The protease inhibitor JO146 demonstrates a critical role for CtHtrA for Chlamydia trachomatis reversion from penicillin persistence

The Chlamydia trachomatis serine protease HtrA (CtHtrA) has recently been demonstrated to be essential during the replicative phase of the chlamydial developmental cycle. A chemical inhibition strategy (serine protease inhibitor JO146) was used to demonstrate this essential role and it was found that the chlamydial inclusions diminish in size and are lost from the cell after CtHtrA inhibition without formation of viable elementary bodies. The inhibitor (JO146) was used in this study to investigate the role of CtHtrA for penicillin persistence and heat stress conditions for Chlamydia trachomatis. JO146 addition during penicillin persistence resulted in only minor reductions (~1 log) in the final viable infectious yield after persistent Chlamydia were reverted from persistence. However, JO146 treatment during the reversion and recovery from penicillin persistence was completely lethal for Chlamydia trachomatis. JO146 was completely lethal when added either during heat stress conditions, or during the recovery from heat stress conditions. These data together indicate that CtHtrA has essential roles during some stress environments (heat shock), recovery from stress environments (heat shock and penicillin persistence), as well as the previously characterized essential role during the replicative phase of the chlamydial developmental cycle. Thus, CtHtrA is an essential protease with both replicative phase and stress condition functions for Chlamydia trachomatis. © 2013 Ong, Marsh, Lawrence, Allan, Timms and Huston

Anomaly-Free Supersymmetric SO(2N+2)/U(N+1) sigma-Model Based on the SO(2N+1) Lie Algebra of the Fermion Operators

The extended supersymmetric (SUSY) sigma-model has been proposed on the bases of SO(2N+1) Lie algebra spanned by fermion annihilation-creation operators and pair operators. The canonical transformation, extension of an SO(2N) Bogoliubov transformation to an SO(2N+1) group, is introduced. Embedding the SO(2N+1) group into an SO(2N+2) group and using SO(2N+2)/U(N+1) coset variables, we have investigated the SUSY sigma-model on the Kaehler manifold, the coset space SO(2N+2)/U(N+1). We have constructed the Killing potential, extension of the potential in the SO(2N)/U(N) coset space to that in the SO(2N+2)/U(N+1) coset space. It is equivalent to the generalized density matrix whose diagonal-block part is related to a reduced scalar potential with a Fayet-Ilipoulos term. The f-deformed reduced scalar potential is optimized with respect to vacuum expectation value of the sigma-model fields and a solution for one of the SO(2N+1) group parameters has been obtained. The solution, however, is only a small part of all solutions obtained from anomaly-free SUSY coset models. To construct the coset models consistently, we must embed a coset coordinate in an anomaly-free spinor representation (rep) of SO(2N+2) group and give corresponding Kaehler and Killing potentials for an anomaly-free SO(2N+2)/U(N+1) model based on each positive chiral spinor rep. Using such mathematical manipulation we construct successfully the anomaly-free SO(2N+2)/U(N+1) SUSY sigma-model and investigate new aspects which have never been seen in the SUSY sigma-model on the Kaehler coset space SO(2N)/U(N). We reach a f-deformed reduced scalar potential. It is minimized with respect to the vacuum expectation value of anomaly-free SUSY sigma-model fields. Thus we find an interesting f-deformed solution very different from the previous solution for an anomaly-free SO(2.5+2)/(SU(5+1)*U(1)) SUSY sigma-model.Comment: 24 pages, no fiure

Watch and Learn: Seeing Is Better than Doing when Acquiring Consecutive Motor Tasks

During motor adaptation learning, consecutive physical practice of two different tasks compromises the retention of the first. However, there is evidence that observational practice, while still effectively aiding acquisition, will not lead to interference and hence prove to be a better practice method. Observers and Actors practised in a clockwise (Task A) followed by a counterclockwise (Task B) visually rotated environment, and retention was immediately assessed. An Observe-all and Act-all group were compared to two groups who both physically practised Task A, but then only observed (ObsB) or did not see or practice Task B (NoB). The two observer groups and the NoB control group better retained Task A than Actors, although importantly only the observer groups learnt Task B. RT data and explicit awareness of the rotation suggested that the observers had acquired their respective tasks in a more strategic manner than Actor and Control groups. We conclude that observational practice benefits learning of multiple tasks more than physical practice due to the lack of updating of implicit, internal models for aiming in the former

Issues potentially affecting quality of life arising from long-term medicines use: a qualitative study

Background Polypharmacy is increasing and managing large number of medicines may create a burden for patients. Many patients have negative views of medicines and their use can adversely affect quality of life. No studies have specifically explored the impact of general long-term medicines use on quality of life. Objective To determine the issues which patients taking long-term medicines consider affect their day-to-day lives, including quality of life. Setting Four primary care general practices in North West England Methods Face-to-face interviews with adults living at home, prescribed four or more regular medicines for at least 1 year. Interviewees were identified from primary care medical records and purposively selected to ensure different types of medicines use. Interviews were recorded, transcribed and analysed thematically. Results Twenty-one interviews were conducted and analysed. Patients used an average of 7.8 medicines, 51 % were preventive, 40 % for symptom relief and 9 % treatment. Eight themes emerged: relationships with health professionals, practicalities, information, efficacy, side effects, attitudes, impact and control. Ability to discuss medicines with health professionals varied and many views were coloured by negative experiences, mainly with doctors. All interviewees had developed routines for using multiple medicines, some requiring considerable effort. Few felt able to exert control over medicines routines specified by health professionals. Over half sought additional information about medicines whereas others avoided this, trusting in doctors to guide their medicines use. Patients recognised their inability to assess efficacy for many medicines, notably those used for prophylaxis. All were concerned about possible side effects and some had poor experiences of discussing concerns with doctors. Medicines led to restrictions on social activities and personal life to the extent that, for some, life can revolve around medicines. Conclusion There is a multiplicity and complexity of issues surrounding medicines use, which impact on day-to-day lives for patients with long-term conditions. While most patients adapt to long-term medicines use, others did so at some cost to their quality of life

Institutional leadership—the historical case study of a religious organisation

In this chapter, I discuss institutional leadership vis-à-vis the value of poverty. To do so, I analyse how poverty has been conceptualised within a Catholic religious organisation, the Jesuits. The chapter shows that, in the Jesuit case, poverty is not strictly defined. Instead, poverty results from the constant dialogue between the individual Jesuit and their leader. This means that the understanding of what constitutes poverty is neither explicit nor implicit. The chapter contributes to our understanding of institutional leadership as the promotion and protection of values, as per Selznick’s classical definition. However, we discuss a less known part of Selznick’s work in which the ambiguous character of values is highlighted. In this sense, and after the Jesuit case, we advance the possibility that the promotion and protection of institutional values by institutional leaders does not necessarily imply the definition of what a value is. As values are not defined beforehand but the result of a constant dialogue between the leader and their followers, institutional leadership can be revisited and freed from the heroic view that has long characterised it

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

Familiarity between patient and general practitioner does not influence the content of the consultation

<p>Abstract</p> <p>Background</p> <p>Personal continuity in general practice is considered to be a prerequisite of high quality patient care based on shared knowledge and mutual understanding. Not much is known about how personal continuity is reflected in the content of GP – patient communication. We explored whether personal continuity of care influences the content of communication during the consultation.</p> <p>Methods</p> <p>Personal continuity was defined as the degree of familiarity between GP and patient, rated by both the GP and the patient. 394 videotaped consultations between GPs and patients aged 18 years and older were analyzed. GP – patient communication was evaluated with an observation checklist, which rated the following topics of conversation: (1) medical issues, (2) psychological themes, and (3) the social environment of the patient. For each of these topics we coded whether or not it received attention, and was built upon prior knowledge. Data were analyzed using multilevel logistic regression analyses.</p> <p>Results</p> <p>No relationship was found between GP – patient familiarity and the discussion of medical issues, psychological themes, or the social environment of the patient. But if the patient and the GP knew each other very well, the GP more often displayed prior knowledge with the topic in question. Few patient and GP characteristics were associated with differences in content of communication.</p> <p>Conclusion</p> <p>Given the relatively small sample size, we carefully conclude that familiarity between a GP and a patient does not influence the content of the communication (medical issues, psychological themes nor topics relating to the social environment). This is remarkable because we expected that familiarity would 'open up the communication' for more psychological and social themes. GPs seem to have the communication skills to put both familiar and non-familiar patients at ease enabling them to freely raise any issue they think necessary.</p

Differing clinical characteristics between influenza strains among young healthy adults in the tropics

<p>Abstract</p> <p>Background</p> <p>Influenza infections may result in different clinical presentations. This study aims to determine the clinical differences between circulating influenza strains in a young healthy adult population in the tropics.</p> <p>Methods</p> <p>A febrile respiratory illness (FRI) (fever ≥ 37.5°C with cough and/or sore throat) surveillance program was started in 4 large military camps in Singapore on May 2009. Personnel with FRI who visited the camp clinics from 11 May 2009 to 25 June 2010 were recruited. Nasal washes and interviewer-administered questionnaires on demographic information and clinical features were obtained from consenting participants. All personnel who tested positive for influenza were included in the study. Overall symptom load was quantified by counting the symptoms or signs, and differences between strains evaluated using linear models.</p> <p>Results</p> <p>There were 434 (52.9%) pandemic H1N1-2009, 58 (7.1%) seasonal H3N2, 269 (32.8%) influenza B, and 10 (1.2%) seasonal H1N1 cases. Few seasonal influenza A (H1N1) infections were detected and were therefore excluded from analyses, together with undetermined influenza subtypes (44 (1.5%)), or more than 1 co-infecting subtype (6 (0.2%)). Pandemic H1N1-2009 cases had significantly fewer symptoms or signs (mean 7.2, 95%CI 6.9-7.4, difference 1.6, 95%CI 1.2-2.0, <it>p </it>< 0.001) than the other two subtypes (mean 8.7, 95%CI 8.5-9.0). There were no statistical differences between H3N2 and influenza B (<it>p </it>= 0.58). Those with nasal congestion, rash, eye symptoms, injected pharynx or fever were more likely to have H3N2; and those with sore throat, fever, injected pharynx or rhinorrhoea were more likely to have influenza B than H1N1-2009.</p> <p>Conclusions</p> <p>Influenza cases have different clinical presentations in the young adult population. Pandemic H1N1 influenza cases had fewer and milder clinical symptoms than seasonal influenza. As we only included febrile cases and had no information on the proportion of afebrile infections, further research is needed to confirm whether the relatively milder presentation of pandemic versus seasonal influenza infections applies to all infections or only febrile illnesses.</p