4-1BBL Enhances CD8+ T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

T cells play a central role in the immune response to many of the world’s major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was shown to increase the frequency of murine antigen-specific IFN-γ secreting CD8⁺ T cells in three vector platforms examined. Enhancement of the response was not limited by co-expression with the antigen, as an increase in CD8⁺ immunogenicity was also observed by co-administration of two vectors each expressing only the antigen or adjuvant. However, when this regimen was tested in non-human primates using a clinical malaria vaccine candidate, no adjuvant effect of 4-1BBL was observed limiting its potential use as a single adjuvant for translation into a clinical vaccine.     

Face or hand,not both: perceptual correlates of reafferentation in a former amputee

The topography of the somatosensory maps of our body can be largely shaped by alterations of peripheral sensory inputs. Following hand amputation, the hand cortical territory becomes responsive to facial cutaneous stimulation. Amputation-induced remapping, however, reverses after transplantation, as the grafted hand (re)gains its sensorimotor representation. Here, we investigate hand tactile perception in a former amputee by touching either grafted hand singly or in combination with another body part. The results showed that tactile sensitivity recovered rapidly, being remarkably good 5 months after transplant. In the right grafted hand, however, the newly acquired somatosensory awareness was strikingly hampered when the ipsilateral face was touched simultaneously, i.e., right face perception extinguished right hand perception. Ipsilateral face-hand extinction was present in the formerly dominant right hand 5 months after transplant and eventually disappeared 6 months afterwards. Control conditions' results showed that right hand tactile awareness was not extinguished either by contralateral left face and left hand stimulation or ipsilateral stimulation of the arm, which is bodily close to, but cortically far from, the hand. We suggest that ipsilateral face-hand extinction is a perceptual counterpart of the remapping that occurs after allograft and eyewitnesses the inherently competitive nature of sensory representations.     

New paleobiogeographical and paleoenvironmental insight through the Tortonian brachiopod and ichnofauna assemblages from the Mediterranean-Atlantic seaway (Guadix Basin,SE Spain)

The paleogeography of the Late Neogene Atlantic-Mediterranean seaway via the Betic-Rifean Domain is quite complex due to the presence of several marine corridors. The study of transitional basins in these seaways is crucial to understand the configuration and evolution of the Mediterranean-Atlantic inter-connection. A mixed skeletal-siliciclastic sandstone succession located in one of these transitional areas (Guadix Basin, Southern Spain) was studied from a comprehensive paleontological standpoint focused on the main benthic assemblages (foraminifera, brachiopods, and trace fossils), integrating the data with the study of planktic foraminifera for an accurate biostratigraphic framework. Brachiopods are mostly represented by the Aphelesia-Gryphus assemblage. Two trace fossil assemblages were observed, dominated by Ophiomorpha with Bichordites (1) and Macaronichnus (2), respectively. The benthic foraminiferal assemblage is mostly represented by Planulina and Cibicides. The data gathered from the benthic communities reveal habitats with high-energy and turbulent conditions in an outer neritic-upper bathyal bathymetric range. Brachiopods from the Alicún section show a Mediterranean paleobiogeographic affinity. They were constrained in the Late Tortonian to the restricted basins of the Betic-Rifean Seaway and after the Messinian Salinity Crisis proliferated in both Mediterranean- and Atlantic-type basins of the Betic-Rifean Domain. The Guadix Basin contributed to the Mediterranean-Atlantic faunal inter-connection through the Betic-Rifean Seaway during the Late Tortonian and facilitated the earliest Pliocene expansion of brachiopods in the Mediterranean.     

Elevated peripheral visfatin levels in narcoleptic patients

Objective

Narcolepsy is a severe sleep disorder that is characterized by excessive daytime sleepiness, cataplexies and a tendency towards obesity. Recent discoveries indicate that the major pathophysiology is a loss of hypocretin (orexin) producing neurons due to immunologically mediated degeneration. Visfatin is a recently described proinflammatory adipokine. It is identical to the immune modulating pre-B-cell colony enhancing factor (PBEF). Our study examines the hypothesis that visfatin levels are altered in narcoleptic patients.

Methods

For the analysis, a total of n = 54 patients (n = 18 males and n = 36 females) with the diagnosis of narcolepsy according to DSM-IV and the International Classification of Sleep Disorders were examined (BMI mean 30.3±5.5, age mean 52.5±16.1 years). As a control group 39 unrelated (n = 12 males and n = 27 females) healthy volunteers with no sleep disorder according to DSM-IV were included (BMI mean 28.5±4.6, age mean 51.1±13.6 years). Peripheral visfatin levels were measured using a commercial enzyme immunoassay kit with a measurement range from 0.1–1000 ng/ml. Narcolepsy symptoms, severity and frequency of symptoms as well as the total duration of various aspects of the symptomatology were assessed by unstructured and structured clinical interviews in including the Stanford Center for Narcolepsy Sleep Inventory.

Results

Circulating visfatin was found to be significantly increased in HLA DR2 positive narcoleptic patients compared to controls.

Conclusion

Taken together, our results add to the evidence of disturbed immunological regulation in patients with narcolepsy.     

LUTEAR CELLS AND HEN-FEATHERING

The experimental evidence had made clear that some substance is produced in the testis of the male Sebright that suppresses in him the development of the secondary sexual plumage of the cock of his species. The detection in his testis of lutear cells like those in hens makes the conclusion highly probable that it is these cells that cause the suppression of cock-feathering in both the Sebright male and in hens of all fowls. Genetic work by Morgan had shown that one or two Mendelian factor-differences are responsible for hen-feathering in the Sebright. These factor-differences produce their effects through the testes. The presence of these genetic factors, we now see, causes the testes of the Sebright to produce a kind of secretory cell that is ordinarily only produced in the female, or possibly to a slight extent in young males (Boring), or in numbers insufficient to suppress the male plumage in the testes of some ordinary cock birds (Reeves).     

Study of p53 expression and post‐transcriptional modifications after GSM‐900 radiofrequency exposure of human amniotic cells

The potential effects of radiofrequency (RF) exposure on the genetic material of cells are very important to determine since genome instability of somatic cells may be linked to cancer development. In response to genetic damage, the p53 protein is activated and can induce cell cycle arrest allowing more time for DNA repair or elimination of damaged cells through apoptosis. The objective of this study was to investigate whether the exposure to RF electromagnetic fields, similar to those emitted by mobile phones of the second generation standard, Global System for Mobile Communications (GSM), may induce expression of the p53 protein and its activation by post‐translational modifications in cultured human cells. The potential induction of p53 expression and activation by GSM‐900 was investigated after in vitro exposure of human amniotic cells for 24 h to average specific absorption rates (SARs) of 0.25, 1, 2, and 4 W/kg in the temperature range of 36.3–39.7 °C. The exposures were carried out using a wire‐patch cell (WPC) under strictly controlled conditions of temperature. Expression and activation of p53 by phosphorylation at serine 15 and 37 were studied using Western blot assay immediately after three independent exposures of cell cultures provided from three different donors. Bleomycin‐exposed cells were used as a positive control. According to our results, no significant changes in the expression and activation of the p53 protein by phosphorylation at serine 15 and 37 were found following exposure to GSM‐900 for 24 h at average SARs up to 4 W/kg in human embryonic cells. Bioelectromagnetics 34:52–60, 2013. © 2012 Wiley Periodicals, Inc.     

Body size as a determinant of small-scale distributions of ants in evergreen woodland southeastern Arizona

Summary Distributions and abundances of ants were determined on the N, E, W and S upper slopes of a conical hill that had a gradient of conditions from moist-cool oakjuniper-pine woodland to warm-dry open shrub woodland. Species distributions varied remarkably with slope, even in terms of subfamilies and unique common species. A formicine was the most abundant species on the north slope. A different species of dolichoderine was most abundant on the other slopes. The assemblages of ant species were much more distinct for these small sites on each slope than are the known groups of species associated with vegetation types on a broad geographical basis. Interpretation of the causes of such specific assemblages awaits detailed information on species ecologies However, there is considerable circumstantial evidence that body size is an important factor. The percentage similarity of body size of pairs of species in the same site was least for common species of the same feeding guild; similarity was greater when one or both members of a pair were uncommon; similarities were highest for species in different guilds. Combinations of species that would have had very high size overlaps did not occur together. Some combinations that occurred were those that had the least overlap possible for the species known to occur on the entire hill.

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Resume La répartition et l'abondance des populations de fourmis ont été analysées sur les versants d'une colline dont le couvert végétal va de la forêt touffue du type chênegenévrier-pin, humide et fraîche, au maquis ouvert, chaud et sec. On a constaté que la répartition des espèces variait de façon très marquée suivant la pente du versant, même en ce que concerne les sous-familles et les espèces uniques abondantes. Les assemblages d'espèces sont plus nettement démarqués dans ce cas que ne le sont ceux des groupes connus d'espèces associées avec des types de végétation sur des aires géographiques plus étendues. Avant de pouvoir donner une interprétation satisfaisante des causes qui déterminent les divers assemblages, il faudra disposer d'informations beaucoup plus détaillées sur l'écologie des diverses espèces. Il existe déjà, portant, beaucoup de preuves indirectes qui montrent l'importance de la taille spécifique. Les pourcentages de ressemblances des tailles spécifiques entre les espèces d'un même site étaient minimum chez les espèces communes appartenant au même groupe trophique. Les ressemblances étaient considérablement plus grandes lorsque l'un des membres d'une paire, ou les deux membres, appartenaient à des espèces rares. Les ressemblances maximum se rencontrent entre espèces appartenant à des groupes trophiques différents. On n'a trouvé aucune combinaison d'espèces communes dont les tailles spécifiques sont à peu près identiques. Les quelques combinaisons d'espèces communes qui ont été observées apparaissent entre espèces à la taille spécifique aussi divergentes que possible parmi toutes les expèces recensées dans l'air délimitée.

     

Effects of 3′ Untranslated Region Mutations on Plus-Strand Priming during Moloney Murine Leukemia Virus Replication

A conserved purine-rich motif located near the 3′ end of retroviral genomes is involved in the initiation of plus-strand DNA synthesis. We mutated sequences both within and flanking the Moloney murine leukemia virus polypurine tract (PPT) and determined the effects of these alterations on viral DNA synthesis and replication. Our results demonstrated that both changes in highly conserved PPT positions and a mutation that left only the cleavage-proximal half of the PPT intact led to delayed replication and reduced the colony-forming titer of replication defective retroviral vectors. A mutation that altered the cleavage proximal half of the PPT and certain 3′ untranslated region mutations upstream of the PPT were incompatible with or severely impaired viral replication. To distinguish defects in plus-strand priming from other replication defects and to assess the relative use of mutant and wild-type PPTs, we examined plus-strand priming from an ectopic, secondary PPT inserted in U3. The results demonstrated that the analyzed mutations within the PPT primarily affected plus-strand priming whereas mutations upstream of the PPT appeared to affect both plus-strand priming and other stages of viral replication.