5, it is expected to be most effective in identifying large-effec

5, it is expected to be most effective in identifying large-effect QTL. Association mapping based on

LD has been proved to be effective for revealing the genetic basis of important traits in maize with high resolution [59], as shown on chromosomes 3, 5, 7, 8, and 9 (Fig. 4), by markers such as PZE-103142893 (qGLS3.07), and PZE-109119001 (qGLS3.07) within candidate genes in chromosome bins 3.07 and 9.07, respectively ( Fig. 3). Previous studies suggested that SNPs significantly associated with phenotypic variance could be located very closely to the causative genetic variants [60] and [61]. In the present study, GSK1210151A concentration three candidate genes, GLScgcb03071, GLScgcb03072, and GLScgcb0907, were identified by their conserved regions including CC and STK, which are shared by many R genes cloned to date [62] and [63]. The CC domain is a conserved motif contained in some nucleotide-binding site/leucine rich repeat (NBS-LRR) proteins (CC-NBS-LRR) that are involved in pathogen sensing and host defense [64], [65] and [66]. These types of domains have been identified in proteins involved in resistance to fungal diseases SB431542 including Dm3, which confers Bremia lactucae resistance

in lettuce [67]; I2, which confers Fusarium oxysporum resistance in tomato [68] and [69]; Mla, which confers Blumeria graminis Selleckchem Paclitaxel resistance in barley [37]; Pib, which confers Magnaporthe grisea resistance in rice [70]; and Rp1, which confers Puccinia sorghi resistance in maize [71]. Proteins containing STK domains, such as the rice bacterial blight resistance gene product Xa21 [72], constitute one category of receptor

protein kinases (RPK) [73] that play important roles in plant–pathogen interaction and defense responses [73], [74], [75] and [76]. Collectively, the candidate genes we have identified suggest that joint linkage–linkage disequilibrium mapping is a powerful tool for revealing candidate genes for complex traits. However, it should be emphasized that these candidate genes should be further validated via other methods. There are two main reasons why only three candidate genes were identified in this study. First, the sequence lengths of regions within the LD blocks containing significant SNPs that were scanned for potential genes were variable. For example, the length of the genomic sequence derived from PZE-103142492 in chromosome bin 3.06 was only 2583 bp. Second, not all conserved domains and motifs useful for identifying candidate genes conferring GLS resistance have yet been identified. To date, most R genes that have been cloned share a limited number of conserved domains and motifs, such as NBS, LRR, and PK motifs, transmembrane domains, leucine zippers, and Toll-interleukin-1 motifs [65].

The transformants became avirulent on rice cultivars that contain

The transformants became avirulent on rice cultivars that contained Pi-ta. For the first time we have demonstrated experimentally that AVR-Pita1 from O-137 can result in avirulence in virulent U.S. field isolates.

These results suggest that field isolates in the U.S. carry functional avirulence alleles toward Pi-ta-carrying rice cultivars. Aligning AVR-Pita1 from O-137 with other U.S. AVR-Pita1 variants revealed 92.4% amino acid sequence identity among the predicted AVR-Pita1 proteins ( Fig. 4). A total of 11 amino acid differences were identified in AVR-Pita1 alleles of 8 common U.S. selleck compound races (isolates). Isolates carrying these AVR-Pita1 variants showed no change in pathogenicity toward Pi-ta-carrying rice cultivars, suggesting that these isolates carry functional AVR-Pita1 variants ( Fig. 4). Previously, it was demonstrated that one amino acid residue of the AVR-Pita1 protease motif determines the degree of avirulence [10], [12], [13] and [33].

Additionally, Böhnert et al. [4] found that a mutation in the putative catalytic site of the B-ketoacyl synthase domain of ACE1 in the M. oryzae avirulence gene ACE1 abolished the selleck chemicals recognition of the fungus by the resistant plant. Tosa et al. [34] determined that selection during the evolutionary process maintained AVR1-Co39′s specificity of recognition by cultivar CO39. In the present study, most of the functional portion of the AVR-Pita1 effector was highly conserved, whereas 7.6% represented a polymorphic region including amino acid substitution V173I within the protease motif. However, although V173I lies in the zinc metalloprotease motif, valine and isoleucine are both hydrophobic, resulting in no functional alteration, given that all isolates containing these AVR-Pita1 variants were avirulent to rice germplasm with Pi-ta. This finding suggests that the amino acid variation in U.S. field isolates has no influence on the avirulence activity of AVR-Pita1. ZD1839 We suggest that these polymorphic regions including V173I of the AVR-Pita1 protein are

not critical for protease activities. We demonstrated that AVR-Pita1 from a Chinese isolate can be used to trigger Pi-ta-mediated resistance in virulent U.S. isolates. It is possible that AVR-Pita1 is involved in pathogenicity as a metalloprotease. To determine whether increased copy numbers of AVR-Pita1 changed pathogenicity, transformants with multiple copies of AVR-Pita1 were inoculated on rice cultivars that do not carry Pi-ta. In repeated inoculations, no differences in pathogenicity were observed relative to that of wild-type field isolates. During these studies, two of the avirulent transformants with multiple copies of AVR-Pita1 exhibited a slight reduction of spore production under standard culture conditions, suggesting that these transformants would not survive under natural conditions. However, no changes in pathogenicity of these two transformants on rice cultivars that lack Pi-ta were observed (data not shown).

, 2006) According to the available

literature the effect

, 2006). According to the available

literature the effect of low temperature (<25 °C) ATES systems on mineral equilibria is expected to be limited. Many of the reactions that occur in groundwater systems are however not determined CHIR-99021 ic50 by chemical equilibria but by kinetic processes (Appelo and Postma, 2005). Examples of kinetically controlled reactions in groundwater systems are weathering reactions of silicates and redox reactions (van Oostrom et al., 2010). ATES field tests at high temperatures (40–100 °C) for example showed that K-feldspar weathering progresses faster around the warm well then around the cold well (Holm et al., 1987 and Perlinger et al., 1987). Prommer and Stuyfzand (2005) demonstrated that redox reactions in groundwater

are affected by small temperature differences. In their study, surface water with a variable temperature (2–23 °C) was injected during two years. Differences in breakthrough in the monitoring wells indicated that the oxidation of pyrite and organic matter by oxygen SCH727965 cost and nitrate proceeds significantly faster at higher temperatures. When the ATES system is in thermal balance, however, no significant temperature effects are expected from the Arrhenius equation when ΔT < 20 °C. If there is an unbalance in energy input and output in the ATES system, or if the temperature differences are larger (ΔT > 20 °C), the effects of the temperature on kinetics increases due to the exponential dependence of reaction rates on temperature ( Hartog, 2011). Laboratory research (Brons et al., 1991) into the effect of temperature on organic matter in aquifers demonstrated that at temperatures above 45 °C organic carbon is mobilized resulting in an increased chemical oxygen demand (COD) of the groundwater. The ability of the remaining organic matter to adsorb organic micro pollutants or trace elements may hereby decrease (TCB, 2009 and van Oostrom et al., 2010). Two more recent studies (Bonte et al., 2013b and Jesußek et al., Ureohydrolase 2012) reported increased concentrations of DOC with increasing temperature in a laboratory setting. It was shown that the occurrence and rate of nitrate,

sulfate and iron reduction are strongly dependent on temperature. At 70 °C, a change in sediment sorption behavior for cations and organic acids was assumed based on changes in pH, Mg and K concentration. At 10–40 °C, on the other hand, no clear changes of pH, total inorganic carbon (TIC) and the major cations occured. Incubation experiments have shown that when organic acids and orthophosphates are present, a strong oversaturation of the carbonates is possible because of precipitation inhibition. An increase in temperature leads, at one hand, to a reduced solubility of calcium and magnesium carbonates (carbonate precipitation) and, on the other hand, carbonate precipitation is inhibited by mobilization of dissolved organic carbon.

It was also time to assess the status of knowledge and what would

It was also time to assess the status of knowledge and what would be the new priorities. Indeed, like a natural ecosystem, the French Polynesia black pearl industry has reached its climax, collapsed, and is now in a recovery stage. The official numbers from the

Institut de la Statistique de Polynésie Française (ISPF) show the changes in total exported production, monetary value per gram and total number of concessions since these variables are monitored ( Fig. 2 and Fig. 3). Prices collapsed in the year 2000s, due primarily to overproduction of lowest quality pearls and poor management and control of the commercial distribution towards international Asian, American and European markets. Prices plummeted from around 100US$ per gram in 1985 down to less than 5US$ in 2010. Consequently, the BMN 673 clinical trial number Capmatinib clinical trial of concessions decreased steadily throughout

the Tuamotu and Gambier. In 2010, respectively 425, 102 and 28 concessions were granted for respectively Tuamotu, Gambier (mostly in Mangareva, a high island with a wide lagoon) and Society Archipelagos, thus a total of 555 concessions. In 2011, the last available overall number is 541. In 1999, 2745 concessions were active. Small family businesses took a heavy toll with the collapse of the prices. They represented in 2011 80% of the farms for 20% of the export market. The total concession area is now limited to 10000 hectares all lagoons included. In 2011, this represented 26 atolls and 4 islands. Among them, 15 atolls are collecting atolls. The industry is now trying to rebuild the equilibrium between offer and demand, with the hope that curves of prices per pearl and per gram will rise. Dimethyl sulfoxide Pearl quality is closely monitored for exportation. Eleven millions pearls have been controlled in 2010, which represented 18.3 tons. Low quality pearls are destroyed and farmers

receive a fixed rate of 0.5 US$ per destroyed gram as a compensation. In 2010, 400 kg of these poor quality pearls have been disregarded. In addition, commercial promotion and selling networks are also restructured. The aquaculture of black pearl in French Polynesia has thus modified the livelihoods of thousands of islanders in the past 30 years. It has also reshaped the atollscape, with numerous farms, buildings, pontoons and boats appearing and disappearing along shores and coral pinnacles. Tens of thousands of buoys and millions of hanging lines dot the lagoons, spread in the official 10000 hectares of concessions all over French Polynesia. Millions of oysters have been artificially hanging in the water column instead of living on deep atoll floors. Naturally separated oyster populations have been mixed, and species of sponges, anemones (in particular Aiptasia pallida) and other epibionts have been introduced in lagoons.

The off-flavour development in soymilk is primarily due to the li

The off-flavour development in soymilk is primarily due to the lipoxygenase

or the oxidative rancidity of unsaturated fatty acids (Wolf, 1975). Therefore, soybean oil content and fatty acid composition play important roles in the flavour attributes, despite their limited amounts in soymilk. In our study, a significant positive correlation between oil content and soymilk selleckchem overall acceptability was observed (r = 0.298∗) ( Table 4), suggesting the oil content benefits the soymilk flavour property. However, for fatty acid composition, the correlations were considerably complicated ( Table 4). For instance, significant negative correlations were observed between soymilk aroma and saturated fatty acids (i.e., palmitic acid (r = −0.350∗) and stearic acid (r = −0.236∗)), whereas significant positive correlation of colour and appearance with palmitic acid (r = 0.405∗∗) and linolenic acid (r = 0.302∗) were observed ( Table 4). Oleic acid and linolenic acid were significantly positively correlated with smoothness in the mouth and sweetness (r = 0.253∗ and r = 0.237∗, respectively), whereas stearic acid was significantly negatively correlated with thickness in the mouth (r = −0.293∗) ( Table 4). Moreover, as the most important sensory parameter, the overall acceptability failed to correlate with any fatty acid components ( Table 4). It has been reported that soybean lipoxygenases catalyse the oxidation of polyunsaturated

fatty acids, forming hydroperoxide derivatives, which undergo a scission and dismutation reaction, resulting in the development of off-flavours ( Iassonova et al., 2009, Wolf, 1975 and Moreira et al., 1993). Especially, CH5424802 concentration the beany flavour that makes soymilk taste unpleasant to Westerners may be due to 2-pentylfuran, which is mainly

formed from linoleic acid by singlet oxygen ( Min et al., 2005). Moreover, free linoleic acid and linolenic acid in soymilk present bitterness and beany odour ( Stephan & Steinhart, 2000). Our results also suggested an important role of fatty acid composition in soymilk sensory attributes, however, the effect of fatty acid composition on soymilk sensory attributes were considerably complicated. Soluble solids content Clomifene is an important parameter for beverage evaluation in food industry. High soluble solids content was desirable soymilk characters for consumers (Lim, Deman, Deman, & Buzzell, 1990). Moreover, the soluble solids content was significantly affected by soybean cultivars (Aziadekey, 2001). Therefore, the soluble solids content was determined as a soymilk chemical character in this study. According to our results, soluble solids content was positively correlated with all of soymilk sensory attributes (Table 4). Especially, significant positive correlations were observed between soluble solids content and soymilk aroma (r = 0.330∗∗), thickness in the mouth (r = 0.410∗∗), and over acceptability (r = 0.427∗∗) ( Table 4).

The negative ξ implies that there is an interaction energy betwee

The negative ξ implies that there is an interaction energy between two kinds of molecules

which is higher than the mean energy of interaction among the same molecules. The interaction energy Δɛ was obtained according to Eq. (7) and the higher this value the more intense the interaction is. equation(7) −Δε=−ξRT6where RT is the product of the gas constant and the Kelvin temperature. The first pseudo-binary mixture analyzed was EPC and DOTAP. Fig. 1A presents the π–A isotherms for EPC/DOTAP mixed monolayers. The profiles are characteristic of expanded liquids, without phase transitions. The higher the DOTAP molar fraction, the more expanded the isotherm is and no profile modification is observed. The collapse pressure, πcol, varies Staurosporine cell line from 47 mN m−1, for pure EPC, to 37 mN m−1, pure DOTAP (with increasing DOTAP molar fraction) ( Table 1). A slight negative deviation of the molecular surface area additivity rule is observed through the non-linear course of the A12 vs. the monolayer composition ( Fig. 1B), depending on the surface compaction of the monolayer. At surface pressures lower than 20 mN m−1

the deviations are evident for DOTAP mol fractions above 0.6, while for higher Metformin surface pressures (20–30 mN m−1), they occur in the whole range of DOTAP concentrations. These deviations together with negative values of excess free energy of mixing, ΔGExc ( Fig. 1C) were interpreted as attractive interactions, confirming the miscibility between the lipid molecules. The ΔGExc reaches a minimum (−1 kJ mol−1), for 0.5 < XDOTAP < 0.7. The interaction parameter (ξ) and interaction energy (Δɛ) for EPC/DOTAP mixed monolayers are presented in Table 2. The ξ values are negative for monolayers with excess of EPC and positive in the case of DOTAP molar excess. The influence of monolayer composition on the EPC monolayer

was also evaluated from Cs−1–π curves, for different XDOTAP, as presented in Fig. 1D. The maximum value of Cs−1 is presented in Table 1 as a function of the monolayer composition. Fig. 1D and Table 1 indicate that EPC and DOTAP pure monolayers Protein tyrosine phosphatase present maximum Cs−1 values of 82.5 and 60 mN m−1, respectively. The increase of XDOTAP promotes the decay of Cs−1, in accordance with the mean area per molecule behavior observed in the isotherms of Fig. 1A. This also means that the addition of DOTAP makes the monolayer more compressible or less elastic, in the sense of surface Young’s modulus. The π–A isotherms for EPC/DOPE mixtures are presented in Fig. 2A. Again, only an expanded liquid phase could be observed without defined phase transitions. However, any EPC/DOPE mixture produced more expanded monolayers than the individual components. The maximum expansion occurred for XDOPE = 0.

Compound signals imply relations between the concepts that they r

Compound signals imply relations between the concepts that they refer to. In natural language, the generic principle for compound signals is asymmetric dependency1 (head-dependent, stem-affix, modified-modifier, main-subordinate clause, etc.). Thus, the conceptualization of asymmetric relations between concepts (CARC) is a cognitive prerequisite for language. From the viewpoint of CARC, the following statements are equivalent: concept A depends

on concept B, A is caused by B, A contains B, A includes B, B belongs to A, B is a part of A, etc. The simplest kind of representations we regard PR-171 concentration as concepts are secondary representations in the sense of Perner (1991): cross-modal mental models capable of representing past, future, or imaginary objects or events, or representing the representational content of other representational systems. According to Perner (1991, p. 7), secondary representations are distinct from (and intermediate between) primary representations and metarepresentations. In addition to relating two concepts asymmetrically, CARC enables conceptual compositionality (e.g. father = male parent, 2 = 1 + 1, etc.) and semantic embedding (explained in the next paragraph). The adaptivity of CARC lies in an increase in the ability to plan one’s behavior owing to the conceptualization of asymmetric relations governing the physical world. The effects of CARC include the conceptualization of

containment hierarchies of depth Baf-A1 in vitro 2 and more, causality, definitions, the concepts of knowledge and ownership, etc. The possibly uniquely human semantic synthesis ability, proposed by Dessalles, is also an effect of CARC. In describing Tau-protein kinase protolanguage, Dessalles (2008, p. 56) gives the following example of semantic synthesis: “Listeners must integrate the different associations triggered by the different words, ‘stranger’, ‘plain’, ‘fire’ into one single state of affairs, instead of imagining several disconnected

situations”. Not only syntactic (clauses) but also morphosyntactic (inflected words) and discourse pragmatic (discourse context) devices are compound signals that subsist on CARC. It should be noted though that while clause and discourse are almost always compound (imply semantic embedding), phrases and word forms are frequently elementary. Thus we have to discern at least these four levels of semantic embedding (cf. below). However, a compound signal is not the first step towards syntax. Concatenation is necessarily a compound signal only from the viewpoint of modern syntax. A protosyntactic concatenation lacks at least two features characteristic of modern syntax: grammar and semantic embedding. We define semantic embedding as follows: a meaningful linguistic unit in another meaningful linguistic unit, e.g. a phrase in a phrase, a word in a phrase, a word in a sentence, a word in a discourse, a morpheme in a word, etc.2 A protosyntactic concatenation of any two signals A and B (e.g.

Initially we developed two sets of outbreak reconstructions, one

Initially we developed two sets of outbreak reconstructions, one constructed INCB018424 chemical structure using the regional lodgepole pine chronology as the non-host and a second constructed using the regional ponderosa pine chronology as the non-host. The average correlation coefficient between the reconstructions was 0.60 (ranging from 0.42 to 0.83) (Fig. 2a), indicating good correspondence between non-hosts and providing confidence that either could be used in the outbreak analyses. The outbreak reconstructions for each non-host are plotted for Site 5 (Fig. 2b), which had an average correlation coefficient between reconstructions (r = 0.58), illustrating that overall the two non-hosts produced similar outbreak histories in terms of timing

and duration. The Alectinib supplier most significant difference between the two reconstructions was the outbreak intensity. Reconstructions based on lodgepole pine generally had a higher ratio of trees meeting the outbreak

parameters than those based on ponderosa pine (e.g., Fig. 2b). This pattern was consistent for all sites suggesting that WSB outbreak reconstructions based on ponderosa pine are likely to be more conservative. Nonetheless, we chose to use only the regional ponderosa pine chronology to construct our final WSB reconstruction as it extended further back in time (>400 years). Our WSB reconstructions show that outbreaks have occurred in the Cariboo Forest Region for the past 300–400 years (Fig. 3). These outbreaks have varied in intensity and duration at individual sites, but at times were highly synchronous across the study area (Fig. 3 and Fig. 5). The sites with the longest outbreak reconstructions (FR, RS, FC, S6, ML and CM; Table 1) all 4-Aminobutyrate aminotransferase recorded outbreaks in the early-1600s and 1630s, where 80–100% of trees recorded outbreaks (Fig. 3). From the 1650s to the early-1700s site-specific outbreaks occurred at generally low levels. In the 1720s a synchronous, moderate outbreak occurred at all sites (Fig. 3). In the 1770s a high intensity (60–80% of trees) outbreak occurred at nearly all the sites, with the exception of FC and S1 (Fig. 3). The 1800s were characterized by a

period of predominately stand-specific outbreaks of variable intensity until the late-1800s when all the sites recoded a severe outbreak (80–100% of trees) (Fig. 3). Our reconstructed outbreak history was compared with survey records from the 20th and 21st centuries. Ninety-one percent of the Douglas-fir stands examined in this study record outbreaks from the late-1930s to mid-1940s (Fig. 3). Although few records exist in the study area prior to 1994, documented outbreaks in the mid-1930s to mid-1940s to the south and west closely coincide to our reconstructed outbreaks (Harris et al., 1985). The 1974 WSB outbreak observed by Erikson (1992) near the FC site chronology (Fig. 1) appears at 64% of our sites, albeit as a low intensity event that impacted from 20% to 40% of the trees at sites recording the outbreak (Fig. 3).

Similarly, orienting

clients to phone holidays and the th

Similarly, orienting

clients to phone holidays and the therapist’s personal limits around phone coaching allows therapists to be proactive rather than reactive when personal limits are breached. Orientation to phone coaching often occurs after an unsuccessful or problematic use of phone coaching. Because clients with BPD can be keenly sensitive, this can feel like a reprimand, and, as such, may deter some clients with BPD from using phone coaching Olaparib solubility dmso in the future. Thus, by properly orienting clients to the contingencies present in DBT phone coaching, problematic and unskillful use of this treatment modality is diminished. “
“The Centers for Disease Control and Prevention (CDC) estimates that there are more than 1.1 million individuals living with HIV/AIDS in the United States (CDC, 2012b). Furthermore, rates of new infections have remained relatively stable in recent years at a rate of approximately 50,000 new infections each year (CDC, 2012a). Given that deaths of individuals living with HIV infection have also remained stable at around 20,000 per year (CDC, 2012b), the RO4929097 population of individuals

living with HIV in the United States is on the rise. The HIV/AIDS epidemic in the United States carries with it a heavy economic burden (Hutchinson et al., 2006), which is exacerbated by high levels of comorbidity with mental and physical health problems (Safren, Blashill, & O’Cleirigh, 2011), and treatments that aim to reduce mental Reverse transcriptase health problems and optimize health among HIV-infected individuals may help to ease this burden. Depression is one of the most frequently occurring comorbidities in HIV-infected individuals (Bing et al., 2001 and Ciesla and Roberts, 2001).

A meta-analysis estimated that 9.4% of HIV-infected adults met DSM criteria for current major depressive disorder (Ciesla & Roberts, 2001), and another large nationally representative survey estimated that 36% of HIV-infected adults met criteria for major depressive disorder in the past 12 months (Bing et al., 2001). Further, meta-analyses and systematic reviews have found that depression is not only associated with nonadherence to antiretroviral therapy (ART) among HIV-infected individuals (Gonzalez, Batchelder, Psaros, & Safren, 2011), but it is also independently associated with HIV disease progression (i.e., decreases in CD4 T lymphocytes, increases in viral load; Leserman, 2008). Depressive symptoms may additionally potentiate risk of HIV transmission to HIV-uninfected individuals, as evidence suggests that moderate levels of depressive symptoms may increase engagement in sexual risk behavior (Koblin et al., 2006, O’Cleirigh et al., 2013, Parsons et al., 2003 and Stall et al., 2003). Moreover, elevated viral load resulting from depression and ART nonadherence increases infectiousness in the HIV-infected individual, thus increasing likelihood of transmission to HIV-uninfected partners (Attia et al., 2009, Cohen et al.

This led to the synthesis of a trichloro analog in Townsend’s lab

This led to the synthesis of a trichloro analog in Townsend’s laboratory at the University of Utah and later the discovery of its see more activity against HCMV in John’s laboratory. Much work, in both their laboratories at the University of Michigan, established that it and its 2-bromo

analog (BDCRB) have excellent activity against HCMV with very low cytotoxicity. Surprisingly, it was found to be inactive against other herpes viruses and it did not need conversion to a triphosphate to be active against HCMV. Collaborative studies with Karen Biron at Burroughs Wellcome established that, unlike many other anti-virals that inhibit viral DNA synthesis such as ganciclovir (GCV), these compounds acted by a novel mechanism, inhibition of viral DNA processing. It was the viral resistance studies which revealed the viral targets, pUL89 and pUL56. These two proteins, with pUL104, form a complex known as the terminase which cuts newly synthesised HCMV DNA into unit lengths for packaging into virions. Although BDCRB had many desirable properties in

vitro, it had poor pharmacokinetics in mice and monkeys due to hydrolysis of its glycosidic bond; therefore it was not developed for human use. Much additional work in Drach’s and Townsend’s laboratories at Michigan and by Biron’s group at Burroughs Wellcome ultimately buy KRX-0401 led to two potential drug candidates, BDCRB pyranoside and maribavir ( Fig. 2). Both compounds have excellent activity against HCMV, low toxicity, and excellent pharmacokinetics. Clearly, their modes of action differed

markedly from that of GCV. Quite unexpectedly, they have different mechanisms of action. BDCRB pyranoside has a mechanism of action very similar to its parent compound BDCRB, inhibition of DNA processing. In contrast, maribavir inhibits DNA synthesis, albeit indirectly. It is a 2-isopropylamine derivative of BDCRB except that it has the unnatural L-sugar configuration. Its mechanism of action involves inhibition of the viral kinase (pUL97), which phosphorylates another viral protein, pUL44. Phosphorylated pUL44 is necessary for viral DNA synthesis. Thus inhibition of pUL97 by maribavir inhibits viral DNA synthesis. Interestingly, Inositol monophosphatase 1 pUL97 is also the kinase that activates (phosphorylates) GCV. Resistance studies confirmed that a single mutation in UL97, resulting in a mutation in the kinase (Leu397Arg), was necessary and sufficient for resistance to maribavir. In a further study of resistance, virus already resistant to BDCRB was passaged in increasing concentrations of maribavir and resistant virus was isolated. This strain grew at the same rate as the wild-type virus and was resistant to both BDCRB and maribavir. As expected, resistance to BDCRB was due to known mutations in UL56 and UL89. However, no mutations were found in UL97.