Caspase-8 and FADD: Where Cell Death and Inflammation Collide.

Caspase-8 is a master regulator of cell death pathways, although its regulation during inflammation remains elusive. Using elegant mouse genetic approaches, Schwarzer et al. and Tummers et al. revealed the importance of FADD in regulating caspase-8-mediated inflammatory responses and gut homeostasis.

Regulation of seed dormancy by histone post-translational modifications in the model plant Arabidopsis thaliana.

Plants synchronize their growth and development with environmental changes, which is critical for their survival. Among their life cycle transitions, seed germination is key for ensuring the survival and optimal growth of the next generation. However, even under favorable conditions, oftentimes germination can be blocked by seed dormancy, a regulatory multilayered checkpoint integrating internal and external signals. Intricate genetic and epigenetic mechanisms underlie seed dormancy establishment, maintenance, and release. In this review, we focus on recent advances that shed light on the complex mechanisms associated with physiological dormancy, prevalent in seed plants, with Arabidopsis thaliana serving as a model. Here, we summarize the role of multiple epigenetic regulators, but with a focus on histone modifications like acetylation and methylation, that finely tune dormancy responses and influence dormancy-associated gene expression. Understanding these mechanisms can lead to a better understanding of seed biology in general, as well as result in the identification of possible targets for breeding climate-resilient plants.

Group Theory of Syntactical Freedom in DNA Transcription and Genome Decoding.

Transcription factors (TFs) are proteins that recognize specific DNA fragments in order to decode the genome and ensure its optimal functioning. TFs work at the local and global scales by specifying cell type, cell growth and death, cell migration, organization and timely tasks. We investigate the structure of DNA-binding motifs with the theory of finitely generated groups. The DNA 'word' in the binding domain-the motif-may be seen as the generator of a finitely generated group Fdna on four letters, the bases A, T, G and C. It is shown that, most of the time, the DNA-binding motifs have subgroup structures close to free groups of rank three or less, a property that we call 'syntactical freedom'. Such a property is associated with the aperiodicity of the motif when it is seen as a substitution sequence. Examples are provided for the major families of TFs, such as leucine zipper factors, zinc finger factors, homeo-domain factors, etc. We also discuss the exceptions to the existence of such DNA syntactical rules and their functional roles. This includes the TATA box in the promoter region of some genes, the single-nucleotide markers (SNP) and the motifs of some genes of ubiquitous roles in transcription and regulation.

DNA Sequence and Structure under the Prism of Group Theory and Algebraic Surfaces.

Taking a DNA sequence, a word with letters/bases A, T, G and C, as the relation between the generators of an infinite group π, one can discriminate between two important families: (i) the cardinality structure for conjugacy classes of subgroups of π is that of a free group on one to four bases, and the DNA word, viewed as a substitution sequence, is aperiodic; (ii) the cardinality structure for conjugacy classes of subgroups of π is not that of a free group, the sequence is generally not aperiodic and topological properties of π have to be determined differently. The two cases rely on DNA conformations such as A-DNA, B-DNA, Z-DNA, G-quadruplexes, etc. We found a few salient results: Z-DNA, when involved in transcription, replication and regulation in a healthy situation, implies (i). The sequence of telomeric repeats comprising three distinct bases most of the time satisfies (i). For two-base sequences in the free case (i) or non-free case (ii), the topology of π may be found in terms of the SL(2,C) character variety of π and the attached algebraic surfaces. The linking of two unknotted curves-the Hopf link-may occur in the topology of π in cases of biological importance, in telomeres, G-quadruplexes, hairpins and junctions, a feature that we already found in the context of models of topological quantum computing. For three- and four-base sequences, other knotting configurations are noticed and a building block of the topology is the four-punctured sphere. Our methods have the potential to discriminate between potential diseases associated to the sequences.

Surrogate test performance for SARS-CoV-2 neutralizing antibodies (nAbs) for convalescent plasma (CCP): How useful could they be?

BACKGROUND: COVID-19 high-titer CCP selection is a concern, because neutralizing antibody (nAb) testing requires sophisticated labs and methods. Surrogate tests are an alternative for measuring nAb levels in plasma bags, including those that are pathogen-reduced. STUDY DESIGN/METHODS: We studied a panel consisting of 191 samples from convalescent donors tested by nAb (CPE-VNT), obtained from 180 CCP donations (collection: March 20-January 21) and 11 negative controls, with a total of 80 and 111 serum and plasma samples (71 amotosalen/UV treated), with nAb titers ranging from negative to 10,240. Samples were blindly tested for several surrogates: one anti-RBD, two anti-spike, and four anti-nucleocapsid tests, either isolated or combined to improve their positive predictive values as predictors of the presence of high-titer nAbs, defined as those with titers ≥160. RESULTS: Except for combined and anti-IgA/M tests, all isolated surrogate tests showed excellent performance for nAb detection: sensitivity (98.3%-100%), specificity (85.7%-100%), PPV (98.9%-100%), NPV (81.3%-100%), and AUC (0.93-0.96), with a variable decrease in sensitivity and considerably lower specificity when using FDA authorization and concomitant nAb titers ≥160. All surrogates had AUCs that were statistically different from CPE-VNT if nAb≥160, including when using combined, orthogonal approaches. CONCLUSIONS: Surrogate tests (isolated or in combination) have an indirect good performance in detecting the presence of nAb, with lower sensitivity and specificity when high nAb titer samples are used, possibly accepting a considerable number of donors whose nAb titers are actually low, which should be evaluated by each laboratory responsible for CCP collection.

Perioperative score for octogenarian patients eligible for rectal cancer surgery.

BACKGROUND AND OBJECTIVES: Colorectal cancer incidence increases with age; therefore, rectal cancer treatment in elderly patients is increasingly common. Surgery is a common rectal cancer treatment, and the risks involve complicated surgical decisions. There are currently few surgical outcome data for rectal cancer in elderly patients. The aim of this study is to identify new perioperative risk factors that could be associated with higher 30- and 180-day mortality in elderly patients in good clinical condition considering traditional perioperative risk scores and to develop a risk score. METHODS: A single-centre, retrospective cohort study was performed by reviewing the medical records of patients from the National Cancer Institute of Brazil aged 80 years or older who electively underwent rectal cancer surgery; several independent variables correlated with death from all causes at 30 and 180 days were studied. RESULTS: Multivariate analysis found new variables (CEA, albumin and reoperation) that had independent correlations with increased 30- and 180-day mortality. A clinical risk score was developed with survival profiles ranging from 29.3% to 97.2% within 30 days and 2.45% to 91.8% within 180 days. CONCLUSIONS: This score can aid in deciding whether a patient should undergo rectal cancer surgery.

Metabolism of abscisic acid in two contrasting rice genotypes submitted to recurrent water deficit.

Drought is the main constrain for crops worldwide, however, the effects of recurrent water deficit remain still hidden. We analysed two rice genotypes, 'BRS-Querência' (lowlands) and 'AN-Cambará' (uplands), after 7 days of recurrent drought followed by 24 h of rehydration, hypothesising that genotypes grown in regions with different water availabilities respond differently to water deficits, and that a previous exposure to stress could alter abscisic acid (ABA) metabolism. The results showed that both genotypes reduced stomatal conductance and increased ABA concentration. After rehydration, the ABA levels decreased, mainly in the plants of BRS-Querência subjected to recurrent stress. However, the levels of ABA were higher in plants in recurrent water deficit compared to non-recurrent stress plants in both genotypes. Remarkably in the lowland genotype, the ABA glucosyl-ester (ABA-GE) concentration increased after recovery in the plants under recurrent stress. Regarding of gene expression, the genes associated in ABA biosynthesis with the highest expression levels were NCED2, NCED3, NCED4 and AAO2. However, 'AN-Cambará' showed less transcriptional activation. Taking into account the genes involved in ABA catabolism, ABAH1 appears to play an important role related to the recurrent stress in upland plants. These results indicate that one of the factors that can promote greater tolerance for the upland genotype is the tradeoff between ABA and ABA-GE when plants are subjected to water deficits. In addition, they indicate that abscisic acid metabolism is altered due to the genotype (upland or lowland) and pre-exposure to stress can also modify adaptive responses in rice varieties (recurrent stress).

Long-term transcriptional memory in rice plants submitted to salt shock.

MAIN CONCLUSION: A first salt shock event alters transcriptional and physiological responses to a second event, being possible to identify 26 genes associated with long-term memory. Soil salinity significantly affects rice cultivation, resulting in large losses in growth and productivity. Studies report that a disturbing event can prepare the plant for a subsequent event through memory acquisition, involving physiological and molecular processes. Therefore, genes that provide altered responses in subsequent events define a category known as "memory genes". In this work, the RNA-sequencing (RNA-Seq) technique was used to analyse the transcriptional profile of rice plants subjected to different salt shock events and to characterise genes associated with long-term memory. Plants subjected to recurrent salt shock showed differences in stomatal conductance, chlorophyll index, electrolyte leakage, and the number of differentially expressed genes (DEGs), and they had lower Na+/K+ ratios than plants that experienced only one stress event. Additionally, the mammalian target of rapamycin (mTOR) pathways, and carbohydrate and amino acid-associated pathways were altered under all conditions. Memory genes can be classified according to their responses during the first event (+ or -) and the second shock event (+ or -), being possible to observe a larger number of transcripts for groups [+ /-] and [-/ +], genes characterised as "revised response." This is the first long-term transcriptional memory study in rice plants under salt shock, providing new insights into the process of plant memory acquisition.

Screening for SARS-CoV-2 antibodies in convalescent plasma in Brazil: Preliminary lessons from a voluntary convalescent donor program.

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) collection began in two Brazilian hospitals for treatment of severe/critical patients. METHODS AND MATERIALS: Mild/moderate COVID-19 convalescents were selected as CCP donors after reverse transcription polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and absence of symptoms for ≥14 days plus (a) age (18-60 years), body weight greater than 55 kg; (b) immunohematological studies; (c) no infectious markers of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus-1/2, Chagas and syphilis infection; (d) no HLA antibodies (multiparous); (e) second RT-PCR (nasopharyngeal swab and/or blood) negativity; (f) virus neutralization test (cytopathic effect-based virus neutralization test neutralizing antibody) and anti-nucleocapsid protein SARS-CoV-2 IgM, IgG, and IgA enzyme-linked immunosorbent assays. RESULTS: Among 271 donors (41 females, 230 males), 250 presented with neutralizing antibodies. Final RT-PCR was negative on swab (77.0%) or blood (88.4%; P = .46). Final definition of RT-PCR was only defined at more than 28 days after full recovery in 59 of 174 (33.9%) RT-PCR -ve, and 25/69 RT-PCR +ve (36.2%; 13 between 35 and 48 days). Neutralizing antibody titers of 160 or greater were found in 63.6%. Correlation between IgG signal/cutoff of 5.0 or greater and neutralizing antibody of 160 or greater was 82.4%. Combination of final RT-PCR -ve with neutralizing antibody ≥160 was 41.3% (112/271). Serial plasma collection showed decline in neutralizing antibody titers and IgA levels (P < .05), probably denoting a "golden period" for CCP collection (≤28 days after joining the program); IgA might have an important role as neutralizing antibody. Donor's weight, days between disease onset and serial plasma collection, and IgG and IgM levels are important predictors for neutralizing antibody titer. CONCLUSIONS: RT-PCR +ve cases are still detected in 36.2% within 28 to 48 days after recovery. High anti-nucleocapsid protein IgG levels may be used as a surrogate marker to neutralizing antibody.

Long-term somatic memory of salinity unveiled from physiological, biochemical and epigenetic responses in two contrasting rice genotypes.

Plants are constantly exposed to environmental fluctuations, that may occur in a single day or over longer periods. In many cases, abiotic stresses are transient and recurrent, impacting how plants respond in subsequent adverse conditions. Adaptation mechanisms may occur at the physiological, biochemical and molecular level, modifying transcriptional response, regulatory proteins, epigenetic marks or metabolites. Here, we aimed to uncover the different strategies that rice uses to respond to recurrent stress. We tested varieties with contrasting behavior towards salinity (tolerance or sensitivity) and imposed salt stress (150 mM NaCl) during 48 h at vegetative and/or reproductive stages. After 48 h of stress in reproductive stage, leaves and roots were harvested separately or otherwise the plants were submitted to a 24 h recovery, prior to sample harvesting. Plants submitted to a recurrent stress responded differently from those suffering a single stress event. In the case of the sensitive genotype, recurrent stress led to lower Na/K ratio in roots and lower hydrogen peroxide accumulation and lipid peroxidation in leaves, but maintenance of global DNA methylation levels. In the tolerant genotype, recurrent stress did neither affect the Na/K ratio nor the stomatal conductance, although the levels of superoxide anion and hydrogen peroxide accumulation were lower, as also observed for global levels of DNA methylation. Our work shows that a short pre-exposure to salt stress may improve rice tolerance to subsequent stress, trough biochemical, physiological and epigenetic processes, with more significant changes visible in the tolerant genotype.

The Self-Simulation Hypothesis Interpretation of Quantum Mechanics.

We modify the simulation hypothesis to a self-simulation hypothesis, where the physical universe, as a strange loop, is a mental self-simulation that might exist as one of a broad class of possible code theoretic quantum gravity models of reality obeying the principle of efficient language axiom. This leads to ontological interpretations about quantum mechanics. We also discuss some implications of the self-simulation hypothesis such as an informational arrow of time.

Validation of reference genes for RT-qPCR studies in Stevia rebaudiana in response to elicitor agents.

Stevia rebaudiana is an important source of natural steviol glycosides and is of increasing interest in various fields of study. Therefore, understanding the molecular processes regulating its metabolism is of great importance. In this study, the stability of seven reference genes (18S ribosomal RNA, Actin, Aquaporin, Calmodulin, Eukaryote elongation factor 1-α, Malate dehydrogenase, and Ubiquitin) under the effect of three stress-related elicitors (methyl jasmonate, salicylic acid, and spermidine) was evaluated in stevia plants. We used RefFinder software, which makes use of the four main currently available algorithms for reference gene selection: geNorm, NormFinder, BestKeeper, and the Comparative ∆Ct method. The results indicated that Ubiquitin and Actin can be used as reference genes under all tested experimental conditions. The genes, 18S ribosomal RNA, traditionally used as a reference gene, along with Calmodulin, showed the lowest stability. The expression of Deoxyxylulose-5-phosphate synthase and Kaurenoic acid hydroxylase genes was used to confirm the validated reference genes, showing that inadequacy of the reference gene may lead to erroneous results. This is the first study on the stability of reference genes in Stevia rebaudiana plants, and is of great relevance for further analysis of the gene expression of the steviol glycoside biosynthetic pathway.

Molecular responses to recurrent drought in two contrasting rice genotypes.

MAIN CONCLUSION: The set of variables analyzed as integrated by multivariate analysis of principal components consistently showed a memory effect induced by the drought pre-treatment in AN Cambará plants. The effects of drought can vary ddepending on many factors. Among these the occurrence of a previous water stress may leave a residual effect (memory), influencing the future performance of a plant in response to a new drought event. This study tested the hypothesis that plants experiencing recurrent drought would show more active mechanisms of water deficit tolerance, mainly plants of the genotype that is cultivated often experiencing water shortages periods. Additionally, all the plants subjected to water deficit were rehydrated by 24 h and the expression of transcription factors related to drought responses was re-evaluated. To this end, the water status of two rice genotypes, BRS Querência (flooded) and AN Cambará (dryland), was evaluated to identify molecular alterations likely underpinning drought-memory. In growth stage V5, some plants were exposed to water stress (10% VWC soil moisture-pre-treatment). Thereafter, the pots were rehydrated at the same level as the control pots and maintained under this condition until drought was reapplied (10% VWC) at the reproductive stage (R1-R2). Then, the plants were rehydrated and maintained at pot capacity for 24 h. Overall, the set of variables analyzed integrally by multivariate analysis of principal components consistently showed a memory effect induced by the drought pre-treatment in AN Cambará plants (the dryland genotype). This conclusion, based on data of the biochemical and molecular analyses, was supported by the greater capacity of maintenance of the water status by stomatal regulation of the pre-treated and rehydrated plants after the second drought stimulus.

Gene expression and activity of antioxidant enzymes in rice plants, cv. BRS AG, under saline stress.

The rice cultivar (Oryza sativa L.) BRS AG, developed by Embrapa Clima Temperado, is the first cultivar designed for purposes other than human consumption. It may be used in ethanol production and animal feed. Different abiotic stresses negatively affect plant growth. Soil salinity is responsible for a serious reduction in productivity. Therefore, the objective of this study was to evaluate the gene expression and the activity of antioxidant enzymes (SOD, CAT, APX and GR) and identify their functions in controlling ROS levels in rice plants, cultivar BRS AG, after a saline stress period. The plants were grown in vitro with two NaCl concentrations (0 and 136 mM), collected at 10, 15 and 20 days of cultivation. The results indicated that the activity of the enzymes evaluated promotes protection against oxidative stress. Although, there was an increase of reactive oxygen species, there was no increase in MDA levels. Regarding genes encoding isoforms of antioxidant enzymes, it was observed that OsSOD3-CU/Zn, OsSOD2-Cu/Zn, OsSOD-Cu/Zn, OsSOD4-Cu/Zn, OsSODCc1-Cu/Zn, OsSOD-Fe, OsAPX1, OsCATB and OsGR2 were the most responsive. The increase in the transcription of all genes among evaluated isoforms, except for OsAPX6, which remained stable, contributed to the increase or the maintenance of enzyme activity. Thus, it is possible to infer that the cv. BRS AG has defense mechanisms against salt stress.

Comparative transcriptomics of rice plants under cold, iron, and salt stresses.

Abiotic stresses such as salinity, iron toxicity, and low temperatures are the main limiting factors of rice (Oryza sativa L.) yield. The elucidation of the genes involved in responses to these stresses is extremely important to understand the mechanisms that confer tolerance, as well as for the development of cultivars adapted to these conditions. In this study, the RNA-seq technique was used to compare the transcriptional profile of rice leaves (cv. BRS Querência) in stage V3, exposed to cold, iron, and salt stresses for 24 h. A range of 41 to 51 million reads was aligned, in which a total range of 88.47 to 89.21 % was mapped in the reference genome. For cold stress, 7905 differentially expressed genes (DEGs) were observed, 2092 for salt and 681 for iron stress; 370 of these were common to the three DEG stresses. Functional annotation by software MapMan demonstrated that cold stress usually promoted the greatest changes in the overall metabolism, and an enrichment analysis of overrepresented gene ontology (GO) terms showed that most of them are contained in plastids, ribosome, and chloroplasts. Saline stress induced a more complex interaction network of upregulated overrepresented GO terms with a relatively low number of genes compared with cold stress. Our study demonstrated a high number of differentially expressed genes under cold stress and a greater relationship between salt and iron stress levels. The physiological process most affected at the molecular level by the three stresses seems to be photosynthesis.

Status of pyrethroid resistance and mechanisms in Brazilian populations of Tuta absoluta.

The tomato leafminer, Tuta absoluta, is a major pest of tomato crops worldwide. This study surveyed the resistance of T. absoluta populations from four regions in Brazil to pyrethroid insecticides, the frequencies of L1014F, T929I and M918T Na channel mutations, and the role of detoxification metabolism in the resistance. Resistance ratios varied from 1- to 11-times among populations and insecticides, but control failure likelihood assays showed that all pyrethroids assessed exhibited no efficacy at all (and thus, 98-100% control failure likelihood) against all T. absoluta populations. The activity of glutathione S-transferase and cytochrome P450-mediated N-demethylation in biochemical assays was significantly correlated with the level of resistance to deltamethrin and permethrin suggesting that these enzymes may play a role in resistance. TaqMan assays were used to screen for the presence of knockdown resistance (kdr) mutations and revealed that the L1014F kdr mutation was fixed in all populations and associated with two super-kdr mutations, M918T and particularly T929I, at high frequency. Altogether, results suggest that control failures are because of mutations in the domain II of the sodium channel, as a prevailing mechanism of resistance to pyrethroids in populations of T. absoluta in Brazil. But, enhanced cytochrome P450-dependent monooxygenases and GST activities also play an important role in the resistance of some populations, which reinforce that pyrethroids must not be used overall to control T. absoluta.

Juvenile psammomatoid ossifying fibroma with massive mandibular involvement.

Juvenile psammomatoid ossifying fibroma (JPOF) is a histologic variant of an ossifying fibroma. While an ossifying fibroma varies in appearance, it consists of fibrocellular tissue and mineralized material. JPOF is a rare benign lesion; however, it can be extended locally and mimic a malignant tumor. It is considered a specific clinicopathologic entity, due to its occurrence in children and adolescents, the presence of psammomas, and its purported tendency for local aggressive growth and recurrence. It commonly affects the maxilla, nasal cavity, paranasal sinuses, and ethmoid region. This article describes a rare, aggressive case of a large JPOF that led to the total destruction of the mandible.

Evaluation of changes in nasal airway in patients having undergone surgically assisted maxillary expansion.

INTRODUCTION: Surgically assisted maxillary expansion (SAME) is used to treat transverse maxillary discrepancies. The effect of this technique on the nasal airway has been the subject of a large number of studies. OBJECTIVE: The aim of the present study was to identify changes in the nasal airway in patients having undergone SAME. MATERIALS AND METHODS: A prospective study was carried out on a sample of 10 patients having undergone SAME who agreed to participate in all phases of the study. Data acquisition involved a questionnaire, Glatzel mirror, and computed tomography measurements in both the preoperative and postoperative periods. RESULTS: Nasal width increased in all patients following SAME (mean increase: 1.29 mm). The mean opening of the intermaxillary space was 5.30 mm. The postoperative nasal airway was larger in 8 patients (80%), with a mean increase of 0.30 cm(2) (18.52%). A significant overall increase (P < 0.05) in the nasal valve angle occurred in the postoperative period. The use of the Glatzel mirror revealed a smaller area of condensation in the postoperative period in only 1 patient. CONCLUSIONS: The nasal airway underwent a positive change following surgically assisted maxillary expansion. Moreover, the nasal valve angle is suggested as a new parameter for the analysis of this improvement.

Extensive central ossifying fibroma of the maxilla: a case report.

Central ossifying fibroma (COF) is a benign osteogenic neoplasm, with fibrous tissue and calcifications similar to bone, which has the clinical presentation of an asymptomatic bulging. It is more common in the mandibular premolar and molar region, in the third and fourth decades of life, and in women more frequently than men. Surgical removal is the treatment of choice and additional reconstruction is essential due to the functional and esthetic problems faced by the patient. This article describes the surgical treatment and subsequent reconstruction in a 22-year-old man with COF and an expansile lesion of the anterior maxilla. Enucleation of the lesion was performed and porous high-density polyethylene biomaterial was used for reconstruction.

Surgical management of multiple myeloma in the mandible: a case report.

Multiple myeloma (MM), solitary bone plasmacytoma, and extramedullary plasmacytoma are different types of plasma cell neoplasia, which is a lymphoid neoplastic proliferation of ß-cells. While MM is most frequently seen in the vertebrae and long bones, 30% of MM cases are found in the jaws. This case report presents a 58-year-old man with mandibular swelling; his medical history indicated he had a fracture of the humerus 1 month earlier. Panoramic radiography revealed a radiolucent lesion in the mandibular posterior region. Biopsy was performed and the histopathological examination indicated plasmocytoma. However, given the patient's dental and medical history, and the presence of multiple osteolytic lesions, the final diagnosis was MM. The patient underwent chemotherapy for the MM. To treat the pathological fracture of the jaw, a hemimandibulectomy was followed by the installation of a reconstructive plate.