Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited. However, the development of these dendritic nanocarriers is challenging because of the undesired and/or premature degradation observed during their synthesis and/or application. Here, we report new hybrid-biodegradable, biocompatible, non-toxic, and water-soluble azide-terminated PEG–GATGE dendritic block copolymers, based on a gallic acid (GA) core and triethylene glycol (TG) butanoate arms, incorporating ester bonds (E) at the dendritic arms/shell. Their successful functionalization by “click” chemistry with unprotected alkynated amines allowed complexation and delivery of siRNA. The hydrophobic character of the GATGE building unit confers to these hydrolyzable dendritic bionanomaterials a great ability to complex, protect and mediate the cellular internalization of siRNA. Moreover, the localization of the degradation points at the dendritic periphery, close to the complexed siRNA, was found to be important for nucleic acid release from the nanoparticles, rendering a significant improvement of the transfection efficiency compared to their hydrolytically stable PEG–GATG copolymer counterparts. The present study puts forward these biodegradable PEG–dendritic block copolymers not only as suitable vectors for nucleic acids, but also as new avenues for further developments exploring their use in theranosticsThe authors would like to acknowledge the FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE and the Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia (PTDC/CTM-NAN/112428/2009 and PTDC/CTM-NAN/3547/2014) that supported this work and the FCT / MEC through National Funds and, when applicable, co-financed by the FEDER via the PT2020 Partnership Agreement under the 4293 Unit I&D. V. Leiro acknowledges the support by FCT (SFRH/BPD/69110/2010) and by the project NORTE-01-0145-FEDER-000012, financed by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). P.M.D. Moreno acknowledges the support from the Marie Curie Actions of the European Community’s Seventh Framework Program (PIEF-GA-2011-300485) and FCT fellowship (SFRH/BPD/108738/2015). This work was also financially supported by the Spanish Government (MINECO: CTQ2012-34790, CTQ2012-33436) and the Xunta de Galicia (CN2011/037)S

CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression

Sjuksköterskeyrket innebär ofta långvarig stress och bristfällig arbetsmiljö. Personalbrist, hög arbetsbelastning och bristande inflytande på arbetsplatsen är orsaker till att sjuksköterskor väljer att sluta inom yrket. För lite forskning gällande den upplevda stressen på arbetsplatsen inom sjuksköterskeyrket råder. Därför finns anledning till ökad kunskap kring ämnet. Syftet med studien är att undersöka i hur hög utsträckning sjuksköterskor upplever stress i sin arbetsmiljö, och studien är baserad på 1044 yrkesverksamma sjuksköterskor över hela landet som är medlemmar i Facebookgruppen ”Sjuksköterskan”. Dessa personer har fått svara på enkäten Work Stress Questionnaire med 21 frågor. Resultatet från denna studie visar att arbetsbelastningen ökat och personalen har inte möjlighet att påverka beslut som tas på arbetsplatsen. Konflikter är också förekommande där chefen, i de flesta fall, inte gör något för att lösa dessa konflikter. Sjuksköterskorna sätter höga krav på sig själva och är mycket engagerade i arbetet, men har ofta svårt att sätta gränser. Resultatet visar också att en hög andel har svårt att hinna med familj, vänner och fritidsintressen. Det finns tidigare studier med samma mätinstrument som visar att arbetsbelastningen och ansvarstagandet har ökat under de senaste åren. Eventuellt kan detta i slutändan innebära en risk för ökad utbrändhet och fler sjukskrivningar

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

This is an open access article distributed under the terms of the Creative Commons Attribution License.[Introduction]: Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia. [Methods]: We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX™ and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker™ Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells. [Results]: We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy. [Conclusions]: These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.This work was supported by grants FIS PI080500 and FIS EC08/00076, Ministerio de Sanidad, Spain. The authors dedicate this manuscript to FM patients and AFIBROSE (Asociación de Fibromialgia de Sevilla) for their unconditional help.Peer Reviewe

The timing of the deglaciation in the Atlantic Iberian mountains: Insights from the stratigraphic analysis of a lake sequence in Serra da Estrela (Portugal)

Understanding the environmental response to the last glacial termination in regions located in transitional climate zones such as the Atlantic Iberian mountains is crucial to estimate potential changes in regions affected by current glacial melting. We present an 8.5 m-long, solid last deglaciation and Holocene chronostratigraphic record including detailed sediment analysis from Lake Peixao, a pro-glacial lake in the Serra da Estrela (Central Portugal). The age-depth model relies on a Bayesian approach that includes 16 AMS C-14 dates and Pb-210-(CS)-C-137 measurements, robustly dating the lake formation at 14.7 +/- 0.32 cal. ka BP. This chronological reconstruction shows an average sedimentation rate of ca. 0.07 cm yr(-1) (15 yr cm(-1)), enabling proxy analyses at decadal timescales. The sediment sequence is composed of five lithological units: (U1) coarse and unsorted fluvioglacial lacustrine deposits; (U2) massive fluvioglacial lacustrine deposits (863-790 cm below surface [bsf]; 14.7 +/- 0.32-13.8 +/- 0.12 cal. ka BP); (U3) water current fluvioglacial lacustrine deposits (790-766 cm bsf; 13.8 +/- 0.12-12.9 +/- 0.29 cal. ka BP); (U4) laminated/banded lacustrine deposits characterized by terrigenous deposits from ice-covered lake periods and episodic events of ice and snow melting (766-752 cm bsf; 12.9 +/- 0.29-11.7 +/- 0.15 cal. ka BP); and (U5) massive muddy lacustrine deposits (752-0 cm bsf; 11.7 +/- 0.15 cal. ka BP-present). The occurrence of U2 to U4 deposits defines the transition from glacial cold (U1) to net warm postglacial conditions (U5). These climate transitions are marked by changes in sediments and the presence of very low sedimentation rate periods, possibly related to the Intra-Allerod Cold Period and the coldest phase of the Younger Dryas. Our results support the previously proposed timing of the retreat of the Serra da Estrela glaciers ca. 13.8 +/- 0.12 cal. ka BP. The robust chronology of Lake Peixao highlights the potential of Iberian pro-glacial lakes for dating deglaciation processes and will lead to unprecedented decadal-to-centennial timescale palaeoclimate reconstructions in this region since the last glacial-interglacial transition.info:eu-repo/semantics/publishedVersio

The timing of the deglaciation in the Atlantic Iberian mountains: Insights from the stratigraphic analysis of a lake sequence in Serra da Estrela (Portugal)

Understanding the environmental response to the last glacial termination in regions located in transitional climate zones such as the Atlantic Iberian mountains is crucial to estimate potential changes in regions affected by current glacial melting. We present an 8.5 m-long, solid last deglaciation and Holocene chronostratigraphic record including detailed sediment analysis from Lake Peix˜ao, a pro-glacial lake in the Serra da Estrela (Central Portugal). The age–depth model relies on a Bayesian approach that includes 16 AMS 14C dates and 210Pb–137CS measurements, robustly dating the lake formation at 14.7 ± 0.32 cal. ka BP. This chronological reconstruction shows an average sedimentation rate of ca. 0.07 cm yr 1 (15 yr cm 1), enabling proxy analyses at decadal timescales. The sediment sequence is composed of five lithological units: (U1) coarse and unsorted fluvioglacial lacustrine deposits; (U2) massive fluvioglacial lacustrine deposits (863–790 cm below surface [bsf]; 14.7 ± 0.32–13.8 ± 0.12 cal. ka BP); (U3) water current fluvioglacial lacustrine deposits (790–766 cm bsf; 13.8 ± 0.12–12.9 ± 0.29 cal. ka BP); (U4) laminated/banded lacustrine deposits characterized by terrigenous deposits from ice-covered lake periods and episodic events of ice and snow melting (766–752 cm bsf; 12.9 ± 0.29–11.7 ± 0.15 cal. ka BP); and (U5) massive muddy lacustrine deposits (752–0 cm bsf; 11.7 ± 0.15 cal. ka BP–present). The occurrence of U2 to U4 deposits defines the transition from glacial cold (U1) to net warm postglacial conditions (U5). These climate transitions are marked by changes in sediments and the presence of very low sedimentation rate periods, possibly related to the Intra-Allerød Cold Period and the coldest phase of the Younger Dryas. Our results support the previously proposed timing of the retreat of the Serra da Estrela glaciers ca. 13.8 ± 0.12 cal. ka BP. The robust chronology of Lake Peix˜ao highlights the potential of Iberian pro-glacial lakes for dating deglaciation processes and will lead to unprecedented decadal-to-centennial timescale palaeoclimate reconstructions in this region since the last glacial–interglacial transition.info:eu-repo/semantics/publishedVersio

The timing of the deglaciation in the Atlantic Iberian mountains:Insights from the stratigraphic analysis of a lake sequence in Serra da Estrela (Portugal)

Understanding the environmental response to the last glacial termination in regions located in transitional climate zones such as the Atlantic Iberian mountains is crucial to estimate potential changes in regions affected by current glacial melting. We present an 8.5 m-long, solid last deglaciation and Holocene chronostratigraphic record including detailed sediment analysis from Lake Peixão, a pro-glacial lake in the Serra da Estrela (Central Portugal). The age–depth model relies on a Bayesian approach that includes 16 AMS 14C dates and 210Pb–137CS measurements, robustly dating the lake formation at 14.7 ± 0.32 cal. ka BP. This chronological reconstruction shows an average sedimentation rate of ca. 0.07 cm yr−1 (15 yr cm−1), enabling proxy analyses at decadal timescales. The sediment sequence is composed of five lithological units: (U1) coarse and unsorted fluvioglacial lacustrine deposits; (U2) massive fluvioglacial lacustrine deposits (863–790 cm below surface [bsf]; 14.7 ± 0.32–13.8 ± 0.12 cal. ka BP); (U3) water current fluvioglacial lacustrine deposits (790–766 cm bsf; 13.8 ± 0.12–12.9 ± 0.29 cal. ka BP); (U4) laminated/banded lacustrine deposits characterized by terrigenous deposits from ice-covered lake periods and episodic events of ice and snow melting (766–752 cm bsf; 12.9 ± 0.29–11.7 ± 0.15 cal. ka BP); and (U5) massive muddy lacustrine deposits (752–0 cm bsf; 11.7 ± 0.15 cal. ka BP–present). The occurrence of U2 to U4 deposits defines the transition from glacial cold (U1) to net warm postglacial conditions (U5). These climate transitions are marked by changes in sediments and the presence of very low sedimentation rate periods, possibly related to the Intra-Allerød Cold Period and the coldest phase of the Younger Dryas. Our results support the previously proposed timing of the retreat of the Serra da Estrela glaciers ca. 13.8 ± 0.12 cal. ka BP. The robust chronology of Lake Peixão highlights the potential of Iberian pro-glacial lakes for dating deglaciation processes and will lead to unprecedented decadal-to-centennial timescale palaeoclimate reconstructions in this region since the last glacial–interglacial transition

The timing of the deglaciation in the Atlantic Iberian mountains: Insights from the stratigraphic analysis of a lake sequence in Serra da Estrela (Portugal).

Understanding the environmental response to the last glacial termination in regions located in transitional climate zones such as the Atlantic Iberian mountains is crucial to estimate potential changes in regions affected by current glacial melting. We present an 8.5 m-long, solid last deglaciation and Holocene chronostratigraphic record including detailed sediment analysis from Lake Peix¿ao, a pro-glacial lake in the Serra da Estrela (Central Portugal). The age-depth model relies on a Bayesian approach that includes 16 AMS 14C dates and 210Pb-137CS measurements, robustly dating the lake formation at 14.7 ± 0.32 cal. ka BP. This chronological reconstruction shows an average sedimentation rate of ca. 0.07 cm yr-1 (15 yr cm-1), enabling proxy analyses at decadal timescales. The sediment sequence is composed of five lithological units: (U1) coarse and unsorted fluvioglacial lacustrine deposits; (U2) massive fluvioglacial lacustrine deposits (863-790 cm below surface [bsf]; 14.7 ± 0.32-13.8 ± 0.12 cal. ka BP); (U3) water current fluvioglacial lacustrine deposits (790-766 cm bsf; 13.8 ± 0.12-12.9 ± 0.29 cal. ka BP); (U4) laminated/banded lacustrine deposits characterized by terrigenous deposits from ice-covered lake periods and episodic events of iceand snow melting (766-752 cm bsf; 12.9 ± 0.29-11.7 ± 0.15 cal. ka BP); and (U5) massive muddy lacustrine deposits (752-0 cm bsf; 11.7 ± 0.15 cal. ka BP-present). The occurrence of U2 to U4 deposits defines the transition from glacial cold (U1) to net warm postglacial conditions (U5). These climate transitions are marked bychanges in sediments and the presence of very low sedimentation rate periods, possibly related to the Intra-Allerød Cold Period and the coldest phase of the Younger Dryas. Our results support the previously proposed timing of the retreat of the Serra da Estrela glaciers ca. 13.8 ± 0.12 cal. ka BP. The robust chronology of Lake Peixao highlights the potential of Iberian pro-glacial lakes for dating deglaciation processes and will lead to unprecedented decadal-to-centennial timescale palaeoclimate reconstructions in this region since the last glacial-interglacial transition

An Ecological Alternative to Snodgrass & Vanderwart: 360 High Quality Colour Images with Norms for Seven Psycholinguistic Variables

This work presents a new set of 360 high quality colour images belonging to 23 semantic subcategories. Two hundred and thirty-six Spanish speakers named the items and also provided data from seven relevant psycholinguistic variables: age of acquisition, familiarity, manipulability, name agreement, typicality and visual complexity. Furthermore, we also present lexical frequency data derived from Internet search hits. Apart from the high number of variables evaluated, knowing that it affects the processing of stimuli, this new set presents important advantages over other similar image corpi: (a) this corpus presents a broad number of subcategories and images; for example, this will permit researchers to select stimuli of appropriate difficulty as required, (e.g., to deal with problems derived from ceiling effects); (b) the fact of using coloured stimuli provides a more realistic, ecologically-valid, representation of real life objects. In sum, this set of stimuli provides a useful tool for research on visual object-and word- processing, both in neurological patients and in healthy controls