The Most Severe Test for Hydrophobicity Scales: Two Proteins with 88% Sequence Identity but Different Structure and Function

Protein-protein interactions (protein functionalities) are mediated by water, which compacts individual proteins and promotes close and temporarily stable large-area protein-protein interfaces. In their classic paper Kyte and Doolittle (KD) concluded that the "simplicity and graphic nature of hydrophobicity scales make them very useful tools for the evaluation of protein structures". In practice, however, attempts to develop hydrophobicity scales (for example, compatible with classical force fields (CFF) in calculating the energetics of protein folding) have encountered many difficulties. Here we suggest an entirely different approach, based on the idea that proteins are self-organized networks, subject to finite-scale criticality (like some network glasses). We test this proposal against two small proteins that are delicately balanced between alpha and alpha/beta structures, with different functions encoded with only 12% of their amino acids. This example explains why protein structure prediction is so challenging, and it provides a severe test for the accuracy and content of hydrophobicity scales. The new method confirms KD's evaluation, and at the same time suggests that protein structure, dynamics and function can be best discussed without using CFF

La importancia de la propiedad emocional en la empresa familiar

Para que las empresas familiares crezcan y continúen en el tiempo será necesario que la próxima generación se ponga la camiseta con compromiso y participación.La presente entrevista fue realizada el 21 de abril de 2020 a la psicóloga (Doctora) SaraRozenblum de Horowitz, formada en negociación en la estadounidense Universidad deHarvard, Asesora de Empresas Familiares y Directora del Posgrado Interdisciplinario deNegociación en Empresas del Agro de la Escuela para Graduados de FAUBA. La entrevista sebasó en una investigación que realizaron Åsa Björnberg y Nigel Nicholson en el 2008 a más de600 familiares respecto a la próxima generación en 67 países, incluida la Argentina. Losencuestados tenían entre 22 y 40 años y el grupo etario con más participantes es el de 31 a 40años

Metabolomics as a Driver in Advancing Precision Medicine in Sepsis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138226/1/phar1974.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138226/2/phar1974_am.pd

Multidimensional Spectral Phasors of LAURDAN’s Excitation–Emission Matrices: The Ultimate Sensor for Lipid Phases?

Fil: Socas, Luis B. P. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Socas, Luis B. P. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina.Fil: Valdivia-Pérez Jessica A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Valdivia-Pérez Jessica A. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina.Fil: Fanani María L. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Fanani María L. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina.Fil: Ambroggio Ernesto E. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Ambroggio Ernesto E. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina.The impact of lipid diversity on the lateral organization of biological membranes remains a topic of debate. While the existence of domains in lamellar membranes is well-established, the nonlamellar phases occurring in biological systems are less explored due to technical constraints. Here, we present the measurement of the excitation–emission matrices (EEM) of LAURDAN in several lipid structures. LAURDAN is a fluorescence probe widely used for characterizing lipid assemblies. The EEMs were analyzed by multidimensional spectral phasors (MdSP), an approach that seizes information from both the excitation and emission spectra. We developed a computer algorithm to construct EEM data based on a model for LAURDAN’s photophysics. The MdSP calculated from the simulated EEMs reveals that all feasible possibilities lie inside a universal triangle in the phasor’s plot. We use this triangle to propose a ternary representation for the phasors, allowing a better assessment of LAURDAN’s surroundings in terms of hydration, water mobility, and local electronic environment. Building upon this foundation, we constructed a theoretical “phase map” that can assess both lamellar and nonlamellar membranes. We thoroughly validated this theory using well-known lipid mixtures under different phase-state conditions and enzymatically generated systems. Our results confirm that the use of MdSP is a powerful tool for obtaining quantitative information on both lamellar and nonlamellar structures. This study not only advances our understanding of the impact of lipid diversity on membrane organization but also provides a robust and general framework for the assessment of fluorescence properties that can be further extended to other probes.info:eu-repo/semantics/publishedVersion2025-06-15Fil: Socas, Luis B. P. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Socas, Luis B. P. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina.Fil: Valdivia-Pérez Jessica A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Valdivia-Pérez Jessica A. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina.Fil: Fanani María L. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Fanani María L. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina.Fil: Ambroggio Ernesto E. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica, Ranwel Caputto, Argentina.Fil: Ambroggio Ernesto E. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba, Argentina

Metal templated design of protein interfaces

Metal coordination is a key structural and functional component of a large fraction of proteins. Given this dual role we considered the possibility that metal coordination may have played a templating role in the early evolution of protein folds and complexes. We describe here a rational design approach, Metal Templated Interface Redesign (MeTIR), that mimics the time course of a hypothetical evolutionary pathway for the formation of stable protein assemblies through an initial metal coordination event. Using a folded monomeric protein, cytochrome cb562, as a building block we show that its non-self-associating surface can be made self-associating through a minimal number of mutations that enable Zn coordination. The protein interfaces in the resulting Zn-directed, D2-symmetrical tetramer are subsequently redesigned, yielding unique protein architectures that self-assemble in the presence or absence of metals. Aside from its evolutionary implications, MeTIR provides a route to engineer de novo protein interfaces and metal coordination environments that can be tuned through the extensive noncovalent bonding interactions in these interfaces

Four small puzzles that Rosetta doesn't solve

A complete macromolecule modeling package must be able to solve the simplest structure prediction problems. Despite recent successes in high resolution structure modeling and design, the Rosetta software suite fares poorly on deceptively small protein and RNA puzzles, some as small as four residues. To illustrate these problems, this manuscript presents extensive Rosetta results for four well-defined test cases: the 20-residue mini-protein Trp cage, an even smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies, several lines of evidence indicate that conformational sampling is not the major bottleneck in modeling these small systems. Instead, approximations and omissions in the Rosetta all-atom energy function currently preclude discriminating experimentally observed conformations from de novo models at atomic resolution. These molecular "puzzles" should serve as useful model systems for developers wishing to make foundational improvements to this powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special Collectio

Promoción de alimentación saludable y segura, actividad física y huerta orgánica

La pandemia por COVID-19 ha profundizado carencias socio-económicas y nutritivas en poblaciones vulnerables. A través de este proyecto pretendimos reducirlas, fomentando los hábitos saludables y promoviendo la puesta en valor de los beneficios de una huerta orgánica en el hogar y en la escuela. Los objetivos del trabajo fueron: a) Capacitar a los docentes para ser agentes multiplicadores de una alimentación saludable e inocua y de actividad física; y al personal de cocina en buenas prácticas de manipulación de alimentos. b) Promover la huerta escolar con hábitos agroecológicos y reciclaje. Los destinatarios directos fueron los docentes y cocineras (80 personas) y los indirectos, los alumnos de ambas escuelas (436 personas). Se trabajó interdisciplinariamente, cada uno con una visión desde su disciplina, logrando un enfoque integral y efectivo en el logro de los objetivos planteados, además de un enriquecimiento personal. La modalidad de trabajo fue a distancia (virtual), mediante Talleres (Google Meet) con docentes de ambas escuelas, estimulando el intercambio activo de ideas y propuestas de trabajo con sus alumnos. Ofrecimos recursos y actividades en un aula Moodle, proponiendo Foros de intercambio de aportes, saberes y consultas para cada tema tratado en Taller. Se evaluó la participación de los docentes en los talleres a través de su asistencia y de las prácticas frente al alumnado escolar. Los escolares elaboraron enmiendas orgánicas y armaron huertas, donde sembraron, cosecharon y usaron esos productos. La huerta escolar se planteó como estrategia educativa de alto impacto para promover hábitos de “reducir, reutilizar y reciclar” lo que consumimos, y generar un consumo responsable, ecológico y sostenible

?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA