On the extent and role of the small proteome in the parasitic eukaryote Trypanosoma brucei

Background: Although technical advances in genomics and proteomics research have yielded a better understanding of the coding capacity of a genome, one major challenge remaining is the identification of all expressed proteins, especially those less than 100 amino acids in length. Such information can be particularly relevant to human pathogens, such as Trypanosoma brucei, the causative agent of African trypanosomiasis, since it will provide further insight into the parasite biology and life cycle. Results: Starting with 993 T. brucei transcripts, previously shown by RNA-Sequencing not to coincide with annotated coding sequences (CDS), homology searches revealed that 173 predicted short open reading frames in these transcripts are conserved across kinetoplastids with 13 also conserved in representative eukaryotes. Mining mass spectrometry data sets revealed 42 transcripts encoding at least one matching peptide. RNAi-induced down-regulation of these 42 transcripts revealed seven to be essential in insect-form trypanosomes with two also required for the bloodstream life cycle stage. To validate the specificity of the RNAi results, each lethal phenotype was rescued by co-expressing an RNAi-resistant construct of each corresponding CDS. These previously non-annotated essential small proteins localized to a variety of cell compartments, including the cell surface, mitochondria, nucleus and cytoplasm, inferring the diverse biological roles they are likely to play in T. brucei. We also provide evidence that one of these small proteins is required for replicating the kinetoplast (mitochondrial) DNA. Conclusions: Our studies highlight the presence and significance of small proteins in a protist and expose potential new targets to block the survival of trypanosomes in the insect vector and/or the mammalian host

TREM1/3 deficiency impairs tissue repair after acute kidney injury and mitochondrial metabolic flexibility in tubular epithelial cells

Long-term sequelae of acute kidney injury (AKI) are associated with incomplete recovery of renal function and the development of chronic kidney disease (CKD), which can be mediated by aberrant innate immune activation, mitochondrial pathology, and accumulation of senescent tubular epithelial cells (TECs). Herein, we show that the innate immune receptor Triggering receptor expressed on myeloid cells-1 (TREM-1) links mitochondrial metabolism to tubular epithelial senescence. TREM-1 is expressed by inflammatory and epithelial cells, both players in renal repair after ischemia/reperfusion (IR)-induced AKI. Hence, we subjected WT and TREM1/3 KO mice to different models of renal IR. TREM1/3 KO mice displayed no major differences during the acute phase of injury, but increased mortality was observed in the recovery phase. This detrimental effect was associated with maladaptive repair, characterized by persistent tubular damage, inflammation, fibrosis, and TEC senescence. In vitro, we observed an altered mitochondrial homeostasis and cellular metabolism in TREM1/3 KO primary TECs. This was associated with G2/M arrest and increased ROS accumulation. Further exposure of cells to ROS-generating triggers drove the cells into a stress-induced senescent state, resulting in decreased wound healing capacity. Treatment with a mitochondria anti-oxidant partly prevented the senescent phenotype, suggesting a role for mitochondria herein. In summary, we have unraveled a novel (metabolic) mechanism by which TREM1/3 deficiency drives senescence in TECs. This involves redox imbalance, mitochondrial dysfunction and a decline in cellular metabolic activities. These finding suggest a novel role for TREM-1 in maintaining tubular homeostasis through regulation of mitochondrial metabolic flexibility

Silicon on ceramic process. Silicon sheet growth development for the large-area silicon sheet task of the low-cost silicon solar array project

The technical and economic feasibility of producing solar-cell-quality sheet silicon was investigated. The sheets were made by coating one surface of carbonized ceramic substrates with a thin layer of large-grain polycrystalline silicon from the melt. Significant progress was made in all areas of the program

Introduction: Ideologies of Youth

In a number of countries in Africa, such as Uganda and Kenya, national publics have been discussing whether citizens of age 50 or even 60 should be regarded as ‘youth’. Under the current dispensation of donor funding, relief programmes and international aid, these discussions have made the ‘youth’ the major beneficiary of what these policies offer and imply. There is a general feeling, however, that these policies should target all age groups in their youth-oriented programmes. If the donorideology prescribes youthfulness for societal and developmental relevance, it will then dictate practice. This is just one example of what this special issue will address in an attempt to explore what we see as an emerging development in Africa and beyond: the rise of youth as an ideology. Whereas Africa has witnessed the rise of a fast-growing study of youth as a phenomenon and as a concept, the aspect of youth as ideology has, so far, not been elaborated on

Three-dimensional (p,q) AdS superspaces and matter couplings

We introduce N-extended (p,q) AdS superspaces in three space-time dimensions, with p+q=N and p>=q, and analyse their geometry. We show that all (p,q) AdS superspaces with X^{IJKL}=0 are conformally flat. Nonlinear sigma-models with (p,q) AdS supersymmetry exist for p+q4 the target space geometries are highly restricted). Here we concentrate on studying off-shell N=3 supersymmetric sigma-models in AdS_3. For each of the cases (3,0) and (2,1), we give three different realisations of the supersymmetric action. We show that (3,0) AdS supersymmetry requires the sigma-model to be superconformal, and hence the corresponding target space is a hyperkahler cone. In the case of (2,1) AdS supersymmetry, the sigma-model target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations of the two-sphere of complex structures.Comment: 52 pages; V3: minor corrections, version published in JHE

The gauge-Higgs legacy of the LHC Run I

The effective Lagrangian expansion provides a framework to study effects of new physics at the electroweak scale. To make full use of LHC data in constraining higher-dimensional operators we need to include both the Higgs and the electroweak gauge sector in our study. We first present an analysis of the relevant di-boson production LHC results to update constraints on triple gauge boson couplings. Our bounds are several times stronger than those obtained from LEP data. Next, we show how in combination with Higgs measurements the triple gauge vertices lead to a significant improvement in the entire set of operators, including operators describing Higgs couplings

The role of frontal cortex-reticular interactions in performance and extinction of the classically conditioned nictitating membrane response in the rabbit

In order to investigate the behavioral role of interactions between frontal cortex and reticular nuclei, we examined the effects of single and combined lesions of these structures on the classically conditioned nictitating membrane response (NMR) of rabbits. Lesions of frontal cortex decreased latencies of the conditioned NMRs in reacquisition and retarded extinction of the conditioned response. Lesions of nucleus reticularis pontis oralis (NRPO) produced similar effects. In contrast, lesions of nucleus reticularis tegmenti (NRT) increased NMR latencies during reacquisition. The opposite effects of frontal cortex and NRT lesions were abolished when the two lesions were combined, indicating that the two lesion effects summed. In contrast, the deficits due to frontal and NRPO lesions did not sum; combined frontal--NRPO lesions produced deficits very similar in magnitude and time course to those of the NRPO lesions alone. These findings suggest that frontal cortex may exert its inhibitory effects on behavior not by directly interacting with NRT, but by facilitating NRPO, which in turn may inhibit the nucleus of the VIth nerve, the final common pathway to the NMR. NRT may facilitate the motor pathway by modulating the inhibitory effect of NRPO on the VIth nerve nucleus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23959/1/0000208.pd

Extended supersymmetric sigma models in AdS_4 from projective superspace

There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We also develop a novel description of the most general N=2 supersymmetric nonlinear sigma-model in AdS_4 in terms of chiral superfields on three-dimensional N=2 flat superspace without central charge. This superspace naturally originates from a conformally flat realization for the four-dimensional N=2 AdS superspace that makes use of Poincare coordinates for AdS_4. This novel formulation allows us to uncover several interesting geometric results.Comment: 88 pages; v3: typos corrected, version published in JHE