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The management based on the allocation of Territorial Use Rights for Fisheries (TURF) is a mechanism used to achieve the sustainable development of the activity and its fisheries. In Chile, the measure began in the late 1990s, and after 30 years, it remains uncertain whether its implementation has achieved this goal. The objective of the present study is to evaluate the historical performance of the MEABR regime across biological, economic, and administrative dimensions. To achieve this, objectives for each dimension were defined in collaboration with the administrative professionals of the regime, leading to the identification of eight evaluation indicators. The performance results indicate that, in general, during the period from 1998 to 2020, the MEABR regime has met institutional objectives at an “acceptable” level in the biological, economic, and administrative dimensions. Specifically, regarding resource performance, it is observed that species such as loco, sea urchin, and the macroalgae kelps have seen increased initial densities within the areas; however, ecological conditions remain below acceptable levels, generating uncertainty about the future state of these resources. The study identifies the level of success of the regime and proposes strategies to reduce gaps to achieve sustainability objectives.

Adoptive cell transfer with chimeric antigen receptor (CAR)-expressing T cells can induce remarkable complete responses in cancer patients. Therapeutic success has been correlated with central and stem cell-like memory T cell subsets in the infusion product, which are better able to drive efficient CAR T cell in vivo expansion and long-term persistence. We previously reported that inhibition of the mitochondrial pyruvate carrier (MPC) during mouse CAR T cell culture induces a memory phenotype and enhances antitumor efficacy against melanoma. Here, we use a novel MPC inhibitor, MITO-66, which robustly induces a stem cell-like memory phenotype in CD19-CAR T cells generated from healthy donors and patients with relapsed/refractory B cell malignancies. MITO-66-conditioned CAR T cells were superior in controlling human pre-B cell acute lymphoblastic leukemia in mice. Following adoptive cell transfer, MITO-66-conditioned CAR T cells maintained a memory phenotype and protected cured mice against tumor rechallenge. Furthermore, in an in vivo B cell leukemia stress model, CD19-CAR T cells generated in the presence of MITO-66 largely outperformed clinical-stage AKT and PI-3Kδ inhibitors. Thus, we provide compelling preclinical evidence that MPC inhibition with MITO-66 during CAR T cell manufacturing dramatically enhances their antitumor efficacy, thereby paving the way to clinical translation.

Abstract Zoonoses constitute a major risk to human health. Comprehensive assessments on the potential emergence of novel disease outbreaks are essential to ensure the effectiveness of sanitary controls and to establish mitigating actions. Through a continental‐scale survey of rural human settlements conducted over 13 years in 15 Neotropical countries, we document the vast extent of poaching to meet the local demand for pets, resulting in thousands of families living with ca. 275 species of wild animals without any sanitary controls. Parrots account for ca. 80% of wild pets, dying mostly from diseases at an average age of 1 year. This culturally rooted tradition, which dates back to pre‐Columbian times, may lead to health risks by bringing wild animals prone to carrying parasites and pathogens into close contact with humans and their exotic pets and livestock. Although animal pathogens and parasites have been transmitted to humans for centuries, the current trend of human population growth and connectivity can increase the risk of zoonotic outbreaks spreading at an unprecedented pace. Similarly, disease transmission from humans and poultry to wild animals is also expected to be facilitated via wild pets, leading to conservation problems. Several studies have highlighted the risk posed by wildlife city markets for cross‐species disease transmission, ignoring the risk associated with widespread pet ownership of wild animals poached locally in rural areas. Given its geographic and social dimensions, a holistic approach is required to reduce this illegal activity as well as to strengthen health surveillance of seized individuals and people in close contact with poached pets, which would benefit both people and wildlife. Read the free Plain Language Summary for this article on the Journal blog.

Abstract With the exception of a few groups of birds, such as large raptors and colonial seabirds, direct counts of nests cannot be conducted over very large areas for most of the abundant and widely distributed species, and thus indirect methods are used to estimate their relative abundances and population sizes. However, many species of the Family Hirundinidae (swallows and martins) build their mud nests in discrete, predictable and accessible sites, which are reused across years. Therefore, the direct count of active nests could constitute a reliable method for estimating breeding population sizes and their changes at large spatial and temporal scales. We illustrate the feasibility of this monitoring approach through a single year survey of >2700 nests of three coexisting Old‐World species, the barn swallow (Hirundo rustica), the red‐rumped swallow (Cecropis daurica), and the crag martin (Ptyonoprogne rupestris), distributed across Portugal and Spain. Our results revealed changes in the use of nesting substrates and increases in interspecific nest usurpation rates over recent decades. While 56% of the nests of C. daurica were located in rocks five decades ago, almost 100% are nowadays located in anthropogenic substrates such as bridges, road culverts, and abandoned buildings, which could have favored the range expansion of this species. Nest occupation rates were surprisingly low (12% in C. daurica, 21% in H. rustica, and 37% in P. rupestris), and the proportion of abandoned nesting sites was very high (65% in C. daurica, 50% in H. rustica, and 27% in P. rupestris). Abandonment rates reflect the population decline reported for H. rustica. Notably, the usurpation of nests of C. daurica by house sparrows Passer domesticus, which is the main cause of breeding failure, has increased from 2.4% in 1976–1979 to 34.7% of the nests nowadays. The long‐term monitoring of nests may constitute a reliable and affordable method, with the help of citizen science, for assessing changes in breeding population sizes and conservation threats of these and other mud‐nest building hirundines worldwide.

Background: This study aimed to test an artificial intelligence-based reading system (AIRS) capable of reading retinographies of type 2 diabetic (T2DM) patients and a predictive algorithm (DRPA) that predicts the risk of each patient with T2DM of developing diabetic retinopathy (DR). Methods: We tested the ability of the AIRS to read and classify 15,297 retinal photographs from our database of diabetics and 1200 retinal images taken with Messidor-2 into the different DR categories. We tested the DRPA in a sample of 40,129 T2DM patients. The results obtained by the AIRS and the DRPA were then compared with those provided by four retina specialists regarding sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and area under the curve (AUC). Results: The results of testing the AIRS for identifying referral DR (RDR) in our database were ACC = 98.6, S = 96.7, SP = 99.8, PPV = 99.0, NPV = 98.0, and AUC = 0.958, and in Messidor-2 were ACC = 96.78%, S = 94.64%, SP = 99.14%, PPV = 90.54%, NPV = 99.53%, and AUC = 0.918. The results of our DRPA when predicting the presence of any type of DR were ACC = 0.97, S = 0.89, SP = 0.98, PPV = 0.79, NPV = 0.98, and AUC = 0.92. Conclusions: The AIRS performed well when reading and classifying the retinographies of T2DM patients with RDR. The DRPA performed well in predicting the absence of DR based on some clinical variables.

Abstract Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane (CH4) analogues, primarily bromoform (CHBr3). This study aimed to investigate the degradation process of CHBr3 from A. taxiformis in the rumen and whether this process is diet-dependent. An in vitro batch culture system was used according to a 2 × 2 factorial design, assessing two A. taxiformis inclusion rates [0 (CTL) and 2% DM diet (AT)] and two diets [high-concentrate (HC) and high-forage diet (HF)]. Incubations lasted for 72 h and samples of headspace and fermentation liquid were taken at 0, 0.5, 1, 3, 6, 8, 12, 16, 24, 48 and 72 h to assess the pattern of degradation of CHBr3 into dibromomethane (CH2Br2) and fermentation parameters. Additionally, an in vitro experiment with pure cultures of seven methanogens strains (Methanobrevibacter smithii, Methanobrevibacter ruminantium, Methanosphaera stadtmanae, Methanosarcina barkeri, Methanobrevibacter millerae, Methanothermobacter wolfei and Methanobacterium mobile) was conducted to test the effects of increasing concentrations of CHBr3 (0.4, 2, 10 and 50 µmol/L). Results The addition of AT significantly decreased CH4 production (P = 0.002) and the acetate:propionate ratio (P = 0.003) during a 72-h incubation. The concentrations of CHBr3 showed a rapid decrease with nearly 90% degraded within the first 3 h of incubation. On the contrary, CH2Br2 concentration quickly increased during the first 6 h and then gradually decreased towards the end of the incubation. Neither CHBr3 degradation nor CH2Br2 synthesis were affected by the type of diet used as substrate, suggesting that the fermentation rate is not a driving factor involved in CHBr3 degradation. The in vitro culture of methanogens showed a dose-response effect of CHBr3 by inhibiting the growth of M. smithii, M. ruminantium, M. stadtmanae, M. barkeri, M. millerae, M. wolfei, and M. mobile. Conclusions The present work demonstrated that CHBr3 from A. taxiformis is quickly degraded to CH2Br2 in the rumen and that the fermentation rate promoted by different diets is not a driving factor involved in CHBr3 degradation.

El síndrome de sensibilización espinal segmentaria es un cuadro clínico de dolor regional crónico muy frecuente en la consulta fisiátrica cotidiana. Se caracteriza por la presencia de fenómenos de sensibilización periférica y central las cuales son producidas por el bombardeo persistente de impulsos nociceptivos que provienen de una articulación inestable y/o una lesión de los tejidos, e involucran a uno o más segmentos adyacentes de la columna vertebral, sus correspondientes nervios espinales (raíces nerviosas) y a todas las metámeras que estas inervan, con predominio de los sistemas tegumentario y musculoesquelético. musculoesquelético. Este cuadro clínico, que tiene características de un dolor mixto (nociceptivo y nociplástico), causa desconcierto en la mayoría de médicos porque corresponde a una disfunción neuromusculoesquelética que se presenta sin una lesión definida (no se aprecia en los estudios de imágenes ni de electromiografía), o cuando la hay, esta no es proporcional al dolor que manifiesta el paciente. En este sentido, la compresión de su neurofisiopatología es fundamental para establecer un diagnóstico oportuno e iniciar un tratamiento de rehabilitación adecuado, lo cual beneficiará a un gran número de pacientes que sufren de dolor crónico discapacitante a causa de esta condición.

The assessment of fish passage conditions in hydroelectric turbines consists of identifying and quantifying physical magnitudes leading to increased risks of injury of fish passing through turbines in operation. Such assessments are usually carried out either with the use of computer-based methods during design or with field testing of live fish and sensors passing through prototypes. A method in between consists of test rig experimentation, which is critical for testing fish-focused design concepts and offers the opportunity for implementing the most effective design measures for improved fish survivability. However, fish-related assessments in test rigs are not sufficiently documented for industrial applications. This work presents the main findings of an experimental campaign to quantify fish-related hydraulic magnitudes in a physical model of a Kaplan turbine in a commercial test rig. Two operating conditions were tested by releasing miniaturized autonomous sensor devices (termed Sensor Fish Mini) at the turbine intake flow, passing them through the runner in motion and recovering them at the draft tube exit. During passage, time series of acceleration, absolute pressure and rotational velocity were recorded. The recordings were then interpreted to determine the magnitude and likely location of hydraulic stressors hazardous to fish. The statistical tests on the reported measurements indicated that low pressure, collisions on the runner and rotations in the draft tube were not different between the two tested operating points. On the other hand, pressure drop and collision rates on the distributor differed considerably as a function of net head. The outcomes of this investigation showed that test rig evaluations of fish-related properties with Sensor Fish Mini can contribute to an evidence-based development of turbine geometries designed for providing safer passage conditions. Future work will investigate the scaling of test rig measurements to hydraulically equivalent magnitudes in the prototype and their biological consequences.

Abstract Urbanization has reshaped ecosystems and changed natural processes, driving an intense transformation of biomes, biotic community composition and diversity. Despite the growing interest in studying urban ecology over the last decades, the consequences of these changes on species occupying these ecosystems are not yet fully understood. Trophic generalism and tolerance to human disturbance have been proposed as two key traits in the colonization of urban environments. However, most studies focused on species’ average traits, paying less attention to the potential role of inter-individual variability. Here, we examined diet specialization in urban and rural breeding pairs, as well as its relationship with individual behaviour and intraspecific competition, using the burrowing owl as a study model. Our results show that both urban and rural breeding pairs behaved as trophic specialists. The diet of burrowing owl breeding pairs followed a gradient from coleopteran- to micromammal-dominated, which is related to individual behaviour (bolder individuals consuming more coleopterans than shyer ones). Besides, pairs distant from others showed a more diverse diet than those experiencing higher levels of intraspecific competition. Models fitted separately for each habitat showed that the proportion of micromammals in the diet of urban breeding pairs was related to their behavior, while the diet of rural pairs was not affected by individual behavior but by intraspecific competition. However, despite the strong selection of tame and more explorative individuals in urban environments and the higher density they reach in this habitat type, they did not differ in their degree of diet specialization from rural conspecifics. Although it would be necessary to evaluate prey availability on a small scale, our results suggest that burrowing owl breeding pairs behave as specialists, despite the generalist character of the species, and that this specialization is not affected by the occupation of urban environments but to individual behaviour and intraspecific competition.

(1) Underlying Diabetic Retinopathy (DR) is the primary cause of poor vision in young adults. There are automatic image reading systems that can aid screening for DR. (2) Methods: Using our automatic reading system we have counted the number of microaneurysms and hemorrhages in the four quadrants of the ETDRS grid and evaluated the differences between them according to the type of DR. The study was carried out using data from two different databases, MESSIDOR and MIRADATASET. (3) Results: The majority of microaneurysms and hemorrhages are found in the temporal and inferior quadrants of the ETDRS grid. Differences are significant with respect to the other two quadrants at p < 0.001. Differences between the type of DR show that severe-DR has a greater number of microaneurysms and hemorrhages in the temporal and inferior quadrant, being significant at p < 0.001. (4) Conclusions: The count of microaneurysms and hemorrhages is higher in the temporal and inferior quadrants in all types of DR, and those differences are more important in the case of severe-DR.

Abstract Parrots are among the most diverse and widely distributed groups of birds and one of the most threatened bird orders mainly due to habitat loss and illegal poaching. Most parrots are obligate cavity nesters, so the logging of mature trees and the transformation of natural cliffs represent important threats to their conservation. Here, we report novel observations of Neotropical parrots nesting in previously unrecorded substrates. We show the first documented case of the cliff‐nesting burrowing parrots trying to breed at ground level in an abandoned burrowing owl cavity. Additionally, we provide the first documented observations of this species attempting to nest in building cavities in three urbanized areas of Argentina. Moreover, we report data from four countries of 148 pairs of eight species typically breeding in tree cavity using palm tree bracts as nest sites. Behavioral plasticity in nest sites may allow parrots to maximize their nesting success by exploiting alternative breeding substrates. Moreover, these novelties could contribute to cope with habitat loss and further transformation. However, further research is needed to assess the consequences of these nesting innovations in terms of individual fitness and population dynamics as well as potential factors promoting their appearance.

(1) Background: Although DR screening is effective, one of its most significant problems is a lack of attendance. The aim of the present study was to demonstrate the effectiveness of our algorithm in predicting the development of any type of DR and referable DR. (2) Methods: A retrospective study with an 11-year follow-up of a population of 120,389 T2DM patients was undertaken. (3) Results: Applying the results of the algorithm showed an AUC of 0.93 (95% CI, 0.92–0.94) for any DR and 0.90 (95% CI, 0.89–0.91) for referable DR. Therefore, we achieved a promising level of agreement when applying our algorithm. (4) Conclusions: The algorithm is useful for predicting which patients may develop referable forms of DR and also any type of DR. This would allow a personalized screening plan to be drawn up for each patient.

Abstract Fuzzy random forests are well-known machine learning classification mechanisms based on a collection of fuzzy decision trees. An advantage of using fuzzy rules is the possibility to manage uncertainty and to work with linguistic scales. Fuzzy random forests achieve a good classification performance in many problems, but their quality decreases when they face a classification problem with imbalanced data between classes. In some applications, e.g., in medical diagnosis, the classifier is used continuously to classify new instances. In that case, it is possible to collect new examples during the use of the classifier, which can later be taken into account to improve the set of fuzzy rules. In this work, we propose a new iterative method to update the set of trees in the fuzzy random forest by considering trees generated from small sets of new examples. Experiments have been done with a dataset of diabetic patients to predict the risk of developing diabetic retinopathy, and with a dataset about occupancy of an office room. With the proposed method, it has been possible to improve the results obtained when using only standard fuzzy random forests.

Abstract Illegal wildlife trade remains highly active in the Neotropics, as indicated by the thousands of parrots annually sold in illicit city markets. However, little is known about where parrots are poached, whether certain parrot species are selected among those available in the wild, their trade routes, and potential conservation impacts. We conducted a large‐scale survey in Peru and southern Ecuador to simultaneously estimate the relative abundance of parrots in the wild and as household pets in rural areas, determine their origin (locally poached or bought at city markets), and measured the shortest distances to their native ranges and markets through the existing grid of roads. Household‐poached native parrots were found in 96% of the rural localities surveyed. Most pets were locally poached, with only 14% of them bought at markets. Parrot poaching was highly selective, with preferred species (mainly Amazon parrots and large macaws) being collected much more than expected given their abundances in the wild and attaining higher prices than the other species. Individuals that were moved away from their native ranges or bought at distant markets were of those species most preferred by people, and covered large distances (up to 1010 km), even crossing country boundaries. Our results differ from those previously obtained from city markets and seizures of illegally traded parrots in Peru, where preferred species were underrepresented. Local poaching and rural trade activities act at very large spatial scales and negatively affect the population trends of preferred parrot species. This unsustainable scenario is a challenge to the application of effective conservation actions aimed at halting poaching and illegal trade. These actions should focus on very extensive and remote rural areas throughout the Neotropics rather than just on well‐known markets located in large cities.

Summary: The impact of the peptide amino acids side-chain modifications on the immunological recognition has been scarcely explored. We investigate here the effect of methionine oxidation on the antigenicity of the melanoma immunodominant peptide 369-YMDGTMSQV-377 (YMD). Using CD8+ T cell activation assays, we found that the antigenicity of the sulfoxide form is higher when compared to the YMD peptide. This is consistent with free energy computations performed on HLA-A∗02:01/YMD/TCR complex showing that this is lowered upon oxidation, paired with a steep increase in order at atomic level. Oxidized YMD forms were identified at the melanoma cell surface by LC-MS/MS analysis. These results demonstrate that methionine oxidation in the antigenic peptides may generate altered peptide ligands with increased antigenicity, and that this oxidation may occur in vivo, opening up the possibility that high-affinity CD8+ T cells might be naturally primed in the course of melanoma progression, as a result of immunosurveillance.

La contaminación producida en aguas interiores y marinas constituye una problemática que se ha ido agravando durante los últimos años en el mundo. La ubicación en la zona marino-costera de sustancias contaminantes provocada por vertimientos de desechos y residuales depende del comportamiento espacio- temporal de las corrientes marinas. En el golfo de Batabanó se aplicó el Sistema de Cálculo de Corrientes Marinas para Cuba (SISCOM) con el objetivo de estimar este comportamiento. Tal sistema fue creado adicionando nuevas formulaciones matemáticas a un modelo numérico, completamente validado a escala regional, para ajustarlo a las características físico-geográficas del golfo. Su aplicación con alta resolución, brinda estimaciones consideradas válidas para representar el comportamiento espacio-temporal de la dinámica del golfo. Cualquier residual arrojado en Surgidero de Batabanó o la ensenada de La Broa será trasladado muy lentamente por las corrientes marinas (1 cm.s-1 y 4.7 cm.s-1 ) hacia el centro y Suroeste del placer somero y el Oeste de la isla de la Juventud, afectando por un largo periodo de tiempo la costa Suroeste del cuerpo de agua. Los desechos lanzados a las aguas oceánicas adyacentes al golfo serán conducidos a través de su periferia durante el flujo de la marea, con velocidades entre 15 cm.s -1 y 29.5 cm.s-1, hasta el Norte de la isla de la Juventud, afectando inmediatamente las zonas Suroeste y Sureste del golfo; mientras que hacia la parte central y Noreste del golfo el desplazamiento será más lento, con velocidades entre 1 cm.s-1 y 3 cm.s-1.

Abstract Background To evaluate the efficacy of retinal photography obtained by undergraduate students using a smartphone-based device in screening and early diagnosing diabetic retinopathy (DR). Methods We carried out an open prospective study with ninety-nine diabetic patients (194 eyes), who were submitted to an ophthalmological examination in which undergraduate students registered images of the fundus using a smartphone-based device. At the same occasion, an experienced nurse captured fundus photographs from the same patients using a gold standard tabletop camera system (Canon CR-2 Digital Non-Mydriatic Retinal Camera), with a 45º field of view. Two distinct masked specialists evaluated both forms of imaging according to the presence or absence of sings of DR and its markers of severity. We later compared those reports to assess agreement between the two technologies. Results Concerning the presence or absence of DR, we found an agreement rate of 84.07% between reports obtained from images of the smartphone-based device and from the regular (tabletop) fundus camera; Kappa: 0.67; Sensitivity: 71.0% (Confidence Interval [CI]: 65.05–78.16%); Specificity: 94.06% (CI: 90.63–97.49%); Accuracy: 84.07%; Positive Predictive Value (PPV): 90.62%; Negative Predictive Value (NPV): 80.51%. As for the classification between proliferative diabetic retinopathy and non-proliferative diabetic retinopathy, we found an agreement of 90.00% between the reports; Kappa: 0.78; Sensitivity: 86.96%; (CI: 79.07–94.85%); Specificity: 91.49% (CI: 84.95–98.03%); Accuracy: 90.00%; PPV: 83.33%; NPV: 93.48%. Regarding the degree of classification of DR, we found an agreement rate of 69.23% between the reports; Kappa: 0.52. As relating to the presence or absence of hard macular exudates, we found an agreement of 84.07% between the reports; Kappa: 0.67; Sensitivity: 71.60% (CI: 65.05–78.16%); Specificity: 94.06% (CI: 90.63–97.49%); Accuracy: 84.07%; PPV: 90.62%; NPV: 80.51%. Conclusion The smartphone-based device showed promising accuracy in the detection of DR (84.07%), making it a potential tool in the screening and early diagnosis of DR.

This case report describes a new type of perifoveal retinal vascular abnormality (RVA) incidentally discovered during a posterior vitreous detachment (PVD) investigation. A 65-year-old woman with sudden central visual loss displayed a uni-lateral focal telangiectatic venule in the perifoveal area. Multimodal imaging documented the vascular abnormality and associated retinal changes. Despite symptom resolution, the RVA persisted. This case represents a unique presentation of perifoveal RVA, likely an atypical form of macular telangiectasia. The sequential imaging documentation during a process of PVD with central bouquet traction provides insights into the underlying mechanisms in addition to diagnosing and monitoring perifoveal RVAs. [Ophthalmic Surg Lasers Imaging Retina 2024;55:737–741.] [ABSTRACT FROM AUTHOR]

BackgroundThe use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced.MethodsWe recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry.ResultsWe show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141+ DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased.ConclusionsOur study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets.

p38 kinases are key elements of the cellular stress response in animals. They mediate the cell response to a multitude of stress stimuli, from osmotic shock to inflammation and oncogenes. However, it is unknown how such diversity of function in stress evolved in this kinase subfamily. Here, we show that the p38 kinase was already present in a common ancestor of animals and fungi. Later, in animals, it diversified into three JNK kinases and four p38 kinases. Moreover, we identified a fifth p38 paralog in fishes and amphibians. Our analysis shows that each p38 paralog has specific amino acid substitutions around the hinge point, a region between the N-terminal and C-terminal protein domains. We showed that this region can be used to distinguish between individual paralogs and predict their specificity. Finally, we showed that the response to hyperosmotic stress in Capsaspora owczarzaki, a close unicellular relative of animals, follows a phosphorylation–dephosphorylation pattern typical of p38 kinases. At the same time, Capsaspora's cells upregulate the expression of GPD1 protein resembling an osmotic stress response in yeasts. Overall, our results show that the ancestral p38 stress pathway originated in the root of opisthokonts, most likely as a cell's reaction to salinity change in the environment. In animals, the pathway became more complex and incorporated more stimuli and downstream targets due to the p38 sequence evolution in the docking and substrate binding sites around the hinge region. This study improves our understanding of p38 evolution and opens new perspectives for p38 research.

Abstract In fragile ecosystems, the introduction of exotic species could alter some ecological processes. The Austral parakeet (Enicognathus ferrugineous) shows close ecological and evolutionary relationships with the Andean Araucaria (Araucaria araucana), so any alteration in these interactions may have negative consequences for both partners and for ecosystem functioning and structure. We conducted extensive roadside surveys to estimate the abundance of parakeets in the northern Patagonian Andes over 4 years and recorded the food plants consumed by foraging flocks. The use of native habitats and humanized areas like villages and farms was influenced by the Araucaria seed crop. In masting years, the large seed crop allowed a massive use of this resource during the non‐breeding season, and even during the breeding season. The exploitation of exotic plants was minor in the masting year, but became predominant in non‐masting years, especially during the non‐breeding season. This feeding switch towards exotic plants primarily arose because the low Araucaria seed crop in non‐masting years is entirely consumed just after production by domestic and wild exotic mammals living in Araucaria forests year‐round, thus forcing the displacement of parakeets towards anthropic habitats to exploit exotic plants. Given the degradation of the remaining Andean Araucaria forests due to the impact of exotic mammals on the ecological interaction between Araucaria and Austral parakeets, ambitious programs to exclude or reduce the density of these alien mammals, including livestock, are warranted.

Autologous T cells expressing the Chimeric Antigen Receptor (CAR) have been approved as advanced therapy medicinal products (ATMPs) against several hematological malignancies. However, the generation of patient-specific CAR-T products delays treatment and precludes standardization. Allogeneic off-the-shelf CAR-T cells are an alternative to simplify this complex and time-consuming process. Here we investigated safety and efficacy of knocking out the TCR molecule in ARI-0001 CAR-T cells, a second generation αCD19 CAR approved by the Spanish Agency of Medicines and Medical Devices (AEMPS) under the Hospital Exemption for treatment of patients older than 25 years with Relapsed/Refractory acute B cell lymphoblastic leukemia (B-ALL). We first analyzed the efficacy and safety issues that arise during disruption of the TCR gene using CRISPR/Cas9. We have shown that edition of TRAC locus in T cells using CRISPR as ribonuleorproteins allows a highly efficient TCR disruption (over 80%) without significant alterations on T cells phenotype and with an increased percentage of energetic mitochondria. However, we also found that efficient TCRKO can lead to on-target large and medium size deletions, indicating a potential safety risk of this procedure that needs monitoring. Importantly, TCR edition of ARI-0001 efficiently prevented allogeneic responses and did not detectably alter their phenotype, while maintaining a similar anti-tumor activity ex vivo and in vivo compared to unedited ARI-0001 CAR-T cells. In summary, we showed here that, although there are still some risks of genotoxicity due to genome editing, disruption of the TCR is a feasible strategy for the generation of functional allogeneic ARI-0001 CAR-T cells. We propose to further validate this protocol for the treatment of patients that do not fit the requirements for standard autologous CAR-T cells administration.

Objective The aim of present study was to evaluate our clinical decision support system (CDSS) for predicting risk of diabetic retinopathy (DR). We selected randomly a real population of patients with type 2 diabetes (T2DM) who were attending our screening programme.Methods and analysis The sample size was 602 patients with T2DM randomly selected from those who attended the DR screening programme. The algorithm developed uses nine risk factors: current age, sex, body mass index (BMI), duration and treatment of diabetes mellitus (DM), arterial hypertension, Glicated hemoglobine (HbA1c), urine–albumin ratio and glomerular filtration.Results The mean current age of 67.03±10.91, and 272 were male (53.2%), and DM duration was 10.12±6.4 years, 222 had DR (35.8%). The CDSS was employed for 1 year. The prediction algorithm that the CDSS uses included nine risk factors: current age, sex, BMI, DM duration and treatment, arterial hypertension, HbA1c, urine–albumin ratio and glomerular filtration. The area under the curve (AUC) for predicting the presence of any DR achieved a value of 0.9884, the sensitivity of 98.21%, specificity of 99.21%, positive predictive value of 98.65%, negative predictive value of 98.95%, α error of 0.0079 and β error of 0.0179.Conclusion Our CDSS for predicting DR was successful when applied to a real population.

This article critically examines the recent debate on growth models in Comparative Political Economy (CPE). It proposes a framework that combines the strengths of the Growth Model Perspective and the subsequent post-Keynesian criticism, arguing for an extension of Kalecki’s work's influence on the growth model literature. Particularly, it refers to considering the role played by the distributive conflict within the political business cycle, as it implies articulating economic and socio-political determinants of growth models under the same theoretical basis. Given the characteristics of the political business cycle, the Kaleckian-based approach to growth models becomes suitable for analyzing redistributive growth experiences, such as the South American ‘Pink Tide’ and its specific manifestation in Brazil (2003–2016). By stressing how the distributive conflict has shaped Brazil’s recent growth model, the findings highlight the importance of a social classes disputes for the growth model literature and contribute to a more nuanced understanding of growth models, suggesting analytical alternatives for evaluating similar experiences in peripheral economies. [ABSTRACT FROM AUTHOR]

Group 2 innate lymphoid cells (ILC2s) are a component of type 2 immune response recently described to be involved in the regulation of anti-tumor immune responses. Here, the authors show that the expression of the peroxisome proliferator-activated receptor γ (PPAPγ) in human and mouse ILC2 sustains type-2 cytokines secretion and support their pro-tumorigenic role in preclinical cancer models.

This study aimed to evaluate the predictive value of diabetic retinopathy (DR) and its stages with the incidence of major cardiovascular events and all-cause mortality in type 2 diabetes mellitus (T2DM) persons in our large primary healthcare database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated incidence rates of major cardiovascular events [coronary heart disease (CHD), stroke, or both—macrovascular events] and all-cause mortality for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the probability of occurrence between DR and the study events. About 22,402 T2DM subjects with DR were identified in the database and 196,983 subjects without DR. During the follow-up period among the subjects with DR, we observed the highest incidence of all-cause mortally. In the second place were the macrovascular events among the subjects with DR. In the multivariable analysis, fully adjusted for DR, sex, age, body mass index (BMI), tobacco, duration of T2DM, an antiplatelet or antihypertensive drug, and HbA1c, we observed that subjects with any stage of DR had higher risks for all of the study events, except for stroke. We observed the highest probability of all-cause death events (adjusted hazard ratios, AHRs: 1.34, 95% CI: 1.28; 1.41). In conclusion, our results show that DR is related to CHD, macrovascular events, and all-cause mortality among persons with T2DM.

Therapy by adoptive transfer of ex vivo-expanded tumor-infiltrating or genetically modified T cells may lead to impressive clinical responses. However, there is a need to improve in vivo persistence and functionality of the transferred T cells, in particular, to face the highly immunosuppressive environment of solid tumors. Here, we investigate the potential of miR-155, a microRNA known to play an important role in CD8+ T cell fitness. We show that forced expression of miR-155 in tumor antigen-specific T cells improves the tumor control of B16 tumors expressing a low-affinity antigen ligand. Importantly, miR-155-transduced T cells exhibit increased proliferation and effector functions associated with a higher glycolytic activity independent of exogenous glucose. Altogether, these data suggest that miR-155 may optimize the antitumor activity of adoptively transferred low-affinity tumor-infiltrating lymphocytes (TILs), in particular, by rendering them more resistant to the glucose-deprived environment of solid tumors. Thus, transgenic expression of miR-155 may enable therapeutic targeting of self-antigen-specific T cells in addition to neoantigen-specific ones. Keywords: microRNA-155, CD8+ T cells, TCR antigen affinity, therapeutic vaccine, adoptive cell transfer, oncoimmunology

Palms, like all plants, show coevolutionary relationships with animals that have been traditionally categorized as mutualistic (seed dispersers and pollinators) or antagonistic (seed predators). This dual perspective, however, has prevented a full understanding of their true interactions with some animal groups, mainly those that do not ingest entire fruits. One clear example is parrots, which have been described to use palm species as feeding resources, while their role as seed dispersers has been largely neglected. Here, we combined fieldwork data with information from the literature and citizen science (i.e., naturalists and nature photographers) on parrot foraging ecology worldwide to evaluate the spatial and taxonomic extent of parrot-palm interactions and to identify the eco-evolutionary factors involved. We identified 1,189 interactions between 135 parrots and 107 palm species in more than 50 countries across the six realms where palms are present as natives or introduced. Combining this information, we identified 427 unique parrot-palm interacting pairs (i.e., a parrot species interacting with a palm species). Pure antagonistic interactions (i.e., parrots just preying on seeds or eating or destroying their non-reproductive parts) were less common (5%) than mutualistic ones (i.e., parrots benefiting by partially preying on the seed or fruit or consuming the pulp of the fruit or the flower but also contributing to seed dispersal and, potentially, pollination; 89%). After controlling for phylogeny, the size of consumed seeds and parrot body mass were positively related. Seed dispersal distances varied among palm species (range of estimated median dispersal distances: 9–250 m), with larger parrots dispersing seeds at greater distances, especially large fruits commonly categorized as megafauna anachronisms (>4 cm length). Although parrot-palm interactions are widespread, several factors (e.g., social behavior, predation fear, food availability, or seasonality) may affect the actual position of parrots on the antagonism-mutualism continuum for different palm species and regions, deserving further research. Meanwhile, the pervasiveness of parrot-palm mutualistic interactions, mainly involving seed dispersal and pollination, should not be overlooked in studies of palm ecology and evolution.

In 1986, Mosmann and Coffman identified 2 functionally distinct subsets of activated CD4 T cells, Th1 and Th2 cells, being key in distinct T cell mediated responses. Over the past three decades, our understanding of CD4 T cell differentiation has expanded and the initial paradigm of a dichotomic CD4 T cell family has been revisited to accommodate a constantly growing number of functionally distinct CD4 T helper and regulatory subpopulations. Of note, CD4 T cells with cytotoxic functions have also been described, initially in viral infections, autoimmune disorders and more recently also in cancer settings. Here, we provide an historical overview on the discovery and characterization of cytotoxic CD4 T cells, followed by a description of their mechanisms of cytotoxicity. We emphasize the relevance of these cells in disease conditions, particularly in cancer, and we provide insights on how to exploit these cells in immunotherapy.

Objective: The question addressed in this study is the possible effect of mothers' use of parental leave on the share of childcare and housework assumed by each parent. Background: Whilst the length of parental leave is greater in Spain than in other European countries, as it is unpaid, take-up rates are low. Such leaves are taken more frequently and for longer periods by women than men. Method: To determine the answer, two multivariate regression models were applied to National Statistics Institute 2018 Fertility Survey data. The main independent variables were fathers' and mothers' use of parental leave. The models also controlled for the effects of family and socio-economic variables on the share of childcare and housework assumed by each parent. Results: The findings showed that mothers' use of unpaid full-time parental leave traditionalises the distribution of domestic chores only when the leave extends beyond one year, whereas part-time leave-taking has no effect whatsoever. That such reversion to tradition can be neutralised when fathers take leaves attests to the advisability of encouraging paternal use. The effects apply to childcare only, however, for other household chores are still distributed along very traditional lines. Conclusion: Unpaid parental leave use by mothers "traditionalizes" the allocation of childcare within the couple, but only when it takes longer than a year.

Although the utility of Ecological Niche Models (ENM) and Species Distribution Models (SDM) has been demonstrated in many ecological applications, their suitability for modelling epidemics or pandemics, such as SARS-Cov-2, has been questioned. In this paper, contrary to this viewpoint, we show that ENMs and SDMs can be created that can describe the evolution of pandemics, both in space and time. As an illustrative use case, we create models for predicting confirmed cases of COVID-19, viewed as our target “species”, in Mexico through 2020 and 2021, showing that the models are predictive in both space and time. In order to achieve this, we extend a recently developed Bayesian framework for niche modelling, to include: (i) dynamic, non-equilibrium “species” distributions; (ii) a wider set of habitat variables, including behavioural, socio-economic and socio-demographic variables, as well as standard climatic variables; (iii) distinct models and associated niches for different species characteristics, showing how the niche, as deduced through presence-absence data, can differ from that deduced from abundance data. We show that the niche associated with those places with the highest abundance of cases has been highly conserved throughout the pandemic, while the inferred niche associated with presence of cases has been changing. Finally, we show how causal chains can be inferred and confounding identified by showing that behavioural and social factors are much more predictive than climate and that, further, the latter is confounded by the former.

In marine environments, poaching can become a key threat to marine ecosystem conservation. Poaching can occur in marine protected areas and/or in fishery management areas. Unfortunately, understanding the magnitude and characteristics of poaching under community based and co-management governance schemes in coastal and marine environments, has not received the attention it deserves. In Chile, a system of Territorial Users Rights for Fisheries (TURF) has been recognized as one of the largest experiences of small-scale fisheries co-management at a global scale. Currently, poaching is one of the main threats to the TURF system in Chile. In this article, we assessed poaching of a highly valuable benthic resource (Concholepas concholepas) from TURF management areas. We estimated artisanal fisher association leaders’ perceptions of poaching within their TURFs and explore determinants of poaching for Concholepas concholepas. Poaching of Concholepas concholepas showed differences along the studied sites. As expected, the greater abundance of Concholepas concholepas in the management areas generates an increased incentive to poach. Areas that make the greatest investment in surveillance are those most affected by poaching. However, our study cannot determine the effectiveness of current levels of surveillance on illegal extraction. Results show older areas tend to reduce the levels of illegal extraction, which could indicate a greater capacity and experience to control poaching. Supporting fisher associations in enforcing TURFs and following up on sanctions against perpetrators are conditioning factors, highlighted by fisher leaders, for TURF sustainability. The approach used in this study provides insights to prioritize geographies and opportunities to address poaching in small-scale co-managed fisheries.