La candidata a defensora del Pueblo habló de los proyectos que implementaría en la Defensoría si resulta electa.

Panelistas debatieron sobre los últimos hechos de violencia en el país y las claridades que trae el borrador de decreto que contiene líneas operativas para el funcionamiento de la Paz Total.

Panelistas creen que el llamado del ELN no implicará la reanudación del diálogo, pero sí creen que es el primer paso para trazar nuevas líneas rojas en el proceso.

Panelistas debatieron sobre las negociaciones y acuerdos a los que deberán llegar los 196 países presentes en la COP16 que se desarrolla en Cali.

Resiliencia y compasión para la reconciliación.

Este es el Personaje del Día de Orlando Villar.

Escuche el programa de este miércoles 31 de enero. La Luciérnaga un espacio de humor y opinión que acompaña por más de 30 años a sus oyentes en su regreso a casa. 

Escuche el programa de este lunes 11 de marzo. La Luciérnaga, un espacio de humor y opinión de Caracol Radio que desde hace 31 años acompaña a sus oyentes en su regreso casa.

López fue designada como la ministra de Agricultura del gobierno de Gustavo Petro.

Andrey Avendaño, vocero de la comisión de paz de la disidencia del Estado Mayor Central de las FARC, mencionó en Caracol Radio que esperan que los colombianos participen en la construcción de la paz. 

El ministro de Minas y Energía, habló en los micrófonos de Caracol Radio, de la incertidumbre en torno al abastecimiento de combustible para aviones en Colombia. 

James Rodríguez dejó la Liga de Qatar para marcharse al Olympiacos de Grecia ¿Es positivo para su carrera?

El uruguayo Gustavo Poyet, técnico de la selección de Grecia, dedicó grandes elogios a James Rodríguez, en un diálogo con Sarah Castro en la sección Con Mucha Cancha de El Alargue de Caracol Radio. Poyet comentó que en Grecia los hinchas del Olympiacos “aman” al volante colombiano, de quien dijo se encuentra en un gran momento deportivo.

En 6AM Hoy por Hoy de Caracol Radio estuvo Denis Silva, vocero de la Asociación de Pacientes de Colombia, para hablar sobre la razón por la cual protestarán en el Ministerio de Salud este martes 20 de febrero.

El doctor Mauricio Castaño Ramírez, presidente Junta Directiva de la Asociación Colombiana de Psiquiatría, reiteró que es un problema que se viene presentando desde el 2023, y podría afectar a niños, adolescentes y otros pacientes con conductas agresivas

Alfonso Medrano, presidente de la Cámara Intergemial del  Transporte, descartó en 6AM que el sector esté contemplando ir a paro, tal como lo habría asegurado el jefe de cartera de Hacienda, Ricardo Bonilla

En Caracol Radio estuvo Gloria Elena Quinceno, presidenta de la Asociación de Usuarios de Sanitas, explicando detalles sobre la intervención a la EPS

La renovación del convenio es por 12 meses.

Gloria Luz Gutiérrez, literata. Hoy en la Feria Internacional del Libro de Bogotá será la premiación de poesía inédita de la tertulia de Gloria Luz Gutiérrez.

Enrique Martínez explicó en 6AM las reiteradas solicitudes al Gobierno nacional de una ayuda a los pobladores que vuelven a padecer una sutuación crítica por cuenta de la ruptura del dique en Caregato

En Caracol Radio estuvo Edison Mena, presidente de la Asociación Colombiana de Camioneros, ACC de la seccional Ipiales, conversando sobre los acuerdos que lograron con el Gobierno para levantar el paro de camioneros en Nariño

El director Nilson Antonio Liz, estuvo invitado en el programa 6AM de Caracol radio, para hablar sobre cuáles son los incumplimientos de este y los otros gobiernos con los campesinos del país

Ivonne González, presidenta de la Asociación de Mineros y Joyeros de Vetas, estuvo en 6AM para abordar la problemática alrededor del decreto 044 del 2024.

Carlos Fernando Galán, alcalde de Bogotá, habló en 6AM sobre qué pasará con la ampliación de la Avenida Boyacá 

Rodrigo Negrete, director de la ANLA, aseguró que una vez subsanen los problemas actuales, esta organización tomará una nueva decisión dentro de tres meses

Physical chemist Giacinto Scoles, Princeton’s Donner Professor of Science, Emeritus, died in Sassenheim, the Netherlands, on Sept. 25 with his wife of nearly 60 years at his side. He was 89.

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.

Chi-Liang Eric Yen
Nov 1, 2008; 49:2283-2301
Thematic Reviews

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

Abudukadier Abulizi
Dec 1, 2020; 61:1565-1576
Research Articles

Amyloid fibrils are polymeric structures originating from aggregation of misfolded proteins. In vivo, proteolysis may modulate amyloidogenesis and fibril stability. In light chain (AL) amyloidosis, fragmented light chains (LCs) are abundant components of amyloid deposits; however, site and timing of proteolysis are debated. Identification of the N and C termini of LC fragments is instrumental to understanding involved processes and enzymes. We investigated the N and C terminome of the LC proteoforms in fibrils extracted from the hearts of two AL cardiomyopathy patients, using a proteomic approach based on derivatization of N- and C-terminal residues, followed by mapping of fragmentation sites on the structures of native and fibrillar relevant LCs. We provide the first high-specificity map of proteolytic cleavages in natural AL amyloid. Proteolysis occurs both on the LC variable and constant domains, generating a complex fragmentation pattern. The structural analysis indicates extensive remodeling by multiple proteases, largely taking place on poorly folded regions of the fibril surfaces. This study adds novel important knowledge on amyloid LC processing: although our data do not exclude that proteolysis of native LC dimers may destabilize their structure and favor fibril formation, the data show that LC deposition largely precedes the proteolytic events documentable in mature AL fibrils.

Microsomal triglyceride transfer protein (MTTP) deficiency results in a syndrome of hypolipidemia and accelerated NAFLD. Animal models of decreased hepatic MTTP activity have revealed an unexplained dissociation between hepatic steatosis and hepatic insulin resistance. Here, we performed comprehensive metabolic phenotyping of liver-specific MTTP knockout (L-Mttp^–/–) mice and age-weight matched wild-type control mice. Young (10–12-week-old) L-Mttp^–/– mice exhibited hepatic steatosis and increased DAG content; however, the increase in hepatic DAG content was partitioned to the lipid droplet and was not increased in the plasma membrane. Young L-Mttp^–/– mice also manifested normal hepatic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamps, no PKC activation, and normal hepatic insulin signaling from the insulin receptor through AKT Ser/Thr kinase. In contrast, aged (10-month-old) L-Mttp^–/– mice exhibited glucose intolerance and hepatic insulin resistance along with an increase in hepatic plasma membrane sn-1,2-DAG content and PKC activation. Treatment with a functionally liver-targeted mitochondrial uncoupler protected the aged L-Mttp^–/– mice against the development of hepatic steatosis, increased plasma membrane sn-1,2-DAG content, PKC activation, and hepatic insulin resistance. Furthermore, increased hepatic insulin sensitivity in the aged controlled-release mitochondrial protonophore-treated L-Mttp^–/– mice was not associated with any reductions in hepatic ceramide content. Taken together, these data demonstrate that differences in the intracellular compartmentation of sn-1,2-DAGs in the lipid droplet versus plasma membrane explains the dissociation of NAFLD/lipid-induced hepatic insulin resistance in young L-Mttp^–/– mice as well as the development of lipid-induced hepatic insulin resistance in aged L-Mttp^–/– mice.

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.

Cardiac MRI of an animal that has undergone photosynthetic therapy. CREDIT: Stanford University School of Medicine, Department of Cardiothoracic Surgery

Read more at http://www.smithsonianmag.com/travel/Savoring-Puebla.html The streets of Puebla are filled with the sound of Mariachis who sing at most traditional Mexican ceremony.

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners

Bob Iaccino, Path Trading Partners