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Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue., Competing Interests: MM, FF, CQ, FA, RR, MR, SB, YP, MC, IB, CK, RA, JG, MB No competing interests declared, (© 2024, Medina et al.)

Background: Those receiving the diagnosis of multiple sclerosis (MS) over the next ten years will predominantly be part of Generation Z (Gen Z). Recent observations within our clinic suggest that younger people with MS utilize online generative artificial intelligence (AI) platforms for personalized medical advice prior to their first visit with a specialist in neuroimmunology. The use of such platforms is anticipated to increase given the technology driven nature, desire for instant communication, and cost-conscious nature of Gen Z. Our objective was to determine if ChatGPT (Generative Pre-trained Transformer) could diagnose MS in individuals earlier than their clinical timeline, and to assess if the accuracy differed based on age, sex, and race/ethnicity., Methods: People with MS between 18 and 59 years of age were studied. The clinical timeline for people diagnosed with MS was retrospectively identified and simulated using ChatGPT-3.5 (GPT-3.5). Chats were conducted using both actual and derivatives of their age, sex, and race/ethnicity to test diagnostic accuracy. A Kaplan-Meier survival curve was estimated for time to diagnosis, clustered by subject. The p-value testing for differences in time to diagnosis was accomplished using a general Wilcoxon test. Logistic regression (subject-specific intercept) was used to capture intra-subject correlation to test the accuracy prior to and after the inclusion of MRI data., Results: The study cohort included 100 unique people with MS. Of those, 50 were members of Gen Z (38 female; 22 White; mean age at first symptom was 20.6 years (y) (standard deviation (SD)=2.2y)), and 50 were non-Gen Z (34 female; 27 White; mean age at first symptom was 37.0y (SD=10.4y)). In addition, a total of 529 people that represented digital simulations of the original cohort of 100 people (333 female; 166 White; 136 Black/African American; 107 Asian; 120 Hispanic, mean age at first symptom was 31.6y (SD=12.4y)) were generated allowing for 629 scripted conversations to be analyzed. The estimated median time to diagnosis in clinic was significantly longer at 0.35y (95% CI=[0.28, 0.48]) versus that by ChatGPT at 0.08y (95% CI=[0.04, 0.24]) (p<0.0001). There was no difference in the diagnostic accuracy between ages and by race/ethnicity prior to the inclusion of MRI data. However, prior to including the MRI data, males had a 47% less likely chance of a correct diagnosis relative to females (p=0.05). Post-MRI data inclusion within GPT-3.5, the odds of an accurate diagnosis was 4.0-fold greater for Gen Z participants, relative to non-Gen Z participants (p=0.01) with the diagnostic accuracy being 68% less in males relative to females (p=0.009), and 75% less for White subjects, relative to non-White subjects (p=0.0004)., Conclusion: Although generative AI platforms enable rapid information access and are not principally designed for use in healthcare, an increase in use by Gen Z is anticipated. However, the obtained responses may not be generalizable to all users and bias may exist in select groups., Competing Interests: Declaration of competing interest M.P., F.V., K.S., K.B., T.M., A.S., K.B., and M.M. report no disclosures. L.T. received personal compensation for advisory services from EMD Serono. L.H. received personal compensation for consulting services from Biogen Inc. and EMD Serono. P.S. received personal compensation for consulting services from Genentech, EMD Serono, Horizon Therapeutics, and Bristol Myers Squibb and research support from Genentech and Clene Nanomedicine. S.M. reports personal compensation for consulting services from Horizon Therapeutics, Bristol Myers Squibb, Novartis, and TG Therapeutics and research support from Genentech. D.T.O. received personal compensation for consulting and advisory services from Biogen Inc., Eisai, EMD Serono, Genentech, Genzyme/Sanofi, Immunic Therapeutics, Moderna, RVL Pharmaceuticals, Inc., and Zenas BioPharma along with research support from EMD Serono/Merck and Novartis. D.T.O. has issued national and international patents along with pending patents related to other developed technologies. D.T.O. received royalties for intellectual property licensed by The Board of Regents of The University of Texas System. D.T.O. is the Founder of Revert Health Inc., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, a systematic investigation of MoS 2 nanostructure growth on a SiO 2 substrate was conducted using a two-stage process. Initially, a thin layer of Mo was grown through sputtering, followed by a sulfurization process employing the CVD technique. This two-stage process enables the control of diverse nanostructure formations of both MoS 2 and MoO 3 on SiO 2 substrates, as well as the formation of bulk-like grain structures. Subsequently, the addition of reduced graphene oxide (rGO) was examined, resulting in MoS 2 /rGO(n), where graphene is uniformly deposited on the surface, exposing a higher number of active sites at the edges and consequently enhancing electroactivity in the HER. The influence of the synthesis time on the treated MoS 2 and also MoS 2 /rGO(n) samples is evident in their excellent electrocatalytic performance with a low overpotential.

Olive trees, alongside grapevines, dominate the Mediterranean tree crop landscape. However, as climate change intensifies, the Mediterranean region, which encompasses 95% of the global olive cultivation area, faces significant challenges. Rising carbon dioxide (CO 2 ) levels, increasing temperatures, and declining precipitation pose substantial threats to olive tree performance. Photosynthesis, respiration, phenology, water use and ultimately yield are possibly the main factors affected. To address this future scenario, it is crucial to develop adaptation and mitigation strategies. Nevertheless, breeding programs and field management practice testing for tree crops are time-consuming endeavors. Fortunately, models can accelerate the evaluation of tailored solutions. In this review, we critically examine the current state of olive tree modeling and highlight key areas requiring improvement. Given the expected impact of climate change, prioritizing research on phenology, particularly regarding bloom and pollination, is essential. Simulations of biomass should incorporate approaches that account for the interactive effects of CO 2 and temperature on photosynthesis and respiration. Furthermore, accurately simulating the influence of water stress on yield necessitates the development of models that integrate canopy behavior with root performance under conditions of water scarcity. By addressing these critical aspects, olive tree models can enhance our understanding of climate change impacts and inform sustainable agricultural practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Villalobos, López-Bernal, García-Tejera and Testi.)

Environmental temperature is one of the most significant factors influencing the developmental rate and survival of embryos and larvae of many marine animals, including polychaetes. The aim of this study was to experimentally evaluate the effect of temperature increase on the embryonic development and larval survival of Spirobranchus incrassatus and S. cf. corniculatus. Adult worms of both species were collected from the western margin of the Gulf of Tehuantepec, Mexico. Embryos and larvae were obtained from these worms and exposed to four temperature treatments (28, 30, 32 and 34°C). The optimal temperature for embryonic development of S. incrassatus and S. cf. corniculatus was 30 and 28°C, respectively. For both species, the maximum critical temperature was 32°C and the lethal temperature was 34°C. The embryonic stages of S. cf. corniculatus were most negatively affected by elevated temperatures. Larval survivorship of S. incrassatus and S. cf. corniculatus was higher at 30°C and 28°C (76.2±2.8%; 72.6±4.2%) and lower at 34°C (28.9±2.6%; 26.3±2.9%), respectively. These results suggest that S. cf. corniculatus has the lowest thermal tolerance. Both Spirobranchus species already live near their upper limit of thermal tolerance in the study region (30°C). In the near future, under a global warming scenario, the distribution of both species could be modified, causing a loss of biodiversity, changes in the trophic chain, and alterations in the water column, such as excess organic matter., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Sea urchins play a key role in the marine environment, contributing to maintain a balance in benthic ecosystems. Toxopneustes roseus acts as a regulator of rhodolith beds and is a key species as a bioturbation promoter, while Rhyncholampas pacificus moderates the detritus content of sediment through various mechanisms and contributes to accelerating the circulation of organic matter. However, nothing is known about their early development, so the objective of this research is to characterize the embryonic and larval development of specimens of the two species from the southern Mexican Pacific and identify the causes that produce their differences. The embryonic development of T. roseus lasted approximately 20 ​h; the echinopluteus larva appeared at 23 ​h and culminated in around 12 days with an eight-armed larva. Metamorphosis was reached at 18 days. The embryonic development of R. pacificus lasted about 15 ​h; the larva emerged at 20 ​h and culminated in about two days with an eight-armed larva. The metamorphosis was completed in 9 days. The reproductive output of both species determines their development time and the structure of their larvae; therefore, the energy of R. pacificus is invested in reaching metamorphosis earlier to ensure that its larvae, which are not very abundant, settle and recruit to the population. Regarding T. roseus, the longest permanence in the plankton is efficiently maintained by its numerous larvae through the presence of mobile arms and the shift of the swimming function to the epauletes. This is the first work that characterizes the early development of a species of the genus Toxopneustes and of the only living species of the genus Ryncholampas. The information generated in this work is essential to gaining knowledge about these groups of echinoids, especially the effect of the environment on their early development., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The use of ML in agronomy has been increasing exponentially since the start of the century, including data-driven predictions of crop yields from farm-level information on soil, climate and management. However, little is known about the effect of data partitioning schemes on the actual performance of the models, in special when they are built for yield forecast. In this study, we explore the effect of the choice of predictive algorithm, amount of data, and data partitioning strategies on predictive performance, using synthetic datasets from biophysical crop models. We simulated sunflower and wheat data using OilcropSun and Ceres-Wheat from DSSAT for the period 2001-2020 in 5 areas of Spain. Simulations were performed in farms differing in soil depth and management. The data set of farm simulated yields was analyzed with different algorithms (regularized linear models, random forest, artificial neural networks) as a function of seasonal weather, management, and soil. The analysis was performed with Keras for neural networks and R packages for all other algorithms. Data partitioning for training and testing was performed with ordered data (i.e., older data for training, newest data for testing) in order to compare the different algorithms in their ability to predict yields in the future by extrapolating from past data. The Random Forest algorithm had a better performance (Root Mean Square Error 35-38%) than artificial neural networks (37-141%) and regularized linear models (64-65%) and was easier to execute. However, even the best models showed a limited advantage over the predictions of a sensible baseline (average yield of the farm in the training set) which showed RMSE of 42%. Errors in seasonal weather forecasting were not taken into account, so real-world performance is expected to be even closer to the baseline. Application of AI algorithms for yield prediction should always include a comparison with the best guess to evaluate if the additional cost of data required for the model compensates for the increase in predictive power. Random partitioning of data for training and validation should be avoided in models for yield forecasting. Crop models validated for the region and cultivars of interest may be used before actual data collection to establish the potential advantage as illustrated in this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morales and Villalobos.)

Trioecy is a sexual system that consists of the co-occurrence of females, males and hermaphrodites in a population and is common in plants; however, in animals it is uncommon and poorly understood. In echinoderms, trioecy had never been recorded until now. Frequencies of females, males, and hermaphrodites were evaluated and gametogenic development was histologically characterized in a population of Toxopneustes roseus inhabiting the Mexican Pacific. Trioecy in this population is functional and temporally stable, since the three sexes coexisted in each sampling month. The hermaphrodites presented similar gametogenic development as the females and males and participated during the spawning season, contributing to the population's reproductive process. Trioecy is considered an evolutionarily transitory state, and it is extremely difficult to explain its presence in a species. We hypothesize that continuous ocean warming represents a threat to the survival of this population of T. roseus, since its early developmental stages, which represent a population bottleneck, are more vulnerable to high temperatures than other sea urchins inhabiting the area, while its population density is significantly lower. These conditions generate a strongly stressed environment, which is the determining factor that maintains the stability of trioecy in the species in which it has been studied., (© 2022. The Author(s).)

Tropical coastal lagoons are important ecosystems that support high levels of biodiversity and provide several goods and services. Monitoring of benthic biodiversity and detection of harmful or invasive species is crucial, particularly in relation to seasonal and spatial variation of environmental conditions. In this study, eDNA metabarcoding was used in two tropical coastal lagoons, Chacahua (CH) and Corralero (C) (Southern Mexican Pacific), to describe the benthic biodiversity and its spatial-temporal dynamics. The distribution of benthic diversity within the lagoons showed a very particular pattern evidencing a transition from freshwater to seawater. Although the two lagoon systems are similar in terms of the species composition of metazoans and microeukaryotes, our findings indicate that they are different in taxa richness and structure, resulting in regional partitioning of the diversity with salinity as the driving factor of community composition in CH. Harmful, invasive, non-indigenous species, bioindicators and species of commercial importance were detected, demonstrating the reach of this technique for biodiversity monitoring along with the continued efforts of building species reference libraries., (© 2022. The Author(s).)

Despite SARS-CoV-2 being a "novel" virus, early detection of anti-spike IgG in severe COVID-19 patients may be caused by the amplification of humoral memory responses against seasonal coronaviruses. Here, we examine this phenomenon by characterizing anti-spike IgG responses in non-hospitalized convalescent individuals across a spectrum of COVID-19 severity. We observe that disease severity positively correlates with anti-spike IgG levels, IgG cross-reactivity against other betacoronaviruses (β-CoVs), and FcγR activation. Analysis of IgG targeting β-CoV-conserved and non-conserved immunodominant epitopes within the SARS-CoV-2 spike protein revealed epitope-specific relationships: IgG targeting the conserved heptad repeat (HR) 2 region significantly correlates with milder disease, while targeting the conserved S2'FP region correlates with more severe disease. Furthermore, a lower HR2-to-S2'FP IgG-binding ratio correlates with greater disease severity, with ICU-hospitalized COVID-19 patients showing the lowest HR2/S2'FP ratios. These findings suggest that HR2/S2'FP IgG profiles may predict disease severity and offer insight into protective versus deleterious humoral recall responses., Competing Interests: Declaration of interests J.L.G., F.B., and R.A.A. were partially supported by Ichor Biologics LLC. R.A.A. and R.A.B. are inventors on a provisional patent related to this study. The remaining authors declare no commercial or financial relationships that are potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 (COVID19) pandemic has left researchers scrambling to identify the humoral immune correlates of protection from COVID-19. To date, the antibody mediated correlates of virus neutralization have been extensively studied. However, the extent that non-neutralizing functions contribute to anti-viral responses are ill defined. In this study, we profiled the anti-spike antibody subtype/subclass responses, along with neutralization and antibody-dependent natural killer cell functions in 83 blood samples collected between 4 and 201 days post-symptoms onset from a cohort of COVID-19 outpatients. We observed heterogeneous humoral responses against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Overall, anti-spike profiles were characterized by a rapid rise of IgA and sustained IgG titers. In addition, strong antibody-mediated natural killer effector responses correlated with milder disease and being female. While higher neutralization profiles were observed in males along with increased severity. These results give an insight into the underlying function of antibodies beyond neutralization and suggest that antibody-mediated natural killer cell activity is a key function of the humoral response against the SARS-CoV-2 spike protein., Competing Interests: Authors JLG and RA were employed by company Ichor Biologics LLC. JLG and RA were partially supported by Ichor Biologics LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fuentes-Villalobos, Garrido, Medina, Zambrano, Ross, Bravo, Gaete-Argel, Oyarzún-Arrau, Amanat, Soto-Rifo, Valiente-Echeverría, Ocampo, Esveile, Ferreira, Cabrera, Torres, Rioseco, Riquelme, Barría, Alvarez, Pinos, Krammer, Calvo, Barria and COVID-19 South Chile Group.)

Background: New World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections., Methods: For this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry., Results: High titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals., Conclusion: A Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies., Competing Interests: JG, FB, and RA were partially supported by Ichor Biologics LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Salinas, Garrido, Salazar, Gonzalez, Zambrano, Fuentes-Villalobos, Bravo, Fica-Leon, Salas-Burgos, Calvo, Alvarez, Armien and Barria.)

Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune response is suspected to contribute to pathogenesis, hence is important to understand the balance between protective and harmfully immunity. CD4 + T regulatory cells (Treg) are essential to control an exacerbated immune response. In human ANDV infection, little is known about CD4 + Treg cells, which may be involved in control immunopathology associated to the infection. In this report, we characterize the phenotype of memory CD4 + Tregs in a HCPS survivor's cohort. Based on the expression of CXCR3, CCR4, and CCR6, we identified different Th-like Treg populations in ANDV survival's PBMCs. In addition, the effect of ANDV-glycoprotein virus like particles (VLP) was determined. We demonstrated that memory CD4 + Treg from HCPS present a specific phenotype, showing higher frequency of PD-1 compared to healthy donors (HD). In addition, it was observed a decrease in the frequency of Th1-like memory CD4 + Treg in HCPS, important to highlight that this signature could be preserved even years after resolution of infection. Moreover, to gain insight in the mechanism involved, we evaluated whether ANDV-glycoprotein (GP) VLP could modulate CD4 + Treg. Interestingly, ANDV-GP VLP induced a decrease in the frequency of CXCR3 (Th1-like) and an increase in CCR4 (Th2-like) memory CD4 + Treg in both HD and HCPS PBMCs, indicating that ANDV-GP could specifically act over CXCR3 and CCR4 in CD4 + Treg. This report contributes to the study of human CD4 + Treg cells in ANDV infection., (Copyright © 2020 Saavedra, Garrido, Fuentes-Villalobos, Calvo, Riquelme, Rioseco, Chahín, Ferreira, Alvarez, Nova-Lamperti and Barria.)

Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples ( n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing., Competing Interests: José Luis Garrido is a co-founder of Ichor Biologics LLC and is currently employed by Ichor Biologics LLC, New York, United States. The rest of the authors currently work in the academia and do not belong to industrial/comercial enterprises. All of the authors declared that they have no competing interests., (© 2020 Farkas et al.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron death. A 20% of familial ALS cases are associated with mutations in the gene coding for superoxide dismutase 1 (SOD1). The accumulation of abnormal aggregates of different proteins is a common feature in motor neurons of patients and transgenic ALS mice models, which are thought to contribute to disease pathogenesis. Developmental morphogens, such as the Wnt family, regulate numerous features of neuronal physiology in the adult brain and have been implicated in neurodegeneration. β-catenin is a central mediator of both, Wnt signaling activity and cell-cell interactions. We previously reported that the expression of mutant SOD1 in the NSC34 motor neuron cell line decreases basal Wnt pathway activity, which correlates with cytosolic β-catenin accumulation and impaired neuronal differentiation. In this work, we aimed a deeper characterization of β-catenin distribution in models of ALS motor neurons. We observed extensive accumulation of β-catenin supramolecular structures in motor neuron somas of pre-symptomatic mutant SOD1 mice. In cell-cell appositional zones of NSC34 cells expressing mutant SOD1, β-catenin displays a reduced co-distribution with E-cadherin accompanied by an increased association with the gap junction protein Connexin-43; these findings correlate with impaired intercellular adhesion and exacerbated cell coupling. Remarkably, pharmacological inhibition of the glycogen synthase kinase-3β (GSK3β) in both NSC34 cell lines reverted both, β-catenin aggregation and the adverse effects of mutant SOD1 expression on neuronal differentiation. Our findings suggest that early defects in β-catenin distribution could be an underlying factor affecting the onset of neurodegeneration in familial ALS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Toxopneustes roseus performs a key role in the eastern tropical Pacific as a strategic herbivore and bioturbation promoter. We evaluated the effect of temperature on the fertilization success, embryonic development and larval survival of T. roseus under laboratory conditions, to understand how the increase in ocean temperature could affect it in a global warming. The highest percentage of fertilization occurred in gametes that were exposed to 30 °C, and a significant negative effect of 32 °C was evidenced by the lowest percentage. There was also a deleterious effect in embryos exposed to 32 °C, resulting in an abnormal development at all the time points. The highest percentage of larval survival occurred at 30 °C, while the lowest percentage occurred at 32 °C. The results suggest that T. roseus probably lives near its upper thermal limit, and future ocean warming could threaten the permanence of the species in the eastern tropical Pacific, or at least lead to contraction or fragmentation of its range limits. Therefore if sea temperature rises globally, it could cause the disappearance of these populations that are living at the edge of their thermal tolerance, but for other populations located in more temperate latitudes, it could propitiate favorable conditions for fertilization and survival of embryos and larvae., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Variation in Disrupted-in-Schizophrenia 1 (DISC1) increases the risk for neurodegenerative diseases, schizophrenia, and other mental disorders. However, the functions of DISC1 associated with the development of these diseases remain unclear. DISC1 has been reported to inhibit Akt/mTORC1 signaling, a major regulator of translation, and recent studies indicate that DISC1 could exert a direct role in translational regulation. Here, we present evidence of a novel role of DISC1 in the maintenance of protein synthesis during oxidative stress. In order to investigate DISC1 function independently of Akt/mTORC1, we used Tsc2-/- cells, where mTORC1 activation is independent of Akt. DISC1 knockdown enhanced inhibition of protein synthesis in cells treated with sodium arsenite (SA), an oxidative agent used for studying stress granules (SGs) dynamics and translational control. N-acetyl-cysteine inhibited the effect of DISC1, suggesting that DISC1 affects translation in response to oxidative stress. DISC1 decreased SGs number in SA-treated cells, but resided outside SGs and maintained protein synthesis independently of a proper SG nucleation. DISC1-dependent stimulation of translation in SA-treated cells was supported by its interaction with eIF3h, a component of the canonical translation initiation machinery. Consistent with a role in the homeostatic maintenance of translation, DISC1 knockdown or overexpression decreased cell viability after SA exposure. Our data suggest that DISC1 is a relevant component of the cellular response to stress, maintaining certain levels of translation and preserving cell integrity. This novel function of DISC1 might be involved in its association with pathologies affecting tissues frequently exposed to oxidative stress., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Several simulation models of the olive crop have been formulated so far, but none of them is capable of analyzing the impact of environmental conditions and management practices on water relations, growth and productivity under both well-irrigated and water-limiting irrigation strategies. This paper presents and tests OliveCan, a process-oriented model conceived for those purposes. In short, OliveCan is composed of three main model components simulating the principal elements of the water and carbon balances of olive orchards and the impacts of some management operations. To assess its predictive power, OliveCan was tested against independent data collected in two 3-year field experiments conducted in Córdoba, Spain, each of them applying different irrigation treatments. An acceptable level of agreement was found between measured and simulated values of seasonal evapotranspiration ( ET , range 393 to 1016 mm year -1 ; RMSE of 89 mm year -1 ), daily transpiration ( E p , range 0.14-3.63 mm d -1 ; RMSE of 0.32 mm d -1 ) and oil yield ( Y oil , range 13-357 g m -2 ; RMSE of 63 g m -2 ). Finally, knowledge gaps identified during the formulation of the model and further testing needs are discussed, highlighting that there is additional room for improving its robustness. It is concluded that OliveCan has a strong potential as a simulation platform for a variety of research applications.

Stomatal oscillations have long been disregarded in the literature despite the fact that the phenomenon has been described for a variety of plant species. This study aims to characterize the occurrence of oscillations in olive trees (Olea europaea L.) under different growing conditions and its methodological implications. Three experiments with young potted olives and one with large field-grown trees were performed. Sap flow measurements were always used to monitor the occurrence of oscillations, with additional determinations of trunk diameter variations and leaf-level stomatal conductance, photosynthesis and water potential also conducted in some cases. Strong oscillations with periods of 30-60 min were generally observed for young trees, while large field trees rarely showed significant oscillations. Severe water stress led to the disappearance of oscillations, but moderate water deficits occasionally promoted them. Simultaneous oscillations were also found for leaf stomatal conductance, leaf photosynthesis and trunk diameter, with the former presenting the highest amplitudes. The strong oscillations found in young potted olive trees preclude the use of infrequent measurements of stomatal conductance and related variables to characterize differences between trees of different cultivars or subjected to different experimental treatments. Under these circumstances, our results suggest that reliable estimates could be obtained using measurement intervals below 15 min.

Available sap flow methods are still far from being simple, cheap and reliable enough to be used beyond very specific research purposes. This study presents and tests a new single-probe heat pulse (SPHP) method for monitoring sap velocity in trees using a single-probe sensor, rather than the multi-probe arrangements used up to now. Based on the fundamental conduction-convection principles of heat transport in sapwood, convective velocity (V h ) is estimated from the temperature increase in the heater after the application of a heat pulse (ΔT). The method was validated against measurements performed with the compensation heat pulse (CHP) technique in field trees of six different species. To do so, a dedicated three-probe sensor capable of simultaneously applying both methods was produced and used. Experimental measurements in the six species showed an excellent agreement between SPHP and CHP outputs for moderate to high flow rates, confirming the applicability of the method. In relation to other sap flow methods, SPHP presents several significant advantages: it requires low power inputs, it uses technically simpler and potentially cheaper instrumentation, the physical damage to the tree is minimal and artefacts caused by incorrect probe spacing and alignment are removed., (© 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.)

The DING protein family consists of proteins of great biological importance due to their ability to inhibit carcinogenic cell growth. A DING peptide with Mr ∼7.57 kDa and pI ∼5.06 was detected in G10P1.7.57, a protein fraction from Capsicum chinense Jacq. seeds. Amino acid sequencing of the peptide produced three smaller peptides showing identity to the DING protein family. G10P1.7.57 displayed a phosphatase activity capable of dephosphorylating different phosphorylated substrates and inhibited the growth of Saccharomyces cerevisiae cells. Western immunoblotting with a custom-made polyclonal antibody raised against a sequence (ITYMSPDYAAPTLAGLDDATK), derived from the ∼7.57 kDa polypeptide, immunodetected an ∼ 39 kDa polypeptide in G10P1.7.57. Purification by electroelution followed by amino acid sequencing of the ∼39 kDa polypeptide yielded seven new peptide sequences and an additional one identical to that of the initially identified peptide. Western immunoblotting of soluble proteins from C. chinense seeds and leaves revealed the presence of the ∼39 kDa polypeptide at all developmental stages, with increased accumulation when the organs reached maturity. Immunolocalization using Dabsyl chloride- or Alexa fluor 488-conjugated antibodies revealed a specific fluorescent signal in the cell cytoplasm at all developmental stages, giving support to the idea that the ∼39 kDa polypeptide is a soluble DING protein. Thus, we have identified and characterized a protein fraction with a DING protein from C. chinense., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Tuberous sclerosis complex (TSC) disease results from inactivation of the TSC1 or TSC2 gene, and is characterized by benign tumors in several organs. Because TSC tumorigenesis correlates with hyperactivation of mTORC1, current therapies focus on mTORC1 inhibition with rapamycin or its analogs. Rapamycin-induced tumor shrinkage has been reported, but tumor recurrence occurs on withdrawal from rapamycin. Autophagy has been associated with development of TSC tumors and with tumor cell survival during rapamycin treatment. mTORC1 and AMPK directly inhibit and activate autophagy, respectively. AMPK is hyperactivated in TSC cells and tumors, and drives cytoplasmic sequestration of the cell-cycle inhibitor p27KIP (p27). Whether AMPK and p27 are involved in rapamycin-induced autophagy and survival of TSC cells remain unexplored. Here, we show that inhibition of AMPK by compound C or by shRNA-mediated depletion of LKB1 reduces activation of autophagy by rapamycin in Tsc2-null cells. Similarly, shRNA-mediated depletion of p27 inhibited rapamycin-induced autophagy. In support of p27 lying downstream of AMPK on the activation of autophagy in Tsc2-null cells, a p27 mutant that preferentially localizes in the cytosol recovered the effect of rapamycin on autophagy in both p27- and LKB1-depleted cells, but a nuclear p27 mutant was inactive. Finally, we show that p27-dependent activation of autophagy is involved in Tsc2-null cell survival under rapamycin treatment. These results indicate that an AMPK/p27 axis is promoting a survival mechanism that could explain in part the relapse of TSC tumors treated with rapamycin, exposing new avenues for designing more efficient treatments for TSC patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Rheb is a conserved small GTPase that belongs to the Ras superfamily, and is mainly involved in activation of cell growth through stimulation of mTORC1 activity. Because deregulation of the Rheb/mTORC1 signaling is associated with proliferative disorders and cancer, inhibition of mTORC1 has been therapeutically approached. Although this therapy has proven antitumor activity, its efficacy is not as expected. Here, we will review the main work on the identification of the role of Rheb in cell growth, and on the relevance of Rheb in proliferative disorders, including cancer. We will also review the Rheb functions that could explain tumor resistance to therapies with mTORC1 inhibitors, and will mainly focus our discussion on mTORC1-independent Rheb functions that could also be implicated in cancer cell survival and tumorigenesis. The current progress on the understanding of the noncanonical Rheb functions prompts future studies to establish their relevance in cancer and in the context of current cancer therapies., (© 2015 UICC.)

The effect of temperature on radial root hydraulic specific resistance (Rp) is a known phenomenon; however, the impact ofRpvariations expected from soil temperature changes over the tree root system is unknown. The present article analyses the relations hip ofRpwith temperature in olive 'Picual' and a hybrid rootstock, GF677, at five different temperatures, showing that a variation of 3- and 4.5-folds exists for olive 'Picual' and GF677 in the range from 10 to 20 °C. The functions obtained were scaled up to show the theoretical changes of total radial root system resistance in a common tree orchard in a Mediterranean climate at a daily and seasonal scale, using recorded soil temperature values: a difference between summer and winter of 3.5-fold for olive 'Picual' and 9-fold for GF677 was observed. Nevertheless,Rpchanges are not only related to temperature, as cavitation or circadian rhythms in aquaporin expression may also play a role. The results obtained from an experiment with the two cultivars submitted to constant pressure and temperature during several hours exhibited a variation inRp, but this was of lower magnitude than that observed due to temperature changes. Finally, a comparison ofRpat 25 °C between GF677 and GN15 (another rootstock obtained from the same parental as GF677) showed significant differences. According to our results, diurnal and seasonal changes inRpdue to temperature variations are of significant importance, and it would therefore be advisable to assess them explicitly into soil-plant-atmosphere continuum models., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Basal cell carcinomas are rare in non-sun-exposed skin, and are even rarer in the perianal region. Alertness to the unusual occurrence of this tumor at perianal site, with understanding of its clinical course, can prevent delay in its diagnosis and morbid aggressiveness in the management of the disease., Presentation of Case: A 93 year old female, referred to our hospital because of a three month bleeding ulcerative lesion, with a diameter approximately of 4.5×3.2cm, located in the perianal region., Discussion: Tumors of the anus and perianal are infrequent neoplasms of the digestive tract. There are many diseases that can be confused with this diagnosis and it is commonly delayed because the tumor is rarely thought of in this particular cutaneous topography. Suspicion and early diagnosis, give the opportunity for a timely and appropriate treatment and also prevent tumor extension., Conclusion: Treatment modalities include early wide local excision to clear margins, ensuring further local recurrence and distant metastasis. The use of local V-Y advancement fasciocutaneous flaps may be another valid option for the reconstruction of perianal skin defects, with less morbidity than other flaps described in the literature., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Serratia marcescens is a Gram negative bacterium (Enterobacteriaceae) often associated with infection of insects. In order to find pathogenic bacteria with the potential to control scarab larvae, several bacterial strains were isolated from the hemocoel of diseased Phyllophaga spp (Coleoptera:Scarabaeidae) larvae collected from cornfields in Mexico. Five isolates were identified as Serratia marcescens by 16S rRNA gene sequencing and biochemical tests. Oral and injection bioassays using healthy Phyllophaga blanchardi larvae fed with the S. marcescens isolates showed different degrees of antifeeding effect and mortality. No insecticidal activity was observed for Spodoptera frugiperda larvae (Lepidoptera: Noctuidae) by oral inoculation. S. marcescens (Sm81) cell-free culture supernatant caused significant antifeeding effect and mortality to P. blanchardi larvae by oral bioassay and also mortality by injection bioassay. Heat treated culture broths lost the ability to cause disease symptoms, suggesting the involvement of proteins in the toxic activity. A protein of 50.2 kDa was purified from the cell-free broth and showed insecticidal activity by injection bioassay towards P. blanchardi. Analysis of the insecticidal protein by tandem- mass spectrometry (LC-MS/MS) showed similarity to a Serralysin-like protein from S. marcescens spp. This insecticidal protein could have applications in agricultural biotechnology.

The links between water and crop yield are well known. In agricultural systems, maximum yield and maximum water productivity (WP; yield divided by water use) are not always compatible goals. In water-limited situations, optimal solutions must be reached by finding a compromise between the levels of crop production and WP. The tradeoffs between production and WP are reviewed here and the dominant effects of the environment on WP are examined. Genetic improvement for WP generally has yield tradeoffs, whereas management measures devised to improve WP also enhance yield. It is shown that partial closure of the stomata in response to environmental stimuli has a variable impact on canopy transpiration, depending on the degree of coupling between the canopy and the atmosphere. In contrast to the behaviour of the major herbaceous crops, WP increases in some woody crops in response to water stress, suggesting that biomass and transpiration are not linearly related, and that deficit irrigation should be successful in these species. Avoiding high evaporative demand periods (e.g. through tolerance to low temperatures) is an important option that aims to increase production and WP. A case study is presented for improving sunflower (Helianthus annuus L.) yield and WP in temperate environments.

Studying the dynamics of stem water content (θ) in living trees has an outstanding physiological interest but all the available techniques to measure θ exhibit major drawbacks. In this work, we present a new methodology to estimate variations in θ along with sap velocity using the compensated heat pulse (CHP) technique. One lab experiment was performed on several wooden blocks obtained from three different tree species. Samples were slowly dried and their moisture loss was monitored by both gravimetric approaches and time-domain reflectometry (TDR) or CHP probes in order to contrast the validity of our methodology (volumetric specific heat (VSH)-CHP) over a range of water contents. In addition, a field experiment was conducted to monitor θ fluctuations in standing olive trees (Olea europaea L. cv. 'Arbequina') growing under three different irrigation regimes. In the lab test, the actual θ values deduced gravimetrically differed from the estimates yielded by the VSH-CHP method. However, it could successfully track relative changes in the water stored for the range of θ expected in living wood. Furthermore, the field experiment showed a seasonal change in θ, which was similar in shape and magnitude to those reported in the literature for olive and other Mediterranean tree species. On the other hand, differences in the seasonal patterns of θ between irrigation treatments strongly corresponded with those of sap flow and some leaf water potential measurements. The results of this work suggest that the CHP technique could be employed to monitor the dynamics of both θ and sap flow simultaneously in standing trees and evidence that seasonal changes in θ might be used as a long-term water status indicator.

The Mexican bacteria Serratia entomophila strain Mor4.1 (Enterobacteriaceae) is pathogenic to coleopteran species of the Phyllophaga genus, which are considered important soil-dwelling pests. Mor4.1 causes anti-feeding activity and mortality to larvae after oral and injection bio-assay either, by bacteria or by cell free culture broth inoculation. The pathogenic determinants of Mor4.1 have not been elucidated. We hypothesize that Mor4.1 produces several toxins and other virulence factors, some acting at the level of the insect gut and others at the hemocoel. To identify and characterize virulence factors, a fosmid library of S. entomophila Mor4.1 was made in Escherichia coli. Five different insecticidal clones were isolated by injecting individual clones into Phyllophaga blanchardi larvae. The complete 40 kb DNA sequence and gene organization of clone G8 was determined. By comparative genomics, 21 genes were associated with virulence. By transposon (Tn5) insertion mutagenesis of G8 and further bio-assays we show that a dUTPase, a flavoprotein and a heptosyltransferase III, are key factors for G8 toxic activity. The heptosyltransferase III, is part of the lipopolysaccharide (LPS) biosynthesis core. We demonstrated that purified LPS from G8 and Mor4.1 are toxic to P. blanchardi larvae by injection bio-assay., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The compensation heat pulse (CHP) method is widely used to estimate sap flow and transpiration in conducting organs of woody plants. Previous studies have reported a natural azimuthal variability in sap flow, which could have practical implications in locating the CHP probes and integrating their output. Sap flow of several olive trees (Olea europaea L. cv. 'Arbequina') previously grown under different irrigation treatments were monitored by the CHP method, and their xylem anatomical characteristics were analyzed from wood samples taken at the same location in which the probes were installed. A significant azimuthal variability in the sap flow was found in a well-irrigated olive tree monitored by eight CHP probes. The azimuthal variability was well related to crown architecture, but poorly to azimuthal differences in the xylem anatomical characteristics. Well-irrigated and deficit-irrigated olive trees showed similar xylem anatomical characteristics, but they differed in xylem growth and in the ratio of nocturnal-to-diurnal sap flow (N/D index). The results of this work indicate that transpiration cannot be accurately estimated by the CHP method in olive trees if a small number of sensors are employed and that the N/D index could be used as a sensitive water status indicator.

The larvae of scarab beetles, known as "white grubs" and belonging to the genera Phyllophaga and Anomala (Coleoptera: Scarabaeidae), are regarded as soil-dwelling pests in Mexico. During a survey conducted to find pathogenic bacteria with the potential to control scarab larvae, a native Serratia sp. (strain Mor4.1) was isolated from a dead third-instar Phyllophaga blanchardi larva collected from a cornfield in Tres Marías, Morelos, Mexico. Oral bioassays using healthy P. blanchardi larvae fed with the Mor4.1 isolate showed that this strain was able to cause an antifeeding effect and a significant loss of weight. Mortality was observed for P. blanchardi, P. trichodes, and P. obsoleta in a multidose experiment. The Mor4.1 isolate also caused 100% mortality 24 h after intracoelomic inoculation of the larvae of P. blanchardi, P. ravida, Anomala donovani and the lepidopteran insect Manduca sexta. Oral and injection bioassays were performed with concentrated culture broths of the Mor4.1 isolate to search for disease symptoms and mortality caused by extracellular proteins. The results have shown that Mor4.1 broths produce significant antifeeding effects and mortality. Mor4.1 broths treated with proteinase K lost the ability to cause disease symptoms and mortality, in both the oral and the injection bioassays, suggesting the involvement of toxic proteins in the disease. The Mor4.1 isolate was identified as a putative Serratia entomophila Mor4.1 strain based on numerical taxonomy and phylogenetic analyses done with the 16S rRNA gene sequence. The potential of S. entomophila Mor4.1 and its toxins to be used in an integrated pest management program is discussed.

We tested the hypothesis that the transpiration (λE p ) of high-coupled canopies, such as olive groves, may be calculated on a daily basis with sufficient precision by the Penman-Monteith 'big leaf' equation, by a model of bulk daily canopy conductance (g c ) capable of scaling for canopy dimension. Given the limited data required, such a model could replace the standard approach (ET 0 × K c ) for calculating olive water requirements, enhancing the precision of estimates. We developed a specific model of daily g c for unstressed olive canopies that was calibrated by transpiration measurements obtained by water balance from a 2-year experiment in a mature orchard with λE p ranging from 0.6 (February 1993) to 11.5 (July 1994) MJ m -2  day -1 and where leaf area index (L) changed from 1.25 to 2.5. The model uses the intercepted fraction of daily PAR and a linear function of average daytime temperature. The model was validated with λE p data collected by eddy covariance in a 3-year experiment conducted in a growing orchard that differed in L and cultivar from the one used in the calibration. The g c model, when used in the Penman-Monteith equation, gave very good daily λE p predictions for all seasons during 3 years, ranging from 0.5 (November 1998) to 5.5 (June 2000) MJ m -2  day -1 , indicating that the goals of dealing with the dependence of olive g c on L and of simulating the seasonal variations in g c were achieved. A comparison with the Jarvis g c model, calibrated with 2 months of measured g c hourly data, showed that the g c model developed here performed better than the Jarvis model for the 3-year dataset. The exception to this was the period in which the Jarvis model was calibrated. This indicates that (1) the Jarvis model did not account for the seasonal variations in g c of the olive trees; and (2) the spatial and temporal scale assumptions required in the calibration of g c generate seasonal errors in the simulated bulk daily λE p for this crop. The applicability of this bulk g c model is restricted to well watered olive canopies and to the one-layer approach of calculating λE p but it could be adapted to rain-fed canopies in the future.