. The downregulation of TbMic20, TbMic32 and TbMic34 also interferes with mitochondrial protein import and reduces the size of the TbMic10‐containing complexes. Thus, the diverged MICOS of trypanosomes contains two subcomplexes: a nonessential membrane‐integrated one, organized around the conserved Mic10 and Mic60, that mediates cristae formation, and an essential membrane‐peripheral one consisting of four kinetoplastid‐specific subunits, that is required for import of intermembrane space proteins.     

A gene for resistance to the Varroa mite (Acari) in honey bee (Apis mellifera) pupae

Social insect colonies possess a range of defences which protect them against highly virulent parasites and colony collapse. The host–parasite interaction between honey bees (Apis mellifera) and the mite Varroa destructor is unusual, as honey bee colonies are relatively poorly defended against this parasite. The interaction has existed since the mid‐20th Century, when Varroa switched host to parasitize A. mellifera. The combination of a virulent parasite and relatively naïve host means that, without acaricides, honey bee colonies typically die within 3 years of Varroa infestation. A consequence of acaricide use has been a reduced selective pressure for the evolution of Varroa resistance in honey bee colonies. However, in the past 20 years, several natural‐selection‐based breeding programmes have resulted in the evolution of Varroa‐resistant populations. In these populations, the inhibition of Varroa's reproduction is a common trait. Using a high‐density genome‐wide association analysis in a Varroa‐resistant honey bee population, we identify an ecdysone‐induced gene significantly linked to resistance. Ecdysone both initiates metamorphosis in insects and reproduction in Varroa. Previously, using a less dense genetic map and a quantitative trait loci analysis, we have identified Ecdysone‐related genes at resistance loci in an independently evolved resistant population. Varroa cannot biosynthesize ecdysone but can acquire it from its diet. Using qPCR, we are able to link the expression of ecdysone‐linked resistance genes to Varroa's meals and reproduction. If Varroa co‐opts pupal compounds to initiate and time its own reproduction, mutations in the host's ecdysone pathway may represent a key selection tool for honey bee resistance and breeding.     

Feeding in the frequency domain: coarser‐grained environments increase consumer sensitivity to resource variability,covariance and phase

Theory predicts that resource variability hinders consumer performance. How this effect depends on the temporal structure of resource fluctuations encountered by individuals remains poorly understood. Combining modelling and growth experiments with Daphnia magna, we decompose the complexity of resource fluctuations and test the effect of resource variance, supply peak timing (i.e. phase) and co‐limiting resource covariance along a gradient from high to low frequencies reflecting fine‐ to coarse‐grained environments. Our results show that resource storage can buffer growth at high frequencies, but yields a sensitivity of growth to resource peak timing at lower ones. When two resources covary, negative covariance causes stronger growth depression at low frequencies. However, negative covariance might be beneficial at intermediate frequencies, an effect that can be explained by digestive acclimation. Our study provides a mechanistic basis for understanding how alterations of the environmental grain size affect consumers experiencing variable nutritional quality in nature.