Incident light orientation lets C4 monocotyledonous leaves make light work differently

Photosynthesis is an important driver of ecosystem sustainability in the face of climate change. Monocotyledonous crop species with C4 photosynthesis such as maize (Zea mays L; corn) and sugar cane are crucial for future food security and biofuel crop requirements, while C4 pasture grasses such as Paspalum are central to natural ecosystems. The global demand for corn will exceed that for wheat and rice by 2020, making it the world's most important crop. Light-driven photosynthesis supports plant biomass production, but plants have also evolved safety valve mechanisms that attenuate the absorption of potentially lethal levels of excess light. The array of survival responses that enables leaves to evade photoinhibition is complex and involves chloroplast and leaf movement as well as the molecular rearrangements that facilitate thermal energy dissipation. Here we report a novel morphological mechanism that allows C4 monocotyledonous leaves to regulate photosynthesis independently on each surface with respect to incident light allowing better adaptation to water deficits and light stress. We show that under abaxial illumination as occurs when monocotyledonous leaves curl in response to water stress the stomata close and photosynthetic metabolism shuts down on the adaxial surface of C4 leaves but these parameters increase in function to the abaxial surface. We discuss how this regulation confers a survival advantage to the C4 relative to C3 leaves which are unable to regulate their dorso-ventral functions in relation to light

mTORC2 signaling drives the development and progression of pancreatic cancer

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

To-many or to-one? All-in-one! Efficient purely functional multi-maps with type-heterogeneous hash-tries

An immutable multi-map is a many-to-many map data structure with expected fast insert and lookup operations. This data structure is used for applications processing graphs or many-to-many relations as applied in compilers, runtimes of programming languages, or in static analysis of object-oriented systems. Collection data structures are assumed to carefully balance execution time of operations with memory consumption characteristics and need to scale gracefully from a few elements to multiple gigabytes at least. When processing larger in-memory data sets the overhead of the data structure encoding itself becomes a memory usage bottleneck, dominating the overall performance. In this paper we propose AXIOM, a novel hash-trie data structure that allows for a highly efficient and type-safe multi-map encoding by distinguishing inlined values of singleton sets from nested sets of multi-mappings

Testing for pharmacogenomic predictors of ppRNFL thinning in individuals exposed to vigabatrin

BACKGROUND: The anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, especially infantile spasms. However, use is limited by VGB-associated visual field loss (VAVFL). The mechanisms by which VGB causes VAVFL remains unknown. Average peripapillary retinal nerve fibre layer (ppRNFL) thickness correlates with the degree of visual field loss (measured by mean radial degrees). Duration of VGB exposure, maximum daily VGB dose, and male sex are associated with ppRNFL thinning. Here we test the hypothesis that common genetic variation is a predictor of ppRNFL thinning in VGB exposed individuals. Identifying pharmacogenomic predictors of ppRNFL thinning in VGB exposed individuals could potentially enable safe prescribing of VGB and broader use of a highly effective drug. METHODS: Optical coherence topography (OCT) and GWAS data were processed from VGB-exposed individuals (n = 71) recruited through the EpiPGX Consortium. We conducted quantitative GWAS analyses for the following OCT measurements: (1) average ppRNFL, (2) inferior quadrant, (3) nasal quadrant, (4) superior quadrant, (5) temporal quadrant, (6) inferior nasal sector, (7) nasal inferior sector, (8) superior nasal sector, and (9) nasal superior sector. Using the summary statistics from the GWAS analyses we conducted gene-based testing using VEGAS2. We conducted nine different PRS analyses using the OCT measurements. To determine if VGB-exposed individuals were predisposed to having a thinner RNFL, we calculated their polygenic burden for retinal thickness. PRS alleles for retinal thickness were calculated using published summary statistics from a large-scale GWAS of inner retinal morphology using the OCT images of UK Biobank participants. RESULTS: The GWAS analyses did not identify a significant association after correction for multiple testing. Similarly, the gene-based and PRS analyses did not reveal a significant association that survived multiple testing. CONCLUSION: We set out to identify common genetic predictors for VGB induced ppRNFL thinning. Results suggest that large-effect common genetic predictors are unlikely to exist for ppRNFL thinning (as a marker of VAVFL). Sample size was a limitation of this study. However, further recruitment is a challenge as VGB is rarely used today because of this adverse reaction. Rare variants may be predictors of this adverse drug reaction and were not studied here

Dorsoventral variations in dark chilling effects on photosynthesis and stomatal function in Paspalum dilatatum leaves

The effects of dark chilling on the leaf-side-specific regulation of photosynthesis were characterized in the C4 grass Paspalum dilatatum. CO2- and light-response curves for photosynthesis and associated parameters were measured on whole leaves and on each leaf side independently under adaxial and abaxial illumination before and after plants were exposed to dark chilling for one or two consecutive nights. The stomata closed on the adaxial sides of the leaves under abaxial illumination and no CO2 uptake could be detected on this surface. However, high rates of whole leaf photosynthesis were still observed because CO2 assimilation rates were increased on the abaxial sides of the leaves under abaxial illumination. Under adaxial illumination both leaf surfaces contributed to the inhibition of whole leaf photosynthesis observed after one night of chilling. After two nights of chilling photosynthesis remained inhibited on the abaxial side of the leaf but the adaxial side had recovered, an effect related to increased maximal ribulose-1,5-bisphosphate carboxylation rates (Vcmax) and enhanced maximal electron transport rates (Jmax). Under abaxial illumination, whole leaf photosynthesis was decreased only after the second night of chilling. The chilling-dependent inhibition of photosynthesis was located largely on the abaxial side of the leaf and was related to decreased Vcmax and Jmax, but not to the maximal phosphoenolpyruvate carboxylase carboxylation rate (Vpmax). Each side of the leaf therefore exhibits a unique sensitivity to stress and recovery. Side-specific responses to stress are related to differences in the control of enzyme and photosynthetic electron transport activities

Progress report no. 4

Statement of responsibility on title-page reads: editors: M.J. Driscoll, D.D. Lanning, I. Kaplan, A.T. Supple ; contributors: A. Alvim, G.J. Brown, J.K. Chan, T.P. Choong, M.J. Driscoll, G. A. Ducat, I.A. Forbes, M.V. Gregory, S.Y. Ho, C.M. Hove, O. K. Kadiroglu, R.J. Kennerley, D.D. Lanning, J.L. Lazewatsky, L. Lederman, A.S. Leveckis, V.A. Miethe, P. A. Scheinert, A.M. Thompson, N.E. Todreas, C.P. Tzanos, and P.J. WoodIncludes bibliographical referencesProgress report; June 30, 1973U.S. Atomic Energy Commission contract: AT(11-1)225

Progress report no. 3

Statement of responsibility on title-page reads: editors: M.J. Driscoll, D.D. Lanning, I. Kaplan; contributors: S. T. Brewer, G.J. Brown, P. Delaquil, M.J. Driscoll, G.A. Ducat, I.A. Forbes, M. V. Gregory, S.Y. Ho, M.S. Kalra, C.S. Kang, L.T. Kim, D.D. Lanning, J.L. Lazewatsky, T.C. Leung, E.A. Mason, N.R. Ortiz, N.C. Rasmussen, I.C. Rickard, K.D. Roberson, A.T. Supple, A.M. Thompson, and C.P. TzanosIncludes bibliographical referencesProgress report ; June 30, 1972U.S. Atomic Energy Commission contracts: AT(11-1)306