Sepsis expands a CD39+ plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity.

Sepsis results in elevated adenosine in circulation. Extracellular adenosine triggers immunosuppressive signaling via the A2a receptor (A2aR). Sepsis survivors develop persistent immunosuppression with increased risk of recurrent infections. We utilized the cecal ligation and puncture (CLP) model of sepsis and subsequent infection to assess the role of adenosine in post-sepsis immune suppression. A2aR-deficient mice showed improved resistance to post-sepsis infections. Sepsis expanded a subset of CD39hi B cells and elevated extracellular adenosine, which was absent in mice lacking CD39-expressing B cells. Sepsis-surviving B cell-deficient mice were more resistant to secondary infections. Mechanistically, metabolic reprogramming of septic B cells increased production of ATP, which was converted into adenosine by CD39 on plasmablasts. Adenosine signaling via A2aR impaired macrophage bactericidal activity and enhanced interleukin-10 production. Septic individuals exhibited expanded CD39hi plasmablasts and adenosine accumulation. Our study reveals CD39hi plasmablasts and adenosine as important drivers of sepsis-induced immunosuppression with relevance in human disease.

Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi∗ZZ).

BACKGROUND & AIMS: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown. METHODS: Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi∗ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated noninvasively via the serum test AST-to-platelet ratio index and via transient elastography-based liver stiffness measurement. Histologic parameters were compared in 15 Pi∗ZZ adults with and 35 without augmentation. RESULTS: Compared with nonaugmented subjects, augmented Pi∗ZZ individuals displayed lower serum liver enzyme levels (AST 71% vs 75% upper limit of normal, P < .001; bilirubin 49% vs 58% upper limit of normal, P = .019) and lower surrogate markers of fibrosis (AST-to-platelet ratio index 0.34 vs 0.38, P < .001; liver stiffness measurement 6.5 vs 7.2 kPa, P = .005). Among biopsied participants, augmented individuals had less pronounced liver fibrosis and less inflammatory foci but no differences in AAT accumulation were noted. CONCLUSIONS: The first evaluation of AAT augmentation on the Pi∗ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi∗ZZ-associated liver disease.

GlyT1 Inhibition by NFPS Promotes Neuroprotection in Amyloid-ß-Induced Alzheimer's Disease Animal Model.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-ß, leading to N-methyl-D-aspartate (NMDA) receptor-dependent synaptic depression, spine elimination, and memory deficits. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission via NMDA receptors (NMDAR), presenting a potential alternative therapeutic approach for AD. This study investigates the neuroprotective potential of GlyT1 inhibition in an amyloid-ß-induced AD mouse model. C57BL/6 mice were treated with N-[3-([1,1-Biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine (NFPS), a GlyT1 inhibitor, 24 h prior to intrahippocampal injection of amyloid-ß. NFPS pretreatment prevented amyloid-ß-induced cognitive deficits in short-term and long-term memory, evidenced by novel object recognition and spatial memory tasks. Moreover, NFPS pretreatment curbed microglial activation, astrocytic reactivity, and subsequent neuronal damage from amyloid-ß injection. An extensive label-free quantitative UPLC-MSE proteomic analysis was performed on the hippocampi of mice treated with NFPS. In proteomics, KEGG enrichment analysis revealed increased in dopaminergic synapse, purine-containing compound biosynthetic process and long-term potentiation, and a reduction in Glucose catabolic process and glycolytic process pathways. The western blot analysis confirmed that NFPS treatment elevated BDNF levels, correlating with enhanced TRKB phosphorylation and mTOR activation. Moreover, NFPS treatment reduced the GluN2B expression after 6 h, which was associated with an increase on CaMKIV and CREB phosphorylation. Collectively, these findings demonstrate that GlyT1 inhibition by NFPS activates diverse neuroprotective pathways, enhancing long-term potentiation signaling and countering amyloid-ß-induced hippocampal damage.

Development and validation of a predictive tool for adverse drug reactions in neonates under intensive care.

AIMS: Neonates hospitalized in neonatal intensive care units (NICUs) commonly experience adverse drug reactions (ADRs). Thus, we aimed to develop and validate a tool for predicting ADRs in neonates hospitalized in NICUs. METHODS: A nested case-control study in an open cohort with neonates admitted to the NICU of a maternity hospital in Natal, Brazil was conducted from January 2019 to January 2022 [Correction added on 4 December 2023, after first online publication: 2023 has been changed to 2019 in the preceding sentence.]. Neonates with ADR were randomly paired with 2 controls. For the development of the tool, a multivariate logistic regression was applied on 2/3 of the sample (cases with respective controls). The model's fit was evaluated using the Hosmer-Lemeshow test for calibration and the Brier score for performance assessment. Validation of the tool was performed by determining the area under the receiver operating characteristic curve with bootstrap adjusted c-statistics. RESULTS: In all, 450 neonates (150 cases and 300 controls) were included in the study. We identified 5 independent risk factors for ADR, 4 related to the neonate (current mechanical ventilation, heart rate ≥178 beats/min, intravenous medications, ≥5 prescription medications) and 1 to the mother (gestational hypertension). The tool had a classification cut-off point of ≥15, and its total score ranged from 0 to 34. In validation, the tool had an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI] 0.66-0.81) with sensitivity of 52.02% (95% CI 47.40-56.64) and specificity of 81.35% (95% CI 77.75-84.95). CONCLUSION: The tool demonstrated adequate discriminative ability and utilized 5 commonly monitored variables in the NICU.

RAWS4all project: validation of a new silicone model for robotic TAPP inguinal hernia repair.

BACKGROUND: Trans-abdominal pre-peritoneal (TAPP) hernia repair is a complex procedure that presents several challenges. Even though, due to the high prevalence of inguinal hernia, TAPP technique is increasing in frequency and robotic Abdominal Wall Surgery (rAWS) is emerging as a valuable tool in this regard. Although inguinal TAPP procedure principles have been published and simulation is needed, the availability of validated models remains scarce. METHODS: A new low-cost model was developed to simulate inguinal rTAPP repair. For validity assessment, a new TAPP-specific fidelity questionnaire and assessment scale were developed to compare the performance of novices and experts in the simulated procedure. The models used were assessed at 60 min for execution and quality score. RESULTS: Twenty-five residents and specialists from all over the country participated in this study. Execution, quality, and global performance was higher in the seniors group compared to juniors (8.91 vs 6.36, p = 0.02; 8.09 vs 5.14, p < .001; and 17 vs. 11,5, p < .001, respectively). Overall fidelity was assessed as being very high [4.41 (3.5-5.0), α = .918] as well as face [4.31 (3.0-5.0), α = .867] and content validity [4.44 (3.2-5.0), α = .803]. Participants strongly agreed that the model is adequate to be used with the DaVinci® Robot [4.52 (3.5-5.0), α = .758]. CONCLUSION: This study shows face, content, and construct validity of the model for inguinal TAPP simulation, including for robotic surgery. Therefore, the model can be a valuable tool for learning, understanding, practicing, and mastering the TAPP technique prior to participating in the operating room.

Retrospective application of ICH M7 to anti-hypertensive drugs in Brazil: Risk assessment of potentially mutagenic impurities.

Potentially mutagenic impurities are likely to be formed in any drug substance, since their synthesis requires reactive intermediates which may also react with DNA. The ICH M7 guideline, which defines how to risk assess and control mutagenic impurities, was first published in 2014 and is not to be applied retrospectively; however, some impurities have been found above the permitted limits in drug products which were already on the market. This study assessed the implications of applying ICH M7 retrospectively to anti-hypertensive drugs marketed in Brazil by performing a risk assessment and establishing control strategies. The manufacturing processes of 15 drug substances were evaluated and 262 impurities were identified, from which 21% were classified as potentially mutagenic. Most of the impurities were identified below ICH M7 acceptable limits, except for impurities described in a pharmacopoeial monograph. Compendial specifications are defined based on scientific evidence and play an important role in setting quality and safety standards for pharmaceuticals, however there are opportunities for further alignment with ICH guidelines, aiming for a holistic assessment of the impurities profile to ensure the safety of medicines.

Exploring the Fluconazole-Resistance Modifying Activity and Potential Mechanism of Action of Fixed Oil from Caryocar coriaceum Wittm. (Caryocaraceae) against Candida Species.

The fixed oil from the inner mesocarp of Caryocar coriaceum Wittm. is used in the Chapada do Araripe region of Brazil for the treatment of genitourinary candidiasis. This study aimed to evaluate the chemical composition, antifungal activity, reduction of fungal virulence, and the preliminary toxicity of the fixed oil from the inner mesocarp of C. coriaceum tested against three Candida yeasts. The oil was characterized by gas chromatography (GC-MS and GC-FID). Antifungal activity was assessed using the serial microdilution method. Additionally, the potential of the oil as an enhancer of fluconazole action was tested at sub-inhibitory concentrations (MIC/8). The mechanism of action of C. coriaceum fixed oil was determined by evaluating the inhibition of morphological transition in Candida spp. The chemical composition of the fixed oil of C. coriaceum comprised both unsaturated and saturated fatty acids. Oleic (61 %) and palmitic (33 %) acids were the major constituents. Regarding its anti-Candida activity, the oil inhibited the growth of C. albicans (IC50 : 371 µg/mL) and C. tropicalis (IC50 : 830 µg/mL). Furthermore, the oil reversed the antifungal resistance of C. albicans and C. tropicalis, restoring the susceptibility to fluconazole and reducing their IC50 from 12.33 µg/mL and 362 µg/mL to 0.22 µg/mL and 13.93 µg/mL, respectively. The fixed oil of C. coriaceum completely inhibited the morphological transition of C. albicans and C. tropicalis at a concentration of 512 µg/mL, but exhibited limited low antifungal potential against C. krusei. The observed antifungal activity may be attributed to the overproduction of reactive oxygen species. Additionally, the oil showed no toxic effect on the Drosophila melanogaster in vivo model. The fixed oil from the inner mesocarp of C. coriaceum emerge as a strong candidate for the development of new pharmaceutical formulations to treat infections caused by Candida spp.

Molecular Mechanisms Linking Osteoarthritis and Alzheimer's Disease: Shared Pathways, Mechanisms and Breakthrough Prospects.

Alzheimer's disease (AD) is a progressive neurodegenerative disease mostly affecting the elderly population. It is characterized by cognitive decline that occurs due to impaired neurotransmission and neuronal death. Even though deposition of amyloid beta (Aß) peptides and aggregation of hyperphosphorylated TAU have been established as major pathological hallmarks of the disease, other factors such as the interaction of genetic and environmental factors are believed to contribute to the development and progression of AD. In general, patients initially present mild forgetfulness and difficulty in forming new memories. As it progresses, there are significant impairments in problem solving, social interaction, speech and overall cognitive function of the affected individual. Osteoarthritis (OA) is the most recurrent form of arthritis and widely acknowledged as a whole-joint disease, distinguished by progressive degeneration and erosion of joint cartilage accompanying synovitis and subchondral bone changes that can prompt peripheral inflammatory responses. Also predominantly affecting the elderly, OA frequently embroils weight-bearing joints such as the knees, spine and hips leading to pains, stiffness and diminished joint mobility, which in turn significantly impacts the patient's standard of life. Both infirmities can co-occur in older adults as a result of independent factors, as multiple health conditions are common in old age. Additionally, risk factors such as genetics, lifestyle changes, age and chronic inflammation may contribute to both conditions in some individuals. Besides localized peripheral low-grade inflammation, it is notable that low-grade systemic inflammation prompted by OA can play a role in AD pathogenesis. Studies have explored relationships between systemic inflammatory-associated diseases like obesity, hypertension, dyslipidemia, diabetes mellitus and AD. Given that AD is the most common form of dementia and shares similar risk factors with OA-both being age-related and low-grade inflammatory-associated diseases, OA may indeed serve as a risk factor for AD. This work aims to review literature on molecular mechanisms linking OA and AD pathologies, and explore potential connections between these conditions alongside future prospects and innovative treatments.

Anti-Neuroinflammatory Effects of a Macrocyclic Peptide-Peptoid Hybrid in Lipopolysaccharide-Stimulated BV2 Microglial Cells.

Inflammation processes of the central nervous system (CNS) play a vital role in the pathogenesis of several neurological and psychiatric disorders like depression. These processes are characterized by the activation of glia cells, such as microglia. Clinical studies showed a decrease in symptoms associated with the mentioned diseases after the treatment with anti-inflammatory drugs. Therefore, the investigation of novel anti-inflammatory drugs could hold substantial potential in the treatment of disorders with a neuroinflammatory background. In this in vitro study, we report the anti-inflammatory effects of a novel hexacyclic peptide-peptoid hybrid in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. The macrocyclic compound X15856 significantly suppressed Interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10 expression and release in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compound are partially explained by the modulation of the phosphorylation of p38 mitogen-activated protein kinases (MAPK), p42/44 MAPK (ERK 1/2), protein kinase C (PKC), and the nuclear factor (NF)-κB, respectively. Due to its remarkable anti-inflammatory properties, this compound emerges as an encouraging option for additional research and potential utilization in disorders influenced by inflammation, such as depression.

MODCEL-MHUS: a comprehensive multilayer hydrodynamic unified simulation for stormwater, sanitary sewer systems, and urban surface.

Numerous countries and regions have embraced implementing a separate sewer system, segregating sanitary and storm sewers into distinct systems. However, the functionality of these systems often needs to improve due to irregular interconnections, resulting in a mixed and malfunctioning system. Sewage collection is crucial for residential sanitation, but untreated collection significantly contributes to environmental degradation. Analyzing the simultaneous operation of both systems becomes vital for effective management. Using mathematical tools for precise and unified diagnosis and prognosis becomes imperative. However, municipal professionals and companies need more tools specifically designed to evaluate these systems in a unified way, mapping all the hydraulic connections observed in practice. This study proposes a unified simulation method for stormwater and sanitary sewer urban systems, addressing real-world scenarios and potential interferences. The primary goal is to develop a simulation method for both systems, considering system interconnections and urban layouts, involving hydrodynamic and water quality simulations. The practical application of this method, the Multilayer Hydrodynamic Simulation Method (MODCEL-MHUS), successfully identifies issues in urban water networks and suggests solutions, making it a valuable tool for urban water management and environmental engineering professionals.

MS-Driven Metabolic Alterations Are Recapitulated in iPSC-Derived Astrocytes.

OBJECTIVE: Astrocytes play a significant role in the pathology of multiple sclerosis (MS). Nevertheless, for ethical reasons, most studies in these cells were performed using the Experimental Autoimmune Encephalomyelitis model. As there are significant differences between human and mouse cells, we aimed here to better characterize astrocytes from patients with MS (PwMS), focusing mainly on mitochondrial function and cell metabolism. METHODS: We obtained and characterized induced pluripotent stem cell (iPSC)-derived astrocytes from three PwMS and three unaffected controls, and performed electron microscopy, flow cytometry, cytokine and glutamate measurements, gene expression, in situ respiration, and metabolomics. We validated our findings using a single-nuclei RNA sequencing dataset. RESULTS: We detected several differences in MS astrocytes including: (i) enrichment of genes associated with neurodegeneration, (ii) increased mitochondrial fission, (iii) increased production of superoxide and MS-related proinflammatory chemokines, (iv) impaired uptake and enhanced release of glutamate, (v) increased electron transport capacity and proton leak, in line with the increased oxidative stress, and (vi) a distinct metabolic profile, with a deficiency in amino acid catabolism and increased sphingolipid metabolism, which have already been linked to MS. INTERPRETATION: Here we describe the metabolic profile of iPSC-derived astrocytes from PwMS and validate this model as a very powerful tool to study disease mechanisms and to perform non-invasive drug targeting assays in vitro. Our findings recapitulate several disease features described in patients and provide new mechanistic insights into the metabolic rewiring of astrocytes in MS, which could be targeted in future therapeutic studies. ANN NEUROL 2022;91:652-669.

Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation.

Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.

The International Oryza Map Alignment Project (IOMAP): the Americas-past achievements and future directions.

The wild relatives of rice hold unexplored genetic diversity that can be employed to feed an estimated population of 10 billion by 2050. The Oryza Map Alignment Project (OMAP) initiated in 2003 has provided comprehensive genomic resources for comparative, evolutionary, and functional characterization of the wild relatives of rice, facilitating the cloning of >600 rice genes, including those for grain width (GW5) and submergence tolerance (SUB1A). Following in the footsteps of the original project, the goal of 'IOMAP: the Americas' is to investigate the present and historic genetic diversity of wild Oryza species endemic to the Americas through the sequencing of herbaria and in situ specimens. The generation of a large diversity panel describing past and current genetic status and potential erosion of genetic variation in the populations will provide useful knowledge for the conservation of the biodiversity in these species. The wild relatives of rice in the Americas present a wide range of resistance traits useful for crop improvement and neodomestication approaches. In the race against time for a sustainable food future, the neodomestication of the first cereal species recently accomplished in O. alta opens the door to the potential neodomestication of the other wild Oryza species in Americas.

Caryocar coriaceum fruits as a potential alternative to combat fungal and bacterial infections: In vitro evaluation of methanolic extracts.

Caryocar coriaceum, commonly known as 'pequi', is a medicinal species used traditionally for the herbal treatment of infectious and parasitic diseases in the Brazilian Northeast region. In this study, we investigated whether the fruits of C. coriaceum have bioactive chemical constituents against etiological agents of infectious diseases. The methanolic extract of the internal mesocarp of the fruits of C. coriaceum (MECC) was chemically analyzed and evaluated for its antimicrobial and drug-enhancing activity against multidrug-resistant pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and Candida spp. strains. The extract had flavones, flavonols, xanthones, catechins, and flavanones as major classes. A total of 11.26 mg GAE/g of phenolics, and 5.98 mg QE/g of flavonoids were found. No intrinsic antibacterial activity was observed; however, the extract was able to intensify the action of gentamicin and erythromycin against multi-resistant strains. The anti-Candida effect observed in this study was mainly due to the formation of reactive oxygen species. The extract was capable of causing damage to the plasmatic membrane of Candida tropicalis through pores formation. Our findings partially support the ethnopharmacological uses of the fruit pulp of C. coriaceum against infectious and parasitic diseases.

Effects of selenium supplementation on glycaemic control markers in healthy rodents: a systematic review and meta-analysis.

Overexposure to Se is detrimental to glucose metabolism, mainly because of its pro-oxidant effects and the overexpression of selenoproteins. This systematic review evaluated the effects of Se supplementation on glycaemic control in healthy rodents. The methodology followed the PRISMA. We searched the databases for articles published up to May 2022. The risk of bias and the methodological quality were assessed using the SYRCLE and CAMARADES. The results are presented as meta-analytic estimates of the overall standardised mean difference (SMD) and 95 % CI. Of the 2359 records retrieved, thirteen studies were included, of which eleven used sodium selenite and two used zero-valent Se nanoparticles as supplement. Nine studies were included in the meta-analysis. Generally, the risk of bias was high, and 23·1 % of the studies were of high quality. Supplementation with sodium selenite significantly increased fasting blood glucose (SMD = 2·57 (95 % CI (1·07, 4·07)), I2 = 93·5 % (P = 0·001). Subgroup analyses showed effect size was larger for interventions lasting between 21 and 28 d (SMD = 25·74 (95 % CI (2·29, 9·18)), I2 = 96·1 % (P = 0·001)) and for a dose of 864·7 µg/kg/d of sodium selenite (SMD = 10·26 (95 % CI (2·42, 18·11), I2 = 97·1 % (P = 0·010)). However, it did not affect glutathione peroxidase activity (SMD = 0·60 (95 % CI (-0·71, 1·91)), I2 = 83·2 % (P = 0·37)). The current analysis demonstrated the adverse effects of sodium selenite supplementation on glycaemic control in healthy rodents.

Wheat blast: The last enemy of hunger fighters.

Effective strategies for disease control are crucial for sustaining world food production and ensuring food security for the population. Wheat blast, a disease caused by the pathogen Magnaporthe oryzae pathotype Triticum, has been a concern for cereal producers and researchers due to its aggressiveness and rapid expansion. To solve this problem, the development of resistant varieties with durable resistance is an effective, economical and sustainable way to control the disease. Conventional breeding can be aided by several molecular tools to facilitate the mining of many sources of resistance, such as R genes and QTLs. The identification of new sources of resistance, whether in the wheat crop or in other cereals are an opportunity for efficient wheat breeding through the application of different techniques. Since this disease is still poorly studied in wheat, knowledge of the rice Magnaporthe pathotype may be adapted to control wheat blast. Thus, genetic mapping, molecular markers, transgenic approaches, and genomic editing are valuable technologies to fight wheat blast. This review aimed to compile the biotechnological alternatives available to accelerate the development of improved cultivars for resistance to wheat blast.

Enhancing global and local decision making for chemical safety assessments through increasing the availability of data.

Toxicity safety assessments are a fundamental part of the lifecycle of products and aim to protect human health and the environment from harmful exposures to chemical substances. To make decisions regarding the suitability of testing strategies, the applicability of individual tests or concluding an assessment for an individual chemical requires data. This review outlines how different forms of data sharing, from enhancing publicly-available data to extracting knowledge from commercially-sensitive data, leads to increased quantity and quality of evidence being available for safety assessors to review. This can result in more confident decisions for different use cases in the context of chemical safety assessments. Although a number of challenges remain with progressing the evolution of toxicity safety assessments, data sharing should be considered as a key approach to accelerating the development and uptake of new best practices.

Transcriptome profiling of cashew apples (Anacardium occidentale) genotypes reveals specific genes linked to firmness and color during pseudofruit development.

KEY MESSAGE: We found 34 and 71 key genes potentially involved in flavonoid biosynthesis and cell wall disassembly, respectively, which could be associated with specific peel coloration and softening of each genotype. Cashew apple (Anacardium occidentale) has a great economic importance worldwide due to its high nutritional value, peculiar flavor and aroma. During ripening, the peduncle develops different peel color and becomes quickly fragile due to its oversoftening, impacting its consumers' acceptance. In view of this, the understanding about its transcriptional dynamics throughout ripening is imperative. In this study, we performed a transcriptome sequencing of two cashew apple genotypes (CCP 76 and BRS 265), presenting different firmness and color peel, in the immature and ripe stages. Comparative transcriptome analysis between immature and ripe cashew apple revealed 4374 and 3266 differentially expressed genes (DEGs) to CCP 76 and BRS 265 genotypes, respectively. These genes included 71 and 34 GDEs involved in the cell wall disassembly and flavonoid biosynthesis, respectively, which could be associated with firmness loss and anthocyanin accumulation during cashew apple development. Then, softer peduncle of CCP 76 could be justified by down-regulated EXP and up-regulation of genes involved in pectin degradation (PG, PL and PAE) and in cell wall biosynthesis. Moreover, genes related to flavonoid biosynthesis (PAL, C4H and CHS) could be associated with early high accumulation of anthocyanin in red-peel peduncle of BRS 265. Finally, expression patterns of the selected genes were tested by real-time quantitative PCR (qRT-PCR), and the qRT-PCR results were consistent with transcriptome data. The information generated in this work will provide insights into transcriptome responses to cashew apple ripening and hence, it will be helpful for cashew breeding programs aimed at developing genotypes with improved quality traits.

The roles of WRKY transcription factors in Malus spp. and Pyrus spp.

The WRKY transcription factor gene family is known to be involved in plant defense against pathogens and in tolerance to different environmental stresses at different stages of development. The response mechanisms through which these genes act can be influenced by different phytohormones as well as by many trans- and cis-acting elements, making this network an important topic for analysis, but still something complex to fully understand. According to available reports, these genes can also perform important roles in pome species (Malus spp. and Pyrus spp.) metabolism, especially in adaptation of these plants to stressful conditions. Here, we present a quick review of what is known about WRKY genes in Malus and Pyrus genomes offering a simple way to understand what is already known about this topic. We also add information connecting the evolution of these transcription factors with others that can also be found in pomes.

An empirical analysis of mtSSRs: could microsatellite distribution patterns explain the evolution of mitogenomes in plants?

Microsatellites (SSRs) are tandem repeat sequences in eukaryote genomes, including plant cytoplasmic genomes. The mitochondrial genome (mtDNA) has been shown to vary in size, number, and distribution of SSRs among different plant groups. Thus, SSRs contribute with genomic diversity in mtDNAs. However, the abundance, distribution, and evolutionary significance of SSRs in mtDNA from a wide range of algae and plants have not been explored. In this study, the mtDNAs of 204 plant and algal species were investigated related to the presence of SSRs. The number of SSRs was positively correlated with genome size. Its distribution is dependent on plant and algal groups analyzed, although the cluster analysis indicates the conservation of some common motifs in algal and terrestrial plants that reflect common ancestry of groups. Many SSRs in coding and non-coding regions can be useful for molecular markers. Moreover, mitochondrial SSRs are highly abundant, representing an important source for natural or induced genetic variation, i.e., for biotechnological approaches that can modulate mtDNA gene regulation. Thus, this comparative study increases the understanding of the plant and algal SSR evolution and brings perspectives for further studies.