Probabilistic Clustering of Sequences: Inferring new bacterial regulons by comparative genomics

Genome wide comparisons between enteric bacteria yield large sets of conserved putative regulatory sites on a gene by gene basis that need to be clustered into regulons. Using the assumption that regulatory sites can be represented as samples from weight matrices we derive a unique probability distribution for assignments of sites into clusters. Our algorithm, 'PROCSE' (probabilistic clustering of sequences), uses Monte-Carlo sampling of this distribution to partition and align thousands of short DNA sequences into clusters. The algorithm internally determines the number of clusters from the data, and assigns significance to the resulting clusters. We place theoretical limits on the ability of any algorithm to correctly cluster sequences drawn from weight matrices (WMs) when these WMs are unknown. Our analysis suggests that the set of all putative sites for a single genome (e.g. E. coli) is largely inadequate for clustering. When sites from different genomes are combined and all the homologous sites from the various species are used as a block, clustering becomes feasible. We predict 50-100 new regulons as well as many new members of existing regulons, potentially doubling the number of known regulatory sites in E. coli.Comment: 27 pages including 9 figures and 3 table

Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition

Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular Graphic (InsP6) is involved in mRNA export and editing or chromatin remodeling among other events. InsP6 accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology. Human diets that are exclusively grain-based provide an excess of InsP6 that, through chelation of metal ions, may have a detrimental effect on human health. Ins(1,3,4,5,6)P5 2-kinase (InsP5 2-kinase or Ipk1) catalyses the synthesis of InsP6 from InsP5 and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide. We present the first structure for an InsP5 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH. This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates

A viscoelastic deadly fluid in carnivorous pitcher plants

Background : The carnivorous plants of the genus Nepenthes, widely distributed in the Asian tropics, rely mostly on nutrients derived from arthropods trapped in their pitcher-shaped leaves and digested by their enzymatic fluid. The genus exhibits a great diversity of prey and pitcher forms and its mechanism of trapping has long intrigued scientists. The slippery inner surfaces of the pitchers, which can be waxy or highly wettable, have so far been considered as the key trapping devices. However, the occurrence of species lacking such epidermal specializations but still effective at trapping insects suggests the possible implication of other mechanisms. Methodology/Principal Findings : Using a combination of insect bioassays, high-speed video and rheological measurements, we show that the digestive fluid of Nepenthes rafflesiana is highly viscoelastic and that this physical property is crucial for the retention of insects in its traps. Trapping efficiency is shown to remain strong even when the fluid is highly diluted by water, as long as the elastic relaxation time of the fluid is higher than the typical time scale of insect movements. Conclusions/Significance : This finding challenges the common classification of Nepenthes pitchers as simple passive traps and is of great adaptive significance for these tropical plants, which are often submitted to high rainfalls and variations in fluid concentration. The viscoelastic trap constitutes a cryptic but potentially widespread adaptation of Nepenthes species and could be a homologous trait shared through common ancestry with the sundew (Drosera) flypaper plants. Such large production of a highly viscoelastic biopolymer fluid in permanent pools is nevertheless unique in the plant kingdom and suggests novel applications for pest control

Playing the game: service users' management of risk status in a UK medium secure forensic mental health service

In this article we examine how forensic mental health service users actively attempt to manage their risk status through playing the game of containing frustration and demonstrating compliance. The article draws on an observational study (2006 to 2009) which explored the practices of risk assessment and management within one inner city forensic mental health medium secure service in the UK. We used a grounded theory approach to explore service users and providers experiences of risk assessment and management. We interviewed forensic mental health service users and providers. We also collected data using participant and non-participant observation. Since access to forensic mental health services is tightly controlled, there are participant observation studies undertaken in these settings. We found that service users attempted to understand the system of assessment and sought to affect and reduce their risk status by engaging in overt, compliant behaviours. We argue that in doing so service users are active agents in the process of risk management. However, we indicate that there are adverse effects of this approach to risk management as the risk assessment process is subverted by the restriction of the flow of information, and service users are left with frustrations that they must contain and manage

How people with chronic illnesses view their care in general practice: a qualitative study

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Objectives: To explore the perceptions of patients with chronic conditions about the nature and quality of their care in general practice. Design: Qualitative study using focus group methods conducted 1 June to 30 November 2002. Participants and setting: 76 consumers in 12 focus groups in New South Wales and South Australia. Main outcome measures: Recurring issues and themes on care received in general practice. Results: Three groups of priorities emerged. One centred on the quality of doctors, including technical competence, interpersonal skills, time for the patient in the consultation and continuity of care. A second concerned the role of patients and consumer organisations, with patients wanting (i) recognition of their knowledge about their condition and self-management, and (ii) for GPs to develop closer links with consumer organisations and inform patients about them. The third focused on the practice team and the importance of practice nurses and receptionists. Conclusion: GPs should consider the amount of time they spend with chronically ill patients, and their interpersonal skills and understanding of patients’ needs. They need to be better informed about the benefits of patient self-management and consumer organisations, and to incorporate them into their care. They also need to review how their practice nurses and receptionists can maximise the care of patients.Fernando A Infante, Judith G Proudfoot, Gawaine Powell Davies, Tanya K Bubner, Chris H Holton, Justin J Beilby and Mark F Harri

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Isospin-violating dark matter at liquid noble detectors: new constraints, future projections, and an exploration of target complementarity

There is no known reason that dark matter interactions with the Standard Model should couple to neutrons and protons in the same way. This isospin violation can have large consequences, modifying the sensitivity of existing and future direct detection experimental constraints by orders of magnitude. Previous works in the literature have focused on the zero-momentum limit which has its limitations when extending the analysis to the Non-Relativistic Effective Field Theory basis (NREFT). In this paper, we study isospin violation in a detailed manner, paying specific attention to the experimental setups of liquid noble detectors. We analyse two effective Standard Model gauge invariant models as interesting case studies as well as the more model-independent NREFT operators. This work demonstrates the high degree of complementarity between the target nuclei xenon and argon. Most notably, we show that the Standard Model gauge-invariant formulation of the standard spin-dependent interaction often generates a sizeable response from argon, a target nuclei with zero spin. This work is meant as an update and a useful reference to model builders and experimentalists.Comment: 22 pages in total, 13 figures, 1 table, 3 appendices. Data from the main results of this paper is available at https://doi.org/10.1140/epjc/s10052-023-11826-