Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing.

Telomerase is a ribonucleoprotein complex responsible for the maintenance of the length of the telomeres during cell division, which is active in germ-line cells as well as in the vast majority of tumors but not in most normal tissues. The wide expression of the human telomerase catalytic subunit (hTERT) in tumors makes it an interesting candidate vaccine for cancer. hTERT-derived peptide 540-548 (hTERT(540)) has been recently shown to be recognized in an HLA-A*0201-restricted fashion by T cell lines derived from peptide-stimulated peripheral blood mononuclear cells (PBMC) from healthy donors. As a first step to the inclusion of this peptide in immunotherapy clinical trials, it is crucial to assess hTERT(540)-specific T cell reactivity in cancer patients as well as the ability of hTERT-specific CD8(+) T lymphocytes to recognize and lyse hTERT-expressing target cells. Here, we have analyzed the CD8(+) T cell response to peptide hTERT(540) in HLA-A*0201 melanoma patients by using fluorescent HLA-A*0201/hTERT(540) peptide tetramers. HLA-A*0201/hTERT(540) tetramer(+) CD8(+) T cells were readily detected in peptide-stimulated PBMC from a significant proportion of patients and could be isolated by tetramer-guided cell sorting. hTERT(540)-specific CD8(+) T cells were able to specifically recognize HLA-A*0201 cells either pulsed with peptide or transiently transfected with a minigene encoding the minimal epitope. In contrast, they failed to recognize hTERT-expressing HLA-A*0201(+) target cells. Furthermore, in vitro proteasome digestion studies revealed inadequate hTERT processing. Altogether, these results raise questions on the use of hTERT(540) peptide for cancer immunotherapy.

Lateralization of olfactory processing: Differential impact of right and left temporal lobe epilepsies.

Olfactory processes were reported to be lateralized. The purpose of this study was to further explore this phenomenon and investigate the effect of the hemispheric localization of epileptogenic foci on olfactory deficits in patients with temporal lobe epilepsy (TLE). Olfactory functioning was assessed in 61 patients and 60 healthy control (HC) subjects. The patients and HC subjects were asked to rate the intensity, pleasantness, familiarity, and edibility of 12 common odorants and then identify them. Stimulations were delivered monorhinally in the nostril ipsilateral to the epileptogenic focus in TLE and arbitrarily in either the left or the right nostril in the HC subjects. The results demonstrated that regardless of the side of stimulation, patients with TLE had reduced performance in all olfactory tasks compared with the HC subjects. With regard to the side of the epileptogenic focus, patients with left TLE judged odors as less pleasant and had more difficulty with identification than patients with right TLE, underlining a privileged role of the left hemisphere in the emotional and semantic processing of odors. Finally, irrespective of group, a tendency towards a right-nostril advantage for judging odor familiarity was found in agreement with a prominent role of the right hemisphere in odor memory processing.

Do plants adjust their sex allocation and secondary sexual morphology in response to their neighbours?

BACKGROUND AND AIMS: Changes in the sex allocation (i.e. in pollen versus seed production) of hermaphroditic plants often occur in response to the environment. In some homosporous ferns, gametophytes choose their gender in response to chemical cues sent by neighbours, such that spores develop as male gametophytes if they perceive a female or hermaphrodite nearby. Here it is considered whether a similar process might occur in the androdioecious angiosperm species Mercurialis annua, in which males co-occur with hermaphrodites; previous work on a Spanish population of M. annua found that individuals were more likely to develop as males at high density. METHODS: Using a novel approach to treat plants with leachate from pots containing males or hermaphrodites of M. annua, the hypothesis that individuals assess their mating opportunities, and adjust their sex expression accordingly, was tested through an exchange of chemical cues through the soil. KEY RESULTS: For the population under study, from Morocco, no evidence was found for soil-signal-dependent sex expression: neither sex ratios nor sex allocation differed among experimental treatments. CONCLUSIONS: The results imply either that the Moroccan population under study behaves differently from that previously studied in Spain (pointing to potential geographical variation in plasticity for sex expression), or that our method failed to capture the signals used by M. annua for adjustment of sex expression.

Polyhydroxyalkanoate synthesis in transgenic plants as a new tool to study carbon flow through beta-oxidation.

Transgenic plants producing peroxisomal polyhydroxy- alkanoate (PHA) from intermediates of fatty acid degradation were used to study carbon flow through the beta-oxidation cycle. Growth of transgenic plants in media containing fatty acids conjugated to Tween detergents resulted in an increased accumulation of PHA and incorporation into the polyester of monomers derived from the beta-oxidation of these fatty acids. Tween-laurate was a stronger inducer of beta-oxidation, as measured by acyl-CoA oxidase activity, and a more potent modulator of PHA quantity and monomer composition than Tween-oleate. Plants co-expressing a peroxisomal PHA synthase with a capryl-acyl carrier protein thioesterase from Cuphea lanceolata produced eightfold more PHA compared to plants expressing only the PHA synthase. PHA produced in double transgenic plants contained mainly saturated monomers ranging from 6 to 10 carbons, indicating an enhanced flow of capric acid towards beta-oxidation. Together, these results support the hypothesis that plant cells have mechanisms which sense levels of free or esterified unusual fatty acids, resulting in changes in the activity of the beta-oxidation cycle as well as removal and degradation of these unusual fatty acids through beta-oxidation. Such enhanced flow of fatty acids through beta-oxidation can be utilized to modulate the amount and composition of PHA produced in transgenic plants. Furthermore, synthesis of PHAs in plants can be used as a new tool to study the quality and relative quantity of the carbon flow through beta-oxidation as well as to analyse the degradation pathway of unusual fatty acids.

Informed Control Over Inputs and Extent of Industrial Processing, June 2005

Stylized facts regarding the industrial process include emphases on obtaining information about and control over the quality of raw materials. We provide a model that establishes conditions under which informed control involves ensuring uniformity in inputs and increased uniformity encourages more extensive processing. We show when the Boltzmann-Shannon entropy statistic is an appropriate measure of uniformity.

@neurIST infrastructure for advanced disease management through integration of heterogeneous data, computing, and complex processing services

The increasing volume of data describing humandisease processes and the growing complexity of understanding, managing, and sharing such data presents a huge challenge for clinicians and medical researchers. This paper presents the@neurIST system, which provides an infrastructure for biomedical research while aiding clinical care, by bringing together heterogeneous data and complex processing and computing services. Although @neurIST targets the investigation and treatment of cerebral aneurysms, the system’s architecture is generic enough that it could be adapted to the treatment of other diseases.Innovations in @neurIST include confining the patient data pertaining to aneurysms inside a single environment that offers cliniciansthe tools to analyze and interpret patient data and make use of knowledge-based guidance in planning their treatment. Medicalresearchers gain access to a critical mass of aneurysm related data due to the system’s ability to federate distributed informationsources. A semantically mediated grid infrastructure ensures that both clinicians and researchers are able to seamlessly access andwork on data that is distributed across multiple sites in a secure way in addition to providing computing resources on demand forperforming computationally intensive simulations for treatment planning and research.

Genetic causes of transitions from sexual reproduction to asexuality in plants and animals.

The persistence of sexual reproduction in the face of competition from asexual invaders is more likely if asexual lineages are produced infrequently or have low fitness. The generation rate and success of new asexual lineages will be influenced by the proximate mechanisms underlying transitions to asexuality. As such, characterization of these mechanisms can help explain the distribution of reproductive modes among natural populations. Here, we synthesize the literature addressing proximate causes of transitions from sexual to asexual reproduction in plants and animals. In cyclical and facultatively asexual taxa, individual mutations can cause obligate asexuality. The evolution of asexuality in obligately sexual groups is more complex, requiring the simultaneous acquisition of two traits generally controlled by different genetic factors: unreduced gamete formation and spontaneous development of unfertilized gametes. At least three 'pre-adaptations' could favour transitions to obligate asexuality in obligate sexuals. First, linkage among loci affecting separate key components of asexuality facilitates its spread, with evidence for these linkage blocks in plants. Second, asexuality should evolve more readily in haplodiploids; support for this hypothesis comes from two examples where a single locus causes transitions to asexuality. Third, standing genetic variation for the production of unreduced gametes could facilitate transitions to asexuality, but whether the ability to produce unreduced gametes contributes to the evolution of obligate asexuality remains unclear. We close by reviewing the associations between asexuality, hybridization and polyploidy, and argue that current data suggest that hybridization is more likely to play a causal role in transitions to asexuality than polyploidy.

What is the value of joint processing of pilots and data in block-fading channels?

The spectral efficiency achievable with joint processing of pilot and data symbol observations is compared with that achievable through the conventional (separate) approach of first estimating the channel on the basis of the pilot symbols alone, and subsequently detecting the datasymbols. Studied on the basis of a mutual information lower bound, joint processing is found to provide a non-negligible advantage relative to separate processing, particularly for fast fading. It is shown that, regardless of the fading rate, only a very small number of pilot symbols (at most one per transmit antenna and per channel coherence interval) shouldbe transmitted if joint processing is allowed.

Production of renewable polymers from crop plants

Plants produce a range of biopolymers for purposes such as maintenance of structural integrity, carbon storage, and defense against pathogens and desiccation. Several of these natural polymers are used by humans as food and materials, and increasingly as an energy carrier. In this review, we focus on plant biopolymers that are used as materials in bulk applications, such as plastics and elastomers, in the context of depleting resources and climate change, and consider technical and scientific bottlenecks in the production of novel or improved materials in transgenic or alternative crop plants. The biopolymers discussed are natural rubber and several polymers that are not naturally produced in plants, such as polyhydroxyalkanoates, fibrous proteins and poly-amino acids. In addition, monomers or precursors for the chemical synthesis of biopolymers, such as 4-hydroxybenzoate, itaconic acid, fructose and sorbitol, are discussed briefly

Phosphate and zinc transport and signalling in plants: toward a better understanding of their homeostasis interaction.

Inorganic phosphate (Pi) and zinc (Zn) are two essential nutrients for plant growth. In soils, these two minerals are either present in low amounts or are poorly available to plants. Consequently, worldwide agriculture has become dependent on external sources of Pi and Zn fertilizers to increase crop yields. However, this strategy is neither economically nor ecologically sustainable in the long term, particularly for Pi, which is a non-renewable resource. To date, research has emphasized the analysis of mineral nutrition considering each nutrient individually, and showed that Pi and Zn homeostasis is highly regulated in a complex process. Interestingly, numerous observations point to an unexpected interconnection between the homeostasis of the two nutrients. Nevertheless, despite their fundamental importance, the molecular bases and biological significance of these interactions remain largely unknown. Such interconnections can account for shortcomings of current agronomic models that typically focus on improving the assimilation of individual elements. Here, current knowledge on the regulation of the transport and signalling of Pi and Zn individually is reviewed, and then insights are provided on the recent progress made towards a better understanding of the Zn-Pi homeostasis interaction in plants.

High elevation Plantago lanceolata plants are less resistant to herbivory than their low elevation conspecifics: is it just temperature?

Traits that mediate species interactions are evolutionarily shaped by biotic and abiotic drivers, yet we know relatively little about the relative importance of these factors. Herbivore pressure, along with resource availability and third-party' mutualists, are hypothesized to play a major role in the evolution of plant defence traits. Here, we used the model system Plantago lanceolata, which grows along steep elevation gradients in the Swiss Alps, to investigate the effect of elevation, herbivore pressure, mycorrhizal inoculation and temperature on plant resistance. Over a 1200 m elevation gradient, the levels of herbivory and iridoid glycosides (IGs) declined with increasing elevation. By planting seedlings at three different elevations, we further showed that both low-elevation growing conditions and mycorrhizal inoculation resulted in increased plant resistance to herbivores. Finally, using a temperature-controlled experiment comparing high- and low-elevation ecotypes, we showed that high-elevation ecotypes are less resistant to herbivory, and that lower temperatures impair IGs deployment after herbivore attack. We thus propose that both lower herbivore pressure, and colder temperatures relax the defense syndrome of high elevation plants.

Role of the superior parietal lobules in letter-identity processing within strings: FMRI evidence from skilled and dyslexic readers.

Traditionally, the ventral occipito-temporal (vOT) area, but not the superior parietal lobules (SPLs), is thought as belonging to the neural system of visual word recognition. However, some dyslexic children who exhibit a visual attention span disorder - i.e. poor multi-element parallel processing - further show reduced SPLs activation when engaged in visual multi-element categorization tasks. We investigated whether these parietal regions further contribute to letter-identity processing within strings. Adult skilled readers and dyslexic participants with a visual attention span disorder were administered a letter-string comparison task under fMRI. Dyslexic adults were less accurate than skilled readers to detect letter identity substitutions within strings. In skilled readers, letter identity differs related to enhanced activation of the left vOT. However, specific neural responses were further found in the superior and inferior parietal regions, including the SPLs bilaterally. Two brain regions that are specifically related to substituted letter detection, the left SPL and the left vOT, were less activated in dyslexic participants. These findings suggest that the left SPL, like the left vOT, may contribute to letter string processing.

What is "clinical data"? Why and how can they be collected during field surveys on medicinal plants?

ETHNOPHARMACOLOGICAL RELEVANCE: "Reverse pharmacology", also called "bedside-to-bench" or "field to pharmacy" approach, is a research process starting with documentation of clinical outcome as observed by patients with different therapeutic regimens. The treatment most significantly associated with cure is selected for future studies: first, clinical safety and efficacy; then in vivo and vitro studies. Some clinical data, i.e. details on patient status and progress, can be collected during ethnobotanical surveys; they will help clinical researchers and, once effectiveness and safety are established, will also help users of traditional medicine make safer and more effective choices. To gather clinical data successfully, ethnopharmacologists need to be backed by an appropriate team of specialists in medicine and epidemiology. Ethnopharmacologists can also gather important data on traditional medicine safety. MATERIALS AND METHODS: The first step is to create a consensus on the meaning of "clinical data", their interest and importance. An understanding of why "a cure is not a proof of effectiveness" is a starting point to avoid faulty interpretation of the clinical observations. RESULTS: Experience showed that, with the "bedside-to-bench" approach, a treatment derived from traditional recipe can be scientifically validated (in terms of safety and effectiveness) with a cost of less than a million euros, thus providing an end-product that is affordable, available and sustainable. CONCLUSIONS: With rigorous clinical study results, medicinal plant users gain the possibility to refine heath strategies. The field surveyor may gain a better relationship with the population, once she/he is seen as bringing information useful for the quality of care in the community.