Translesion DNA synthesis-assisted non-homologous end-joining of complex double-strand breaks prevents loss of DNA sequences in mammalian cells

Double strand breaks (DSB) are severe DNA lesions, and if not properly repaired, may lead to cell death or cancer. While there is considerable data on the repair of simple DSB (sDSB) by non-homologous end-joining (NHEJ), little is known about the repair of complex DSBs (cDSB), namely breaks with a nearby modification, which precludes ligation without prior processing. To study the mechanism of cDSB repair we developed a plasmid-based shuttle assay for the repair of a defined site-specific cDSB in cultured mammalian cells. Using this assay we found that repair efficiency and accuracy of a cDSB with an abasic site in a 5′ overhang was reduced compared with a sDSB. Translesion DNA synthesis (TLS) across the abasic site located at the break prevented loss of DNA sequences, but was highly mutagenic also at the template base next to the abasic site. Similar to sDSB repair, cDSB repair was totally dependent on XrccIV, and altered in the absence of Ku80. In contrast, Artemis appears to be specifically involved in cDSB repair. These results may indicate that mammalian cells have a damage control strategy, whereby severe deletions are prevented at the expense of the less deleterious point mutations during NHEJ

Exact Analytic Solution for the Rotation of a Rigid Body having Spherical Ellipsoid of Inertia and Subjected to a Constant Torque

The exact analytic solution is introduced for the rotational motion of a rigid body having three equal principal moments of inertia and subjected to an external torque vector which is constant for an observer fixed with the body, and to arbitrary initial angular velocity. In the paper a parametrization of the rotation by three complex numbers is used. In particular, the rows of the rotation matrix are seen as elements of the unit sphere and projected, by stereographic projection, onto points on the complex plane. In this representation, the kinematic differential equation reduces to an equation of Riccati type, which is solved through appropriate choices of substitutions, thereby yielding an analytic solution in terms of confluent hypergeometric functions. The rotation matrix is recovered from the three complex rotation variables by inverse stereographic map. The results of a numerical experiment confirming the exactness of the analytic solution are reported. The newly found analytic solution is valid for any motion time length and rotation amplitude. The present paper adds a further element to the small set of special cases for which an exact solution of the rotational motion of a rigid body exists.Comment: "Errata Corridge Postprint" In particular: typos present in Eq. 28 of the Journal version are HERE correcte

Adjustment to colostomy: stoma acceptance, stoma care self-efficacy and interpersonal relationships

‘The definitive version is available at www.blackwell-synergy.com.’ Copyright Blackwell Publishing. DOI: 10.1111/j.1365-2648.2007.04446.xThis paper is a report of a study to examine adjustment and its relationship with stoma acceptance and social interaction, and the link between stoma care self-efficacy and adjustment in the presence of acceptance and social interactions.Peer reviewe

Exact Analytic Solutions for the Rotation of an Axially Symmetric Rigid Body Subjected to a Constant Torque

New exact analytic solutions are introduced for the rotational motion of a rigid body having two equal principal moments of inertia and subjected to an external torque which is constant in magnitude. In particular, the solutions are obtained for the following cases: (1) Torque parallel to the symmetry axis and arbitrary initial angular velocity; (2) Torque perpendicular to the symmetry axis and such that the torque is rotating at a constant rate about the symmetry axis, and arbitrary initial angular velocity; (3) Torque and initial angular velocity perpendicular to the symmetry axis, with the torque being fixed with the body. In addition to the solutions for these three forced cases, an original solution is introduced for the case of torque-free motion, which is simpler than the classical solution as regards its derivation and uses the rotation matrix in order to describe the body orientation. This paper builds upon the recently discovered exact solution for the motion of a rigid body with a spherical ellipsoid of inertia. In particular, by following Hestenes' theory, the rotational motion of an axially symmetric rigid body is seen at any instant in time as the combination of the motion of a "virtual" spherical body with respect to the inertial frame and the motion of the axially symmetric body with respect to this "virtual" body. The kinematic solutions are presented in terms of the rotation matrix. The newly found exact analytic solutions are valid for any motion time length and rotation amplitude. The present paper adds further elements to the small set of special cases for which an exact solution of the rotational motion of a rigid body exists.Comment: "Errata Corridge Postprint" version of the journal paper. The following typos present in the Journal version are HERE corrected: 1) Definition of \beta, before Eq. 18; 2) sign in the statement of Theorem 3; 3) Sign in Eq. 53; 4)Item r_0 in Eq. 58; 5) Item R_{SN}(0) in Eq. 6

HUBUNGAN PENINGKATAN BERAT BADAN FE4NGAN KONVERSI SPUTUM PADA PASIEN TUBERKULOSIS DI RSUDZA BANDA ACEH

ABSTRAKKonversi sputum pada fase awal pengobatan merupakan salah satu indikator awal keberhasilan terapi obat anti tuberkulosis (OAT). Nutrisi merupakan faktor penting yang juga mempengaruhi kesembuhan pasien tuberkulosis Penelitian ini bertujuan untuk mengetahui hubungan peningkatan berat badan dengan konversi sputum setelah fase awal pada pasien TB di Rumah Sakit Umum dr. Zainoel Abidin Banda Aceh (RSUDZA). Jenis penelitian yang digunakan adalah Cross sectional. Subjek penelitian terdiri atas 92 pasien tuberkulosis di poliklinik DOTS RSUDZA Banda Aceh yang diperoleh dengan metode total sampling terhitung dari Januari sampai dengan Desember 2013. Hasil penelitian dianalisis menggunakan uji statistik Fisher dengan Confident interval 95%. Hasil uji statistik menunjukkan p = 0,107 (p > 0,05) yang menunjukkan bahwa tidak ada hubungan antara peningkatan berat badan dengan konversi sputum pada penderita tuberkulosis yang telah mendapatkan OAT fase awal. Diharapkan adanya penelitian yang lebih lanjut mengenai hubungan nutrisi dengan konversi sputum dengan jumlah sampel yang lebih besar dan desain penelitian yang lebih baik. Kata Kunci : Tuberkulosis, Konversi sputum, Berat badan ABSTRACTSputum conversion at the initial phase of treatment is one of the early indicators of the success of anti-tuberculosis drug therapy (OAT). Nutrition is an important factor that also effects the recovery of tuberculosis patients The aim of this study was to determine the relationship of weight gain and sputum conversion after the initial phase of TB patients at the General Hospital dr. Zainoel Abidin Banda Aceh (RSUDZA). This research was cross sectional study. Subjects consisted of 92 outpatient DOTS tuberculosis in RSUDZA Banda Aceh obtained with total sampling method starting from January to December 2013. Results were analyzed using Fisher test with 95% confident interval. Statistical test results p= 0,107 (p > 0,05) that showed there is no association between increased weight to conversion of sputum in patients with tuberculosis who have earned OAT initial phase, It is expected that the presence of further reaserh on the relationship of nutrition with sputum convertion with a larger number of sampel and design better research. Keywords: Tuberculosis, Sputum conversion, Weight los

Temperature-dependent Raman study of CeFeAsO0.9F0.1 Superconductor: Crystal field excitations, phonons and their coupling

We report temperature-dependent Raman spectra of CeFeAsO0.9F0.1 from 4 K to 300 K in spectral range of 60 to 1800 cm-1 and interpret them using estimates of phonon frequencies obtained from first-principles density functional calculations. We find evidence for a strong coupling between the phonons and crystal field excitations; in particular Ce3+ crystal field excitation at 432 cm-1 couples strongly with Eg oxygen vibration at 389 cm-1 . Below the superconducting transition temperature, the phonon mode near 280 cm-1 shows softening, signaling its coupling with the superconducting gap. The ratio of the superconducting gap to Tc thus estimated to be ~ 10 suggests CeFeAsO0.9F0.1 as a strong coupling superconductor. In addition, two high frequency modes observed at 1342 cm-1 and 1600 cm-

International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor–Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome

Objective: Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor–associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS). Methods: PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de‐identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment. Results: A total of 134 patients were analyzed: FMF (n = 49), TRAPS (n = 47), and MKD/HIDS (n = 38). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute‐phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8‐year delay in FMF patients. An equal proportion of TRAPS patients first received anti–interleukin‐1 (anti‐IL‐1) and anti–tumor necrosis factor (anti‐TNF) biologic agents, whereas IL‐1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti‐TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P = 0.03 and P < 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts. Conclusion: Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real‐world treatment assessment supports the need for further refinement of treatment practices

Familial Mediterranean Fever and Hyperimmunoglobulinemia D syndrome: two diseases with distinct clinical, serologic, and genetic features

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Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.National Institutes of Health (U.S.) (Award 1R25-MH092912-01)National Institute of Mental Health (U.S.) (Grant R01- MH102441-01)National Institutes of Health (U.S.) (Award DP2- DK-102256-01