Cell biology:Collagen secretion explained

Cells package proteins into vesicles for secretion to the extracellular milieu. A study shows that an enzyme modifies the packaging machinery to encapsulate unusually large proteins such as collagen

Point-to-Multipoint Communication Enablers for the Fifth Generation of Wireless Systems

(c) 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.[EN] 3GPP has enhanced the point-to-multipoint (PTM) communication capabilities of 4G LTE in all releases since the adoption of eMBMS in Release-9. Recent enhancements cover not only television services, but also critical machine-type and vehicular communications, following the backward-compatibility design philosophy of LTE. This article discusses the opportunity in the design and standardization of 5G to break with the existing paradigm for PTM transmissions in 4G LTE, where broadcast PTM transmissions were initially conceived as an add-on and pre-positioned service. 5G brings the opportunity to incorporate PTM capabilities as built-in delivery features from the outset, integrating point-to-point and PTM modes under one common framework and enabling dynamic use of PTM to maximize network and spectrum efficiency. This approach will open the door to completely new levels of network management and delivery cost efficiency. The article also discusses the implications of PTM for network slicing to customize and optimize network resources on a common 5G infrastructure to accommodate different use cases and services taking into account user densityThis work was supported in part by the European Commission under the 5G-PPP project Broadcast and Multicast Communication Enablers for the Fifth-(H2020-ICT-2016-2 call, grant number 761498). The views expressed in this contribution are those of the authors and do not necessarily represent the project.Generation of Wireless Systems 5G-XcastGomez-Barquero, D.; Navratil, D.; Appleby, S.; Stagg, M. (2018). Point-to-Multipoint Communication Enablers for the Fifth Generation of Wireless Systems. IEEE Communications Standards Magazine. 2(1):53-59. https://doi.org/10.1109/MCOMSTD.2018.170006953592

The structures of natively assembled clathrin-coated vesicles

Clathrin-coated vesicles mediate trafficking of proteins and nutrients in the cell and between organelles. Proteins included in the clathrin-coated vesicles (CCVs) category include clathrin heavy chain (CHC), clathrin light chain (CLC), and a variety of adaptor protein complexes. Much is known about the structures of the individual CCV components, but data are lacking about the structures of the fully assembled complexes together with membrane and in complex with cargo. Here, we determined the structures of natively assembled CCVs in a variety of geometries. We show that the adaptor β2 appendages crosslink adjacent CHC β-propellers and that the appendage densities are enriched in CCV hexagonal faces. We resolve how adaptor protein 2 and other associated factors in hexagonal faces form an assembly hub with an extensive web of interactions between neighboring β-propellers and propose a structural model that explains how adaptor binding can direct the formation of pentagonal and hexagonal faces

Mendelian randomisation identifies priority groups for prophylactic EBV vaccination

BACKGROUND: Epstein Barr virus (EBV) infects ~ 95% of the population worldwide and is known to cause adverse health outcomes such as Hodgkin’s, non-Hodgkin’s lymphomas, and multiple sclerosis. There is substantial interest and investment in developing infection-preventing vaccines for EBV. To effectively deploy such vaccines, it is vital that we understand the risk factors for infection. Why particular individuals do not become infected is currently unknown. The current literature, describes complex, often conflicting webs of intersecting factors—sociodemographic, clinical, genetic, environmental-, rendering causality difficult to decipher. We aimed to use Mendelian randomization (MR) to overcome the issues posed by confounding and reverse causality to determine the causal risk factors for the acquisition of EBV. METHODS: We mapped the complex evidence from the literature prior to this study factors associated with EBV serostatus (as a proxy for infection) into a causal diagram to determine putative risk factors for our study. Using data from the UK Biobank of 8422 individuals genomically deemed to be of white British ancestry between the ages of 40 and 69 at recruitment between the years 2006 and 2010, we performed a genome wide association study (GWAS) of EBV serostatus, followed by a Two Sample MR to determine which putative risk factors were causal. RESULTS: Our GWAS identified two novel loci associated with EBV serostatus. In MR analyses, we confirmed shorter time in education, an increase in number of sexual partners, and a lower age of smoking commencement, to be causal risk factors for EBV serostatus. CONCLUSIONS: Given the current interest and likelihood of a future EBV vaccine, these factors can inform vaccine development and deployment strategies by completing the puzzle of causality. Knowing these risk factors allows identification of those most likely to acquire EBV, giving insight into what age to vaccinate and who to prioritise when a vaccine is introduced

Multiple Notch signaling events control Drosophila CNS midline neurogenesis, gliogenesis and neuronal identity

The study of how transcriptional control and cell signaling influence neurons and glia to acquire their differentiated properties is fundamental to understanding CNS development and function. The Drosophila CNS midline cells are an excellent system for studying these issues because they consist of a small population of diverse cells with well-defined gene expression profiles. In this paper, the origins and differentiation of midline neurons and glia were analyzed. Midline precursor (MP) cells each divide once giving rise to two neurons; here, we use a combination of single-cell gene expression mapping and time-lapse imaging to identify individual MPs, their locations, movements and stereotyped patterns of division. The role of Notch signaling was investigated by analyzing 37 midline-expressed genes in Notch pathway mutant and misexpression embryos. Notch signaling had opposing functions: it inhibited neurogenesis in MP1,3,4 and promoted neurogenesis in MP5,6. Notch signaling also promoted midline glial and median neuroblast cell fate. This latter result suggests that the median neuroblast resembles brain neuroblasts that require Notch signaling, rather than nerve cord neuroblasts, the formation of which is inhibited by Notch signaling. Asymmetric MP daughter cell fates also depend on Notch signaling. One member of each pair of MP3–6 daughter cells was responsive to Notch signaling. By contrast, the other daughter cell asymmetrically acquired Numb, which inhibited Notch signaling, leading to a different fate choice. In summary, this paper describes the formation and division of MPs and multiple roles for Notch signaling in midline cell development, providing a foundation for comprehensive molecular analyses

Macromolecular crowding modulates folding mechanism of alpha/beta protein apoflavodoxin

Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.Comment: to appear in Biophysical Journal (2009). to appear in Biophysical Journal (2009

Universal HIV testing in London tuberculosis clinics: a cluster randomised controlled trial

We assessed whether implementation of a combination of interventions in London tuberculosis clinics raised the levels of HIV test offers, acceptance and coverage. A stepped-wedge cluster randomised controlled trial was conducted across 24 clinics. Interventions were training of clinical staff and provision of tailor-made information resources with or without a change in clinic policy from selective to universal HIV testing. The primary outcome was HIV test acceptance amongst those offered a test, before and after the intervention; the secondary outcome was an offer of HIV testing. Additionally, the number and proportion of HIV tests among all clinic attendees (coverage) was assessed. 1,315 patients were seen in 24 clinics. The offer and coverage of testing rose significantly in clinics without (p = 0.002 and p = 0.004, respectively) and with an existing policy of universal testing (p = 0.02 and p = 0.04, respectively). However, the level of HIV test acceptance did not increase in 18 clinics without routine universal testing (p = 0.76) or the six clinics with existing universal testing (p = 0.40). The intervention significantly increased the number of HIV tests offered and proportion of participants tested, although acceptance did not change significantly. However, the magnitude of increase is modest due to the high baseline coverage