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Opuntia dillenii (Ker Gawl.) Haw. belongs to the Cactaceae family and is native to the arid and semi-arid regions of Mexico and the southern United States. O. dillenii are now used as medicinal plants in various countries. In this study, we investigated the chemical composition of ethanolic extracts obtained from seeds, juice, and peel of O. dillenii fruits collected from Morocco, and we evaluated their antibacterial, antifungal, and antidiabetic activities. Phytochemical screening revealed high quantities of polyphenols (193.73 ± 81.44 to 341.12 ± 78.90 gallic acid eq [g/100 g dry weight]) in the extracts. The major phenolic compounds determined by HPLC were gallic acid, vanillic acid, and syringic acid. Regarding flavonoids, quercetin 3-O-β-D-glucoside and kaempferol were the predominant molecules. Juice extracts showed weak to moderate antibacterial activity against the bacteria species Listeria monocytogenes, Escherichia coli, and Salmonella braenderup. All tested extracts displayed a significant inhibitory effect on α-glucosidase and α-amylase activities in vitro, with the peel extracts showing the greatest inhibitory effects. Together, these findings suggest that O. dillenii fruits are a promising source for the isolation of novel compounds with antibacterial or antidiabetic activities. For the most abundant phytochemicals identified in O. dillenii peel ethanolic extract, molecular docking simulations against human pancreatic α-amylase enzyme were performed. These indicated the presence of bioactive compounds in the extract with a better potential to decrease the enzyme activity than the commercial drug acarbose.

A new family of pyrazole-based compounds (1–15) was synthesized and characterized using different physicochemical analyses, such as FTIR, UV-Visible, 1H, 13C NMR, and ESI/LC-MS. The compounds were evaluated for their in vitro antifungal and antibacterial activities against several fungal and bacterial strains. The results indicate that some compounds showed excellent antibacterial activity against E. coli, S. aureus, C. freundii, and L. monocytogenes strains. In contrast, none of the compounds had antifungal activity. Molecular electrostatic potential (MEP) map analyses and inductive and mesomeric effect studies were performed to study the relationship between the chemical structure of our compounds and the biological activity. In addition, molecular docking and virtual screening studies were carried out to rationalize the antibacterial findings to characterize the modes of binding of the most active compounds to the active pockets of NDM1 proteins.

Diagnosing patients with syndromic neurodevelopmental disorders presents a significant challenge for clinicians due to the considerable clinical and genetic heterogeneity associated with these rare conditions. The aim of this study was to determine the genetic cause of a Moroccan patient presenting with eye anomalies, hypogonadism, craniofacial dysmorphism and neurodevelopmental abnormalities. Whole exome sequencing (WES) identified a novel homozygous nonsense variant c.2704C > T (p.Gln902Ter) in the RAB3GAP1 gene associated with two clinically similar syndromes (Martsolf syndrome (MS) and Warburg micro syndrome type 1 (WARBM1)). Comparison of the clinical features of the patient with those of MS and WARBM1 syndromes led to the diagnosis of WARBM1. In summary, this report expands the mutational spectrum associated with WARBM1, highlights the diagnostic challenges of syndromic neurodevelopmental disorders and underlines the role of WES in establishing an accurate diagnosis, thereby enabling appropriate clinical management.

Background Cancer is one of the major health problems worldwide. In this article, we present for the first time the cancer incidence trends, the distribution and the socioeconomic profile of incident cancer cases in Eastern Morocco over a period of eight years. Methods Retrospective descriptive study of patients diagnosed with cancer at the Hassan II Regional Oncology Center (ROC) since it was created in October 2005 until December 2012. During the study period, the ROC was the only hospital specialized in cancer care in Eastern Morocco. Results A total of 7872 incident cases of cancer were registered in Eastern Morocco. Among these incident cases 5220 cases were women and 2652 were men, with a female to male ratio of 1.97. The mean age at diagnosis was 58 years for males and 52 for females and 94% of the patients aged over 30 years. For both sexes combined and for all cancer sites, breast cancer was the commonest followed by cervix uteri, colon-rectum, lung, nasopharynx, and stomach cancers. The most common cancer in women was breast cancer, followed respectively by cervix uteri cancer, colon-rectum cancer, ovary cancer, and stomach cancer. In men, the lung cancer ranked first, followed respectively by colon-rectum cancer, nasopharynx cancer, prostate cancer, and stomach cancer. For most cancers, crude incidence rates (CR) have increased significantly. The CR for all cancers combined has increased from 56.6 to 80.3 per 100,000 females and from 32.3 to 42.6 per 100,000 males during the study period. Patients profile analysis showed that 79% of cancer patients were from urban areas, 83% were unemployed and 85% had no health insurance. Conclusions The distribution of cancers in Eastern Morocco is different from those observed in other regions of Morocco. Unlike most countries, women were much more affected with cancer than men in Eastern Morocco. More importantly, the rates of many cancers are rising. Therefore, our data justify the need to develop effective programs for cancer control and prevention in Eastern Morocco. A better access to cancer care should be a priority of the health policies, given that the majority of cancer patients in Eastern Morocco are unemployed, and do not have medical care coverage.

We performed a systematic screen of the set of ≈5,000 viable Saccharomyces cerevisiae haploid gene deletion mutants and have identified 103 genes whose deletion causes sensitivity to the DNA-damaging agent methyl methanesulfonate (MMS). In total, 40 previously uncharacterized alkylation damage response genes were identified. Comparison with the set of genes known to be transcriptionally induced in response to MMS revealed surprisingly little overlap with those required for MMS resistance, indicating that transcriptional regulation plays little, if any, role in the response to MMS damage. Clustering of the MMS response genes on the basis of their cross-sensitivities to hydroxyurea, UV radiation, and ionizing radiation revealed a DNA damage core of genes required for responses to a broad range of DNA-damaging agents. Of particular significance, we identified a subset of genes that show a specific MMS response, displaying defects in S phase progression only in the presence of MMS. These genes may promote replication fork stability or processivity during encounters between replication forks and DNA damage.

Homologous recombination is an important mechanism for genome integrity maintenance, and several homologous recombination genes are mutated in various cancers and cancer-prone syndromes. However, since in some cases homologous recombination can lead to mutagenic outcomes, this pathway must be tightly regulated, and mitotic hyper-recombination is a hallmark of genomic instability. We performed two screens in Saccharomyces cerevisiae for genes that, when deleted, cause hyper-recombination between direct repeats. One was performed with the classical patch and replica-plating method. The other was performed with a high-throughput replica-pinning technique that was designed to detect low-frequency events. This approach allowed us to validate the high-throughput replica-pinning methodology independently of the replicative aging context in which it was developed. Furthermore, by combining the two approaches, we were able to identify and validate 35 genes whose deletion causes elevated spontaneous direct-repeat recombination. Among these are mismatch repair genes, the Sgs1-Top3-Rmi1 complex, the RNase H2 complex, genes involved in the oxidative stress response, and a number of other DNA replication, repair and recombination genes. Since several of our hits are evolutionarily conserved, and repeated elements constitute a significant fraction of mammalian genomes, our work might be relevant for understanding genome integrity maintenance in humans.

Thirty-four imidazole-based compounds synthesized by one-pot catalytic method were evaluated for their antifungal and antibacterial activities against several fungal and bacterial strains. None of the compounds had antibacterial activity. Interestingly, compounds 1, 2, 3, 10 and 15 displayed a strong antifungal activity against all the tested fungal species, while compounds 5, 7, 9, 11, 21 and 27 showed a moderate antifungal activity. To better understand the biological activity of the most active compounds ADME–Tox and molecular docking studies were carried out. Interestingly, compounds 1, 2, 3, 7, 10 and 15 showed excellent bioavailability. In addition, compounds 1, 2 and 3, exhibited good toxicity profiles. Docking studies of the two most active compounds 2 (IC50 of 95 ± 7.07 μM) and 10 (IC50 of 235 ± 7.07 μM) suggested that they might act by inhibiting the fungal lanosterol 14α-demethylase. Therefore, these novel antifungal agents merit further characterization for the development of new antifungal therapeutics.

[This corrects the article DOI: 10.1371/journal.pone.0151987.].

Malignant diseases have been believed to be more common in some areas of Eastern Morocco, but until now, cancer patterns have not been reported for this region. In this paper we present for the first time the cancer prevalence analysis in Eastern Morocco. Cross-sectional study carried out among all patients diagnosed and/or treated with cancer at the Hassan II Regional Oncology Center (ROC) since it was established in October 2005 until December 2012. The ROC is the only hospital specialized in cancer care in Eastern Morocco. A total of 8,508 cases of cancer were registered among residents in Eastern Morocco, with a female to male ratio of 2.1. The mean age at diagnosis was 53.9 ± 15.2 years (median age = 53 years). Thus, unlike in Western countries, cancer in Eastern Morocco afflicts younger population. The areas of Eastern Morocco did not differ significantly by mean age at diagnosis (p = 0.061). However, these regions differed significantly by sex ratio (p < 0.001). The highest sex ratio was observed in Figuig, with a female to male ratio of 3.1 (75.4% of the registered case were females), followed respectively by Taourirt, Oujda-Angad, Berkane, Nador-Driouch and Jerada. Clear variation in the distribution of cancer types between areas of Eastern Morocco was observed, both in males and females (p < 0.001). Furthermore, the areas of Eastern Morocco differed significantly by cancer prevalence (p < 0.001). The highest age-standardized five-year prevalence proportion was observed in Oujda-Angad with 420.2 per 100,000, followed respectively by Berkane (311.4), Jerada (287.8), Taourirt (269.3), Nador-Driouch (213.6) and Figuig (194.4). Trends in the five-year prevalence proportions decreased in Oujda-Angad, Berkane and Jerada throughout the study period, while an increasing trend was observed in Nador-Driouch, Taourirt and Figuig. For the first time, our study presents the pattern and distribution of diagnosed cancers in Eastern Morocco. Our study illustrates substantial differences in cancer patterns between areas of Eastern Morocco. These findings are important for cancer control and highlight the need to develop program aiming at controlling and preventing the spread of major cancer sites in Eastern Morocco, particularly in areas with increased cancer prevalence rates.

Background β‐thalassemia syndromes are the most common hereditary blood disorders in the world and are recognized as a major health problem in Morocco. They are characterized by the reduction or the absence of β‐globin chain synthesis. The severity of the disease depends on the nature of the variants affecting the β‐globin gene (HBB), and each ethnic group has its own mutation spectrum. Hereby, we present, for the first time, the molecular profile of β‐thalassemia in the Eastern region of Morocco. Methods This study concerns 39 cases from 33 families who were enrolled in the BRO Biobank. Nineteen were diagnosed with β‐thalassemia major and 20 with β‐thalassemia minor. To detect mutations of the β‐globin gene, we have used RFLP‐PCR and Sanger sequencing. Results Nine known β‐thalassemia variants have been identified. Among these, we reported, for the first time in the Moroccan population, the Czechoslovakian variant C38/39(‐C) at homozygous state. The C39(C > T) was the most frequent variant (72.54%), followed by FSC5(‐CT) (5.88%), FSC6(−A), IVS‐1‐110(G > A), −29(A > G), C38/39(‐C) (3.92% each), and finally by IVS‐I‐1(G > A), IVS‐II‐1(G > A), and −56(G > C) (1.96%). Of particular interest this mutational spectrum of β‐thalassemia is very different from that found in previous studies in Morocco or in other North African countries. Conclusion This study is the first contribution to the description of the molecular profile of β‐thalassemia in the Eastern region of Morocco. It shows the high molecular heterogeneity of β‐thalassemia in our country. Therefore, these results can be valuable for the implementation of carrier screening, genetic counseling, and prenatal diagnosis programs. The molecular investigation of β‐thalassemia in eastern region of Morocco indicates a high molecular heterogeneity and unique variant spectrum compared to that reported in other region of Morocco or in other North African countries. These data can be valuable for the implementation of carrier screening, genetic counseling and prenatal diagnosis programs.