Thermoreversible gels for the encapsulation of macrophages: evaluation of polymer type on rheology and cytocompatibility

Thermoresponsive polymers have become a highly sought-after “smart material” due to their ability to modify their physical characteristics due to temperature changes. This research aimed to determine the biocompatibility of specific thermoreversible gels for immunocompetent cell models containing ImmuPHAGETM, human alveolar macrophage-like cells. Four polymers were selected based on their transition temperatures, including three commercially available pharmaceutical excipients, namely poloxamer 407, soluplus, and methylcellulose. The fourth system, poly(N-isopropyl acrylamide)-b-poly(ethylene oxide)-b-poly(N-isopropyl acrylamide), was synthesised in-house. Initially, the phase behaviour of these four polymers was evaluated visually by warming the polymer solutions and determining the state of the solution by vial inversion. Subsequently, a combination of rheological measurements was employed to compare the properties of these thermoreversible gels in culture media. The physical characterisation was followed by conducting cytocompatibility tests using human alveolar macrophages to assess their suitability as a scaffold for cell culture in vitro and to determine the cell response to different culturing environments. The study concluded that methylcellulose is the most promising and cost-effective material worth further exploration as a responsive matrix for immune cell encapsulation. Keywords: Thermoresponsive, Thermogelling, Alveolar macrophages, Foamy macrophages, immunocompetent in vitro models

The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation

Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.Comment: To appear in Molecular Systems Biolog

Complementarity of ultrasound and fluorescence imaging in an orthotopic mouse model of pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is a devastating disease characterized by dismal 5-year survival rates and limited treatment options. In an effort to provide useful models for preclinical evaluation of new experimental therapeutics, we and others have developed orthotopic mouse models of pancreatic cancer. The utility of these models for pre-clinical testing is dependent upon quantitative, noninvasive methods for monitoring <it>in vivo </it>tumor progression in real time. Toward this goal, we performed whole-body fluorescence imaging and ultrasound imaging to evaluate and to compare these noninvasive imaging modalities for assessing tumor burden and tumor progression in an orthotopic mouse model of pancreatic cancer.</p> <p>Methods</p> <p>The human pancreatic cancer cell line XPA-1, engineered for stable, high-level expression of red fluorescent protein (RFP), was implanted into the pancreas of nude mice using orthotopic implantation. The tumors were allowed to grow over a period of one to several weeks during which time the mice were imaged using both fluorescence imaging and ultrasound imaging to measure tumor burden and to monitor tumor growth.</p> <p>Results</p> <p>Whole-body fluorescence imaging and ultrasound imaging both allowed for the visualization and measurement of orthotopic pancreatic tumor implants <it>in vivo</it>. The imaging sessions were well-tolerated by the mice and yielded data which correlated well in the quantitative assessment of tumor burden. Whole-body fluorescence and two-dimensional ultrasound imaging showed a strong correlation for measurement of tumor size over a range of tumor sizes (R²= 0.6627, P = 0.003 for an exposure time of 67 msec and R²= 0.6553, P = 0.003 for an exposure time of 120 msec).</p> <p>Conclusion</p> <p>Our findings suggest a complementary role for fluorescence imaging and ultrasound imaging in assessing tumor burden and tumor progression in orthotopic mouse models of human cancer.</p

What we observe is biased by what other people tell us: beliefs about the reliability of gaze behavior modulate attentional orienting to gaze cues

For effective social interactions with other people, information about the physical environment must be integrated with information about the interaction partner. In order to achieve this, processing of social information is guided by two components: a bottom-up mechanism reflexively triggered by stimulus-related information in the social scene and a top-down mechanism activated by task-related context information. In the present study, we investigated whether these components interact during attentional orienting to gaze direction. In particular, we examined whether the spatial specificity of gaze cueing is modulated by expectations about the reliability of gaze behavior. Expectations were either induced by instruction or could be derived from experience with displayed gaze behavior. Spatially specific cueing effects were observed with highly predictive gaze cues, but also when participants merely believed that actually non-predictive cues were highly predictive. Conversely, cueing effects for the whole gazed-at hemifield were observed with non-predictive gaze cues, and spatially specific cueing effects were attenuated when actually predictive gaze cues were believed to be non-predictive. This pattern indicates that (i) information about cue predictivity gained from sampling gaze behavior across social episodes can be incorporated in the attentional orienting to social cues, and that (ii) beliefs about gaze behavior modulate attentional orienting to gaze direction even when they contradict information available from social episodes

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

The ideal cancer treatment should both destroy the primary tumour and at the same time educate the immune system to recognise the tumour as foreign so that distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the i.v. administration of photosensitisers followed by illumination of the tumour with red light producing reactive oxygen species that eventually cause vascular shutdown and tumour cell death by apoptosis and necrosis. Anti-tumour immunity is stimulated after PDT due to the acute inflammatory response, generation of tumour-specific antigens, and induction of heat-shock proteins. Green fluorescent protein (GFP) is used as an optical reporter to noninvasively image the progression of mouse tumours, and in addition, may act as a foreign (jellyfish) antigen. We asked whether GFP-expressing tumours could be used to monitor the response of tumour-bearing mice to PDT, and whether the tumour response differed when a nonimmunogenic tumour cell line was transduced with GFP. We injected RIF-1 or RIF-1 EGFP (stably transduced with a retroviral vector) cells in the leg of C3H/HeN mice and both the cells and tumour grew equally well. We used PDT with benzoporphyrin derivative and a short drug-light interval. There were complete cures and 100% mouse survival of RIF-1 EGFP while RIF-1 wild-type tumours all recurred. Cured mice were resistant to rechallenge with RIF-1 EGFP cells and a rechallenge with wild-type RIF-1 cells grew significantly slower. There was also slower RIF-1 EGFP rechallenge growth but no rejection when RIF-1 EGFP tumours were surgically removed. There was a low rate of PDT cure of tumours when RIF-1 cells were transduced with an empty retroviral vector. The presence of antibodies against EGFP in mouse serum suggests EGFP can act as a foreign antigen and PDT can then stimulate a long-term memory immune response

Acute lyme infection presenting with amyopathic dermatomyositis and rapidly fatal interstitial pulmonary fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Dermatomyositis has been described in the setting of lyme infection in only nine previous case reports. Although lyme disease is known to induce typical clinical findings that are observed in various collagen vascular diseases, to our knowledge, we believe that our case is the first presentation of acute lyme disease associated with amyopathic dermatomyositis, which was then followed by severe and fatal interstitial pulmonary fibrosis only two months later.</p> <p>Case presentation</p> <p>We present a case of a 64-year-old African-American man with multiple medical problems who was diagnosed with acute lyme infection after presenting with the pathognomonic rash and confirmatory serology. In spite of appropriate antimicrobial therapy for lyme infection, he developed unexpected amyopathic dermatomyositis and then interstitial lung disease.</p> <p>Conclusions</p> <p>This case illustrates a potential for lyme disease to produce clinical syndromes that may be indistinguishable from primary connective tissue diseases. An atypical and sequential presentation (dermatomyositis and interstitial lung disease) of a common disease (lyme infection) is discussed. This case illustrates that in patients who are diagnosed with lyme infection who subsequently develop atypical muscular, respiratory or other systemic complaints, the possibility of severe rheumatological and pulmonary complications should be considered.</p

\u201cGive, but Give until It Hurts\u201d: The Modulatory Role of Trait Emotional Intelligence on the Motivation to Help

Two studies investigated the effect of trait Emotional Intelligence (trait EI) on people\u2019s moti- vation to help. In Study 1, we developed a new computer-based paradigm that tested partic- ipants\u2019 motivation to help by measuring their performance on a task in which they could gain a hypothetical amount of money to help children in need. Crucially, we manipulated partici- pants\u2019 perceived efficacy by informing them that they had been either able to save the chil- dren (positive feedback) or unable to save the children (negative feedback). We measured trait EI using the Trait Emotional Intelligence Questionnaire\u2013Short Form (TEIQue-SF) and assessed participants\u2019 affective reactions during the experiment using the PANAS-X. Results showed that high and low trait EI participants performed differently after the presen- tation of feedback on their ineffectiveness in helping others in need. Both groups showed increasing negative affective states during the experiment when the feedback was negative; however, high trait EI participants better managed their affective reactions, modulating the impact of their emotions on performance and maintaining a high level of motivation to help. In Study 2, we used a similar computerized task and tested a control situation to explore the effect of trait EI on participants\u2019 behavior when facing failure or success in a scenario unre- lated to helping others in need. No effect of feedback emerged on participants\u2019 emotional states in the second study. Taken together our results show that trait EI influences the impact of success and failure on behavior only in affect-rich situation like those in which people are asked to help others in need

Water induced sediment levitation enhances downslope transport on Mars

On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought

Control of magnetic anisotropy by orbital hybridization in (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattice

The asymmetry of chemical nature at the hetero-structural interface offers an unique opportunity to design desirable electronic structure by controlling charge transfer and orbital hybridization across the interface. However, the control of hetero-interface remains a daunting task. Here, we report the modulation of interfacial coupling of (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattices by manipulating the periodic thickness with n unit cells of SrTiO3 and n unit cells La0.67Sr0.33MnO3. The easy axis of magnetic anisotropy rotates from in-plane (n = 10) to out-of-plane (n = 2) orientation at 150 K. Transmission electron microscopy reveals enlarged tetragonal ratio > 1 with breaking of volume conservation around the (La0.67Sr0.33MnO3)n/(SrTiO3)n interface, and electronic charge transfer from Mn to Ti 3d orbitals across the interface. Orbital hybridization accompanying the charge transfer results in preferred occupancy of 3d3z2-r2 orbital at the interface, which induces a stronger electronic hopping integral along the out-of-plane direction and corresponding out-of-plane magnetic easy axis for n = 2. We demonstrate that interfacial orbital hybridization in superlattices of strongly correlated oxides may be a promising approach to tailor electronic and magnetic properties in device applications

Degradation of communal rangelands in South Africa: towards an improved understanding to inform policy

In South Africa, the relative extent of range degradation under freehold compared to communal tenure has been strongly debated. We present a perspective on the processes that drive rangeland degradation on land under communal tenure. Our findings are based on literature as well as extensive field work on both old communal lands and ‘released’ areas, where freehold farms have been transferred to communal ownership. We discuss the patterns of degradation that have accompanied communal stewardship and make recommendations on the direction policy should follow to prevent further degradation and mediate rehabilitation of existing degraded land.Keywords: communal rangelands, land degradation, rehabilitation, social systemsAfrican Journal of Range &amp; Forage Science 2013, 30(1&amp;2): 57–6