Espanola Walkability Workshop

The City of Española, University of New Mexico’s Prevention Research Center, National Park Service, and New Mexico Department of Health led a walkability workshop at Española’s Beatrice V.Q. Martinez Senior Center on June 27, 2018. More than fifty people came together to evaluate and discuss pedestrian safety and accessibility within the City. The three and a half hour workshop began with a presentation on pedestrian planning, signage, and economic development by Marcy DeMillion of the National Park Service’s Rivers, Trails, and Conservation Assistance program. The Department of Health’s Rachel Wexler discussed some of the health and social benefits of walking. Jeff DeBellis and Alison Gillette, with the University of New Mexico’s Prevention Research Center and the City of Española’s Planning Department, respectively, gave an overview of the walkability audit that the participants would complete

Downtown Raton Walkability Workshop Report.

Ramblin’ Round Raton (RRR) aims to promote healthy lifestyles through walking and hiking in Raton and on nearby public lands. Research shows that walking can help us live longer and feel better. Ramblin’ Round Raton promotes use of walkways and trails on public land. It organizes and supports walking groups, sponsors walking events, advocates for walkable streets and highways, promotes the development of trails, and supports the enhancement of walking places. Ramblin’ Round Raton is supported by a coalition established by N.M. State Parks, N.M. Department of Health, Miners’ Colfax Medical Center, Rocky Mountain Physical Therapy, the City of Raton Department of Parks and Recreation, National Park Service, GrowRaton!, and the University of New Mexico Prevention Research Center

Quantized Nambu-Poisson Manifolds and n-Lie Algebras

We investigate the geometric interpretation of quantized Nambu-Poisson structures in terms of noncommutative geometries. We describe an extension of the usual axioms of quantization in which classical Nambu-Poisson structures are translated to n-Lie algebras at quantum level. We demonstrate that this generalized procedure matches an extension of Berezin-Toeplitz quantization yielding quantized spheres, hyperboloids, and superspheres. The extended Berezin quantization of spheres is closely related to a deformation quantization of n-Lie algebras, as well as the approach based on harmonic analysis. We find an interpretation of Nambu-Heisenberg n-Lie algebras in terms of foliations of R^n by fuzzy spheres, fuzzy hyperboloids, and noncommutative hyperplanes. Some applications to the quantum geometry of branes in M-theory are also briefly discussed.Comment: 43 pages, minor corrections, presentation improved, references adde

Ca2+ Homeostasis in the Agonist-sensitive Internal Store: Functional Interactions Between Mitochondria and the ER Measured In Situ in Intact Cells

Mitochondria have a well-established capacity to detect cytoplasmic Ca2+ signals resulting from the discharge of ER Ca2+ stores. Conversely, both the buffering of released Ca2+ and ATP production by mitochondria are predicted to influence ER Ca2+ handling, but this complex exchange has been difficult to assess in situ using conventional measurement techniques. Here we have examined this interaction in single intact BHK-21 cells by monitoring intraluminal ER [Ca2+] directly using trapped fluorescent low-affinity Ca2+ indicators. Treatment with mitochondrial inhibitors (FCCP, antimycin A, oligomycin, and rotenone) dramatically prolonged the refilling of stores after release with bradykinin. This effect was largely due to inhibition of Ca2+ entry pathways at the plasma membrane, but a significant component appears to arise from reduction of SERCA-mediated Ca2+ uptake, possibly as a consequence of ATP depletions in a localized subcellular domain. The rate of bradykinin-induced Ca2+ release was reduced to 51% of control by FCCP. This effect was largely overcome by loading cells with BAPTA-AM, highlighting the importance of mitochondrial Ca2+ buffering in shaping the release kinetics. However, mitochondria-specific ATP production was also a significant determinant of the release dynamic. Our data emphasize the localized nature of the interaction between these organelles, and show that competent mitochondria are essential for generating explosive Ca2+ signals

Magneto-plasmonic heterodimers: Evaluation of different synthesis approaches

Nanomedicine has gained huge attention in recent years with new approaches in medical diagnosis and therapy. Particular consideration has been devoted to the nanoparticles (NPs) in theranostic field with specific interest for magnetic and gold NPs (MNPs and GNPs) due to their peculiar properties under exposition to electromagnetic fields. In this paper, we aim to develop magneto-plasmonic heterodimer by combining MNPs and GNPs through a facile and reproducible synthesis and to investigate the influence of different synthesis parameters on their response to magnetic and optical stimuli. In particular, various syntheses were performed by changing the functionalization step and using or not a reducing agent to obtain stable NP suspensions with tailored properties. The obtained heterodimers were characterized through physical, chemical, optical, and magnetic analysis, in order to evaluate their size, shape, plasmonic properties, and superparamagnetic behavior. The results revealed that the shape and dimensions of the nanocomposites can be tuned by MNPs surface functionalization, as well as by the use of a reducing agent, giving rise to nanoplatform suitable for biomedical application, exploiting the gold absorbing peak in the specific gold absorbing range of GNPs, while maintaining the superparamagnetic behavior typical of the MNPs. The obtained nanocomposites can be proposed as potential candidates for cancer theranostics

A Reassessment of the Effects of Luminal [Ca2+] on Inositol 1,4,5-Trisphosphate-induced Ca2+ Release from Internal Stores

Inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release from intracellular stores displays complex kinetic behavior. While it well established that cytosolic [Ca2+] can modulate release by acting on the InsP3 receptor directly, the role of the filling state of internal Ca2+stores in modulating Ca2+ release remains unclear. Here we have reevaluated this topic using a technique that permits rapid and reversible changes in free [Ca2+] in internal stores of living intact cells without altering cytoplasmic [Ca2+], InsP3 receptors, or sarcoendoplasmic reticulum Ca2+ ATPases (SERCAs). N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylene diamine (TPEN), a membrane-permeant, low affinity Ca2+ chelator was used to manipulate [Ca2+] in intracellular stores, while [Ca2+] changes within the store were monitored directly with the low-affinity Ca2+ indicator, mag-fura-2, in intact BHK-21 cells. 200 microM TPEN caused a rapid drop in luminal free [Ca2+] and significantly reduced the extent of the response to stimulation with 100 nm bradykinin, a calcium-mobilizing agonist. The same effect was observed when intact cells were pretreated with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid(acetoxymethyl ester) (BAPTA-AM) to buffer cytoplasmic [Ca2+] changes. Although inhibition of Ca2+ uptake using the SERCA inhibitor tBHQ permitted significantly larger release of Ca2+ from stores, TPEN still attenuated the release in the presence of tBHQ in BAPTA-AM-loaded cells. These results demonstrate that the filling state of stores modulates the magnitude of InsP3-induced Ca2+release by additional mechanism(s) that are independent of regulation by cytoplasmic [Ca2+] or effects on SERCA pumps

Extracellular calcium acts as a “third messenger” to regulate enzyme and alkaline secretion

It is generally assumed that the functional consequences of stimulation with Ca2+-mobilizing agonists are derived exclusively from the second messenger action of intracellular Ca2+, acting on targets inside the cells. However, during Ca2+ signaling events, Ca2+ moves in and out of the cell, causing changes not only in intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous cell types possess an extracellular Ca2+ “sensor” raises the question of whether these dynamic changes in external [Ca2+] may serve some sort of messenger function. We found that in intact gastric mucosa, the changes in extracellular [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were sufficient and necessary to elicit alkaline secretion and pepsinogen secretion, independent of intracellular [Ca2+] changes. These findings suggest that extracellular Ca2+ can act as a “third messenger” via Ca2+ sensor(s) to regulate specific subsets of tissue function previously assumed to be under the direct control of intracellular Ca2+

NKCC2 activity is inhibited by the Bartter's syndrome type 5 gain-of-function CaR-A843E mutant in renal cells.

The gain-of-function A843E mutation of the calcium sensing receptor (CaR) causes Bartter syndrome type 5. Patients carrying this CaR variant show a remarkably reduced renal NaCl reabsorption in the thick ascending limb (TAL) of Henle's loop resulting in renal loss of NaCl in the absence of mutations in renal Na(+) and Cl(-) ion transporters. The molecular mechanisms underlying this clinical phenotype are incompletely understood. We investigated, in human embryonic kidney 293 (HEK 293) cells and porcine kidney epithelial (LLC-PK1) cells, the functional cross-talk of CaR-A843E with the Na(+):K(+):2Cl(-) co-transporter, NKCC2, which provides NaCl reabsorption in the TAL. RESULTS: The expression of the CaR mutant did not alter the apical localisation of NKCC2 in LLC-PK1 cells. However, the steady-state NKCC2 phosphorylation and activity were decreased in cells transfected with CaR-A843E compared with the control wild-type CaR (CaR WT)-transfected cells. Of note, low-Cl(-)-dependent NKCC2 activation was also strongly inhibited upon the expression of CaR-A843E mutant. The use of either P450 ω-hydroxylase (CYP4)- or phospholipase A2 (PLA2)-blockers suggests that this effect is likely mediated by arachidonic acid (AA) metabolites. CONCLUSIONS: The data suggested that the activated CaR affects intracellular pathways modulating NKCC2 activity rather than NKCC2 intracellular trafficking in renal cells, and throw further light on the pathological role played by active CaR mutants in Bartter syndrome type 5

The Fate of Intranasally Instilled Silver Nanoarchitectures

The intranasal administration of drugs allows an effective and noninvasive therapeutic action on the respiratory tract. In an era of rapidly increasing antimicrobial resistance, new approaches to the treatment of communicable diseases, especially lung infections, are urgently needed. Metal nanoparticles are recognized as a potential last-line defense, but limited data on the biosafety and nano/biointeractions preclude their use. Here, we quantitatively and qualitatively assess the fate and the potential risks associated with the exposure to a silver nanomaterial model (i.e., silver ultrasmall-in-nano architectures, AgNAs) after a single dose instillation. Our results highlight that the biodistribution profile and the nano/biointeractions are critically influenced by both the design of the nanomaterial and the chemical nature of the metal. Overall, our data suggest that the instillation of rationally engineered nanomaterials might be exploited to develop future treatments for (non)communicable diseases of the respiratory tract