Prostaglandin F2 Receptor Negative Regulator (PTGFRN) Expression Correlates With a Metastatic-like Phenotype in Epidermoid Carcinoma, Pediatric Medulloblastoma, and Mesothelioma.

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein associated with metastatic characteristics of certain cancer types. However, it remains poorly characterized and its direct function in cancer remains unclear. The study presented here aims to further examine whether PTGFRN expression affects a cancer cell's phenotype, as well as metastatic-like characteristics. We used stable shRNA and cDNA transfections to respectively knockdown and overexpress PTGFRN in three different cancer cell lines, two of which are representative of rare and aggressive cancers (Mesothelioma and Pediatric Medulloblastoma). We then examined the characteristics of the resulting clones and showed a decrease in proliferation, migration, colony formation, and spheroid growth capabilities in cells where PTGFRN expression had been inhibited, while cells overexpressing PTGFRN showed the opposite. In addition, we showed that PTGFRN displayed direct binding to two protein partners, Integrin ß1 and E. Cadherin, the latter of which is a novel direct binding partner to PTGFRN. Furthermore, silencing PTGFRN expression impacted the cellular process of autophagy, thereby providing another avenue by which PTGFRN potentially contributes to a cancer cell phenotype. Our findings demonstrate the potential role of PTGFRN in cancer metastasis and suggest PTGFRN as a future target for drug development in the treatment of metastatic cancers.

Macrophage NOX2 NADPH oxidase maintains alveolar homeostasis in mice.

The leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation. Genetic defects in NOX2 result in chronic granulomatous disease (CGD), associated with microbial infections and inflammatory disorders, often involving the lung. Alveolar macrophages (AMs) are the predominant immune cell in the airways at steady state, and limiting their activation is important, given the constant exposure to inhaled materials, yet the importance of NOX2 in this process is not well understood. In this study, we showed a previously undescribed role for NOX2 in maintaining lung homeostasis by suppressing AM activation, in CGD mice or mice with selective loss of NOX2 preferentially in macrophages. AMs lacking NOX2 had increased cytokine responses to Toll-like receptor-2 (TLR2) and TLR4 stimulation ex vivo. Moreover, between 4 and 12 week of age, mice with global NOX2 deletion developed an activated CD11bhigh subset of AMs with epigenetic and transcriptional profiles reflecting immune activation compared with WT AMs. The presence of CD11bhigh AMs in CGD mice correlated with an increased number of alveolar neutrophils and proinflammatory cytokines at steady state and increased lung inflammation after insults. Moreover, deletion of NOX2 preferentially in macrophages was sufficient for mice to develop an activated CD11bhigh AM subset and accompanying proinflammatory sequelae. In addition, we showed that the altered resident macrophage transcriptional profile in the absence of NOX2 is tissue specific, as those changes were not seen in resident peritoneal macrophages. Thus, these data demonstrate that the absence of NOX2 in alveolar macrophages leads to their proinflammatory remodeling and dysregulates alveolar homeostasis.

Fractioned-pattern radiation mapping, Part I: modeling.

Here, we present a technique that predicts the radiation's distribution in any optical system. It is based on decomposing the emitting source power by assigning a fraction of the total power to each emitted ray. All kinds of power losses in the rays' optical paths are considered. Fractioned radiation patterns are created in the last optical system surface, each associated with a single ray. We refer to fractioned patterns as those that conform to a whole radiating pattern. Thus, the irradiance of the completely illuminated surface is calculated by adding the optical system's fractioned radiation maps. This method is non-zero étendue. The result presented here allows for predicting the radiation patterns accurately with a handful of equations and can help design any image and non-image-forming optical systems.

Fractioned-pattern radiation mapping, Part II: assessment.

In Part I, the authors proposed a theoretical background for predicting the radiation distribution in any optical system based on decomposing the emitting source power. Here, we describe the validity of this decomposition through a practical example that uses a radiating source and a single surface optical system. This source is calibrated in a metrology testbed that guarantees its traceability to the candela (cd), the International System (SI) base unit for luminous intensity I v. A second example, this time numerical, shows the method's performance in a multisurface optical system.

Cutting Edge: NOX2 NADPH Oxidase Controls Infection by an Intracellular Bacterial Pathogen through Limiting the Type 1 IFN Response.

The NOX2 NADPH oxidase (NOX2) produces reactive oxygen species to kill phagosome-confined bacteria. However, we previously showed that Listeria monocytogenes is able to avoid the NOX2 activity in phagosomes and escape to the cytosol. Thus, despite the established role of NOX2 limiting L. monocytogenes infection in mice, the underlying mechanisms of this antibacterial activity remain unclear. In this article, we report that NOX2 controls systemic L. monocytogenes spread through modulation of the type I IFN response, which is known to be exploited by L. monocytogenes during infection. NOX2 deficiency results in increased expression of IFN-stimulated genes in response to type I IFN and leads to 1) promotion of cell-to-cell spread by L. monocytogenes, 2) defective leukocyte recruitment to infection foci, and 3) production of anti-inflammatory effectors IL-10 and thioredoxin 1. Our findings report a novel antimicrobial role for NOX2 through modulation of type I IFN responses to control bacterial dissemination.

The GARP Domain of the Rod CNG Channel's ß1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim.

Vision begins when light is captured by the outer segment organelle of photoreceptor cells in the retina. Outer segments are modified cilia filled with hundreds of flattened disk-shaped membranes. Disk membranes are separated from the surrounding plasma membrane, and each membrane type has unique protein components. The mechanisms underlying this protein sorting remain entirely unknown. In this study, we investigated the outer segment delivery of the rod cyclic nucleotide-gated (CNG) channel, which is located in the outer segment plasma membrane, where it mediates the electrical response to light. Using Xenopus and mouse models of both sexes, we now show that the targeted delivery of the CNG channel to the outer segment uses the conventional secretory pathway, including protein processing in both ER and Golgi, and requires preassembly of its constituent α1 and ß1 subunits. We further demonstrate that the N-terminal glutamic acid-rich protein (GARP) domain of CNGß1 contains two distinct functional regions. The glutamic acid-rich region encodes specific information targeting the channel to rod outer segments. The adjacent proline-enriched region connects the CNG channel to photoreceptor disk rims, likely through an interaction with peripherin-2. These data reveal fine functional specializations within the structural domains of the CNG channel and suggest that its sequestration to the outer segment plasma membrane requires an interaction with peripherin-2.SIGNIFICANCE STATEMENT Neurons and other differentiated cells have a remarkable ability to deliver and organize signaling proteins at precise subcellular locations. We now report that the CNG channel, mediating the electrical response to light in rod photoreceptors, contains two specialized regions within the N terminus of its ß-subunit: one responsible for delivery of this channel to the ciliary outer segment organelle and another for subsequent channel sequestration into the outer segment plasma membrane. These findings expand our understanding of the molecular specializations used by neurons to populate their critical functional compartments.

On-axis diffraction-limited bi-conical lenses.

A diffraction-limited lens having both surfaces conic is shown. The analytical and numerical calculation for all possible solutions of the conical front and back surfaces is presented. Object and image distances, lens thickness, and refractive index are prescribed. The process to obtain on-axis diffraction-limited images with bi-conic lenses and the proof of the method, corroborated through an example in Oslo, are described here.

Molecular Diversity and Biochemical Content in Two Invasive Alien Species: Looking for Chemical Similarities and Bioactivities.

The biochemical composition, molecular diversity, and two different bioactivities of Asparagopsis armata and Rugulopteryx okamurae (two alien species with different invasive patterns in the southern Iberian Peninsula) were analyzed through spectrophotometric methods and Fourier transform ion cyclotron mass spectroscopy (FT-ICR-MS). A total of 3042 molecular formulas were identified from the different extracts. The dH2O extracts were the most molecularly different. A. armata presented the highest content of nitrogenous compounds (proteins, CHON) and sulphur content, whereas R. okamurae was rich in carbonated compounds (total carbon, lipids, CHO, and CHOP). Antioxidant capacity and phenolic content were higher in R. okamurae than in A. armata. Antimicrobial activity was detected from both species. A. armata showed capacity to inhibit human and fish pathogens (e.g., Staphylococcus aureus or Vibrio anguillarum), whereas R. okamurae only showed inhibition against human bacteria (Staphylococcus aureus and Cutibacterium acnes). In R. okamurae, molecules with a great number of pharmaceutical activities (e.g., anti-inflammatory or antitumoral), antibacterial, biomaterial, and other utilities were found. The main molecules of A. armata had also pharmaceutical applications (e.g., antimalarian, antithrombotic, anti-inflammatory, or antiarthritis). The valorization of these species can help to counteract the environmental effects of the bioinvasions.

Adaptor protein complex-1 (AP-1) is recruited by the HEATR5 protein Laa1 and its co-factor Laa2 in yeast.

Cellular membrane trafficking mediated by the clathrin adaptor protein complex-1 (AP-1) is important for the proper composition and function of organelles of the endolysosomal system. Normal AP-1 function requires proteins of the HEAT repeat-containing 5 (HEATR5) family. Although HEATR5 proteins were first identified based on their ability to interact with AP-1, the functional significance of this interaction was unknown. We used bioinformatics-based phenotypic profiling and information from genome-wide fluorescence microscopy studies in the budding yeast Saccharomyces cerevisiae to identify a protein, Laa2, that mediates the interaction between AP-1 and the yeast HEATR5 protein Laa1. Further characterization of Laa2 revealed that it binds to both Laa1 and AP-1. Laa2 contains a motif similar to the characterized γ-ear-binding sites found in other AP-1-binding proteins. This motif in Laa2 is essential for the Laa1-AP-1 interaction. Moreover, mutation of this motif disrupted AP-1 localization and function and caused effects similar to mutations that remove the γ-ear of AP-1. These results indicate that Laa2 mediates the interaction between Laa1 and AP-1 and reveal that this interaction promotes the stable association of AP-1 with membranes in yeast.

Antioxidant and Cytotoxic Effects on Tumor Cells of Exopolysaccharides From Tetraselmis suecica (Kylin) Butcher Grown Under Autotrophic and Heterotrophic Conditions.

Marine microalgae produce extracellular metabolites such as exopolysaccharides (EPS) with potentially beneficial biological applications to human health, especially antioxidant and antitumor properties, which can be increased with changes in crop trophic conditions. This study aimed to develop the autotrophic and heterotrophic culture of Tetraselmis suecica (Kylin) Butcher in order to increase EPS production and to characterize its antioxidant activity and cytotoxic effects on tumor cells. The adaptation of autotrophic to heterotrophic culture was carried out by progressively reducing the photoperiod and adding glucose. EPS extraction and purification were performed. EPS were characterized by Fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry. The antioxidant capacity of EPS was analyzed by the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) method, and the antitumor capacity was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, showing high activity on human leukemia, breast and lung cancer cell lines. Although total EPS showed no cytotoxicity, acidic EPS showed cytotoxicity over the gingival fibroblasts cell line. Heterotrophic culture has advantages over autotrophic, such as increasing EPS yield, higher antioxidant capacity of the EPS and, to the best of our knowledge, this is the first probe that T. suecica EPS have cytotoxic effects on tumor cells; therefore, they could offer greater advantages as possible natural nutraceuticals for the pharmaceutical industry.

Freeform geometrical optics I: principles.

Lens design uses a calculation of the lens' surfaces that permits us to obtain an image from a given object. A set of general rules and laws permits us to calculate the essential points of the optical system, such as distances, thickness, pupils, and focal distances, among others. Now, the theory on which classical lens design is based has changed radically, as our theoretical foundations do not rely on the classical ray-tracing rules. We show that with the rules expressed in a reduced vector analytical solution set of equations, we can take into account all optical elements, i.e., refractive, reflective, and catadioptric. These foundations permit us to keep under control the system aberration budget in every surface. It reduces the computation time dramatically. The examples presented here were possible because of the versatility of this theoretical approach.

Freeform geometrical optics II: from parametric representation to CAD/CAM.

Freeform optical surfaces are of great importance because of two main properties. The first is their ability to enhance the image quality of image-forming optical systems; the second is their inherent reduction in the number of surfaces in image and nonimage-forming optical systems. However, the main characteristic of freeform surfaces is that they lack symmetry about any spatial axis. This attribute allows describing freeform surfaces with a mathematical parametric representation. Unfortunately, parametric representation can be extremely extended. On the other hand, when describing freeform surfaces, the explicit representation is commonly preferred because of its compactness and CAD-format exportable easiness. Parametrically represented freeform surfaces can nonetheless be exported to a CAD format, with no significant departure of surface shape, as shown here. The vector method presented here guarantees that the surface's sampling density be proportional to the irradiance on the surface.

Catadioptric interfaces for designing VLC antennae.

This paper presents a model to design bi-aspherical catadioptric lenses with limited image diffraction. A first refractive Cartesian oval surface that does not introduce any spherical aberration is used. When total internal reflection occurs, this surface can also be simultaneously used as a mirror. The reflective characteristics of Cartesian ovals are also well described in this paper. The theoretical work described here can considerably reduce computing time in optical system design. This model is applied to examples of antennae design for visible light communications (VLC).

Glucose starvation inhibits autophagy via vacuolar hydrolysis and induces plasma membrane internalization by down-regulating recycling.

Cellular energy influences all aspects of cellular function. Although cells can adapt to a gradual reduction in energy, acute energy depletion poses a unique challenge. Because acute depletion hampers the transport of new energy sources into the cell, the cell must use endogenous substrates to replenish energy after acute depletion. In the yeast Saccharomyces cerevisiae, glucose starvation causes an acute depletion of intracellular energy that recovers during continued glucose starvation. However, how the cell replenishes energy during the early phase of glucose starvation is unknown. In this study, we investigated the role of pathways that deliver proteins and lipids to the vacuole during glucose starvation. We report that in response to glucose starvation, plasma membrane proteins are directed to the vacuole through reduced recycling at the endosomes. Furthermore, we found that vacuolar hydrolysis inhibits macroautophagy in a target of rapamycin complex 1-dependent manner. Accordingly, we found that endocytosis and hydrolysis are required for survival in glucose starvation, whereas macroautophagy is dispensable. Together, these results suggest that hydrolysis of components delivered to the vacuole independent of autophagy is the cell survival mechanism used by S. cerevisiae in response to glucose starvation.

Differentiability of a projection functional in ray-tracing processes: applied study to estimate the coefficients of a single lens with conic surfaces.

In optical design, many error functions can be used to generate an optical system with desired characteristics. These error functions are optimized by iterative algorithms. However, these error functions should be theoretically and mathematically differentiable to be optimized. In this paper, the differentiability of an error function is partially justified. The error function herein is called the projection functional. This proposed projection functional can be used to estimate the coefficients of an arbitrary lens with conic surfaces by means of the spot distributions on two planes produced by a fixed Hartmann plate. The differentiability of the projection functional is required to guarantee the existence of its Jacobian matrix, which is a suitable condition to minimize this functional by iterative methods. Numerical examples of the functional minimization are given.

Multi-step vortex filtering for phase extraction.

A quantized version of a continuous spiral phase filter with unitary topological charge, here denominated multi-step spiral phase filter (MSSPF), is proposed to extract phase from rotated spiral interferograms. Spiral interferograms are usually obtained from phase objects by registering the interference of its vortex filtered complex amplitude with a reference complex amplitude. The structure found in this kind of interferograms, depend on the number of steps used in the MSSPF that usually are assumed with an infinite number of steps for the continuous spiral phase filter. Reducing the number of steps of the MSSPF affects the residual phase error obtained after the phase extraction method. This error is therefore analysed here using a numerical simulation of a Mach-Zender interferometer with a MSSPF and a reduced number of steps. It is shown that, for our proposed method of rotated spiral interferograms, a residual error persists as the number of steps is increased approaching the residual error reported for the phase extraction method of single-shot spiral interferograms. Furthermore, it is shown that this novel technique can be applied without further modifications for phase contrast measurement. Experimental results show similar performance of this phase extraction technique, when compared to the results obtained with a commercial interferometer and with the numerical simulations.

Effect of PTFGRN Expression on the Proteomic Profile of A431 Cells and Determination of the PTGFRN Interactome.

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein whose expression has been previously implicated in cancer metastasis. However, the exact molecular mechanisms by which PTGFRN influences cancer progression are still unknown. As such, our laboratory set out to investigate how PTGFRN knockdown affected the expression of other proteins. We also carried out coimmunoprecipitation experiments using a monoclonal anti-PTGFRN antibody. We employed mass spectrometry-based proteomics for both experiments to identify proteins that were associated with PTGFRN. Our data show that PTGFRN knockdown increased pathways related to innate immune responses and decreased pathways associated with the synthesis of metabolic precursors and protein processing, among others. Additionally, the coimmunoprecipitation experiments indicated that PTGFRN is associated with proteins involved in processing and metabolism, as well as VEGF signaling molecules. These results highlight the role of PTGFRN as a protein processing regulator, which may be influencing cancer progression.

Congenital continuous retrograde basilar flow suggests type B interrupted aortic arch in a neonate: A case report.

Reversed flow in the basilar artery can be acquired or congenital. Acquired reversed flow in the basilar artery can result from acute thrombosis of the basilar artery or retrograde vertebral artery flow. Congenital continuous retrograde basilar artery flow has not been described. We report a 2-day-old male presenting with hypocalcemic seizures which led us to obtain a Duplex echoencephalogram. An echocardiogram was subsequently ordered. In the coronal plane through the anterior fontanelle, retrograde flow was seen in the basilar artery and the right vertebral artery. In the axial plane through the temporal window, the flow was anteroposterior in both posterior communicating arteries. In the posterior cerebral arteries, the flow was retrograde in the P1 segment and anterograde in the P2 and P3 segments. An interrupted aortic arch was suspected. The echocardiogram showed a large perimembranous ventricular septal defect with bidirectional shunting, a hypoplastic and bicuspid aortic valve, an aortic arch interrupted between the left common carotid artery and the left subclavian artery (type B interrupted aortic arch), and a 5 mm patent ductus arteriosus with predominant right to left flow. Because of the patency of the large patent ductus arteriosus, our patient showed no sign of posterior circulation insufficiency. Prostaglandin E1 therapy was initiated immediately. Diagnosis of DiGeorge syndrome was proven. The infant underwent interrupted aortic arch repair and anterograde flow was established in the basilar artery. We conclude that congenital asymptomatic continuous retrograde flow in the basilar artery and left vertebral artery is a medical emergency as it implies the presence of type B interrupted aortic arch with large patent ductus arteriosus in a neonate.

Evaluation of the Differential Postbiotic Potential of Shewanella putrefaciens Pdp11 Cultured in Several Growing Conditions.

The increased knowledge of functional foods has led to the development of a new generation of health products, including those containing probiotics and products derived from them. Shewanella putrefaciens Pdp11 (SpPdp11) is a strain described as a probiotic that exerts important beneficial effects on several farmed fish. However, the use of live probiotic cells in aquaculture has limitations such as uncertain survival and shelf life, which can limit their efficacy. In addition, its efficacy can vary across species and hosts. When probiotics are administered orally, their activity can be affected by the environment present in the host and by interactions with the intestinal microbiota. Furthermore, live cells can also produce undesired substances that may negatively impact the host as well as the risk of potential virulence reversion acquired such as antibiotic resistance. Therefore, new alternatives emerged such as postbiotics. Currently, there is no knowledge about the postbiotic potential of SpPdp11 in the aquaculture industry. Postbiotic refers to the use of bacterial metabolites, including extracellular products (ECPs), to improve host physiology. However, the production of postbiotic metabolites can be affected by various factors such as cultivation conditions, which can affect bacterial metabolism. Thus, the objective of this study was to evaluate the postbiotic potential of ECPs from SpPdp11 under different cultivation conditions, including culture media, temperature, growth phase, and salinity. We analyzed their hydrolytic, antibacterial, antiviral, and cytotoxic capacity on several fish cell lines. The results obtained have demonstrated how each ECP condition can exert a different hydrolytic profile, reduce the biofilm formation by bacterial pathogens relevant to fish, lower the titer of nervous necrosis virus (NNV), and exert a cytotoxic effect on different fish cell lines. In conclusion, the ECPs obtained from SpPdp11 have different capacities depending on the cultivation conditions used. These conditions must be considered in order to recover the maximum number of beneficial capacities or to choose the appropriate conditions for specific activities.

Compensation of the two-stage phase-shifting algorithms in the presence of detuning and harmonics.

The Fourier analysis of two-stage phase-shifting (TSPS) algorithms is growing in interest as a research topic, specifically, the algorithm's insensitivity properties to various error sources. The main motivation of this paper is to propose TSPS algorithms that perform well in the face of detuning and harmonics for each of the two sets of interferograms with different or equal reference frequencies. TSPS algorithms based on the development of generalized equations consider both the frequency sampling functions that represent them and nonconstant phase shifts.