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This study reports the complete genome sequence of Sphaerochaeta associata GLS2T (=VKM B-2742T =DSM 26261T), which was isolated from a consortium with methanogenic archaeon Methanosarcina mazei JL01. The consortium was collected from permafrost of the Kolyma lowland in Russia. The hybrid approach, combining paired-end Illumina reads with Oxford Nanopore Technologies MinION reads, was used to assemble the genome. The final assembly resulted in a circular chromosome that is 3,554,903 bp long. This high-quality genome assembly serves as a basis for algorithmic pathway reconstruction and postgenomic analysis. To further this research, the genome was imported into research portals for the algorithmic reconstruction of metabolic pathways, in both common sense (KEGG) and with special attention to carbohydrate metabolism (CAZy). These portals offer high-quality workplaces for in-depth studies.

The endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients. Overall, the literature suggesting the use of plasma as a therapy for endothelial glycocalyx degradation is non-clinical basic science or exploratory. Plasma is an established therapy in the resuscitation of patients with hemorrhage for restoration of coagulation factors. However, plasma also contains other bioactive components, including sphingosine-1 phosphate, antithrombin, and adiponectin, which may protect and restore the endothelial glycocalyx, thereby helping to maintain or restore vascular homeostasis. This narrative review begins by describing the endothelial glycocalyx in health and disease: we discuss the overlapping disease mechanisms in trauma and sepsis that lead to its damage and introduce plasma transfusion as a potential therapy for prevention and treatment of endothelial glycocalyx degradation. Second, we review the literature on plasma as an exploratory therapy for endothelial glycocalyx degradation in trauma and sepsis. Third, we discuss the safety of plasma transfusion by reviewing the adverse events associated with plasma and other blood product transfusions, and we examine modern transfusion precautions that have enhanced the safety of plasma transfusion. We conclude that the literature proposes that plasma may have the potential to prevent and treat endothelial glycocalyx degradation in trauma and sepsis, indicating the need for further research. [ABSTRACT FROM AUTHOR]

Abstract—A new model of the rupture surface of the Mw = 7.8 Near Islands Aleutian earthquake that occurred on July 17, 2017 in the region of the Commander Islands of the Aleutian Island Arc is presented. The model is based on the displacement fields obtained from Sentinel-1B radar images for the Bering and Mednyi Islands. Among the interferogram pairs calculated from the images covering the period from June 17 to August 28, 2017, the most reliable displacement fields were obtained from the image pair July 11–July 23, 2017. These displacements include coseismic and part of postseismic displacements. The inversion also involved the displacement data recorded by the GNSS GPS stations on the Kamchatka Peninsula, Commander Islands, and the closest to the epicenter Aleutian Islands. Due to the fact that displacements substantially exceeding the noise level were only recorded at two GPS stations on the Bering and Shemya islands, the use of the InSAR data substantially refines the existing earthquake source models. In our models, a seismic rupture zone is approximated by a plane with a length of 370 km along the strike and 19 km along the dip, respectively. Three models have been calculated: a model of uniform displacement across the entire rupture surface; a model in which the rupture surface is divided strikewise into five elements; and a model divided into four elements along the strike and into two levels along the dip, with a total of eight elements. All models demonstrate the same displacement type—right-lateral strike-slip faulting with a relatively small thrust component. According to the constructed models, the displacements in some areas of the rupture surface are slightly smaller than average but, generally, they occur all over the source zone. The models based on satellite geodetic data and on waveform inversion largely agree. The discrepancy between the models utilizing different data types can probably be due to the fact that seismological data characterize the part of the source process that is accompanied by the generation of seismic waves. Surface displacements estimated from InSAR data do not characterize the main event alone but also contain contributions that may reflect various creep processes. The period covered by the radar images also includes the foreshocks with magnitudes up to 6.3 as well as more than 100 aftershocks with magnitudes between 4 to 5.5. Perhaps that is why the displacements obtained in our models are more uniformly distributed over the 370-km rupture surface than in the models based on the waveform analysis. [ABSTRACT FROM AUTHOR]

Aim: Competency frameworks are essential for analyzing capabilities of Schools of Public Health to adequately prepare public health (PH) professionals to address contemporary challenges. This study maps the competency profiles of PH training programs in Israel using a novel curriculum mapping tool., Methods: This study assessed all five Israeli Health Education Institutions (HEIs) offering MPH or Bachelors in Public Health (BPH) degrees across 57 competencies in six domains to determine the extent to which competencies were addressed in the curriculum. The competencies list was based on the Association of Schools of Public Health in the European Region (ASPHER) List of Core Competences for the Public Health Professional, adapted for Israeli HEIs., Results: The core curricula in the four MPH programs addressed 45-84% of all competencies. The BPH program addressed 79% of competencies. In MPH programs, the core curricula addressed most or all competencies in the Methods and the Socioeconomic Determinants of Health domains. Competencies in the domains of Environmental Determinants of Health, Health Policy, Economics & Organization, and Health Promotion and Prevention were less comprehensively addressed in most core curricula. Students' opportunities to broaden their exposure to competencies outside the core curricula were context dependent., Discussion: The curriculum competencies mapping tool that was developed served to assess both strengths and shortcomings in PH education in Israel. The findings demonstrate a highly variable array of PH curriculum models in Israeli HEIs, as well as overall shortcomings in the Environmental, Health Policy Economics and Organization, and Health Promotion and Prevention domains. This analysis has already led to reassessment of the curriculum, and will continue to guide the next steps to increase the harmonization of PH training curricula and to better meet PH challenges in Israel., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Neumark, Hannink Attal, Shapiro, MacLeod, Harrington, Barach, de Nooijer, Dopelt, Duplaga, Leighton, Levine, Mor, Otok, Paillard-Borg, Tulchinsky, Zelber-Sagi and Malowany.)

Purpose: Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial., Methods: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction., Results: Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen's Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) ( p-value-for-interaction = 0.03)., Conclusion: Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.

The genus Clostridium is a large and diverse group within the Bacillota (formerly Firmicutes), whose members can encode useful complex traits such as solvent production, gas-fermentation, and lignocellulose breakdown. We describe 270 genome sequences of solventogenic clostridia from a comprehensive industrial strain collection assembled by Professor David Jones that includes 194 C. beijerinckii, 57 C. saccharobutylicum, 4 C. saccharoperbutylacetonicum, 5 C. butyricum, 7 C. acetobutylicum, and 3 C. tetanomorphum genomes. We report methods, analyses and characterization for phylogeny, key attributes, core biosynthetic genes, secondary metabolites, plasmids, prophage/CRISPR diversity, cellulosomes and quorum sensing for the 6 species. The expanded genomic data described here will facilitate engineering of solvent-producing clostridia as well as non-model microorganisms with innately desirable traits. Sequences could be applied in conventional platform biocatalysts such as yeast or Escherichia coli for enhanced chemical production. Recently, gene sequences from this collection were used to engineer Clostridium autoethanogenum, a gas-fermenting autotrophic acetogen, for continuous acetone or isopropanol production, as well as butanol, butanoic acid, hexanol and hexanoic acid production., (© 2024. The Author(s).)

Objectives. To assess the US incarcerated population's risk of exposure to per- and polyfluoroalkyl substances (PFASs). Methods. We assessed how many of the 6118 US carceral facilities were located in the same hydrologic unit code watershed boundaries as known or likely locations of PFAS contamination. We conducted geospatial analyses on data aggregated from Environmental Protection Agency databases and a PFAS site tracker in 2022 to model the hydrologically feasible known and presumptive PFAS contamination sites for nearly 2 million incarcerated people. Results. Findings indicate that 5% (∼310) of US carceral facilities have at least 1 known source of PFAS contamination in the same watershed boundary and that it is at a higher elevation than the facility; also 47% (∼2285) have at least 1 presumptive source. A minimum of 990 000 people are incarcerated in these facilities, including at least 12 800 juveniles. Exposure risks faced by incarcerated youths are disproportionately underassessed. Conclusions. The long-term impacts from potential exposures to PFAS are preventable and exacerbate health inequities among incarcerated populations. Widespread public attention to PFASs can be parlayed into broader environmental monitoring for imprisoned people. ( Am J Public Health . 2024;114(5):501-510. https://doi.org/10.2105/AJPH.2024.307571).

Warfarin is the only oral anticoagulant recommended in women who are breastfeeding. Although warfarin is a compatible and recommended agent in the postpartum period and during lactation, little is known regarding changes to warfarin dose requirements in this patient population. Here, we report the case of a 40-year-old woman who transitioned from enoxaparin monotherapy back to warfarin at 2 months postpartum, while she was breastfeeding. Despite resuming warfarin at her previously therapeutic dose, her international normalized ratio (INR) remained subtherapeutic and required multiple dose increases. She ultimately required a 100% increase in her warfarin dose postpartum, compared to pre-pregnancy, to achieve a therapeutic INR. This case suggests patients may require higher warfarin doses postpartum, compared to pre-pregnancy, especially if breastfeeding. Clinicians should closely monitor these patients and adjust warfarin doses as necessary., (© 2024 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

In this paper we use quantitative and qualitative methods to examine how death investigations in Los Angeles County jails disproportionately naturalize death among Black and Latino incarcerated people. Our study is based on an assessment of 58 autopsies, coroner investigator narratives, and toxicology reports produced between 2009 and 2018. We found that the Medical Examiner frequently arrived at natural or undetermined death determinations that minimized the culpability of carceral staff for loss of life that occurred within county jail. In our dataset, Black people were disproportionately classified as natural. Undetermined deaths were almost exclusively Latino. More than 75% of the cases in our study were deaths that occurred before standing trial. Our findings reveal how biomedical knowledge about incarcerated Black and Latino people is used to erase the life-diminishing effects of punishment, neglect, and maltreatment that are central to the project of mass incarceration., (© 2023 The Authors. Medical Anthropology Quarterly published by Wiley Periodicals LLC on behalf of American Anthropological Association.)

Objective: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis., Methods: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene., Results: In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified., Interpretation: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Sepsis is a life-threatening disease state characterized by organ dysfunction and a dysregulated response to infection. The heart is one of the many organs affected by sepsis, in an entity termed sepsis-induced cardiomyopathy. This was initially used to describe a reversible depression in ejection fraction with ventricular dilation but advances in echocardiography and introduction of new techniques such as speckle tracking have led to descriptions of other common abnormalities in cardiac function associated with sepsis. This includes not only depression of systolic function, but also supranormal ejection fraction, diastolic dysfunction, and right ventricular dysfunction. These reports have led to inconsistent definitions of sepsis-induced cardiomyopathy. Just as there is heterogeneity among patients with sepsis, there is heterogeneity in the cardiac response; thus resuscitating these patients with a single approach is likely suboptimal. Many factors affect the heart in sepsis including inflammatory mediators, catecholamine responsiveness, and pathogen related toxins. This review will discuss different functional effects characterized by echocardiographic changes in sepsis and their prognostic and management implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shvilkina and Shapiro.)

Quantifying the colors of objects is useful in a wide range of applications, including medical diagnosis, agricultural monitoring, and food safety. Accurate colorimetric measurement of objects is a laborious process normally performed through a color matching test in the laboratory. A promising alternative is to use digital images for colorimetric measurement, due to their portability and ease of use. However, image-based measurements suffer from errors caused by the non-linear image formation process and unpredictable environmental lighting. Solutions to this problem often perform relative color correction among multiple images through discrete color reference boards, which may yield biased results due to the lack of continuous observation. In this paper, we propose a smartphone-based solution, that couples a designated color reference board with a novel color correction algorithm, to achieve accurate and absolute color measurements. Our color reference board contains multiple color stripes with continuous color sampling at the sides. A novel correction algorithm is proposed to utilize a first-order spatial varying regression model to perform the color correction, which leverages both the absolute color magnitude and scale to maximize the correction accuracy. The proposed algorithm is implemented as a "human-in-the-loop" smartphone application, where users are guided by an augmented reality scheme with a marker tracking module to take images at an angle that minimizes the impact of non-Lambertian reflectance. Our experimental results show that our colorimetric measurement is device independent and can reduce up to 90% color variance for images collected under different lighting conditions. In the application of reading pH values from test papers, we show that our system performs 200% better than human reading. The designed color reference board, the correction algorithm, and our augmented reality guiding approach form an integrated system as a novel solution to measure color with increased accuracy. This technique has the flexibility to improve color reading performance in systems beyond existing applications, evidenced by both qualitative and quantitative experiments on example applications such as pH-test reading., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: The authors have filed a provisional patent application on this work., (Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ethanol is a known vertebrate teratogen that causes craniofacial defects as a component of fetal alcohol syndrome (FAS). Our results show that sea urchin embryos treated with ethanol similarly show broad skeletal patterning defects, potentially analogous to the defects associated with FAS. The sea urchin larval skeleton is a simple patterning system that involves only two cell types: the primary mesenchymal cells (PMCs) that secrete the calcium carbonate skeleton and the ectodermal cells that provide migratory, positional, and differentiation cues for the PMCs. Perturbations in RA biosynthesis and Hh signaling pathways are thought to be causal for the FAS phenotype in vertebrates. Surprisingly, our results indicate that these pathways are not functionally relevant for the teratogenic effects of ethanol in developing sea urchins. We found that developmental morphology as well as the expression of some ectodermal and PMC genes was delayed by ethanol exposure. Temporal transcriptome analysis revealed significant impacts of ethanol on signaling and metabolic gene expression, and a disruption in the timing of GRN gene expression that includes both delayed and precocious gene expression throughout the specification network. We conclude that the skeletal patterning perturbations in ethanol-treated embryos likely arise from a loss of temporal synchrony within and between the instructive and responsive tissues., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bacterial strain A52C2 T was isolated from the endophytic microbial community of a Pinus pinaster tree trunk and characterized. Strain A52C2 T stained Gram-negative and formed rod-shaped cells that grew optimally at 30 °C and at pH 6.0-7.0. The G+C content of the DNA was 65.1 mol %. The respiratory quinone was ubiquinone 10, and the major fatty acids were cyclo-C 19:0 ω 8 c and C 18:0 , representing 70.1 % of the total fatty acids. Phylogenetic analyses based on the 16S rRNA gene sequences placed strain A52C2 T in a distinct lineage within the order Hyphomicrobiales , family Pleomorphomonadaceae . The 16S rRNA gene sequence similarities of A52C2 T to that of Mongoliimonas terrestris and Oharaeibacter diazotrophicus were 93.15 and 93.2 %, respectively. The draft genome sequence of strain A52C2 T comprises 4 196 045 bases with a 195-fold mapped coverage of the genome. The assembled genome consists of 43 contigs of more than 1 000 bp ( N50 contig size was 209 720 bp). The genome encodes 4033 putative coding sequences. The phylogenetic, phenotypic and chemotaxonomic data showed that strain A52C2 T (=UCCCB 130 T =CECT 8949 T =LMG 29042 T ) represents the type of a novel species and genus, for which we propose the name Faunimonas pinastri gen. nov., sp. nov.

Here, we report the draft genome sequence of the siderophilic cyanobacterium Fischerella thermalis JSC-11, which was isolated from an iron-depositing hot spring. JSC-11 has bioremediation potential because it is capable of both extracellular absorption and intracellular mineralization of colloidal iron. This genomic information will facilitate the exploration of JSC-11 for bioremediation.

The phylum Actinobacteria includes important human pathogens like Mycobacterium tuberculosis and Corynebacterium diphtheriae and renowned producers of secondary metabolites of commercial interest, yet only a small part of its diversity is represented by sequenced genomes. Here, we present 824 actinobacterial isolate genomes in the context of a phylum-wide analysis of 6,700 genomes including public isolates and metagenome-assembled genomes (MAGs). We estimate that only 30%-50% of projected actinobacterial phylogenetic diversity possesses genomic representation via isolates and MAGs. A comparison of gene functions reveals novel determinants of host-microbe interaction as well as environment-specific adaptations such as potential antimicrobial peptides. We identify plasmids and prophages across isolates and uncover extensive prophage diversity structured mainly by host taxonomy. Analysis of >80,000 biosynthetic gene clusters reveals that horizontal gene transfer and gene loss shape secondary metabolite repertoire across taxa. Our observations illustrate the essential role of and need for high-quality isolate genome sequences., Competing Interests: The authors declare no competing financial interests., (© 2022 The Authors.)

Novel bacterial isolates with the capabilities of lignin depolymerization, catabolism, or both, could be pertinent to lignocellulosic biofuel applications. In this study, we aimed to identify anaerobic bacteria that could address the economic challenges faced with microbial-mediated biotechnologies, such as the need for aeration and mixing. Using a consortium seeded from temperate forest soil and enriched under anoxic conditions with organosolv lignin as the sole carbon source, we successfully isolated a novel bacterium, designated 159R. Based on the 16S rRNA gene, the isolate belongs to the genus Sodalis in the family Bruguierivoracaceae . Whole-genome sequencing revealed a genome size of 6.38 Mbp and a GC content of 55 mol%. To resolve the phylogenetic position of 159R, its phylogeny was reconstructed using (i) 16S rRNA genes of its closest relatives, (ii) multilocus sequence analysis (MLSA) of 100 genes, (iii) 49 clusters of orthologous groups (COG) domains, and (iv) 400 conserved proteins. Isolate 159R was closely related to the deadwood associated Sodalis guild rather than the tsetse fly and other insect endosymbiont guilds. Estimated genome-sequence-based digital DNA-DNA hybridization (dDDH), genome percentage of conserved proteins (POCP), and an alignment analysis between 159R and the Sodalis clade species further supported that isolate 159R was part of the Sodalis genus and a strain of Sodalis ligni. We proposed the name Sodalis ligni str. 159R (=DSM 110549 = ATCC TSD-177). IMPORTANCE Currently, in the paper industry, paper mill pulping relies on unsustainable and costly processes to remove lignin from lignocellulosic material. A greener approach is biopulping, which uses microbes and their enzymes to break down lignin. However, there are limitations to biopulping that prevent it from outcompeting other pulping processes, such as requiring constant aeration and mixing. Anaerobic bacteria are a promising alternative source for consolidated depolymerization of lignin and its conversion to valuable by-products. We presented Sodalis ligni str. 159R and its characteristics as another example of potential mechanisms that can be developed for lignocellulosic applications.

Seven months after the launch of a pilot study to screen newborns for Duchenne Muscular Dystrophy (DMD) in New York State, New York City became an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. All in-person research activities were suspended at the study enrollment institutions of Northwell Health and NewYork-Presbyterian Hospitals, and study recruitment was transitioned to 100% remote. Pre-pandemic, all recruitment was in-person with research staff visiting the postpartum patients 1-2 days after delivery to obtain consent. With the onset of pandemic, the multilingual research staff shifted to calling new mothers while they were in the hospital or shortly after discharge, and consent was collected via emailed e-consent links. With return of study staff to the hospitals, a hybrid approach was implemented with in-person recruitment for babies delivered during the weekdays and remote recruitment for babies delivered on weekends and holidays, a cohort not recruited pre-pandemic. There was a drop in the proportion of eligible babies enrolled with the transition to fully remote recruitment from 64% to 38%. In addition, the proportion of babies enrolled after being approached dropped from 91% to 55%. With hybrid recruitment, the proportion of eligible babies enrolled (70%) and approached babies enrolled (84%) returned to pre-pandemic levels. Our experience adapting our study during the COVID-19 pandemic led us to develop new recruitment strategies that we continue to utilize. The lessons learned from this pilot study can serve to help other research studies adapt novel and effective recruitment methods.

Methylation of specific DNA sequences is ubiquitous in bacteria and has known roles in immunity and regulation of cellular processes, such as the cell cycle. Here, we explored DNA methylation in bacteria of the genus Ensifer , including its potential role in regulating terminal differentiation during nitrogen-fixing symbiosis with legumes. Using single-molecule real-time sequencing, six genome-wide methylated motifs were identified across four Ensifer strains, five of which were strain-specific. Only the GANTC motif, recognized by the cell cycle-regulated CcrM methyltransferase, was methylated in all strains. In actively dividing cell cultures, methylation of GANTC motifs increased progressively from the ori to ter regions in each replicon, in agreement with a cell cycle-dependent regulation of CcrM. In contrast, there was near full genome-wide GANTC methylation in the early stage of symbiotic differentiation. This was followed by a moderate decrease in the overall extent of methylation and a progressive decrease in chromosomal GANTC methylation from the ori to ter regions in later stages of differentiation. Based on these observations, we suggest that CcrM activity is dysregulated and constitutive during terminal differentiation, which we hypothesize is a driving factor for endoreduplication of terminally differentiated bacteroids. IMPORTANCE Nitrogen fixation by rhizobia in symbiosis with legumes is economically and ecologically important. The symbiosis can involve a complex bacterial transformation-terminal differentiation-that includes major shifts in the transcriptome and cell cycle. Epigenetic regulation is an important regulatory mechanism in diverse bacteria; however, the roles of DNA methylation in rhizobia and symbiotic nitrogen fixation have been poorly investigated. We show that aside from cell cycle regulation, DNA methyltransferases are unlikely to have conserved roles in the biology of bacteria of the genus Ensifer . However, we present evidence consistent with an interpretation that the cell cycle methyltransferase CcrM is dysregulated during symbiosis, which we hypothesize may be a key factor driving the cell cycle switch in terminal differentiation required for effective symbioses.