Unravelling the relevance of the polyadenylation factor EhCFIm25 in entamoeba histolytica through proteomic analysis

We recently reported that silencing of the polyadenylation factor EhCFIm25 in Entamoeba histolytica, the protozoan which causes human amoebiasis, affects trophozoite proliferation, death, and virulence, suggesting that EhCFIm25 may have potential as a new biochemical target. Here, we performed a shotgun proteomic analysis to identify modulated proteins that could explain this phenotype. Data are available via ProteomeXchange with identifier PXD027784. Our results revealed changes in the abundance of 75 proteins. Interestingly, STRING analysis, functional GO‐term annotations, KEGG analyses, and literature review showed that modulated proteins are mainly related to glycolysis and carbon metabolism, cytoskeleton dynamics, and parasite virulence, as well as gene expression and protein modifications. Further studies are needed to confirm the hypotheses emerging from this proteomic analysis, to thereby acquire a comprehensive view of the molecular mechanisms involved

VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02)

Aim: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). Methods: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2/d, days 1-4 and 29-32), MMC (10 mg/m2, days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). Results: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. Conclusions: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients’ outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.This work was supported by Amgen S.A

Advances on Aptamers against Protozoan Parasites

Aptamers are single-stranded DNA or RNA sequences with a unique three-dimensional structure that allows them to recognize a particular target with high affinity. Although their specific recognition activity could make them similar to monoclonal antibodies, their ability to bind to a large range of non-immunogenic targets greatly expands their potential as tools for diagnosis, therapeutic agents, detection of food risks, biosensors, detection of toxins, drug carriers, and nanoparticle markers, among others. One aptamer named Pegaptanib is currently used for treating macular degeneration associated with age, and many other aptamers are in different clinical stages of development of evaluation for various human diseases. In the area of parasitology, research on aptamers has been growing rapidly in the past few years. Here we describe the development of aptamers raised against the main protozoan parasites that affect hundreds of millions of people in underdeveloped and developing countries, remaining a major health concern worldwide, i.e. Trypanosoma spp., Plasmodium spp., Leishmania spp., Entamoeba histolytica, and Cryptosporidium parvuum. The latest progress made in this area confirmed that DNA and RNA aptamers represent attractive alternative molecules in the search for new tools to detect and treat these parasitic infections that affect human health worldwide

Aptamers as a promising approach for the control of parasitic diseases

Aptamers are short single-stranded RNA or DNA oligonucleotides that are capable of binding various biological targets with high affinity and specificity. Their identification initially relies on a molecular process named SELEX (Systematic Evolution of Ligands by EXponential enrichment) that has been later modified in order to improve aptamer sensitivity, minimize duration and cost of the assay, as well as increase target types. Several biochemical modifications can help to enhance aptamer stability without affecting significantly target interaction. As a result, aptamers have generated a large interest as promising tools to compete with monoclonal antibodies for detection and inhibition of specific markers of human diseases. One aptamer-based drug is currently authorized and several others are being clinically evaluated. Despite advances in the knowledge of parasite biology and host–parasite interactions from “omics” data, protozoan parasites still affect millions of people around the world and there is an urgent need for drug target discovery and novel therapeutic concepts. In this context, aptamers represent promising tools for pathogen identification and control. Recent studies have reported the identification of “aptasensors” for parasite diagnosis, and “intramers” targeting intracellular proteins. Here we discuss various strategies that have been employed for intracellular expression of aptamers and expansion of their possible application, and propose that they may be suitable for the clinical use of aptamers in parasitic infections. Keywords: Aptamer, Parasite control, Protozoan parasite, SELEX strateg

CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis

Abstract Background Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa in humans. One of the main virulence factors of H. pylori is the cag pathogenicity island (cagPAI), which encodes a type 4-secretion system (T4SS) and the cytotoxin CagA. Translocation of CagA through the T4SS triggers host-signaling pathways. One of the T4SS proteins is CagL, which is necessary for CagA translocation. CagL is a 26-kDa protein that contains a hypervariable motif, which spans residues 58 to 62. Several polymorphisms in this region have been associated with different disease outcomes, e.g. in Mexico, N58 is associated with a higher risk of gastric cancer. The aim of this work is to analyze the sequence of the hypervariable motif (residues 58 to 62) of clinical isolates from Mexican patients with chronic gastritis, and to correlate these polymorphisms with the vacA genotype. Results Of the 164 biopsies analyzed, only 30.5% (50/164) were positive for H. pylori. Thirty-six of the 50 clinical isolates (72%) were cagA positive, and 40 (80%) had the most virulent vacA genotype (s1/m1). Of the cagA positive strains, 94.4% were vacA s1/m1. All the cagA + strains contained the cagL gene. The most prevalent sequence in the polymorphic region (residues 58–62) was DKMGE (75.8%, 25/33), followed by NKMGQ and NEIGQ (6.1%, 2/33), and DEIGQ, NKMGE, DKIGE, and DKIGK (3%, 1/33). Regarding polymorphisms in positions 58 and 59, the most common were D58/K59 (81.8%, 27/33), followed by N58/K59 (9.1%, 3/33), and D58/E59 (3%, 1/33). Only two isolates (6.1%) contained residues N58/E59, which correspond to those found in H. pylori strain ATCC 26695. 92.6% of the clinical isolates having polymorphism D58/K59 had the genotype vacA s1/m1, considered to be the most virulent, while 7.4% had the genotypes vacA s1/m2 and s2/m2. Conclusions In Mexican patients, CagL polymorphisms D58, K59, M60, E62, K122, and I134 are more common in patients with chronic gastritis

Challenge 2: Advanced Photonics

Coordinators: Miguel Cornelles Soriano, Javier Aizpurua Iriazabal.Photonic technologies provide key enabling components for the future digital transformation. This section includes an in-depth overview of the challenges that advanced photonics faces in the coming years in order to become a truly disruptive technology. Based on the expertise of numerous CSIC researchers, relevant key challenging points are identified, which range from the exploration of novel materials to the deployment of complex networks, including the development of photonic integrated circuits and devices.Peer reviewe