Indeed, most of the hypotheses focused on intra-neuronal events,

Indeed, most of the hypotheses focused on intra-neuronal events, such as dopamine oxidation, oxidative stress and excitotoxicity. Yet, recent reports suggested that glia may contribute to METH-induced neuropathology. In the present study, we investigated the hippocampal

dysfunction induced by an acute high dose of METH (30 mg/kg; intraperitoneal injection), focusing on the inflammatory process and changes in several neuronal structural proteins. For that, 3-month-old male wild-type C57BL/6J mice were killed at different time-points post-METH. We observed that METH caused an inflammatory response characterized by astrocytic and microglia reactivity, and tumor necrosis factor (TNF) system alterations. Indeed, glial fibrillary acidic protein (GFAP) and CD11b immunoreactivity were upregulated, likewise TNF-α and TNF receptor 1 protein levels. Furthermore, the effect of METH on hippocampal neurons was also investigated, and we observed a downregulation in beta III tubulin expression. To clarify the possible this website neuronal dysfunction induced by METH, several neuronal proteins were analysed. Syntaxin-1, calbindin D28k and tau protein levels were downregulated,

whereas synaptophysin was upregulated. We also evaluated whether an anti-inflammatory drug could prevent or diminish METH-induced neuroinflammation, and we concluded that indomethacin (10 mg/kg; i.p.) prevented METH-induced glia activation and both TNF system and beta III tubulin alterations. In conclusion, we demonstrated that

METH triggers an inflammatory process and leads to neuronal dysfunction in the hippocampus, which can be prevented by an anti-inflammatory treatment. “
“Neuroscience of the self has focused on high-level mechanisms related to language, memory or imagery of the self. Clomifene However, recent evidence suggests that low-level mechanisms such as multisensory and sensorimotor integration may play a fundamental role in self-related processing. Here we used virtual reality technology and visuo-tactile conflict to study such low-level mechanisms and manipulate where participants experienced their self to be localized (self-location). Frequency analysis and electrical neuroimaging of co-recorded high-resolution electroencephalography revealed body-specific alpha band power modulations in bilateral sensorimotor cortices. Furthermore, alpha power in the medial prefrontal cortex (mPFC) was correlated with the degree of experimentally manipulated self-location. We argue that these alpha oscillations in sensorimotor cortex and mPFC reflect self-location as manipulated through multisensory conflict. “
“Neurons in V1 display orientation selectivity by responding optimally to a preferred orientation edge when it is presented within their receptive fields. Orientation plasticity in striate cortex occurs either by ocular deprivation or by imposition of a non-preferred stimulus for several minutes.

Publication in HIV Medicine Shortened version detailing concise

Publication in HIV Medicine. Shortened version detailing concise summary of recommendations. E-learning module accredited for CME. Educational MK-2206 molecular weight slide set to support local and regional educational meetings. National BHIVA audit programme. The guidelines will be next fully updated and revised in 2014. However, the Writing Group will continue to meet regularly to consider new information from high-quality studies and publish amendments and addendums to the current recommendations before the full revision date where this is thought to be clinically important to ensure

continued best clinical practice. “
“Deinococcus radiodurans tolerates extensive DNA damage and exhibits differential expression of various genes associated with the growth of the organism Compound Library screening and DNA repair. In cells treated with γ radiation, the levels of cyclic AMP (cAMP) and ATP increased rapidly by differentially regulating adenylyl cyclase (AC) and 2′3′ cAMP phosphodiesterase. The levels of cAMP, ATP, AC and protein kinases were high when phosphodiesterase activity was low. These cells exhibited in vivo inhibition of nucleolytic function by reversible protein phosphorylation and contained the comparatively higher levels of total phosphoproteins. We suggest that Deinococcus, a prokaryote, uses DNA damage-induced signaling mechanism as evidenced by γ radiation-induced synthesis

of secondary messengers and signaling enzymes. Protein phosphorylation constitutes an important regulatory network that controls the cellular functions including cell division, cellular differentiation and signal transduction in all organisms (Pawson, 1994). At molecular levels, this regulates metabolic functions such as enzyme activity modulation, protein trafficking, protein–protein and DNA–protein interactions and recycling of proteins (Ubersax & Ferrell, 2007). By reversible protein phosphorylation, the functions of proteins can be rapidly modulated without the need for new protein synthesis

or degradation. This phenomenon Ribociclib chemical structure is regulated by the relative abundance of stress-responsive protein kinases and phosphatases in the cells (Sefton & Hunter, 1998). In eukaryotes, the significance of reversible protein phosphorylation is amply illustrated by the involvement of DNA damage-induced signal transduction and protein kinase C-mediated signaling mechanism in cell cycle regulation (Sancar et al., 2004; Kitagawa & Kastan, 2005). The existence of such mechanisms and their implications in DNA strand break (DSB) repair and bacterial growth would be worth investigating in Deinococcus radiodurans, a bacterium that confers extraordinary tolerance to DNA damage and has acquired a large number of putative sensor kinases and response regulators (White et al., 1999) from other organisms (Makarova et al., 2001).

, 2005; He et al,

2006) As already noted above, RecA is

, 2005; He et al.,

2006). As already noted above, RecA is RAD001 concentration not required for the stationary-phase mutagenesis in P. putida (Tegova et al., 2004). At the same time, nonhomologous end-joining (NHEJ), an essential pathway responsible for the repair of DSBs, composed of the DNA end-binding Ku protein and a multifunctional DNA ligase (LigD), has been identified recently in many prokaryotes including Pseudomonas species and mycobacteria (Pitcher et al., 2007a, b; Shuman & Glickman, 2007). DNA repair provided by the bacterial NHEJ system has been shown to be inaccurate, resulting in single nucleotide additions or deletions with various lengths at the break site (Gong et al., 2005; Malyarchuk et al., 2007; Stephanou et al., 2007). Recent studies with Mycobacterium smegmatis revealed that NHEJ mutant strains are more sensitive to ionizing radiation and desiccation during the stationary phase than the wild-type

strain (Pitcher et al., 2007b). In addition, NHEJ is required for the repair of artificially induced, I-SceI-mediated chromosomal DSBs in stationary-phase cells (Stephanou et al., 2007). In Bacillus subtilis, NHEJ is also growth phase regulated, contributing to DSBR only during the outgrowth of spores or in stationary-phase cells (Wang et al., 2006; Moeller et al., 2007; Simmons et al., 2009). Therefore, it would be important to study whether NHEJ could play a role in learn more stationary-phase mutagenesis in bacteria. These studies are currently in progress in our laboratory. There is no single mechanism for the generation of stationary-phase mutations in bacteria. Multiple factors Edoxaban including oxidative damage of DNA and proteins, other kinds of DNA damage, errors occurring during DNA replication and inefficiency of DNA repair may cause mutations. Additionally, DNA repair synthesis itself may be a source of mutagenesis

under the growth-restricting conditions of bacteria. Moreover, because bacteria differ in the content of DNA polymerases and DNA repair enzymes, several mechanisms that have not discovered with the E. coli model may become apparent in other bacterial species. Bacteria belonging to the genus Pseudomonas, which represents one of the most diverse and ecologically widely distributed groups of microorganisms, carry, similar to many other bacterial species, a different set of specialized DNA polymerases compared with that characterized in enterobacteria. There are also differences in DNA repair enzymes/systems whose connection with stationary-phase mutagenesis needs further exploration. I wish to thank R. Hõrak, M. Putrinš, S. Saumaa, K. Tarassova and M. Tark for their comments on the draft version of this manuscript.

However, Voyich et al (2009) reported that ssl11 and


However, Voyich et al. (2009) reported that ssl11 and

the agr operon in a saeR/S mutant of MW2 strain is downregulated by ∼16- and 2-fold, respectively, at the early stationary growth phase. In concordance with our data, Liang et al. (2006) showed, by RT-PCR analysis, that agrA mRNA levels were significantly upregulated in the saeS null mutant compared with its wild-type strain, WCUH29, a virulent clinical isolate. Taken together, these data suggest that the influence of saeR/S on the transcriptional regulation of virulence genes is probably dependent on multiple factors including the genomic background of the strain studied (Liang et al., 2006; Rogasch et al., 2006). Interestingly, in the agr/sigB double mutant, the expressions of ssl5, ssl8, and sae was downregulated (Fig. 2). However, in the agr mutant strain, these genes were upregulated, whereas the expression of either ssl5 or ssl8 did not change in

a Newman sigB mutant. This suggests that SigB probably acts synergistically with Agr, but not alone, to upregulate ssl5 and ssl8. This could very well be mediated by sae specifically in the Newman strain. An analogous phenomenon such as enhanced repression of exotoxin-encoding genes in double mutants of regulatory genes in S. aureus is not uncommon. For example, sar and agr double mutants are less virulent compared with the agr single mutant (Booth et al., 1997). Differences in the transcript levels of regulatory genes (agr, sarA, sigB, and saeR/S) have been reported between COL and Newman strains that correlate well with the expression of virulence-associated genes (Rogasch et al., 2006). In summary, ssl5 Oligomycin A in vitro and ssl8 expression in S. aureus clinical isolates is strain dependent and not influenced by differences in their alleles. They are positively regulated by Sae and negatively

C1GALT1 by Agr in the Newman strain. Furthermore, the ssl5 and ssl8 repression by Agr is probably achieved by the downregulation of Sae in the Newman strain. This is the first report of a negative regulation of an ssl gene by Agr. This study also highlights the potential challenges in managing infections due to S. aureus strains, which could potentially produce varying amounts of SSLs. Understanding the intricacy of global regulatory genes and their mode of regulation in different genetic backgrounds would provide an important insight into the molecular mechanisms of staphylococcal virulence. This may perhaps reveal specific targets, which would enable therapeutic intervention in S. aureus infections. This research was funded in part by research grant RO1 AI061385 from the National Institutes of Allergy and Infectious Diseases to S.K.S. The authors thank James Burmester and Joseph Mazza, Marshfield Clinic Research Foundation, for critically reviewing the manuscript. Table S1. List of SNPs identified in the ssl5 coding and upstream regions in Staphylococcus aureus strains.

At present there are no specific interventions known to improve t

At present there are no specific interventions known to improve these pathogenic mechanisms; however, there is evidence to suggest that the organisation

of care could have an impact on the onset of foot disease. These patients therefore should have regular foot surveillance, education, and support from appropriate specialists to manage their foot care. All professionals involved in the care of patients with diabetes and renal disease should be aware of the Protease Inhibitor Library extent to which the patient’s feet are at risk. Copyright © 2012 John Wiley & Sons. “
“There have been few studies investigating the use of GLP-1 agonists in patients with insulin-treated type 2 diabetes and none looking at the costing. We compared the efficacy and relative cost of adding exenatide treatment to patients with type 2 diabetes receiving either oral hypoglycaemic agents (OHAs) or insulin. Patients were recruited from West Suffolk Hospital Diabetes Centre. Data were acquired retrospectively from 207 patients completing six months of treatment. Of 207 patients, 188 demonstrated good clinical progress with a mean HbA1c reduction of 1.6% (p<0.0001) and weight loss of 6.9kg (p<0.0001). Nineteen patients discontinued exenatide as HbA1c reduction did not achieve the NICE target (0.4%; p=0.29), but they did achieve significant weight loss (5.6kg; p<0.0001). The 188 patients continuing

on exenatide were sub-divided check details into insulin-treated (n=88) or tablet-treated (n=100). At six months, tablet-treated patients achieved an HbA1c reduction of 1.6% (p<0.0001) and weight loss of 6.5kg (p<0.0001). Insulin-treated patients achieved similar results: HbA1c reduction 1.6% (p<0.0001), weight loss 7.3kg (p<0.0001). After six months of exenatide treatment, the mean reduction in daily insulin dose was 48 units/person in the insulin-treated group. In the tablet-treated group, the cost of diabetic medication (per person/month) after six months was £54.90 above baseline, whereas in the insulin-treated group this was only £36.20 above baseline, because the reduction 4��8C in insulin dose offset the cost of exenatide. It was concluded that exenatide is clinically

effective in both insulin-treated and tablet-treated type 2 diabetes, but is more cost effective in those originally treated with insulin. Copyright © 2011 John Wiley & Sons. “
“The aims of this study were to determine whether the introduction of a diabetes management e-module can increase junior doctors’ confidence in managing inpatients with diabetes and contribute to improvements in patient care. A diabetes e-module was introduced at Barnet and Chase Farm Hospitals NHS Trust in October 2010. Junior doctors completed it and undertook an online exam at the end. Junior doctors were surveyed once, six to eight months after completing the e-module, and retrospectively ranked their confidence and knowledge levels in managing inpatients with diabetes before and after completing the e-module.

Attack rates among Dutch travelers to developing regions declined

Attack rates among Dutch travelers to developing regions declined for hepatitis

A, shigellosis, and typhoid fever. Region-specific trends in attack rates of shigellosis resembled trends of hepatitis A and typhoid fever. Declining attack rates of the three fecal-orally transmitted diseases correlated Apoptosis Compound Library with improvements in socioeconomic, sanitary, and water supply conditions of the local population at travel destination. Conclusions. These findings suggest that improved hygienic standards at travel destination strongly contributed to the overall decline in attack rates of fecal-orally transmitted diseases among visiting travelers. In industrialized countries, the incidence of fecal-orally transmitted infections, such as hepatitis A, typhoid fever, and shigellosis, has declined substantially.1–4 Currently, most cases in these countries arise from visits to non-industrialized countries.2 A few studies have addressed trends in hepatitis A or typhoid fever among international travelers, buy Protease Inhibitor Library finding that, over the past decades, their risk of acquiring

hepatitis A or typhoid fever has decreased.5–7 This decline is often attributed to pretravel vaccination and improvements in hygienic and sanitary conditions at travel destinations. However, their absolute or relative contributions are unknown, given the lack of studies on the influence of hygienic factors on the incidence of fecal-orally transmitted diseases. This study analyzes region-specific trends in attack rates of hepatitis A, typhoid fever, and shigellosis among Dutch travelers, combining Dutch travelers’ statistics with information from the national infectious diseases notification system. All three diseases are transmitted through fecally contaminated water or food. Hepatitis A virus (HAV) infection causes an acute viral liver disease and confers lifelong immunity.

It is a common childhood disease in developing countries, but the prevalence of hepatitis A antibodies is low in developed regions.1,8 In the Netherlands, an inactivated HAV vaccine is available O-methylated flavonoid for risk groups, such as travelers, and is almost 100% effective.9 Typhoid fever is a bacterial systemic infection caused by Salmonella enterica serotype Typhi.3,10 Immunity following infection is limited and can be overcome.9 Two parenteral capsular polysaccharide vaccines are available in the Netherlands, and studies report their efficacy at 35% to 70%.11 Shigellosis is a bacterial enteric disease, caused by one of the four serogroups of Shigella. Immunity following infection is type-specific and probably limited.4 No vaccine is available. To study if the attack rates of fecal-orally transmitted diseases in travelers are influenced by improvements in hygienic standards at travel destinations, we compared trends in vaccine-preventable hepatitis A and typhoid fever with trends in non-vaccine-preventable shigellosis.

Nce102 co-localizes with main cytosolic components

of eis

Nce102 co-localizes with main cytosolic components

of eisosomes, Pil1, and Lsp, and the deletion of Nce102 resulted in an altered number and distribution of eisosomes (Walther et al., 2006). These data suggest that Nce102 is required for normal eisosome and MCC formation. In a recent study, the eisosomal protein homologues (PilA, PilB, and SurG) in Aspergillus nidulans have been characterized (Vangelatos et al., 2010). Detailed analysis of pilA, pilB, or surG deletion strains have confirmed the nonessential role of these proteins in fungal growth. Furthermore, the endocytosis process was not affected in these mutants, demonstrating a possible functional divergence of eisosomal proteins in Aspergilli. A similar study on eisosomal proteins of filamentous fungus Ashbya PLX3397 gossypii confirmed the important role of pil1 homologue in polar growth and the nonessential role of Nce102 homologue

in growth and eisosomal stability (Seger et al., 2011). In the present study, we have characterized Nce102 homologue, AfuNce102, in the human pathogen, Aspergillus fumigatus. Our results indicate that this gene is not essential for hyphal growth or pathogenesis, but it is required for normal sporulation. Localization studies using an enhanced green fluorescent protein (EGFP)-tagged AfuNce102 construct demonstrated that AfuNce102 is primarily localized to endoplasmic reticulum with more intensity at the hyphal tip. Edoxaban During the conidiogenesis, the protein localized to conidiophores and conidia. Aspergillus fumigatus strain AF293 and its PyrG derivative were used for the isolation of the Nce102 gene homologue and in gene disruption experiments. Escherchia coli Top10 (Invitrogen) cells were used in DNA recombinant procedures. pGEM-T Easy cloning system (Promega) was used for cloning of PCR products. Plasmid pGEM-GlaA-EGFP, comprised the Aspergillus niger glaA promoter, EGFP sequence, and glaA termination signal, was used for preparation of NCE-GFP-tagged construct. Plasmid pAN7.1 containing

the hygromycin resistance gene as a fungal selection marker was used in co-transformation experiments of NCE-GFP-tagged construct (Punt et al., 1987). Fungal strains were grown and kept on SAB agar or SAB agar medium supplemented with uridine and uracil (UU). Modified Vogel’s medium (Vogel, 1956) was used in isolation of fungal transformants. For phenotypic analysis of strains, radial growth rates were determined by cultivation of fungal spores (104 spores) on center of SAB and modified Vogel’s agar plates at 30, 37, and 42 °C followed by serial measurement of colonies’ diameter for 5 days. Fungal DNA was prepared as previously described (Moller et al., 1992). RNA samples were purified using a commercial kit (Qiagen, RNA easy® Mini kit). Molecular methods including ligation of DNA fragments, transformation of E.

Clp proteases

including ClpA act as molecular chaperones

Clp proteases

including ClpA act as molecular chaperones with a similar function as DnaK/DnaJ (Wickner et al., 1994). It is likely that the up-regulation of DnaJ-class molecular chaperone in CSM2 mutant is due to the substitution of the partial Clp protease function by DnaJ when Clp protease is dysfunctional. Further, our metabolomic analysis of the Clp protease mutant identified down-regulation of amino acid and oligosaccharide transporters that are part of ABC transporter pathways (Table 2). The mechanism is likely to be similar to that observed in Mycobacterium tuberculosis under hypoxia, where Clp proteases degrade the factors that inhibit DNA replication and transcription to initiate the synthesis of amino acids during stressful conditions (Sherrid et al., 2010). Changes in the levels of TCA cycle enzymes in response to copper identified by the metabolomic analysis (Table 2) were confirmed by the PF-562271 price proteomic analysis with up-regulation of ketol-acid reductoisomerase, which participates

in the production of CoA (Table 1). In addition, down-regulation of MalR, a transcriptional regulatory protein for malate and citrate metabolism (Table 1) under copper stress would result in the accumulation of malate and citrate, the intermediate products in TCA cycle (Papa et al., 2009). Higher levels of malate allow the organism to cope with oxidative stress caused Dabrafenib solubility dmso by copper toxicity, by producing more NADPH, an important antioxidant (Singh et al., 2007). Citrate is a metabolite involved in the sequestration of aluminum and the increase of

citrate accumulation selleck screening library was previously shown in P. fluorescens grown under aluminum stress (Mailloux et al., 2008). Our results suggest that citrate is involved in the sequestration of copper. Based on our results, we propose a model for the response to toxic levels of copper in Pseudomonas sp. TLC6-6.5-4 (Fig. 4). High copper concentrations reduce its cell size, which decreases the amount of copper bound on the cell surface. In addition, smaller cells need less energy for maintenance under copper stress. CopA and lipoprotein mediate sequestration and efflux of copper outside the cytoplasm. Heat shock proteins including Clp protease and DnaJ-class molecular chaperone either degrade the damaged proteins or prevent their irreversible aggregation under copper stress. Furthermore, Clp protease is directly involved in copper resistance by up-regulation of amino acid transporters, proteins related to oxidative stress and proline accumulation. This organism maintains a fine metabolic balance to enable the cells to survive in environment with high copper concentration by increasing amino acid production and regulating TCA cycle. The authors gratefully thank J. Lutz and W. He for technical assistance with proteomic experiments and GC-MS analysis. We also thank R. Shaik for his help on proteomic and metabolomic data analysis. “
“Salmonella enterica serovar Typhi and Typhimurium are closely related serovars. However, S.

Heart rate was also positively correlated with total AMS symptom

Heart rate was also positively correlated with total AMS symptom score; in contrast, fluid intake was RNA Synthesis inhibitor negatively

correlated with total AMS symptom score. When investigating the symptom of high altitude headache alone (model 2 in Table 2), upper respiratory symptoms and stool consistency (where a higher number defines a looser stool) were correlated with headache severity, as did arterial oxygen saturation. However, when investigating presence or absence of clinically defined AMS (model 3 in Table 2), only upper respiratory symptoms (positive correlation) and arterial oxygen saturation (negative correlation) were significant predictors. Odds ratios suggested that a 1 unit increase in upper respiratory symptoms was associated with a 1.040 (1.005–1.262) significantly higher odds of having AMS; a 1 unit decrease in arterial oxygen saturation was associated with a 1.068 (1.000–1.141) significantly higher odds of having AMS. Time-lag models, which investigated whether variables predicted AMS the following day as required to infer causality, explained between 10 and 24% of variance in AMS (Table 3). The following day’s total AMS symptom score was positively correlated with upper respiratory symptoms (model 4 in Table 3). Heart rate and fluid intake also predicted future AMS symptoms. Thus, an increase of upper respiratory symptoms by 5 units

would increase total AMS symptom score the following day by 0.72 units (0.54–0.89); an increase in heart rate of 10 beats per min would

increase AMS score by 0.18 units (0.08–0.28); and a decrease of 10 mL per kg of body mass of fluid PFT�� chemical structure intake per day (∼710 mL per day) would increase total AMS score by 0.07 units (0.01–0.12). When investigating the symptom of high altitude headache alone, only arterial oxygen saturation was negatively correlated with the following day’s headache severity (model 5 in Table 3). Thus, a decrease in arterial oxygen saturation of 5% would increase headache severity HSP90 the next day by 0.06 units (0.02–0.10). This study is the first to use a longitudinal multiple regression analysis of daily illnesses and mental disturbances recorded during a relatively large expedition to high altitude. AMS affected almost half of the expedition participants, with up to one quarter having AMS on any day. However, AMS incidence alone underestimated the total illness symptom burden: all the participants also had upper respiratory symptoms, two thirds had loose stools and one third had diarrhea, and almost everyone reported mild anxiety. Upper respiratory symptoms increased as altitude was gained, and anxiety was also increased on certain days at high altitude. Detailed description of illnesses revealed that the variable contributing most to AMS symptom burden was difficulty sleeping. However, difficulty sleeping was also the least sensitive of the AMS symptoms to altitude change.

avermitilis and S coelicolor) The second trend is that the

avermitilis and S. coelicolor). The second trend is that the

groups with potentially linear chromosomes generally have chromosomes of a larger size, most being larger than 6.5 Mb. This suggests that if you need to increase your see more chromosome size evolutionarily, linearity may be an advantage. “
“Lipoteichoic acid (LTA) is a zwitterionic polymer found in the cell wall of many Gram-positive bacteria. A widespread and one of the best-studied forms of LTA consists of a polyglycerolphosphate (PGP) chain that is tethered to the membrane via a glycolipid anchor. In this review, we will summarize our current understanding of the enzymes involved in glycolipid and PGP backbone synthesis in a variety of different Gram-positive bacteria. The recent identification of key LTA synthesis proteins allowed the construction and analysis of mutant strains with defined defects in glycolipid or backbone synthesis. Using these strains, new information on the functions of LTA for bacterial growth, physiology and during developmental processes was gained and will be discussed. Furthermore, we will reintroduce the idea that LTA remains in close proximity to the bacterial membrane for its function during bacterial growth rather than as a surface-exposed structure. “
“The Gram-negative bacterium

Pseudomonas sp. strain ADP is the best-characterized organism able to mineralize the s-triazine herbicide learn more atrazine. This organism has been the subject of extensive biochemical and genetic characterization that has led to its use in bioremediation programs aimed at the decontamination of atrazine-polluted sites. Here, we focus on the recent advances in the understanding of the mechanisms of genetic regulation operating on the atrazine-degradative genes. The Pseudomonas sp. strain ADP atrazine-degradation pathway is encoded by two sets of genes: the constitutively expressed atzA, atzB and atzC, and the strongly regulated atzDEF operon. A complex

cascade-like circuit is responsible through for the integrated regulation of atzDEF expression in response to nitrogen availability and cyanuric acid. Mechanistic studies have revealed several unusual traits, such as the upstream activating sequence-independent regulation and repression by competition with σ54-RNA polymerase for DNA binding occurring at the σ54-dependent PatzR promoter, and the dual mechanism of transcriptional regulation of the PatzDEF promoter by the LysR-type regulator AtzR in response to two dissimilar signals. These findings have provided new insights into the regulation of the atrazine-biodegradative pathway that are also relevant to widespread bacterial regulatory phenomena, such as global nitrogen control and transcriptional activation by LysR-type transcriptional regulators.