Sectoral Issues and the Multilateral Framework for Trade in Services: An Overview

summary Increased opportunity for developing countries to expand trade in services is one objective of attempts to liberalise trade in services. However, efforts in this direction are continually impeded by the specificity required in trying to effect a workable multilateral framework, The heterogeneity of the services sector does not lend itself to an easily negotiable framework. This article addresses two major issues on this topic: (i) the market structure of trade in services and the basis of comparative advantage of developed countries; (ii) the desirability of a multilateral negotiating framework which takes into account the strategic importance of particular service sectors to growth and development and the present state of international trade and draft segments of the set. Résumé Vue d'ensemble sur les problèmes de secteurs et le cadre multilatéral pour les industries de services L'augmentation des possibilités pour les pays en voie de développement d'élargir le commerce des industries de services constitute l'objectif des tentatives de libéralisation du commerce des industries de services. Cependant, les efforts allant dans cette direction sont continuellement entravés par le besoin d'indications précises que demande la réalisation d'une structure multilatérale. L'hétérogénéité du secteur des services ne se prête pas à la formation d'une structure aisément négotiable. Cet article aborde deux problèmes principaux liés à ce thàme: 1) La structure du marché des industries de services et les conditions des avantages reliatifs des pavs developpés 2) L'avantage d'une structure multilatérale de négotiations, qui tient compte de l'importance stratégique de certains secteurs des services pour le développement, et de l'état actuel du commerce international et des segments sommaires de l'ensemble. Resumen Una revisión de los problemas sectoriales y el marco multilateral para el comercio de servicios Uno de los objetivos de los intentos de los países en desarrollo de liberalizar el comercio de los servicios es mejorar sus oportunidades en este rubro. No obstante, la especificidad requerida para establecer un marco multilateral viable conspira constantemente en contra de los esfuerzos que se despliegan en este sentido. La heterogeneidad del sector servicios, por si misma, no se presta fácilmente para un marco negociable. Este artículo enfoca dos problemas básicos en este tópico: i) la estructura de mercado del comercio de servicios y la base de las ventajas comparativas de los países en desarrollo. ii) la conveniencia de un marco multilateral negociable que considere la importancia estratégica de determinados sectores de servicios y, segmentos de éste en el crecimiento y desarrollo y el estado actual del comercio internacional

Cytomegalovirus microRNAs Facilitate Persistent Virus Infection in Salivary Glands

Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence

Maternal colonisation and early-onset neonatal bacterial sepsis in The Gambia, West Africa: a genomic analysis of vertical transmission.

OBJECTIVES: To define bacterial aetiology of neonatal sepsis and estimate prevalence of neonatal infection from maternal genital tract bacterial carriage among mother-newborn pairs. METHODS: We carried out a cross-sectional study of newborns with clinical sepsis admitted to neonatal wards of three hospitals in The Gambia. Neonatal blood cultures and maternal genital swabs were obtained at recruitment. We used whole-genome sequencing (WGS) to explore vertical transmission for neonates with microbiologically confirmed bloodstream infection by comparing phenotypically matched paired neonatal blood culture and maternal genital tract bacterial isolates. RESULTS: We enrolled 203 maternal-newborn pairs. Two-thirds (67%; 137/203) of neonates presented with early-onset sepsis (days 0 - 6 after birth) of which 26% (36/137) were due to a clinically-significant bacterial pathogen. Blood culture isolates from newborns with early-onset sepsis due to Staphylococcus aureus (n=5), Klebsiella pneumonia (n=2), and Enterococcus faecalis (n=1), phenotypically matched their maternal genital tract isolates. Pairwise SNV comparisons showed differences of 12 - 52 SNVs only between maternal and newborn Staphylococcus aureus isolates, presumably representing vertical transmission with a transmission rate of 14% (5/36). CONCLUSIONS: We found low prevalence of vertical transmission of maternal genital tract colonisation in maternal-newborn pairs for early-onset neonatal sepsis in west African context. Identifying infection acquisition pathways among newborns is essential to prioritise preventive interventions, which could be targeted at mother or infection control in the hospital environment, depending on the major pathways of transmission

Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

<p>Abstract</p> <p>Background</p> <p>All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats.</p> <p>Methods</p> <p>Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied.</p> <p>Results</p> <p>The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1.</p> <p>Conclusion</p> <p>We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.</p

Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system

Discrimination of Timbre in Early Auditory Responses of the Human Brain

The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG).Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1) – testing (S2) paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2) for both same and different conditions in the both hemispheres.Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre