The c15 ring of the Spirulina platensis F-ATP synthase: F1/F0 symmetry mismatch is not obligatory

The oligomeric c ring of the F-ATP synthase from the alkaliphilic cyanobacterium Spirulina platensis was isolated and characterized. Mass spectroscopy analysis indicated a mass of 8,210 Da, reflecting that of a c monomer. The mass increased by 206 Da after treatment with the c-subunit-specific inhibitor dicyclohexylcarbodiimide (DCCD), which indicated modification of the ion-binding carboxylate by DCCD. Atomic force microscopy topographs of c rings from S. platensis showed 15 symmetrically assembled subunits. The c15-mer reported here is the largest c ring that is isolated and does not show the classical c-ring mismatch to the three-fold symmetry of the F1 domain.     

Cell biology as the basis of a better understanding of cancer

Clinicians will argue that cancer can only really receive the treatment that is needed through thorough understanding of medicine. However, even empirical approaches to therapy result in experimental analysis of the agencies involved on test cells, usually in culture. From the obverse perspective, cell biologists will argue that until we fully understand cell cycle regulation, tumour management will be too imprecise to make the best advances. A forum is needed whereby the fundamental studies on cells prior to, during and after transformation in vitro can be freely reported (open access) and discussed. The action of anticancer agents and cancer preventative substances can more easily be studied in vitro before the often excessive complexity of making similar studies in experimental and human cancers is tackled. Cancer Cell International is committed to providing such a forum. Ironically within a few months of launching this open access journal, Elsevier had much the same idea, and there one has to pay for the privilege of downloading vital papers in this biomedical field.     

Genito-sexual dysfunction in patients with a medullary lesion

Multiple dramatic consequences follow medullary lesions. Not only are voluntary motor control and sensitivity of the body segment below the lesion lost, but it also becomes impossible to control erection and ejaculation as well as urinary and faecal continency. The first investigations into genito-sexual function in paraplegics have brought about the idea, commonly admitted in the medical world, that this kind of patient is impotent and sterile. Fortunately this idea is disappearing gradually and many data have demonstrated that appropriate treatment is required and some therapies efficient. This is particularly important in the case of the population concerned, namely young men in 70% of the cases, since the usual age bracket at trauma is between 25 and 35 years old. At this time of life, sexual activity is often at its peak, so that the fertility potential becomes erased.     

Stem cells and cell therapy. Contribution to the ethical debate

Divergent and sometimes conflicting positions with respect to human stem cells and cell therapy do not merely reflect disagreement among scientists and conflicts of interest. They attest the ethical tension resulting from recent progress in understanding the earliest stages of development of the human being that can be observed in vitro. Can the extremely potent notion of the human person starting with conception apply to the very first stage of artificial in vitro fertilisation and disregard the fact that to be a real substitute for natural conception, implantation in the uterus that enables the oocyte to nest and a new human being to develop must also be included? Several arguments are presented that plead in favour of making a clear distinction between the status of in vitro cells obtained by artificial fertilisation and that of the embryo, which becomes a developing human being from the moment it implants in the endometrium of the uterus. This subject could have remained in the sphere of the individual conscience, but it has now become a theme for social debate! The revision of the French 1994 so-called Bioethics Laws, which was recently approved on first reading on 22 January 2002, authorises research on spare embryos from in vitro fertilisation under certain conditions. However, for the sole reason that there is a risk of opening the door wide to reproductive cloning, which is unanimously rejected and condemned, all research on stem cells deriving from the nuclear transfer of a somatic cell is prohibited, irrespective of the distinction between cloning for therapeutic purposes and reproductive cloning. It is undeniable that if the efficacy of somatic stem cells could be demonstrated, they would offer a far more preferable solution, for several reasons, than those involving stem cells obtained from spare embryos from IVF or nuclear transfer. Nevertheless, how will a comparison of the two methods be possible if one of them is prohibited a priori? At present, many fear that French researchers will be prevented from doing essential research that, even if it has far to go, is indispensable if we wish to attempt to control the failures of natural procreation and open the way towards the new regenerative medicine that so many look forward to.     

Nasoalveolar Molding in Cleft Care—Experience in 40 Patients from a Single Centre in Germany

Nasoalveolar molding (NAM) has gained wide acceptance and evidence in cleft therapy. However, standardized treatment protocols and experiences recorded from European centres are lacking. The results of 40 infants with cleft lip and palate treated with presurgical NAM according to the Grayson technique were analyzed. Standardized parameters of cleft width and nasal symmetry were measured in pre- and posttreatment plaster casts and in digitalized 3-dimensional STL models. Statistical analyses were performed by using Student´s t-test in a per-protocol manner. 27 out of 40 infants completed NAM and were analyzed. In 13 patients NAM was either temporarily interrupted or terminated prematurely due to skin irritations or lack of parental support. These cases were excluded from statistical analysis, resulting in a drop-out rate of 32.5%. Intersegmental alveolar distance (ISAD), intersegmental lip distance (ISLD), nostril height (NH), nostril width (NW) and columella deviation angle (CDA) were significantly changed in unilateral cleft lip and palate (UCLP) (n = 8). In unilateral cleft lip (UCL) (n = 9), only ISLD, NH and CDA were significantly changed. ISAD of the right and left side, ISLD of the right and left side, premaxilla deviation angle, nostril height and columella length were changed significantly in bilateral cleft lip and palate (BCLP) cases (n = 10). NAM is a suitable presurgical treatment modality. A positive effect has been seen in UCLP and BCLP infants, as compared with their birth status.     

A Methodological Framework to Estimate the Site Fidelity of Tagged Animals Using Passive Acoustic Telemetry

The rapid expansion of the use of passive acoustic telemetry technologies has facilitated unprecedented opportunities for studying the behavior of marine organisms in their natural environment. This technological advance would greatly benefit from the parallel development of dedicated methodologies accounting for the variety of timescales involved in the remote detection of tagged animals related to instrumental, environmental and behavioral events. In this paper we propose a methodological framework for estimating the site fidelity (“residence times”) of acoustic tagged animals at different timescales, based on the survival analysis of continuous residence times recorded at multiple receivers. Our approach is validated through modeling and applied on two distinct datasets obtained from a small coastal pelagic species (bigeye scad, Selar crumenophthalmus) and a large, offshore pelagic species (yellowfin tuna, Thunnus albacares), which show very distinct spatial scales of behavior. The methodological framework proposed herein allows estimating the most appropriate temporal scale for processing passive acoustic telemetry data depending on the scientific question of interest. Our method provides residence times free of the bias inherent to environmental and instrumental noise that can be used to study the small scale behavior of acoustic tagged animals. At larger timescales, it can effectively identify residence times that encompass the diel behavioral excursions of fish out of the acoustic detection range. This study provides a systematic framework for the analysis of passive acoustic telemetry data that can be employed for the comparative study of different species and study sites. The same methodology can be used each time discrete records of animal detections of any nature are employed for estimating the site fidelity of an animal at different timescales.     

Diffusion Tensor Magnetic Resonance Imaging of Trigeminal Nerves in Relapsing Herpetic Keratouveitis

Background

Corneal hypoesthesia is the landmark of HSV and VZV keratitis and can lead to neurotrophic keratitis. Diffusion tensor imaging (DTI) is a new magnetic resonance imaging (MRI) derived technique, which offers possibilities to study axonal architecture. We aimed at assessing the potential impact of recurrent HSV or VZV-related keratitis on the axonal architecture of trigeminal nerves using DTI.

Design

Prospective non-interventional study.

Participants

Twelve patients and 24 controls.

Methods

DTI using MRI of the trigeminal fibers and corneal esthesiometry using the Cochet-Bonnet esthesiometer were acquired for patients affected by unilateral and recurrent HSV or VZV-related keratitis (3 months after the last corneal inflammatory event), and control subjects with no history of ocular or neuronal disease affecting the trigeminal pathways.

Main Outcome Measures

Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were compared between the 2 eyes of both patients and controls, and correlated with corneal esthesiometry.

Results

FA was lower in the trigeminal fibers ipsilateral to the affected eye compared to the non-affected side (0.39±0.02 versus 0.46±0.04, P=0.03). This difference was more important than the intra-individual variability observed in controls. Concomitantly, the asymmetry in ADC results was significantly correlated with the loss of corneal sensitivity in the affected eye.

Conclusions

Corneal hypoesthesia related to HSV and VZV keratitis is associated with persistent modifications in the architecture and functionality of the trigeminal fibers. These results add further explanation to the pathogenesis of HSV and VZV-induced neurotrophic keratitis, which may occur despite an apparent quiescence of the disease.     

Directed Communication between Nucleus Accumbens and Neocortex in Humans Is Differentially Supported by Synchronization in the Theta and Alpha Band

Here, we report evidence for oscillatory bi-directional interactions between the nucleus accumbens and the neocortex in humans. Six patients performed a demanding covert visual attention task while we simultaneously recorded brain activity from deep-brain electrodes implanted in the nucleus accumbens and the surface electroencephalogram (EEG). Both theta and alpha oscillations were strongly coherent with the frontal and parietal EEG during the task. Theta-band coherence increased during processing of the visual stimuli. Granger causality analysis revealed that the nucleus accumbens was communicating with the neocortex primarily in the theta-band, while the cortex was communicating the nucleus accumbens in the alpha-band. These data are consistent with a model, in which theta- and alpha-band oscillations serve dissociable roles: Prior to stimulus processing, the cortex might suppress ongoing processing in the nucleus accumbens by modulating alpha-band activity. Subsequently, upon stimulus presentation, theta oscillations might facilitate the active exchange of stimulus information from the nucleus accumbens to the cortex.     

UTP is not a biased agonist at human P2Y11 receptors

Biased agonism describes a multistate model of G protein-coupled receptor activation in which each ligand induces a unique structural conformation of the receptor, such that the receptor couples differentially to G proteins and other intracellular proteins. P2Y receptors are G protein-coupled receptors that are activated by endogenous nucleotides, such as adenosine 5′-triphosphate (ATP) and uridine 5′-triphosphate (UTP). A previous report suggested that UTP may be a biased agonist at the human P2Y₁₁ receptor, as it increased cytosolic [Ca²⁺], but did not induce accumulation of inositol phosphates, whereas ATP did both. The mechanism of action of UTP was unclear, so the aim of this study was to characterise the interaction of UTP with the P2Y₁₁ receptor in greater detail. Intracellular Ca²⁺ was monitored in 1321N1 cells stably expressing human P2Y₁₁ receptors using the Ca²⁺-sensitive fluorescent indicator, fluo-4. ATP evoked a rapid, concentration-dependent rise in intracellular Ca²⁺, but surprisingly, even high concentrations of UTP were ineffective. In contrast, UTP was slightly, but significantly more potent than ATP in evoking a rise in intracellular Ca²⁺ in 1321N1 cells stably expressing the human P2Y₂ receptor, with no difference in the maximum response. Thus, the lack of response to UTP at hP2Y₁₁ receptors was not due to a problem with the UTP solution. Furthermore, coapplying a high concentration of UTP with ATP did not inhibit the response to ATP. Thus, contrary to a previous report, we find no evidence for an agonist action of UTP at the human P2Y₁₁ receptor, nor does UTP act as an antagonist.