Scale bars, 3 μm Discussion For the ATPS and coacervate droplets studied, exchange of RNA across the droplet boundary occurred orders of magnitude more rapidly than across the membrane of fatty acid vesicles. Although our FRAP measurements report only on the entry of RNA oligomers into ATPS or coacervate droplets, at steady

state, the rate of efflux of RNA from droplets must equal the rate of influx. Our data therefore imply that Lazertinib concentration RNA molecules do not remain localized within any droplet for longer than a period of seconds, and rapidly exchange between droplets via the surrounding bulk phase. Although a larger RNA such as a ribozyme would diffuse more slowly in solution due to its greater mass, our data indicates that longer RNAs will not reside in a droplet for a significantly longer time before diffusing out of the droplet. Fast RNA exchange coupled with the observed rapid coalescence of droplets suggests that ATPS and coacervate droplets would not confer the stable compartmentalization necessary for multiple generations of RNA selection and replication to occur, which would need to be on the order of many

hours, if not days (Deck et al. 2011; Adamala and Szostak 2013b). If a given RNA molecule only resides in a particular droplet for a Foretinib research buy short period of time before exchanging into a different droplet, the products of any functional check details activity of that RNA (such as the catalytic production of a useful metabolite) would be spread across many droplets, and furthermore would not be heritable. In essence, the rapid exchange of RNA molecules between droplets is equivalent to a lack of compartmentalization in a time-averaged sense. Darwinian evolution requires compartmentalization so that mutations that improve function can lead to a selective advantage for the mutant genomic molecule. As the capacity for Darwinian evolution is a basic requirement for any protocell model, it is clear that

unmodified ATPS and coacervate droplets are unsuitable protocell models. To decrease the rate of RNA exchange between droplets, it may be productive to consider systems in which RNA molecules could covalently attach second to a matrix or to particles that would stay localized within a droplet. Many RNA affinity purification techniques rely on covalent attachments to a matrix such as sepharose (Allerson et al. 2003) or agarose beads (Caputi et al. 1999) and such a system could serve to slow RNA exchange. The coacervate system we studied was composed of a simple polypeptide (pLys) and a simple mononucleotide (ATP). RNA-protein (Lee et al. 1977; Drygin 1998; Baskerville and Bartel 2002) or RNA-nucleotide (Flügel and Wells 1972; Flügel et al. 1973) covalent interactions produced by photo-crosslinking could be good starting points to develop a system in which RNA becomes covalently linked to a matrix within coacervate droplets in a prebiotically plausible manner.

In the McLellan et al. investigations [36–38], soldiers performed a series of tasks over several days, where opportunities for sleep were exceedingly diminished. Experimental challenges included a 4 or 6.3 km run, as well as tests learn more for marksmanship, observation and reconnaissance, and psychomotor vigilance [36–38]. During periods of sustained wakefulness, subjects were provided caffeine in the range of 600-800 mg, and in the form of chewing gum. The caffeine supplement was consumed in this AZD1152 manner as it has been shown

to be more readily absorbed, than if it was provided within a pill based on the proximity to the buccal tissue [39]. In all three studies [36–38], vigilance was either maintained or enhanced for caffeine conditions in comparison to placebo. Additionally, physical performance measures such as run times and completion of an obstacle course were also improved by the effects of caffeine consumption [36, 38]. Lieberman et al. [40] examined the effects of caffeine on cognitive performance during sleep deprivation in U.S. Navy Seals [40]. However, in this investigation [40] the participants were randomly assigned varying doses of caffeine in capsule form delivering either 100, 200, or 300 mg. In a manner similar to previous investigations, participants received either the caffeine Compound C or placebo treatment and one hour post consumption performed

a battery of assessments related to vigilance, reaction time, working memory, and motor learning and memory. In addition, the participants were evaluated at eight hours post consumption

to assess duration of treatment effect in parallel to the half-life of caffeine, in a manner similar to a study conducted by Bell et al. [41]. As to be expected, caffeine had the most significant effect on tasks related to alertness [40]. However, results were also significant for assessments related to vigilance and choice next reaction time for those participants who received the caffeine treatment. Of particular importance are the post-hoc results for the 200 and 300 mg doses. Specifically, there was no statistical advantage for consuming 300, as opposed to 200 mg [40]. In other words, those trainees who received the 300 mg (~4 mg/kg) dose did not perform significantly better than those participants who received 200 mg (~2.5 mg/kg). Meanwhile, a 200 mg dose did result in significant improvements in performance, as compared to 100 mg. In fact, it was evident from post-hoc results that 100 mg was at no point statistically different or more advantageous for performance than a placebo. These studies [36–38, 40] demonstrate the effects of caffeine on vigilance and reaction time in a sleep deprived state, in a distinct and highly trained population. These findings suggest that the general population may benefit from similar effects of caffeine, but at moderate dosages in somewhat similar conditions where sleep is limited.

DNA copy numbers are indicated by colors (black, blue, green, pink, orange and red are 0, 1, 2, 3, 4 and ≥5 copies, respectively). Common copy number gain regions are emphasized by red dotted rectangles. Common copy number loss region is emphasized by blue dotted rectangle. (C) At chromosome 8p23.1, a homozygous deletion of SOX7 occurs in the HCC2935 NSCLC cell line. Red dots show raw data. Blue line denotes total MAPK inhibitor gene dosage by CNAG; level 2 indicates

diploid (2N) amount of DNA. Sample is mostly hemizygous. Green small vertical bars immediately under the chromosome display heterozygous SNP sites. The bottom lines (Red and Green) denote allele-specific gene dosage (one line indicates gene dosage of the maternal allele, and the other indicates gene dosage of the paternal allele). Sample shows that chromosome 8 is hemizygously deleted except at

8p23.1 where the second allele is also lost in a small region resulting in homozygous deletion of the UNQ9391, RP1L1 and the SOX7 genes. Table 1 Common copy number genomic alterations in NSCLC found in two cohorts: TCGA and EGFR mutant, non-smoking Asians Region of Chromosome Candidate target genes Gain of 1q21.1q-24.2 Large fragment Gain of 5p13.2 SKP2 Gain of 7p11.2 EGFR Gain of 8q24.3 PTP4A3 Gain of 8q24.21 MYC, PVT1 Gain of 8q24.12 MTBP Loss of 8p23.1 UNQ9391, RP1|1, SOX7 Gain of 11q13.2-13.3 CYCLIN D1, FGF3, FGF4, FGF19 Gain 12q14.2 TBK1, see more RASSF3 Gain 12q14.3 HMGA2 Gain of 12q13.3-14.1 CDK4 Gain of 12q12.1 KRAS Gain of 12q11.21 DDX11 Gain 14q13.3

PAX9 Gain of 17q12 Her2 Gain of 17q25.3 TK1, BIRC5 Common genomic alterations found in both NSCLC samples with EGFR mutations (9 samples) and those from the TCGA data base [56 samples, probably these Crenigacestat supplier rarely have an EGFR mutation (Zhou et al. [14])]. Table 2 Copy number genomic alterations that predominant in NSCLC from non-smoking Idoxuridine Asians with mutant EGFR compared to TCGA database Region of Chromosome NSCLC with mutant EGFR (n=8) NSCLC from TCGA data base (n=56) Potential target gene(s) Gain of 1p36.32-36.31 8/9(89) 15/56(27%) AJAP1 Gain of Ch2p Fewer alteration More alterations Large fragment Gain of Ch3q Fewer alteration More alterations Large fragment Loss of 6q22.3-27 Fewer alteration More alterations Large fragment Loss of 9p21.3 1/9(11%) 19/56(34%) p14,p15,p16 Gain of 15q23-26.3 0/9(0%) 10/56(18%) Large fragment Gain of 19q12 6/9(70%) 6/56(11%) Cyclin E1 Gain of 20q11.21 0/9(0%) 26/56(46%) BCL2L1, TPX2, MYLK2, DUSP15 Ratio of genomic alterations in NSCLC samples with EGFR mutations (9 samples) and 56 NSCLC samples from the TCGA data base. [Most samples from TCGA are from Caucasians and thus we assume <7% will have EGFR mutation as previously noted (Zhou et al. [14])].

A more refined model would include additional parameters that typically affect the growth process, such as the surface energy [31] or kinetic effects [32]. These parameters are essential in the prediction of

the nucleation sites of some semiconductor systems. For example, in InAs QWires, it has been reported selleck inhibitor that the stacking pattern is determined by the combined effect of strain and surface morphology on the growth front of the ERK inhibitor spacer layers [33]. In the structure considered in the present work, our results have shown that a simplified approximation of the chemical potential considering only the strain component is valid for obtaining accurate results. Figure 3 Strain and SED maps in the growth plane of the upper QD. (a) ϵ xx, (b) ϵ yy, (c) ϵ zz and (d) normalized SED calculated in the surface of the barrier layer. Superimposed to each map, we have included the selleck chemical APT data corresponding to the upper layer of QDs in the form of In concentration isolines, ranging from 25% In (dark blue) to

45% In (red), in steps of 5%. In (d), we have included an inset showing a complete map of the APT data for clarity. On the other hand, our results have shown that the upper QD does not grow vertically aligned with the lower QD, but there is some deviation. Previous theoretical analyses have

shown that this misalignment is, in part, related to the elastic anisotropy in the material [14], where the increase in the degree ADAM7 of anisotropy favours the anti-correlated island growth [19]. It has also been reported that the QD base size and density have a strong influence on this misalignment [11], although the QD shape (truncated-pyramidal or lens-shaped) may not have a major effect in the strain at the surface of the capping layer [14]. These theoretical analyses are very useful for understanding the parameters that influence the QD nucleation sites. However, they have been developed considering ideal structures, for example including perfectly symmetric QDs. Our results have shown that real QDs are far from symmetric, and small composition variations can change the strain distribution of the structure. It has been found that the strain in semiconductor structures such as QRings has a significant importance in its optoelectronic characteristics [16]. This shows that in order to understand the functional properties of real semiconductor nanostructures, it is indispensable considering real compositional data for the FEM calculations, as the APT experimental data considered in the present work.

coli is reversed from the usual orientation of alkaline inside [5] and cannot apparently be used to drive proton uptake into the cell. This is a particular problem when Na+/H+ antiporters are used for alkaline pH homeostasis because, due to the cytotoxicity of Na+[5] it is excluded from the cell and, unlike K+, cannot provide an outwardly-directed driving

force to support an electroneutral exchange. To overcome this, antiporters such as E. coli NhaA [31] and B. subtilis TetL [38], utilise Δψ to catalyse electrogenic Na+/H+ exchange and buy FK228 drive net accumulation of H+ to acidify the cytoplasm at alkaline pH in the presence of Na+. Intriguingly, the MdtM homologue MdfA can catalyse both electrogenic and electroneutral transport of drug substrates [39]; however, the component of the PMF that MdfA utilises to drive Na+/H+ or K+/H+ antiport at alkaline pH has not been reported, although it too is likely to be the Δψ. The results of our fluorescence experiments using the Δψ–sensitive probe Oxonol V revealed that MdtM can utilise Δψ as the driving force

at alkaline pH to catalyse an electrogenic Na+(K+)/H+ antiport, i.e., an exchange stoichiometry of >1 H+ per monovalent metal cation (Figure 9). Further evidence to support a physiological role for MdtM in alkaline pH homeostasis was gleaned from SN-38 estimation of the concentrations of Na+ and K+ required to elicit the half-maximal fluorescence dequench of acridine orange in this website inverted vesicles (Figure 7). Other transporters that function in bacterial pH homeostasis, such as E. coli NhaB [40], ChaA [12] and MdfA [9], and a sodium-specific

Na+/H+ antiporter from Vibrio parahaemolyticus[41], all possess affinity for their respective metal ion substrate(s) in the general millimolar range. Our values of [Na+]1/2 and [K+]1/2 of 38±6 mM and 32±7 mM, respectively, although not directly related to actual K m values [42], suggest MdtM also possesses relatively low affinity for its cognate metal cations and are therefore consistent with a contributory role for the Na+/H+ and K+/H+ antiporter activities of MdtM in alkaline pH homeostasis. In order to function effectively in pH homeostasis, antiporters must be equipped with sensors of the external and/or cytoplasmic pH that can Cepharanthine transduce the changes in pH into changes in transporter activity [5]. The pH profile of MdtM activity (Figure 7A) suggests that, like other antiporters involved in pH homeostasis, it too is capable of sensing and responding to changes in ionic composition, and provides additional support for our contention that the different antiport functions performed by MdtM are dictated by subtle changes in pH and the type of cation present in the external environment. In our experiments, because MdtM expression from a multicopy plasmid was placed under control of a non-native arabinose-inducible promoter, this suggests an ability to sense pH at the protein level.

The “core sequence” is highly conserved amongst the VP4 sequences of EV71 strains from various genotypes based on the alignment data (Figure 1). Our results suggest that VP4N20 peptide may potentially elicit a pan-genotypic immune response once the right segment of VP4 is identified. Figure 8 Effects of peptide length on recognition of VP4 peptides by antibodies raised against

the first MDV3100 mw N- terminal 20 residues of EV71 VP4. The top panel shows the ELISA reaction of the polyclonal serum to peptides truncated at the carboxyl end of the 20-mer. The bottom shows the same with the truncations at the amino end, and the highlighted yellow region shows the minimal apparent “core” of the peptide for antibody recognition. The plus signs on the right of the diagram illustrate whether the polyclonal serum binds to the peptide fragment. OD450: optical density at 450 nm. Discussion Gene mutation and genetic recombination were frequently observed during EV71 epidemics, resulting in substantial genetic variation of EV71

genome and the emergence of the various EV71 subgenotypes [21]. Virus variants which possess a selective advantage in terms of ability to evade host immune surveillance can spread and become established within human populations. EV71 is classified into 11 subgenogroups according to the genetic variation of VP1 gene [15]. EV71 genotype-related HFMD outbreaks were extensively reported previously. Genotype B1 was the major viral strain in circulation from 1970 to 1980 [22]. The co-circulation of four subgenotypes C1, C2, B3, and B4 were observed in Malaysia between

1997 and 2000 GSK1120212 FER [22]. The genotypes B2, C4 and B5 were reported to be the circulating strains from 1998 to 2009 in Taiwan [22, 23]. One exceptional case was observed in China, where genotype C4 was identified as the dominant viral strain responsible for the HFMD outbreak from 2007–2011 [24, 25]. Thus, an ideal vaccine should elicit effective cross-neutralizing antibody responses against different genotypes of EV71. Several different types of EV71 vaccine candidates have been investigated in animal model, including recombinant vaccines [3, 26–28], peptide vaccines [19, 20], live attenuated vaccines [29, 30] and formalin-inactivated virion vaccines [31–34]. Only inactivated EV71 vaccines are being evaluated in human clinical trials due to its superior immunogenicity and more matured manufacturing technologies. Inactivated EV71 virion vaccines have been found to be able to elicit cross-neutralizing antibody responses against EV71 strains of different genotypes in mouse model [34]. However, constant genetic see more evolution has been observed in EV71 genome [35], the efficiency of protective immunity elicited by currently used inactivated EV71 virion vaccines against novel EV71 variants thus still remain to be evaluated.

TCS and SI carried out the antigen identification by mass-spectrometry. CK and SK performed this website the deep sequencing analysis of the HCDR3. CSH and ARMB conceived the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.”
“Background Vibrio anguillarum, a highly motile

marine member of the γ-Proteobacteria, is one of the causative agents of vibriosis, a fatal hemorrhagic septicemic disease of both wild and cultured fish, crustaceans, and bivalves [1]. Fish infected with V. anguillarum display skin discoloration and erythema around the mouth, fins, and vent. Necrotic lesions are also observed in the abdominal muscle [2]. Mortality rates in infected fish populations range as high as 30-100% [1, 3]. Vibriosis has caused severe economic losses to aquaculture worldwide [1, 3] and affects many farm-raised fish including Pacific salmon, Atlantic salmon, sea bass, cod, and eel [3, 4]. V. anguillarum enters its fish host through the gastrointestinal tract (GI) and quickly colonizes this nutrient rich environment [2, 5]. Garcia et al. [6] have HMPL-504 cell line shown that V. anguillarum grows extremely well in salmon intestinal

mucus and that mucus-grown cells specifically express a Protein Tyrosine Kinase inhibitor number of different proteins, including several outer membrane proteins [6] and the extracellular metalloprotease EmpA [2, 5]. Several genes have been reported to be correlated with virulence by V. anguillarum, including the vah1 hemolysin cluster [7, 8], the rtx hemolysin cluster [9], the siderophore mediated iron transport system [10], the empA metalloprotease [2, 5], and the flaA gene [11]. Hemolytic activity of V. anguillarum has been considered

to be the virulence factor responsible for hemorrhagic septicemia during infection [10]. We have identified two hemolysin gene clusters in V. anguillarum that contribute to the virulence of this pathogen [8, 9]. One gene cluster, rtxACHBDE, encodes a MARTX toxin and its type I secretion system [9]. The second hemolysin gene cluster in V. anguillarum strain M93Sm contains the hemolysin gene Molecular motor vah1 flanked by two putative lipase-related genes (llpA and llpB) immediately downstream and upstream by a divergently transcribed hemolysin-like gene (plp) that appears to function as a repressor of vah1-dependent hemolytic activity [8]. The plp-encoded protein has very high sequence similarity to phospholipases found in other pathogenic Vibrio species [8]. However, the enzymatic characteristics of Plp in V. anguillarum were not described. Generally, phospholipases are divided into several subgroups depending on their specificity for hydrolysis of ester bonds at different locations in the phospholipid molecule.

To determine

the identity of the protein(s) contained within the 40 kDa band identified, this region (from both the BamA and the ML323 order control Thio elutions, Figure 3 lanes 4 and 5, respectively) were subsequently excised, trypsin-digested, and subjected to LC-MS/MS analysis. After MASCOT database search, the unknown protein from the BamA co-IP was identified as a 349-residue polypeptide encoded by the B. burgdorferi ORF bb0028. This protein was not identified in the band extracted from the Thio co-IP elution, suggesting that it co-immunoprecipitated specifically with BamA. Similar to BB0324, computer analyses of the BB0028 protein indicated that it contains a signal peptide with a consensus signal peptidase

II lipoprotein modification and processing site, suggesting that BB0028 is also a B. burgdorferi lipoprotein. Interestingly, BlastP analyses failed to identify any BB0028 conserved domains or any significant protein matches outside of the Borrelia genus. Figure 3 SDS-PAGE analysis of anti-BamA co-IP elutions. Cultures of B. burgdorferi strain B31 MI (2 × 1010 organisms per sample) were washed and solubilized, and the protein-containing cell lysate was used for co-immunoprecipitation (co-IP) experiments using anti-Thio and anti-BamA polyclonal antibodies. Lanes 1-4 of the Coomassie-stained SDS-PAGE gel shows the 40 kDa region from elutions of anti-BamA co-IP experiments using ATM/ATR targets increasing amounts (5 μL, 10 μL, 20 μL, or 40 μL) of antibody (titration selleck compound indicated by grey triangle). An unknown protein that was enriched Carnitine palmitoyltransferase II with increasing amount of anti-BamA antibody is indicated at left (arrow). A sample from the anti-Thio elutions (from which 40 μL antibody was used for co-IP) is shown in lane 5. To determine if BB0324 (the putative BamD ortholog) and BB0028 are BAM accessory proteins that specifically associate with BamA,

we performed anti-BamA, anti-BB0324, and anti-BB0028 immunoprecipitation experiments (Figure 4; antibodies used for immunoprecipitation assays are listed above panels). The immunoprecipitation assays were then subjected to immunoblot analysis with specific antibodies to BamA, BB0324, and BB0028 (indicated at left of panels). As shown in Figure 4, B. burgdorferi BamA co-immunoprecipitated BB0324 and BB0028. Additionally, BB0324 antibodies co-immunoprecipitated BamA and BB0028 while BB0028 antibodies co-immunoprecipitated BamA and BB0324 (Figure 4). However, none of the three proteins were detected in the Thio co-immunoprecipitation experiment control sample (Figure 4, left lane of each panel). Additionally, when immunoprecipitated proteins from all experiments were probed with antibodies to Lp6.6, which is a lipoprotein known to be localized to the inner leaflet of the borrelial OM [54], there was no detectable co-immunoprecipitation of Lp6.6 (Figure 4, bottom panel). The Lp6.

J Biol Chem 218: 599–606. Nordal A, Benson AA and Calvin M (1956) Photosynthesis of sedoheptulose- C14. Arch Biochem Biophys 62: 435–445. Mayaudon J, Benson AA and Calvin M (1956) Ribulose-1,5 AZD8931 price diphosphate from and CO2 fixation by Tetragonia expansa leaves extract. Biochim Biophys Acta 23: 342–351. References Barltrop A, Hayes PM, Calvin M (1954) The chemistry of 1, 2-dithiolane (trimethylene disulfide) as a model for the primary quantum conversion act in photosynthesis. J Am Chem Soc 76:4348–4367CrossRef Bassham JA (2003) Mapping the carbon reduction cycle: a personal retrospective. Photosynth Res 76:35–52CrossRefPubMed Bassham J, Benson A, Calvin M (1950) The path of carbon

in photosynthesis.

J Biol Chem 185(2):781–787PubMed Bassham JA, Benson AA, Kay LD, Harris AZ, Wilson AT, Calvin M (1954) The path of carbon in photosynthesis XXI. The cyclic regeneration of carbon GW3965 purchase dioxide acceptor. J Am Chem Soc 76:1760–1770CrossRef Benson AA (1995) Saga of a great theory of photosynthesis. ASPB (American Society of Plant Biology) News Lett 22(6):5–6 Benson AA (2002) Following the path of carbon in photosynthesis: a personal story. Photosynth Res Barasertib 73:29–49CrossRefPubMed Calvin M (1954) Chemical and photochemical reactions of thioctic acid and related disulfides. Fed Proc 13:697–711PubMed Calvin M (1964) The path of carbon in photosynthesis. The Nobel Lecture, delivered on December 11, 1961, From Nobel Lectures, Chemistry 1942–1962. Elsevier Publishing Company, Amsterdam, pp 618–644

Calvin M (1992) Following the trail of light: a Morin Hydrate scientific odyssey. In: Seemen JE (ed) Profiles, pathways, and dreams. American Chemical Society, Washington, DC, pp 3–178 Calvin M, Benson M (1948) The path of carbon in photosynthesis. Science 107:476–480CrossRefPubMed Fuller RC (1999) Forty years of microbial photosynthesis research: where it came from and what it led to. Photosynth Res 62:1–29CrossRef Mayaudon J (1957) Study of association between the main nucleoprotein of green leaves and carboxydismutase. Enzymologia 18:345–354 Quayale JR, Fuller RC, Benson AA, Calvin M (1954) Enzymatic carboxylation of ribulose diphosphate photosynthesis. J Am Chem Soc 76:3610–3611CrossRef Seaborg GT, Benson AA (1998) Melvin Calvin (April 8, 1911–January 1997). In: Biographical Memoirs, vol 75. National Academy of Sciences, Washington, DC, pp 96–115 Wildman SG (1998) Discovery of Rubisco. In: Kung S-D, Yang S-F (eds) Discoveries in plant biology, chap 12. World Scientific Pub. Co, Singapore, pp 163–173 Wildman SG (2002) Along the trail from fraction I protein to Rubisco (ribulose bis phosphate carboxylase-oxygenase). Photosynth Res 73:243–250CrossRefPubMed Wildman SG, Bonner J (1947) The proteins of green leaves. I. Isolation and enzymatic properties and auxin content of spinach cytoplasmic proteins.

Ogren’s retrospective, published at the invitation of one of us (Govindjee), in Photosynthesis Research (Ogren 2003), provides details about the resistance he faced. The research formed a unifying theory of photorespiration which finally explained: (a) the coincident oxygen inhibition of photosynthesis [the “Warburg Effect”, first reported in 1920 (Warburg 1920)]; (b) the oxygen stimulation of photorespiratory glycolate synthesis and CO2 evolution; and (c) reversal of these effects by CO2 (see a review by Ogren 1984). We emphasize here that the equations developed by Laing et al. (1974) Go6983 datasheet provided

the foundation for all kinetic models of photosynthesis, including those currently used to predict the response of plant performance to the rise in global CO2 concentration and change in temperature, topics that remain of major concern. (Richard Hageman, who died in 2002, was a plant physiologist and a professor of agronomy at the UIUC whose collaboration in this project was very www.selleckchem.com/products/ABT-737.html helpful.) With Chris Somerville: Having found that the same enzyme was

the starting point for both processes, Ogren quickly realized that one approach to decrease Selleck eFT-508 the detrimental photorespiratory process was to directly modify the enzyme and not to block the photorespiratory process, which was being promoted by others. This attracted the attention of a young researcher, Chris Somerville, who came to the lab. Chris thought that a relatively unknown plant, Arabidopsis would be a useful model system for a genetic approach to the controversy. Their collaboration resulted in the creation and detailed characterization of the first directed nuclear gene mutants in a higher plant (Arabidopsis), in this case with defects in photosynthetic carbon Arachidonate 15-lipoxygenase metabolism (e.g., Somerville and Ogren 1979; also see Somerville 1982; and Somerville 2001). We note that other nuclear gene mutants in higher plants were known. What Chris did was to make the first plant nuclear gene mutant with lesions in a specific physiological

process. These were not just the first plants with predetermined lesions in photosynthesis, but the first with predetermined lesions of any kind. That is why the experiments are so important. With these mutants they were able to genetically dissect the pathway of photorespiration and provide definitive answers to several remaining and controversial aspects of photorespiratory carbon metabolism. These pioneering studies were instrumental in establishing the usefulness of Arabidopsis as a model genetic system for higher plants and launched the careers of many scientists. One of the mutants isolated by Chris Somerville was characterized as being defective in the light-induced increase in the activity of Rubisco (Somerville et al. 1982).