Sumoylation of The Budding Yeast Kinetochore Protein Ndc10 is Required for Ndc10 Spindle Localization and Regulation of Anaphase Spindle Elongation

Posttranslational modification by the ubiquitin-like protein SUMO (small ubiquitin-like modifier) is emerging as an important regulator in many cellular processes, including genome integrity. In this study, we show that the kinetochore proteins Ndc10, Bir1, Ndc80, and Cep3, which mediate the attachment of chromosomes to spindle microtubules, are sumoylated substrates in budding yeast. Furthermore, we show that Ndc10, Bir1, and Cep3 but not Ndc80 are desumoylated upon exposure to nocodazole, highlighting the possibility of distinct roles for sumoylation in modulating kinetochore protein function and of a potential link between the sumoylation of kinetochore proteins and mitotic checkpoint function. We find that lysine to arginine mutations that eliminate the sumoylation of Ndc10 cause chromosome instability, mislocalization of Ndc10 from the mitotic spindle, abnormal anaphase spindles, and a loss of Bir1 sumoylation. These data suggest that sumoylation of Ndc10 and other kinetochore proteins play a critical role during the mitotic process

Disruption of Mycobacterium avium subsp. paratuberculosis-specific genes impairs in vivo fitness

Background: Mycobacterium avium subsp. paratuberculosis (MAP) is an obligate intracellular pathogen that infects many ruminant species. The acquisition of foreign genes via horizontal gene transfer has been postulated to contribute to its pathogenesis, as these genetic elements are absent from its putative ancestor, M. avium subsp. hominissuis (MAH), an environmental organism with lesser pathogenicity. In this study, high-throughput sequencing of MAP transposon libraries were analyzed to qualitatively and quantitatively determine the contribution of individual genes to bacterial survival during infection. Results: Out of 52384 TA dinucleotides present in the MAP K-10 genome, 12607 had a MycoMarT7 transposon in the input pool, interrupting 2443 of the 4350 genes in the MAP genome (56%). Of 96 genes situated in MAP-specific genomic islands, 82 were disrupted in the input pool, indicating that MAP-specific genomic regions are dispensable for in vitro growth (odds ratio = 0.21). Following 5 independent in vivo infections with this pool of mutants, the correlation between output pools was high for 4 of 5 (R = 0.49 to 0.61) enabling us to define genes whose disruption reproducibly reduced bacterial fitness in vivo. At three different thresholds for reduced fitness in vivo, MAP-specific genes were over-represented in the list of predicted essential genes. We also identified additional genes that were severely depleted after infection, and several of them have orthologues that are essential genes in M. tuberculosis. Conclusions: This work indicates that the genetic elements required for the in vivo survival of MAP represent a combination of conserved mycobacterial virulence genes and MAP-specific genes acquired via horizontal gene transfer. In addition, the in vitro and in vivo essential genes identified in this study may be further characterized to offer a better understanding of MAP pathogenesis, and potentially contribute to the discovery of novel therapeutic and vaccine targets. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-415) contains supplementary material, which is available to authorized users

New Shortwave Infrared Albedo Measurements for Snow Specific Surface Area Retrieval

Snow grain-size characterization, its vertical and temporal evolution is a key parameter for the improvement and validation of snow and radiative transfer models (optical and microwave) as well as for remote-sensing retrieval methods. We describe two optical methods, one active and one passive shortwave infrared, for field determination of the specific surface area (SSA) of snow grains. We present a new shortwave infrared (SWIR) camera approach. This new method is compared with a SWIR laser- based system measuring snow albedo with an integrating sphere (InfraRed Integrating Sphere (IRIS)). Good accuracy (10%) and reproducibility in SSA measurements are obtained using the IRIS system on snow samples having densities greater than 200 kg m-3, validated against X-ray microtomography measurements. The SWIRcam approach shows improved sensitivity to snow SSA when compared to a near-infrared camera, giving a better contrast of the snow stratigraphy in a snow pit

Mutations in the Gene Encoding the Ancillary Pilin Subunit of the Streptococcus suis srtF Cluster Result in Pili Formed by the Major Subunit Only

Pili have been shown to contribute to the virulence of different Gram-positive pathogenic species. Among other critical steps of bacterial pathogenesis, these structures participate in adherence to host cells, colonization and systemic virulence. Recently, the presence of at least four discrete gene clusters encoding putative pili has been revealed in the major swine pathogen and emerging zoonotic agent Streptococcus suis. However, pili production by this species has not yet been demonstrated. In this study, we investigated the functionality of one of these pili clusters, known as the srtF pilus cluster, by the construction of mutant strains for each of the four genes of the cluster as well as by the generation of antibodies against the putative pilin subunits. Results revealed that the S. suis serotype 2 strain P1/7, as well as several other highly virulent invasive S. suis serotype 2 isolates express pili from this cluster. However, in most cases tested, and as a result of nonsense mutations at the 5′ end of the gene encoding the minor pilin subunit (a putative adhesin), pili were formed by the major pilin subunit only. We then evaluated the role these pili play in S. suis virulence. Abolishment of the expression of srtF cluster-encoded pili did not result in impaired interactions of S. suis with porcine brain microvascular endothelial cells. Furthermore, non-piliated mutants were as virulent as the wild type strain when evaluated in a murine model of S. suis sepsis. Our results show that srtF cluster-encoded, S. suis pili are atypical compared to other Gram-positive pili. In addition, since the highly virulent strains under investigation are unlikely to produce other pili, our results suggest that pili might be dispensable for critical steps of the S. suis pathogenesis of infection

Regulating Assisted Reproduction in Canada, Switzerland, and the USA: Comparing the Judicialization of Policy-making

This article analyses the extent to which courts shape policies for assisted reproduction. While the USA is considered to be the most litigious country, Canada has observed a growing involvement of the courts from the 1980’s onward, and Switzerland is characterized by a modest degree of judicialization. Based on national patterns, we would expect litigation and court impact to vary across these three countries. As this paper demonstrates, policy-process specific variables such as the structure of policy conflicts, the novelty of regulation, self-regulation by key stakeholders, and the policies in place better explain the variation in the judicialization of policy-making

Variation at the NFATC2 Locus Increases the Risk of Thiazolidinedione-Induced Edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) Study

Objective: Thiazolidinediones are used to treat type 2 diabetes. Their use has been associated with peripheral edema and congestive heart failure - outcomes that may have a genetic etiology. Research Design and Methods: We genotyped 4,197 participants of the multiethnic DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) trial with a 50k single nucleotide polymorphisms (SNP) array, which captures ∼2000 cardiovascular, inflammatory, and metabolic genes. We tested 32,088 SNPs for an association with edema among Europeans who received rosiglitazone (n = 965). Results: One SNP, rs6123045, in NFATC2 was significantly associated with edema (odds ratio 1.89 [95% CI 1.47-2.42]; P = 5.32 × 10-7, corrected P = 0.017). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 × 10-4) when compared with individuals homozygous for the protective allele, with heterozygous individuals having an intermediate risk. The interaction between the SNP and rosiglitazone for edema was significant (P = 7.68 × 10-3). Six SNPs in NFATC2 were significant in both Europeans and Latin Americans (P < 0.05). Conclusions: Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone

An Extremes of outcome strategy provides evidence that multiple sclerosis severity is determined by alleles at the <i>HLA-DRB1</i> locus

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system unsurpassed for variability in disease outcome. A cohort of sporadic MS cases (n=63), taken from opposite extremes of the distribution of long-term outcome, was used to determine the role of the HLA-DRB1 locus on MS disease severity. Genotyping sets of benign and malignant MS patients showed that HLA-DRB1*01 was significantly underrepresented in malignant compared with benign cases. This allele appears to attenuate the progressive disability that characterizes MS in the long term. The observation was doubly replicated in (i) Sardinian benign and malignant patients and (ii) a cohort of affected sibling pairs discordant for HLA-DRB1*01. Among the latter, mean disability progression indices were significantly lower in those carrying the HLA-DRB1*01 allele compared with their disease-concordant siblings who did not. The findings were additionally supported by similar transmission distortion of HLA-DRB1*04 subtypes closely related to HLA-DRB1*01. The protective effect of HLA-DRB1*01 in sibling pairs may result from a specific epistatic interaction with the susceptibility allele HLA-DRB1*1501. A high-density (&gt;700) SNP examination of the MHC region in the benign and malignant patients could not identify variants differing significantly between the two groups, suggesting that HLA-DRB1 may itself be the disease-modifying locus. We conclude that HLA-DRB1*01, previously implicated in disease resistance, acts as an independent modifier of disease progression. These results closely link susceptibility to long-term outcome in MS, suggesting that shared quantitative MHC-based mechanisms are common to both, emphasizing the central role of this region in pathogenesis

Inter-Destination Multimedia Synchronization; Schemes, Use Cases and Standardization

Traditionally, the media consumption model has been a passive and isolated activity. However, the advent of media streaming technologies, interactive social applications, and synchronous communications, as well as the convergence between these three developments, point to an evolution towards dynamic shared media experiences. In this new model, geographically distributed groups of consumers, independently of their location and the nature of their end-devices, can be immersed in a common virtual networked environment in which they can share multimedia services, interact and collaborate in real-time within the context of simultaneous media content consumption. In most of these multimedia services and applications, apart from the well-known intra and inter-stream synchronization techniques that are important inside the consumers playout devices, also the synchronization of the playout processes between several distributed receivers, known as multipoint, group or Inter-destination multimedia synchronization (IDMS), becomes essential. Due to the increasing popularity of social networking, this type of multimedia synchronization has gained in popularity in recent years. Although Social TV is perhaps the most prominent use case in which IDMS is useful, in this paper we present up to 19 use cases for IDMS, each one having its own synchronization requirements. Different approaches used in the (recent) past by researchers to achieve IDMS are described and compared. As further proof of the significance of IDMS nowadays, relevant organizations (such as ETSI TISPAN and IETF AVTCORE Group) efforts on IDMS standardization (in which authors have been and are participating actively), defining architectures and protocols, are summarized.This work has been financed, partially, by Universitat Politecnica de Valencia (UPV), under its R&D Support Program in PAID-05-11-002-331 Project and in PAID-01-10, and by TNO, under its Future Internet Use Research & Innovation Program. The authors also want to thank Kevin Gross for providing some of the use cases included in Sect. 1.2.Montagud, M.; Boronat Segui, F.; Stokking, H.; Van Brandenburg, R. (2012). Inter-Destination Multimedia Synchronization; Schemes, Use Cases and Standardization. Multimedia Systems. 18(6):459-482. https://doi.org/10.1007/s00530-012-0278-9S459482186Kernchen, R., Meissner, S., Moessner, K., Cesar, P., Vaishnavi, I., Boussard, M., Hesselman, C.: Intelligent multimedia presentation in ubiquitous multidevice scenarios. IEEE Multimedia 17(2), 52–63 (2010)Vaishnavi, I., Cesar, P., Bulterman, D., Friedrich, O., Gunkel, S., Geerts, D.: From IPTV to synchronous shared experiences challenges in design: distributed media synchronization. Signal Process Image Commun 26(7), 370–377 (2011)Geerts, D., Vaishnavi, I., Mekuria, R., Van Deventer, O., Cesar, P.: Are we in sync?: synchronization requirements for watching on-line video together, CHI ‘11, New York, USA (2011)Boronat, F., Lloret, J., García, M.: Multimedia group and inter-stream synchronization techniques: a comparative study. Inf. Syst. 34(1), 108–131 (2009)Chen, M.: A low-latency lip-synchronized videoconferencing system. In: SIGCHI Conference on Human Factors in Computing Systems, CHI’03, ACM, pp. 464–471, New York (2003)Ishibashi, Y., Tasaka, S., Ogawa, H.: Media synchronization quality of reactive control schemes. IEICE Trans. Commun. E86-B(10), 3103–3113 (2003)Ademoye, O.A., Ghinea, G.: Synchronization of olfaction-enhanced multimedia. IEEE Trans. Multimedia 11(3), 561–565 (2009)Cesar, P., Bulterman, D.C.A., Jansen, J., Geerts, D., Knoche, H., Seager, W.: Fragment, tag, enrich, and send: enhancing social sharing of video. ACM Trans. Multimedia Comput. Commun. Appl. 5(3), Article 19, 27 pages (2009)Van Deventer, M.O., Stokking, H., Niamut, O.A., Walraven, F.A., Klos, V.B.: Advanced Interactive Television Service Require Synchronization, IWSSIP 2008. Bratislava, June (2008)Premchaiswadi, W., Tungkasthan, A., Jongsawat, N.: Enhancing learning systems by using virtual interactive classrooms and web-based collaborative work. In: Proceedings of the IEEE Education Engineering Conference (EDUCON 2010), pp. 1531–1537. Madrid, Spain (2010)Diot, C., Gautier, L.: A distributed architecture for multiplayer interactive applications on the internet. IEEE Netw 13(4), 6–15 (1999)Mauve, M., Vogel, J., Hilt, V., Effelsberg, W.: Local-lag and timewarp: providing consistency for replicated continuous applications. IEEE Trans. Multimedia 6(1), 45–57 (2004)Hosoya, K., Ishibashi, Y., Sugawara, S., Psannis, K.E.: Group synchronization control considering difference of conversation roles. In: IEEE 13th International Symposium on Consumer Electronics, ISCE ‘09, pp. 948–952 (2009)Roccetti, M., Ferretti, S., Palazzi, C.: The brave new world of multiplayer online games: synchronization issues with smart solution. In: 11th IEEE Symposium on Object Oriented Real-Time Distributed Computing (ISORC), pp. 587–592 (2008)Ott, D.E., Mayer-Patel, K.: An open architecture for transport-level protocol coordination in distributed multimedia applications. ACM Trans. Multimedia Comput. Commun. Appl. 3(3), 17 (2007)Boronat, F., Montagud, M., Guerri, J.C.: Multimedia group synchronization approach for one-way cluster-to-cluster applications. In: IEEE 34th Conference on Local Computer Networks, LCN 2009, pp. 177–184, Zürich (2009)Boronat, F., Montagud, M., Vidal, V.: Smooth control of adaptive media playout to acquire IDMS in cluster-based applications. In: IEEE LCN 2011, pp. 617–625, Bonn (2011)Huang, Z., Wu, W., Nahrstedt, K., Rivas, R., Arefin, A.: SyncCast: synchronized dissemination in multi-site interactive 3D tele-immersion. In: Proceedings of MMSys, USA (2011)Kim, S.-J., Kuester, F., Kim, K.: A global timestamp-based approach for enhanced data consistency and fairness in collaborative virtual environments. ACM/Springer Multimedia Syst. J. 10(3), 220–229 (2005)Schooler, E.: Distributed music: a foray into networked performance. In: International Network Music Festival, Santa Monica, CA (1993)Miyashita, Y., Ishibashi, Y., Fukushima, N., Sugawara, S., Psannis K.E.: QoE assessment of group synchronization in networked chorus with voice and video. In: Proceedings of IEEE TENCON’11, pp. 393–397 (2011)Hesselman, C., Abbadessa, D., Van Der Beek, W., et al.: Sharing enriched multimedia experiences across heterogeneous network infrastructures. IEEE Commun. Mag. 48(6), 54–65 (2010)Montpetit, M., Klym, N., Mirlacher, T.: The future of IPTV—Connected, mobile, personal and social. Multimedia Tools Appl J 53(3), 519–532 (2011)Cesar, P., Bulterman, D.C.A., Jansen, J.: Leveraging the user impact: an architecture for secondary screens usage in an interactive television environment. ACM/Springer Multimedia Syst. 15(3), 127–142 (2009)Lukosch, S.: Transparent latecomer support for synchronous groupware. In: Proceedings of 9th International Workshop on Groupware (CRIWG), Grenoble, France, pp. 26–41 (2003)Steinmetz, R.: Human perception of jitter and media synchronization. IEEE J. Sel. Areas Commun. 14(1), 61–72 (1996)Stokking, H., Van Deventer, M.O., Niamut, O.A., Walraven, F.A., Mekuria, R.N.: IPTV inter-destination synchronization: a network-based approach, ICIN’2010, Berlin (2010)Mekuria, R.N.: Inter-destination media synchronization for TV broadcasts, Master Thesis, Faculty of Electrical Engineering, Mathematics and Computer Science, Department of Network architecture and Services, Delft University of Technology (2011)Pitt Ian, CS2511: Usability engineering lecture notes, localisation of sound sources. http://web.archive.org/web/20100410235208/http:/www.cs.ucc.ie/~ianp/CS2511/HAP.htmlNielsen, J.: Response times: the three important limits. http://www.useit.com/papers/responsetime.html (1994)ITU-T Rec G. 1010: End-User Multimedia QoS Categories. International Telecommunication Union, Geneva (2001)Biersack, E., Geyer, W.: Synchronized delivery and playout of distributed stored multimedia streams. ACM/Springer Multimedia Syst 7(1), 70–90 (1999)Xie, Y., Liu, C., Lee, M.J., Saadawi, T.N.: Adaptive multimedia synchronization in a teleconference system. ACM/Springer Multimedia Syst. 7(4), 326–337 (1999)Laoutaris, N., Stavrakakis, I.: Intrastream synchronization for continuous media streams: a survey of playout schedulers. IEEE Netw. Mag. 16(3), 30–40 (2002)Ishibashi, Y., Tsuji, A., Tasaka, S.: A group synchronization mechanism for stored media in multicast communications. In: Proceedings of the INFOCOM ‘97, Washington (1997)Ishibashi, Y., Tasaka, S.: A group synchronization mechanism for live media in multicast communications. IEEE GLOBECOM’97, pp. 746–752 (1997)Boronat, F., Guerri, J.C., Lloret, J.: An RTP/RTCP based approach for multimedia group and inter-stream synchronization. Multimedia Tools Appl. J. 40(2), 285–319 (2008)Ishibashi, I., Tasaka, S.: A distributed control scheme for group synchronization in multicast communications. In: Proceedings of International Symposium Communications, Kaohsiung, Taiwan, pp. 317–323 (1999)Lu, Y., Fallica, B., Kuipers, F.A., Kooij, R.E., Van Mieghem, P.: Assessing the quality of experience of SopCast. Int. J. Internet Protoc. Technol 4(1), 11–19 (2009)Shamma, D.A., Bastea-Forte, M., Joubert, N., Liu, Y.: Enhancing online personal connections through synchronized sharing of online video, ACM CHI’08 Extended Abstracts, Florence (2008)Ishibashi, Y., Tasaka, S.: A distributed control scheme for causality and media synchronization in networked multimedia games. In: Proceedings of 11th International Conference on Computer Communications and Networks, pp. 144–149, Miami, USA (2002)Ishibashi, Y., Tomaru, K., Tasaka, S., Inazumi, K.: Group synchronization in networked virtual environments. In: Proceedings of the 38th IEEE International Conference on Communications, pp. 885–890, Alaska, USA (2003)Tasaka, S., Ishibashi, Y., Hayashi, M.: Inter–destination synchronization quality in an integrated wired and wireless network with handover. IEEE GLOBECOM 2, 1560–1565 (2002)Kurokawa, Y., Ishibashi, Y., Asano, T.: Group synchronization control in a remote haptic drawing system. In: Proceedings of IEEE International Conference on Multimedia and Expo, pp. 572–575, Beijing, China (2007)Hashimoto, T., Ishibashi, Y.: Group Synchronization Control over Haptic Media in a Networked Real-Time Game with Collaborative Work, Netgames’06, Singapore (2006)Nunome, T., Tasaka, S.: Inter-destination synchronization quality in a multicast mobile ad hoc network. In: Proceedings of IEEE 16th International Symposium on Personal, Indoor and Mobile Radio Communications, pp. 1366–1370, Berlin, Germany (2005)Brandenburg, R., van Stokking, H., Van Deventer, M.O., Boronat, F., Montagud, M., Gross, K.: RTCP for inter-destination media synchronization, draft-brandenburg-avtcore-rtcp-for-idms-03.txt. In: IETF Audio/Video Transport Core Maintenance Working Group, Internet Draft, March 9 (2012)ETSI TS 181 016 V3.3.1 (2009-07) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); Service Layer Requirements to integrate NGN Services and IPTVETSI TS 182 027 V3.5.1 (2011-03) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); IPTV Architecture; IPTV functions supported by the IMS subsystemETSI TS 183 063 V3.5.2 (2011-03) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); IMS-based IPTV stage 3 specificationBrandenburg van, R., et al.: RTCP XR Block Type for inter-destination media synchronization, draft-brandenburg-avt-rtcp-for-idms-00.txt. In: IETF Audio/Video Transport Working Group, Internet Draft, Sept 24, 2010Williams, A., et al.: RTP Clock Source Signalling, draft-williams-avtcore-clksrc-00. In: IETF Audio/Video Transport Working Group, Internet Draft, February 28, 201