Identification and evaluation of regulatory factors modulating the expression of LEE4 in enterohemorrhagic Escherichia coli O157:H7

The locus of enterocyte effacement (LEE) encoded operons (LEE1 - LEE5) enable enterohemorrhagic Escherichia coli (EHEC) O157:H7 to produce attaching and effacing lesions on intestinal cells (A/E). We have previously reported that hha-deleted EHEC O157:H7 up-regulated LEE4 through increased expression of ler, the regulatory gene encoded by the LEE1 operon. In the present study, we demonstrate that a transpositional insertion in clpXP abrogated the increased expression of the LEE4 in the hha-deleted strain. The loss of LEE4 up-regulation in an EHEC O157:H7 [Delta]hha, [Delta]clpXP mutant was restored by transposon insertions immediately upstream of grlR of the grlR-grlA operon, suggesting that grIR represses the expression of LEE4 in the absence of Hha and ClpXP. RT-PCR analysis revealed that grlR transcription increased by about 100-fold in strains lacking hha but remained the same in the presence or absence of clpXP thus indicating that hha acts as a negative regulator of grlR transcription. RT-PCR data also showed a 10-fold reduction in LEE4 transcription for EHEC O157:H7 [Delta]clpXP thus suggesting that the absence of clpXP resulted in an increased accumulation of GrlR and presumably Hha thereby causing an additional reduction in LEE4 transcription compared to that observed for LEE4 in EHEC O157:H7. Western blot analysis of the cell-free extracts of EHEC O157:H7 [Delta]clpXP revealed increased accumulation of Hha. Altogether, the results described in this report indicate that ClpXP is important for maintaining a critical intracellular pool of Hha, which in turn modulates transcription of grlR-grlA so that a basal level of transcription could continue through LEE4 and the other LEE operons

Introduction to the nonequilibrium functional renormalization group

In these lectures we introduce the functional renormalization group out of equilibrium. While in thermal equilibrium typically a Euclidean formulation is adequate, nonequilibrium properties require real-time descriptions. For quantum systems specified by a given density matrix at initial time, a generating functional for real-time correlation functions can be written down using the Schwinger-Keldysh closed time path. This can be used to construct a nonequilibrium functional renormalization group along similar lines as for Euclidean field theories in thermal equilibrium. Important differences include the absence of a fluctuation-dissipation relation for general out-of-equilibrium situations. The nonequilibrium renormalization group takes on a particularly simple form at a fixed point, where the corresponding scale-invariant system becomes independent of the details of the initial density matrix. We discuss some basic examples, for which we derive a hierarchy of fixed point solutions with increasing complexity from vacuum and thermal equilibrium to nonequilibrium. The latter solutions are then associated to the phenomenon of turbulence in quantum field theory.Comment: Lectures given at the 49th Schladming Winter School `Physics at all scales: The Renormalization Group' (to appear in the proceedings); 24 pages, 3 figure

Doubled lattice Chern–Simons–Yang–Mills theories with discrete gauge group

We construct doubled lattice Chern–Simons–Yang–Mills theories with discrete gauge group G in the Hamiltonian formulation. Here, these theories are considered on a square spatial lattice and the fundamental degrees of freedom are defined on pairs of links from the direct lattice and its dual, respectively. This provides a natural lattice construction for topologically-massive gauge theories, which are invariant under parity and time-reversal symmetry. After defining the building blocks of the doubled theories, paying special attention to the realization of gauge transformations on quantum states, we examine the dynamics in the group space of a single cross, which is spanned by a single link and its dual. The dynamics is governed by the single-cross electric Hamiltonian and admits a simple quantum mechanical analogy to the problem of a charged particle moving on a discrete space affected by an abstract electromagnetic potential. Such a particle might accumulate a phase shift equivalent to an Aharonov–Bohm phase, which is manifested in the doubled theory in terms of a nontrivial ground-state degeneracy on a single cross. We discuss several examples of these doubled theories with different gauge groups including the cyclic group Z(k)⊂U(1), the symmetric group S3⊂O(2), the binary dihedral (or quaternion) group View the MathML source, and the finite group Δ(27)⊂SU(3). In each case the spectrum of the single-cross electric Hamiltonian is determined exactly. We examine the nature of the low-lying excited states in the full Hilbert space, and emphasize the role of the center symmetry for the confinement of charges. Whether the investigated doubled models admit a non-Abelian topological state which allows for fault-tolerant quantum computation will be addressed in a future publication

American Family Cohort, a data resource description

This manuscript is a research resource description and presents a large and novel Electronic Health Records (EHR) data resource, American Family Cohort (AFC). The AFC data is derived from Centers for Medicare and Medicaid Services (CMS) certified American Board of Family Medicine (ABFM) PRIME registry. The PRIME registry is the largest national Qualified Clinical Data Registry (QCDR) for Primary Care. The data is converted to a popular common data model, the Observational Health Data Sciences and Informatics (OHDSI) Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The resource presents approximately 90 million encounters for 7.5 million patients. All 100% of the patients present age, gender, and address information, and 73% report race. Nealy 93% of patients have lab data in LOINC, 86% have medication data in RxNorm, 93% have diagnosis in SNOWMED and ICD, 81% have procedures in HCPCS or CPT, and 61% have insurance information. The richness, breadth, and diversity of this research accessible and research ready data is expected to accelerate observational studies in many diverse areas. We expect this resource to facilitate research in many years to come

A New Concept to Secure Food Safety Standards against Fusarium Species and Aspergillus Flavus and Their Toxins in Maize

Commercial maize hybrids are exposed to different degrees of ear infection by toxigenic fungal species and toxin contamination. Their resistance to different fungi and toxin relationships are largely unknown. Without this knowledge, screening and breeding are not possible for these pathogens. Seven- to tenfold differences were found in resistance to Fusarium spp., and there was a five-fold difference in ear coverage (%) in response to A. flavus. Three hybrids of the twenty entries had lower infection severity compared with the general means for toxigenic species. Three were highly susceptible to each, and 14 hybrids reacted differently to the different fungi. Differences were also observed in the toxin content. Again, three hybrids had lower toxin content in response to all toxigenic species, one had higher values for all, and 16 had variable resistance levels. Correlations between infection severity and deoxynivalenol (DON) content were 0.95 and 0.82 (p = 0.001) for F. graminearum and F. culmorum, respectively. For fumonisin and F. verticillioides ear rot, the Pearson correlation coefficient (r) was 0.45 (p = 0.05). Two independent isolates with different aggressiveness were used, and their mean X values better described the resistance levels. This increased the reliability of the data. With the introduction of this methodological concept (testing the resistance levels separately for different fungi and with two isolates independently), highly significant resistance differences were found. The resistance to different fungal species correlated only in certain cases; thus, each should be tested separately. This is very useful in registration tests and post-registration screening and breeding. This would allow a rapid increase in food and feed safety

Perspectives on global mycotoxin issues and management from the mycokey maize working group

Open Access Article; Published online: 11 Sept 2020During the last decade, there have been many advances in research and technology that have greatly contributed to expanded capabilities and knowledge in detection and measurement, characterization, biosynthesis, and management of mycotoxins in maize. MycoKey, an EU‐funded Horizon 2020 project, was established to advance knowledge and technology transfer around the globe to address mycotoxins impacts in key food and feed chains. MycoKey included several working groups comprised of international experts in different fields of mycotoxicology. The MycoKey Maize Working Group recently convened to gather information and strategize for the development and implementation of solutions to the maize mycotoxin problem in light of current and emerging technologies. This feature summarizes the Maize WG discussion and recommendations for addressing mycotoxin problems in maize. Discussions focused on aflatoxins, deoxynivalenol, fumonisins, and zearalenone, which are the most widespread and persistently important mycotoxins in maize. Although regional differences were recognized, there was consensus about many of the priorities for research and effective management strategies. For pre-harvest management, genetic resistance and selecting adapted maize genotypes, along with insect management, were among the most fruitful strategies identified across the mycotoxin groups. For post-harvest management, the most important practices included timely harvest, rapid grain drying, grain cleaning, and carefully managed storage conditions. Remediation practices such as optical sorting, density separation, milling, and chemical detoxification were also suggested. Future research and communication priorities included advanced breeding technologies, development of risk assessment tools, and the development and dissemination of regionally relevant management guidelines