Is bundling anticompetitive?

I analyze the implications of bundling on price competition in a market for complementary products. Using a model of imperfect competition with product differentiation, I identify the incentives to bundle for two types of demand functions and study how they change with the size of the bundle. With an inelastic demand, bundling creates an advantage over uncoordinated rivals who cannot improve by bundling. I show that this no longer holds with an elastic demand. The incentives to bundle are stronger and the market outcome is symmetric bundling, the most competitive one. Profits are lowest and consumer surplus is maximized.

Genome-wide patterns of latitudinal differentiation among populations of Drosophila melanogaster from North America.

Understanding the genetic underpinnings of adaptive change is a fundamental but largely unresolved problem in evolutionary biology. Drosophila melanogaster, an ancestrally tropical insect that has spread to temperate regions and become cosmopolitan, offers a powerful opportunity for identifying the molecular polymorphisms underlying clinal adaptation. Here, we use genome-wide next-generation sequencing of DNA pools ('pool-seq') from three populations collected along the North American east coast to examine patterns of latitudinal differentiation. Comparing the genomes of these populations is particularly interesting since they exhibit clinal variation in a number of important life history traits. We find extensive latitudinal differentiation, with many of the most strongly differentiated genes involved in major functional pathways such as the insulin/TOR, ecdysone, torso, EGFR, TGFβ/BMP, JAK/STAT, immunity and circadian rhythm pathways. We observe particularly strong differentiation on chromosome 3R, especially within the cosmopolitan inversion In(3R)Payne, which contains a large number of clinally varying genes. While much of the differentiation might be driven by clinal differences in the frequency of In(3R)P, we also identify genes that are likely independent of this inversion. Our results provide genome-wide evidence consistent with pervasive spatially variable selection acting on numerous loci and pathways along the well-known North American cline, with many candidates implicated in life history regulation and exhibiting parallel differentiation along the previously investigated Australian cline.

Environmental Degradation and the Limits to LOV

We show how consumers’ environmental concerns may limit ‘love of variety’ (LOV) and be reflected in consumers decisions. We investigate how the impact of environmental degradation on LOV influences demand and optimal product variety, and how a pollution tax on firms might be used to improve upon the market outcome and increase welfare.

Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen.

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.

Are vectors able to learn about their hosts? A case study with Aedes aegypti mosquitoes

The way in which vectors distribute themselves amongst their hosts has important epidemiological consequences. While the role played by active host choice is largely unquestioned, current knowledge relates mostly to the innate response of vectors towards stimuli signalling the presence or quality of their hosts. Many of those cues, however, can be unpredictable, and therefore prevent the incorporation of the appropriate response into the vector's behavioural repertoire unless some sort of associative learning is possible. We performed a wide range of laboratory experiments to test the learning abilities of the mosquito, Aedes aegypti. Mosquitoes were exposed to choice procedures in (1) an olfactomenter and (2) a 'visual arena'. Our goal was to determine whether the mosquitoes were able to associate unconditional stimuli (blood feeding, human breath, vibration and electrical shock) with particular odours (citral, carvone, citronella oil and eugenol) and visual patterns (horizontal or vertical black bars) to which they had been previously observed to be responsive. We found no evidence supporting the hypothesis that associative learning abilities are present in adult Ae. aegypti. We discuss the possibilities that the assays employed were either inappropriate or insufficient to detect associative learning, or that associative learning is not possible in this species.

Communally breeding Bechstein's bats have a stable social system that is independent from the postglacial history and location of the populations.

Investigating macro-geographical genetic structures of animal populations is crucial to reconstruct population histories and to identify significant units for conservation. This approach may also provide information about the intraspecific flexibility of social systems. We investigated the history and current structure of a large number of populations in the communally breeding Bechstein's bat (Myotis bechsteinii). Our aim was to understand which factors shape the species' social system over a large ecological and geographical range. Using sequence data from one coding and one noncoding mitochondrial DNA region, we identified the Balkan Peninsula as the main and probably only glacial refugium of the species in Europe. Sequence data also suggest the presence of a cryptic taxon in the Caucasus and Anatolia. In a second step, we used seven autosomal and two mitochondrial microsatellite loci to compare population structures inside and outside of the Balkan glacial refugium. Central European and Balkan populations both were more strongly differentiated for mitochondrial DNA than for nuclear DNA, had higher genetic diversities and lower levels of relatedness at swarming (mating) sites than in maternity (breeding) colonies, and showed more differentiation between colonies than between swarming sites. All these suggest that populations are shaped by strong female philopatry, male dispersal, and outbreeding throughout their European range. We conclude that Bechstein's bats have a stable social system that is independent from the postglacial history and location of the populations. Our findings have implications for the understanding of the benefits of sociality in female Bechstein's bats and for the conservation of this endangered species.

Mycobacterium tuberculosis complex differentiation using gyrB-restriction fragment length polymorphism analysis

Mycobacterium tuberculosis complex (MTBC) members are causative agents of human and animal tuberculosis. Differentiation of MTBC members is required for appropriate treatment of individual patients and for epidemiological purposes. Strains from six MTBC species - M. tuberculosis, M. bovis subsp. bovis, M. bovis BCG, M. africanum, M. pinnipedii, and "M. canetti" - were studied using gyrB-restriction fragment length polymorphism (gyrB-RFLP) analysis. A table was elaborated, based on observed restriction patterns and published gyrB sequences. To evaluate applicability of gyrB-RFLP at Instituto Adolfo Lutz, São Paulo, Mycobacterial Reference Laboratory, 311 MTBC clinical isolates, previously identified using traditional methods as M. tuberculosis (306), M. bovis (3), and M. bovis BCG (2), were analyzed by gyrB-RFLP. All isolates were correctly identified by the molecular method, but no distinction between M. bovis and M. bovis BCG was obtained. Differentiation of M. tuberculosis and M. bovis is of utmost importance, because they require different treatment schedules. In conclusion, gyrB-RFLP is accurate and easy-to-perform, with potential to reduce time needed for conventional differentiation methods. However, application for epidemiological studies remains limited, because it cannot differentiate M. tuberculosis from M. africanum subtype II, and "M. canetti", M. africanum subtype I from M. pinnipedii, and. M. bovis from M. bovis BCG.

Dengue virus detection by using reverse transcription-polymerase chain reaction in saliva and progeny of experimentally infected Aedes albopictus from Brazil

Oral susceptibility and vertical transmission of dengue virus type 2 (DENV-2) in an Aedes albopictus sample from Rio de Janeiro was estimated. The infection (36.7%) and transmission (83.3%) rates for Ae. albopictus were higher than those of an Ae. aegypti colony used as control, 32.8 and 60%, respectively. Fourth instar larvae and females descendants of 48.5 and 39.1% of experimentally infected Ae. albopictus showed to harbor the virus. The oral susceptibility and the high capacity to assure vertical transmission exhibited by Ae. albopictus from Brazil reinforce that this species may play a role in the maintenance of the virus in nature and be a threat for dengue control in the country.

Hepatitis B virus screening in contacts of blood donors with antibodies against core protein (anti-HBc), but without surface antigen (HBsAg)

To increase blood safety Brazil introduced screening for anti-HBc among blood donors in 1993. There was a decrease in the hepatitis B virus (HBV) transmission, but this measure identified a great number of HBsAg-negative, anti-HBc-positive donors. Surveillance policy determines that contacts of HBV carriers should be screened to HBV markers, but there is no recommendation about how to guide contacts of HBsAg-negative, anti-HBc-positive donors. Aiming to evaluate whether the contacts of this group are at greater risk for HBV infection, a cross-sectional study was performed to compare prevalence of HBV infection between contacts of HBsAg-positive blood donors (group I) and contacts of HBsAg-negative, anti-HBc-positive donors (group II). Contacts were submitted to a questionnaire and blood tests for HBV markers. In group I (n = 143), 53 (37.1%) were anti-HBc-positive and 11 (7.7%) were HBsAg-positive. In group II (n = 111), there were 9 and 0.9%, respectively. HBV exposure was associated with group I, sexual activity, blood transfusion, being one of the donor's parents, and living for more than ten years with the donor. Regarding the families as sample units, it was more common to find at least one member with HBV markers (p < 0.05) among the families of group I compared to group II. Contacts of HBsAg-negative, anti-HBc-positive individuals presented a much lower risk of having already been exposed to HBV and there is no need to screen them for HBV in low to moderate prevalence populations.

Population structure and diversity of the pathogenic fungus Aspergillus fumigatus isolated from different sources and geographic origins

Fifty-five clinical and environmental Aspergillus fumigatus isolates from Mexico, Argentina, France and Peru were analyzed to determine their genetic variability, reproductive system and level of differentiation using amplified fragment length polymorphism markers. The level of genetic variability was assessed by measuring the percentage of polymorphic loci, number of effective alleles, expected heterozygocity and by performing an association index test (I A). The degree of genetic differentiation and variation was determined using analysis of molecular variance at three levels. Using the paired genetic distances, a dendrogram was built to detect the genetic relationship among alleles. Finally, a network of haplotypes was constructed to determine the geographic relationship among them. The results indicate that the clinical isolates have greater genetic variability than the environmental isolates. The I A of the clinical and environmental isolates suggests a recombining population structure. The genetic differentiation among isolates and the dendrogram suggest that the groups of isolates are different. The network of haplotypes demonstrates that the majority of the isolates are grouped according to geographic origin.

Genetic investigation of the functions of c-Myc and N-Myc in Hematopoietic stem cells

Résumé : c-Myc, le premier facteur de transcription de la famille Myc a été découvert il y a maintenant trente ans. Il reste à l'heure actuelle parmi les plus puissants proto-oncogènes connus. c-Myc est dérégulé dans plus de 50% des cancers, où il promeut la prolifération, la croissance cellulaire, et la néoangiogenèse. Myc peut aussi influencer de nombreuses autres fonctions de par sa capacité à activer ou à réprimer la transcription de nombreux gènes, et à agir globalement sur le génome à travers des modifications épigénétiques de la chromatine. La famille d'oncogènes Myc comprend, chez les mammifères, trois protéines structurellement proches: c-Myc, N-Myc et L-Myc. Ces protéines ont les mêmes proprietés biochimiques, exercent les mêmes fonctions mais sont le plus souvent exprimées de façon mutuellement exclusive. Myc a été récemment identifié comme un facteur clef dans la maintenance des cellules souches embryonnaires et adultes ainsi que dans la réacquisition des proprietés des cellules souches. Nous avons précédemment démontré que l'élimination de c-Myc provoque une accumulation de cellules souches hématopoïétiques (CSH) suite à un défaut de différenciation lié à la niche. Les CSH sont responsables de la production de tous les éléments cellulaires du sang pour toute la vie de l'individu et sont définies par leur capacité à s'auto-renouveler tout en produisant des précurseurs hématopoïétiques. Afin de mieux comprendre la fonction de Myc dans les CSH, nous avons choisi de combiner l'utilisation de modèles de souris génétiquement modifiées à une caractérisation systématique des schémas d'expression de c-Myc, N-Myc et L-Myc dans tout le système hématopoïétique. Nous avons ainsi découvert que les CSH les plus immatures expriment des quantités équivalentes de transcrits de c-myc et N-myc. Si les CSH déficientes en N-myc seulement ont une capacité d'auto-renouvellement à long-terme réduite, l'invalidation combinée des gènes c-myc et N-myc conduit à une pan-cytopénie suivie d'une mort rapide de l'animal, pour cause d'apoptose de tous les types cellulaires hématopoïétiques. En particulier, les CSH en cours d'auto-renouvelemment, mais pas les CSH quiescentes, accumulent du Granzyme B (GrB), une molécule fortement cytotoxique qui provoque une mort cellulaire rapide. Ces données ont ainsi mis au jour un nouveau mécanisme dont dépend la survie des CSH, à savoir la répression du GrB, une enzyme typiquement utilisée par le système immunitaire inné pour éliminer les tumeurs et les cellules infectées par des virus. Dans le but d'évaluer l'étendue de la redondance entre c-Myc et N-Myc dans les CSH, nous avons d'une part examiné des souris dans lesquelles les séquences codantes de c-myc sont remplacées par celles de N-myc (NCR) et d'autre part nous avons géneré une série allèlique de myc en éliminant de façon combinatoire un ou plusieurs allèles de c-myc et/ou de N-myc. Alors que l'analyse des souris NCR suggère que c-Myc et N-Myc sont qualitativement redondants, la série allélique indique que les efficiences avec lesquelles ces deux protéines influencent des procédés essentiels à la maintenance des CSH sont différentes. En conclusion, nos données génétiques montrent que l'activité générale de MYC, fournie par c-Myc et N-Myc, contrôle plusieurs aspects cruciaux de la fonction des CSH, notamment l'auto-renouvellement, la survie et la différenciation. Abstract : c-Myc, the first Myc transcription factor was discovered 30 years ago and is to date one of the most potent proto-oncogenes described. It is found to be misregulated in over 50% of all cancers, where it drives proliferation, cell growth and neo-angiogenesis. Myc can also influence a variety of other functions, owing to its ability to activate and repress transcription of many target genes and to globally regulate the genome via epigenetic modifications of the chromatin. The Myc family of oncogenes consists of three closely related proteins in mammals: c-Myc, N-Myc and L-Myc. These proteins share the same biochemical properties, exert mostly the same functions, but are most often expressed in mutually exclusive patterns. Myc is now emerging as a key factor in maintenance of embryonic and adult stem cells as well as in reacquisition of stem cell properties, including induced reprogramming. We previously showed that c-Myc deficiency can cause the accumulation of hematopoietic stem cells (HSCs) due to a niche dependent differentiation defect. HSCs are responsible for life-long replenishment of all blood cell types, and are defined by their ability to self-renew while concomitantly giving rise to more commited progenitors. To gain further insight into the function of Myc in HSCs, in this study we combine the use of genetically-modified mouse models with the systematic characterization of c-myc, N-myc and L-myc transcription patterns throughout the hematopoietic system. Interestingly, the most immature HSCs express not only c-myc, but also about equal amounts of N-myc transcripts. Although conditional deletion of N-myc alone in the bone marrow does not affect steady-state hematopoiesis, N-myc null HSCs show impaired long-term self-renewal capacity. Strikingly, combined deficiency of c-Myc and N-Myc results in pan-cytopenia and rapid lethality, due to the apoptosis of most hematopoietic cell types. In particular, self-renewing HSCs, but not quiescent HSCs or progenitor cell types rapidly up-regulate and accumulate the potent cytotoxic molecule GranzymeB (GrB), causing their rapid cell death. These data uncover a novel pathway on which HSC survival depends on, namely repression of GrB, a molecule typically used by the innate immune system to eliminate tumor and virus infected cells. To evaluate the extent of redundancy between c-Myc and N-Myc in HSCs, we examined mice in which c-myc coding sequences are replaced by that of N-myc (NCR) and also generated an allelic series of myc, by combinatorially deleting one or several c-myc and/or N-myc alleles. While the analysis of NCR mice suggests that c-Myc and N-Myc are qualitatively functionally redundant, our allelic series indicates that the efficiencies with which these two proteins affect crucial HSC maintenance processes are likely to be distinct. Collectively, our genetic data show that general "MYC" activity delivered by c-Myc and N-Myc controls crucial aspects of HSC function, including self-renewal, survival and niche dependent differentiation.

Effects of Different Postural Conditions on Handwriting Variability

During their career, forensic document examiners will inevitably be confronted with handwriting carried out under unusual conditions (UnC). A questioned document signed on top of a car or on a vertical surface like a wall are two examples. These atypical circumstances may give rise to more variability of the signatures or written words, in particular if the body was in non-traditional writing position without the traditional support. Few studies were devoted to handwriting variability under unusual writing conditions. The current study investigates whether individual variability changes with special writing conditions. In a previous study (Sciacca & al, 2009), we found that eight repetitions were sufficient to obtain a correct estimation of the variance. In the present study, twelve subjects were asked to write two word sets eight times in upper and eight times in lower case, under different conditions : sitting and writing on a horizontal (usual condition UC) or vertical support; and standing, kneeling or laying while writing on a horizontal or vertical support (unusual conditions UnC). Words were written on a pen tablet, normalized in space and time and then averaged. The variance of the eight words was measured under all conditions. Results showed only an increase in variability under the laying and kneeling / vertical UnC. Within the five other postural conditions tested, handwriting was shown to be very stable.

Molecular divergence in the timeless and cpr genes among three sympatric cryptic species of the Anopheles triannulatus complex

Anopheles triannulatus s.l. is a malaria vector with a wide geographic distribution, ranging from Argentina-Nicaragua and Trinidad. Here we analysed sequences of two genes, timeless and cpr, to assess the genetic variability and divergence among three sympatric cryptic species of this complex from Salobra, central-western Brazil. The timeless gene sequences did not conclusively differentiate Anopheles halophylus and An. triannulatus species "C". However, a partial separation has been observed between these species and An. triannulatus s.s. Importantly, the analysis of the cpr gene sequences revealed fixed differences, no shared polymorphisms and considerable genetic differentiation among the three species of the An. triannulatus complex. The results confirm that An. triannulatus s.s., An. halophylus and An. triannulatus species C are distinct taxa, with the latter two likely representing a more recent speciation event.

Interplay between keratinocytes and immune cells--recent insights into psoriasis pathogenesis.

Psoriasis is one of the most common human inflammatory skin diseases characterised by hyperproliferation and aberrant differentiation of keratinocytes. The trigger of the typical epidermal changes seen in psoriasis was considered to be a dysregulated immune response with Th-1/Tc1 cells playing a central role. Recent studies have provided new insights into psoriasis pathogenesis in defining intraepidermal alpha(1)beta(1)+ T cells as key effectors driving keratinocyte changes. Critical roles for IFN-alpha secreted by plasmacytoid dendritic cells and the IL-23/Th-17 axis were postulated. Initially, these subsequent stages are at least partially driven by the endogenous antimicrobial peptide LL37 that converts inert self-DNA into a potent trigger of interferon production by binding and delivering the DNA into plasmacytoid dendritic cells to trigger toll-like receptor 9. As LL37 is expressed by keratinocytes upon various stimuli, keratinocytes might regain momentum as instigators of an aberrant immune response which then precedes the characteristic changes in the epidermis. Data from these new studies indicate a complex interplay between keratinocytes overexpressing antimicrobial peptides and immune cells driving epidermal hyperproliferation and aberrant keratinocyte differentiation in the pathogenesis of psoriasis.

Unilateral cricothyroid contraction and glottic configuration.

It is frequently stated that unilateral cricothyroid muscle (CT) paralysis can be diagnosed by physical examination, noting rotation of the glottis, and shortening and vertical displacement of the ipsilateral vocal fold. These signs, however, are inconsistently observed, and there is considerable controversy regarding the direction of glottic rotation. To determine the effects of CT contraction on three-dimensional glottic configuration, we performed computerized tomography on cadaver larynges before and after simulated CT contraction. Radiopaque makers were used to compute distances. Unilateral CT contraction equally increased the length of both membranous vocal folds, and rotated the posterior glottis less than 1 mm. CT contraction neither adducted the vocal processes, nor significantly their altered vertical level. These results suggest that unilateral CT paralysis cannot be diagnosed on the basis of any clinically apparent change in glottal configuration.