Evolutionary history of the Corallinales (Corallinophycidae, Rhodophyta) inferred from nuclear, plastidial and mitochondrial genomes

Systematics of the red algal order Corallinales has a long and convoluted history. In the present study, molecular approaches were used to assess the phylogenetic relationships based on the analyses of two datasets: a large dataset of SSU sequences including mainly sequences from GenBank; and a combined dataset including four molecular markers (two nuclear: SSU, LSU; one plastidial: psbA; and one mitochondrial: COI). Phylogenetic analyses of both datasets re-affirmed the monophyly of the Corallinales as well as the two families (Corallinaceae and Hapalidiaceae) currently recognized within the order. Three of the four subfamilies of the Corallinaceae (Corallinoideae, Lithophylloideae, Metagoniolithoideae) were also resolved as a monophyletic lineage whereas members of the Mastophoroideae were resolved as four distinct lineages. We therefore propose to restrict the Mastophoroideae to the genera Mastophora, Metamastophora, and possibly Lithoporella in the aim of rendering this subfamily monophyletic. In addition, our phylogenies resolved the genus Hydrolithon in two unrelated lineages, one containing the generitype Hydrolithon reinboldii and the second containing Hydrolithon onkodes, which used to be the generitype of the now defunct genus Porolithon. We therefore propose to resurrect the genus Porolithon for the second lineage encompassing those species with primarily monomerous thalli, and trichocyte arrangements in large pustulate horizontal rows. Moreover, our phylogenetic analyses revealed the presence of cryptic diversity in several taxa, shedding light on the need for further studies to better circumscribe species frontiers within the diverse order Corallinales, especially in the genera Mesophyllum and Neogoniolithon.     

Phylogenetics, species boundaries and timing of resource tracking in a highly specialized group of seed beetles (Coleoptera: Chrysomelidae: Bruchinae)

Though for a long time it was hypothesized that the extraordinary diversity of phytophagous insects was better explained by a synchronous pattern of co-diversification with plants, the results of recent studies have led to question this theory, suggesting that the diversification of insects occurred well after that of their hosts. In this study we address this issue by investigating the timing of diversification of a highly specialized group of seed beetles, which mostly feeds on legume plants from the tribe Indigofereae. To that purpose, a total of 130 specimens were sequenced for six genes and analyzed under a Bayesian phylogenetic framework. Based on the resulting trees we performed several analyses that allowed a better definition of the group boundaries and to investigate the status of several taxa through the use of molecular species delimitation analyses in combination with morphological evidences. In addition the evolution of host plant use was reconstructed and different molecular-dating approaches were carried out in order to assess the ages of several clades of interest. The resulting framework suggests a more ancient than previously thought origin for seed beetles, and a pattern of rapid host plant colonization. These findings call for further similar studies in other highly specialized groups of phytophagous insects.     

Caveolin-3 is a direct molecular partner of the Cav1.1 subunit of the skeletal muscle L-type calcium channel

Caveolin-3 is the striated muscle specific isoform of the scaffolding protein family of caveolins and has been shown to interact with a variety of proteins, including ion channels. Mutations in the human CAV3 gene have been associated with several muscle disorders called caveolinopathies and among these, the P104L mutation (Cav-3(P104L)) leads to limb girdle muscular dystrophy of type 1C characterized by the loss of sarcolemmal caveolin. There is still no clear-cut explanation as to specifically how caveolin-3 mutations lead to skeletal muscle wasting. Previous results argued in favor of a role for caveolin-3 in dihydropyridine receptor (DHPR) functional regulation and/or T-tubular membrane localization. It appeared worth closely examining such a functional link and investigating if it could result from the direct physical interaction of the two proteins. Transient expression of Cav-3(P104L) or caveolin-3 specific siRNAs in C2C12 myotubes both led to a significant decrease of the L-type Ca(2+) channel maximal conductance. Immunolabeling analysis of adult skeletal muscle fibers revealed the colocalization of a pool of caveolin-3 with the DHPR within the T-tubular membrane. Caveolin-3 was also shown to be present in DHPR-containing triadic membrane preparations from which both proteins co-immunoprecipitated. Using GST-fusion proteins, the I-II loop of Ca(v)1.1 was identified as the domain interacting with caveolin-3, with an apparent affinity of 60nM. The present study thus revealed a direct molecular interaction between caveolin-3 and the DHPR which is likely to underlie their functional link and whose loss might therefore be involved in pathophysiological mechanisms associated to muscle caveolinopathies.     

Surface Water Linkages Regulate Trophic Interactions in a Groundwater Food Web

Groundwaters are increasingly viewed as resource-limited ecosystems in which fluxes of dissolved organic carbon (DOC) from surface water are efficiently mineralized by a consortium of microorganisms which are grazed by invertebrates. We tested for the effect of groundwater recharge on resource supply and trophic interactions by measuring physico-chemistry, microbial activity and biomass, structure of bacterial communities and invertebrate density at three sites intensively recharged with surface water. Comparison of measurements made in recharge and control well clusters at each site showed that groundwater recharge significantly increased fluxes of DOC and phosphate, elevated groundwater temperature, and diminished dissolved oxygen (DO). Microbial biomass and activity were significantly higher in recharge well clusters but stimulation of autochthonous microorganisms was not associated with a major shift in bacterial community structure. Invertebrate assemblages were not significantly more abundant in recharge well clusters and did not show any relationship with microbial biomass and activity. Microbial communities were bottom-up regulated by DOC and nutrient fluxes but trophic interactions between microorganisms and invertebrates were apparently limited by environmental stresses, particularly DO depletion and groundwater warming. Hydrological connectivity is a key factor regulating the function of DOC-based groundwater food webs as it influences both resource availability for microorganisms and environmental stresses which affect energy transfer to invertebrates and top-down control on microorganisms.     

2nd Charles Richet et Jules Héricourt Workshop: Therapeutic antibodies and anaphylaxis; May 31–June 1, 2011; Tours,France

The Charles Richet and Jules Héricourt workshops honor the memory of Jules Héricourt (1850–1938) and Charles Richet (1850–1935) who described the principle of serotherapy in 1888 and made the very first attempts to fight cancer with serotherapy in 1895. In 1902, Charles Richet and Paul Portier described “anaphylaxis,” a discovery awarded the Nobel Prize in 1913. The first workshop, “Towards the clinical use of monoclonal antibodies with higher cytolytic efficacy in cancer” was held in Tours, France on November 20–21, 2008. The second Charles Richet and Jules Héricourt workshop, held May 31–June 1, 2011 at the University of Tours, France, was also organized by the Cancéropôle Grand Ouest. The topic of the workshop was therapeutic antibodies and anaphylaxis, a subject rarely addressed in congresses focused on mAbs. To have discussions about mAb side effects with complete objectivity, the congress was organized independently of any sponsorship from pharmaceutical companies. This academic event was motivated by the high incidence of shocks to cetuximab and the need to compile and evaluate scattered information. This growing public health concern was thus analyzed from different scientific and medical angles. The first session was devoted to acute infusion reactions, with an emphasis on deconvolution of the terms “cytokine-release syndrome,” “cytokine storms,” “anaphylaxis” and their epidemiology. This session concluded with the Charles Richet lecture on cetuximab anaphylaxis and anti-αGal IgE by Thomas Platts-Mills, its discoverer. In the next session, the involvement of anti-glycan antibodies in both anaphylaxis and delayed hypersensitivity reactions to therapeutic antibodies was discussed. A gala dinner was held in the gardens of the beautiful château of Villandry, which was acquired and restored by Joachim Carvalho, a pupil of Charles Richet''s and great-grandfather of the present owner. The final session focused on strategies to prevent cetuximab anaphylaxis in clinical practice included a variety of topics, e.g., premedication, biobetters and biosimilars, skin testing and predictive assays. All speakers and attendees enjoyed this very stimulating and rewarding meeting, which gathered many people with divergent scientific backgrounds and medical specialties.Key words: cetuximab, anaphylaxis, α-Gal epitope, anti-αGal IgE, anti-cetuximab IgE, allergy, monoclonal antibodies, glycosylation     

Effect of dental status on changes in mastication in patients with obesity following bariatric surgery

Background

Patients scheduled for bariatric surgery (BS) are encouraged to chew slowly in order to optimise the digestion process. The influence of dental status on patients'' ability to comply with advice on chewing behaviour is poorly documented. This study aims to compare modifications of chewing function before and after BS in three groups of obese patients differing in dental status.

Method and Findings

A cohort of 46 obese women provided three groups: FD group: fully dentate (7–10 functional dental units [FU]); PD group: partially dentate (4–6 FU) without partial dentures; DW group: partial and complete denture wearers. Chewing time (CT), number of chewing cycles (CC), and chewing frequency (CF) were measured before and after surgery during mastication of standardised samples of raw carrot, peanuts, banana, apple and jelly. The median particle-size distribution (D50) of the pre-swallowed bolus was also evaluated for peanut and carrot. Before surgery, the PD and DW groups exhibited greater mean CCs and CTs than the FD group (SNK p<0.05) and produced a bolus with higher granulometry (SNK, p<0.05) than the FD group. After surgery, CT and CC increased for all groups and for all foods, but not statistically significant for jelly. The resulting changes in bolus granulometry observed depended on both food and dental status. The granulometry of carrot bolus remained as fine or as coarse in FD and DW groups respectively as it was before surgery while it was significantly decreased in the PD group (Student''s test, p<0.001).

Conclusions

After bariatric surgery, all the obese patients, regardless of dental status modified their chewing kinematics. The effects of this chewing behaviour on bolus granulometry depended on dental status and type of food. Further studies are needed to understand better the impact of dental status on feeding behaviour and nutrition in patients with obesity.     

Shedding light on the chemical diversity of ectopic calcifications in kidney tissues: diagnostic and research aspects

In most industrialized countries, different epidemiologic studies show that chronic renal failure is dramatically increasing. Such major public health problem is a consequence of acquired systemic diseases such as type II diabetes, which is now the first cause for end stage renal failure. Furthermore, lithogenic diseases may also induce intratubular crystallization, which may finally result in end-stage renal failure (ESRF). Up to now, such rare diseases are often misdiagnosed. In this study, based on twenty four biopsies, we show that SR μFTIR (Synchrotron Radiation-μFourier transform infrared) spectroscopy constitutes a significant opportunity to characterize such pathological μcalcifications giving not only their chemical composition but also their spatial distribution in the tissues. This experimental approach offers new opportunities to the clinicians to describe at the cell level the physico-chemical processes leading to the formation of the pathological calcifications which lead to ESRF.     

T cells contribute to tumor progression by favoring pro-tumoral properties of intra-tumoral myeloid cells in a mouse model for spontaneous melanoma

Tumors affect myelopoeisis and induce the expansion of myeloid cells with immunosuppressive activity. In the MT/ret model of spontaneous metastatic melanoma, myeloid cells are the most abundant tumor infiltrating hematopoietic population and their proportion is highest in the most aggressive cutaneous metastasis. Our data suggest that the tumor microenvironment favors polarization of myeloid cells into type 2 cells characterized by F4/80 expression, a weak capacity to secrete IL-12 and a high production of arginase. Myeloid cells from tumor and spleen of MT/ret mice inhibit T cell proliferation and IFNγ secretion. Interestingly, T cells play a role in type 2 polarization of myeloid cells. Indeed, intra-tumoral myeloid cells from MT/ret mice lacking T cells are not only less suppressive towards T cells than corresponding cells from wild-type MT/ret mice, but they also inhibit more efficiently melanoma cell proliferation. Thus, our data support the existence of a vicious circle, in which T cells may favor cancer development by establishing an environment that is likely to skew myeloid cell immunity toward a tumor promoting response that, in turn, suppresses immune effector cell functions.     

Neural correlates of ongoing conscious experience: both task-unrelatedness and stimulus-independence are related to default network activity

The default mode network (DMN) is a set of brain regions that consistently shows higher activity at rest compared to tasks requiring sustained focused attention toward externally presented stimuli. The cognitive processes that the DMN possibly underlies remain a matter of debate. It has alternately been proposed that DMN activity reflects unfocused attention toward external stimuli or the occurrence of internally generated thoughts. The present study aimed at clarifying this issue by investigating the neural correlates of the various kinds of conscious experiences that can occur during task performance. Four classes of conscious experiences (i.e., being fully focused on the task, distractions by irrelevant sensations/perceptions, interfering thoughts related to the appraisal of the task, and mind-wandering) that varied along two dimensions ("task-relatedness" and "stimulus-dependency") were sampled using thought-probes while the participants performed a go/no-go task. Analyses performed on the intervals preceding each probe according to the reported subjective experience revealed that both dimensions are relevant to explain activity in several regions of the DMN, namely the medial prefrontal cortex, posterior cingulate cortex/precuneus, and posterior inferior parietal lobe. Notably, an additive effect of the two dimensions was demonstrated for midline DMN regions. On the other hand, lateral temporal regions (also part of the DMN) were specifically related to stimulus-independent reports. These results suggest that midline DMN regions underlie cognitive processes that are active during both internal thoughts and external unfocused attention. They also strengthen the view that the DMN can be fractionated into different subcomponents and reveal the necessity to consider both the stimulus-dependent and the task-related dimensions of conscious experiences when studying the possible functional roles of the DMN.     

Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception

Analgesic therapies are still limited and sometimes poorly effective, therefore finding new targets for the development of innovative drugs is urgently needed. In order to validate the potential utility of blocking T-type calcium channels to reduce nociception, we explored the effects of intrathecally administered oligodeoxynucleotide antisenses, specific to the recently identified T-type calcium channel family (CaV3.1, CaV3.2, and CaV3.3), on reactions to noxious stimuli in healthy and mononeuropathic rats. Our results demonstrate that the antisense targeting CaV3.2 induced a knockdown of the CaV3.2 mRNA and protein expression as well as a large reduction of 'CaV3.2-like' T-type currents in nociceptive dorsal root ganglion neurons. Concomitantly, the antisense treatment resulted in major antinociceptive, anti-hyperalgesic, and anti-allodynic effects, suggesting that CaV3.2 plays a major pronociceptive role in acute and chronic pain states. Taken together, the results provide direct evidence linking CaV3.2 T-type channels to pain perception and suggest that CaV3.2 may offer a specific molecular target for the treatment of pain.