La Crisis Antropológica de la Innovación Científica

This articles suggests that the root of the current crisis in modern scientific innovation is mainly due to the method that science applies towards the real world. The scientific method reduces its possibilities by not considering the comprehensiveness of the human person, i.e. science is impersonal. Philosophers of science in the 20th century have identified this anthropological reductionism and further detected the limits of the scientific method. The lack of alternative solutions leads science into a cul-de-sac. The notion of crisis, recently pointed out by Leonardo Polo’s Transcendental Anthropology, allows us to detect the limit, to abandon that limit and to open knowledge to further dimensions of unrestricted novelty such as freedom or love. Here we highlight the following distinctions: firstly, the state of crisis and the critical conscience, secondly, the ‘desperate vs. puzzle-solver’ critical conscience, thirdly, the limit of science and its abandonment.Proponemos que la actual crisis de innovación en la ciencia moderna radica en las limitaciones que aparecen en el método experimental cuando se ejerce al margen de la integralidad de la persona humana. La conciencia crítica de los filósofos de la ciencia del siglo XX ha puesto de manifiesto esta despersonalización de la ciencia y ha detectado los límites del método científico; sin embargo, al no encontrar alternativas de superación ha dejado a la ciencia en una situación de desesperanza. La noción de crisis a partir de la Antropología Trascendental de Leonardo Polo permite –además de detectar el límite– abandonarlo y abrir el conocimiento a temas de novedad irrestricta: la libertad y el amor. Tres son las distinciones que aborda este trabajo: 1) estar en crisis y la conciencia crítica, 2) la conciencia crítica desesperada y la conciencia crítica solucionadora; 3) el límite y su abandono.Proponemos que la actual crisis de innovación en la ciencia moderna radica en las limitaciones que aparecen en el método experimental cuando se ejerce al margen de la integralidad de la persona humana. La conciencia crítica de los filósofos de la ciencia del siglo XX ha puesto de manifi esto esta despersonalización de la ciencia y ha detectado los límites del método científico; sin embargo, al no encontrar alternativas de superación ha dejado a la ciencia en una situación de desesperanza. La noción de crisis a partir de la Antropología Trascendental de Leonardo Polo permite –además de detectar el límite– abandonarlo y abrir el conocimiento a temas de novedad irrestricta: la libertad y el amor. Tres son las distinciones que aborda este trabajo: 1) estar en crisis y la conciencia crítica, 2) la conciencia crítica desesperada y la conciencia crítica solucionadora; 3) el límite y su abandono. 

La Crisis Antropológica de la Innovación Científica

Proponemos que la actual crisis de innovación en la ciencia moderna radica en las limitaciones que aparecen en el método experimental cuando se ejerce al margen de la integralidad de la persona humana. La conciencia crítica de los filósofos de la ciencia del siglo XX ha puesto de manifiesto esta despersonalización de la ciencia y ha detectado los límites del método científico; sin embargo, al no encontrar alternativas de superación ha dejado a la ciencia en una situación de desesperanza. La noción de crisis a partir de la Antropología Trascendental de Leonardo Polo permite además de detectar el límite abandonarlo y abrir el conocimiento a temas de novedad irrestricta: la libertad y el amor. Tres son las distinciones que aborda este trabajo: 1) estar en crisis y la conciencia crítica, 2) la conciencia crítica desesperada y la conciencia crítica solucionadora; 3) el límite y su abandono.This articles suggests that the root of the current crisis in modern scientific innovation is mainly due to the method that science applies towards the real world. The scientific method reduces its possibilities by not considering the comprehensiveness of the human person, i.e. science is impersonal. Philosophers of science in the 20th century have identified this anthropological reductionism and further detected the limits of the scientific method. The lack of alternative solutions leads science into a cul-de-sac. The notion of crisis, recently pointed out by Leonardo Polo’s Transcendental Anthropology, allows us to detect the limit, to abandon that limit and to open knowledge to further dimensions of unrestricted novelty such as freedom or love. Here we highlight the following distinctions: firstly, the state of crisis and the critical conscience, secondly, the ‘desperate vs. puzzle-solver’ critical conscience, thirdly, the limit of science and its abandonment

El paradigma neurogenómico: La libertad y las dimensiones antropológicas del paciente

La ciencia experimental introduce sistemáticamente una división entre cuerpo- mente-espíritu. La unidad antropológica está ausente en el curso de la aplicación del método. Esta crisis incrementa la incidencia de enfermedades con entidad epidémica para las que cualquier sistema sanitario es insuficiente. Un cuidado terapéutico abierto a la integración de la libertad y otras dimensiones antropológicas consigue superar las distorsiones en la comprensión del paciente generadas por un omnipresente paradigma terapéutico limitado.The experimental scientific method disengages the body from the mind and the spirit. Ascertaining the meaning of each individual may overcome the methodological limitations within the current scientific paradigm. The noetic clues afforded by Neurogenomics via an integrative anthropological perspective should pave the way to heal the individual who feels ill, at the heart of his or her disease

Shared apical sorting of anion exchanger isoforms AE2a, AE2b1, and AE2b2 in primary hepatocytes

AE2 (SLC4A2) is the member of the Na(+)-independent anion exchanger (AE) family putatively involved in the secretion of bicarbonate to bile. In humans, three variants of AE2 mRNA have been described: the full-length transcript AE2a (expressed from the upstream promoter in most tissues), and alternative transcripts AE2b(1) and AE2b(2) (driven from alternate promoter sequences in a tissue-restricted manner, mainly in liver and kidney). These transcripts would result in AE protein isoforms with short N-terminal differences. To ascertain their translation, functionality, and membrane sorting, we constructed expression vectors encoding each AE2 isoform fused to GFP at the C-terminus. Transfected HEK293 cells showed expression of functional GFP-tagged AE2 proteins, all three isoforms displaying comparable AE activities. Primary rat hepatocytes transfected with expression vectors and repolarized in a collagen-sandwich configuration showed a microtubule-dependent apical sorting of each AE2 isoform. This shared apical sorting is liver-cell specific, as sorting of AE2 isoforms was basolateral in control experiments on polarized kidney MDCK cells. Hepatocytic apical targeting of AE2 isoforms suggests that they all may participate in the canalicular secretion of bicarbonate to bile

Oral Methylthioadenosine Administration Attenuates Fibrosis and Chronic Liver Disease Progression in Mdr2−/− Mice

BACKGROUND: Inflammation and fibrogenesis are directly related to chronic liver disease progression, including hepatocellular carcinoma (HCC) development. Currently there are few therapeutic options available to inhibit liver fibrosis. We have evaluated the hepatoprotective and anti-fibrotic potential of orally-administered 5'-methylthioadenosine (MTA) in Mdr2(-/-) mice, a clinically relevant model of sclerosing cholangitis and spontaneous biliary fibrosis, followed at later stages by HCC development. METHODOLOGY: MTA was administered daily by gavage to wild type and Mdr2(-/-) mice for three weeks. MTA anti-inflammatory and anti-fibrotic effects and potential mechanisms of action were examined in the liver of Mdr2(-/-) mice with ongoing fibrogenesis and in cultured liver fibrogenic cells (myofibroblasts). PRINCIPAL FINDINGS: MTA treatment reduced hepatomegaly and liver injury. α-Smooth muscle actin immunoreactivity and collagen deposition were also significantly decreased. Inflammatory infiltrate, the expression of the cytokines IL6 and Mcp-1, pro-fibrogenic factors like TGFβ2 and tenascin-C, as well as pro-fibrogenic intracellular signalling pathways were reduced by MTA in vivo. MTA inhibited the activation and proliferation of isolated myofibroblasts and down-regulated cyclin D1 gene expression at the transcriptional level. The expression of JunD, a key transcription factor in liver fibrogenesis, was also reduced by MTA in activated myofibroblasts. CONCLUSIONS/SIGNIFICANCE: Oral MTA administration was well tolerated and proved its efficacy in reducing liver inflammation and fibrosis. MTA may have multiple molecular and cellular targets. These include the inhibition of inflammatory and pro-fibrogenic cytokines, as well as the attenuation of myofibroblast activation and proliferation. Downregulation of JunD and cyclin D1 expression in myofibroblasts may be important regarding the mechanism of action of MTA. This compound could be a good candidate to be tested for the treatment of (biliary) liver fibrosis

¿Ketamina para una epidemia espiritual? La libertad y las dimensiones antropológicas del paciente

(The Neurogenomic Paradigm. Anthropological Dimensions and Freedom in the Care of the Patient)The experimental scientific method disengages the body from the mind and the spirit. Ascertaining the meaning of each individual may overcome the methodological limitations within the current scientific paradigm. The noetic clues afforded by Neurogenomics via an integrative anthropological perspective should pave the way to heal the individual who feels ill, at the heart of his or her disease.La ciencia experimental introduce sistemáticamente una división entre cuerpo-mente-espíritu. La unidad antropológica está ausente en el curso de la aplicación del método. Esta crisis incrementa la incidencia de enfermedades con entidad epidémica para las que cualquier sistema sanitario es insuficiente. Un cuidado terapéutico abierto a la integración de la libertad y otras dimensiones antropológicas consigue superar las distorsiones en la comprensión del paciente generadas por un omnipresente paradigma terapéutico limitado

La Crisis Antropológica de la Innovación Científica

Proponemos que la actual crisis de innovación en la ciencia moderna radica en las limitaciones que aparecen en el método experimental cuando se ejerce al margen de la integralidad de la persona humana. La conciencia crítica de los filósofos de la ciencia del siglo XX ha puesto de manifiesto esta despersonalización de la ciencia y ha detectado los límites del método científico; sin embargo, al no encontrar alternativas de superación ha dejado a la ciencia en una situación de desesperanza. La noción de crisis a partir de la Antropología Trascendental de Leonardo Polo permite además de detectar el límite abandonarlo y abrir el conocimiento a temas de novedad irrestricta: la libertad y el amor. Tres son las distinciones que aborda este trabajo: 1) estar en crisis y la conciencia crítica, 2) la conciencia crítica desesperada y la conciencia crítica solucionadora; 3) el límite y su abandono.This articles suggests that the root of the current crisis in modern scientific innovation is mainly due to the method that science applies towards the real world. The scientific method reduces its possibilities by not considering the comprehensiveness of the human person, i.e. science is impersonal. Philosophers of science in the 20th century have identified this anthropological reductionism and further detected the limits of the scientific method. The lack of alternative solutions leads science into a cul-de-sac. The notion of crisis, recently pointed out by Leonardo Polo’s Transcendental Anthropology, allows us to detect the limit, to abandon that limit and to open knowledge to further dimensions of unrestricted novelty such as freedom or love. Here we highlight the following distinctions: firstly, the state of crisis and the critical conscience, secondly, the ‘desperate vs. puzzle-solver’ critical conscience, thirdly, the limit of science and its abandonment

El paradigma neurogenómico: La libertad y las dimensiones antropológicas del paciente

La ciencia experimental introduce sistemáticamente una división entre cuerpo- mente-espíritu. La unidad antropológica está ausente en el curso de la aplicación del método. Esta crisis incrementa la incidencia de enfermedades con entidad epidémica para las que cualquier sistema sanitario es insuficiente. Un cuidado terapéutico abierto a la integración de la libertad y otras dimensiones antropológicas consigue superar las distorsiones en la comprensión del paciente generadas por un omnipresente paradigma terapéutico limitado.The experimental scientific method disengages the body from the mind and the spirit. Ascertaining the meaning of each individual may overcome the methodological limitations within the current scientific paradigm. The noetic clues afforded by Neurogenomics via an integrative anthropological perspective should pave the way to heal the individual who feels ill, at the heart of his or her disease

Estrogen and progesterone regulate p27kip1 levels via the ubiquitin-proteasome system: pathogenic and therapeutic implications for endometrial cancer.

The levels of proteins that control the cell cycle are regulated by ubiquitin-mediated degradation via the ubiquitin-proteasome system (UPS) by substrate-specific E3 ubiquitin ligases. The cyclin-dependent kinase inhibitor, p27kip1 (p27), that blocks the cell cycle in G1, is ubiquitylated by the E3 ligase SCF-Skp2/Cks1 for degradation by the UPS. In turn, Skp2 and Cks1 are ubiquitylated by the E3 ligase complex APC/Cdh1 for destruction thereby maintaining abundant levels of nuclear p27. We previously showed that perpetual proteasomal degradation of p27 is an early event in Type I endometrial carcinogenesis (ECA), an estrogen (E2)-induced cancer. The present studies demonstrate that E2 stimulates growth of ECA cell lines and normal primary endometrial epithelial cells (EECs) and induces MAPK-ERK1/2-dependent phosphorylation of p27 on Thr187, a prerequisite for p27 ubiquitylation by nuclear SCF-Skp2/Cks1 and subsequent degradation. In addition, E2 decreases the E3 ligase [APC]Cdh1 leaving Skp2 and Cks1 intact to cause p27 degradation. Furthermore, knocking-down Skp2 prevents E2-induced p27 degradation and growth stimulation suggesting that the pathogenesis of E2-induced ECA is dependent on Skp2-mediated degradation of p27. Conversely, progesterone (Pg) as an inhibitor of endometrial proliferation increases nuclear p27 and Cdh1 in primary EECs and ECA cells. Pg, also increases Cdh1 binding to APC to form the active E3ligase. Knocking-down Cdh1 obviates Pg-induced stabilization of p27 and growth inhibition. Notably, neither E2 nor Pg affected transcription of Cdh1, Skp2, Cks1 nor p27. These studies provide new insights into hormone regulation of cell proliferation through the UPS. The data implicates that preventing nuclear p27 degradation by blocking Skp2/Cks1-mediated degradation of p27 or increasing Cdh1 to mediate degradation of Skp2-Cks1 are potential strategies for the prevention and treatment of ECA