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Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

In the field of insect chemosensation, knowledge of basic principles has come from the model organism, Drosophila melanogaster. However, the different life histories of Culicids result in behaviors that are unique to mosquitoes. In hematophagous species, these behaviors facilitate the transmission of mosquito-borne diseases that pose grave threats to humans. Currently, we have a better understanding of the olfactory system despite many critical taste-driven behaviors such as blood-feeding. To better understand the role of the taste system and how it helps guide taste-driven behaviors, we aimed to characterize the neuronal responses of the mosquito labellum. A comprehensive survey was carried out on the labellar sensilla of the yellow fever mosquito Aedes aegypti using a panel of different categories of compounds (sweet, bitter, salt, water, and amino acids). The qualitative and quantitative differences observed across the different taste categories revealed five functional groups. Our survey showed that in addition to sweet, bitter, water, and salt taste responses, mosquito labellar sensilla exhibit neuronal sensitivity to amino acids. Analysis of responses to mixtures suggests that amino acid sensitivity maps to a neuron distinct from those that respond to the other four taste categories. We then investigated whether the sensitivity of the peripheral taste organs is modulated by physiological changes that the female mosquito undergoes throughout the gonotrophic cycle using a diagnostic panel of tastants. We first measured and compared the sensitivity of non-mated females to that of mated females and found that sensillar sensitivity to sucrose correlates to the meal preference during both states. We then measured labellar sensitivity before a blood meal and 18-20 hours after obtaining a blood meal. Lastly, we measured the sensitivity of male mosquitoes and compared them to the female response. We found that the male sensitivities are higher than the mated females but more similar to non-mated female labellar sensitivities. Overall, this dissertation presents the first map of the functional organization of taste sensilla of the labellum for a major mosquito vector. Our results raise the possibility that alterations in peripheral taste sensitivity underlie shifts in feeding preference during a female’s gonotrophic cycle.

While cancer treatment modalities have improved in recent decades, each subsequent improvement in therapy has brought mixed results and has fallen short of achieving a lasting cure. From chemotherapy and radiotherapy to small molecule inhibitors and monoclonal antibodies to antibody-drug conjugates, each has brought a unique approach and improvement to preceding modalities. Yet, the limitations of these approaches are evident. The discovery of RNA interference (RNAi) and its potential to treat genetic diseases like cancer opened a new therapeutic avenue. Yet, for many years, RNAi faced multiple setbacks and limitations at both the biological and chemical levels.Among the challenges faced in the RNAi field are the inherently large size (>14,000 Da) and highly charged (>40 phosphates) nature of siRNA molecules, which prevents them from passively diffusing across the cell membrane the way that small molecular inhibitors do. Other obstacles include nucleases, innate immunity, and potential off-target silencing effects from siRNAs. Many of the same problems that affect siRNAs also affect antisense oligonucleotides. Delivery with an antibody would significantly improve the prospects of an oligonucleotide reaching its target. But building an antibody with a clearly defined drug-antibody ratio comes with difficulties. Other challenges include delivery and identification of suitable target receptors that are expressed in sufficiently high numbers and can rapidly internalize via endocytosis. The most limiting barrier preventing adequate delivery of siRNA is the difficulty of achieving endosomal escape, which prevents oligonucleotides from reaching the cytoplasm and nucleus of cells. Over the past decade, our laboratory has worked extensively to address these challenges. Oligonucleotide stability and protection from the immune system were achieved in large part through chemical modifications during the oligo synthesis process. Furthermore, a site-specific conjugation approach was developed to create clearly defined antibody-RNA conjugates (ARCs). Currently, a work-in-progress on the chemistry side is the development of universal endosomal escape domains (uEEDs). The work described herein encompasses the development and building of a complex ARC macromolecular therapeutic that, under the right conditions, could hold great potential for the specific knockdown of previously undruggable oncogenes, such as Kras and Myc, and other aberrant genetic targets in viral infections and chronic diseases.

14 páginas, 3 figuras, 2 tablas, Research aimed at understanding the mechanisms underlying the relationship between tree diversity and antagonist infestation is often neglecting resource-use complementarity among plant species. We investigated the effects of tree species identity, species richness, and mycorrhizal type on leaf herbivory and pathogen infestation. We used a tree sapling experiment manipulating the two most common mycorrhizal types, arbuscular mycorrhiza and ectomycorrhiza, via respective tree species in monocultures and two-species mixtures. We visually assessed leaf herbivory and pathogen infestation rates, and measured concentrations of a suite of plant metabolites (amino acids, sugars, and phenolics), leaf elemental concentrations (carbon, nitrogen, and phosphorus), and tree biomass. Tree species and mycorrhizal richness had no significant effect on herbivory and pathogen infestation, whereas species identity and mycorrhizal type had. Damage rates were higher in arbuscular mycorrhizal (AM) than in ectomycorrhizal (EM) trees. Our structural equation model (SEM) indicated that elemental, but not metabolite concentrations, determined herbivory and pathogen infestation, suggesting that the investigated chemical defence strategies may not have been involved in the effects found in our study with tree saplings. Other chemical and physical defence strategies as well as species identity as its determinant may have played a more crucial role in the studied saplings. Furthermore, the SEM indicated a direct positive effect of AM trees on herbivory rates, suggesting that other dominant mechanisms, not considered here, were involved as well. We found differences in the attribution of elemental concentrations between the two rates. This points to the fact that herbivory and pathogen infestation are driven by distinct mechanisms. Our study highlights the importance of biotic contexts for understanding the mechanisms underlying the effects of biodiversity on tree-antagonist interactions, We thank Nicole M. van Dam, Henriette Uthe, Fredd Vergara, Martin Volf, and Alexander Weinhold for their valuable advice on metabolite analyses as well as Beate Rothe and Michael Reichelt for their help with chemical analyses. Moreover, comments by two anonymous reviewers helped to improve the paper. This work was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 677232). Further support came from the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig and the EcoMetEoR platform, funded by the German Research Foundation (FZT 118). AMM acknowledges support from the program for attracting talent to Salamanca from Fundación Salamanca Ciudad de Cultura y Saberes and Ayuntamiento de Salamanca.

18 p.-9 fig., Premise: Light and gravity are fundamental cues for plant development. Our understanding of the effects of light stimuli on plants in space, without gravity, is key to providing conditions for plants to acclimate to the environment. Here we tested the hypothesis that the alterations caused by the absence of gravity in root meristematic cells can be counteracted by light., Methods: Seedlings of wild‐type Arabidopsis thaliana and two mutants of the essential nucleolar protein nucleolin (nuc1, nuc2) were grown in simulated microgravity,either under a white light photoperiod or under continuous darkness. Key variables of cell proliferation (cell cycle regulation), cell growth (ribosome biogenesis),and auxin transport were measured in the root meristem using in situ cellular markers and transcriptomic methods and compared with those of a 1 g control., Results: The incorporation of a photoperiod regime was sufficient to attenuate or suppress the effects caused by gravitational stress at the cellular level in the root meristem. In all cases, values for variables recorded from samples receiving light stimuli in simulated microgravity were closer to values from the controls than values from samples grown in darkness. Differential sensitivities were obtained for the two nucleolin mutants., Conclusions: Light signals may totally or partially replace gravity signals, significantly improving plant growth and development in microgravity. Despite that, molecular alterations are still compatible with the expected acclimation mechanisms, which need to be better understood. The differential sensitivity of nuc1 and nuc2 mutants to gravitational stress points to new strategies to produce more resilient plants to travel with humans in new extraterrestrial endeavors., This work was funded by the Agencia Estatal de Investigación of the Spanish Ministry of Science an Innovation, Grants#ESP2015‐64323‐R and #RTI2018‐099309‐B‐I00 (co‐funded by EU‐ERDF) to F.J.M., and Bonus Recherche from the UPVD to J.S.V. The use of the facilities of microgravity simulation was provided by the ESA‐CORA‐Ground Based Facilities Program, contract Ref. #4000105761 to F.J.M. and R.H. A.M. was recipient of a contract of the Program for Young Researchers Training of the Agencia Estatal de Investigación of the Spanish Ministry of Science an Innovation Ref. #BES‐2013‐063933.

Resumen Introduccion En el mundo, alrededor de 50 millones de personas padecen demencia; la forma mas comun es la enfermedad de Alzheimer (EA), que representa el 60-70% de los casos. Dada su alta incidencia, se hace imperativo disenar estudios que permitan ampliar el conocimiento sobre su aparicion y desarrollo, para proponer diagnosticos tempranos y/o posibles tratamientos. Una de las estrategias metodologicas que se han desarrollado son los modelos transgenicos murinos para el estudio de los factores involucrados en su etiologia, y entre ellos, el estres oxidativo y la respuesta inmune. Desarrollo Se realizo una busqueda de articulos originales y revisiones en PubMed, Scopus y Google Scholar (2013-2019). En esta revision abordamos dos factores que han sido estudiados de forma independiente: el estres oxidativo y la respuesta inmune en modelos transgenicos para la EA, y se discute la relacion que existe entre ellos y que impacta en la perdida de la plasticidad sinaptica y estructural, produciendo como efecto final el deterioro cognitivo. Conclusion Esta revision describe posibles mecanismos en donde participan el estres oxidativo y la respuesta inmune sobre los efectos moleculares, celulares y conductuales en la EA, observando una estrecha relacion entre estos elementos que conducen hacia el deterioro cognitivo.

Spirulina is a cyanobacterium rich in proteins, polyunsaturated fatty acids, and bioactive compounds, such as C-phycocyanin, which has anti-inflammatory and antioxidant properties and possible lipid and glucose metabolism effects. This systematic review aimed to analyze the effects of spirulina on lipid profile, glucose metabolism, and anti-inflammatory markers (CRD42018097156). After systematically searching for randomized controlled trials evaluating spirulina supplementation in adults with obesity, diabetes, or dyslipidemia on Scopus, Embase, PubMed/MEDLINE, Web of Science, and Cochrane Library databases and assessing the risk of bias (Rob 2.0), a random-effects meta-analysis (Mean Difference, CI 95%) was conducted on seven selected articles (n = 338). We found that spirulina supplementation significantly reduced the triglycerides (TG) (mean difference (MD): −15.34 mg/dL; 95% CI: −29.76 to −0.91) and total cholesterol (TC) levels (MD: −11.83 mg/dL; 95% CI: −20.56 to −3.10). However, low-density lipoprotein cholesterol (LDL-C) (MD: −7.80 mg/dL; 95% CI: −16.94 to 1.33), fasting blood glucose (FBS) (MD: −3.38 mg/dL; 95% CI: −9.88 to 3.12), and glycosylated hemoglobin (HbA1c) (MD: −0.27%; 95% CI: −0.94 to 0.39) levels were not significantly reduced. High-density lipoprotein cholesterol (HDL C) (MD: 0.73 mg/dL; 95% CI: −2.49 to 3.94) was also increased but not significantly. Spirulina supplementation resulted in a decrease in TG and TC levels; it improved the lipid profile of patients with type 2 diabetes, metabolic syndrome, overweight, or obesity, showing its significant role as an adjuvant treatment.

Chillies and chilli-based products are important spices on a global basis. The production, processing, transport and storage phases of chillies are prone to infection by Aspergillus Section Flavi and contamination with aflatoxins (AFs), especially aflatoxin B1 (AFB1) for which legislative limits exist in many countries. We have examined the effect of the interacting abiotic factors of water availability (water activity, aw; 0.995-0.850 aw) and temperature (15-37 °C) on (a) lag phases prior to growth, (b) growth, (c) AFB1 production and (d) contour maps of optimum and boundary conditions for colonisation and toxin production by three Aspergillus flavus strains on a 10% chilli-based medium. Additional studies with whole red chillies + A. flavus conidial inoculum on AFB1 contamination during storage for 10-20 days at 30 °C were also carried out. In vitro, the lag phases before growth were delayed by lower temperatures (15, 20 °C) and aw levels (0.928-0.901 aw). There was no statistical difference in growth between the three strains. Optimal growth was at 37 °C and 0.982 aw with no growth at 0.85 aw. Optimal temperature × aw conditions for AFB1 production were at 30 °C and 0.982 aw with no statistical difference in production between strains. No AFB1 was produced at 15-20 °C at 0.901 and 0.928 aw levels, respectively. In situ studies with A. flavus inoculated whole red chillies at 0.90 and 0.95 aw found that this species became the major component of the total fungal populations at 30 °C after 10-20 days storage. AFB1 contamination was above the European legislative limits (5 μg/kg) for spices at 0.90 aw after 20 days storage and at 0.95 aw after 10 and 20 days. This suggests that storage conditions of ≥0.90 aw, especially at ≥25-30 °C represents a significant risk of contamination with AFB1 at levels where rejection might occur, even after only 10-20 days storage.

Ectohydrolytic enzyme activity (EEA) potential of 37 bacterial isolates derived from Orbicella annularis coral and 2 coral pathogens (Vibrio shilonii and V. coralliilyticus) was measured as model to infer the role of bacteria in organic matter processing within coral reef ecosystems. Bacterial cell-specific activities of eight enzyme types were measured after incubation in organic matter enriched and unenriched filtered seawater. Max value of activities of alkaline phosphatase, oleate-lipase, stearate-lipase and proteinase were 769.3, 327.6, 82.9 and 36.7 amol cell−1 h−1, respectively. Chitinase, α-mannosidase, α-glucosidase and β-glucosidase were generally lower by comparison (max 4.7–20.7 amol cell−1 h−1). No “super” isolates (bacteria expressing high levels of all ectohydrolases) were found suggesting a “specialization” among individual bacterial strains. Cumulatively, the 39 isolates tested displayed a broad range of cell-specific enzyme activities in both organic matter conditions. Culture-independent measurement of coral mucus layer EEA in O. annularis off a Panama reef showed comparable EEA patterns and diversity as the isolates. Volume-specific EEAs of all enzymes except alkaline phosphatase were 8–48 times higher in mucus than in surrounding seawater (SSW) samples. However, cell-specific EEAs in mucus were generally lower than in the SSW partly due to more abundant cells in the mucus than in SSW. For field samples, ≥ 85% of proteinase was cell-bound, while lipase was preferentially dissolved (40–96%). In general, the production of dissolved EEAs varied among measurements depending on sample source and enzyme types, suggesting a potential role of ectoenzyme size distribution in linking the whole reef ecosystem. Our findings support that the cumulative ectoenzyme expression (“ectoenzymome”) of the coral microbiome has the potential to maintain the functional resilience of the coral holobiont and response to stress through its contribution to organic matter processing within coral reef ecosystems.

Objective To evaluate the protective effect of house-screening (HS) on indoor Ae. aegypti infestation, abundance and arboviral infection in Merida, Mexico. Methods In 2019, we performed a cluster randomized controlled trial (6 control and 6 intervention areas: 100 households/area). Intervention clusters received permanently fixed fiberglass HS on all windows and doors. The study included two cross-sectional entomologic surveys, one baseline (dry season in May 2019) and one post-intervention (PI, rainy season between September-October 2019). The presence and number of indoor Aedes females and blood-fed females (indoor mosquito infestation) as well as arboviral infections with dengue (DENV) and Zika (ZIKV) viruses were evaluated in a subsample of 30 houses within each cluster. Results HS houses had significatively lower risk for having Aedes aegypti female mosquitoes (odds ratio [OR]=0.56, 95% C. I. 0.33-0.97, P=0.04) and blood-fed females (OR=0.53, 95% C. I. 0.28-0.97, P=0.04) than unscreened households from the control arm. Compared to control houses, HS houses had significantly lower indoor Ae. aegypti abundance (rate ratio [RR]=0.50, 95% C. I. 0.30-0.83, P=0.01), blood-fed Ae. aegypti females (RR=0.48, 95% C. I. 0.27-0.85, P=0.01) and female Ae. aegypti positive for arboviruses (OR=0.29, 95% CI 0.10-0.86, P=0.02). The estimated intervention efficacy in reducing Ae. aegypti arbovirus infection was 71%. Conclusions These results provide evidence supporting the use of HS as an effective pesticide-free method to control house infestations with Aedes aegypti and reduce the transmission of Aedes-transmitted viruses such as DENV, chikungunya (CHIKV), and ZIKV.

Nosema ceranae, es un parásito obligatorio del intestino medio de las abejas melíferas que causa destrucción de las células epiteliales afectando la digestión y asimilación del alimento, impactando negativamente el desarrollo y sobrevivencia de las colonias de abejas. Con la finalidad de reducir los efectos negativos, se evaluó la eficacia del timol en el control de esta parasitosis. El estudio se realizó en dos apiarios experimentales con un total de 56 colonias de abejas distribuidas en tres grupos experimentales: G1) 18 colonias que recibieron tratamiento con fumagilina como producto de referencia (25.2 mg de fumagilina/semana); G2) 19 colonias que recibieron tratamiento con timol como producto alternativo (66 mg de cristales/semana) y G3) 19 colonias que no recibieron ningún tratamiento (grupo testigo). Los tratamientos con la fumagilina y timol se aplicaron a través del jarabe de azúcar una vez por semana durante cuatro semanas consecutivas. Los niveles de infección de N. ceranae se estimaron en el macerado del abdomen de 60 abejas adultas colectadas de cada colonia experimental. Los resultados al final de los tratamientos indican que las colonias que recibieron fumagilina (G1) disminuyeron sus niveles de infección de 123,529 a 1,805 esporas por abeja; para G2 (timol), la reducción fue de 133,438 a 28,099 esporas por abeja, y para las colonias del grupo testigo (G3) fue de 119,306 a 36,447 esporas por abeja. Los tres grupos experimentales presentaron diferencias estadísticas significativas en los niveles de infección de N. ceranae al final de los tratamientos. La fumagilina presentó una mayor eficacia (95.2 %) en comparación con el timol la, cual fue baja (31.1 % de eficacia) indicando que se requieren estudios adicionales para determinar la concentración más efectiva a nivel de colonia bajo condiciones tropicales de Yucatán, a fin de que este aceite esencial de origen vegetal sea incorporado como producto alternativo para el control de esta parasitosis.

The cytosol of eukaryotic host cells is an intrinsically hostile environment for bacteria. Understanding how cytosolic pathogens adapt to and survive in the cytosol is critical to developing novel therapeutic interventions for these pathogens. The cytosolic pathogen Listeria monocytogenes requires glmR (previously known as yvcK), a gene of unknown function, for resistance to cell wall stress, cytosolic survival, inflammasome avoidance and ultimately virulence in vivo. A genetic suppressor screen revealed that blocking utilization of UDP-GlcNAc by a non-essential wall teichoic acid decoration pathway restored resistance to cell wall stress and partially restored virulence of ΔglmR mutants. In parallel, metabolomics revealed that ΔglmR mutants are impaired in the production of UDP-GlcNAc, an essential peptidoglycan and wall teichoic acid (WTA) precursor. We next demonstrated that purified GlmR can directly catalyze the synthesis of UDP-GlcNAc from GlcNAc-1P and UTP, suggesting that it is an accessory uridyltransferase. Biochemical analysis of GlmR orthologues suggest that uridyltransferase activity is conserved. Finally, mutational analysis resulting in a GlmR mutant with impaired catalytic activity demonstrated that uridyltransferase activity was essential to facilitate cell wall stress responses and virulence in vivo. Taken together these studies indicate that GlmR is an evolutionary conserved accessory uridyltransferase required for cytosolic survival and virulence of L. monocytogenes.ImportanceBacterial pathogens must adapt to their host environment in order to cause disease. The cytosolic bacterial pathogen Listeria monocytogenes requires a highly conserved protein of unknown function, GlmR (previously known as YvcK) to survive in the host cytosol. GlmR is important for resistance to some cell wall stresses and is essential for virulence. The ΔglmR mutant is deficient in production of an essential cell wall metabolite, UDP-GlcNAc, and suppressors which increase metabolite levels also restore virulence. Purified GlmR can directly catalyze the synthesis of UDP-GlcNAc and this enzymatic activity is conserved in pathogens from Firmicutes and Actinobacteria phyla. These results highlight the importance accessory cell wall metabolism enzymes in responding to cell wall stress in a variety of bacterial pathogens.

Introducción. La creciente resistencia bacteriana a los antibióticos representa una amenaza mundial de salud pública. Las excreciones y secreciones larvarias derivadas de moscas necrófagas de la familia Calliphoridae podrían configurar una fuente promisoria para contrarrestar sus efectos.Objetivo. Comparar la actividad antimicrobiana de las excreciones y secreciones larvarias nativas, y de las mayores y menores de 10 kDa de Calliphora vicina y Sarconesiopsis magellanica (Diptera: Calliphoridae).Materiales y métodos. El bioensayo se hizo a partir de la técnica de turbidimetría y en el caso de las excreciones y secreciones menores de 10 kDa se determinó la concentración inhibitoria mínima (CIM).Resultados. Las excreciones y secreciones nativas y las menores de 10 kDa de C. vicina y S. magellanica, evidenciaron una potente actividad antibacteriana contra tres cepas de Staphylococcus aureus y cuatro bacterias Gram negativas, siendo las menores de 10 kDa más efectivas que las nativas en las dos especies de moscas evaluadas. Además, las menores de 10 kDa presentaron la misma efectividad, aunque en las pruebas de CIM se observó que las de S. magellanica fueron más potentes en todas las bacterias evaluadas, excepto contra la cepa de S. aureus ATCC 25923. Las mayores de 10 kDa no inhibieron el crecimiento bacteriano.Conclusión. Los resultados validaron, en general, que estas sustancias son fuente importante para el aislamiento y la caracterización de agentes antimicrobianos.

Aims Plastic debris are constantly released into oceans where, due to weathering processes, they suffer fragmentation into micro- and nanoplastics. Diverse microbes often colonize these persisting fragments, contributing to their degradation. However, there are scarce reports regarding the biofilm formation of eukaryotic decomposing microorganisms on plastics. Here, we evaluated five yeast isolates from deep-sea sediment for catabolic properties and early adhesion ability on high-density polyethylene (HDPE). Methods and Results We assessed yeast catabolic features and adhesion ability on HDPE fragments subjected to abiotic weathering. Adhered cells were evaluated through Crystal Violet Assay, Scanning Electron Microscopy, Atomic Force Microscopy and Infrared Spectroscopy. Isolates were identified as Candida parapsilosis and exhibited wide catabolic capacity. Two isolates showed high adhesion ability on HDPE, consistently higher than the reference C. parapsilosis strain, despite an increase in fragment roughness due to weathering. Isolate Y5 displayed the most efficient colonization, with production of polysaccharides and lipids after 48 h of incubation. Conclusion This work provides insights on catabolic metabolism and initial yeast-HDPE interactions of marine C. parapsilosis strains. Significance and Impact of the Study Our findings represent an essential contribution to the characterization of early interactions between deep-sea undescribed yeast strains and plastic pollutants found in oceans.

Fumonisins (FBs), a widespread group of mycotoxins produced by Fusarium spp., are natural contaminants in cereals and foodstuffs. Fumonisin B1 (FB1) is the most toxic and prevalent mycotoxin of this group, and it has been reported that FB1 accounts for 70-80% of FBs produced by the mycotoxigenic strains. The mode of action of FB1 depends on the structural similarity with sphinganine/sphingosine N-acyltransferase. This fact causes an accumulation of sphingoid bases and blocks the sphingolipid biosynthesis or the function of sphingolipids. Diverse toxic effects and diseases such as hepatocarcinogenicity, hepatotoxicity, nephrotoxicity, and cytotoxicity have been reported, and diseases like leukoencephalomalacia in horses and pulmonary oedema in horses and swine have been described. In humans, FBs have been associated with oesophageal cancer, liver cancer, neural tube defects, and infantile growth delay. However, despite the International Agency for Research on Cancer designated FB1 as a possibly carcinogenic to humans, its genotoxicity and epigenetic properties have not been clearly elucidated. This review aims to summarise the progress in research about the genotoxic and epigenetics effects of FB1.

The objective of this study was to evaluate the potential intra-species variability of 3 Fusarium langsethiae strains in response to extreme climate change (CC) conditions on an oat-based matrix. The impact of elevated temperature (25 vs 30-34 °C) coupled with increasing drought stress (0.98 vs 0.95 aw) and elevated CO2 (400 vs 1000 ppm) were examined on lag phases prior to growth, growth rate, and production of the mycotoxins T-2 and HT-2 and their ratio. In comparison to the control conditions (25 °C; 0.98; 400 ppm), exposure to increased temperature (30-34 °C), showed similar reductions in the lag phase and fungal growth rates of all 3 strains. However, with elevated CO2 a reduction in both lag phases prior to growth and growth rate occurred regardless of the aw examined. For T-2 and HT-2 mycotoxin production, T-2 showed the most intra-species variability in response to the interacting abiotic stress factors, with the 3 strains having different environmental conditions for triggering increases in T-2 production: Strain 1 produced higher T-2 toxin at 25 °C, while Strain 2 and the type strain (Fl201059) produced most at 0.98 aw/30 °C. Only Strain 2 showed a reduction in toxin production when exposed to elevated CO2. HT-2 production was higher at 25 °C for the type strain and higher at 30-34 °C for the other two strains, regardless of the aw or CO2 level examined. The HT-2/T-2 ratio showed no significant differences due to the imposed interacting CC abiotic conditions.

Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC.

The objective of this study was to quantify intraoperative bleeding in patients with cirrhosis and correlate it with clinical characteristics and laboratory coagulation tests.A case-control study was carried out with 74 patients with cirrhosis who were submitted to preoperative coagulation tests (complete blood count, platelet count, prothrombin time/international normalized ratio, thrombin time, activated partial thrombin time, platelet aggregation, fibrinogen, protein C, protein S, antithrombin, and von Willebrand factor level and activity). The levels of nitrogen compounds that can affect the platelet function were determined in saliva and blood by using automated enzymatic-colorimetric assays.Patients with cirrhosis had changes in almost all coagulation tests. The average volumes of intraoperative bleeding and blood lost per minute in the study group (5.36 mL/min and 0.19 mL/min, respectively) were greater than those in the control group (3.05 mL/min and 0.11 mL/min, respectively; P.05). In the control group, ascites (P = .012) and presence of periapical lesion (0.034) were positively correlated with bleeding (mL/min). With regard to coagulation tests and nitrogen compounds, only a positively moderate correlation with the platelet aggregation test was observed.No patients had hemorrhagic events and it was not possible to correlate a greater amount of bleeding with coagulation tests or nitrogen compounds in the study group.

Dengue virus (DENV) is transmitted to humans by the bite of the vector Aedes aegypti. Several researchers have suggested that the mechanism of vertical transmission of DENV in the vector is a key a...

29 páginas, 6 figuras, Volatile compounds (VCs) of Trichoderma fungi trigger an induced systemic resistance (ISR) in Arabidopsis that is effective against a broad spectrum of pathogens. The root-specific transcription factor MYB72 is an early regulator of ISR and also controls the activation of iron deficiency responses. Nitric oxide (NO) is involved in the regulation of MYB72-dependent iron deficiency responses in Arabidopsis roots, but the role of NO in the regulation of MYB72 and ISR by Trichoderma VCs remains unexplored. Using in vitro bioassays, Trichoderma VCs were applied to Arabidopsis seedlings. Plant perception of Trichoderma VCs triggered a burst of NO in Arabidopsis roots. By suppressing this burst using a NO scavenger, we show the involvement of NO in Trichoderma VCs-mediated regulation of MYB72. Using a NO scavenger and the Arabidopsis lines myb72 and nia1nia2 in in planta bioassays, we demonstrate that NO-signalling is required in the roots for the activation of Trichoderma VCs-mediated ISR against the leaf pathogen Botrytis cinerea. Analysis of the defence-related genes PR1 and PDF1.2 point to the involvement of root NO in priming leaves for enhanced defence. Our results support a key role of root NO-signalling in the regulation of MYB72 during the activation of ISR by Trichoderma VCs., This research was supported by the grants OTR04036 from Fundación Salamanca Ciudad de Cultura y Saberes and Ayuntamiento de Salamanca; P12BIO296 from Junta de Andalucía; RTI2018-094350-B-C31 and GC2018-098372-B-100 from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (MCIU/AEI/ERDF); and Marie Skłodowska-Curie Intra-European Fellowship FP7-PEOPLE-2011-IEF no. 301662 (to AMM). AMM and LP acknowledge the support of the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig funded by the German Research Foundation (FZT 118). LP further acknowledges to the PhD International Mobility Programme from University of Granada.

24 p.-9 fig., Gravitropism and phototropism play a primary role in orienting root growth. Tropistic responses of roots mediated by gravity and light have been extensively investigated, and a complex mutual interaction occurs between these two tropisms. To date, most studies have been conducted in 1 g, microgravity, or simulated microgravity, whereas no studies investigated root phototropism in hypergravity. Therefore, we studied the effects of several gravity treatments with those of different light wavelengths on root growth orientation. Here, we report growth and curvature of Brassica oleracea roots under different g levels, from simulated microgravity up to 20 g, and unilateral illumination with different spectral treatments provided by light emitting diodes. Microgravity was simulated with a random positioning machine whereas hypergravity conditions were obtained using the Large Diameter Centrifuge at the laboratories of the European Space Agency in the Netherlands. Four light treatments (white light, blue light, red light, and dark) were used in this study. Overall, roots of seedlings grown in the dark were longer than those developed under unilateral light treatments, regardless of the gravity level. Unilateral blue light or white light stimulated a negative phototropism of roots under all g levels, and root curvature was not affected by either hypergravity or simulated microgravity compared to 1 g. Results also confirmed previous findings on the effect of light intensity on root curvature and highlighted the relevance of blue-light photon flux density in root phototropism. Roots illuminated with red light showed a weak curvature in simulated microgravity but not in hypergravity. Moreover, root curvature under red light was similar to dark-grown roots in all g levels, suggesting a possible involvement of surface-dependent phenomena in root skewing under either red light or dark conditions. Further studies can confirm phototropic responses of B. oleracea in the weightless environment of orbiting spacecraft. Nevertheless, according to our findings, directional lighting represents an effective stimulus to guide root growth in a wide range of gravity conditions., This work was supported by the ESA-HRE CORA contract #4000127705/19/NL/PG/pt. Financial support was also provided by ESA-TEC contract #4000116223/16/NL/KML/hh to Jack J.W.A. van Loon, by Spanish Agencia Estatal de Investigación (Grant RTI2018-099309-B-I00, co-funded by EU- ERDF) to F. Javier Medina, and by NASA (Grant 80NSSC17K0546) to John Z. Kiss.

31 p.-5 fig.-2 tab.-2 fig. supl., Plant cell proliferation is affected by microgravity during spaceflight, but involved molecular mechanisms, key for space agronomy goals, remain unclear. To investigate transcriptomic changes in cell cycle phases caused by simulated microgravity, an Arabidopsis immobilized synchronous suspension culture was incubated in a Random Positioning Machine. After simulation, a transcriptomic analysis was performed with two subpopulations of cells (G2/M and G1 phases enriched) and an asynchronous culture sample. Differential expression was found at cell proliferation, energy/redox and stress responses, plus unknown biological processes gene ontology groups. Overall expression inhibition was a common response to simulated microgravity, but differences peak at the G2/M phase and stress response components change dramatically from G2/M to the G1 subpopulation suggesting a differential adaptation response to simulated microgravity through the cell cycle. Cell cycle adaptation using both known stress mechanisms and unknown function genes may cope with reduced gravity as an evolutionary novel environment., This work was supported by the Spanish “Plan Estatal de Investigación Científica y Técnica y de Innovación” of the Ministry of Economy, Industry and Competitiveness [to F.J.M., Grant numbers AYA2012-33982 and ESP2015-64323-R, co-funded by ERDF], by a pre-doctoral fellowship from CSIC, Spain [to K.Y.K., JAE-PreDoc Program, Ref. JAEPre_2010_01894], the ESA-ELIPS Program [to R.H., ESA GIA Project, contract number 4000105761], and ESA support [to J.v.L., via contract TEC-MMG/2012/263 and 4000107455/12/NL/PA].

38 p.-5 fig.-2 tab.-8 fig. supl., PREMISE:Plants synthesize information from multiple environmental stimuli when determining their direction of growth. Gravity, being ubiquitous on Earth, plays a major role in determining the direction of growth and overall architecture of the plant. Here, we utilized the microgravity environment on board the International Space Station (ISS) to identify genes involved influencing growth and development of phototropically stimulated seedlings of Arabidopsis thaliana., METHODS:Seedlings were grown on the ISS, and RNA was extracted from 7 samples (pools of 10-15 plants) grown in microgravity (μg) or Earth gravity conditions (1-g). Transcriptomic analyses via RNA sequencing (RNA-seq) of differential gene expression was performed using the HISAT2-Stringtie-DESeq2 RNASeq pipeline. Differentially expressed genes were further characterized by using Pathway Analysis and enrichment for Gene Ontology classifications., RESULTS:For 296 genes that were found significantly differentially expressed between plants in microgravity compared to 1-g controls, Pathway Analysis identified eight molecular pathways that were significantly affected by reduced gravity conditions. Specifically, light-associated pathways (e.g., photosynthesis-antenna proteins, photosynthesis, porphyrin, and chlorophyll metabolism) were significantly downregulated in microgravity., CONCLUSIONS:Gene expression in A. thaliana seedlings grown in microgravity was significantly altered compared to that of the 1-g control. Understanding how plants grow in conditions of microgravity not only aids in our understanding of how plants grow and respond to the environment but will also help to efficiently grow plants during long-range space missions., Funding was provided by grants NNX12A065G and 80NSSC17K0546 from NASA (PI = J. Z. Kiss).

Most traditional research on snake venoms has focused on front-fanged snake families (Viperidae, Elapidae, and Atractaspididae). However, venom is now generally accepted as being a much more broadly possessed trait within snakes, including species traditionally considered harmless. Unfortunately, due to historical inertia and methodological challenges, the toxin repertoires of non-front-fanged snake families (e.g., Colubridae, Dipsadidae, and Natricidae) have been heavily neglected despite the knowledge of numerous species capable of inflicting medically relevant envenomations. Integrating proteomic data for validation, we perform a de novo assembly and analysis of the Duvernoy's venom gland transcriptome of the Central American Road Guarder (Dipsadidae: Xenodontinae: Conophis lineatus), a species known for its potent bite. We identified 28 putative toxin transcripts from 13 toxin families in the Duvernoy's venom gland transcriptome, comprising 63.7% of total transcriptome expression. In addition to ubiquitous snake toxin families, we proteomically confirmed several atypical venom components. The most highly expressed toxins (55.6% of total toxin expression) were recently described snake venom matrix metalloproteases (svMMPs), with 48.0% of svMMP expression contributable to a novel svMMP isoform. We investigate the evolution of the new svMMP isoform in the context of rear-fanged snakes using phylogenetics. Finally, we examine the morphology of the venom apparatus using μCT and explore how the venom relates to autecology and the highly hemorrhagic effects seen in human envenomations. Importantly, we provide the most complete venom characterization of this medically relevant snake species to date, producing insights into the effects and evolution of its venom, and point to future research directions to better understand the venoms of 'harmless' non-front-fanged snakes.

Ureaplasma parvum is a commensal bacterium in the female reproductive tract but has been associated with pregnancy complications such as preterm prelabor rupture of membranes and preterm birth (PTB). However, the pathologic effects of U. parvum in the cervix, which prevents ascending infections during pregnancy, are still poorly understood. To determine the impact of U. parvum on the cervix, ectocervical (ecto) and endocervical (endo) epithelial and stromal cells were incubated with U. parvum. Macrophages were also tested as a proxy for cervical macrophages to determine the antigenicity of U. parvum. The effects of U. parvum, including influence on cell cycle and cell death, antimicrobial peptide (AMP) production, epithelial-to-mesenchymal transition (EMT), and inflammatory cytokine levels, were assessed. U. parvum colonized cervical epithelial and stromal cells 4 h post-infection. Like uninfected control, U. parvum neither inhibited cell cycle progression and nor caused cell death in cervical epithelial and stromal cells. U. parvum increased the production of the AMPs cathelicidin and human β-defensin 3 and exhibited weak signs of EMT evidenced by decreased cytokeratin 18 and increased vimentin expression in cervical epithelial cells. U. parvum induced a proinflammatory environment (cytokines) and increased MMP-9 in cervical epithelial cells but promoted pro- and anti-inflammatory response in cervical stromal cells and macrophages. U. parvum may colonize the cervical epithelial layer, but induction of AMPs and anti-inflammatory response may protect the cervix and may prevent ascending infections that can cause PTB. These findings suggest that U. parvum is a weak inducer of inflammation in the cervix.

Background: Marine fungi are considered as a promising source of pharmacologically important extracts and compounds owing to the new chemical structures that they can synthesize due to the environmental conditions of their habitat. The aim of this work is to evaluate the free radical scavenging capacity of methanolic extracts from marine fungi and their relationship to their total phenolic content. For this, the radical tests ABTS, DPPH, and Galvinoxyl were used, comparing these results with the antioxidant Trolox as reference. The total phenol content was quantified using the Folin-Ciocalteu method. All data were analyzed by ANOVA followed by Tukey's post hoc tests (p

In this work, we present a novel portable, flexible and easy-to-use experimental setup for investigating salinity-based information transmission in microfluidic channels. At the receiver, the different salinity-levels are detected by a customized electronic circuit, which measures electrical conductivity via electrodes in the microfluidic channel. We provide a detailed description of the setup, including the microfluidic chip fabrication. Moreover, we develop a rigorous mathematical model of each testbed component and an end-to-end model of the system, which we have verified through experiments. Finally, we analyzed the error performance of the setup using optimum and sub-optimum detection algorithms, such as the Viterbi algorithm and threshold detection. Version of record

Background/Purpose (s): Nosocomial pathogens can develop biofilms on hospital surfaces and medical devices; however, few studies have focused on the evaluation of mono-and dual-species biofilms developed by nosocomial pathogens under different growth conditions. Methods: This study investigated biofilm development by nosocomial pathogens (Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) on biomaterials in different culture media and their components of the extracellular matrix biofilm. Results: The mono-species biofilms showed cell densities from 7.50 to 9.27 Log10 CFU/cm2 on natural rubber latex type I (NLTI) and from 7.58 to 8.79 Log10 CFU/cm2 on stainless steel (SS). Dual-species biofilms consisted of S. aureus + P. aeruginosa (7.87–8.27 Log10 CFU/cm2 in TSBP and TSBME onto SS; p

Background: Cystic echinococcosis is a parasitic disease that develops in endemic areas due to the transmission of Echinococcus granulosus. The liver is the organ most affected. The most frequent s...

We describe four new records of Abronia fuscolabialis at Sierra Juárez, northern Oaxaca. These records are separated between 33 and 35 km to the south of the specimen previously reported from Sierra Júarez, and between 34 and 36 km to the west of the nearest specimen reported from Sierra Mixe. Despite being reported only for cloud forests, we recorded it in pine-oak forests

Aquí reportamos una observación in situ de una malformación ocular conocida como anoftalmia (ojo ausente) en la rana arborícola continental, Isthmohyla graceae, especie endémica y en peligro crítico de extinción en la serranía de Tabasará, Comarca Ngäbe-Buglé, Panamá, en marzo 2020. Esta nota documenta la malformación como la primera reportada en Panamá y primer registro para el género en Centroamérica, mencionando que este tipo de casos puede deberse a distintos factores.

The Allium cepa L. (onion) crop is affected by leaf blight disease caused by Stemphylium vesicarium; the shifts that S. vesicarium infection causes in the primary metabolism of onion plants are not known. In this study, the profiling of primary metabolites obtained by nuclear magnetic resonance (1H NMR) spectroscopy of organs from onion plants uninfected (control) and infected with S. vesicarium were compared. Twenty-eight metabolites were identified in the 1H NMR spectra of onion bulbs, thirty in leaves and thirty-eight in roots. Twenty-four metabolites were the same in bulbs, leaves and roots (fructose, glucose, myo-inositol, sucrose, alanine, asparagine, 4-aminobutyrate, glutamine, glutamic acid, isoleucine, leucine, phenylalanine, tryptophan, tyrosine, valine, citric acid, formic acid, lactic acid, malic acid, pyruvic acid, adenosine, guanosine, and uridine), but galactose, proline and acetoin were only identified in leaves; and trehalose, methionine, cytidine and methanol were only found in roots. Compared to uninfected plants, the concentration of sucrose, succinic, citric and formic acids and several amino acids that participate in the tricarboxylic acid cycle were reduced; which suggest that the processes involved in energy production are reduced by the infection with S. vesicarium. The concentration of formic acid was reduced in bulbs and leaves, which indicates that might infection induces the oxidation of formic acid to CO2 under conditions of low sucrose availability in onion plants. The increases of pyruvic acid, amino acids derived from pyruvic acid (alanine, leucine and valine), glutamine, glutamic acid, nucleosides of pyrimidine and purine, and GABA could be used for the successful growth of the pathogen.

The widespread Scolytinae and Platypodinae beetles are capable to colonize a broad range of host plants and several species are considered serious pests in agri-forest environments. In this work, we report the abundance and seasonal variation of scolytine and platypodine beetles associated to a Hass avocado orchard in West-central Mexico. During 2018 and 2019, specimens were captured using bottle traps baited with ethyl alcohol. We tested whether the climatic conditions explain the abundance and species richness. A total of 3,548 specimens from 30 species and 13 genera were collected. Thirteen species are new records for Nayarit State. The most abundant species were Corthylocurus aguacatensis (Schedl 1940), Xyleborus volvulus (Fabricius 1775) and Xyleborus affinis (Eichhoff 1868), these Scolytinae representing 54% of total collected. Abundance and species richness peaked during the fall season (from October to December). Differential responses to temperature and humidity across the temporal scale was found between species. Temperatures below 30 ° but above 26 ° C, and relative humidity (70 to 85%) favored the highest abundance and species richness of most Scolytinae (e.g. C. aguacatensis, Corthylus papulans and X. affinis). Thus, for sustainable management of these pest species we suggest regularly monitoring them in the avocado plantations from Nayarit and other producing states in Mexico.

The transcription factor FOXM1 that regulates multiple proliferation-related genes through selective protein-DNA and protein-protein interactions is now considered an attractive oncotarget. There are several small-molecule inhibitors that indirectly suppress the expression of FOXM1 or block its DNA binding domain (FOXM1-DBD). However, insufficient specificity or/and efficacy are two potential drawbacks. Here, we employed in silico modeling of FOXM1-DBD with inhibitors to enable the design of an effective CRBN-recruiting molecule that induced significant FOXM1 protein degradation and exerted promising in vivo antitumor activity against TNBC xenograft models. This study is the first of its kind showcasing the use of an approach described in the literature as protein-targeting chimeras to degrade the elusive FOXM1, providing an alternative strategy to counter the pathological effects resulting from the increased transcriptional activity of FOXM1 observed in cancer cells.

Aims To describe oral manifestations in children born with microcephaly attributed to congenital Zika virus syndrome (CZS). Methods Data was collected in semiannual intervals from 2017 to 2019, by oral exams of the children and interview with caregivers at a Public Dental Center in Rio de Janeiro, Brazil. A single calibrated examiner performed clinical examinations. Results Of 38 eligible children, 34 were followed-up from 12 to 30 months of age, 20 boys and 14 girls. The mean age of emergence of their first primary tooth was 12.4 months (SD = 2.9). By 30 months of age only 14.7% (n = 5) had complete primary dentition. Alteration in the sequence of tooth emergence was observed in 41.1% (n = 14). Radiographic examination demonstrated dental agenesis (14.7% n = 5). Dental developmental alterations (38.2%, n = 13), enamel defects (14.7%, n = 5), eruption cysts/hematoma (23.5%, n = 8), gingival bleeding (55.8%, n = 19), narrow palate, and bruxism (64.7%, n = 22) were also observed. No child had dental caries. Conclusion Children with microcephaly attributed to CZS presented oral manifestations early in life.

Environmental heterogeneity can interact with ecosystem processes to alter individual plant reproduction. A better understanding of the factors that contribute to variation in plant reproduction between and within populations will increase our ability to predict larger-scale plant persistence. Longleaf pine (Pinus palustris) savannas are mostly open, heterogeneous landscapes characterized by occasional patches of trees that create partially closed canopies. This creates a mosaic of microsite conditions that can alter plant reproduction. Frequent, low-intensity fires that occur during different seasons are also considered fundamental drivers of plant reproduction in this system. The effects of varying fire season on plant reproduction have produced mixed results, likely because fire season interacts with microsite conditions, such as canopy cover. We investigated fire season and canopy cover effects on reproduction of wiregrass (Aristida beyrichiana), a species whose reproduction can be fire stimulated. We established plots under open and partially closed canopies in three pine savanna management units burned during different seasons (i.e., early dry, mid-dry, and early wet). We recorded reproductive state and number of inflorescences produced by individuals occurring within plots and germinated seeds from reproducing individuals. We found that wiregrass burned during the early dry season had the lowest reproduction with few individuals flowering. When burned during the mid-dry season, probability of reproduction was the highest, but seed germination was low. Plants burned during the early wet season produced seeds with the highest probability of germination, especially under partial canopy. Our results indicate that wiregrass reproduction is affected by both small-scale environmental variation and large-scale ecosystem processes, with fires during the early wet season most likely to promote the production of viable seeds.

Myeloid-derived suppressor cells (MDSCs) are a compendium of immature myeloid cells that exhibit potent T-cell suppressive capacity and expand during pathological conditions such as cancer and chronic infections. Although well-characterized in cancer, the physiology of MDSCs in the infection setting remains enigmatic. Here, we integrated single-cell RNA sequencing (scRNA-seq) and functional metabolic profiling to gain deeper insights into the factors governing the generation and maintenance of MDSCs in chronic Staphylococcus aureus infection. We found that MDSCs originate not only in the bone marrow but also at extramedullary sites in S. aureus-infected mice. scRNA-seq showed that infection-driven MDSCs encompass a spectrum of myeloid precursors in different stages of differentiation, ranging from promyelocytes to mature neutrophils. Furthermore, the scRNA-seq analysis has also uncovered valuable phenotypic markers to distinguish mature myeloid cells from immature MDSCs. Metabolic profiling indicates that MDSCs exhibit high glycolytic activity and high glucose consumption rates, which are required for undergoing terminal maturation. However, rapid glucose consumption by MDSCs added to infection-induced perturbations in the glucose supplies in infected mice hinders the terminal maturation of MDSCs and promotes their accumulation in an immature stage. In a proof-of-concept in vivo experiment, we demonstrate the beneficial effect of increasing glucose availability in promoting MDSC terminal differentiation in infected mice. Our results provide valuable information of how metabolic alterations induced by infection influence reprogramming and differentiation of MDSCs.

The overexpression of RXam2, a cassava NLR (nucleotide-binding leucine-rich repeat) gene, by stable transformation and gene expression induction mediated by dTALEs, reduce cassava bacterial blight symptoms. Cassava (Manihot esculenta) is a tropical root crop affected by different pathogens including Xanthomonas phaseoli pv. manihotis (Xpm), the causal agent of cassava bacterial blight (CBB). Previous studies have reported resistance to CBB as a quantitative and polygenic character. This study sought to validate the functional role of a NLR (nucleotide-binding leucine-rich repeat) associated with a QTL to Xpm strain CIO151 called RXam2. Transgenic cassava plants overexpressing RXam2 were generated and analyzed. Plants overexpressing RXam2 showed a reduction in bacterial growth to Xpm strains CIO151, 232 and 226. In addition, designer TALEs (dTALEs) were developed to specifically bind to the RXam2 promoter region. The Xpm strain transformed with dTALEs allowed the induction of the RXam2 gene expression after inoculation in cassava plants and was associated with a diminution in CBB symptoms. These findings suggest that RXam2 contributes to the understanding of the molecular basis of quantitative disease resistance.