Study of a dual-mode array integrated in a multi-element transducer for imaging and therapy of prostate cancer

The development of endocavitary dual-mode probes is essential for the accurate treatment of many deep-seated cancers, which require a high imaging resolution and the capacity to selectively treat focal areas in the region of interest. The MULTIP project is aimed at using state-of-art piezoelectric technologies to design dual-mode ultrasonic probes for cancer-foci treatment and monitoring. In order to allow an efficient surgery planning, the technical study has been accompanied by a volume processing study permitting the design of the ultrasonic imaging/therapy process based on high-resolution–high-quality MRI images. Several prototypes were designed based on a simulation study and implemented: 1) two successive wide-band dual-mode transducer allowing imaging at high-resolution (6 MHz) on a wide field of view, and therapy at 3 MHz with a good transduction efficiency (48% and 70%); 2) a therapy-only transducer matrix adapted to the desired curvature with a high transduction efficiency (70%). Finally, a registration study of MRI volumes on ultrasound volumes has shown that, because of the texture of the ultrasound images, it is more efficient to search at registering the surfaces of the volumes once they have been segmented in each modality, rather than trying to register the two data volumes directly.     

Resistance Mutations and CTL Epitopes in Archived HIV-1 DNA of Patients on Antiviral Treatment: Toward a New Concept of Vaccine

Eleven patients responding successfully to first-line antiretroviral therapy (ART) were investigated for proviral drug resistance mutations (DRMs) in RT by ultra-deep pyrosequencing (UDPS). After molecular typing of the class I alleles A and B, the CTL epitopes in the Gag, Nef and Pol regions of the provirus were sequenced and compared to the reference HXB2 HIV-1 epitopes. They were then matched with the HLA alleles with determination of theoretical affinity (TA). For 3 patients, the results could be compared with an RNA sample of the circulating virus at initiation of therapy. Five out of 11 patients exhibited DRMs by UDPS. The issue is whether a therapeutic switch is relevant in these patients by taking into account the identity of the archived resistance mutations. When the archived CTL epitopes were determined on the basis of the HLA alleles, different patterns were observed. Some epitopes were identical to those reported for the reference with the same TA, while others were mutated with a decrease in TA. In 2 cases, an epitope was observed as a combination of subpopulations at entry and was retrieved as a single population with lower TA at success. With regard to immunological stimulation and given the variability of the archived CTL epitopes, we propose a new concept of curative vaccine based on identification of HIV-1 CTL epitopes after prior sequencing of proviral DNA and matching with HLA class I alleles.     

Impact of Alginate Composition: From Bead Mechanical Properties to Encapsulated HepG2/C3A Cell Activities for In Vivo Implantation

Recently, interest has focused on hepatocytes’ implantation to provide end stage liver failure patients with a temporary support until spontaneous recovery or a suitable donor becomes available. To avoid cell damage and use of an immunosuppressive treatment, hepatic cells could be implanted after encapsulation in a porous biomaterial of bead or capsule shape. The aim of this study was to compare the production and the physical properties of the beads, together with some hepatic cell functions, resulting from the use of different material combinations for cell microencapsulation: alginate alone or combined with type I collagen with or without poly-L-lysine and alginate coatings. Collagen and poly-L-lysine increased the bead mechanical resistance but lowered the mass transfer kinetics of vitamin B12. Proliferation of encapsulated HepG2/C3A cells was shown to be improved in alginate-collagen beads. Finally, when the beads were subcutaneously implanted in mice, the inflammatory response was reduced in the case of alginate mixed with collagen. This in vitro and in vivo study clearly outlines, based on a systematic comparison, the necessity of compromising between material physical properties (mechanical stability and porosity) and cell behavior (viability, proliferation, functionalities) to define optima hepatic cell microencapsulation conditions before implantation.     

Making the most of 'omics' for crop breeding

Adoption of new breeding technologies is likely to underpin future gains in crop productivity. The rapid advances in 'omics' technologies provide an opportunity to generate new datasets for crop species. Integration of genome and functional omics data with genetic and phenotypic information is leading to the identification of genes and pathways responsible for important agronomic phenotypes. In addition, high-throughput genotyping technologies enable the screening of large germplasm collections to identify novel alleles from diverse sources, thus offering a major expansion in the variation available for breeding. In this review, we discuss these advances, which have opened the door to new techniques for construction and screening of breeding populations, to increase ultimately the efficiency of selection and accelerate the rates of genetic gain.     

Isolation and functional characterization of an allatotropin receptor from Manduca sexta

Manduca sexta allatotropin (Manse-AT) is a multifunctional neuropeptide whose actions include the stimulation of juvenile hormone biosynthesis, myotropic stimulation, cardioacceleratory functions, and inhibition of active ion transport. Manse-AT is a member of a structurally related peptide family that is widely found in insects and also in other invertebrates. Its precise role depends on the insect species and developmental stage. In some lepidopteran insects including M. sexta, structurally-related AT-like (ATL) peptides can be derived from alternatively spliced mRNAs transcribed from the AT gene. We have isolated a cDNA for an AT receptor (ATR) from M. sexta by a PCR-based approach using the sequence of the ATR from Bombyx mori. The sequence of the M. sexta ATR is similar to several G protein-coupled receptors from other insect species and to the mammalian orexin receptor. We demonstrate that the M. sexta ATR expressed in vertebrate cell lines is activated in a dose-responsive manner by Manse-AT and each Manse-ATL peptide in the rank order ATL-I > ATL-II > ATL-III > AT, and functional analysis in multiple cell lines suggest that the receptor is coupled through elevated levels of Ca(2+) and cAMP. In feeding larvae, Manse-ATR mRNA is present at highest levels in the Malpighian tubules, followed by the midgut, hindgut, testes, and corpora allata, consistent with its action on multiple target tissues. In the adult corpora cardiaca--corpora allata complex, Manse-ATR mRNA is present at relatively low levels in both sexes.     

Taenia solium disease in humans and pigs: an ancient parasitosis disease rooted in developing countries and emerging as a major health problem of global dimensions

This article reviews current knowledge on human and porcine cysticercosis caused by Taenia solium. It highlights the conditions favorable for its prevalence and transmission, as well as current trends in research on its natural history, epidemiology, immunopathology, diagnosis, treatment and prevention. Our opinions on the most urgent needs for further research are also presented.     

Human Papillomavirus Type 16 Pseudovirions with Few Point Mutations in L1 Major Capsid Protein FG Loop Could Escape Actual or Future Vaccination for Potential Use in Gene Therapy

HPV prophylactic vaccination based on VLPs was implemented 7 years ago and has now shown a high degree of efficiency to reduce HPV-induced lesions. Moreover, it was shown that HPV-derived virus-like particles or pseudovirions could be used as gene therapy vectors. As a consequence, characterization of the antigenic structure of HPV capsids is crucial for designing future HPV vaccines with better or broader efficacy and for the design of HPV-derived gene therapy vectors with reduced immunogenicity or vaccination escaping. In this study, we have generated 10 HPV16 FG loop L1 protein mutants and analyzed their ability to self-assemble into VLP, their immunogenicity, and their ability to transduce cells when used as pseudovirions. Most of the mutants had lost their ability to transduce cells at the exception of two chimeric HPV16/31 L1 protein FG loop mutants. Sera from mice immunized with HPV16 L1 wt VLPs very weakly neutralized pseudovirions derived from these two HPV16/31 L1 protein FG loop mutants. These findings suggest that only a few point substitutions within the FG loop are sufficient to generate a new serotype escaping vaccination. As a consequence, derived pseudovirions might be suitable as gene therapy vectors in vaccinated subjects.