Rapid changes in phenotype distribution during range expansion in a migratory bird

The capacity of species to track changing environmental conditions is a key component of population and range changes in response to environmental change. High levels of local adaptation may constrain expansion into new locations, while the relative fitness of dispersing individuals will influence subsequent population growth. However, opportunities to explore such processes are rare, particularly at scales relevant to species-based conservation strategies. Icelandic black-tailed godwits, Limosa limosa islandica, have expanded their range throughout Iceland over the last century. We show that current male morphology varies strongly in relation to the timing of colonization across Iceland, with small males being absent from recently occupied areas. Smaller males are also proportionately more abundant on habitats and sites with higher breeding success and relative abundance of females. This population-wide spatial structuring of male morphology is most likely to result from female preferences for small males and better-quality habitats increasing both small-male fitness and the dispersal probability of larger males into poorer-quality habitats. Such eco-evolutionary feedbacks may be a key driver of rates of population growth and range expansion and contraction

Effects of therapeutic and aerobic exercise programs in temporomandibular disorder-associated headaches

Objective: To assess the effects of three 8-week exercise programs on the frequency, intensity, and impact of headaches in patients with headache attributed to temporomandibular disorder (TMD). Methodology: Thirty-six patients diagnosed with headache attributed to TMD participated in the study and were divided into three groups of 12 patients: a therapeutic exercise program (G1, mean age: 26.3±5.6 years), a therapeutic and aerobic exercise program (G2, mean age: 26.0±4.6 years), and an aerobic exercise program (G3, 25.8±2.94 years). Headache frequency and intensity were evaluated using a headache diary, and the adverse headache impact was evaluated using the Headache Impact Test (HIT-6). The intensity was reported using the numerical pain rating scale. These parameters were evaluated twice at baseline (A01/A02), at the end of the 8-week intervention period (A1), and 8-12 weeks after the end of the intervention (A2). Results: At A1, none of the G2 patients reported having headaches, in G1, only two patients reported headaches, and in G3, ten patients reported headache. The headache intensity scores (0.3 [95% CI: -0.401, 1.068]), (0.0 [95% CI: -0.734, 0.734]) and HIT-6 (50.7 [95% CI: 38.008, 63.459]), (49.5 [95% CI: 36.808, 62.259]), significantly decreased in G1 and G2 at A1. At A2 headache intensity scores (0.5 [95% CI: -0.256, 1.256]), (0.0 [95% CI: -0.756, 0.756]) and HIT-6 (55.1 [95% CI: 42.998, 67.268]), (51.7 [95% CI: 39.532, 63.802]) in G1 and G2 haven't change significantly. The effects obtained immediately after the completion of the intervention programs were maintained until the final follow-up in all groups. Conclusion: The programs conducted by G1 (therapeutic exercises) and G2 (therapeutic and aerobic exercise) had significant results at A1 and A2.info:eu-repo/semantics/publishedVersio

Dermatological remedies in the traditional pharmacopoeia of Vulture-Alto Bradano, inland southern Italy

Dermatological remedies make up at least one-third of the traditional pharmacopoeia in southern Italy. The identification of folk remedies for the skin is important both for the preservation of traditional medical knowledge and in the search for novel antimicrobial agents in the treatment of skin and soft tissue infection (SSTI). Our goal is to document traditional remedies from botanical, animal, mineral and industrial sources for the topical treatment of skin ailments. In addition to SSTI remedies for humans, we also discuss certain ethnoveterinary applications. Field research was conducted in ten communities in the Vulture-Alto Bradano area of the Basilicata province, southern Italy. We randomly sampled 112 interviewees, stratified by age and gender. After obtaining prior informed consent, we collected data through semi-structured interviews, participant-observation, and small focus groups techniques. Voucher specimens of all cited botanic species were deposited at FTG and HLUC herbaria located in the US and Italy. We report the preparation and topical application of 116 remedies derived from 38 plant species. Remedies are used to treat laceration, burn wound, wart, inflammation, rash, dental abscess, furuncle, dermatitis, and other conditions. The pharmacopoeia also includes 49 animal remedies derived from sources such as pigs, slugs, and humans. Ethnoveterinary medicine, which incorporates both animal and plant derived remedies, is addressed. We also examine the recent decline in knowledge regarding the dermatological pharmacopoeia. The traditional dermatological pharmacopoeia of Vulture-Alto Bradano is based on a dynamic folk medical construct of natural and spiritual illness and healing. Remedies are used to treat more than 45 skin and soft tissue conditions of both humans and animals. Of the total 165 remedies reported, 110 have never before been published in the mainland southern Italian ethnomedical literature

Norbornene-chitosan spray-dried microspheres for peptide conjugation using thiol-ene “photoclick” chemistry

This work was financed by Portuguese funds through FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação) in the framework of the projects 2022.06048.PTDC (i3S), UIDB/50006/2020 (LAQV-REQUIMTE), LA/P/0045/2020 (ALiCE) and UIDB/00511/2020 (LEPABE). P.A. (SFRH/BD/145471/2019) and D.F. (SFRH/ BD/146890/2019) doctoral grants, were financially supported by national (FCT/Norte 2020 Framework) and European Union (ESF – European Social Fund) funds. B.E. acknowledges FCT for the contract based on the “Lei do Emprego Científico” (DL 57/2016). Maria Cristina L. Martins also acknowledges FCT (LA/P/0070/2020), project Bio2Skin Advanced (2021-24):NORTE-01-0247-FEDER-047225; and MOBILIsE Project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 951723.The action of bioactive peptides, such as antimicrobial peptides (AMP), in the human body is often compromised by limited residence time and stability in the target site. Bioconjugation of peptides to biomaterial surfaces is one of the strategies that may overcome these limitations. Herein, norbornene-chitosan (NorChit) microspheres were engineered to react with thiolated peptides by thiolene “photoclick” chemistry. NorChit microspheres were produced by spray drying and crosslinked with dithiothreitol (DTT) to prevent their solubilization. Microspheres with a diameter of 5 ± 2 µm showed round and smooth morphology with pockets over the surface that could be related with hydrophobic interactions between internal norbornene groups. Thiol-ene bioconjugation carried out using a fluorescent model peptide, showed a yield of 45%, whereas using the peptide but without UV exposure indicated a maximum of peptide adsorption of 30%. Altogether, NorChit microspheres show the potential for carrying bioactive peptides, which may open avenues for AMP activity onto harsh environments in the bod

Arrendamento privado em Portugal: uma leitura a partir da regulação das rendas

Este artigo contribui para o debate do papel do Estado na regulação do sector de arrendamento privado em Portugal num momento em que é implementado um Novo Regime de Arrendamento Urbano. A informação estatística disponível, nomeadamente sobre a duração dos contratos e os valores das rendas, alerta para uma tendência de precarização dos contratos de arrendamento entre 2001 e 2011 e para o declínio da oferta de arrendamento a preços acessíveis. Este artigo enfatiza a importância de medidas de apoio ao mercado de arrendamento privado, focadas simultaneamente no lado da oferta e da procura, que estimulem a oferta de habitação a preços acessíveis

Screening of Dementia in Portuguese Primary Care: Methodology, Assessment Tools, and Main Results

The objectives of this article are as follows: (1) to describe the assessment protocol used to outline people with probable dementia in Primary Health Care; (2) to show the methodological design and procedure to obtain a representative sample of patients with probable dementia; and (3) to report the main characteristics of the sample collected in the context of the study “Characteristics and needs of people with probable dementia.” The study protocol was based on the “Community Assessment of Risk and Treatment Strategies (CARTS) Program” and is composed by a set of instruments that allow the assessment of older adults with probable dementia in several areas (health, psychological, functionality, and other). Descriptive analysis was used to characterize the final sample (n = 436). The study protocol as well as the methodological procedure to obtain the referral of research participants and data collection on the condition of people with probable dementia in Primary Health Care proved to be a valuable tool to obtain a sample of patients distributed by the full range of probable dementia in a large geographical area. Results may allocate the design of care pathways for old people with cognitive disorders to prevent, delay impairment, and/or optimize quality of life of patients

Leveraging vectored vaccine candidates manufacturing to GMP compatible bioprocesse

Background Vectored vaccines are very efficient in the in vivo delivery of antigens either in the form of antigen protein and peptides or genetic material. The bioprocess of vectored vaccines poses however several challenge since the viral particles to be effective must maintain their infectivity. Lentiviral and adenoviral vectors are among the particles more used in the treatment of cancer diseases modulating the immune system. Both viral vectors are currently produced in transient upstream process. While the adenoviral vectors are produced at high titers the lentiviral vector upstream process still requires further improvement. The non-lytic nature of lentivirus enables the design of stable cell lines which may improve its yields through perfusion and longer term productions, reducing costs. The application of novel methods for the downstream processing such as continuous purification will contribute to increase the yield and lower the overall cost of the manufacturing processes. Experimental approach At the upstream process, many of the challenges lentiviral bioproducts present in its manufacturing are related to the apoptosis-leading cytotoxicity of some of the vector components. Supported on our long track experience and enabling tools developed for gammaretrovirus manufacturing, we undertook the challenge of establishing a constitutive stable lentiviral producer cell line. To address this challenge we proposed to eliminate or reduce the cytotoxicity of the lentiviral vector expression components. At the downstream process lentiviral vectors face the challenges common to retroviridae family of vectors namely short half-lives at room temperature, sensitivity to pH variations and salt concentrations, and shear stress. The purification strategy developed was designed to be based on disposable and easily scalable technologies. A final concentration achieving 108 TU mL-1 was targeted since the concentration step itself allows to reduce the burden on process and improve the transduction efficiency. To address the high doses requirements we will report an improved oncolytic adenovirus purification process for phase I and II clinical trials and present a case on the use of Polysorb 20 as a replacement for Triton X-100 during cell lysis. Product recovery, potency, purity and the effect of manufacturing holding points will be discussed. Results and discussion A lentiviral producer cell line constitutively producing titers above 106 TU.mL-1.day-1 was established. The cell line showed to be stable, consistently maintaining vector productivity over one month in the absence of antibiotics. At the bioreaction process it was possible to maintain the cells continuously producing over 10 days. At downstream we implemented scalable protocols for lentiviral and adenoviral vectors that is easy to transfer to GMP environment, combining microfiltration, anion-exchange, and ultrafiltration membranes technologies toward maximization of infectious virus recovery, allowing generation of clinical-grade viral vectors without the need for cleaning validation in a cost-effective manner. Herein we will present and discuss the challenges on the biomanufacturing of lentiviral as well as adenoviral virus, the strategies and novel technologies to be adopted in order to enable a faster development of novel vectored vaccine candidates focusing on several case studies, supported by process technology innovation

Influence of Immobilization Strategies on the Antibacterial Properties of Antimicrobial Peptide-Chitosan Coatings

It is key to fight bacterial adhesion to prevent biofilm establishment on biomaterials. Surface immobilization of antimicrobial peptides (AMP) is a promising strategy to avoid bacterial colonization. This work aimed to investigate whether the direct surface immobilization of Dhvar5, an AMP with head-to-tail amphipathicity, would improve the antimicrobial activity of chitosan ultrathin coatings. The peptide was grafted by copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry by either its C- or N- terminus to assess the influence of peptide orientation on surface properties and antimicrobial activity. These features were compared with those of coatings fabricated using previously described Dhvar5-chitosan conjugates (immobilized in bulk). The peptide was chemoselectively immobilized onto the coating by both termini. Moreover, the covalent immobilization of Dhvar5 by either terminus enhanced the antimicrobial effect of the chitosan coating by decreasing colonization by both Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. Relevantly, the antimicrobial performance of the surface on Gram-positive bacteria depended on how Dhvar5-chitosan coatings were produced. An antiadhesive effect was observed when the peptide was grafted onto prefabricated chitosan coatings (film), and a bactericidal effect was exhibited when coatings were prepared from Dhvar5-chitosan conjugates (bulk). This antiadhesive effect was not due to changes in surface wettability or protein adsorption but rather depended on variations in peptide concentration, exposure, and surface roughness. Results reported in this study show that the antibacterial potency and effect of immobilized AMP vary greatly with the immobilization procedure. Overall, independently of the fabrication protocol and mechanism of action, Dhvar5-chitosan coatings are a promising strategy for the development of antimicrobial medical devices, either as an antiadhesive or contact-killing surface.This work was financed by the FCT- Fundação para a Ciência e a Tecnologia through projects POCI-01-0145-FEDER-031781 (AntINFECT), UIB/50006/2020 (LAQV-REQUIMTE) and FEDER—Fundo Europeu de Desenvolvimento Regional through NORTE 2020—Programa Operacional Regional do Norte-Bio2Skin Advanced (NORTE-01-0247-FEDER-047225). M Barbosa (SFRH/BD/108966/2015) and Pedro Alves (SFRH/BD/145471/2019) Ph.D. grants were financially supported by national (FCT/Norte 2020 Framework) and European Union funds (ESF—European Social Fund). Paula Parreira (CEECIND/01210/2018) and Maria Cristina L. Martins (LA/P/0070/2020) also thank FCT for funding. Maria Cristina L. Martins also acknowledges the MOBILIsE Project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 951723

Impacts of climate extremes in Brazil the development of a web platform for understanding long-term sustainability of ecosystems and human health in amazonia (pulse-Brazil)

This is the final version of the article. Available from the American Meteorological Society via the DOI in this record.This work was funded by the joint FAPESP 2011/51843-2 and NERC NE/J016276/1 International Opportunities Fund. PULSE-Brazil development is also funded by the FAPESP grant (2012/51876-0) under the Belmont Forum Cooperation Agreement. Marengo and Aragão thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for their Research Productivity Fellowship

Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus.

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T-cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL-7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C-C motif) receptor-like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1(hi) ) develop normally in immunocompetent and Rag2(-/-) thymi, their differentiation is partially blocked in Rag2(-/-) Il2rg(-/-) counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross-talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)(+) mTEC subtypes expressing intermediate CCRL1 levels (CCRL1(int) ) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2(-/-) thymi, CCRL1(int) mTECs are restored in Rag2(-/-) Marilyn TCR-Tg mice, indicating that the appearance of postnatal-restricted mTECs is closely linked with T-cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.We thank James Di Santo, Jocelyne Demengeot, and Thomas Boehm for Rag2−/−Il2rg−/−, CCRL1-reporter, and Marilyn-Rag2−/− mice, respectively. We thank Dr. Catarina Leit˜ao for critical reading of the manuscript and technical assistance. We thank FEDER funds through the Operational Competitiveness Programme – COMPETE and by National Funds through Fundaçao para a Ciência e a Tecnologia (FCT) under the project PTDC/SAU-IMU/117057/2010 funded this work. N.L.A., A.R.R.,C.M., and P.M.R. are supported by FCT Investigator program and PhD fellowships