Correction: A Straightforward Access to New Families of Lipophilic Polyphenols by Using Lipolytic Bacteria.

[This corrects the article DOI: 10.1371/journal.pone.0166561.].

Influence of vascular imaging acquisition at local stroke centers on workflows in the drip-n-ship model: a RACECAT post hoc analysis.

BACKGROUND: The influence of vascular imaging acquisition on workflows at local stroke centers (LSCs) not capable of performing thrombectomy in patients with a suspected large vessel occlusion (LVO) stroke remains uncertain. We analyzed the impact of performing vascular imaging (VI+) or not (VI- at LSC arrival on variables related to workflows using data from the RACECAT Trial. OBJECTIVE: To compare workflows at the LSC among patients enrolled in the RACECAT Trial with or without VI acquisition. METHODS: We included patients with a diagnosis of ischemic stroke who were enrolled in the RACECAT Trial, a cluster-randomized trial that compared drip-n-ship versus mothership triage paradigms in patients with suspected acute LVO stroke allocated at the LSC. Outcome measures included time metrics related to workflows and the rate of interhospital transfers and thrombectomy among transferred patients. RESULTS: Among 467 patients allocated to a LSC, vascular imaging was acquired in 277 patients (59%), of whom 198 (71%) had a LVO. As compared with patients without vascular imaging, patients in the VI+ group were transferred less frequently as thrombectomy candidates to a thrombectomy-capable center (58% vs 74%, P=0.004), without significant differences in door-indoor-out time at the LSC (median minutes, VI+ 78 (IQR 69-96) vs VI- 76 (IQR 59-98), P=0.6). Among transferred patients, the VI+ group had higher rate of thrombectomy (69% vs 55%, P=0.016) and shorter door to puncture time (median minutes, VI+ 41 (IQR 26-53) vs VI- 54 (IQR 40-70), P<0.001). CONCLUSION: Among patients with a suspected LVO stroke initially evaluated at a LSC, vascular imaging acquisition might improve workflow times at thrombectomy-capable centers and reduce the rate of futile interhospital transfers. These results deserve further evaluation and should be replicated in other settings and geographies.

Identification of an acetyl esterase in the supernatant of the environmental strain Bacillus sp. HR21-6.

Bacillus sp. HR21-6 is capable of the chemo- and regioselective synthesis of lipophilic partially acetylated phenolic compounds derived from olive polyphenols, which are powerful antioxidants important in the formulation of functional foods. In this work, an acetyl esterase was identified in the secretome of this strain by non-targeted proteomics, and classified in the GDSL family (superfamily SGNH). The recombinant protein was expressed and purified from Escherichia coli in the soluble form, and biochemically characterized. Site-directed mutagenesis was performed to understand the role of different amino acids that are conserved among GDSL superfamily of esterases. Mutation of Ser-10, Gly-45 or His-185 abolished the enzyme activity, while mutation of Asn-77 or Thr-184 altered the substrate specificity of the enzyme. This new enzyme is able to perform chemoselective conversions of olive phenolic compounds with great interest in the food industry, such as hydroxytyrosol, 3,4-dihydroxyphenylglycol, and oleuropein.

An arsRB resistance operon confers tolerance to arsenite in the environmental isolate Terribacillus sp. AE2B 122.

Terribacillus sp. AE2B 122 is an environmental strain isolated from olive-oil agroindustry wastes. This strain displays resistance to arsenic, one of the most ubiquitous carcinogens found in nature. Terribacillus sp. AE2B 122 possesses an unusual ars operon, consisting of the transcriptional regulator (arsR) and arsenite efflux pump (arsB) but no adjacent arsenate reductase (arsC) locus. Expression of arsR and arsB was induced when Terribacillus was exposed to sub-lethal concentrations of arsenate. Heterologous expression of the arsB homologue in Escherichia coli∆arsRBC demonstrated that it conferred resistance to arsenite and reduced the accumulation of arsenic inside the cells. Two members of the arsC-like family (Te3384 and Te2854) found in the Terribacillus genome were not induced by arsenic, but their heterologous expression in E. coli ∆arsC and ∆arsRBC increased the accumulation of arsenic in both strains. We found that both Te3384 and Te2854 slightly increased resistance to arsenate in E. coli ∆arsC and ∆arsRBC, possibly by chelation of arsenic or by increasing the resistance to oxidative stress. Finally, arsenic speciation assays suggest that Terribacillus is incapable of arsenate reduction, in agreement with the lack of an arsC homologue in the genome.

Progression of carotid near-occlusion to complete occlusion: related factors and clinical implications.

BACKGROUND: The clinical consequences and factors related to the progression from a carotid near-occlusion (CNO) to a complete occlusion are not well established. Our aim is to describe the rate, predictive factors and clinical implications of the progression to complete carotid occlusion (PCCO) in a population of patients with symptomatic CNO. METHODS: We conducted a multicenter, nationwide, prospective study from January 2010 to May 2016. Patients with angiography-confirmed CNO were included. We collected information on demographic data, clinical manifestations, radiological and hemodynamic findings, and treatment modalities. A 24 month carotid-imaging follow-up of the CNO was performed. RESULTS: 141 patients were included in the study, and carotid-imaging follow-up was performed in 122 patients. PCCO occurred in 40 patients (32.8%), and was more frequent in medically-treated patients (34 out of 61; 55.7%) compared with patients treated with revascularization (6 out of 61; 9.8%) (p<0.001). 7 of the 40 patients with PCCO (17.5%) suffered ipsilateral symptoms. Factors independently related with PCCO in the multivariate analysis were: age ≥75 years (OR 2.93, 95% CI 1.05 to 8.13), revascularization (OR 0.07, 95% CI 0.02 to 0.20), and collateral circulation through the ipsilateral ophthalmic artery (OR 3.25, 95% CI 1.01 to 10.48). CONCLUSIONS: PCCO occurred within 24 months in more than half of the patients under medical treatment. Most episodes of PCCO were not associated with ipsilateral symptoms. Revascularization reduces the risk of PCCO.

Correlation of blood biomarkers with early-onset seizures after an acute stroke event.

INTRODUCTION: Blood biomarkers have not been widely studied in stroke-related seizures. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and to analyze their association with early-onset seizures. METHODS: We retrospectively evaluated a panel of 14 blood biomarkers in 1115 patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z scores. We also recorded stroke and epilepsy-related variables, including stroke severity (National Institute of Health Stroke Scale [NIHSS] scores), type, and causes, time from onset of stroke to occurrence of early seizures, and type of seizure. Adjusted logistic regression models were built to identify clinical variables and biomarkers independently associated with early seizures. RESULTS: Mean ±â€¯standard deviation (SD) age was 72.3 ±â€¯13.2 years, and 56.8% of the patients were men. Thirty-eight patients (3.9%) developed early seizures with a median time to onset of 1 day (interquartile range (IQR), 0-4). A higher NIHSS score (odds ratio [OR] = 1.046; 95% confidence interval (CI): 1.001-1.094; p = 0.044) and hemorrhagic stroke (OR = 2.133; 95% CI: 1.010-4.504; p = 0.047) were independently associated with a greater risk of early seizures. Independent blood biomarkers predictive of early seizures were lower levels of tumor necrosis factor receptor 1 (TNF-R1) (<0.013) (p = 0.006; OR = 3.334; 95% CI: 1.414-7.864) and higher levels of neural cell adhesion molecule (NCAM) (>0.326) (p = 0.009; OR = 2.625; 95% CI: 1.271-5.420). The predictive power of the regression model was greater when clinical variables were combined with blood biomarkers (73.5%; 95% CI: 65.1%-81.9%) than when used alone (64%; 95% CI: 55%-72.9%). CONCLUSION: Higher NCAM and lower TNF-R1 levels may help predict the occurrence of early seizures. The combined use of these biomarkers and clinical variables could be useful for identifying patients at risk of seizures. This article is part of the Special Issue "Seizures & Stroke".

Revalidation of the RACE scale after its regional implementation in Catalonia: a triage tool for large vessel occlusion.

BACKGROUND AND PURPOSE: Our aim was to revalidate the RACE scale, a prehospital tool that aims to identify patients with large vessel occlusion (LVO), after its region-wide implementation in Catalonia, and to analyze geographical differences in access to endovascular treatment (EVT). METHODS: We used data from the prospective CICAT registry (Stroke Code Catalan registry) that includes all stroke code activations. The RACE score evaluated by emergency medical services, time metrics, final diagnosis, presence of LVO, and type of revascularization treatment were registered. Sensitivity, specificity, and area under the curve (AUC) for the RACE cut-off value ≥5 for identification of both LVO and eligibility for EVT were calculated. We compared the rate of EVT and time to EVT of patients transferred from referral centers compared with those directly presenting to comprehensive stroke centers (CSC). RESULTS: The RACE scale was evaluated in the field in 1822 patients, showing a strong correlation with the subsequent in-hospital evaluation of the National Institute of Health Stroke Scale evaluated at hospital (r=0.74, P<0.001). A RACE score ≥5 detected LVO with a sensitivity 0.84 and specificity 0.60 (AUC 0.77). Patients with RACE ≥5 harbored a LVO and received EVT more frequently than RACE <5 patients (LVO 35% vs 6%; EVT 20% vs 6%; all P<0.001). Direct admission at a CSC was independently associated with higher odds of receiving EVT compared with admission at a referral center (OR 2.40; 95% CI 1.66 to 3.46), and symtoms onset to groin puncture was 133 min shorter. CONCLUSIONS: This large validation study confirms RACE accuracy to identify stroke patients eligible for EVT, and provides evidence of geographical imbalances in the access to EVT to the detriment of patients located in remote areas.

Hybrid in silico/in vitro target fishing to assign function to "orphan" compounds of food origin - The case of the fungal metabolite atromentin.

Many small molecules of food origin may effect human health but lack an adequate description of their biological activity. To fill this knowledge gap, a first-line workflow is needed to assign putative functions, rank the endpoints for testing and guide wet-lab experiments. In this framework, the identification of potential biological targets can be used to probe the activity of orphan compounds using a so-called "target fishing" approach. Here, we present a proof of concept study using an in silico/in vitro target fishing approach on the fungal secondary metabolite atromentin. The procedure relies on a computational screening for activity identification coupled with experimental trials for dose-response characterization. Computational results identified estrogen receptors and 17-ß-hydroxysteroid dehydrogenase as potential targets. Experiments confirmed a weak estrogenic activity, supporting the reliability of the procedure. Despite limited estrogenicity of atromentin, the proposed inhibition of 17-ß-hydroxysteroid dehydrogenase should be considered as a source for endocrine disruptive effects.

Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus.

BACKGROUND: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. RESULTS: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli. CONCLUSIONS: Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.

A Straightforward Access to New Families of Lipophilic Polyphenols by Using Lipolytic Bacteria.

The chemical synthesis of new lipophilic polyphenols with improved properties presents technical difficulties. Here we describe the selection, isolation and identification of lipolytic bacteria from food-processing industrial wastes, and their use for tailoring a new set of compounds with great interest in the food industry. These bacteria were employed to produce lipolytic supernatants, which were applied without further purification as biocatalysts in the chemoselective and regioselective synthesis of lipophilic partially acetylated phenolic compounds derived from olive polyphenols. The chemoselectivity of polyphenols acylation/deacylation was analyzed, revealing the preference of the lipases for phenolic hydroxyl groups and phenolic esters. In addition, the alcoholysis of peracetylated 3,4-dihydroxyphenylglycol resulted in a series of lipophilic 2-alkoxy-2-(3,4-dihydroxyphenyl)ethyl acetate through an unexpected lipase-mediated etherification at the benzylic position. These new compounds are more lipophilic and retained their antioxidant properties. This approach can provide access to unprecedented derivatives of 3,4-dihydroxyphenylglycol with improved properties.

Endovascular treatment for M2 occlusions in the era of stentrievers: a descriptive multicenter experience.

BACKGROUND: Patients with M2 middle cerebral artery (MCA) occlusions are not always considered for endovascular treatment. OBJECTIVE: To study outcomes in patients with M2 occlusion treated with endovascular procedures in the era of stentrievers. METHODS: We studied patients prospectively included in the SONIIA registry (years 2011-2012)-a mandatory, externally audited registry that monitors the quality of reperfusion therapies in Catalonia in routine practice. Good recanalization was defined as postprocedure Thrombolysis in Cerebral Infarction (TICI) score 2b-3; dramatic recovery as drop in National Institutes of Health Stroke Scale (NIHSS) score >10 points or NIHSS score <2 at 24-36 h; and good outcome as modified Rankin score (mRS) 0-2 at 3months. A 24 h CT scan determined symptomatic intracranial hemorrhage (SICH) and infarct volume. RESULTS: Of 571 patients who received endovascular treatment, 65 (11.4%) presented an M2 occlusion on initial angiogram, preprocedure NIHSS 16 (IQR 6). Mean time from symptom onset to groin puncture was 289 ± 195 min. According to interventionalist preferences 86.2% (n=56) were treated with stentrievers (n=7 in combination with intra-arterial tissue plasminogen activator (tPA), 4.6% (n=3) received intra-arterial tPA only, and 9.2% (n=6) diagnostic angiography only. Good recanalization (78.5%) was associated with dramatic improvement (48% vs 14.8%; p=0.02), smaller infarct volumes (8 vs 82 cc; p=0.01) and better outcome (mRS 0-2: 66.3% vs 30%; p=0.03). SICH (9%) was not associated with treatment modality or device used. After adjusting for age and preprocedure NIHSS, good recanalization emerged as an independent predictor of dramatic improvement (OR=5.9 (95% CI 1.2 to 29.2), p=0.03). Independent predictors of good outcome at 3 months were age ( OR=1.067 (95% CI 1.005 to 1132), p=0.03) and baseline NIHSS ( OR=1.162 (95% CI 1.041 to 1.297), p<0.01). CONCLUSIONS: Endovascular treatment of M2 MCA occlusion with stentrievers seems safe. Induced recanalization may double the chances of achieving a favorable outcome, especially for patients with moderate or severe deficit.

Selection and characterization of biofuel-producing environmental bacteria isolated from vegetable oil-rich wastes.

Fossil fuels are consumed so rapidly that it is expected that the planet resources will be soon exhausted. Therefore, it is imperative to develop alternative and inexpensive new technologies to produce sustainable fuels, for example biodiesel. In addition to hydrolytic and esterification reactions, lipases are capable of performing transesterification reactions useful for the production of biodiesel. However selection of the lipases capable of performing transesterification reactions is not easy and consequently very few biodiesel producing lipases are currently available. In this work we first isolated 1,016 lipolytic microorganisms by a qualitative plate assay. In a second step, lipolytic bacteria were analyzed using a colorimetric assay to detect the transesterification activity. Thirty of the initial lipolytic strains were selected for further characterization. Phylogenetic analysis revealed that 23 of the bacterial isolates were Gram negative and 7 were Gram positive, belonging to different clades. Biofuel production was analyzed and quantified by gas chromatography and revealed that 5 of the isolates produced biofuel with yields higher than 80% at benchtop scale. Chemical and viscosity analysis of the produced biofuel revealed that it differed from biodiesel. This bacterial-derived biofuel does not require any further downstream processing and it can be used directly in engines. The freeze-dried bacterial culture supernatants could be used at least five times for biofuel production without diminishing their activity. Therefore, these 5 isolates represent excellent candidates for testing biofuel production at industrial scale.

Atypically low spontaneous sister chromatid exchange formation in uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular cancer of adults and is characterized by several well-established chromosomal changes. More recently, a specific mutation of guanine nucleotide binding protein Gq alpha subunit (GNAQ) has also been identified in a proportion of UM. Although some of these alterations have been suggested to be early changes, the genetic alterations responsible for the development of UM have yet to be clearly determined. Cancers are characterized by increased genetic instability, and analysis of established cancer cell lines and blood from cancer patients has universally been associated with an increased level of sister chromatid exchange (SCE). We have observed that the spontaneous frequency of SCE in primary cultures of UM and UM-derived cell lines is decreased below normal baseline levels, a phenomenon unique to UM when compared with multiple other cancers. This finding was specific to the tumor and not found in lymphocytes from the patients. Although we cannot exclude the possibility that low SCE (LSCE) is peculiar to the uveal melanocytes lineage, as it was consistently observed in all UM studied, regardless of other genetic defects, we propose that this phenomenon contributes to the molecular pathogenesis of UM.

The engagement of selectins and their ligands in colorectal cancer liver metastases.

he colonization of the liver by colorectal cancer (CRC) cells is a complicated process which includes many stages, until macrometastases occur. The entrapment of malignant cells within the hepatic sinusoids and their interactions with resident non-parenchymal cells are considered very important for the whole metastatic sequence. In the sinusoids, cell connection and signalling is mediated by multiple cell adhesion molecules, such as the selectins. The three members of the selectin family, E-, P- and L-selectin, in conjunction with sialylated Lewis ligands and CD44 variants, regulate colorectal cell communication and adhesion with platelets, leucocytes, sinusoidal endothelial cells and stellate cells. Their role in CRC liver metastases has been investigated in animal models and human tissue, in vivo and in vitro, in static and shear flow conditions, and their key-function in several molecular pathways has been displayed. Therefore, trials have already commenced aiming to exploit selectins and their ligands in the treatment of benign and malignant diseases. Multiple pharmacological agents have been developed that are being tested for potential therapeutic applications.

The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis.

Cell adhesion molecules (CAMs) play a significant role in the metastatic potential of colorectal cancer and thus mediate the prognosis of this common malignancy. The downregulation of cadherins and catenins facilitates tumour cell detachment from the primary site, while the expression of selectins, integrins and members of the immunoglobulin superfamily may support neoplastic progression, intravasation and malignant cell attachment to foreign tissue, leading to the development of metastases. The liver is the main host organ of colorectal metastatic lesions. The process of hepatic invasion originates in the sinusoids, where non-parenchymal cells interact with metastasising ones, through the expression of numerous CAMs, following complex molecular pathways. Concurrently, the selective expression of cell adhesion molecules on different organs and endothelia, in conjunction with the presence of dissimilar adhesion ligands on various colorectal cancer cell lines, suggest that CAMs may also mediate the selection of the host organ, for the development of distant colorectal metastases.

Local environmental influences on uveal melanoma: vitreous humor promotes uveal melanoma invasion, whereas the aqueous can be inhibitory.

BACKGROUND: Uveal melanomas of the choroid and ciliary body are aggressive tumors causing the death of approximately 50% of patients. In contrast, iris melanomas only infrequently metastasize; why these differences exist is not known. The local environment can regulate cancer growth and development, and it is probable the aqueous and vitreous humors have an important role in regulating uveal melanoma behavior. METHODS: To explore this possibility cultures of uveal melanoma were exposed to aqueous and vitreous and the effects investigated using invasion and proliferation assays. ChemiArrays (Chemicon International, Temecula, Calif) were performed to determine which regulatory factors might influence the process. RESULTS: The vitreous universally promoted uveal melanoma invasion, whereas the aqueous mainly had no effect or was inhibitory. Tumor location, and the baseline invasion of the melanoma, affected the ability of aqueous and vitreous from different patients to regulate invasive behavior. Proliferation was not significantly altered as a result of exposure to the aqueous or vitreous. The ability of the humors to regulate uveal melanomas may involve TIMP-2, TIMP-3, and TGF-beta2, as high expression was found by ChemiArray analysis and there were differences in the levels of the regulators in the aqueous compared with the vitreous. CONCLUSIONS: The findings suggest that in situ uveal melanoma development reflects an interaction between the tumor and the environment of the eye. Exposure to the aqueous would therefore contribute to the benign nature of iris melanomas, whereas potential interaction with the vitreous appears to promote the aggressive behavior of posterior uveal melanomas.

Uncoupling of choline-O-sulphate utilization from osmoprotection in Pseudomonas putida.

The genomic context of the recognized bet genes for choline-O-sulphate (COS) utilization in Pseudomonas putida KT2440 is such that betC (choline sulphatase) lies adjacent to an ATP-binding cassette transporter and a LysR type regulator, but well away from betBA, encoding enzymes for transformation of choline into glycine betaine. The consequences of such genetic layout of the functions for COS metabolism have been examined with a suite of genetic and biochemical approaches. An early clue of the utilities of the betencoded products was exposed by the phenotypes of a betC deletion. This mutant still accumulated intact COS but failed to use this compound as carbon or nitrogen source. Furthermore, betC expression was downregulated at high salt concentrations, showing that the principal role of this gene lied in COS metabolism, not in osmoprotection. In contrast, the betBA genes were required for choline transformation into the highly effective compatible solute glycine betaine (and the concomitant endurance to high salt) and also for its utilization as carbon or nitrogen source. Thus, unlike in the cases of Bacillus subtilis and Sinorhizobium meliloti, betC is unrelated to osmoprotection in Pseudomonas putida while the betBA genes are required for both betaine synthesis and tolerance to high osmotic pressure.

The role of thiol species in the hypertolerance of Aspergillus sp. P37 to arsenic.

Aspergillus sp. P37 is an arsenate-hypertolerant fungus isolated from a river in Spain with a long history of contamination with metals. This strain is able to grow in the presence of 0.2 M arsenate, i.e. 20-fold higher than the reference strain, Aspergillus nidulans TS1. Although Aspergillus sp. P37 reduces As(V) to As(III), which is slowly pumped out of the cell, the measured efflux of oxyanions is insufficient to explain the high tolerance levels of this strain. To gain an insight into this paradox, the accumulation of acid-soluble thiol species in Aspergillus sp. P37 when exposed to arsenic was compared with that of the arsenic-sensitive A. nidulans TS1 strain. Increasing levels of arsenic in the medium did not diminish the intracellular pool of reduced glutathione in Aspergillus sp. P37, in sharp contrast with the decline of glutathione in A. nidulans under the same conditions. Furthermore, concentrations of arsenic that were inhibitory for the sensitive A. nidulans strain (e.g. 50 mM and above) provoked a massive formation of vacuoles filled with thiol species. Because the major fraction of the cellular arsenic was present as the glutathione conjugate As(GS)3, it is plausible that the arsenic-hypertolerant phenotype of Aspergillus sp. P37 is in part due to an enhanced capacity to maintain a large intracellular glutathione pool under conditions of arsenic exposure and to sequester As(GS)3 in vacuoles. High pressure liquid chromatography analysis of cell extracts revealed that the contact of Aspergillus sp. P37 (but not A. nidulans) with high arsenic concentrations (> or =150 mM) induced the production of small quantities of a distinct thiol species indistinguishable from plant phytochelatin-2. Yet, we argue that phytochelatins do not explain arsenic resistance in Aspergillus, and we advocate the role of As(GS)3 complexes in arsenic detoxification.

Genes for the synthesis of the osmoprotectant glycine betaine from choline in the moderately halophilic bacterium Halomonas elongata DSM 3043, USA.

The genes involved in the oxidative pathway of choline to glycine betaine in the moderate halophile Halomonas elongata DSM 3043 were isolated by functional complementation of an Escherichia coli strain defective in glycine betaine synthesis. The cloned region was able to mediate the oxidation of choline to glycine betaine in E. coli, but not the transport of choline, indicating that the gene(s) involved in choline transport are not clustered with the glycine betaine synthesis genes. Nucleotide sequence analysis of a 4.6 kb segment from the cloned DNA revealed the occurrence of three ORFs (betIBA) apparently arranged in an operon. The deduced betI gene product exhibited features typical for DNA-binding regulatory proteins. The deduced BetB and BetA proteins showed significant similarity to soluble glycine betaine aldehyde dehydrogenases and membrane-bound choline dehydrogenases, respectively, from a variety of organisms. Evidence is presented that BetA is able to oxidize both choline and glycine betaine aldehyde and therefore can mediate both steps in the synthesis of glycine betaine.