Growth differentiation factor 9: bone morphogenetic protein 15 synergism and the potential involvement of heterodimerization

LetterDavid G. Mottershead, Craig A. Harrison, Thomas D. Mueller, Peter G. Stanton, Robert B. Gilchrist and Kenneth P. McNatt

Historical factors associated with past environments influence the biogeography of thermophilic endospores in Arctic marine sediments

Selection by the local, contemporary environment plays a prominent role in shaping the biogeography of microbes. However, the importance of historical factors in microbial biogeography is more debatable. Historical factors include past ecological and evolutionary circumstances that may have influenced present-day microbial diversity, such as dispersal and past environmental conditions. Diverse thermophilic sulphate-reducing Desulfotomaculum are present as dormant endospores in marine sediments worldwide where temperatures are too low to support their growth. Therefore, they are dispersed to here from elsewhere, presumably a hot, anoxic habitat. While dispersal through ocean currents must influence their distribution in cold marine sediments, it is not clear whether even earlier historical factors, related to the source habitat where these organisms were once active, also have an effect. We investigated whether these historical factors may have influenced the diversity and distribution of thermophilic endospores by comparing their diversity in 10 Arctic fjord surface sediments. Although community composition varied spatially, clear biogeographic patterns were only evident at a high level of taxonomic resolution (>97% sequence similarity of the 16S rRNA gene) achieved with oligotyping. In particular, the diversity and distribution of oligotypes differed for the two most prominent OTUs (defined using a standard 97% similarity cutoff). One OTU was dominated by a single ubiquitous oligotype, while the other OTU consisted of ten more spatially localised oligotypes that decreased in compositional similarity with geographic distance. These patterns are consistent with differences in historical factors that occurred when and where the taxa were once active, prior to sporulation. Further, the influence of history on biogeographic patterns was only revealed by analysing microdiversity within OTUs, suggesting that populations within standard OTU-level groupings do not necessarily share a common ecological and evolutionary history

Deep Inelastic Scattering in Conformal QCD

We consider the Regge limit of a CFT correlation function of two vector and two scalar operators, as appropriate to study small-x deep inelastic scattering in N=4 SYM or in QCD assuming approximate conformal symmetry. After clarifying the nature of the Regge limit for a CFT correlator, we use its conformal partial wave expansion to obtain an impact parameter representation encoding the exchange of a spin j Reggeon for any value of the coupling constant. The CFT impact parameter space is the three-dimensional hyperbolic space H3, which is the impact parameter space for high energy scattering in the dual AdS space. We determine the small-x structure functions associated to the exchange of a Reggeon. We discuss unitarization from the point of view of scattering in AdS and comment on the validity of the eikonal approximation. We then focus on the weak coupling limit of the theory where the amplitude is dominated by the exchange of the BFKL pomeron. Conformal invariance fixes the form of the vector impact factor and its decomposition in transverse spin 0 and spin 2 components. Our formalism reproduces exactly the general results predict by the Regge theory, both for a scalar target and for gamma*-gamma* scattering. We compute current impact factors for the specific examples of N=4 SYM and QCD, obtaining very simple results. In the case of the R-current of N=4 SYM, we show that the transverse spin 2 component vanishes. We conjecture that the impact factors of all chiral primary operators of N=4 SYM only have components with 0 transverse spin.Comment: 44+16 pages, 7 figures. Some correction

Estimating the Burden of Malaria: The Need for Improved Surveillance

Ivo Mueller, Laurence Slutsker, and Marcel Tanner highlight the importance of using complementary methods to estimate the burden of malaria and call for a renewed focus on efficient malaria surveillance

Integration of molecules and new fossils supports a Triassic origin for Lepidosauria (lizards, snakes, and tuatara)

Background Lepidosauria (lizards, snakes, tuatara) is a globally distributed and ecologically important group of over 9,000 reptile species. The earliest fossil records are currently restricted to the Late Triassic and often dated to 227 million years ago (Mya). As these early records include taxa that are relatively derived in their morphology (e.g. Brachyrhinodon), an earlier unknown history of Lepidosauria is implied. However, molecular age estimates for Lepidosauria have been problematic; dates for the most recent common ancestor of all lepidosaurs range between approximately 226 and 289 Mya whereas estimates for crown-group Squamata (lizards and snakes) vary more dramatically: 179 to 294 Mya. This uncertainty restricts inferences regarding the patterns of diversification and evolution of Lepidosauria as a whole. Results Here we report on a rhynchocephalian fossil from the Middle Triassic of Germany (Vellberg) that represents the oldest known record of a lepidosaur from anywhere in the world. Reliably dated to 238–240 Mya, this material is about 12 million years older than previously known lepidosaur records and is older than some but not all molecular clock estimates for the origin of lepidosaurs. Using RAG1 sequence data from 76 extant taxa and the new fossil specimens two of several calibrations, we estimate that the most recent common ancestor of Lepidosauria lived at least 242 Mya (238–249.5), and crown-group Squamata originated around 193 Mya (176–213). Conclusion A Early/Middle Triassic date for the origin of Lepidosauria disagrees with previous estimates deep within the Permian and suggests the group evolved as part of the faunal recovery after the end-Permain mass extinction as the climate became more humid. Our origin time for crown-group Squamata coincides with shifts towards warmer climates and dramatic changes in fauna and flora. Most major subclades within Squamata originated in the Cretaceous postdating major continental fragmentation. The Vellberg fossil locality is expected to become an important resource for providing a more balanced picture of the Triassic and for bridging gaps in the fossil record of several other major vertebrate groups

A novel locus for Meckel-Gruber syndrome, MKS3, maps to chromosome 8q24

Meckel-Gruber syndrome (MKS), the most common monogenic cause of neural tube defects, is an autosomal recessive disorder characterised by a combination of renal cysts and variably associated features, including developmental anomalies of the central nervous system (typically encephalcoele), hepatic ductal dysplasia and cysts, and polydactyly. Locus heterogeneity has been demonstrated by the mapping of the MKS1 locus to 17q21-24 in Finnish kindreds, and of MKS2 to 11q13 in North African-Middle Eastern cohorts. In the present study, we have investigated the genetic basis of MKS in eight consanguineous kindreds, originating from the Indian sub-continent, that do not show linkage to either MKS1 or MKS2. We report the localisation of a third MKS locus (MKS3) to chromosome 8q24 in this cohort by a genome-wide linkage search using autozygosity mapping. We identified a 26-cM region of autozygosity between D8S586 and D8S1108 with a maximum cumulative two-point LOD score at D8S1179 (Z(max)=3.04 at theta=0.06). A heterogeneity test provided evidence of one unlinked family. Exclusion of this family from multipoint analysis maximised the cumulative multipoint LOD score at locus D8S1128 (Z(max)=5.65). Furthermore, a heterozygous SNP in DDEF1, a putative candidate gene, suggested that MKS3 mapped within a 15-cM interval. Comparison of the clinical features of MKS3-linked cases with reports of MKS1- and MKS2-linked kindreds suggests that polydactyly (and possibly encephalocele) appear less common in MKS3-linked families

Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-specific growth factors with central roles in mammalian reproduction, regulating species-specific fecundity, ovarian follicular somatic cell differentiation, and oocyte quality. In the human, GDF9 is produced in a latent form, the mechanism of activation being an open question. Here, we produced a range of recombinant GDF9 and BMP15 variants, examined their in silico and physical interactions and their effects on ovarian granulosa cells (GC) and oocytes. We found that the potent synergistic actions of GDF9 and BMP15 on GC can be attributed to the formation of a heterodimer, which we have termed cumulin. Structural modeling of cumulin revealed a dimerization interface identical to homodimeric GDF9 and BMP15, indicating likely formation of a stable complex. This was confirmed by generation of recombinant heterodimeric complexes of pro/mature domains (pro-cumulin) and covalent mature domains (cumulin). Both pro-cumulin and cumulin exhibited highly potent bioactivity on GC, activating both SMAD2/3 and SMAD1/5/8 signaling pathways and promoting proliferation and expression of a set of genes associated with oocyte-regulated GC differentiation. Cumulin was more potent than pro-cumulin, pro-GDF9, pro-BMP15, or the two combined on GC. However, on cumulus-oocyte complexes, pro-cumulin was more effective than all other growth factors at notably improving oocyte quality as assessed by subsequent day 7 embryo development. Our results support a model of activation for human GDF9 dependent on cumulin formation through heterodimerization with BMP15. Oocyte-secreted cumulin is likely to be a central regulator of fertility in mono-ovular mammals

Information Literacy Needs Open Access or: Open Access is not Only for Researchers

The Open Access was initially (blandly) conceived in view not only of researchers but also of lay readers, then this perspective slowly faded out. The Information Literacy movement wants to teach citizens how to arrive at trustable information but the amount of paywalled knowledge is still big. So, their lines of development are somehow complementary: Information Literacy needs Open Access for the citizens to freely access high quality information while Open Access truly fulfils its scope when it is conceived and realized not only for the researchers (an aristocratic view which was the initial one) but for the whole society

Jet coherence in QCD media: the antenna radiation spectrum

We study the radiation of a highly energetic partonic antenna in a colored state traversing a dense QCD medium. Resumming multiple scatterings of all involved constituents with the medium we derive the general gluon spectrum which encompasses both longitudinal color coherence between scattering centers in the medium, responsible for the well known Landau-Pomeranchuk-Migdal (LPM) effect, and transverse color coherence between partons inside a jet, leading, in vacuum, to angular ordering of the parton shower. We discuss shortly the onset of transverse decoherence which is reached in opaque media. In this regime, the spectrum consists of independent radiation off the antenna constituents.Comment: 15 pages, 2 figures, paper shortened and partly rewritten, references added, results unchange

Retaining product value in post-consumer textiles: How to scale a closed-loop system

This is the final version. Available on open access from Elsevier via the DOI in this recordIn the face of rapidly growing sustainability challenges, pressure is mounting on businesses to decouple production from virgin resources, reduce waste and phase-out pollution. The Circular Economy (CE) is important for addressing resource efficiency within the textiles sector. In a CE for textiles, clothes would be used more, made to be recycled, and made from safe and renewable inputs. Textiles-to-textiles (T-T) recycling is a key component of a circular textiles industry yet represents only 1% of global textiles production. This paper sets out to answer how a closed-loop system for recycling post-consumer textiles (PCT) can be scaled. Whilst T-T recycling is a rapidly emerging industry, there is a lack of clarity on the enabling conditions needed to scale significantly throughout the value chain. By means of semi-structured interviews with practitioners participating in textiles CE activities, a holistic analysis of the barriers and enablers at all stages of the value chain has been conducted. The paper concludes with practical recommendations addressing each T-T supply chain actor. It makes an important contribution to understanding how actors in the circular value chain, policymakers and convening bodies can act in concert to successfully scale a system for collecting and recycling PCT.Engineering and Physical Sciences Research Council (EPSRC