Discrete breathers in nonlinear network models of proteins

We introduce a topology-based nonlinear network model of protein dynamics with the aim of investigating the interplay of spatial disorder and nonlinearity. We show that spontaneous localization of energy occurs generically and is a site-dependent process. Localized modes of nonlinear origin form spontaneously in the stiffest parts of the structure and display site-dependent activation energies. Our results provide a straightforward way for understanding the recently discovered link between protein local stiffness and enzymatic activity. They strongly suggest that nonlinear phenomena may play an important role in enzyme function, allowing for energy storage during the catalytic process.Comment: 4 pages, 5 figures. Minor change

Endometrial Stromal Cells Circulate in the Bloodstream of Women with Endometriosis: A Pilot Study

Endometriosis; Circulating endometrial cells; CD10Endometriosis; Células endometriales circulantes; CD10Endometriosi; Cèl·lules endometrials circulants; CD10Endometriosis is characterized by the presence of endometrial tissue outside the uterus. While endometriotic tissue is commonly localized in the pelvic cavity, it can also be found in distant sites, including the brain. The origin and pathophysiology of tissue migration is poorly understood; retrograde menstruation is thought to be the cause, although the presence of endometrium at distant sites is not explained by this hypothesis. To determine whether dissemination occurs via the bloodstream in women with endometriosis, we analyzed circulating blood for the presence of endometrial cells. Circulating endometrial stromal cells were identified only in women with endometriosis but not in controls, while endometrial epithelial cells were not identified in the circulation of either group. Our results support the hypothesis that endometrial stromal cells may migrate through circulation and promote the pathophysiology of endometriosis. The detection of these cells in circulation creates avenues for the development of less invasive diagnostic tools for the disease, and opens possibilities for further study of the origin of endometriosis.This research was funded by a Centro de Desarrollo Tecnologico Industrial (CDTI) grant (IDI-2013039). The Industrial Doctorate AGAUR (Agency for Administration of University and Research Grants, Catalonia, Spain) also supported this work (DI2015_ 074

La teoría-práctica del tejido : al alcance de todo el que sepa tejer

Document original a: Centre de Documentació del Museu de Disseny de Barcelona (topogràfic : A-XX-360 )Digitalitzat per Artyplan per encàrrec del Centre de Documentació del Museu del Disseny de Barcelon

Functional Dynamics of PDZ Binding Domains: A Normal Mode Analysis

PDZ (Post-synaptic density-95/discs large/zonula occludens-1) domains are relatively small (80 to 120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino-acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible of communication between distant regions of the protein, in agreement with recent Nuclear Magnetic Resonance (NMR) experiments. Thus PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbonding events.Comment: 25 pages, 10 figures, submitted to Biophysical Journa

Predicting Important Residues and Interaction Pathways in Proteins Using Gaussian Network Model: Binding and Stability of HLA Proteins

A statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway. The structure-function relationships, ligand binding and allosteric activities of ten structures of HLA Class I proteins of the immune system are studied by the Gaussian Network Model. Five of these models are associated with inflammatory rheumatic disease and the remaining five are properly functioning. In the Gaussian Network Model, the protein structures are modeled as an elastic network where the inter-residue interactions are harmonic. Important residues and the interaction pathways in the proteins are identified by focusing on the largest eigenvalue of the residue interaction matrix. Predicted important residues match those known from previous experimental and clinical work. Graph perturbation is used to determine the response of the important residues along the interaction pathway. Differences in response patterns of the two sets of proteins are identified and their relations to disease are discussed

A laboratory-numerical approach for modelling scale effects in dry granular slides

Granular slides are omnipresent in both natural and industrial contexts. Scale effects are changes in physical behaviour of a phenomenon at different geometric scales, such as between a laboratory experiment and a corresponding larger event observed in nature. These scale effects can be significant and can render models of small size inaccurate by underpredicting key characteristics such as ow velocity or runout distance. Although scale effects are highly relevant to granular slides due to the multiplicity of length and time scales in the flow, they are currently not well understood. A laboratory setup under Froude similarity has been developed, allowing dry granular slides to be investigated at a variety of scales, with a channel width configurable between 0.25-1.00 m. Maximum estimated grain Reynolds numbers, which quantify whether the drag force between a particle and the surrounding air act in a turbulent or viscous manner, are found in the range 102-103. A discrete element method (DEM) simulation has also been developed, validated against an axisymmetric column collapse and a granular slide experiment of Hutter and Koch (1995), before being used to model the present laboratory experiments and to examine a granular slide of significantly larger scale. This article discusses the details of this laboratory-numerical approach, with the main aim of examining scale effects related to the grain Reynolds number. Increasing dust formation with increasing scale may also exert influence on laboratory experiments. Overall, significant scale effects have been identified for characteristics such as ow velocity and runout distance in the physical experiments. While the numerical modelling shows good general agreement at the medium scale, it does not capture differences in behaviour seen at the smaller scale, highlighting the importance of physical models in capturing these scale effects

Molecular alterations in eutopic endometrium of women with endometriosis and implications in its diagnostic /

La endometriosi és una malaltia benigna que afecta a un 10-15% de les dones en edat reproductiva I els seus símptomes principals són dolor i infertilitat. El seu diagnòstic pot ser retardat fins a 6,7 anys de mitjana, i el diagnòstic principal és per laparoscòpia. L'objectiu principal d'aquesta tesi era trobar una nova eina diagnòstica menys invasiva que la cirurgia. Per aconseguir-ho, es van dur a terme dos objectius; trobar nous biomarcadors per la malaltia a l'endometri eutòpic i estudiar el marcador Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) com a possible biomarcador per a l'endometriosi. Per al primer objectiu, es va fer un estudi de Discovery de biomarcadors a partir de RNA-High-Sequencing i es va desenvolupar un classificador utilitzant el leave one out cross validation model de Partial Least Squares (PLS) a partir de mostres fixades i incloses en parafina de tots els tipus d'endometriosi i controls. No vam ser capaços de discernir entre tipus d'endometriosi però es va trobar una elevada sensitivitat i especificitat per a diagnosticar la malaltia en global. No obstant, al validar el model amb un increment del nombre de mostres, només el 60% de les pacients amb endometriosi van poder ser diagnosticades com a endometriosi. En conclusió, el model validat no es pot traslladar a la pràctica clínica. En el segon objectiu, vam estudiar LGR5 a l'endometri eutòpic amb RNA-High-Sequencing i vam descobrir que aquestes cèl·lules tenen un fenotip de macròfags. No vam observar diferències significants entre dones sanes i malaltes, per tant, LGR5 no és un bon biomarcador per a la malaltia. No obstant, vam trobar que l'endometriosi profunda, el tipus més agressiu de la malaltia, sobre-expressava gens únics relacionats amb infertilitat. Així doncs, concloem que LGR5 podria estar relacionat amb l'agressivitat de la malaltia així com en els resultats reproductius. Sabent que les cèl·lules LGR5 positives tenien un fenotip de macròfag, vam estudiar els macròfags a l'endometri eutòpic de dones amb la malaltia i vam trobar que presenten un fenotip més pro-inflamatori que les de l'endometri sa, el que podria influir en la fisiopatologia de la malaltia i en els resultats reproductius en aquestes dones.Endometriosis is a benign disease that affects 10-15% of reproductive age women and the main symptoms are pain and infertility. Its diagnostic can be delayed for 6.7 years in average, and the final diagnostic is by laparoscopy. The main objective of this thesis was to find a new and less invasive diagnostic approach for the disease than surgery. For this purpose, two objectives were performed; to find new biomarkers for the disease in eutopic endometrium and to study Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) as a putative biomarker for endometriosis. For the first objective, a discover study of biomarkers was done by RNA-High-Sequencing and a classifier was developed by using Partial Least Squares (PLS) leave one out cross validation model using formalin-fixed paraffin embedded samples from all types of endometriosis and controls. We were not able to distinguish between types of disease but there was a high sensitivity and specificity to diagnose the disease in global. However, when we validated the model by increasing the sample size, only the 60% of patients could be diagnosed as endometriosis. In conclusion, the validated model cannot be translated to the clinics. In the second objective, we studied LGR5 in eutopic endometrium by RNA-High-Sequencing and we discovered that these cells have a macrophage-like phenotype. We did not observe significant differences between healthy and diseased women and thus, LGR5 is not a good biomarker for the disease. However, we found that deep infiltrating endometriosis (DIE), the most aggressive type of the disease, overexpressed unique genes related to infertility. Hence, we concluded that LGR5 could be related to the aggressiveness of the disease as well as in reproductive outcomes. Knowing that LGR5 positive cells phenotype was macrophage-like, we studied macrophages in eutopic endometrium of diseased women and we found that they present a more pro-inflammatory phenotype than healthy endometrium which could also influence to the pathophysiology of the disease and to the reproductive outcomes in this women

Les portes de la percepció

La crisi existencial que la humanitat viu actualment com a societat globalitzada a través del model capitalista necessita respostes. Amb aquest treball es pretén indagar en un estudi en profunditat sobre la consciència i la seva naturalesa, posant en dubte el racionalisme imperant segons el que s'ha construït la societat occidental al llarg del temps, que ha acabat resultant en psicopolítica, crisi ambiental, totalitarismes... William Blake és la principal inspiració que porta la veu de fons en tot el treball, que s'estructura a través de l'anàlisi d'obres com "El espectro de la conciencia", de Ken Wilber, "Filosofías del underground", de Luis Racionero, o "Psicología transpersonal", de Stanislav Grof, entre d'altres. Aquest anàlisi ens permet elaborar connexions entre la física quàntica moderna i la mística, així com entrar en comparacions sobre l'origen de les religions i els cultes espirituals arreu del món i al llarg de la història, així com parlar sobre estats de la consciència i la seva relació amb la pròpia naturalesa de l'univers.La crisis existencial que la humanidad vive actualmente como sociedad globalizada a través del modelo capitalista necesita respuestas. Con este trabajo se pretende indagar en un estudio en profundidad sobre la conciencia y su naturaleza, poniendo en duda el racionalismo imperante según el cual se ha construido la sociedad occidental a lo largo del tiempo, que ha acabado resultando en psicopolítica, crisis ambiental, totalitarismos... William Blake es la principal inspiración que lleva la voz de fondo en todo el trabajo, que se estructura a través del análisis de obras como "El espectro de la conciencia", de Ken Wilber, "Filosofías del underground", de Luis Racionero, o "Psicología transpersonal", de Stanislav Grof, entre otros. Este análisis nos permite elaborar conexiones entre la física cuántica moderna y la mística, así como entrar en comparaciones sobre el origen de las religiones y los cultos espirituales alrededor del mundo y a lo largo de la historia, así como hablar sobre estados de la conciencia y su relación con la propia naturaleza del universo.The existential crisis that humanity is currently experiencing as a globalized society under the capitalist model requires answers. This work aims to delve into an in-depth study of consciousness and its nature, questioning the prevailing rationalism upon which western society has been built over time, which has resulted in psychopolitics, environmental crisis, totalitarianism, and more. William Blake serves as the main inspiration that carries the underlying voice throughout the work, which is structured through the analysis of works such as "The Spectrum of Consciousness" by Ken Wilber, "Filosofías del underground" by Luis Racionero, or "Transpersonal Psychology" by Stanislav Grof, among others. This analysis allows us to establish connections between modern quantum physics and mysticism, as well as draw comparisons regarding the origins of religions and spiritual cults around the world throughout history. Furthermore, it delves into discussions about states of consciousness and their relationship with the very nature of the universe

Endometrial stromal cells circulate in the bloodstream of women with endometriosis : A pilot study

Funding: This research was funded by a Centro de Desarrollo Tecnológico Industrial (CDTI) grant (IDI-2013039). The Industrial Doctorate AGAUR (Agency for Administration of University and Research Grants, Catalonia, Spain) also supported this work (DI2015_074).Endometriosis is characterized by the presence of endometrial tissue outside the uterus. While endometriotic tissue is commonly localized in the pelvic cavity, it can also be found in distant sites, including the brain. The origin and pathophysiology of tissue migration is poorly understood; retrograde menstruation is thought to be the cause, although the presence of endometrium at distant sites is not explained by this hypothesis. To determine whether dissemination occurs via the bloodstream in women with endometriosis, we analyzed circulating blood for the presence of endometrial cells. Circulating endometrial stromal cells were identified only in women with endometriosis but not in controls, while endometrial epithelial cells were not identified in the circulation of either group. Our results support the hypothesis that endometrial stromal cells may migrate through circulation and promote the pathophysiology of endometriosis. The detection of these cells in circulation creates avenues for the development of less invasive diagnostic tools for the disease, and opens possibilities for further study of the origin of endometriosis

Endometrial stromal cells circulate in the bloodstream of women with endometriosis : A pilot study

Funding: This research was funded by a Centro de Desarrollo Tecnológico Industrial (CDTI) grant (IDI-2013039). The Industrial Doctorate AGAUR (Agency for Administration of University and Research Grants, Catalonia, Spain) also supported this work (DI2015_074).Endometriosis is characterized by the presence of endometrial tissue outside the uterus. While endometriotic tissue is commonly localized in the pelvic cavity, it can also be found in distant sites, including the brain. The origin and pathophysiology of tissue migration is poorly understood; retrograde menstruation is thought to be the cause, although the presence of endometrium at distant sites is not explained by this hypothesis. To determine whether dissemination occurs via the bloodstream in women with endometriosis, we analyzed circulating blood for the presence of endometrial cells. Circulating endometrial stromal cells were identified only in women with endometriosis but not in controls, while endometrial epithelial cells were not identified in the circulation of either group. Our results support the hypothesis that endometrial stromal cells may migrate through circulation and promote the pathophysiology of endometriosis. The detection of these cells in circulation creates avenues for the development of less invasive diagnostic tools for the disease, and opens possibilities for further study of the origin of endometriosis