Breast Cancer Cells Stimulate Neutrophils to Produce Oncostatin M: Potential Implications for Tumor Progression

Tumor-associated and tumor-infiltrating neutrophils (TAN) and macrophages (TAM) can account for as much as 50% of the total tumor mass in invasive breast carcinomas. It is thought that tumors secrete factors that elicit a woundrepair response from TAMs and TANs and that this response inadvertently stimulates tumor progression. Oncostatin M is a pleiotropic cytokine belonging to the interleukin-6 family that is expressed by several cell types including activated human T lymphocytes, macrophages, and neutrophils. Whereas oncostatin M can inhibit the proliferation of breast cancer cells in vitro, recent studies suggest that oncostatin M may promote tumor progression by enhancing angiogenesis and metastasis. In addition, neutrophils can be stimulated to synthesize and rapidly release large quantities of oncostatin M. In this article, we show that human neutrophils secrete oncostatin M when cocultured with MDA-MB-231 and T47D human breast cancer cells. Neutrophils isolated from whole blood or breast cancer cells alone express little oncostatin M by immunocytochemistry and ELISA, but neutrophils express and release high levels of oncostatin M when they are cocultured with breast cancer cells. In addition, we show that granulocyte-macrophage colony-stimulating factor produced by breast cancer cells and cell-cell contact are both necessary for the release of oncostatin M from neutrophils. Importantly, neutrophilderived oncostatin M induces vascular endothelial growth factor from breast cancer cells in coculture and increases breast cancer cell detachment and invasive capacity, suggesting that neutrophils and oncostatin M may promote tumor progression in vivo

Oncostatin M Binds to Extracellular Matrix in a Bioactive Conformation: Implications for Inflammation and Metastasis

Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26 kDa protein that can be proteolytically processed into 24 kDa and 22 kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic bonds that involves charged amino acids of both the ECM and OSM. The C-terminal extensions of 24 kDa and 26 kDa OSM, which contains six and thirteen basic amino acids, respectively, enhanced electrostatic binding to ECM at pH 6.5–7.5 when compared to 22 kDa OSM. The highest levels of OSM binding to ECM, though, were observed at acidic pH 5.5, where all forms of OSM bound to ECM proteins to a similar extent. This indicates additional electrostatic binding properties independent of the OSM C-terminal extensions. The reducing agent dithiothreitol also inhibited the binding of OSM to ECM suggesting a role for disulfide bonds in OSM immobilization. OSM immobilized to ECM was protected from cleavage by tumor-associated proteases and maintained activity following incubation at acidic pH for extended periods of time. Importantly, immobilized OSM remained biologically active and was able to induce and sustain the phosphorylation of STAT3 in T47D and ZR-75-1 human breast cancer cells over prolonged periods, as well as increase levels of STAT1 and STAT3 protein expression. Immobilized OSM also induced epithelial–mesenchymal transition-associated morphological changes in T47D cells. Taken together, these data indicate that OSM binds to ECM in a bioactive state that may have important implications for the development of chronic inflammation and tumor metastasis

Geographic Distribution: \u3ci\u3eAnolis sagrei\u3c/i\u3e (Brown Anole). USA: Arizona.

We discovered the first distributional records for the exotic, Caribbean lizard, Anolis sagrei (Brown Anole), in Arizona

Exotic Differentiable Structures and General Relativity

We review recent developments in differential topology with special concern for their possible significance to physical theories, especially general relativity. In particular we are concerned here with the discovery of the existence of non-standard (``fake'' or ``exotic'') differentiable structures on topologically simple manifolds such as $S^7$, \R and $S^3\times {\bf R^1}.$ Because of the technical difficulties involved in the smooth case, we begin with an easily understood toy example looking at the role which the choice of complex structures plays in the formulation of two-dimensional vacuum electrostatics. We then briefly review the mathematical formalisms involved with differentiable structures on topological manifolds, diffeomorphisms and their significance for physics. We summarize the important work of Milnor, Freedman, Donaldson, and others in developing exotic differentiable structures on well known topological manifolds. Finally, we discuss some of the geometric implications of these results and propose some conjectures on possible physical implications of these new manifolds which have never before been considered as physical models.Comment: 11 pages, LaTe

Isotropy and Stability of the Brane

We reexamine Wald's no-hair theorem for global anisotropy in the brane world scenarios. We derive a set of sufficient conditions which must be satisfied by the brane matter and bulk metric so that a homogeneous and anisotropic brane asymptotically evolves to a de Sitter spacetime in the presence of a positive cosmological constant on the brane. We discuss the violations of these sufficient conditions and we show that a negative nonlocal energy density or the presence of strong anisotropic stress (i.e., a magnetic field) may lead the brane to collapse. We discuss the generality of these conditions.Comment: 8 pages, 2 figures, corrected some typos and titl

Early-universe constraints on a time-varying fine structure constant

Higher-dimensional theories have the remarkable feature of predicting a time (and hence redshift) dependence of the `fundamental' four dimensional constants on cosmological timescales. In this paper we update the bounds on a possible variation of the fine structure constant alpha at the time of BBN (z =10^10) and CMB (z=10^3). Using the recently-released high-resolution CMB anisotropy data and the latest estimates of primordial abundances of 4He and D, we do not find evidence for a varying alpha at more than one-sigma level at either epoch.Comment: 5 pages, 1 figure, minor misprints corrected, references added. The analysis has been updated using new BOOMERanG and DASI data on CMB anisotrop

Space Systems: Emerging Technologies and Operations

SPACE SYSTEMS: EMERGING TECHNOLOGIES AND OPERATIONS is our seventh textbook in a series covering the world of UASs / CUAS/ UUVs. Other textbooks in our series are Drone Delivery of CBNRECy – DEW Weapons: Emerging Threats of Mini-Weapons of Mass Destruction and Disruption (WMDD); Disruptive Technologies with applications in Airline, Marine, Defense Industries; Unmanned Vehicle Systems & Operations On Air, Sea, Land; Counter Unmanned Aircraft Systems Technologies and Operations; Unmanned Aircraft Systems in the Cyber Domain: Protecting USA’s Advanced Air Assets, 2nd edition; and Unmanned Aircraft Systems (UAS) in the Cyber Domain Protecting USA\u27s Advanced Air Assets, 1st edition. Our previous six titles have received considerable global recognition in the field. (Nichols & Carter, 2022) (Nichols et al., 2021) (Nichols R. K. et al., 2020) (Nichols R. et al., 2020) (Nichols R. et al., 2019) (Nichols R. K., 2018) Our seventh title takes on a new purview of Space. Let\u27s think of Space as divided into four regions. These are Planets, solar systems, the great dark void (which fall into the purview of astronomers and astrophysics), and the Dreamer Region. The earth, from a measurement standpoint, is the baseline of Space. It is the purview of geographers, engineers, scientists, politicians, and romantics. Flying high above the earth are Satellites. Military and commercial organizations govern their purview. The lowest altitude at which air resistance is low enough to permit a single complete, unpowered orbit is approximately 80 miles (125 km) above the earth\u27s surface. Normal Low Earth Orbit (LEO) satellite launches range between 99 miles (160 km) to 155 miles (250 km). Satellites in higher orbits experience less drag and can remain in Space longer in service. Geosynchronous orbit is around 22,000 miles (35,000 km). However, orbits can be even higher. UASs (Drones) have a maximum altitude of about 33,000 ft (10 km) because rotating rotors become physically limiting. (Nichols R. et al., 2019) Recreational drones fly at or below 400 ft in controlled airspace (Class B, C, D, E) and are permitted with prior authorization by using a LAANC or DroneZone. Recreational drones are permitted to fly at or below 400 ft in Class G (uncontrolled) airspace. (FAA, 2022) However, between 400 ft and 33,000 ft is in the purview of DREAMERS. In the DREAMERS region, Space has its most interesting technological emergence. We see emerging technologies and operations that may have profound effects on humanity. This is the mission our book addresses. We look at the Dreamer Region from three perspectives:1) a Military view where intelligence, jamming, spoofing, advanced materials, and hypersonics are in play; 2) the Operational Dreamer Region; whichincludes Space-based platform vulnerabilities, trash, disaster recovery management, A.I., manufacturing, and extended reality; and 3) the Humanitarian Use of Space technologies; which includes precision agriculture wildlife tracking, fire risk zone identification, and improving the global food supply and cattle management. Here’s our book’s breakdown: SECTION 1 C4ISR and Emerging Space Technologies. C4ISR stands for Command, Control, Communications, Computers, Intelligence, Surveillance, and Reconnaissance. Four chapters address the military: Current State of Space Operations; Satellite Killers and Hypersonic Drones; Space Electronic Warfare, Jamming, Spoofing, and ECD; and the challenges of Manufacturing in Space. SECTION 2: Space Challenges and Operations covers in five chapters a wide purview of challenges that result from operations in Space, such as Exploration of Key Infrastructure Vulnerabilities from Space-Based Platforms; Trash Collection and Tracking in Space; Leveraging Space for Disaster Risk Reduction and Management; Bio-threats to Agriculture and Solutions From Space; and rounding out the lineup is a chapter on Modelling, Simulation, and Extended Reality. SECTION 3: Humanitarian Use of Space Technologies is our DREAMERS section. It introduces effective use of Drones and Precision Agriculture; and Civilian Use of Space for Environmental, Wildlife Tracking, and Fire Risk Zone Identification. SECTION 3 is our Hope for Humanity and Positive Global Change. Just think if the technologies we discuss, when put into responsible hands, could increase food production by 1-2%. How many more millions of families could have food on their tables? State-of-the-Art research by a team of fifteen SMEs is incorporated into our book. We trust you will enjoy reading it as much as we have in its writing. There is hope for the future.https://newprairiepress.org/ebooks/1047/thumbnail.jp