Feedback control architecture and the bacterial chemotaxis network.

PMCID: PMC3088647This 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.Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance

Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics

DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to ‘sloppy’ transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences

Measure of Activity Performance in the Hand (MAP-Hand) questionnaire

Background: Developed in the Norway, the Measure of Activity Performance of the Hand (MAP-Hand) assesses 18 activities performed using the hands. It was developed for people with rheumatoid arthritis (RA) using patient generated items, which are scored on a 0-3 scale and summarised into a total score range (0 to 54). This study reports the development and psychometric testing of the British English MAP-Hand in a UK population of people with RA. Methods: Recruitment took place in the National Health Service (NHS) through 17 Rheumatology outpatient clinics. Phase 1 (cross-cultural adaptation) involved: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews with people with RA. Phase 2 (psychometric testing) involved postal completion of the MAP-Hand, Health Assessment Questionnaire (HAQ), Upper Limb HAQ (ULHAQ), Short-Form 36 (SF-36v2) and Disabilities of the Arm Shoulder Hand (DASH) to measure internal consistency (Cronbach’s alpha); concurrent validity (Spearman’s correlations) and Minimal Detectable Difference (MDC95). The MAP-Hand was repeated three-weeks later to assess test-retest reliability (linear weighted kappa and Intra-Class Correlations (ICC (2,1)). Unidimensionality (internal construct validity) was assessed using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. The RUMM2030 software was used, applying the Rasch partial credit model. Results: In Phase 1, 31 participants considered all items relevant. In Phase 2, 340 people completed Test-1 and 273 (80%) completed Test-2 questionnaires. Internal consistency was excellent (α=0.96). Test-retest reliability was good (ICC (2,1) = 0.96 (95% CI 0.94, 0.97)). The MAP-Hand correlated strongly with HAQ20 (rs=.88), ULHAQ (rs=.91), SF-36v2 Physical Functioning (PF) Score (rs=-.80) and DASH (rs=.93), indicating strong concurrent validity. CFA failed to support unidimensionality (Chi-Square 236.0 (df 120; p <0.001)). However, Mokken scaling suggested a probabilistic ordering. There was differential item functioning (DIF) for gender. Four testlets were formed, resulting in much improved fit and unidimensionality. Following this, testlets were further merged in pairs where opposite bias existed. This resulted in perfect fit to the model. Conclusions: The British English version of the MAP-Hand has good validity and reliability in people with RA and can be used in both research and clinical practice. Keywords: PROMS; Patient Reported Outcome Measures; hand activity performance; hand function; hand pain; psychometric testing; Rasch analysis; validity; reliabilit

Oscillatory Dynamics of Cell Cycle Proteins in Single Yeast Cells Analyzed by Imaging Cytometry

Progression through the cell division cycle is orchestrated by a complex network of interacting genes and proteins. Some of these proteins are known to fluctuate periodically during the cell cycle, but a systematic study of the fluctuations of a broad sample of cell-cycle proteins has not been made until now. Using time-lapse fluorescence microscopy, we profiled 16 strains of budding yeast, each containing GFP fused to a single gene involved in cell cycle regulation. The dynamics of protein abundance and localization were characterized by extracting the amplitude, period, and other indicators from a series of images. Oscillations of protein abundance could clearly be identified for Cdc15, Clb2, Cln1, Cln2, Mcm1, Net1, Sic1, and Whi5. The period of oscillation of the fluorescently tagged proteins is generally in good agreement with the inter-bud time. The very strong oscillations of Net1 and Mcm1 expression are remarkable since little is known about the temporal expression of these genes. By collecting data from large samples of single cells, we quantified some aspects of cell-to-cell variability due presumably to intrinsic and extrinsic noise affecting the cell cycle

Whole genome sequencing-based detection of antimicrobial resistance and virulence in non-typhoidal Salmonella enterica isolated from wildlife

The aim of this study was to generate a reference set of Salmonella enterica genomes isolated from wildlife from the United States and to determine the antimicrobial resistance and virulence gene profile of the isolates from the genome sequence data. We sequenced the whole genomes of 103 Salmonella isolates sampled between 1988 and 2003 from wildlife and exotic pet cases that were submitted to the Oklahoma Animal Disease Diagnostic Laboratory, Stillwater, Oklahoma. Among 103 isolates, 50.48% were from wild birds, 0.9% was from fish, 24.27% each were from reptiles and mammals. 50.48% isolates showed resistance to at least one antibiotic. Resistance against the aminoglycoside streptomycin was most common while 9 isolates were found to be multi-drug resistant having resistance against more than three antibiotics. Determination of virulence gene profile revealed that the genes belonging to csg operons, the fim genes that encode for type 1 fimbriae and the genes belonging to type III secretion system were predominant among the isolates. The universal presence of fimbrial genes and the genes encoded by pathogenicity islands 1-2 among the isolates we report here indicates that these isolates could potentially cause disease in humans. Therefore, the genomes we report here could be a valuable reference point for future traceback investigations when wildlife is considered to be the potential source of human Salmonellosis.Peer reviewedOklahoma Animal Disease Diagnostic Laborator

Meta-omics approaches to understand and improve wastewater treatment systems

Biological treatment of wastewaters depends on microbial processes, usually carried out by mixed microbial communities. Environmental and operational factors can affect microorganisms and/or impact microbial community function, and this has repercussion in bioreactor performance. Novel high-throughput molecular methods (metagenomics, metatranscriptomics, metaproteomics, metabolomics) are providing detailed knowledge on the microorganisms governing wastewater treatment systems and on their metabolic capabilities. The genomes of uncultured microbes with key roles in wastewater treatment plants (WWTP), such as the polyphosphate-accumulating microorganism Candidatus Accumulibacter phosphatis, the nitrite oxidizer Candidatus Nitrospira defluvii or the anammox bacterium Candidatus Kuenenia stuttgartiensis are now available through metagenomic studies. Metagenomics allows to genetically characterize full-scale WWTP and provides information on the lifestyles and physiology of key microorganisms for wastewater treatment. Integrating metagenomic data of microorganisms with metatranscriptomic, metaproteomic and metabolomic information provides a better understanding of the microbial responses to perturbations or environmental variations. Data integration may allow the creation of predictive behavior models of wastewater ecosystems, which could help in an improved exploitation of microbial processes. This review discusses the impact of meta-omic approaches on the understanding of wastewater treatment processes, and the implications of these methods for the optimization and design of wastewater treatment bioreactors.Research was supported by the Spanish Ministry of Education and Science (Contract Project CTQ2007-64324 and CONSOLIDER-CSD 2007-00055) and the Regional Government of Castilla y Leon (Ref. VA038A07). Research of AJMS is supported by the European Research Council (Grant 323009

Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package.

BACKGROUND: The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. RESULTS: As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. CONCLUSIONS: Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI's BioSample database

Gravitational Wave Detection by Interferometry (Ground and Space)

Significant progress has been made in recent years on the development of gravitational wave detectors. Sources such as coalescing compact binary systems, neutron stars in low-mass X-ray binaries, stellar collapses and pulsars are all possible candidates for detection. The most promising design of gravitational wave detector uses test masses a long distance apart and freely suspended as pendulums on Earth or in drag-free craft in space. The main theme of this review is a discussion of the mechanical and optical principles used in the various long baseline systems in operation around the world - LIGO (USA), Virgo (Italy/France), TAMA300 and LCGT (Japan), and GEO600 (Germany/U.K.) - and in LISA, a proposed space-borne interferometer. A review of recent science runs from the current generation of ground-based detectors will be discussed, in addition to highlighting the astrophysical results gained thus far. Looking to the future, the major upgrades to LIGO (Advanced LIGO), Virgo (Advanced Virgo), LCGT and GEO600 (GEO-HF) will be completed over the coming years, which will create a network of detectors with significantly improved sensitivity required to detect gravitational waves. Beyond this, the concept and design of possible future "third generation" gravitational wave detectors, such as the Einstein Telescope (ET), will be discussed.Comment: Published in Living Reviews in Relativit