Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation

Grant BBM_TRA_0203 PD/BD/148028/2019 UIDB/04378/2020The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Ca, 13Cb, 1Ha, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated a-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca21, but do bind Zn21, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested.publishersversionpublishe

Implications for phase separation

Funding Information: The authors would also like to acknowledge Prof. Dr. Jaime Mota, Dra. Irina Franco for the technical assistance with the microscopic experiments, Philip O'Toole for the aid in protein production and Dr. Aldino Viegas and Dr. David Pantoja-Uceda for the support and valuable discussions regarding NMR spectroscopy. This work was supported by Fundação para a Ciência e a Tecnologia (FCT-Portugal) for funding UCIBIO project (UIDP/04378/2020 and UIDB/04378/2020) and Associate Laboratory Institute for Health and Bioeconomy – i4HB Project (LA/P/0140/2020). The authors also thank FCT-Portugal for the PhD grant attributed to SF (PD/BD/148028/2019) under the PTNMRPhD Program. JO is a recipient of a Leonardo Grant from the Spanish BBVA Foundation (BBM_TRA_0203) and a Ramón y Cajal Grant (RYC2018-026042-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future.”) JO and DVL are supported by the Spanish Grants PID-2019-109276RA-I00 and PID-2019-109306RB-I00, respectively, both funded by MCIN/AEI/10.13039/501100011033. The NMR spectrometers are part of the National NMR Facility supported by FCT-Portugal (ROTEIRO/0031/2013–PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The 800 MHz spectrometer present in the “Manuel Rico” NMR laboratory (LMR-CSIC) is a node of the Spanish Large-Scale National Facility (ICTS R-LRB-MR). Publisher Copyright: © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.The mediation of liquid–liquid phase separation (LLPS) for fused in sarcoma (FUS) protein is generally attributed to the low-complexity, disordered domains and is enhanced at low temperature. The role of FUS folded domains on the LLPS process remains relatively unknown since most studies are mainly based on fragmented FUS domains. Here, we investigate the effect of metabolites on full-length (FL) FUS LLPS using turbidity assays and differential interference contrast (DIC) microscopy, and explore the behavior of the folded domains by nuclear magnetic resonance (NMR) spectroscopy. FL FUS LLPS is maximal at low concentrations of glucose and glutamate, moderate concentrations of NaCl, Zn2+, and Ca2+ and at the isoelectric pH. The FUS RNA recognition motif (RRM) and zinc-finger (ZnF) domains are found to undergo cold denaturation above 0°C at a temperature that is determined by the conformational stability of the ZnF domain. Cold unfolding exposes buried nonpolar residues that can participate in LLPS-promoting hydrophobic interactions. Therefore, these findings constitute the first evidence that FUS globular domains may have an active role in LLPS under cold stress conditions and in the assembly of stress granules, providing further insight into the environmental regulation of LLPS.publishersversionpublishe

A un año de la declaración de inconstitucionalidad de la publicidad de información financiera de empresas no supervisadas por la SMV

El objetivo principal de este artículo es demostrar que la declaración de inconstitucionalidad de la publicidad de información financiera de empresas no supervisadas por la Superintendencia de Mercado de Valores (SMV) no ha sido nada acertada, lo cual ha causado perjuicio a nuestra sociedad, al desconocer la publicidad de los estados financieros auditados. La investigación permite concluir en sugerir la expedición de un nuevo marco normativo por parte del Congreso, de forma excepcional teniendo en cuenta la decisión del Tribunal constitucional, que permita al Estado y la ciudadanía acceder a la información financiera de empresas no supervisadas, con la finalidad de evitar evasión fiscal y actos de corrupción

Taller: Encerrados pero enREDados

Este proyecto desarrollado en Primavera 2022 se llevó a cabo en el contexto de la pandemia por COVID 19 y dirigió sus esfuerzos en la atención a las personas mayores que habitan en el área metropolitana de Guadalajara y que conforman grupos de personas mayores organizadas mediante los grupos que trabajan en los sistemas DIF de Guadalajara, Tlaquepaque, Tlajomulco y Zapopan. Tuvo la particularidad de contar con personas mayores habitantes del Estado de México. La principal problemática atendida en este periodo escolar fue la exclusión social que viven las personas mayores ocasionada por la insensibilización, desinformación y las condiciones inadecuadas para favorecer su bienestar. Ante ésta, se definió como objetivo desarrollar estrategias inclusivas basadas en la sensibilización e información sobre las condiciones que favorecen el bienestar de las personas mayores en torno a la activación física, hospitalidad, actividades comunitarias, comunidad en línea y rediseño de la vivienda que posibiliten la integración y cohesión social entre y con este grupo etario. El trabajo se realizó mediante encuentros virtuales desde la plataforma Zoom y WhatsApp. En este reporte se presenta el desarrollo del proyecto de aplicación profesional que, en colaboración con las personas mayores participantes, se diseñaron cuatro propuestas que abonan a la calidad de vida de las personas mayores.ITESO, A.C

Differential effects of food restriction and warming in the two-spotted goby: impaired reproductive performance and stressed offspring

Climate change is a growing threat to marine organisms and ecosystems, and it is already modifying ocean properties by, for example, increasing temperature and decreasing pH. Increasing water temperature may also lead to an impairment of primary productivity and an overall depletion of available zooplankton. Understanding how the crossover between warming and zooplankton availability impacts fish populations has paramount implications for conservation and mitigation strategies. Through a cross factorial design to test the effects of ocean temperature and food availability in a temperate marine teleost, Pomatochistus flavescens, we showed that hindered feeding impacted sheltering and avoidance behaviour. Also, low food availability impaired fish reproduction, particularly male reproduction, as the expression of cyp11b1, a gene with a pivotal role in the synthesis of the most important fish androgen, 11-ketotestosterone, was significantly reduced under a low food regime. In contrast, temperature alone did not affect reproductive success, but offspring showed increased saturated fatty acid content (embryos) and increased lipid peroxidation (larvae). Altogether, food availability had a stronger effect on fitness, showing that coping with elevated temperatures, an ability that may be expected in shallow-water fish, can be indirectly impacted, or even overwhelmed, by the effects of ocean warming on primary productivity and downstream ecological processes.info:eu-repo/semantics/publishedVersio

Hyaluronic acid hydrogels reinforced with laser spun bioactive glass micro- and nanofibres doped with lithium

The repair of articular cartilage lesions in weight-bearing joints remains as a significant challenge due to the low regenerative capacity of this tissue. Hydrogels are candidates to repair lesions as they have similar properties to cartilage extracellular matrix but they are unable to meet the mechanical and biological requirements for a successful outcome. Here, we reinforce hyaluronic acid (HA) hydrogels with 13-93-lithium bioactive glass micro- and nanofibres produced by laser spinning. The glass fibres are a reinforcement filler and a platform for the delivery of therapeutic lithium-ions. The elastic modulus of the composites is more than three times higher than in HA hydrogels. Modelling of the reinforcement corroborates the experimental results. ATDC5 chondrogenic cells seeded on the composites are viable and more proliferation occurs on the hydrogels containing fibres than in HA hydrogels alone. Furthermore, the chondrogenic behavior on HA constructs with fibres containing lithium is more marked than in hydrogels with no-lithium fibres.Xunta de Galicia | Ref. ED431B 2016/042Xunta de Galicia | Ref. POS-A/2013/161Xunta de Galicia | Ref. ED481D 2017/010Xunta de Galicia | Ref. ED481B 2016/047-

Performance indicators for clinical practice management in primary care in Portugal : consensus from a Delphi study

Early OnlineBackground: Performance indicators assessing the quality of medical care and linked to pay for performance may cause disagreement. Portuguese indicators included in recent health care reform are controversial. Objectives: To obtain consensus from opinion leaders in family medicine regarding the performance indicators for practice management used in the evaluation of Family Health Units in Portugal. Methods: Eighty-nine specialists in primary care were invited to answer the following question in an online Delphi study: 'Which performance indicators should be assessed regarding the organization and management of clinical practice in primary care in Portugal?' A Likert scale was used to evaluate validity, reliability, feasibility and sensitivity to change. Twenty-seven experts participated in the second round and achieved a high degree of consensus. Eight categories were created for analysis. Results: The experts suggested the use of existing indicators as well as new indicators. Thirty-nine indicators suggested by the experts are currently in use in Portugal. The assessment of the number of clinical acts performed, the number of administrative acts, and evaluation of the clinical demographic profile achieved a high degree of consensus. The expert panel suggested fifty new indicators. Five categories of these new indicators had a high degree of consensus, and three categories had a low degree of consensus. Conclusion: The expert panel recommended that performance indicators of practice management should first assess the quantity of clinical and administrative activities undertaken. These indicators must take into account the human and financial resources available to the clinic and its demographic context

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world

Purpose: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice

Effects of fishery protection on biometry and genetic structure of two target sea cucumber species from the Mediterranean Sea

Sea cucumber fisheries are now occurring in most of the tropical areas of the world, having expanded from its origin in the central Indo-Pacific. Due to the overexploitation of these resources and the increasing demand from Asian countries, new target species from Mediterranean Sea and northeastern Atlantic Ocean are being caught. The fishery effects on biometry and genetic structure of two target species (Holothuria polii and H. tubulosa) from Turkey, were assessed. The heaviest and largest individuals of H. polii were found into the non-fishery area of Kusadasi, also showing the highest genetic diversity. Similar pattern was detected in H. tubulosa, but only the weight was significantly higher in the protected area. However, the observed differences on the fishery effects between species, could be explained considering the different percentage of catches (80% for H. polii and 20% for H. tubulosa)