Acid-sensing ion channels 1a (ASIC1a) inhibit neuromuscular transmission in female mice

Acid-sensing ion channels (ASIC) open in response to extracellular acidosis. ASIC1a, a particular subtype of these channels, has been described to have a postsynaptic distribution in the brain, being involved not only in ischemia and epilepsy, but also in fear and psychiatric pathologies. High-frequency stimulation of skeletal motor nerve terminals (MNTs) can induce presynaptic pH changes in combination with an acidification of the synaptic cleft, known to contribute to muscle fatigue. Here, we studied the role of ASIC1a channels on neuromuscular transmission. We combined a behavioral wire hanging test with electrophysiology, pharmacological, and immunofluorescence techniques to compare wild-type and ASIC1a lacking mice (ASIC1a −/− knockout). Our results showed that 1) ASIC1a −/− female mice were weaker than wild type, presenting shorter times during the wire hanging test; 2) spontaneous neurotransmitter release was reduced by ASIC1a activation, suggesting a presynaptic location of these channels at individual MNTs; 3) ASIC1a-mediated effects were emulated by extracellular local application of acid saline solutions (pH = 6.0; HEPES/MES-based solution); and 4) immunofluorescence techniques revealed the presence of ASIC1a antigens on MNTs. These results suggest that ASIC1a channels might be involved in controlling neuromuscular transmission, muscle contraction and fatigue in female mice.Fil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Lino, Noelia Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: González Inchauspe, Carlota María Fabiola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Gonzalez, Laura Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Wunsch, Amanda M.. University of Iowa; Estados UnidosFil: Wemmie, John A.. University of Iowa; Estados UnidosFil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Dimensions of Religiousness and Cancer Screening Behaviors among Church-Going Latinas

Churches are a promising setting through which to reach Latinas with cancer control efforts. A better understanding of the dimensions of religiousness that impact health behaviors could inform efforts to tailor cancer control programs for this setting. The purpose of this study was to explore relationships between dimensions of religiousness with adherence to cancer screening recommendations among church-going Latinas. Female Spanish-speaking members, aged 18 and older from a Baptist church in Boston, Massachusetts (N = 78), were interviewed about cancer screening behaviors and dimensions of religiousness. We examined adherence to individual cancer screening tests (mammography, Pap test, and colonoscopy), as well as adherence to all screening tests for which participants were age-eligible. Dimensions of religiousness assessed included church participation, religious support, active and passive spiritual health locus of control, and positive and negative religious coping. Results showed that roughly half (46 %) of the sample had not received all of the cancer screening tests for which they were age-eligible. In multivariate analyses, positive religious coping was significantly associated with adherence to all age-appropriate screening (OR = 5.30, p \u3c .01). Additional research is warranted to replicate these results in larger, more representative samples and to examine the extent to which enhancement of religious coping could increase the impact of cancer control interventions for Latinas

Heterogeneous Photocatalytic Degradation of Ibuprofen Over TiO2–Ag Supported on Activated Carbon from Waste Tire Rubber

In recent years it has been discovered that some common use medicines, such as ibuprofen and other nonsteroidal anti-inflammatory drugs, are found in water sources in concentrations that have the potential to affect aquatic organisms. On the other hand, waste used tires are a massive problem for the environment due to the leaching of toxic compounds to soils and water. Also, the exposition to environmental conditions can make them sources of vectors like mosquitoes. In this work, three activated carbon (AC) catalysts derived from waste tire rubber, titanium dioxide and silver were synthesized using the sol–gel method. Morphological characterizations such as SEM and TEM were performed in which, the agglomeration of titanium particles and silver crystals on the surface of the AC is evident. In the XRD analysis, the presence of elemental silver nanoparticles was detected. In the diffuse reflectance spectroscopy analysis, the decrease in the titanium band gap, as well as activity in the visible spectrum, was observed. The photocatalytic tests were performed at pH 3 and 7 in the presence of UV/Vis radiation. These tests show that there are differences between the catalyst in both, UV and visible regions. Adsorption is a major phenomenon for the removal of ibuprofen, followed by photolytic decomposition. In visible spectra, the catalysts show a good performance for the removal of ibuprofen

Effect of Steel Fibre Reinforcement on Flexural Fatigue Behaviour of Notched Structural Concrete

ABSTARCT: One of the biggest challenges in facilitating the installation of concrete is the development of fibre-reinforced concrete. Although nowadays fibre reinforced concrete is relatively common, it is still necessary to deepen in the study on its behaviour, especially regarding its fatigue behaviour. This paper proposes a new methodology to analyse the bending fatigue behaviour of notched test specimens. From these tests, it was possible to verify that, despite carrying out the tests with load control, the presence of fibres extends the fatigue life of the concrete after cracking. This effect is of great importance since during the extra lifetime with the cracked concrete, the damage to the concrete will be evident and the corresponding maintenance measures can be carried out. Regarding the analysis of the results, in addition to obtaining a traditional S-N curve, two new criteria have been applied, namely energy and notch growth. From these two new approaches, it was possible to determine critical energy values that can be used as predictive indicators of the collapse of the element. Moreover, from the notch growth analysis, it was possible to determine crack growth rate as a function of the stress conditions for the concrete and the specific geometry. From the comparison among the results obtained from the different tests, a limit cracking index of 0.05 mm can be defined

Recycled polyethylene fibres for structural concrete

Modern society demands more sustainable and economical construction elements. One of the available options for manufacturing this type of element is the valorisation of end-of-life waste, such as, for example, the recycling of polymers used in industry. The valorisation of these wastes reduces costs and avoids the pollution generated by their landfill disposal. With the aim of helping to obtain this type of material, this work describes a methodology for recycling polyethylene for the manufacture of fibres that will later be used as reinforcement for structural concrete. These fibres are manufactured using an injection moulding machine. Subsequently, their physical and mechanical properties are measured and compared with those of the material before it is crushed and injected. The aim of this comparison is to evaluate the recycling process and analyse the reduction of the physical-mechanical properties of the recycled polyethylene in the process. Finally, to determine the properties of the fibre concrete, three types of concrete were produced: a control concrete, a reinforced concrete with 2 kg/m³ of fibres, and a reinforced concrete with 4 kg/m³ of fibres. The results show an enhancement of mechanical properties when the fibres are incorporated, particularly the tensile strength; and they also show excellent performance controlling cracking in concrete.This research was funded by the LADICIM (Laboratory of Materials Science and Engineering), Universidad de Cantabria. E.T.S. de Ingenieros de Caminos, Canales y Puertos, Av./Los Castros 44, 39005 Santander, Spain

Cancer cell plasticity defines response to immunotherapy in cutaneous squamous cell carcinoma

Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune checkpoint (IC) ligand profile according to their features, dictating the IC pathways involved in immune evasion. Epithelial cancer cells, through the PD-1/PD-L1 pathway, and mesenchymal cancer cells, through the CTLA-4/CD80 and TIGIT/CD155 pathways, differentially block antitumor immune responses and determine the response to ICB therapies. Accordingly, the anti-PD-L1/TIGIT combination is the most effective strategy for blocking the growth of cSCCs that contain both epithelial and mesenchymal cancer cells. The expression of E-cadherin/Vimentin/CD80/CD155 proteins in cSCC, HNSCC and melanoma patient samples predicts response to anti-PD-1/PD-L1 therapy. Collectively, our findings indicate that the selection of ICB therapies should take into account the epithelial/mesenchymal features of cancer cells. Immune surveillance is critical to prevent the development and progression of cutaneous squamous cell carcinoma (cSCC). Here, the authors show that epithelial-mesenchymal plasticity in cancer cells is associated with changes in their immune checkpoint ligand profile during mouse cSCC progression, which dictates differential responses to immune checkpoint blockade

Symptom-led staging for semantic and non-fluent/agrammatic variants of primary progressive aphasia

INTRODUCTION: Here we set out to create a symptom-led staging system for the canonical semantic and non-fluent/agrammatic variants of primary progressive aphasia (PPA), which present unique diagnostic and management challenges not well captured by functional scales developed for Alzheimer's disease and other dementias. METHODS: An international PPA caregiver cohort was surveyed on symptom development under six provisional clinical stages and feedback was analyzed using a mixed-methods sequential explanatory design. RESULTS: Both PPA syndromes were characterized by initial communication dysfunction and non-verbal behavioral changes, with increasing syndromic convergence and functional dependency at later stages. Milestone symptoms were distilled to create a prototypical progression and severity scale of functional impairment: the PPA Progression Planning Aid ("PPA-Squared"). DISCUSSION: This work introduces a symptom-led staging scheme and functional scale for semantic and non-fluent/agrammatic variants of PPA. Our findings have implications for diagnostic and care pathway guidelines, trial design, and personalized prognosis and treatment for PPA. HIGHLIGHTS: We introduce new symptom-led perspectives on primary progressive aphasia (PPA). The focus is on non-fluent/agrammatic (nfvPPA) and semantic (svPPA) variants. Foregrounding of early and non-verbal features of PPA and clinical trajectories is featured. We introduce a symptom-led staging scheme for PPA. We propose a prototype for a functional impairment scale, the PPA Progression Planning Aid

Turismo y Género. Una mirada desde Iberoamérica

En las últimas cuatro décadas ha crecido el interés de la academia, gobiernos y organizaciones internacionales por estudiar cómo ha sido, en qué circunstancias y qué efectos ha traído la incorporación de las mujeres al turismo. De esta forma se inicia un debate internacional en el que se cuestionan, por un lado, los efectos negativos de esta actividad en la vida de las mujeres y, por el otro, se realzan beneficios económicos que mejoran su calidad de vida y la de sus familias. A pesar del interés y la importante participación de mujeres en el sector turístico, aún son insuficientes los estudios enfocados en explicar y evidenciar su situación laboral. En este contexto, surge la idea de publicar un libro que compilara trabajos recientes en torno a las condiciones de las trabajadoras en el sector turístico de Iberoamérica.Esta obra se compone de tres secciones, Aproximaciones teórico metodológicas, Mujer y turismo en zonas rurales y La mujer en empresas turísticas, cuyas investigaciones abordan distintos temas para evidenciar los problemas enfrentados por las mujeres, proponer diversas soluciones y comprender su escenario laboral. En la primera sección, hay dos capítulos que proponen marcos teóricos para analizar el empoderamiento de las mujeres en el turismo rural. Los resultados de investigaciones de la segunda sección visibilizan las desigualdades, reflexionan y proponen acciones para mejorar las condiciones de las trabajadoras turísticas. En la última, en los tres capítulos, concentrados en las actividades empresariales, se estudian las desventajas y obstáculos de la empleada en alguna compañía turística.Universidad Autónoma del Estado de México

Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p>Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by γ-radiation.</p> <p>Methods</p> <p>To explore this hypothesis, 246 GC cases and 246 matched controls were recruited in our case-control study. TRAP-ELISA was used to assess the levels of telomerase activity at baseline and after γ-radiation and the γ-radiation-induced telomerase activity (defined as after γ-irradiation/baseline) in cultured peripheral blood lymphocytes (PBLs).</p> <p>Results</p> <p>Our data showed that there was no significant difference for the baseline telomerase activity between GC cases and controls (10.17 ± 7.21 <it>vs. </it>11.02 ± 8.03, <it>p </it>= 0.168). However, after γ-radiation treatment, γ-radiation-induced telomerase activity was significantly higher in the cases than in the controls (1.51 ± 0.93 <it>vs</it>. 1.22 ± 0.66, <it>p </it>< 0.001). Using the median value of γ-radiation-induced telomerase activity in the controls as a cutoff point, we observed that high γ-radiation-induced telomerase activity was associated with a significantly increased GC risk (adjusted odds ratio, 2.45; 95% confidence interval, 1.83-3.18). Moreover, a dose response association was noted between γ-radiation-induced telomerase activity and GC risk. Age, but not sex, smoking and drinking status seem to have a modulating effect on the γ-radiation-induced telomerase activities in both cases and controls.</p> <p>Conclusion</p> <p>Overall, our findings for the first time suggest that the increased γ-radiation-induced telomerase activity in PBLs might be associated with elevated GC risk. Further confirmation of this association using a prospective study design is warranted.</p