Ocean acidification slows nitrogen fixation and growth in the dominant diazotroph Trichodesmium under low-iron conditions

Dissolution of anthropogenic CO(2) increases the partial pressure of CO(2) (pCO(2)) and decreases the pH of seawater. The rate of Fe uptake by the dominant N(2)-fixing cyanobacterium Trichodesmium declines as pH decreases in metal-buffered medium. The slower Fe-uptake rate at low pH results from changes in Fe chemistry and not from a physiological response of the organism. Contrary to previous observations in nutrient-replete media, increasing pCO(2)/decreasing pH causes a decrease in the rates of N(2) fixation and growth in Trichodesmium under low-Fe conditions. This result was obtained even though the bioavailability of Fe was maintained at a constant level by increasing the total Fe concentration at low pH. Short-term experiments in which pCO(2) and pH were varied independently showed that the decrease in N(2) fixation is caused by decreasing pH rather than by increasing pCO(2) and corresponds to a lower efficiency of the nitrogenase enzyme. To compensate partially for the loss of N(2) fixation efficiency at low pH, Trichodesmium synthesizes additional nitrogenase. This increase comes partly at the cost of down-regulation of Fe-containing photosynthetic proteins. Our results show that although increasing pCO(2) often is beneficial to photosynthetic marine organisms, the concurrent decreasing pH can affect primary producers negatively. Such negative effects can occur both through chemical mechanisms, such as the bioavailability of key nutrients like Fe, and through biological mechanisms, as shown by the decrease in N(2) fixation in Fe-limited Trichodesmium.

Recent Reticulate Evolution in the Ecologically Dominant Lineage of Coccolithophores

The coccolithophore family Noëlaerhabdaceae contains a number of taxa that are very abundant in modern oceans, including the cosmopolitan bloom-forming Emiliania huxleyi. Introgressive hybridization has been suggested to account for incongruences between nuclear, mitochondrial and plastidial phylogenies of morphospecies within this lineage, but the number of species cultured to date remains rather limited. Here, we present the characterization of 5 new Noëlaerhabdaceae culture strains isolated from samples collected in the south-east Pacific Ocean. These were analyzed morphologically using scanning electron microscopy and phylogenetically by sequencing 5 marker genes (nuclear 18S and 28S rDNA, plastidial tufA, and mitochondrial cox1 and cox3 genes). Morphologically, one of these strains corresponded to Gephyrocapsa ericsonii and the four others to Reticulofenestra parvula. Ribosomal gene sequences were near identical between these new strains, but divergent from G. oceanica, G. muellerae, and E. huxleyi. In contrast to the clear distinction in ribosomal phylogenies, sequences from other genomic compartments clustered with those of E. huxleyi strains with which they share an ecological range (i.e., warm temperate to tropical waters). These data provide strong support for the hypothesis of past (and potentially ongoing) introgressive hybridization within this ecologically important lineage and for the transfer of R. parvula to Gephyrocapsa. These results have important implications for understanding the role of hybridization in speciation in vast ocean meta-populations of phytoplankton.

Recent Reticulate Evolution in the Ecologically Dominant Lineage of Coccolithophores

The coccolithophore family Noëlaerhabdaceae contains a number of taxa that are very abundant in modern oceans, including the cosmopolitan bloom-forming Emiliania huxleyi. Introgressive hybridization has been suggested to account for incongruences between nuclear, mitochondrial and plastidial phylogenies of morphospecies within this lineage, but the number of species cultured to date remains rather limited. Here, we present the characterization of 5 new Noëlaerhabdaceae culture strains isolated from samples collected in the south-east Pacific Ocean. These were analyzed morphologically using scanning electron microscopy and phylogenetically by sequencing 5 marker genes (nuclear 18S and 28S rDNA, plastidial tufA, and mitochondrial cox1 and cox3 genes). Morphologically, one of these strains corresponded to Gephyrocapsa ericsonii and the four others to Reticulofenestra parvula. Ribosomal gene sequences were near identical between these new strains, but divergent from G. oceanica, G. muellerae, and E. huxleyi. In contrast to the clear distinction in ribosomal phylogenies, sequences from other genomic compartments clustered with those of E. huxleyi strains with which they share an ecological range (i.e., warm temperate to tropical waters). These data provide strong support for the hypothesis of past (and potentially ongoing) introgressive hybridization within this ecologically important lineage and for the transfer of R. parvula to Gephyrocapsa. These results have important implications for understanding the role of hybridization in speciation in vast ocean meta-populations of phytoplankton.

Exploring value propositions and service innovation : a service-dominant logic study

This paper presents an eight-firm study, conducted from the service-dominant logic perspective, which makes a contribution regarding knowledge of the anatomy of value propositions and service innovation. The paper suggests that value propositions are configurations of several different practices and resources. The paper finds that ten common practices, organized in three main aggregates, constitute and fulfill value propositions: i.e. provision practices, representational practices, and management and organizational practices. Moreover, the paper suggests that service innovation can be equated with the creation of new value propositions by means of developing existing or creating new practices and/or resources, or by means of integrating practices and resources in new ways. It identifies four types of service innovation (adaptation, resource-based innovation, practice-based innovation, and combinative innovation) and three types of service innovation processes (practice-based, resource-based, and combinative). The key managerial insight provided by the paper is that service innovation must be conducted and value propositions must be evaluated from the perspective of the customers’ value creation, the service that the customer experiences. Successful service innovation is not only contingent on having the right resources, established methods and practices for integrating these resources into attractive value propositions are also needed.

Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome

Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.

A multi-component pheromone in the urine of dominant male tilapia (Oreochromis mossambicus) reduces aggression in rivals

Males often use scent to communicate their domi- nance, and to mediate aggressive and breeding behaviors. In teleost fish, however, the chemical composition of male pher- omones is poorly understood. Male Mozambique tilapia, Oreochromis mossambicus, use urine that signals social status and primes females to spawn. The urinary sex pheromone di- rected at females consists of 5β-pregnane-3α,17α,20β-triol 3- glucuronate and its 20α-epimer. The concentration of these is positively correlated with male social rank. This study tested whether dominant male urine reduces aggression in receiver males, and whether the pregnanetriol 3-glucuronates also re- duce male-male aggression. Males were allowed to fight their mirror image when exposed to either: i) water control or a chemical stimulus; ii) dominant male urine (DMU); iii) C18- solid phase (C18-SPE) DMU eluate; iv) C18-SPE DMU eluate plus filtrate; v) the two pregnanetriol 3-glucuronates (P3Gs); or vi) P3Gs plus DMU filtrate. Control males mounted an increas- ingly aggressive fight against their image over time. However, DMU significantly reduced this aggressive response. The two urinary P3Gs did not replicate the effect of whole DMU. Neither did the C18-SPE DMU eluate, containing the P3Gs, alone, nor the C18-SPE DMU filtrate to which the two P3Gs were added. Only exposure to reconstituted DMU (C18-SPE eluate plus filtrate) restored the aggression-reducing effect of whole DMU. Olfactory activity was present in the eluate and the polar filtrate in electro-olfactogram studies. We conclude that P3Gs alone have no reducing effect on aggression and that the urinary signal driving off male competition is likely to be a multi-component pheromone, with components present in both the polar and non-polar urine fractions.

Compulsory licensing of standard-essential patents and injunctive relief as abuse of dominant position in violation of Article 102 TFEU

When a dominant undertaking holding a standard-essential patent uses its exclusive right to the IP to seek injunctions against those wishing to produce either de jure or de facto standard compliant products, it creates a conflict between the exclusive right to the use of the IP on the one hand and the possible abuse of dominance due to the exclusionary conduct on the other. The aim of the thesis is to focus on the issues concerning abuse of dominance in violation of Article 102 TFEU when the holder of the standard-essential patent seeks an injunction against a would-be licensee. The thesis is mainly based on the most recent ECJ case law in Huawei and the Commission’s recent decisions in Samsung and Motorola. The case law in Europe prior to those decisions was mainly focused on the German case law from Orange Book Standard which provided IP holders great leverage due to the almost automatic granting of injunctions against infringers. The ECJ in Huawei set out the requirements for when a de jure standard-essential patent holder would not be violating Article 102 TFEU when seeking an injunction, requiring that negotiations in good faith must take place prior to the seeking of the injunction and that all offers must comply with FRAND terms, thus limiting the scope of case law derived from Orange Book Standard in Germany. The ECJ chose not to follow all of the reasoning the Commission had laid out in Samsung and Motorola which provided a more licensee-friendly approach on the matter, but rather chose a compromise between the IP holder friendly German case law and the Commission’s decisions. However, the ECJ did not disclose how FRAND terms themselves should be interpreted, but rather left it for the national courts to decide. Furthermore, the thesis strongly argues that Huawei did not change the fact that only vertically integrated IP holders who have made a FRAND declaration are subject to the terms laid out in Huawei, thus leaving non-practicing entities such as patent trolls and entities that have not made a FRAND declaration outside its scope. The resulting conclusion from the thesis is that while the ECJ in Huawei presented new exceptional circumstances for when an IP holder could be abusing its dominant position when it seeks an injunction, it still left many more questions answered, such as the meaning of FRAND and whether deception in giving a FRAND declaration is prohibited under Article 102 TFEU or not.

Structural Basis for Clonal Diversity of the Public T Cell Response to Dominant Epitopes from Cytomegalovirus and Influenza

A diverse T cell receptor (TCR) repertoire is a prerequisite for effective viral clearance. However, knowledge of human TCR repertoire to defined viral antigens is limited. Recent advances in high-throughput sequencing (HTS) and single-cell sorting have revolutionized the study of human TCR repertoires to different types of viruses. In collaboration with the laboratory of Dr. Nan-ping Weng (National Institute on Aging, NIH), we applied unique molecular identifier (UMI)-labelled HTS, single-cell paired TCR analysis, surface plasmon resonance, and X-ray crystallography to exhaustively interrogate CD8+ TCR repertoires specific for cytomegalovirus (CMV) and influenza A (Flu) in HLA-A2+ humans. Our two CMV-specific TCR-pMHC structures and two Flu-specific TCR-pMHC structures provide a plausible explanation for the much higher diversity of CMV-specific than Flu-specific TCR repertoires in humans. Our comprehensive biochemical and structural portrait of two different anti-viral T cell responses may contribute to the future development of predictors of immunity or disease at the individual level.

A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability

International audience

Congenital fiber-type disproportion myopathy: a case study

Congenital fiber-type disproportion myopathy causes impaired muscle maturation or development. It is characterized by moderate to severe hypotonia and generalized muscle weakness at birth or during the first year of life, especially in the lower extremities. It is inherited as an autosomal recessive, dominant and X-linked. It is diagnosed by clinical data confirmation, generalized hypotonia and a muscle biopsy in which muscle fibers type I are smaller in caliber, 12% smaller than those of type II and type I fibers are more common than type II. Treatment is multidisciplinary. The following describes the case of a patient who was born in the ‘‘Dr. José Eleuterio González’’ University Hospital in Monterrey, N.L, who presented clinical and muscle biopsy compatible with this myopathy.