A SUMO-dependent pathway controls elongating RNA Polymerase II upon UV-induced damage

RNA polymerase II (RNAPII) is the workhorse of eukaryotic transcription and produces messenger RNAs and small nuclear RNAs. Stalling of RNAPII caused by transcription obstacles such as DNA damage threatens functional gene expression and is linked to transcription-coupled DNA repair. To restore transcription, persistently stalled RNAPII can be disassembled and removed from chromatin. This process involves several ubiquitin ligases that have been implicated in RNAPII ubiquitylation and proteasomal degradation. Transcription by RNAPII is heavily controlled by phosphorylation of the C-terminal domain of its largest subunit Rpb1. Here, we show that the elongating form of Rpb1, marked by S2 phosphorylation, is specifically controlled upon UV-induced DNA damage. Regulation of S2-phosphorylated Rpb1 is mediated by SUMOylation, the SUMO-targeted ubiquitin ligase Slx5-Slx8, the Cdc48 segregase as well as the proteasome. Our data suggest an RNAPII control pathway with striking parallels to known disassembly mechanisms acting on defective RNA polymerase III

Neuropsychiatric symptoms in patients with thymoma-associated and non-thymoma myasthenia gravis

Background. Around 10 - 15% of patients with myasthenia gravis (MG) have a thymoma, and non-motor symptoms are more frequent in these patients. We hypothesised that neuropsychiatric symptoms would also be more frequent. Methods. A cross-sectional study of 30 consecutive MG patients attending a clinic at Groote Schuur Hospital, Cape Town, South Africa, was done over a 6-month period in 2010. Each patient underwent a series of single-blinded neuropsychiatric assessments, including the 16-item, self-reported Flanagan Quality of Life (QOL) scale, the Beck Depression Inventory second version, the Young Mania Rating Scale, the Hamilton Anxiety Rating Scale and the Brief Psychiatric Rating Scale (BPRS). Results. The frequency and nature of neuropsychiatric symptoms were similar between thymoma (n=9) and non-thymoma (n=21) MG patients. Symptoms of moderate or severe depression and anxiety were present in around 30%. The severity of depression symptoms correlated with MG severity. Prednisone dosing was not associated with neuropsychiatric symptoms or QOL scores. Those with longer duration of MG were more likely to have higher scores on the BPRS and anxiety scales. Those with younger-onset MG had higher BPRS scores and a tendency to suicidal behaviour. Conclusion. Although no association with thyoma was found, this study shows that neuropsychiatric conditions may be underdiagnosed in patients with MG. Systematic depression screening should be done at outpatient clinics, particularly for those who developed symptoms at a young age, those with severe disease and those with a long duration of illness

Homogeneity, Flatness and "Large" Extra Dimensions

We consider a model in which the universe is the direct product of a (3+1)-dimensional Friedmann, Robertson-Walker (FRW) space and a compact hyperbolic manifold (CHM). Standard Model fields are confined to a point in the CHM (i.e. to a brane). In such a space, the decay of massive Kaluza-Klein modes leads to the injection of any initial bulk entropy into the observable (FRW) universe. Both Kolmogoro-Sinai mixing due to the non-integrability of flows on CHMs and the large statistical averaging inherent in the collapse of the initial entropy onto the brane smooth out any initial inhomogeneities in the distribution of matter and of 3-curvature on any slice of constant 3-position. If, as we assume, the initial densities and curvatures in each fundamental correlation volume are drawn from some universal underlying distributions independent of location within the space, then these smoothing mechanisms effectively reduce the density and curvature inhomogeneities projected onto the FRW. This smoothing is sufficient to account for the current homogeneity and flatness of the universe. The fundamental scale of physics can be \gsim 1TeV. All relevant mass and length scales can have natural values in fundamental units. All large dimensionless numbers, such as the entropy of the universe, are understood as consequences of the topology of spacetime which is not explained. No model for the origin of structure is proffered.Comment: minor changes, matches version published in Phys. Rev. Let

Pathological and ecological host consequences of infection by an introduced fish parasite

The infection consequences of the introduced cestode fish parasite Bothriocephalus acheilognathi were studied in a cohort of wild, young-of-the-year common carp Cyprinus carpio that lacked co-evolution with the parasite. Within the cohort, parasite prevalence was 42% and parasite burdens were up to 12% body weight. Pathological changes within the intestinal tract of parasitized carp included distension of the gut wall, epithelial compression and degeneration, pressure necrosis and varied inflammatory changes. These were most pronounced in regions containing the largest proportion of mature proglottids. Although the body lengths of parasitized and non-parasitized fish were not significantly different, parasitized fish were of lower body condition and reduced weight compared to non-parasitized conspecifics. Stable isotope analysis (δ15N and δ13C) revealed trophic impacts associated with infection, particularly for δ15N where values for parasitized fish were significantly reduced as their parasite burden increased. In a controlled aquarium environment where the fish were fed ad libitum on an identical food source, there was no significant difference in values of δ15N and δ13C between parasitized and non-parasitized fish. The growth consequences remained, however, with parasitized fish growing significantly slower than non-parasitized fish, with their feeding rate (items s−1) also significantly lower. Thus, infection by an introduced parasite had multiple pathological, ecological and trophic impacts on a host with no experience of the parasite

Identity and integration of Russian speakers in the Baltic states: a framework for analysis

Following a review of current scholarship on identity and integration patterns of Russian speakers in the Baltic states, this article proposes an analytical framework to help understand current trends. Rogers Brubaker's widely employed triadic nexus is expanded to demonstrate why a form of Russian-speaking identity has been emerging, but has failed to become fully consolidated, and why significant integration has occurred structurally but not identificationally. By enumerating the subfields of political, economic, and cultural ‘stances’ and ‘representations’ the model helps to understand the complicated integration processes of minority groups that possess complex relationships with ‘external homelands’, ‘nationalizing states’ and ‘international organizations’. Ultimately, it is argued that socio-economic factors largely reduce the capacity for a consolidated identity; political factors have a moderate tendency to reduce this capacity, whereas cultural factors generally increase the potential for a consolidated group identity

Fixed point results for generalized cyclic contraction mappings in partial metric spaces

Rus (Approx. Convexity 3:171–178, 2005) introduced the concept of cyclic contraction mapping. P˘acurar and Rus (Nonlinear Anal. 72:1181–1187, 2010) proved some fixed point results for cyclic φ-contraction mappings on a metric space. Karapinar (Appl. Math. Lett. 24:822–825, 2011) obtained a unique fixed point of cyclic weak φ- contraction mappings and studied well-posedness problem for such mappings. On the other hand, Matthews (Ann. New York Acad. Sci. 728:183–197, 1994) introduced the concept of a partial metric as a part of the study of denotational semantics of dataflow networks. He gave a modified version of the Banach contraction principle, more suitable in this context. In this paper, we initiate the study of fixed points of generalized cyclic contraction in the framework of partial metric spaces. We also present some examples to validate our results.S. Romaguera acknowledges the support of the Ministry of Science and Innovation of Spain, grant MTM2009-12872-C02-01.Abbas, M.; Nazir, T.; Romaguera Bonilla, S. (2012). Fixed point results for generalized cyclic contraction mappings in partial metric spaces. Revista- Real Academia de Ciencias Exactas Fisicas Y Naturales Serie a Matematicas. 106(2):287-297. https://doi.org/10.1007/s13398-011-0051-5S2872971062Abdeljawad T., Karapinar E., Tas K.: Existence and uniqueness of a common fixed point on partial metric spaces. Appl. Math. Lett. 24(11), 1894–1899 (2011). doi: 10.1016/j.aml.2011.5.014Altun, I., Erduran A.: Fixed point theorems for monotone mappings on partial metric spaces. Fixed Point Theory Appl. article ID 508730 (2011). doi: 10.1155/2011/508730Altun I., Sadarangani K.: Corrigendum to “Generalized contractions on partial metric spaces” [Topology Appl. 157 (2010), 2778–2785]. Topol. 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Appl. 6, 33–40 (2011)Heckmann R.: Approximation of metric spaces by partial metric spaces. Appl. Cat. Struct. 7, 71–83 (1999)Karapinar E.: Fixed point theory for cyclic weak $${\phi}$$ -contraction. App. Math. Lett. 24, 822–825 (2011)Karapinar, E.: Generalizations of Caristi Kirk’s theorem on partial metric spaces. Fixed Point Theory Appl. 2011,4 (2011). doi: 10.1186/1687-1812-2011-4Karapinar E.: Weak $${\varphi}$$ -contraction on partial metric spaces and existence of fixed points in partially ordered sets. Math. Aeterna. 1(4), 237–244 (2011)Karapinar E., Erhan I.M.: Fixed point theorems for operators on partial metric spaces. Appl. Math. Lett. 24, 1894–1899 (2011)Karpagam S., Agrawal S.: Best proximity point theorems for cyclic orbital Meir–Keeler contraction maps. Nonlinear Anal. 74, 1040–1046 (2011)Kirk W.A., Srinavasan P.S., Veeramani P.: Fixed points for mapping satisfying cylical contractive conditions. Fixed Point Theory. 4, 79–89 (2003)Kosuru, G.S.R., Veeramani, P.: Cyclic contractions and best proximity pair theorems). arXiv:1012.1434v2 [math.FA] 29 May (2011)Matthews S.G.: Partial metric topology. in: Proc. 8th Summer Conference on General Topology and Applications. Ann. New York Acad. Sci. 728, 183–197 (1994)Neammanee K., Kaewkhao A.: Fixed points and best proximity points for multi-valued mapping satisfying cyclical condition. Int. J. Math. Sci. Appl. 1, 9 (2011)Oltra S., Valero O.: Banach’s fixed theorem for partial metric spaces. Rend. Istit. Mat. Univ. Trieste. 36, 17–26 (2004)Păcurar M., Rus I.A.: Fixed point theory for cyclic $${\phi}$$ -contractions. Nonlinear Anal. 72, 1181–1187 (2010)Petric M.A.: Best proximity point theorems for weak cyclic Kannan contractions. Filomat. 25, 145–154 (2011)Romaguera, S.: A Kirk type characterization of completeness for partial metric spaces. Fixed Point Theory Appl. (2010, article ID 493298, 6 pages).Romaguera, S.: Fixed point theorems for generalized contractions on partial metric spaces. Topol. Appl. (2011). doi: 10.1016/j.topol.2011.08.026Romaguera S., Valero O.: A quantitative computational model for complete partial metric spaces via formal balls. Math. Struct. Comput. Sci. 19, 541–563 (2009)Rus, I.A.: Cyclic representations and fixed points. Annals of the Tiberiu Popoviciu Seminar of Functional equations. Approx. Convexity 3, 171–178 (2005), ISSN 1584-4536Schellekens M.P.: The correspondence between partial metrics and semivaluations. Theoret. Comput. Sci. 315, 135–149 (2004)Valero O.: On Banach fixed point theorems for partial metric spaces. Appl. Gen. Top. 6, 229–240 (2005)Waszkiewicz P.: Quantitative continuous domains. Appl. Cat. Struct. 11, 41–67 (2003

Holocentric Chromosomes of Luzula elegans Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability. Copyright (C) 2011 S. Karger AG, Base