N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.

APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition

Pepper pectin methylesterase inhibitor protein CaPMEI1 is required for antifungal activity, basal disease resistance and abiotic stress tolerance

Pectin is one of the main components of the plant cell wall that functions as the primary barrier against pathogens. Among the extracellular pectinolytic enzymes, pectin methylesterase (PME) demethylesterifies pectin, which is secreted into the cell wall in a highly methylesterified form. Here, we isolated and functionally characterized the pepper (Capsicum annuum L.) gene CaPMEI1, which encodes a pectin methylesterase inhibitor protein (PMEI), in pepper leaves infected by Xanthomonascampestris pv. vesicatoria (Xcv). CaPMEI1 transcripts are localized in the xylem of vascular bundles in leaf tissues, and pathogens and abiotic stresses can induce differential expression of this gene. Purified recombinant CaPMEI1 protein not only inhibits PME, but also exhibits antifungal activity against some plant pathogenic fungi. Virus-induced gene silencing of CaPMEI1 in pepper confers enhanced susceptibility to Xcv, accompanied by suppressed expression of some defense-related genes. Transgenic ArabidopsisCaPMEI1-overexpression lines exhibit enhanced resistance to Pseudomonas syringae pv. tomato, mannitol and methyl viologen, but not to the biotrophic pathogen Hyaloperonospora parasitica. Together, these results suggest that CaPMEI1, an antifungal protein, may be involved in basal disease resistance, as well as in drought and oxidative stress tolerance in plants

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Determination of some heavy metals (Fe, Cu, Zn and Pb) in blood by total reflection X-ray fluorescence

The main purpose of this study is the interaction between nutrition (micronutrients heavy metals: Fe, Zn, Cu) and toxic heavy metals such as Pb in blood of children living in Gharb region of Morocco. This region receives all pollution carried by the Sebou river coming mainly from industrial activities. A rapid and simple analytical procedure was used for the determination of Fe, Cu and Zn trace amounts in blood by total-reflection X-ray fluorescence technique. This method is an energy dispersive XRF technique in a special geometry of primary beam, sample and detector. The sample is deposited on a plane polished surface of a suitable reflector material. It is presented as a few drops (25 $\mu$l) from a solution of blood digested in a mixture of HNO$_3$ and H$_2$O$_2$ using a microwaves accelerated reaction system. The accuracy of measurements has been investigated by using certified materials. The concentration of Cu was found to be normal in all samples ($\cong$1 ppm) which ruled out any interaction between this element and the others. On the other hand, amounts of Fe and Zn are very variables, suggesting an interaction between Fe and Zn. However, amounts of Pb in blood are inferior to 50 ppb, suggesting that no interaction exist with this metal and micronutrients

Human papillomavirus DNA in cervical lesions from Morocco and its implications for cancer control

To determine the types of human papillomaviruses (HPV) in northern Morocco, information which is needed for the design and use of HPV vaccines, we have analysed 129 cervical biopsies from this region. In our study, 91 cases were HPV positive, 45 cases had HPV-16 DNA, and 20 cases had HPV-18 DNA. This distribution of virus type was similar in inflammatory cervical lesions and in invasive cervical carcinomas. In conclusion, the HPV type distribution in Morocco is similar to that in other African Mediterranean countries, where the proportion of HPV-18 cases is significantly higher than in Europe. Determination of virus-type distribution is essential for vaccination programsThis work was mainly supported by CNESTEN, and in part by a co-operation project (2000-MA- 0015) between Morocco (CNPRST) and Spain (CSIC), and Ministerio de Ciencia y Tecnologı´a (SAF2000–0169).Peer reviewe

Human papillomavirus DNA in cervical lesions from Morocco and its implications for cancer control

ABSTRACTTo determine the types of human papillomaviruses (HPV) in northern Morocco, information which is needed for the design and use of HPV vaccines, we have analysed 129 cervical biopsies from this region. In our study, 91 cases were HPV positive, 45 cases had HPV-16 DNA, and 20 cases had HPV-18 DNA. This distribution of virus type was similar in inflammatory cervical lesions and in invasive cervical carcinomas. In conclusion, the HPV type distribution in Morocco is similar to that in other African Mediterranean countries, where the proportion of HPV-18 cases is significantly higher than in Europe. Determination of virus—type distribution is essential for vaccination programs

Molecular detection of human papillomavirus in 594 uterine cervix samples from moroccan women, 147 biopsies and 447 swabs

Uterine cervix cancer is the second most frequent female cancer after breast cancer in Morocco and represents a public health problem. Cervical cancer is highly linked to human papillomavirus (HPV) especially types 16 and 18 which are the highly oncogenic genotypes. To identify the contribution of HPV testing in the prevention of cervical cancer in Morocco, 147 biopsies collected at the Institut National d’Oncologie and 447 swabs from pathology laboratories and gynaecologist offices in Rabat were HPV analysed. HPV testing were made without any presumption of the histopathological diagnosis. A total of 147 paraffin-embedded biopsies and 447 exfoliated cervical samples were included. Based on histopathology results of the 147 biopsies, most cervical lesions were invasive carcinomas and non specific inflammations (NSI). With the molecular assay, HPV was detected in 91/147 (62%) patients. The high risk types 16 and 18 were found in 45% of the cases (41/91) and HPV 18 in 19% of the cases (17/91). Double infection with HPV 16 and 18 was found in 3 cases. Among the 447 swabs tested, 28 were HPV positives. Cytology results showed that 46% were inflammations (13/28). Among them, 10 patients had a NSI and only 3 patients had a cytology diagnosis of HPV infection. Based on these data, HPV testing should be associated to cervical cytology screening according to two algorithms established in function of the age of the patient and viral natural history. Combination of cytology and HPV testing allow identification of patient with high risk for development of high grade cervical lesions and improve cervical cancer prevention.Peer reviewe