Charge cluster occurrence in land plants' mitochondrial proteomes with functional and structural insights.

The Charge Clusters (CCs) are involved in key functions and are distributed according to the organism, the protein's type, and the charge of amino acids. In the present study, we have explored the occurrence, position, and annotation as a first large-scale study of the CCs in land plants mitochondrial proteomes. A new python script was used for data curation. The Finding Clusters Charge in Protein Sequences Program was performed after adjusting the reading window size. A 44316 protein sequences belonging to 52 species of land plants were analysed. The occurrence of Negative Charge Clusters (NCCs) (1.2%) is two times more frequent than the Positive Charge Clusters (PCCs) (0.64%). Moreover, 39 and 30 NCCs were conserved in 88 and 41 proteins in intra and in inter proteomes respectively, while 14 and 21 PCCs were conserved in 53 and 85 protein sequences in intra and inter proteomes consecutively. Sequences carrying mixed CCs are rare (0.12%). Despite this low abundance, CCs play a crucial role in protein function. The CCs tend to be located mainly in the terminal regions of proteins which guarantees specific protein targeting and import into the mitochondria. In addition, the functional annotation of CCs according to Gene Ontology shows that CCs are involved in binding functions of either proteins or macromolecules which are deployed in different metabolic and cellular processes such as RNA editing and transcription. This study may provide valuable information while considering the CCs in understanding the environmental adaptation of plants.Communicated by Ramaswamy H. Sarma.

Prevalence of self-reported food allergy in Tunisia: General trends and probabilistic modeling.

Background: Food allergy (FA) has become a major public health concern affecting millions of children and adults worldwide. In Tunisia, published data on FA are scarce. Methods: This study, was intended to fill the gap and estimate the frequency of allergy to different foods in the Sfax region, Tunisia, within self-reported FA. One hundred twenty-five (125) children (56% males, 1-17 years old), and 306 adults (17% males, 18-70 years old) were interviewed using a bilingual questionnaire. Results: The number of self-reported food allergens in this sample was 105; allergens were clustered in 8 foods: fruits, seafood, eggs, milk and dairy, cereals, nuts, vegetables, and peanuts. Cutaneous reactions were the most frequent symptoms, in both children and adults. About 40% of children and 30% of adults had a family history of FA. About 81% of adults and 38% of children are allergic to at least 1 non-food allergen. The most prevalent food allergen was the fruit group in both adults and children, followed by seafood. Most food allergies were mutually exclusive and 90% of individuals have a single FA. The relationship between self-declared FA was modeled using a Bayesian network graphical model in order to estimate conditional probabilities of each FA when other FA is present. Conclusions: Our findings suggest that the prevalence of self-reported FA in Tunisia depends on dietary habits and food availability since the most frequent allergens are from foods that are highly consumed by the Tunisian population.

γ-tocopherol methyltransferase gene sequencing and SNP discovery associated with olive oil quality.

γ-tocophérol methyltransferase (GTMT), a key enzyme in the tocopherols biosynthesis pathway, is involved in the conversion of δ- and l'γ-tocophérol to ß- et l'α-tocophérol, respectively. In fact, it plays an important role in the α-tocopherol composition and the quality of olive oil. A total of 14 olive tree cultivars (Olea Europaea L.) were chosen and used in this study. They were sampled from different regions of Tunisia. Four cultivars from four Mediterranean regions (Greece, Algeria, Morocco, and Spain) were included for comparison. For each variety, DNA was extracted from young leaves. The Vte4 gene was PCR amplified from the 14 olive varieties and verified by electrophoresis on a 2% agarose gel for each variety. DNA sequencing of the olive cultivars revealed several single-nucleotide polymorphisms (SNPs). Statistical and bioinformatics analysis  draw attention to some associations between some of the SNPs, tocopherols contents and oleic acid content. In fact, two significant associations are obtained between SUBS24 and both Total-Tocopherols and Beta-Tocopherol. Moreover, dendrograms reveals that there is a correlation between genetic variability and chemical characteristics which make the Vte4 gene more interesting in terms of tocopherols levels.

Effect of Aerobic/Strength Training on RANKL Gene DNA Methylation Levels.

BACKGROUND: The osteoclastogenesis RANKL gene plays a key role in bone remodeling. The hypomethylation of its promoter region may cause osteoporosis. The present study aimed to elucidate the influence of physical activity on DNA methylation changes of RANKL promoter cytosine-phosphate-guanine (CpG)-rich region in active and sedentary adults and to assess the effect of aerobic and strength training on RANKL DNA methylation changes among Tunisian-North African adults. METHODS: A total of 104 participants including 52 adults (58% males and 42% females) and 52 adults (31% males and 69% females) were recruited for the observational and interventional part of the study, respectively. The intervention consisted of 12 weeks of aerobic training (30 min/session) followed by 10 minutes of strengthening exercises. All participants completed the International Physical Activity Questionnaire and provided blood samples for quantitative methylation-specific polymerase chain reaction (PCR) analysis. RESULTS: The study revealed a significant difference (P = 6 × 10-10) in the methylation level of the RANKL promoter region between active and sedentary adults, with a 6.68-fold increase observed in the active group. After the intervention, both the trained (P = 41 × 10-5) and untrained (P = .002) groups displayed high methylation levels in the RANKL promoter region. In addition, the trained group exhibited significant improvements in heart rate (P = 2.2 × 10-16), blood pressure (P = 39 × 10-3), maximal oxygen uptake (P = 1.5 × 10-7), and fat mass (P = 7 × 10-4). CONCLUSION: Exploring epigenetic modifications in the RANKL promoter region may contribute to a more comprehensive understanding of the complexity of osteoporosis. This suggests that aerobic/strength training could potentially improve the bone system, reducing its vulnerability to osteoporosis by increasing RANKL DNA methylation.

Inspiratory muscle training, with or without concomitant pulmonary rehabilitation, for chronic obstructive pulmonary disease (COPD).

BACKGROUND: Inspiratory muscle training (IMT) aims to improve respiratory muscle strength and endurance. Clinical trials used various training protocols, devices and respiratory measurements to check the effectiveness of this intervention. The current guidelines reported a possible advantage of IMT, particularly in people with respiratory muscle weakness. However, it remains unclear to what extent IMT is clinically beneficial, especially when associated with pulmonary rehabilitation (PR).   OBJECTIVES: To assess the effect of inspiratory muscle training (IMT) on chronic obstructive pulmonary disease (COPD), as a stand-alone intervention and when combined with pulmonary rehabilitation (PR). SEARCH METHODS: We searched the Cochrane Airways trials register, CENTRAL, MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Physiotherapy Evidence Database (PEDro) ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 20 October 2021. We also checked reference lists of all primary studies and review articles. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared IMT in combination with PR versus PR alone and IMT versus control/sham. We included different types of IMT irrespective of the mode of delivery. We excluded trials that used resistive devices without controlling the breathing pattern or a training load of less than 30% of maximal inspiratory pressure (PImax), or both. DATA COLLECTION AND ANALYSIS: We used standard methods recommended by Cochrane including assessment of risk of bias with RoB 2. Our primary outcomes were dyspnea, functional exercise capacity and health-related quality of life.  MAIN RESULTS: We included 55 RCTs in this review. Both IMT and PR protocols varied significantly across the trials, especially in training duration, loads, devices, number/ frequency of sessions and the PR programs. Only eight trials were at low risk of bias. PR+IMT versus PR We included 22 trials (1446 participants) in this comparison. Based on a minimal clinically important difference (MCID) of -1 unit, we did not find an improvement in dyspnea assessed with the Borg scale at submaximal exercise capacity (mean difference (MD) 0.19, 95% confidence interval (CI) -0.42 to 0.79; 2 RCTs, 202 participants; moderate-certainty evidence).   We also found no improvement in dyspnea assessed with themodified Medical Research Council dyspnea scale (mMRC) according to an MCID between -0.5 and -1 unit (MD -0.12, 95% CI -0.39 to 0.14; 2 RCTs, 204 participants; very low-certainty evidence).  Pooling evidence for the 6-minute walk distance (6MWD) showed an increase of 5.95 meters (95% CI -5.73 to 17.63; 12 RCTs, 1199 participants; very low-certainty evidence) and failed to reach the MCID of 26 meters. In subgroup analysis, we divided the RCTs according to the training duration and mean baseline PImax. The test for subgroup differences was not significant. Trials at low risk of bias (n = 3) demonstrated a larger effect estimate than the overall. The summary effect of the St George's Respiratory Questionnaire (SGRQ) revealed an overall total score below the MCID of 4 units (MD 0.13, 95% CI -0.93 to 1.20; 7 RCTs, 908 participants; low-certainty evidence).  The summary effect of COPD Assessment Test (CAT) did not show an improvement in the HRQoL (MD 0.13, 95% CI -0.80 to 1.06; 2 RCTs, 657 participants; very low-certainty evidence), according to an MCID of -1.6 units.  Pooling the RCTs that reported PImax showed an increase of 11.46 cmH2O (95% CI 7.42 to 15.50; 17 RCTs, 1329 participants; moderate-certainty evidence) but failed to reach the MCID of 17.2 cmH2O.  In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.  One abstract reported some adverse effects that were considered "minor and self-limited". IMT versus control/sham Thirty-seven RCTs with 1021 participants contributed to our second comparison. There was a trend towards an improvement when Borg was calculated at submaximal exercise capacity (MD -0.94, 95% CI -1.36 to -0.51; 6 RCTs, 144 participants; very low-certainty evidence). Only one trial was at a low risk of bias. Eight studies (nine arms) used the Baseline Dyspnea Index - Transition Dyspnea Index (BDI-TDI). Based on an MCID of +1 unit, they showed an improvement only with the 'total score' of the TDI (MD 2.98, 95% CI 2.07 to 3.89; 8 RCTs, 238 participants; very low-certainty evidence). We did not find a difference between studies classified as with and without respiratory muscle weakness. Only one trial was at low risk of bias. Four studies reported the mMRC, revealing a possible improvement in dyspnea in the IMT group (MD -0.59, 95% CI -0.76 to -0.43; 4 RCTs, 150 participants; low-certainty evidence). Two trials were at low risk of bias. Compared to control/sham, the MD in the 6MWD following IMT was 35.71 (95% CI 25.68 to 45.74; 16 RCTs, 501 participants; moderate-certainty evidence). Two studies were at low risk of bias. In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.  Six studies reported theSGRQ total score, showing a larger effect in the IMT group (MD -3.85, 95% CI -8.18 to 0.48; 6 RCTs, 182 participants; very low-certainty evidence). The lower limit of the 95% CI exceeded the MCID of -4 units. Only one study was at low risk of bias. There was an improvement in life quality with CAT (MD -2.97, 95% CI -3.85 to -2.10; 2 RCTs, 86 participants; moderate-certainty evidence). One trial was at low risk of bias. Thirty-two RCTs reported PImax, showing an improvement without reaching the MCID (MD 14.57 cmH2O, 95% CI 9.85 to 19.29; 32 RCTs, 916 participants; low-certainty evidence). In subgroup analysis, we did not find a difference between different training durations and between studies judged with and without respiratory muscle weakness.   None of the included RCTs reported adverse events. AUTHORS' CONCLUSIONS: IMT may not improve dyspnea, functional exercise capacity and life quality when associated with PR. However, IMT is likely to improve these outcomes when provided alone. For both interventions, a larger effect in participants with respiratory muscle weakness and with longer training durations is still to be confirmed.

Prevalence of comorbid asthma in Tunisian patients with COVID-19: clinical features and outcomes.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in around 1 million COVID-19 infection cases and over 29,000 deaths in Tunisia thus far. There is great variability in the prevalence of asthma among patients with COVID-19, but the impact of asthma on patients with COVID-19 is not clear. We sought to describe the clinical features of Tunisian patients with COVID-19 and to compare asthmatic and non-asthmatic patients. METHODOLOGY: This retrospective study included 675 Tunisian patients who were hospitalized with COVID-19. Clinical characteristics were collected from medical records. Bivariate analyses and multivariate regression models were used to assess the associations between asthma and the risk of severe symptoms, including death/recovery. RESULTS: The prevalence of asthma in the sample was 14.5%. The results show that asthmatic patients with COVID-19 have significantly less severe symptoms and better outcomes than non-asthmatic patients. CONCLUSIONS: Asthma was not found to be associated with higher severity or worse prognosis among patients with COVID-19 in Tunisia.

Editorial: Advances in genomic and genetic tools, and their applications for understanding embryonic development and human diseases.

Significant advances have been recently made in the development of the genetic and genomic platforms. This has greatly contributed to a better understanding of gene expression and regulation machinery. Consequently, this led to considerable progress in unraveling evidence of the genotype-phenotype correlation between normal/abnormal embryonic development and human disease complexity. For example, advanced genomic tools such as next-generation sequencing, and microarray-based CGH have substantially helped in the identification of gene and copy number variants associated with diseases as well as in the discovery of causal gene mutations. In addition, bioinformatic analysis tools of genome annotation and comparison have greatly aided in data analysis for the interpretation of the genetic variants at the individual level. This has unlocked potential possibilities for real advances toward new therapies in personalized medicine for the targeted treatment of human diseases. However, each of these genomic and bioinformatics tools has its limitations and hence further efforts are required to implement novel approaches to overcome these limitations. It could be possible that the use of more than one platform for genotype-phenotype deep analysis is an effective approach to disentangling the cause and treatment of the disease complexities. Our research topic aimed at deciphering these complexities by shedding some light on the recent applications of the basic and advanced genetic/genomic and bioinformatics approaches. These include studying gene-gene, protein-protein, and gene-environment interactions. We, in addition, aimed at a better understanding of the link between normal/abnormal embryonic development and the cause of human disease induction.

Oxidative stress markers-driven prognostic model to predict post-discharge mortality in heart failure with reduced ejection fraction.

Background: Current predictive models based on biomarkers reflective of different pathways of heart failure with reduced ejection fraction (HFrEF) pathogenesis constitute a useful tool for predicting death risk among HFrEF patients. The purpose of the study was to develop a new predictive model for post-discharge mortality risk among HFrEF patients, based on a combination of clinical patients' characteristics, N-terminal pro-B-type Natriuretic peptide (NT-proBNP) and oxidative stress markers as a potentially valuable tool for routine clinical practice. Methods: 116 patients with stable HFrEF were recruited in a prospective single-center study. Plasma levels of NT-proBNP and oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GPX), uric acid (UA), total bilirubin (TB), gamma-glutamyl transferase (GGT) and total antioxidant capacity (TAC)] were measured in the stable predischarge condition. Generalized linear model (GLM), random forest and extreme gradient boosting models were developed to predict post-discharge mortality risk using clinical and laboratory data. Through comprehensive evaluation, the most performant model was selected. Results: During a median follow-up of 525 days (7-930), 33 (28%) patients died. Among the three created models, the GLM presented the best performance for post-discharge death prediction in HFrEF. The predictors included in the GLM model were age, female sex, beta blockers, NT-proBNP, left ventricular ejection fraction (LVEF), TAC levels, admission systolic blood pressure (SBP), angiotensin-converting enzyme inhibitors/angiotensin receptor II blockers (ACEI/ARBs) and UA levels. Our model had a good discriminatory power for post-discharge mortality [The area under the curve (AUC) = 74.5%]. Based on the retained model, an online calculator was developed to allow the identification of patients with heightened post-discharge death risk. Conclusion: In conclusion, we created a new and simple tool that may allow the identification of patients at heightened post-discharge mortality risk and could assist the treatment decision-making.

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

A potential oral microbiome signature associated with coronary artery disease in Tunisia.

The coronary artery disease (CAD) is a chronic inflammatory disease involving genetic as well as environmental factors. Recent evidence suggests that the oral microbiome has a significant role in triggering atherosclerosis. The present study assessed the oral microbiome composition variation between coronary patients and healthy subjects in order to identify a potential pathogenic signature associated with CAD. We performed metagenomic profiling of salivary microbiomes by 16S ribosomal RNA (rRNA) next-generation sequencing. Oral microbiota profiling was performed for 30 individuals including 20 patients with CAD and ten healthy individuals without carotid plaques or previous stroke or myocardial infarction. We found that oral microbial communities in patients and healthy controls are represented by similar global core oral microbiome. The predominant taxa belonged to Firmicutes (genus Streptococcus, Veillonella, Granulicatella, Selenomonas), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Rothia), Bacteroidetes (genus Prevotella, Porphyromonas), and Fusobacteria (genus Fusobacterium, Leptotrichia). More than 60% relative abundance of each sample for both CAD patients and controls is represented by three major genera including Streptococcus (24.97 and 26.33%), Veillonella (21.43 and 19.91%), and Neisseria (14.23 and 15.33%). Using penalized regression analysis, the bacterial genus Eikenella was involved as the major discriminant genus for both status and Syntax score of CAD. We also reported a significant negative correlation between Syntax score and Eikenella abundance in coronary patients' group (Spearman rho = -0.68, P=0.00094). In conclusion, the abundance of Eikenella in oral coronary patient samples compared with controls could be a prominent pathological indicator for the development of CAD.

Novel combined UGT1A1 mutations in Crigler Najjar Syndrome type I.

BACKGROUND: Uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5-8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type. The A (TA) 7TAA allele has been identified as the most frequent allele in the Caucasian populations while A (TA) 8TAA allele remains the rarest allele worldwide in North Africa, including the Arab populations. METHODS: The spectrum of UGT1A1 genetic mutations in seventeen Tunisian children affected by persistent unconjugated hyperbilirubinemias is represented in addition to their relatives, notably parents, sisters, and brothers. Tunisian children, from 16 unrelated families as well as a 17th family without CN1 affected child, were originated from the West Center of Tunisia. The promoter region and coding exons of the UGT1A1 were PCR amplified, subsequently subjected to Sanger sequencing. RESULTS: The frequencies of genotypes in CN1 patients were as follows (TA) (7/7) (12/17: 70.6%) and (TA) (8/8) (5/17: 29.4%). All patients harbored the c.1070A>G mutation of exon 3 (UGT1A1*16) in the homozygous state. Among relatives of our patients (n = 16), who were all heterozygotes for UGT1A1*16, 13/16 (81.25%) had a heterozygous state for UGT1A1∗1/UGT1A1∗28 or (TA) (6/7) and, 18.75% (3/16) were heterozygous for UGT1A1∗28/UGT1A1∗37 or (TA) (7/8) of the promoter polymorphisms. CONCLUSION: UGT1A1*16 accompanied with UGT1A1*28 or UGT1A1*37 had a specific geographic and ethnic distribution for CN pathogenesis in this Tunisian cohort.

Integration of Innovative Technologies in the Agri-Food Sector: The Fundamentals and Practical Case of DNA-Based Traceability of Olives from Fruit to Oil.

Several socio-economic problems have been hidden by the COVID-19 pandemic crisis. Particularly, the agricultural and food industrial sectors have been harshly affected by this devastating disease. Moreover, with the worldwide population increase and the agricultural production technologies being inefficient or obsolete, there is a great need to find new and successful ways to fulfill the increasing food demand. A new era of agriculture and food industry is forthcoming, with revolutionary concepts, processes and technologies, referred to as Agri-food 4.0, which enables the next level of agri-food production and trade. In addition, consumers are becoming more and more aware about the origin, traceability, healthy and high-quality of agri-food products. The integration of new process of production and data management is a mandatory step to meet consumer and market requirements. DNA traceability may provide strong approach to certify and authenticate healthy food products, particularly for olive oil. With this approach, the origin and authenticity of products are confirmed by the means of unique nucleic acid sequences. Selected tools, methods and technologies involved in and contributing to the advance of the agri-food sector are presented and discussed in this paper. Moreover, the application of DNA traceability as an innovative approach to authenticate olive products is reported in this paper as an application and promising case of smart agriculture.

SNP discovery and structural insights into OeFAD2 unravelling high oleic/linoleic ratio in olive oil.

Fatty Acid Desaturase 2 (FAD2), a key enzyme in the fatty acid biosynthesis pathway, is involved in the desaturation and conversion of oleic acid to linoleic acid. Therefore, it plays a crucial role in oleic/linoleic acid ratio and the quality of olive oil. DNA sequencing of 19 FAD2 genes from a set of olive oil varieties revealed several single-nucleotide polymorphisms (SNPs) and highlighted associations between some of the SNPs and saturated fatty acids contents. This was further confirmed by SNP-interaction and machine learning approach. Haplotype diversity analysis led to the discovery of three highly polymorphic SNPs and four haplotypes harboring differential oleic/linoleic acid ratios. Moreover, a combination of molecular modeling and docking experiments allowed a deeper and better understanding of the structure-function relationship of the FAD2 enzyme. Sequence patterns and variations involved in the regulation of the FAD2 activity were also identified. Furthermore, S82C and H213N substitutions in OeFAD2 make the Oueslati variety more interesting in terms of fatty acid profile and oleic acid level.

Evidence of SARS-CoV-2 symptomatic reinfection in four healthcare professionals from the same hospital despite the presence of antibodies.

OBJECTIVES: Since the onset of the COVID-19 pandemic, cases of reinfection with SARS-CoV-2 have been reported, raising additional public health concerns. SARS-CoV-2 reinfection was assessed in healthcare workers (HCWs) in Tunisia because they are at the greatest exposure to infection by different variants. METHODS: We conducted whole-genome sequencing of the viral RNA from clinical specimens collected during the initial infection and the suspected reinfection from 4 HCWs, who were working at the Habib Bourguiba University Hospital (Sfax, Tunisia) and retested positive for SARS-CoV-2 through reverse transcriptase-polymerase chain reaction (RT-PCR) after recovery from a first infection. A total of 8 viral RNAs from the patients' respiratory specimens were obtained, which allowed us to characterize the differences between viral genomes from initial infection and positive retest. The serology status for total Ig, IgG, and IgM against SARS-CoV-2 was also determined and followed after the first infection. RESULTS: We confirmed through whole-genome sequencing of the viral samples that all 4 cases experienced a reinfection event. The interval between the 2 infection events ranged between 45 and 141 days, and symptoms were milder in the second infection for 2 patients and more severe for the remaining 2 patients. Reinfection occurred in all 4 patients despite the presence of antibodies in 3 of them. CONCLUSION: This study adds to the rapidly growing evidence of COVID-19 reinfection, where viral sequences were used to confirm infection by distinct isolates of SARS-CoV-2 in HCWs. These findings suggest that individuals who are exposed to different SARS-CoV-2 variants might not acquire sufficiently protective immunity through natural infection and emphasize the necessity of their vaccination and the regular follow-up of their immune status both in quantitative and qualitative terms.

Application of data fusion modeling for the prediction of auxin response elements in Zea mays for food security purposes.

Food security will be affected by climate change worldwide, particularly in the developingworld, where the most important food products originate from plants. Plants are often exposed to environmental stresses that may affect their growth, development, yield, and foodquality. Auxin is a hormone that plays a critical role in improving plants' tolerance of environmental conditions. Auxin controls the expression of many stress-responsive genes inplants by interacting with specific cis-regulatory elements called auxin-responsive elements (AuxREs). In this work, we performed an in silico prediction of AuxREs in promotersof five auxin-responsive genes in Zea mays. We applied a data fusion approach based onthe combined use of Dempster-Shafer evidence theory and fuzzy sets. Auxin has a directimpact on cell membrane proteins. The short-term auxin response may be represented bythe regulation of transmembrane gene expression. The detection of an AuxRE in the promoter of prolyl oligopeptidase (POP) in Z. mays and the 3-fold overexpression of this geneunder auxin treatment for 30 min indicated the role of POP in maize auxin response. POP isregulated by auxin to perform stress adaptation. In addition, the detection of two AuxRETGTCTC motifs in the upstream sequence of the bx1 gene suggests that bx1 can be regulated by auxin. Auxin may also be involved in the regulation of dehydration-responsive element-binding and some members of the protein kinase superfamily.

An Evidence Theory and Fuzzy Logic Combined Approach for the Prediction of Potential ARF-Regulated Genes in Quinoa.

Quinoa constitutes among the tolerant plants to the challenging and harmful abiotic environmental factors. Quinoa was selected as among the model crops destined for bio-saline agriculture that could contribute to the staple food security for an ever-growing worldwide population under various climate change scenarios. The auxin response factors (ARFs) constitute the main contributors in the plant adaptation to severe environmental conditions. Thus, the determination of the ARF-binding sites represents the major step that could provide promising insights helping in plant breeding programs and improving agronomic traits. Hence, determining the ARF-binding sites is a challenging task, particularly in species with large genome sizes. In this report, we present a data fusion approach based on Dempster-Shafer evidence theory and fuzzy set theory to predict the ARF-binding sites. We then performed an "In-silico" identification of the ARF-binding sites in Chenopodium quinoa. The characterization of some known pathways implicated in the auxin signaling in other higher plants confirms our prediction reliability. Furthermore, several pathways with no or little available information about their functions were identified to play important roles in the adaptation of quinoa to environmental conditions. The predictive auxin response genes associated with the detected ARF-binding sites may certainly help to explore the biological roles of some unknown genes newly identified in quinoa.

Assessment of population structure, genetic diversity and relationship of Mediterranean olive accessions using SSR markers and computational tools.

Olive tree is an emblematic crop of the Mediterranean region, mainly renowned for its fruit oil, although the species provides several industrial purposes. The Mediterranean basin constitutes the origin of olive species diversification and represents a valuable source of genetic variability of olive germplasm. Therefore, the evaluation of the diversity and the population structure of this Mediterranean germplasm is a challenge for olive species preservation, crop breeding and genetic improvement. In this context, our study aims to analyze the genetic diversity and the population structure of 79 Mediterranean olive accessions using 15 genomic SSRs and by applying computational model-based approaches. The used SSRs revealed a total number of 225 alleles with a mean of 15 alleles per locus. Observed and expected heterozygosity (Ho = 0.79, He = 0.805) with a Polymorphism Information Content value of 0.775 indicate high level of genetic diversity. All results of the Unweighted Pair Group Method with Arithmetic (UPGMA), Jaccard similarity index, Principal Coordinate Analysis (PCoA) and the Bayesian analyses supported the separation of the Mediterranean varieties in two sub-populations, one of which mainly composed by Spanish accessions.

Immune checkpoint CD155 promoter methylation profiling reveals cancer-associated behaviors within breast neoplasia.

BACKGROUND: CD155 immune checkpoint has recently emerged as a compelling immunotherapeutic target. Epigenetic DNA methylation changes are recognized as key molecular mechanisms in cancer development. Hence, the identification of methylation markers that are sensitive and specific for breast cancer may improve early detection and predict prognosis. We speculate that CD155 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its immunoregulatory functions. METHODS: Methylation analyses were conducted on 14 CpGs sites in the CD155 promoter region by bisulfite pyrosequencing. To elucidate the related gene expression changes, a transcriptional study using RT-qPCR was performed. Statistical analyses were performed to evaluate correlations of CD155 methylation profiles with mRNA expression together with clinical-pathological features, prognosis and immune infiltrate. RESULTS: CD155 promoter methylation profile was significantly associated with SBR grade, tumor size, molecular subgroups, HER2 and hormonal receptors expression status. Low CD155 methylation rates correlated with better prognosis in univariate cox proportional hazard analysis and appeared as an independent survival predictor in cox-regression multivariate analysis. Further, methylation changes at CD155 specific CpG sites were consistent with CD155 membranous mRNA isoform expression status. Statistical analyses also showed a significant association with immune Natural Killer cell infiltrate when looking at the CpG7, CpG8, CpG9 and CpG11 sites. CONCLUSION: Altogether, our results contribute to a better understanding of the impact of CD155 immune checkpoint modality expression in breast tumors, revealing for the first time that specific CpG sites from CD155 promoter may be a potential biomarker in breast cancer monitoring.