The Dynamic Role of Breathing and Cellular Membrane Potentials in the Experience of Consciousness

Understanding the mechanics of consciousness remains one of the most important challenges in modern cognitive science. One key step toward understanding consciousness is to associate unconscious physiological processes with subjective experiences of sensory, motor, and emotional contents. This article explores the role of various cellular membrane potential differences and how they give rise to the dynamic infrastructure of conscious experience. This article explains that consciousness is a body-wide, biological process not limited to individual organs because the mind and body are unified as one entity; therefore, no single location of consciousness can be pinpointed. Consciousness exists throughout the entire body, and unified consciousness is experienced and maintained through dynamic repolarization during inhalation and expiration. Extant knowledge is reviewed to provide insight into how differences in cellular membrane potential play a vital role in the triggering of neural and non-neural oscillations. The role of dynamic cellular membrane potentials in the activity of the central nervous system, peripheral nervous system, cardiorespiratory system, and various other tissues (such as muscles and sensory organs) in the physiology of consciousness is also explored. Inspiration and expiration are accompanied by oscillating membrane potentials throughout all cells and play a vital role in subconscious human perception of feelings and states of mind. In addition, the role of the brainstem, hypothalamus, and complete nervous system (central, peripheral, and autonomic)within the mind-body space combine to allow consciousness to emerge and to come alive. This concept departs from the notion that the brain is the only organ that gives rise to consciousness

Development of a genetic tool for functional screening of anti-malarial bioactive extracts in metagenomic libraries

Ajuts: Departamento Administrativo de Ciencias, Tecnología e Innovación (Colciencias), República de Colombia; Convocatoria 489 - 2009, Código 657048925406, Contrato de financiación RC. 427 - 2009 Colciencias - CorpoGen; Programa de Asistencias Graduadas de Universidad de los Andes, Bogotá, Colombia; i Programa Jóvenes Investigadores de ColcienciasBACKGROUND: The chemical treatment of Plasmodium falciparum for human infections is losing efficacy each year due to the rise of resistance. One possible strategy to find novel anti-malarial drugs is to access the largest reservoir of genomic biodiversity source on earth present in metagenomes of environmental microbial communities. METHODS: A bioluminescent P. falciparum parasite was used to quickly detect shifts in viability of microcultures grown in 96-well plates. A synthetic gene encoding the Dermaseptin 4 peptide was designed and cloned under tight transcriptional control in a large metagenomic insert context (30 kb) to serve as proof-of-principle for the screening platform. RESULTS: Decrease in parasite viability consistently correlated with bioluminescence emitted from parasite microcultures, after their exposure to bacterial extracts containing a plasmid or fosmid engineered to encode the Dermaseptin 4 anti-malarial peptide. Here, a new technical platform to access the anti-malarial potential in microbial environmental metagenomes has been develope

Genome analysis and physiological comparison of Alicycliphilus denitrificans strains BC and K601T

The genomes of the Betaproteobacteria Alicycliphilus denitrificans strains BC and K601T have been sequenced to get insight into the physiology of the two strains. Strain BC degrades benzene with chlorate as electron acceptor. The cyclohexanol-degrading denitrifying strain K601T is not able to use chlorate as electron acceptor, while strain BC cannot degrade cyclohexanol. The 16S rRNA sequences of strains BC and K601T are identical and the fatty acid methyl ester patterns of the strains are similar. Basic Local Alignment Search Tool (BLAST) analysis of predicted open reading frames of both strains showed most hits with Acidovorax sp. JS42, a bacterium that degrades nitro-aromatics. The genomes include strain-specific plasmids (pAlide201 in strain K601T and pAlide01 and pAlide02 in strain BC). Key genes of chlorate reduction in strain BC were located on a 120 kb megaplasmid (pAlide01), which was absent in strain K601T. Genes involved in cyclohexanol degradation were only found in strain K601T. Benzene and toluene are degraded via oxygenase-mediated pathways in both strains. Genes involved in the meta-cleavage pathway of catechol are present in the genomes of both strains. Strain BC also contains all genes of the ortho-cleavage pathway. The large number of mono- and dioxygenase genes in the genomes suggests that the two strains have a broader substrate range than known thus far.This research was supported by the Technology Foundation, the Applied Science Division (STW) of the Netherlands Organization for Scientific Research (NWO), project number 08053, the graduate school WIMEK (Wageningen Institute for Environment and Climate Research, which is part of SENSE Research School for Socio-Economic and Natural Sciences of the Environment, www.wimek-new.wur.nl and www.sense.nl), SKB (Dutch Centre for Soil Quality Management and Knowledge Transfer, www.skbodem.nl) and the Consolider project CSD-2007-00055. The research was incorporated in the TRIAS (TRIpartite Approaches 469 toward Soil systems processes) program (http://www.nwo.nl/en/research-and-results/programmes/alw/trias-tripartite-approach-to-soil-system-processes/index. html). Flávia Talarico Saia was supported by a FAPESP (the State of São Paulo Research Foundation) scholarship (2006-01997/5). The work conducted by the DOE JGI is supported by the Office of Science of the United States Department of Energy under contract number DE-AC02-05CH11231. Alfons Stams acknowledges support by an ERC (European Research Counsil) advanced grant (project 323009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Persistence of Chronic Lymphocytic Leukemia Stem-like Populations under Simultaneous In Vitro Treatment with Curcumin, Fludarabine, and Ibrutinib: Implications for Therapy Resistance

Alkaline phosphatase; Curcumin; Flow cytometryFosfatasa alcalina; Curcumina; Citometria de fluxFosfatasa alcalina; Curcumina; Citometría de flujoLeukemic stem cells (LSCs) possess similar characteristics to normal hematopoietic stem cells, including self-renewal capacity, quiescence, ability to initiate leukemia, and drug resistance. These cells play a significant role in leukemia relapse, persisting even after apparent remission. LSCs were first described in 1994 by Lapidot et al. Although they have been extensively studied in acute leukemia, more LSC research is still needed in chronic lymphocytic leukemia (CLL) to understand if reduced apoptosis in mature cells should still be considered as the major cause of this disease. Here, we provide new evidence suggesting the existence of stem-like cell populations in CLL, which may help to understand the disease as well as to develop effective treatments. In this study, we identified a potential leukemic stem cell subpopulation using the tetraploid CLL cell line I83. This subpopulation is characterized by diploid cells that were capable of generating the I83 tetraploid population. Furthermore, we adapted a novel flow cytometry analysis protocol to detect CLL subpopulations with stem cell properties in peripheral blood samples and primary cultures from CLL patients. These cells were identified by their co-expression of CD19 and CD5, characteristic markers of CLL cells. As previously described, increased alkaline phosphatase (ALP) activity is indicative of stemness and pluripotency. Moreover, we used this method to investigate the potential synergistic effect of curcumin in combination with fludarabine and ibrutinib to deplete this subpopulation. Our results confirmed the effectiveness of this ALP-based analysis protocol in detecting and monitoring leukemic stem-like cells in CLL. This analysis also identified limitations in eradicating these populations using in vitro testing. Furthermore, our findings demonstrated that curcumin significantly enhanced the effects of fludarabine and ibrutinib on the leukemic fraction, exhibiting synergistic effects (combination drug index, CDI 0.97 and 0.37, respectively). Our results lend support to the existence of potential stem-like populations in CLL cell lines, and to the idea that curcumin could serve as an effective adjuvant in therapies aimed at eliminating these populations and improving treatment efficacy.Grant Sponsor: Thermo Fisher Scientific, Eugene, Oregon, USA. Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Spain (PI/17/0575 and PI 20/00531, co-funded by European Regional Development Fund. ERDF, a way to build Europe); CERCA, Centres de Recerca de Catalunya (2021 SGR 00560; 2021 SGR 00002); La Caixa Foundation, Obra Social la Caixa, Fundació Internacional Josep Carreras, Barcelona, Spain

Flow cytometric significance of cellular alkaline phosphatase activity in acute myeloid leukemia

In this prospective hospital-based cohort study that included 43 newly diagnosed patients with acute myeloid leukemia, flow cytometric cellular alkaline phosphatase (ALP) activity within primitive leukemic cells allowed us to identify two groups of patients at diagnosis according to the numbers of leukemic blasts expressing ≥ 12% of ALP+ cells (27 patients, Group A) and less than 12% of ALP+ cells (16 patients, Group B). Differences in outcome for complete response, relapse or treatment resistance, and exitus were statistically analyzed and were significant, when comparing the two groups. The overall survival (OS) and event-free survival (EFS) differences between Group A and B were statistically significant. The survival of Group A patients was significantly shorter than those for Group B. No significant relationship was detected in outcome when comparing ELN prognostic-risk group based on cytogenetic and molecular profile (patients in the favorable, intermediate, and adverse risk groups). Flow cytometric cellular ALP activity at diagnosis may be used to estimate relapses and disease persistence more accurately. The limitations of our study include the small number of patients enrolled and a short follow-up, due to its prospective nature

Unmasking the expression of PD-L1 in Myeloid Derived Suppressor Cells : a case study in lung cancer to discover new drugs with specific on-target efficacy

Altres ajuts: We thank CERCA Programme/Generalitat de Catalunya and The Josep Carreras Foundation for institutional support. The authors are also very grateful for their advice and technical support to Sergio Ramón, Víctor Querol, Clara Streiff, Paola Paglia, and Lluís Sainz from Thermo Fisher for all his comments and discussions on earlier work in this research field. Jordi Petriz also acknowledges the financial support from The Obra Social La Caixa and Thermo Fisher Scientific

Neutron imaging with a Micromegas detector

The micropattern gaseous detector Micromegas has been developed for several years in Saclay and presents good performance for neutron detection. A prototype for neutron imaging has been designed and new results obtained in thermal neutron beams are presented. Based on previous results demonstrating a good 1D spatial resolution, a tomographic image of a multiwire cable has been performed using a 1D Micromegas prototype. The number of pillars supporting the micromesh is too large and leads to local losses of efficiency that distort the tomographic reconstruction. Nevertheless, this first tomographic image achieved with this kind of detector is very encouraging. The next worthwhile development for neutron imaging is to achieve a bi-dimensional detector, which is presented in the second part of this study. The purpose of measurements was to investigate various operational parameters to optimize the spatial resolution. Through these measurements the optimum spatial resolution has been found to be around 160 microns (standard deviation) using Micromegas operating in double amplification mode. Several 2D imaging tests have been carried out. Some of these results have revealed fabrication defects that occurred during the manufacture of Micromegas and that are limiting the full potential of the present neutron imaging system.Comment: 6 pages, 10 figures, presented at IEEE 2004 conference in Roma, Ital

DEFINICIÓN DE UN MODELO DE SEGURIDAD PARA LA RED DE INVESTIGACIÓN DE TECNOLOGÍA AVANZADA DE LA UNIVERSIDAD DISTRITAL “FRANCISCO JOSÉ DE CALDAS” RITA-UD

Uno de los aspectos más importantes dentro de las networking se relaciona con la protección de la información. Este trabajo permite identificar los aspectos más importantes a considerar en la definición de un modelo de seguridad para la red de investigación de tecnología avanzada de la Universidad Distrital Francisco José de Caldas RITA-UD basado en la aplicación de las normas ISO27001 y NTC-ISO/IEC17799.El diseño final obtenido es una propuesta para la implementación de un Firewall Cisco ASA5520

Análisis de Recepción Sobre la Narco Serie "Pablo Escobar: el Patrón del Mal" y su Influencia en las Nuevas Generaciones

Realizar un análisis de recepción de audiencias con base en la narcoserie 'Pablo Escobar: el patrón del mal' con el fin de demostrar las interacciones del producto en una población juvenil.En el presente trabajo se desarrolla un análisis de recepción con el fin de determinar si la narcoserie “Pablo Escobar: el patrón del mal” tiene influencia en la población juvenil. Para esta investigación se tomó una población de jóvenes entre los 18 (dieciocho) y 21 (veintiún) años, la cual se dividió en dos grupos focales, el primer grupo con estudiantes de la Corporación Universitaria Minuto de Dios (Centro Regional Girardot) y el segundo, con jóvenes habitantes del barrio Portachuelo de Girardot. Para este análisis se tomaron en cuenta referentes teóricos de las teorías de comunicación como el funcionalismo, la Escuela de Frankfurt y los estudios sobre recepción de Guillermo Orozco Gómez, con el fin de cotejar los conceptos seminales de la comunicación como disciplina, campo y objeto de estudio con las percepciones de las audiencias.In the present work, an analysis of content and reception is developed in order to know if the narco series Pablo Escobar: el patron del mal has an influence on the youth population. For this research, a population of young people between 18 (eighteen) and 21 (twenty-one) years old was taken, which was divided into two focus groups, the first group with students from the Minuto de Dios University Corporation (Girardot regional headquarters) and the second, with young residents of the Portachuelo de Girardot neighborhood. For this analysis, the study of the members of the Frankfurt School and the studies on reception by Guillermo Orozco were taken into account, in order to understand a little more the work of the media and the receiver

Motile sperm organelle morphology examination (MSOME): intervariation study of normal sperm and sperm with large nuclear vacuoles

<p>Abstract</p> <p>Background</p> <p>Although the motile sperm organelle morphology examination (MSOME) was developed only as a selection criterion, its application as a method for classifying sperm morphology may represent an improvement in evaluation of semen quality, with potential clinical repercussions. The present study aimed to evaluate individual variations in the motile sperm organelle morphology examination (MSOME) analysis after a time interval.</p> <p>Methods</p> <p>Two semen samples were obtained from 240 men from an unselected group of couples undergoing infertility investigation and treatment. Mean time interval between the two semen evaluations was 119 +/- 102 days. No clinical or surgical treatment was realized between the two observations. Spermatozoa were analyzed at greater than or equal to 8400× magnification by inverted microscope equipped with DIC/Nomarski differential interference contrast optics. At least 200 motile spermatozoa per semen sample were evaluated and percentages of normal spermatozoa and spermatozoa with large nuclear vacuoles (LNV/one or more vacuoles occupying >50% of the sperm nuclear area) were determined. A spermatozoon was classified as morphologically normal when it exhibited a normal nucleus (smooth, symmetric and oval nucleus, width 3.28 +/- 0.20 μm, length 4.75 +/- 0.20 μm/absence of vacuoles occupying >4% of nuclear area) as well as acrosome, post-acrosomal lamina, neck and tail, besides not presenting cytoplasm around the head. One examiner, blinded to subject identity, performed the entire study.</p> <p>Results</p> <p>Mean percentages of morphologically normal and LNV spermatozoa were identical in the two MSOME analyses (1.6 +/- 2.2% vs. 1.6 +/- 2.1% <it>P </it>= 0.83 and 25.2 +/- 19.2% vs. 26.1 +/- 19.0% <it>P </it>= 0.31, respectively). Regression analysis between the two samples revealed significant positive correlation for morphologically normal and for LNV spermatozoa (r = 0.57 95% CI:0.47-0.65 <it>P </it>< 0.0001 and r = 0.50 95% CI:0.38-0.58 <it>P </it>< 0.0001, respectively).</p> <p>Conclusions</p> <p>The significant positive correlation and absence of differences between two sperm samples evaluated after a time interval with respect to normal morphology and LNV spermatozoa indicated that MSOME seems reliable (at least for these two specific sperm forms) for analyzing semen. The present result supports the future use of MSOME as a routine method for semen analysis.</p