Histologic, metabolomic, and transcriptomic differences in fir trees from a peri-urban forest under chronic ozone exposure.

Urbanization modifies ecosystem conditions and evolutionary processes. This includes air pollution, mostly as tropospheric ozone (O3), which contributes to the decline of urban and peri-urban forests. A notable case are fir (Abies religiosa) forests in the peripheral mountains southwest of Mexico City, which have been severely affected by O3 pollution since the 1970s. Interestingly, some young individuals exhibiting minimal O3-related damage have been observed within a zone of significant O3 exposure. Using this setting as a natural experiment, we compared asymptomatic and symptomatic individuals of similar age (≤15 years old; n = 10) using histologic, metabolomic, and transcriptomic approaches. Plants were sampled during days of high (170 ppb) and moderate (87 ppb) O3 concentration. Given that there have been reforestation efforts in the region, with plants from different source populations, we first confirmed that all analyzed individuals clustered within the local genetic group when compared to a species-wide panel (Admixture analysis with ~1.5K SNPs). We observed thicker epidermis and more collapsed cells in the palisade parenchyma of needles from symptomatic individuals than from their asymptomatic counterparts, with differences increasing with needle age. Furthermore, symptomatic individuals exhibited lower concentrations of various terpenes (ß-pinene, ß-caryophylene oxide, α-caryophylene, and ß-α-cubebene) than asymptomatic trees, as evidenced through GC-MS. Finally, transcriptomic analyses revealed differential expression for 13 genes related to carbohydrate metabolism, plant defense, and gene regulation. Our results indicate a rapid and contrasting phenotypic response among trees, likely influenced by standing genetic variation and/or plastic mechanisms. They open the door to future evolutionary studies for understanding how O3 tolerance develops in urban environments, and how this knowledge could contribute to forest restoration.

La urbanización altera tanto las condiciones del ecosistema como los procesos evolutivos, siendo la contaminación del aire, principalmente el ozono troposférico (O3), un factor que contribuye al declive de los bosques urbanos y periurbanos. Un ejemplo destacado son los bosques de oyamel (Abies religiosa) en las montañas periféricas al suroeste de la Ciudad de México, que han sufrido graves afectaciones por la contaminación de O3 desde la década de 1970. Resulta curioso observar que algunos individuos jóvenes presentan un daño mínimo relacionado con el O3 dentro de zonas con una exposición significativa a este contaminante. Aprovechando este entorno como un experimento natural, hemos comparado individuos asintomáticos y sintomáticos de edad similar (≤15 años; n = 10) mediante enfoques histológicos, metabolómicos y transcriptómicos. Las muestras de plantas se recolectaron durante días con concentraciones altas (170 ppb) y moderadas (87 ppb) de O3. Dado que se han llevado a cabo esfuerzos de reforestación en la región con plantas de diferentes poblaciones, primero confirmamos que todos los individuos analizados se organizaron dentro del grupo genético local en comparación con un amplio panel poblacional de esta misma especie (Análisis de Admixture con ~1.5 K SNPs). Observamos una epidermis más gruesa y más células colapsadas en el parénquima en empalizada de las agujas de los individuos sintomáticos que de sus contrapartes asintomáticas, y estas diferencias aumentaban con la edad de la aguja. Además, los individuos sintomáticos exhibieron concentraciones más bajas de varios terpenos (ß­pineno, óxido de ß­cariofileno, α­cariofileno y ß­α­cubebeno) que los árboles asintomáticos, según se evidenció mediante GC­MS. Por último, los análisis transcriptómicos revelaron una expresión diferencial para trece genes relacionados con el metabolismo de carbohidratos, la defensa de plantas y la regulación génica. Nuestros resultados indican una respuesta fenotípica rápida y contrastante entre los árboles, probablemente influenciada por la variación genética presente y/o mecanismos plásticos. Estos hallazgos abren la puerta a futuros estudios evolutivos para comprender cómo se desarrolla la tolerancia al O3 en entornos urbanos y cómo este conocimiento podría contribuir a la restauración forestal.

Potential strategic allocation of nuptial gift proteins of the neotropical katydid Conocephalus ictus (Orthoptera Tettigoniidae).

In many katydids, the male feeds his mate with a large gelatinous spermatophore. While providing large spermatophores can increase female fecundity and lifespan, it may also decrease their sexual receptivity, benefiting male fitness. Allocating resources to these edible gifts may entail a lower apportionment of them to other functions, generating a trade-off between somatic and reproductive functions. Despite their effect on male and female fitness, little is known of the compounds associated with katydid spermatophores. Our study found 177 different putative proteins in the spermatophore of Conocephalus ictus, with no correlation between male body size with spermatophore mass, number, concentration and mass of proteins. However, we did observe a negative relationship between male forewing length and protein concentration, and a negative relationship between the mass of the spermatophore transferred to the females and their body size, suggesting a resource allocation trade-off in males, but also strategic transference of resources based on female quality.

A Trip Back Home: Resistance to Herbivores of Native and Non-Native Plant Populations of Datura stramonium.

When colonizing new ranges, plant populations may benefit from the absence of the checks imposed by the enemies, herbivores, and pathogens that regulated their numbers in their original range. Therefore, rates of plant damage or infestation by natural enemies are expected to be lower in the new range. Exposing both non-native and native plant populations in the native range, where native herbivores are present, can be used to test whether resistance mechanisms have diverged between populations. Datura stramonium is native to the Americas but widely distributed in Spain, where populations show lower herbivore damage than populations in the native range. We established experiments in two localities in the native range (Mexico), exposing two native and two non-native D. stramonium populations to natural herbivores. Plant performance differed between the localities, as did the abundance of the main specialist herbivore, Lema daturaphila. In Teotihuacán, where L. daturaphila is common, native plants had significantly more adult beetles and herbivore damage than non-native plants. The degree of infestation by the specialist seed predator Trichobaris soror differed among populations and between sites, but the native Ticumán population always had the lowest level of infestation. The Ticumán population also had the highest concentration of the alkaloid scopolamine. Scopolamine was negatively related to the number of eggs deposited by L. daturaphila in Teotihuacán. There was among-family variation in herbivore damage (resistance), alkaloid content (scopolamine), and infestation by L. daturaphila and T. soror, indicating genetic variation and potential for further evolution. Although native and non-native D. stramonium populations have not yet diverged in plant resistance/constitutive defense, the differences between ranges (and the two experimental sites) in the type and abundance of herbivores suggest that further research is needed on the role of resource availability and adaptive plasticity, specialized metabolites (induced, constitutive), and the relationship between genealogical origin and plant defense in both ranges.

Plasmonic Coupled Modes in a Metal-Dielectric Periodic Nanostructure.

In this study we investigate the optical properties of a 2D-gap surface plasmon metasurface composed of gold nanoblocks (nanoantennas) arranged in a metal-dielectric configuration. This novel structure demonstrates the capability of generating simultaneous multi-plasmonic resonances and offers tunability within the near-infrared domain. Through finite difference time domain (FDTD) simulations, we analyze the metasurface's reflectance spectra for various lattice periods and identify two distinct dips with near-zero reflectance, indicative of resonant modes. Notably, the broader dip at 1150 nm exhibits consistent behavior across all lattice periodicities, attributed to a Fano-type hybridization mechanism originating from the overlap between localized surface plasmons (LSPs) of metallic nanoblocks and surface plasmon polaritons (SPPs) of the underlying metal layer. Additionally, we investigate the influence of dielectric gap thickness on the gap surface plasmon resonance and observe a blue shift for smaller gaps and a spectral red shift for gaps larger than 100 nm. The dispersion analysis of resonance wavelengths reveals an anticrossing region, indicating the hybridization of localized and propagating modes at wavelengths around 1080 nm with similar periodicities. The simplicity and tunability of our metasurface design hold promise for compact optical platforms based on reflection mode operation. Potential applications include multi-channel biosensors, second-harmonic generation, and multi-wavelength surface-enhanced spectroscopy.

Spectroscopic and Microestructural Evidence for T-2 Toxin Adsorption Mechanism by Natural Bentonite Modified with Organic Cations.

Aluminosilicates are adsorbents able to bind mycotoxins, and their chemical modification increases their affinity to adsorb low-polarity mycotoxins. To further investigate if the inclusion of salts in bentonite modifies its adsorptive capacity, we studied T-2 toxin adsorption in natural bentonite (NB) and when modified with quaternary ammonium salts differing in polarity and chain length: myristyl trimethyl ammonium bromide (B14), cetyl trimethyl ammonium bromide (B16) and benzyl dimethyl stearyl ammonium chloride (B18). The results showed that quaternary salts made bentonite: displace monovalent (Na+1, K+1) and divalent (Mg+2, Ca+2) ions; reduce its porosity; change its compaction and structure, becoming more crystalline and ordered; and modify the charge balance of sheets. T-2 adsorption was higher in all modified materials compared to NB (p ≤ 0.0001), and B16 (42.96%) better adsorbed T-2 compared to B18 (35.80%; p = 0.0066). B14 (38.40%) showed no differences compared to B16 and B18 (p > 0.05). We described the T-2 adsorption mechanism in B16, in which hydrogen bond interactions, Van der Waals forces and the replacement of the salt by T-2 were found. Our results showed that interaction types due to the inclusion in B16 might be more important than the hydrocarbon chain length to improve the adsorptive capacity of bentonite.

Zearalenone Does Not Show Genotoxic Effects in the Drosophila melanogaster Wing Spot Test, but It Induces Oxidative Imbalance, Development, and Fecundity Alterations.

Zearalenone (ZEN) is a non-steroidal mycoestrogen produced by the Fusarium genus. ZEN and its metabolites compete with 17-beta estradiol for cytosolic estrogen receptors, causing reproductive alterations in vertebrates. ZEN has also been associated with toxic and genotoxic effects, as well as an increased risk for endometrial adenocarcinomas or hyperplasia, breast cancer, and oxidative damage, although the underlying mechanisms remain unclear. Previous studies have monitored cellular processes through levels of transcripts associated with Phase I Xenobiotic Metabolism (Cyp6g1 and Cyp6a2), oxidative stress (hsp60 and hsp70), apoptosis (hid, grim, and reaper), and DNA damage genes (Dmp53). In this study, we evaluated the survival and genotoxicity of ZEN, as well as its effects on emergence rate and fecundity in Drosophila melanogaster. Additionally, we determined levels of reactive oxygen species (ROS) using the D. melanogaster flare and Oregon R(R)-flare strains, which differ in levels of Cyp450 gene expression. Our results showed that ZEN toxicity did not increase mortality by more than 30%. We tested three ZEN concentrations (100, 200, and 400 µM) and found that none of the concentrations were genotoxic but were cytotoxic. Taking into account that it has previously been demonstrated that ZEN administration increased hsp60 expression levels and apoptosis gene transcripts in both strains, the data agree with an increase in ROS and development and fecundity alterations. Since Drosophila lacks homologous genes for mammalian estrogen receptors alpha and beta, the effects of this mycotoxin can be explained by a mechanism different from estrogenic activity.

Presentación simultánea de quiste epidermoide del ángulo pontocerebeloso y colesteatoma infiltrante del oído medio. Reporte de caso y revisión de literatura / Simultaneous presentation of an epidermoid cyst of the cerebellopontine angle and infiltrating cholesteatoma of the middle ear. Case report and literature review

Introducción: los quistes epidermoides son el tercer tumor más común del ángulo pontocerebeloso (APC). Es infrecuente detectar simultáneamente un colesteatoma infiltrativo del oído medio (OM). Caso clínico: paciente de 51 años acude a urgencias por cefalea hemicraneal intensa, pulsátil secundaria a hidrocefalia aguda, requirió ventriculostomía. En la resonancia magnética nuclear (RMN) cerebral contrastada se reporta una masa en el APC sugestivo de quiste epidermoide y simultáneamente un colesteatoma infiltrativo del OM. La paciente fue intervenida primero con resección de colesteatoma del OM; en un segundo tiempo resección del quiste epidermoide del APC por vía translaberíntica. El posoperatorio la evolución clínica fue satisfactoria. Discusión: los quistes epidermoides del APC son histopatológicamente idénticos al colesteatoma del OM y pueden ser secundarios a estos. Conclusión: se debe individualizar el manejo sin descartar la posibilidad de tener las dos enfermedades de manera simultánea.

Introduction: cysts are the third most common tumor of the cerebellopontine angle (CPA). It is rare to simultaneously detect an infiltrative cholesteatoma of the middle ear (OM). Clinical case: a 51-year-old patient attended the emergency department due to intense throbbing hemicranial headache secondary to acute hydrocephalus, requiring ventriculostomy. Contrast-enhanced cerebral magnetic resonance imaging (MRI) reported a mass in the APC suggestive of an epidermoid cyst and simultaneously an infiltrative cholesteatoma of the OM. The patient underwent first surgery with resection of the OM cholesteatoma; in a second stage, resection of the epidermoid cyst of the APC through a translabyrinthine approach. The postoperative clinical evolution was satisfactory. Discussion: APC epidermoid cysts are histopathologically identical to OM cholesteatoma and may be secondary to them. Conclusion: management must be individualized without ruling out the possibility of having both diseases simultaneously.

Brewing a Craft Belgian-Style Pale Ale Using Pichia kudriavzevii 4A as a Starter Culture.

There is an expanding market for beer of different flavors. This study aimed to prepare a craft Belgian-style pale ale with a non-Saccharomyces yeast. Pichia kudriavzevii 4A was used as a sole starter culture, and malted barley as the only substrate. The ingredients and brewing process were carefully monitored to ensure the quality and innocuousness of the beverage. During fermentation, the yeast consumed 89.7% of total sugars and produced 13.8% v/v of ethanol. The product was fermented and then aged for 8 days, adjusted to 5% v/v alcohol, and analyzed. There were no traces of mycotoxins, lead, arsenic, methanol, or microbiological contamination that would compromise consumer health. According to the physicochemical analysis, the final ethanol concentration (5.2% v/v) and other characteristics complied with national and international guidelines. The ethyl acetate and isoamyl alcohol present are known to confer sweet and fruity flavors. The sensory test defined the beverage as refreshing and as having an apple and pear flavor, a banana aroma, and a good level of bitterness. The judges preferred it over a commercial reference sample of Belgian-style pale ale made from S. cerevisiae. Hence, P. kudriavzevii 4A has the potential for use in the beer industry.

M2 macrophages drive leukemic transformation by imposing resistance to phagocytosis and improving mitochondrial metabolism.

It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukemia (AML) reveal a shift toward a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD+ generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra-bone marrow coinjection of M2 macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A 2-day in vitro exposure to M2 macrophages results in the accumulation of CALRlow leukemic blast cells, which are now protected against phagocytosis. Moreover, M2-exposed "trained" leukemic blasts display increased mitochondrial metabolism, in part mediated via mitochondrial transfer. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for targeting strategies aimed at the tumor microenvironment.

Molecular Docking and In Vitro Studies of Ochratoxin A (OTA) Biodetoxification Testing Three Endopeptidases.

Ochratoxin A (OTA) is considered one of the main mycotoxins responsible for health problems and considerable economic losses in the feed industry. The aim was to study OTA's detoxifying potential of commercial protease enzymes: (i) Ananas comosus bromelain cysteine-protease, (ii) bovine trypsin serine-protease and (iii) Bacillus subtilis neutral metalloendopeptidase. In silico studies were performed with reference ligands and T-2 toxin as control, and in vitro experiments. In silico study results showed that tested toxins interacted near the catalytic triad, similar to how the reference ligands behave in all tested proteases. Likewise, based on the proximity of the amino acids in the most stable poses, the chemical reaction mechanisms for the transformation of OTA were proposed. In vitro experiments showed that while bromelain reduced OTA's concentration in 7.64% at pH 4.6; trypsin at 10.69% and the neutral metalloendopeptidase in 8.2%, 14.44%, 45.26% at pH 4.6, 5 and 7, respectively (p < 0.05). The less harmful α-ochratoxin was confirmed with trypsin and the metalloendopeptidase. This study is the first attempt to demonstrate that: (i) bromelain and trypsin can hydrolyse OTA in acidic pH conditions with low efficiency and (ii) the metalloendopeptidase was an effective OTA bio-detoxifier. This study confirmed α-ochratoxin as a final product of the enzymatic reactions in real-time practical information on OTA degradation rate, since in vitro experiments simulated the time that food spends in poultry intestines, as well as their natural pH and temperature conditions.

Non-chlorophyllous and crypto-chlorophyllous fern spores differ in their mobilisation of fatty acids during priming.

During fern spore germination, lipid hydrolysis primarily provides the energy to activate their metabolism. In this research, fatty acids (linoleic, oleic, palmitic and stearic) were quantified in the spores exposed or not to priming (hydration-dehydration treatments). Five fern species were investigated, two from xerophilous shrubland and three from a cloud forest. We hypothesised that during the priming hydration phase, the fatty acids profile would change in concentration, depending on the spore type (non-chlorophyllous and crypto-chlorophyllous). The fatty acid concentration was determined by gas chromatograph-mass spectrometer. Chlorophyll in spores was vizualised by epifluorescence microscopy and quantified by high-resolution liquid chromatography with a DAD-UV/Vis detector. Considering all five species and all the treatments, the oleic acid was the most catabolised. After priming, we identified two patterns in the fatty acid metabolism: (1) in non-chlorophyllous species, oleic, palmitic, and linoleic acids were catabolised during imbibition and (2) in crypto-chlorophyllous species, these fatty acids increased in concentration. These patterns suggest that crypto-chlorophyllous spores with homoiochlorophylly (chlorophyll retained after drying) might not require the assembly of new photosynthetic apparatus during dark imbibition. Thus, these spores might require less energy from pre-existing lipids and less fatty acids as 'building blocks' for cell membranes than non-chlorophyllous spores, which require de novo synthesis and structuring of the photosynthetic apparatus.

Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia.

Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA.

FASN inhibition sensitizes metastatic OSCC cells to cisplatin and paclitaxel by downregulating cyclin B1.

OBJECTIVES: To investigate the potential effect of fatty acid synthase (FASN) inhibitor orlistat to enhance the effectiveness of chemotherapy drugs widely used to treat oral squamous cell carcinomas (OSCC), such as 5-fluorouracil, cisplatin, and paclitaxel. METHODS: The OSCC SCC-9 LN-1 metastatic cell line, which expresses high levels of FASN, was used for drug combination experiments. Cell viability was analyzed by crystal violet staining and automatic cell counting. Apoptosis and cell cycle were analyzed by flow cytometry with Annexin-V/7-AAD and propidium iodide staining, respectively. Cyclin B1, Cdc25C, Cdk1, FASN, and ERBB2 levels were assessed by Western blotting. Finally, cell scratch and transwell assays were performed to assess cell migration and invasion. RESULTS: Inhibition of FASN with orlistat sensitized SCC-9 LN-1 cells to the cytotoxic effects of paclitaxel and cisplatin, but not 5-fluorouracil, which was accompanied by a significant reduction in cyclin B1. The suppression of proliferation, migration, and invasion of SCC-9 LN-1 cells induced by orlistat plus cisplatin or paclitaxel was not superior to the effects of chemotherapy drugs alone. CONCLUSION: Our results suggest that orlistat enhances the chemosensitivity of SCC-9 LN-1 cells to cisplatin and paclitaxel by downregulating cyclin B1.

Quantifying Cardinal Temperatures of Chia (Salvia hispanica L.) Using Non-Linear Regression Models.

Temperature is the main factor that impacts germination and therefore the success of annual crops, such as chia (Salvia hispanica L.), whose seeds are known for their high nutritional value related to its oil. The effect of temperature on germination is related to cardinal-temperature concepts that describe the range of temperature over which seeds of a particular species can germinate. Therefore, in this study, in addition to calculated germinative parameters such as total germination and germination rate of S. hispanica seeds, the effectiveness of non-linear models for estimating the cardinal temperatures of chia seeds was also determined. We observed that germination of S. hispanica occurred in cold to moderate-high temperatures (10-35 °C), having an optimal range between 25 and 35 °C, with the highest GR and t50 at 30 °C. Temperatures higher than 35 °C significantly reduced germination. Output parameters of the different non-linear models showed that the response of chia germination to temperature was best explained by beta models (B). Cardinal temperatures calculated by the B1 model for chia germination were: 2.52 ± 6.82 °C for the base, 30.45 ± 0.32 °C for the optimum, and 48.58 ± 2.93 °C for the ceiling temperature.

Regulatory perturbations of ribosome allocation in bacteria reshape the growth proteome with a trade-off in adaptation capacity.

Bacteria regulate their cellular resource allocation to enable fast growth-adaptation to a variety of environmental niches. We studied the ribosomal allocation, growth, and expression profiles of two sets of fast-growing mutants of Escherichia coli K-12 MG1655. Mutants with only three of the seven copies of ribosomal RNA operons grew faster than the wild-type strain in minimal media and show similar phenotype to previously studied fast-growing rpoB mutants. Comparing these two different regulatory perturbations (rRNA promoters or rpoB mutations), we show how they reshape the proteome for growth with a concomitant fitness cost. The fast-growing mutants shared downregulation of hedging functions and upregulated growth functions. They showed longer diauxic shifts and reduced activity of gluconeogenic promoters during glucose-acetate shifts, suggesting reduced availability of the RNA polymerase for expressing hedging proteome. These results show that the regulation of ribosomal allocation underlies the growth/hedging phenotypes obtained from laboratory evolution experiments.

Potential Distribution of Cedrela odorata L. in Mexico according to Its Optimal Thermal Range for Seed Germination under Different Climate Change Scenarios.

Cedrela odorata is a native tree of economic importance, as its wood is highly demanded in the international market. In this work, the current and future distributions of C. odorata in Mexico under climate change scenarios were analyzed according to their optimal temperature ranges for seed germination. For the present distribution, 256 localities of the species' presence were obtained from the Global Biodiversity Information Facility (GBIF) database and modelled with MaxEnt. For the potential distribution, the National Center for Atmospheric Research model (CCSM4) was used under conservative and drastic scenarios (RCP2.6 and RCP8.5 Watts/m2, respectively) for the intermediate future (2050) and far future (2070). Potential distribution models were built from occurrence data within the optimum germination temperature range of the species. The potential distribution expanded by 5 and 7.8% in the intermediate and far future, respectively, compared with the current distribution. With the increase in temperature, adequate environmental conditions for the species distribution should be met in the central Mexican state of Guanajuato. The states of Chihuahua, Mexico, Morelos, Guerrero, and Durango presented a negative trend in potential distribution. Additionally, in the far future, the state of Chihuahua it is likely to not have adequate conditions for the presence of the species. For the prediction of the models, the precipitation variable during the driest month presented the greatest contribution. When the humidity is not limiting, the thermal climatic variables are the most important ones. Models based on its thermal niche for seed germination allowed for the identification of areas where temperature will positively affect seed germination, which will help maximize the establishment of plant populations and adaptation to different climate change scenarios.

Thermal Niche for Seed Germination and Species Distribution Modelling of Swietenia macrophylla King (Mahogany) under Climate Change Scenarios.

Swietenia macrophylla is an economically important tree species propagated by seeds that lose their viability in a short time, making seed germination a key stage for the species recruitment. The objective of this study was to determine the cardinal temperatures and thermal time for seed germination of S. macrophylla; and its potential distribution under different climate change scenarios. Seeds were placed in germination chambers at constant temperatures from 5 to 45 °C and their thermal responses modelled using a thermal time approach. In addition, the potential biogeographic distribution was projected according to the Community Climate System Model version 4 (CCSM4). Germination rate reached its maximum at 37.3 ± 1.3 °C (To); seed germination decreased to near zero at 52.7 ± 2.2 °C (ceiling temperature, Tc) and at 12.8 ± 2.4 °C (base temperature, Tb). The suboptimal thermal time θ150 needed for 50% germination was ca. 190 °Cd, which in the current scenario is accumulated in 20 days. The CCSM4 model estimates an increase of the potential distribution of the species of 12.3 to 18.3% compared to the current scenario. The temperature had an important effect on the physiological processes of the seeds. With the increase in temperature, the thermal needs for germination are completed in less time, so the species will not be affected in its distribution. Although the distribution of the species may not be affected, it is crucial to generate sustainable management strategies to ensure its long-term conservation.

The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells.

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34+ samples. However, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. Despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. Here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. We observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34+ samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. The EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. Therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients.

Differences in treatment strategies in the management of acute appendicitis in a county hospital in Guatemala and an academic teaching institution in the United States.

Laparoscopy and antibiotic-first (NOM) strategies have been introduced in the management of acute appendicitis in industrialised countries. Data regarding the feasibility of these strategies in low-income nations are sparse. A retrospective analysis of adult patients undergoing appendicectomy at a county non-teaching hospital in San Benito, Guatemala (Hospital Nacional (HNSB)) was compared to an academic, teaching institution in Dallas, USA (Veterans Medical Centre). Most patients at the VA (92%) underwent computed tomography prior to being operated upon while none did so at HNSB. Whilst all patients at HNSB underwent an open approach, 95% of VA patients underwent a laparoscopic appendicectomy with a 4.7% conversion rate. General anaesthesia was universally used at Veterans Medical Centre, whilst spinal anaesthesia was utilised in 88% of cases at HNSB. NOM of acute appendicitis was undertaken only rarely at the Veterans Medical Centre and never at HNSB, where it was not thought expedient.