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BACKGROUND Dementia causes a progressive loss of brain function which is often associated with a significant decline in autonomy to carry out activities of daily living, which can lead to functional impairments. Thanks to the current technological advances, resources aimed at cognitive stimulation have emerged. The importance of social robots is given by the ease with which they can promote interaction with the elder adults and the development of cognitive stimulation activities. OBJECTIVE The objectives of the present study were to assess the acceptability and level of interaction of the EBO social-care robot in day centre patients and to analyse whether the systematic viewing of the videos proposed in this study is a suitable tool for assessing the acceptability and interaction of the participants (day centre users) and the EBO robot of the Robolab laboratory. METHODS This study is a descriptive observational pilot study conducted on users of the AZTIDE social and health centre in Cáceres, Extremadura (Spain) who were beneficiaries of the cognitive therapy provided in the occupational therapy service. The inclusion criteria were women and men over 56 years old with a Minimental State Examination (MMSE) equal or over 21 (mild to moderate cognitive impairment). The "robot-participant" interactions took place in two individual interventions, lasting 10-15 min each, for each participant. The interactions replicated the Wizard of Oz technique where the human teleoperator acts as a robot without this being perceived by the elderly person. For this purpose, a user interface was displayed on the teleoperator's terminal and the commands were reproduced by the EBO robot. EBO is a robotic platform consisting of the following hardware for the experiment in question: display capable of generating emotions, RGB (red, green, blue) camera and basic navigation system. RESULTS A total of 6 users participated in the study. During the conversation between the participants and the EBO robot, eye contact was in all cases and in both interactions 100%, the attention paid by the participants to the robot is 10 out of 10 in 83.3%. All participants felt comfortable and calmed during the conversations (9 and 10 points out of 10). The values good and excellent were what the participants considered as regards conversational factors such as attentiveness, naturalness, meaningful conversation and feeling comfortable during both interactions with the EBO robot. CONCLUSIONS There was a high acceptability and level of interaction of the EBO social-care robot with the patients with mild to moderate cognitive impairment attending the day centre. Our results suggest that the systematic viewing of the videos proposed in this study provided enough data regarding the user-robot interaction for assessing the acceptability and interaction of the participants (day centre users) and the EBO robot of the Robolab laboratory. CLINICALTRIAL ClinicalTrials.gov registration identifier: NCT04896333

Cutaneous Melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors (PD-1 and CTLA4) constituted a main breakthrough in the treatment of metastatic CM, particularly in the long-term benefit. However, several molecular pathways are responsible for the failure of this strategy in about 50-70% of CM patients. Some Long Non-coding RNAs (lncRNAs), and circular RNAs (circRNA) are implicated in triggering pro- and antitumorigenic responses to various cancer treatments. The relationship between lncRNA, circRNA and Immune Checkpoint Blockade (ICB) immunotherapy is not extensively explored in cutaneous metastatic melanoma (CMM). The aim of this study is to evaluate the potential role of both circRNA and lncRNA as a predictive immunotherapy biomarker in CMM. RNA-seq from 12 FFPE samples from the metastatic biopsy of metastatic melanoma patients treated with Nivolumab were analyzed. Our findings indicate that specific lncRNA and circRNA are involved in regulatory networks of the immune response against metastatic melanoma under treatment with nivolumab. Moreover, we have established a risk score that allows the prediction of Overall survival (OS) and Progression-free survival (PFS) of CMM patients with high accuracy. This proof of principle work provides a possible insight on the function of ceRNA, contributing to decipher the complex molecular mechanism of ICB cancer treatment response.

One of the main distinguishing features of bacteria belonging to the Cellulomonas genus is their ability to secrete multiple polysaccharide degrading enzymes. However, their application in biomass deconstruction still constitutes a challenge. We addressed the optimisation of the xylanolytic activities in extracellular enzymatic extracts of Cellulomonas sp. B6 and Cellulomonas fimi B-402 for their subsequent application in lignocellulosic biomass hydrolysis by culture in several substrates. As demonstrated by secretomic profiling, wheat bran and waste paper resulted to be suitable inducers for the secretion of xylanases of Cellulomonas sp. B6 and C. fimi B-402, respectively. Both strains showed high xylanolytic activity in culture supernatant although Cellulomonas sp. B6 was the most efficient xylanolytic strain. Upscaling from flasks to fermentation in a bench scale bioreactor resulted in equivalent production of extracellular xylanolytic enzymatic extracts and freeze drying was a successful method for concentration and conservation of the extracellular enzymes, retaining 80% activity. Moreover, enzymatic cocktails composed of combined extra and intracellular extracts effectively hydrolysed the hemicellulose fraction of extruded barley straw into xylose and xylooligosaccharides. Instituto de Biotecnología Fil: Ontañon, Ornella. Instituto Nacional de Tecnología Agropecuaria (INTA). UEDD IABIMO. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Ontañon, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bedő, Soma. Budapest University of Technology and Economics. Faculty of Chemical Technology and Biotechnology. Department of Applied Biotechnology and Food Science. Biorefinery Research Group; Hungría Fil: Ghio, Silvina. Instituto Nacional de Tecnología Agropecuaria (INTA). UEDD IABIMO. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Ghio, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Garrido, Mercedes Maria. Instituto Nacional de Tecnología Agropecuaria (INTA). UEDD IABIMO. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Garrido, Mercedes Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Topalian, Juliana. Instituto Nacional de Tecnología Agropecuaria (INTA). UEDD IABIMO. Instituto de Agrobiotecnología y Biología Molecular. Fil: Topalian, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Jahola, Dóra. Budapest University of Technology and Economics. Faculty of Chemical Technology and Biotechnology. Department of Applied Biotechnology and Food Science. Biorefinery Research Group; Hungría Fil: Fehér, Anikó. Budapest University of Technology and Economics. Faculty of Chemical Technology and Biotechnology. Department of Applied Biotechnology and Food Science. Biorefinery Research Group; Hungría Fil: Valacco, Maria Pia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Centro de Estudios Químicos y Biológicos por Espectrometría de Masa; Argentina Fil: Valacco, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Campos, Eleonora. Instituto Nacional de Tecnología Agropecuaria (INTA). UEDD IABIMO. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Campos, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Fehér, Csaba. Budapest University of Technology and Economics. Faculty of Chemical Technology and Biotechnology. Department of Applied Biotechnology and Food Science. Biorefinery Research Group; Hungría

Background - SCLC is the most aggressive lung cancer type and with the worst prognosis. There are four molecular subtypes based on the high expression of distinct transcription factors and with different therapeutic vulnerabilities. However, all share transcriptional addiction as pathogenic mechanism. Lurbinectedin is a novel oncogenic transcription inhibitor, approved in the United States and other countries for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The aim of this study was to analyze the activity of lurbinectedin in the different SCLC molecular subtypes and to investigate new biomarkers of response. Methods and Results - We have characterized a panel of 20 SCLC human cell lines based on the expression of ASCL1, NEUROD1, YAP1 and POU2F3, where lurbinectedin yielded a mean IC50 value of 6.52 nM, which is considerable greater than the activity exerted by topotecan, irinotecan, carboplatin, etoposide, olaparib, alisertib and navitoclax (IC50 100 µM-100 nM). Lurbinectedin potency is high in the four molecular subtypes, with IC50 values of 4.1, 14.9, 7.2, and 0.2 nM for SCLC-A, -N, -I and -P, respectively. However, high expression of POU2F3 correlated with better responses. In fact, mean IC50 was 0.28 nM for POU2F3high cells versus 12.1 nM for all POU2F3low cells (p=0.0443). Additionally, basal SLFN11 levels were evaluated, observing that SLFN11high cells responded better to lurbinectedin, with IC50 values of 1.1 nM versus 11.8 nM for SLFN11low (p=0.05). Likewise, lurbinectedin treatment induced greater antitumor activity in SLFN11high tumor-bearing mice (H526: T/C, 18% on day 11) than in SLFN11low tumor-bearing mice (H82: T/C, 65% on day 7) after intravenous treatment at 0.18 mg/kg (on days 0, 7 and 14). Finally, SLFN11 expression was evaluated by IHC in FFPE tumor samples from SCLC patients participating in a multicenter phase II clinical trial in advanced solid tumors (NCT02454972), which allowed lurbinectedin accelerated approval in this indication by FDA. Patients with higher expression of SLFN11 had a slightly better overall survival (OS at 6 months: 68.4% ( Conclusions - Lurbinectedin is highly effective in all molecular subtypes of SCLC in vitro and in vivo, with IC50 values at least two logs more potent than for other antitumoral agents and its activity is even greater in tumors with high POU2F3 expression and/or high SLFN11 expression. Citation Format: Marta Martínez Diez, Gema Santamaría Nuñez, María José Guillén, Daniel Rueda, Eva Maria Garrido-Martin, Pablo Avilés, Carmen Cuevas. Lurbinectedin shows potent activity in all four molecular subtypes of small cell lung cancer (SCLC) and POU2F3 and SLFN11 are biomarkers for a better response. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6247.

Immunotherapy based on Immune Checkpoint blockade (ICB) has become a significant therapeutic option for advanced Non Small Cell Lung Cancer (NSCLC) patients. However, there is an urgent need to find novel biomarkers that to reliably stratify good responders to immunotherapy. Currently, the available biomarkers are not specific enough. Exosomes are small membrane vesicles with sizes of 30-100 nm secreted by most cell types including cancer cells. Exosomes operate as an intercellular communication system by sending proteins, mRNA and miRNAs among other relevant RNA molecules. Exosomes enriched with miRNAS are involved in proliferation, differentiation, maduration and immune cell activation. Moreover, in cancer cells miRNA and other small RNA molecule expressions are dysregulated. Exosomes produced from cancer patient's plasma have been shown to be accurate diagnostic tools for the disease. In this study we profiled miRNAs and other small RNA cargo by exosome of plasma samples from 77 Non Small Cell Lung Cancer (NSCLC) metastatic patients before and after the first cycle of immunotherapy to evaluate the potentiality of predicting response to immunotherapy. We perform exosomes together with RNA isolation and small RNAseq sequencing from plasma samples before and after the first ICB cycle. Two independent softwares were used to identify small RNAs (RNAtoolbox and mirMaster). Prior ICB treatment we did not find differentially expressed miRNAs or other small RNA between good and bad responders. Interestingly we identified 12 exosomal miRNA differentially expressed between good and bad responders after the first cycle of ICB. Intriguingly, levels of miR-134-5p, miR-142-3p, miR-143-3p among others previously associated with NSCLC were found to be considerably higher in the good responder group than the bad responder group. Regarding other smallRNA molecules we observed a great variety and variability of piRNA, rRNA, scaRNA, lncRNA, snoRNA, snRNA, miscRNA and circRNA. To address the function of miRNA and other differentially expressed RNA molecules, we consulted KEGG, GO and Reactome for gene regulatory networks. Interestingly, KEGG results show pathways in cancer as top hit and Reactome highlight Immune System and cancer hits. In conclusion, we observed that patients that have favorable response to ICB have distinctive plasma exosomal miRNA patterns that could be used as possible biomarkers for predicting the effectiveness of immunotherapy in advanced NSCLC patients Citation Format: Maria Garrido-Barros, Javier Oliver, Juan Luis Onieva, Beatriz Martinez-Galvez, Jaime Duddelman, Antonio Rueda, Elisabeth Perez, Emilio Alba, Inmaculada Ramos, Juan Zafra, Manuel Cobo, Isabel Barragán. Dynamic characterization of small RNAs in non small cell lung cancer exosomes under immune-checkpoint inhibitor treatments. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3746.

Background: Microtubule targeting agents have demonstrated to be very effective antitumoral drugs. The development of novel anti-tubulin agents with more efficient mechanisms of action presents several challenges due to their poor solubility, troublesome synthesis or purification, and toxicities. In this work, we present the novel anti-tubulin agent PM534, a synthetic small molecule that shows efficient antitumoral and antiangiogenic properties in vitro and in vivo. Methods and Results: PM534 exhibits a potent antitumor activity in vitro with a mean GI50 value in the low nanomolar range in several different human cancer cell lines. Washout in vitro experiments show irreversible cellular effects after 1h in contact with the compound, compelling the cells to apoptotic cell death likely due to PM534 induced disorganization of the tubulin cytoskeleton. PM534 inhibits migration and invasion of tumor cells in vitro, and arrests the cell cycle in the G2/M phase, forcing them to apoptosis. In addition, PM534 presents potent antiangiogenic effects in vitro, robustly inhibiting endothelial cells proliferation and migration, and the formation of angiotubes. The in vivo antitumor activity of PM534 was characterized in human-derived tumors xenografted in athymic nu/nu mice, namely breast (MDA-MB-231), and pancreas (Mia-Paca-2). PM534 was intravenously administered once per week for three consecutive weeks at 5.0 mg/kg. In vivo PM534-induced antitumor activity (vs. placebo) was seen in MDA-MB-231 (T/C, 0.3% on Day 28; TV, p Conclusions: Based on in vitro activity against different human tumor cell lines, in vivo activity in xenografted human tumors, as well as on its anti-angiogenic properties, the safety, pharmacology and preliminary antitumor activity of PM534 will be evaluated in a first-in-human clinical trial to be conducted in patients with advanced solid tumors. Citation Format: Marta Martínez Diez, María José Muñoz-Alonso, Gema Santamaría Nuñez, María José Guillén, María Ángela Oliva, Eva Maria Garrido-Martin, Pablo Avilés, J. Fernando Díaz, Carmen Cuevas. The novel antitubulin agent PM534 exhibits potent antitumoral and antiangiogenic properties in vitro and in vivo. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6243.

The irruption of the immunotherapy for the treatment of non-small cell lung cancer (NSCLC) based on Immune Checkpoint Inhibitors (ICI) PD-1 and PD-L1 inhibitors is considered a treatment revolution. However, only a small percentage of patients benefit with ICI treatment over the long term, and precise biomarkers that can recognize these individuals before or early during treatment have so far eluded. PD-L1 expression and tumor mutational burden (TMB) are the most well studied biomarkers for predicting response to PD- (L)1 blockade-based ICI prior to treatment. TMB is still being clinically assessed whereas PD-L1 has several drawbacks for prediction of persistent benefit. Our aim is to evaluate the basal state and dynamic changes of cell-free DNA (cfDNA) concentration to predict and monitor response in NSCLC patients starting ICI. A total of 248 cfDNA concentration measurements were performed from 87 NSCLC patients. The quantification was done before the start of the treatment, at the second ICI cycle, after 6 and 12 months in treatment, and at progression if it was within the first 12 months. Quality and quantity of the cfDNA was assessed using Qubit High Sensitivity and Bioanalyzer 2100. We first explored the association with response of the basal cell-free DNA concentration using Mann-Whitney-Wilcoxon test. The longitudinal analysis between different time points was tested with Wilcoxon signed-rank tests. Response was ascertained using RECIST parameters at 3, 6, and 12 months. We evaluated the utility of the cfDNA concentration as a prognostic factor using Mantel-Cox test. The response association results indicate that early and long-term response is associated with lower levels of basal cfDNA (p Citation Format: Isabel Barragan, Elisabeth Perez-Ruiz, Juan Luis Onieva, Maria Garrido-Ramos, Beatriz Martinez-Galvez, Jaime Dubbelman, Emilio Alba, Juan Zafra, Manuel Cobo, Javier Oliver, Antonio Rueda-Dominguez. Cell-free DNA concentration as a prognostic biomarker in patients with non-small cell lung cancer under immunotherapy treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1044.

Background - Ecubectedin (PM14) is a novel transcriptional inhibitor related to ecteinascidins family. In this work, we present its antiproliferative activity and mechanism of action. The in vitro antitumor activity obtained in cellular models has been also demonstrated in in vivo models. Methods and results - The antineoplastic activity of ecubectedin was evaluated in a panel of cell lines representative of different solid human cancers, by MTT assays. Ecubectedin exhibits potent antitumor in vitro activity with mean GI50 values in the very low nanomolar range. Electrophoretic Mobility Shift assays demonstrate that ecubectedin binds to DNA and experiments of 3H-uridine incorporation show that the drug efficiently inhibits mRNA synthesis (85% reduction after 90 min). Moreover, ecubectedin specifically inhibits transactivated transcription, as evaluated in a reporter system of the transcriptional activity mediated by NF-κB after activation with TNFα. In the presence of ecubectedin, transactivation was almost completely abolished. The mechanism of transcriptional inhibition involves the stalling and irreversible proteasomal degradation of elongating RNA Pol II. As a final event, ecubectedin induces double strand breaks in the DNA, inducing cell cycle arrest in the S-phase that can be followed through flow cytometry and triggers apoptotic death of the tumor cell as seen through Annexin V flow cytometry assays. The in vivo antitumor activity of ecubectedin was characterized in xenografted tumors of human origin in athymic nu/nu mice, namely breast (MDA-MB-231), soft tissue sarcoma (HT-1080), SCLC (H526 and H82) and prostate (22Rv1). Ecubectedin was intravenously administered (at 1.25 mg/kg) on days 0, 7 and 14. Compared to placebo, ecubectedin treatment of mice bearing xenografts resulted in a statistically significant reduction of volume in MDA-MB-231 (p≤0.0005 on days 7-35), HT-1080 (p≤0.0004 on days 2-14), H82 (p≤0.0001 on days 5-14), H526 (p≤0.0001 from day 4 to the end of the experimental period), and 22Rv1 (p≤0.0001 on days 3-14) tumors. In mice bearing MDA-MB-231, H526 and 22Rv1 tumors, complete tumor remissions were seen in 1/10 (lasting 103 days), 9/10 (lasting 220 days) and 7/10 (lasting 13 days) ecubectedin-treated animals, respectively. Conclusions - Ecubectedin is a novel transcriptional inhibitor that displays potent antiproliferative activity in different human solid cancer models in vitro and in vivo. The drug is currently in clinical development in Phase II trials. Citation Format: Gema Santamaría Nuñez, Marta Martínez Diez, María José Guillén, Eva Maria Garrido-Martin, Pablo Avilés, Carmen Cuevas. Ecubectedin is a novel transcriptional inhibitor that displays potent antitumor effects in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1622.

Woody biomass represents an important source of carbon on earth, and its global recycling is highly dependent on Agaricomycetes fungi. White-rot Basidiomycetes are a very important group in this regard, as they possess a large and diverse enzymatic repertoire for biomass decomposition. Among these enzymes, the recently discovered lytic polysaccharide monooxygenases (LPMOs) have revolutionized biomass processing with their novel oxidative mechanism of action. The strikingly high representation of LPMOs in fungal genomes raises the question of their functional versatility. In this work, we studied an AA9 LPMO from the white-rot basidiomycete Pycnoporus sanguineus, PsAA9A. Successfully produced as a recombinant secreted protein in Pichia pastoris, PsAA9A was found to be a C1-specific LPMO active on cellulosic substrates, generating native and oxidized cello-oligosaccharides in the presence of an external electron donor. PsAA9A boosted cellulolytic activity of glysoside hydrolases from families GH1, GH5, and GH6.This study serves as a starting point towards understanding the functional versatility and biotechnological potential of this enzymatic family, highly represented in wood decay fungi, in Pycnoporus genus. KEY POINTS: • PsAA9A is the first AA9 from P. sanguineus to be characterized. • PsAA9A has activity on cellulose, producing C1-oxidized cello-oligosaccharides. • Boosting activity with GH1, GH5, and GH6 was proven.

This article sheds light on the collection and use of data by libraries in sixteen countries across Africa. It highlights the challenges that librarians and library organizations face in gathering, analyzing, and presenting data of various types for self-advocacy. In this study, qualitative data from a meeting of library representatives was analyzed to identify main challenges including: data integrity in terms of completeness, accuracy, credibility, and relevancy; infrastructure; capacity; local investment in libraries; time; and participation of data collectors and respondents. Implications for those collecting data on African libraries as well as those supporting the use of data in these contexts are discussed. The purpose of this paper is not to feed into representations of African libraries as chronically under-resourced and lacking in capacity, but rather, to constructively engage with first-hand accounts of how librarians are experiencing and navigating barriers in order to offer potential avenues forward for the field.

Small-Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes, SCLC-A and SCLC-N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E-box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes, such as BCL2, INSM1, MYC, and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles's heel, and how this is effectively exploited by lurbinectedin as a novel SCLC therapeutic endeavor.

13 Pág., Plant non-specific lipid transfer proteins (nsLTPs) are usually defined as small, basic proteins, with a wide distribution in all orders of higher plants. Structurally, nsLTPs contain a conserved motif of eight cysteines, linked by four disulphide bonds, and a hydrophobic cavity in which the ligand is housed. This structure confers stability and enhances the ability to bind and transport a variety of hydrophobic molecules. Their highly conserved structural resemblance but low sequence identity reflects the wide variety of ligands they can carry, as well as the broad biological functions to which they are linked to, such as membrane stabilization, cell wall organization and signal transduction. In addition, they have also been described as essential in resistance to biotic and abiotic stresses, plant growth and development, seed development, and germination. Hence, there is growing interest in this family of proteins for their critical roles in plant development and for the many unresolved questions that need to be clarified, regarding their subcellular localization, transfer capacity, expression profile, biological function, and evolution., KM was supported through funding by the Ministry of Higher Education and Scientific Research of Tunisia (CP_2019–2022), ZGK was funded by the Community of Madrid (FOODAL-CM_S2018/BAAA-4574). DPC was granted by Universidad Politécnica de Madrid and Banco Santander for a predoctoral Programa Propio grant. GHR was funded by European Commission (H2020-NMBP-X-KET-2017-768641 AllerScreening). JTA was funded by Instituto de Salud Carlos III (ISCIII) co-founded by FEDER Thematic Networks and Cooperative Research Centers: ARADYAL (RD16/0006/0003). This work was also funded by the Spanish Ministry of Science and Innovation (LISSENTRA; PID2020-113629RB-I00).

The addition of melatonin in seminal extenders due to its antioxidant properties and its beneficial role in sperm preservation has been previously described, especially in seasonal species. The aim of this study was to study a potential seasonal effect based on photoperiod duration when adding a physiological concentration of melatonin in the canine ejaculate. A total of 24 ejaculates were obtained from 10 healthy dogs during the increasing photoperiod (from December 21 to June 21), whereas 12 ejaculates were collected from five healthy individuals during the decreasing photoperiod (from June 22 to December 20). Each ejaculate was separated into two aliquots, and one of them remained as a control, whereas melatonin (100 pM) was added to the other one (C and M treatment groups, respectively). Diluted semen was refrigerated at 5°C. On days 0, 1, 2, 3, and 6, sperm motility analyses were performed using a CASA system and hypoosmotic swelling test (HOST), osmotic resistance test (ORT), and flow cytometry analysis. No effect of melatonin on motility was detected in either photoperiod. Negative effects of melatonin were found for acrosomal defects, apoptosis, and viability in the decreasing photoperiod. The addition of melatonin to sperm in the decreasing photoperiod could create such a high level that it would cause the described negative effects. We found a beneficial effect of melatonin in the increasing photoperiod on acrosomal defects and apoptosis during 0–6 days. Melatonin treatment also increased viability in the short term (days 1 and 2) for both photoperiods. Also, melatonin can provide certain beneficial effects on mitochondrial activity in the medium term (days 2 and 3) in the decreasing photoperiod.

17 Pág., Non-specific lipid transfer proteins (nsLTPs) are small, cysteine-rich proteins, a part of the pathogenesis-related protein family, and numerous of them act as positive regulators during plant disease resistance, growth, and reproduction. These proteins are involved also in the intracellular transfer of lipids, as well as in plant immune responses. Besides their differences in sequences, they show similar features in their structure. However, they show distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. This study reports the identification, in silico characterization and purification of a novel member of the nsLTP2 protein family from durum wheat, TdLTP2. It was generated and purified using the combination of gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). Its identity was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry (MALDI-TOF). TdLTP2 had been expressed in different stress to detect its localization; therefore, fluor-immunolocalization studies accomplished this data. In this approach, to assess the allergenicity of TdLTP2, thirty patients with baker's asthma were enrolled and ELISA to detect the presence of specific IgE antibodies tested their sera. Moreover, the lipid-binding properties of TdLTP2 were examined in vitro and validated using a molecular docking study. In summary, our results demonstrate a new addition of member in plant nsLTPs family, TdLTP2, which can develop a better understanding about its biological functions and shed light on future applications., This work was funded by the Spanish Ministry of Science and Innovation through the project LISENTRA, granted by the Spanish Research State Agency (PID2020-113629RBI00/AEI/10.13039/501100011033), the Comunidad de Madrid (FOODAL-CM: S2018/BAA4574) Spain, and a grant from the Ministry of Higher Education, and Scientific Research of Tunisia, and a grant from. There was no additional external funding received for this study

This article proposes a historical, multispecies, and ontological approach to human–wildlife conflict (HWC) in the Colombian páramos. Focusing on the páramos surrounding the capital city of Bogotá, we reconstruct the historically changing relationship between cattle-farming campesino communities and the Andean bear, Tremarctos ornatus. Using ethnographic and historical research methods, we conceptualise this relationship as embedded in localised landscapes and multispecies assemblages, in which scientists, conservation practitioners, water infrastructures, public environmental agencies, and cows participate as well. This article demonstrates that insufficient attention to the practices and relationships of historically marginalised humans and non-humans in the management of HWCs contributes to new dynamics of exclusion and friction, and can reduce the effectiveness of conservation programmes. We conclude that opening up conservation to the interests and knowledges of local communities is imperative in moving towards more historically informed, pluralistic and effective conservation strategies.

The gut is home to millions of microscopic organisms, which together are called the gut microbiota. Most of these microorganisms live in peace with the rest of our cells, help us get energy from food, and give us essential nutrients that we cannot make ourselves. The cells lining the gut’s surface keep these microorganisms separated from the rest of the body, like the “Great Wall” of our kingdom. On the inside of this Great Wall, the heroes of the mighty immune system watch over and protect us. But how can the immune system tell the difference between our own cells and the gut microorganisms? Or between helpful microorganisms and disease-causing ones? It is an amazing storey, full of secrets. In this article, we will explain how the gut coaches the immune system to recognise enemies, and how some aspects of modern life might be interfering with this process.

Background: In international cooperation projects that are carried out in less developed and developing countries, a large number of children with disabilities present cerebral palsy (CP). Orthopaedic disorders are frequent complications associated with this disorder. Their prevention and early intervention are essential to achieve an appropriate therapeutic approach for children with PC and to improve their quality of life. Objective: To describe the treatment approach that is currently used in international cooperation projects for the rehabilitation management of the orthopaedic disorders in children with cerebral palsy. Methods: This is an observational, descriptive, cross-sectional study, carried out by means of an online questionnaire to professionals in the field of Physiotherapy and Rehabilitation working in international cooperation projects. The inclusion criteria were professionals working in the rehabilitation field in development aid, humanitarian action or emergency projects that provided rehabilitation services, working with children with cerebral palsy from 0 to 18 years old. Results: Ninety-eight questionnaires were analysed. The average age of the participants was 33.2 years, they were mainly working in development cooperation projects (83.33%) that were implemented in rehabilitation centres and through community-based rehabilitation services (60%). The projects were located in countries all over the world but mainly on the Asian continent (71.4%). Physiotherapists and orthopaedic technicians (72.22%) were the main professionals working in these projects, followed by occupational therapists and social workers (55.56%). The results indicated that the orthopaedic disorders were very frequent in the sample (66.67%), with hip subluxation (50%), scoliosis (77.78%), kyphosis (61.1%), clubfoot (88.7%) and varus foot (61.11%) standing out. The most commonly used treatment approaches were positioning (88.89%) and the Bobath concept (83.33%). The technical aids that were used by the professionals were ankle foot orthosis (AFO) (94.44%), bracing (66.67%), standing frames (83.33%), moulded seats (100%), corner seats (93.75%) and adapted seats (92.85%). Conclusions: In international cooperation projects, the rehabilitation treatment of children with cerebral palsy is based on a holistic approach. This is reflected in the interventions that are carried out to treat their orthopaedic disorders and in locally produced devices, awareness raising and community education. However, the professionals surveyed considered that the aids or orthoses used are insufficient in the treatment and prevention of orthopaedic disorders in cerebral palsy.

Allergic sensitization is initiated by protein and epithelia interaction, although the molecular mechanisms leading this encounter toward an allergic phenotype remain unknown. Here, we apply the two-hit hypothesis of inflammatory diseases to the study of food allergy sensitization. First, we studied the effects of long-term depilation in mice by analyzing samples at different time points. Several weeks of depilation were needed until clear immunological changes were evidenced, starting with upregulation of NLRP3 protein levels, which was followed by overexpression of Il1b and Il18 transcripts. Secondly, we assessed the effects of allergen addition (in this case, Pru p 3 in complex with its natural lipid ligand) over depilated skin. Systemic sensitization was evaluated by intraperitoneal provocation with Pru p 3 and measure of body temperature. Anaphylaxis was achieved, but only in mice sensitized with Prup3_complex and not treated with the NLRP3 inhibitor MCC950, thus demonstrating the importance of both hits (depilation + allergen addition) in the consecution of the allergic phenotype. In addition, allergen encounter (but not depilation) promoted skin remodeling, as well as CD45+ infiltration not only in the sensitized area (the skin), but across several mucosal tissues (skin, lungs, and gut), furtherly validating the systemization of the response. Finally, a low-scale study with human ILC2s is reported, where we demonstrate that Prup3_complex can induce their phenotype switch (↑CD86, ↑S1P1) when cultured in vitro, although more data is needed to understand the implications of these changes in food allergy development., This research was funded by the Spanish Government (MINECO, grant BIO2017-84548- R); Instituto de Salud Carlos III (ISCIII) co-founded by FEDER Thematic Networks and Cooperative Research Centers: ARADYAL (RD16/0006/0003; RD16/0006/0013) and the Community of Madrid (FOODAL-CM_S2018/BAAA-4574). DPC was funded by Universidad Politécnica de Madrid and Banco Santander with a predoctoral Programa Propio grant. ARS was funded from the Community of Madrid included in the project FOOD-AL (FOODAL-CM_S2018/BAAA-4574). GHR was funded by European Comission (H2020-NMBP-X-KET-2017-768641—AllerScreening). JTA was funded from Instituto de Salud Carlos III (ISCIII) co-founded by FEDER Thematic Networks and Cooperative Research Centers: ARADYAL (RD16/0006/0003).

Arqueoxarxa es una red que, desde el año 2010, aglutina a los principales museos de arqueología, equipamientos y yacimientos museizados de Cataluña, así como otros museos de ámbito local con colecciones de interés arqueológico. Desde esta red, encabezada por el Museu d’Arqueologia de Catalunya, se ha promocionado desde el inicio el trabajo colaborativo y la maximización de los recursos. Entre sus principales objetivos se encuentra el de dar a conocer los diferentes museos y sus extensas colecciones arqueológicas; por este motivo se ha puesto en marcha un programa transversal con el propósito de agrupar las colecciones arqueológicas y ponerlas en línea a disposición de toda la ciudadanía. Este proyecto llega en un momento especialmente crítico, debido a las dificultades que impone la pandemia COVID19 para acceder presencialmente a un patrimonio ya de por sí muy distribuido en el territorio. El formato inicial escogido para la presentación de las colecciones arqueológicas es un catálogo virtual colectivo dotado de las facetas y controladores para poder filtrar y obtener resultados de manera dinámica. Se trata de un primer paso en la voluntad de dar acceso a las colecciones mediante formatos enriquecidos orientados a la consulta y el descubrimiento del patrimonio arqueológico: mapas de georreferenciación, narrativas digitales (storytelling), anotaciones en objetos 3D y vinculación de documentación histórica (fotografía , fichas de intervención...). El desarrollo de esta plataforma común ha requerido de un esfuerzo para poder superar algunos obstáculos sistémicos como los distintos enfoques en la gestión de la documentación, la diversidad de programas de gestión, la escasez de criterios y pautas comunes, la falta de recursos económicos… Asimismo, este proyecto ha permitido enlazar y poner en valor algunas de las líneas de trabajo transversales impulsadas en los últimos años como, por ejemplo, los esfuerzos de normalización documental o el escaneo 3D de determinadas piezas que forman parte del catálogo en línea, la vinculación de los registros con LOD. El uso de software libre (OMEKA S) ha permitido extender el proyecto a un gran número de instituciones y profesionales sin el coste añadido de las licencias de usuario creando de este modo economías de escala. También ha permitido empoderar tanto la red de museos como sus diferentes miembros y mancomunar el esfuerzo de documentación compartiendo el conocimiento especializado en una plataforma común. Territorio, innovación, accesibilidad y transversalidad son los valores que guian este proyecto de plataforma común de colecciones arqueológicos.