Effects of grape seed extract on properties of type I collagen scaffolds

 To obtain a material with potential for use in tissue engineering, anionic collagen was obtained from porcine serosa (S) and bovine tendon (T) by alkaline hydrolysis for 72h. Part of this collagen was mixed with water to obtain 4 % (weight/weight) collagen suspension and part was solubilized in acetic acid pH 3.5 to obtain 1.5% (w/w) gel. The suspensions were mixed with their respective gels (2:1) (suspension: gel) and grape seed extract, whose main product is proanthocyanidin, was added at concentrations of 0.03% and 0.5%, thus obtaining the scaffolds SC (serosa collagen suspension and gel), TC (tendon collagen suspension and gel), SCP003 (SC with 0.03% extract), TCP003 (TC with 0.03% extract), SCP05 (SC with 0.5% extract added) and TCP05 (TC with 0.5% extract). The materials were analyzed by differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and characterized by phosphate buffered saline absorption assay and in vitro biological stability assay. By DSC it is observed that the addition of 0.5% of extract increases the denaturation temperature (Td) of collagen, indicating that at this concentration the extract acts as polymer crosslinking agent. SEM shows disorganized cross-section pores in all scaffolds, not exceeding 130 ?m. Absorption and degradation assays indicated that the addition of 0.5% extract increases the absorption of phosphate buffered saline (PBS) by the scaffolds and decreases the degradation percentage by collagenase. These results suggests that the scaffolds can be used for different applications, e.g. as hemostatic agent. 

Determination of activation energy in polymeric hydrogels using thermogravimetric analysis

Curvas termogravimétricas com diferentes razões de aquecimento foram utilizadas para a determinação de parâmetros cinéticos seguindo o método de Flynn-Wall. Para isso, foi utilizado um hidrogel preparado a partir da mistura de dois polissacarídeos, quitosana/xantana (QX) e outro, contendo além destes, colágeno (QXC). Os resultados mostraram que o valor de energia de ativação para o hidrogel QX foi de 3,44 kJ.mol-1, enquanto que para o QXC foi de 14,84 kJ.mol-1, sugerindo que a água presente no hidrogel contendo colágeno está mais fortemente ligada aos biopolímeros. Isto pode ter ocorrido devido à presença de grupos carboxílicos na estrutura colagênica.Polyelectrolyte hydrogels formed by chitosan/xanthan (QX) and chitosan/xanthan/collagen (QXC) were prepared and thermogravimetric curves at different heating rates were obtained, with the aim of determining kinetic parameters using the Flynn-Wall method. The calculated activation energy was 3.44 kJ.mol-1 (QX ) and 14.84 kJ.mol-1 (QXC), suggesting stronger interactions in QXC hydrogel structure than in the QX hydrogel, probably due to the presence of carboxyl groups of collagen molecules.Conselho Nacional de Pesquisa (CNPq

TLR4-pathway impairs synaptic number and cerebrovascular functions through astrocyte activation following traumatic brain injury

Background and purpose: Activation of astrocytes contributes to synaptic remodelling, tissue repair and neuronal survival following traumatic brain injury (TBI). The mechanisms by which these cells interact to resident/infiltrated inflammatory cells to rewire neuronal networks and repair brain functions remain poorly understood. Here, we explored how TLR4-induced astrocyte activation modified synapses and cerebrovascular integrity following TBI. Experimental approach: To determine how functional astrocyte alterations induced by activation of TLR4 pathway in inflammatory cells regulate synapses and neurovascular integrity after TBI, we used pharmacology, genetic approaches, live calcium imaging, immunofluorescence, flow cytometry, blood-brain barrier (BBB) integrity assessment and molecular and behavioural methods. Key results: Shortly after a TBI, there is a recruitment of excitable and reactive astrocytes mediated by TLR4 pathway activation with detrimental effects on post-synaptic density-95 (PSD-95)/vesicular glutamate transporter 1 (VGLUT1) synaptic puncta, BBB integrity and neurological outcome. Pharmacological blockage of the TLR4 pathway with resatorvid (TAK-242) partially reversed many of the observed effects. Synapses and BBB recovery after resatorvid administration were not observed in IP3 R2-/- mice, indicating that effects of TLR4 inhibition depend on the subsequent astrocyte activation. In addition, TBI increased the astrocytic-protein thrombospondin-1 necessary to induce a synaptic recovery in a sub-acute phase. Conclusions and implications: Our data demonstrate that TLR4-mediated signalling, most probably through microglia and/or infiltrated monocyte-astrocyte communication, plays a crucial role in the TBI pathophysiology and that its inhibition prevents synaptic loss and BBB damage accelerating tissue recovery/repair, which might represent a therapeutic potential in CNS injuries and disorders.This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) (Programa Miguel Servet II Grants CPII19/00005;PI16/00735; PI19/00082 to JE; and PI18/00357 to DC, partiallyfunded by FEDER - European Union ‘Una manera de hacer Europa’) and Fundación Mutua Madrileña to JE; European Union's Horizon2020 research and innovation programme under the H2020 MarieSkłodowska-Curie Actions grant agreement no. 794926 and StopFuga de Cerebros Roche Pharma to JMR; and Ministerio de Ciencia e Innovación RTI2018-094887-B-I00 and RYC-2016-20414 to MN andRYC2019-026870-I to JMR. DC, MCO, VVS and EFL are hired bySESCAM

Emancipation under the great recession in Spain.

ABSTRACT: In this paper we document the behavior of emancipation over one of the biggest boom–bust cycles experienced by the Spanish economy. In principle, the economic difficulties faced by the Spanish youth during the last recession would have hampered a normal emancipation pace. However, we find that the proportion living away from parents among those aged 18–40 has not decreased but increased from 44 % during the boom (2005–2008) to 46 % during the bust (2009–2013). A simple decomposition reveals that this is mainly driven by the substantial rise in the emancipation rate among the full-time employed workers during the bust. To explain this change we discuss several factors such as macroeconomic conditions, rental subsidy policy, higher labor mobility, selection bias, reverse causation, timelag in adjustment and secular trend.MEC(IP: María Paz Espinosa Alejos, UPV

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer\u27s disease

The relationship between body-mass index (BMI) and Alzheimeŕs disease (AD) has been extensively investigated. However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to diverge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global Aβ brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time

Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease

BACKGROUND: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. RESULTS: Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. CONCLUSIONS: We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Global and regional ecological boundaries explain abrupt spatial discontinuities in avian frugivory interactions

Species interactions can propagate disturbances across space via direct and indirect effects, potentially connecting species at a global scale. However, ecological and biogeographic boundaries may mitigate this spread by demarcating the limits of ecological networks. We tested whether large-scale ecological boundaries (ecoregions and biomes) and human disturbance gradients increase dissimilarity among plant-frugivore networks, while accounting for background spatial and elevational gradients and differences in network sampling. We assessed network dissimilarity patterns over a broad spatial scale, using 196 quantitative avian frugivory networks (encompassing 1496 plant and 1004 bird species) distributed across 67 ecoregions, 11 biomes, and 6 continents. We show that dissimilarities in species and interaction composition, but not network structure, are greater across ecoregion and biome boundaries and along different levels of human disturbance. Our findings indicate that biogeographic boundaries delineate the world’s biodiversity of interactions and likely contribute to mitigating the propagation of disturbances at large spatial scales.The authors acknowledge the following funding: University of Canterbury Doctoral Scholarship (L.P.M.); The Marsden Fund grant UOC1705 (J.M.T., L.P.M.); The São Paulo Research Foundation - FAPESP 2014/01986-0 (M.G., C.E.), 2015/15172-7 and 2016/18355-8 (C.E.), 2004/00810-3 and 2008/10154-7 (C.I.D., M.G., M.A.P.); Earthwatch Institute and Conservation International for financial support (C.I.D., M.G., M.A.P.); Carlos Chagas Filho Foundation for Supporting Research in the Rio de Janeiro State – FAPERJ grant E-26/200.610/2022 (C.E.); Brazilian Research Council grants 540481/01-7 and 304742/2019-8 (M.A.P.) and 300970/2015-3 (M.G.); Rufford Small Grants for Nature Conservation No. 22426–1 (J.C.M., I.M.), No. 9163-1 (G.B.J.) and No. 11042-1 (MCM); Universidade Estadual de Santa Cruz (Propp-UESC; No. 00220.1100.1644/10-2018) (J.C.M., I.M.); Fundação de Amparo à Pesquisa do Estado da Bahia - FAPESB (No. 0525/2016) (J.C.M., I.M.); European Research Council under the European Union’s Horizon 2020 research and innovation program (grant 787638) and The Swiss National Science Foundation (grant 173342), both awarded to C. Graham (D.M.D.); ARC SRIEAS grant SR200100005 Securing Antarctica’s Environmental Future (D.M.D.); German Science Foundation—Deutsche Forschungsgemeinschaft PAK 825/1 and FOR 2730 (K.B.G., E.L.N., M.Q., V.S., M.S.), FOR 1246 (K.B.G., M.S., M.G.R.V.) and HE2041/20-1 (F.S., M.S.); Portuguese Foundation for Science and Technology - FCT/MCTES contract CEECIND/00135/2017 and grant UID/BIA/04004/2020 (S.T.) and contract CEECIND/02064/2017 (L.P.S.); National Scientific and Technical Research Council, PIP 592 (P.G.B.); Instituto Venezolano de Investigaciones Científicas - Project 898 (V.S.D.)