Enamel Matrix Derivative Decreases Pyroptosis-Related Genes in Macrophages.

Background: Pyroptosis is a caspase-dependent catabolic process relevant to periodontal disorders for which inflammation is central to the pathophysiology of the disease. Although enamel matrix derivative (EMD) has been applied to support periodontal regeneration, its capacity to modulate the expression of pyroptosis-related genes remains unknown. Considering EMD has anti-inflammatory properties and pyroptosis is linked to the activation of the inflammasome in chronic periodontitis, the question arises whether EMD could reduce pyroptosis signalling. Methods: To answer this question, primary macrophages obtained from murine bone marrow and RAW 264.7 macrophages were primed with EMD before being challenged by lipopolysaccharide (LPS). Cells were then analysed for pyroptosis-signalling components by gene expression analyses, interleukin-1β (IL-1β) immunoassay, and the detection of caspase-1 (CAS1). The release of mitochondrial reactive oxygen species (ROS) was also detected. Results: We report here that EMD, like the inflammasome (NLRP3) and CAS1 specific inhibitors-MCC950 and Ac-YVAD-cmk, respectively-lowered the LPS-induced expression of NLRP3 in primary macrophages (EMD: p = 0.0232; MCC950: p = 0.0426; Ac-YVAD-cmk: p = 0.0317). EMD further reduced the LPS-induced expression of NLRP3 in RAW 264.7 cells (p = 0.0043). There was also a reduction in CAS1 and IL-1β in RAW 264.7 macrophages on the transcriptional level (p = 0.0598; p = 0.0283; respectively), in IL-1β protein release (p = 0.0313), and CAS1 activity. Consistently, EMD, like MCC950 and Ac-YVAD-cmk, diminished the ROS release in activated RAW 264.7 cells. In ST2 murine mesenchymal cells, EMD could not be tested because LPS, saliva, and IL-1β + TNF-α failed to provoke pyroptosis signalling. Conclusion: These findings suggest that EMD is capable of dampening the expression of pyroptosis-related genes in macrophages

Chemotherapy in Cutaneous Melanoma: Is There Still a Role?

Purpose of review: In the preceding decade, the management of metastatic cutaneous melanoma has been revolutionised with the development of highly effective therapies including immune checkpoint inhibitors (specifically CTLA-4 and PD-1 inhibitors) and targeted therapies (BRAF and MEK inhibitors). The role of chemotherapy in the contemporary management of melanoma is undefined. Recent findings: Extended analyses highlight substantially improved 5-year survival rates of approximately 50% in patients with metastatic melanoma treated with first-line therapies. However, most patients will progress on these first-line treatments. Sequencing of chemotherapy following failure of targeted and immunotherapies is associated with low objective response rates and short progression-free survival, and thus, meaningful benefits to patients are minimal. Chemotherapy has limited utility in the contemporary management of cutaneous melanoma (with a few exceptions, discussed herein) and should not be the standard treatment sequence following failure of first-line therapies. Instead, enrolment onto clinical trials should be standard-of-care in these patients. Summary: Chemotherapy has limited utility in the contemporary management of cutaneous melanoma (with a few exceptions, discussed herein) and should not be the standard treatment sequence following failure of first-line therapies. Instead, enrolment onto clinical trials should be standard-of-care in these patients

A Relativistic Thomas-Fermi Description of Collective Modes in Droplets of Nuclear Matter

Isoscalar collective modes in a relativistic meson-nucleon system are investigated in the framework of the time-dependent Thomas-Fermi method. The energies of the collective modes are determined by solving consistently the dispersion relations and the boundary conditions. The energy weighted sum rule satisfied by the model allows the identification of the giant ressonances. The percentage of the energy weighted sum rule exhausted by the collective modes is in agreement with experimental data, but the energies come too high.Comment: 21 pages (RevTex) and 2 postscript figures as a compressed uuencode fil

New p-i-n Si : H imager configuration for spatial resolution improvement

Amorphous glass/ZnO-Al/p(a-Si:H)/i(a-Si:H)/n(a-Si1-xCx:H)/Al imagers with different n-layer resistivities were produced by plasma enhanced chemical vapour deposition technique (PE-CVD). An image is projected onto the sensing element and leads to spatially confined depletion regions that can be readout by scanning the photodiode with a low-power modulated laser beam. The essence of the scheme is the analog readout, and the absence of semiconductor arrays or electrode potential manipulations to transfer the information coming from the transducer. The influence of the intensity of the optical image projected onto the sensor surface is correlated with the sensor output characteristics (sensitivity, linearity blooming, resolution and signal-to-noise ratio) are analysed for different material compositions (0.5 < x < 1). The results show that the responsivity and the spatial resolution are limited by the conductivity of the doped layers. An enhancement of one order of magnitude in the image intensity signal and on the spatial resolution are achieved at 0.2 mW cm(-2) light flux by decreasing the n-layer conductivity by the same amount. A physical model supported by electrical simulation gives insight into the image-sensing technique used

Modeling the impacts of climate extremes and multiple water uses to support water management in the Icó-Mandantes Bay, Northeast Brazil

The hydropower production, water supply and aquaculture services of the Itaparica Reservoir are of immense importance for the Brazilian Northeast. Uncontrolled water resources consumption (e.g. irrigation, water supply), climate and land use change effects deteriorated the water quantity and quality in the reservoir, leading to socio-economic and environmental problems. In this work, a depth-averaged shallow water model was set up for the Icó-Mandantes Bay, one major branch of the reservoir, using the open TELEMAC-MASCARET system. The aim was to assess the impacts of the newly built water diversion channel, as well as the effects of a flood and tracer transport from an intermittent tributary, both located in the bay. An alternative approach to estimate the water retention times was additionally implemented. The simulations showed that though the diversion channel did not significantly influence the hydrodynamics of the bay, it is necessary to continuously monitor water quality parameters in the withdrawal, especially during rainy periods after droughts, because of the nutrient inputs from the tributary and the overflows of the nearby drainage systems. Management measures adapting to the continuously changing natural conditions and anthropogenic impacts are thus indispensable and the model presented can be a valuable supporting tool for this purpose.BMBF, 01LL0904A, Verbundvorhaben INNOVATE: Nachhaltige Nutzung von Stauseen durch innovative Kopplung von aquatischen und terrestrischen Ökosystemfunktionen - Teilvorhaben 1: Verbundkoordination, Grüne Leber und Ökonomi

Detection of \u3ci\u3eGiardia duodenalis\u3c/i\u3e antigen in coprolites using a commercially available enzyme-linked immunosorbent assay

The objective of this experiment was to assess the utility of a commercially available enzyme-linked immunosorbent assay (ELISA) kit for diagnosis of giardiasis in archaeological human remains. The kit, a monoclonal antibody assay, is used to detect the presence of Giardia-specific antigen 65 (GSA65) in human feces. We utilized the assay in ancient fecal material. The material included desiccated feces found in mummies or in archaeological sites, and sediments from latrines. A total of 83 specimens, previously examined microscopically for parasites, were examined. The ELISA detected 3 positive samples, dated to about 1200 AD, 1600 AD, and 1700 AD. The ELISA was superior to direct observation. It was possible to identify G. duodenalis cysts by direct microscopy in only one of these samples. The results did not show cross-reactivity between this protozoan and helminths. The use of ELISA to detect G. duodenalis coproantigen could help the diagnosis of giardiasis in ancient human remains

Reflected Light from Sand Grains in the Terrestrial Zone of a Protoplanetary Disk

We show that grains have grown to ~mm size (sand sized) or larger in the terrestrial zone (within ~3 AU) of the protoplanetary disk surrounding the 3 Myr old binary star KH 15D. We also argue that the reflected light in the system reaches us by back scattering off the far side of the same ring whose near side causes the obscuration.Comment: 22 pages, 5 figures. To be published in Nature, March 13, 2008. Contains a Supplemen

A reference guide for tree analysis and visualization

The quantities of data obtained by the new high-throughput technologies, such as microarrays or ChIP-Chip arrays, and the large-scale OMICS-approaches, such as genomics, proteomics and transcriptomics, are becoming vast. Sequencing technologies become cheaper and easier to use and, thus, large-scale evolutionary studies towards the origins of life for all species and their evolution becomes more and more challenging. Databases holding information about how data are related and how they are hierarchically organized expand rapidly. Clustering analysis is becoming more and more difficult to be applied on very large amounts of data since the results of these algorithms cannot be efficiently visualized. Most of the available visualization tools that are able to represent such hierarchies, project data in 2D and are lacking often the necessary user friendliness and interactivity. For example, the current phylogenetic tree visualization tools are not able to display easy to understand large scale trees with more than a few thousand nodes. In this study, we review tools that are currently available for the visualization of biological trees and analysis, mainly developed during the last decade. We describe the uniform and standard computer readable formats to represent tree hierarchies and we comment on the functionality and the limitations of these tools. We also discuss on how these tools can be developed further and should become integrated with various data sources. Here we focus on freely available software that offers to the users various tree-representation methodologies for biological data analysis

A join-based hybrid parameter for constraint satisfaction

We propose joinwidth, a new complexity parameter for the Constraint Satisfaction Problem (CSP). The definition of joinwidth is based on the arrangement of basic operations on relations (joins, projections, and pruning), which inherently reflects the steps required to solve the instance. We use joinwidth to obtain polynomial-time algorithms (if a corresponding decomposition is provided in the input) as well as fixed-parameter algorithms (if no such decomposition is provided) for solving the CSP. Joinwidth is a hybrid parameter, as it takes both the graphical structure as well as the constraint relations that appear in the instance into account. It has, therefore, the potential to capture larger classes of tractable instances than purely structural parameters like hypertree width and the more general fractional hypertree width (fhtw). Indeed, we show that any class of instances of bounded fhtw also has bounded joinwidth, and that there exist classes of instances of bounded joinwidth and unbounded fhtw, so bounded joinwidth properly generalizes bounded fhtw. We further show that bounded joinwidth also properly generalizes several other known hybrid restrictions, such as fhtw with degree constraints and functional dependencies. In this sense, bounded joinwidth can be seen as a unifying principle that explains the tractability of several seemingly unrelated classes of CSP instances