The Structural Organization of Photosystem II Polypeptides.

The structural organization of Photosystem II polypeptides has been investigated using the protein crosslinking reagent 1-ethyl-3-(dimethyl-aminopropyl)-carbodiimide (EDC), and a library of mono- and polyclonal antibodies. The first phase of this research was to generate the antibody probes against specific PS II polypeptides. A murine monoclonal antibody, FQC3, was characterized. It recognized the D2 protein of Spinacia oleracea L. The second phase of this research utilized antibodies against D1, D2, CPa-1, CPa-2, Cyt b\sb{559}, 33 kDa manganese stabilizing protein (MSP), 24 kDa extrinsic protein, and the 17 kDa extrinsic protein to identify PS II subunits crosslinked by EDC. Several intra-complex crosslinked products were identified. One crosslinked species at 110 kDa (called XL) was identified by two different antibodies and is composed of CPa-1 and the extrinsic 33 kDa MSP. The third phase of this research characterized XL. This was of particular interest considering both CPa-1 and the 33 kDa MSP are required for maximal O\sb2-evolving rates. EDC modified PS II membranes evolve normal rates of O\sb2. An increase in EDC concentration results in increased retention of the O\sb2-evolving rate by CaCl\sb2 washed EDC modified PS II membranes. XL (the crosslinked species between CPa-1 and the 33 kDa MSP) was isolated. Chemical and proteolytic cleavage techniques were used to identify peptide fragments of CPa-1 and the 33 kDA MSP involved in crosslinkage. CNBr generated fragments from XL were identified at 50 kDa and 25 kDa. N-terminal sequence analysis of the 50 kDa species indicated that the 15.7 kDa C-terminal CNBr fragment of CPa-1 is unequivocally crosslinked to the 33 kDa MSP. Additional N-terminal sequence analysis of the 25 kDa species strongly suggests that the 15.7 kDa C-terminal CNBr fragment of CPa-1 is crosslinked to the 7 kDa N-terminal CNBr fragment of the 33 kDa MSP. The large extrinsic loop of the apoprotein of CPa-1 thus appears to anchor the extrinsic 33 kDa MSP of the O\sb2-evolving complex to the thylakoid membrane through charge pair interactions. By helping elucidate the nature of the non-covalent interactions among PS II proteins, these results provide a more integrated view of the structural and functional organization of PS II polypeptides

Protection of CpG islands from DNA methylation is DNA-encoded and evolutionarily conserved.

DNA methylation is a repressive epigenetic modification that covers vertebrate genomes. Regions known as CpG islands (CGIs), which are refractory to DNA methylation, are often associated with gene promoters and play central roles in gene regulation. Yet how CGIs in their normal genomic context evade the DNA methylation machinery and whether these mechanisms are evolutionarily conserved remains enigmatic. To address these fundamental questions we exploited a transchromosomic animal model and genomic approaches to understand how the hypomethylated state is formed in vivo and to discover whether mechanisms governing CGI formation are evolutionarily conserved. Strikingly, insertion of a human chromosome into mouse revealed that promoter-associated CGIs are refractory to DNA methylation regardless of host species, demonstrating that DNA sequence plays a central role in specifying the hypomethylated state through evolutionarily conserved mechanisms. In contrast, elements distal to gene promoters exhibited more variable methylation between host species, uncovering a widespread dependence on nucleotide frequency and occupancy of DNA-binding transcription factors in shaping the DNA methylation landscape away from gene promoters. This was exemplified by young CpG rich lineage-restricted repeat sequences that evaded DNA methylation in the absence of co-evolved mechanisms targeting methylation to these sequences, and species specific DNA binding events that protected against DNA methylation in CpG poor regions. Finally, transplantation of mouse chromosomal fragments into the evolutionarily distant zebrafish uncovered the existence of a mechanistically conserved and DNA-encoded logic which shapes CGI formation across vertebrate species

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

Effects of Short-Term Exposure to Diesel Exhaust on the Ecophysiology, Growth, and Fecundity of Soybean (Glycine max (L.) Merr.) and Chicory (Cichorium intybus L.)

Plants growing along roadways are often exposed to vehicle exhaust containing both particulate matter (PM) and various gases that could affect gas exchange and thus plant reproduction. To investigate effects of diesel exhaust exposure on plant ecophysiology, growth, and fecundity, individuals of soybean (Glycine max (L.) Merr.) and chicory (Cichorium intybus L.) were exposed to either exhaust from a diesel generator or ambient air. Exposure occurred daily over a 5-day period (beginning 18 June 2013) using open-top chambers in an agricultural field in southwestern Ohio, United States. Plants were evaluated at 3 times (before, directly after exposure, and following a 5.5-week post-treatment recovery period) for photosynthetic rate (A), stomatal conductance (g), water use efficiency (WUE), stomatal clogging due to PM deposition, and number of nodes. Aboveground biomass, fruit number, mean seed number, and seed mass were measured for soybean after the recovery period. In soybean, A minimally decreased with exposure to diesel exhaust (compared to the control), but an increase in g and a decrease in WUE were detected after the exhaust treatment. Chicory exhibited a relatively low increase in A after the treatment, but there were no clear differences in g or WUE. Growth and fecundity were similar among all soybean plants directly after treatment, but after 5.5 weeks plants exposed to diesel exhaust had increased vegetative biomass while exhibiting no difference in fecundity. These plant species reacted differently to short-term diesel exhaust exposure, suggesting that the impact of diesel exhaust will depend on both the plant species and its physiology

Long-term Observations in Acoustics - the Ocean Acoustic Observatory Federation

The Ocean Acoustic Observatory Federation (OAOF) includes several laboratories and universities: the Institute of Geophysics and Planetary Physics (IGPP) and the Marine Physical Laboratory (MPL) at the Scripps Institution of Oceanography, the Pacific Meteorological and Environmental Laboratory (PMEL) of NOAA, the Naval Postgraduate School (NPS), and the Applied Physics Laboratory at the University of Washington (UW/APL)

Ageing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species.

BACKGROUND: Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species. RESULTS: A large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu. CONCLUSIONS: Overall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals

Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis

The use of palliative care programs and the number of trials assessing their effectiveness have increased

Un nouveau test de la spectroscopie translationnelle: la prédissociation rotationnelle de l'état X1Sigma de HeH+.

peer reviewedWe reported the experiment on the accurate measurement of the kinetic energy released during the predissociation of HeH+ ions into the fragments H+ and He. This experiment was carried out on two machines specially designed for this purpose. The new results differ from those of the original experiment and agree now very well with the theoretical predictions