The hetZ Gene Regulates Heterocyst Formation in Anabaena sp. strain PCC 7120

To form a complex multicellular organism, stem cells must differentiate into each cell/tissue type along proper spatiotemporal scales. The study of differentiation and organismal development has historically been conducted in prokaryotes due to their genetic and morphological simplicity. Anabaena sp. strain PCC 7120 is a multicellular filamentous cyanobacterium that differentiates a morphologically distinct secondary cell type, the heterocyst, in response to a lack of combined environmental nitrogen. Heterocysts are regularly spaced along filaments and fix atmospheric dinitrogen to maintain organismal viability in its absence. Previous work suggested that the hetZ gene is involved in heterocyst differentiation, but the insertional mutants created produced inconsistent phenotypes, so a specific role was not assigned. In this work, a clean hetZ mutant incapable of heterocyst differentiation was generated and the mutation was complemented with the reintroduction of hetZ alone. Overexpression of hetZ bypassed a mutation of hetR, the master regulator of heterocyst differentiation that controls biological pattern formation, but not a mutation of hetP, a regulator of commitment to a differentiated cell fate, which places hetZ roughly between these processes. A protein-protein interaction study showed that HetZ interacts with both HetR and itself. Assessment of transcriptional fusions between the hetZ, hetR, hetP, and patS (an inhibitor of HetR) promoter regions and GFP, and overexpression of HetR in a hetZ mutant resulted in the differentiation of heterocyst-like cells, together indicated that HetZ may act in concert with HetR as an early regulator of development. Taken together, these data describe a non-linear pathway of regulation leading to heterocyst development governed by both HetR and HetZ

In vitro variability in propofol absorption by different membrane oxygenators

Meeting abstract focusing on the sequestration of drugs, such as fentanyl [1,2], thiopental, nitroglycerine and propofol [3] in the extracorporeal circuit in vitro. This phenomenon can change the pharmacokinetic behaviour of drugs during cardiopulmonary bypass, thus potentially leading to problems in achieving adequate dosing regimens. The aim of this in vitro laboratory study was to compare the binding of propofol to different oxygenator membranes, and to examine the effects of the type of prime solution and temperature on the rate of binding. The SM-35 membrane bound significantly more propofol than the membranes from the CML and the SAFE II. Binding of propofol in diluted blood was significantly less than in crystalloid solution. Temperature had little effect on propofol binding in either prime solution type

Towards a novel carbon device for the treatment of sepsis

Sepsis is a systemic inflammatory response to infection in which the balance of pro- andanti-inflammatory mediators, which normally isolate and eliminate infection, is disrupted[1]. Gram negative sepsis is initiated by bacterial endotoxin release which activatesmacrophages and circulating monocytes to release TNF and IL-1β followed by IL-6 andother inflammatory cytokines [2]. As the disease progresses, an unregulatedinflammatory response results in, tissue injury, haematological dysfunction and organdysfunction. Severe sepsis, involving organ hypoperfusion may be further complicatedby hypotension that is unresponsive to adequate fluid replacement, resulting in septicshock and finally death [3].Despite improvements in anti-microbial and supportive therapies, sepsis remains asignificant cause of morbidity and mortality in ICUs worldwide [4]. The complexity ofprocesses mediating the progression of sepsis suggests that an extracorporeal devicecombining blood filtration with adsorption of a wide range of toxins, and inflammatorymediators offers the most comprehensive treatment strategy. However, no such deviceexists at present. A novel, uncoated, polymer pyrolysed synthetic carbon device isproposed which combines the superior adsorption properties of uncoated activatedcarbons with the capacity to manipulate porous structure for controlled adsorption oftarget plasma proteins and polypeptides [5]. Preliminary haemocompatibility andadsorptive capacity was assessed using a carbon matrix prototype

Approaches to discontinuing efalizumab: an open-label study of therapies for managing inflammatory recurrence

BACKGROUND: Efalizumab is a humanised recombinant monoclonal IgG1 antibody for the treatment of moderate-to-severe plaque psoriasis. When treatment discontinuation is necessary, however, some patients may experience inflammatory recurrence of the disease, which can progress to rebound if untreated. This analysis evaluated approaches for managing inflammatory recurrence after discontinuation of efalizumab. METHODS: An open-label, multicentre, investigational study was performed in 41 patients with moderate-to-severe plaque psoriasis who had recently completed clinical studies with efalizumab and had developed signs of inflammatory recurrence following abrupt cessation of treatment. Patients were assigned by the attending physicians to receive one of five standardised alternative systemic psoriasis treatment regimens for 12 weeks. Efficacy of the different therapy options was assessed using the physician's global assessment (PGA) of change over time. RESULTS: More favourable PGA responses were observed in patients changing to cyclosporin (PGA of 'good', 'excellent' or 'cleared': 7/10 patients, 70.0%) or methotrexate (9/20, 45.0%), compared with those receiving systemic corticosteroids (2/8, 25.0%), retinoids (0/1, 0.0%) or combined corticosteroids plus methotrexate (0/2, 0.0%). While the majority (77.8%) of patients showed inflammatory morphology at baseline, following 12 weeks of the alternative therapies the overall prevalence of inflammatory disease was decreased to 19.2%. CONCLUSION: Inflammatory recurrence after discontinuation of efalizumab therapy is a manageable event, with a number of therapies and approaches available to physicians, including short courses of cyclosporin or methotrexate