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

Interactions between thresholds and spatial discretizations of snow: insights from estimates of wolverine denning habitat in the Colorado Rocky Mountains

Thresholds can be used to interpret environmental data in a way that is easily communicated and useful for decision-making purposes. However, thresholds are often developed for specific data products and time periods, changing findings when the same threshold is applied to datasets or periods with different characteristics. Here, we test the impact of different spatial discretizations of snow on annual estimates of wolverine denning opportunities in the Colorado Rocky Mountains, defined using a snow water equivalent (SWE) threshold (0.20 m) and threshold date (15 May) from previous habitat assessments. Annual potential wolverine denning area (PWDA) was thresholded from a 36-year (1985–2020) snow reanalysis model with three different spatial discretizations: (1) 480 m grid cells (D480), (2) 90 m grid cells (D90), and (3) 480 m grid cells with implicit representations of subgrid snow spatial heterogeneity (S480). Relative to the D480 and S480 discretizations, D90 resolved shallower snow deposits on slopes between 3050 and 3350 m elevation, decreasing PWDA by 10 %, on average. In years with warmer and/or drier winters, S480 discretizations with subgrid representations of snow heterogeneity increased PWDA, even within grid cells where mean 15 May SWE was less than the SWE threshold. These simulations increased PWDA by upwards of 30 % in low-snow years, as compared to the D480 and D90 simulations without subgrid snow heterogeneity. Despite PWDA sensitivity to different snow spatial discretizations, PWDA was controlled more by annual variations in winter precipitation and temperature. However, small changes to the SWE threshold (±0.07 m) and threshold date (±2 weeks) also affected PWDA by as much as 82 %. Across these threshold ranges, PWDA was approximately 18 % more sensitive to the SWE threshold than the threshold date. However, the sensitivity to the threshold date was larger in years with late spring snowfall, when PWDA depended on whether modeled SWE was thresholded before, during, or after spring snow accumulation. Our results demonstrate that snow thresholds are useful but may not always provide a complete picture of the annual variability in snow-adapted wildlife denning opportunities. Studies thresholding spatiotemporal datasets could be improved by including (1) information about the fidelity of thresholds across multiple spatial discretizations and (2) uncertainties related to ranges of realistic thresholds.</p

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

Familial Mediterranean fever, Inflammation and Nephrotic Syndrome: Fibrillary Glomerulopathy and the M680I Missense Mutation

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by inflammatory serositis (fever, peritonitis, synovitis and pleuritis). The gene locus responsible for FMF was identified in 1992 and localized to the short arm of chromosome 16. In 1997, a specific FMF gene locus, MEFV, was discovered to encode for a protein, pyrin that mediates inflammation. To date, more than forty missense mutations are known to exist. The diversity of mutations identified has provided insight into the variability of clinical presentation and disease progression. CASE REPORT: We report an individual heterozygous for the M680I gene mutation with a clinical diagnosis of FMF using the Tel-Hashomer criteria. Subsequently, the patient developed nephrotic syndrome with biopsy-confirmed fibrillary glomerulonephritis (FGN). Further diagnostic studies were unremarkable with clinical workup negative for amyloidosis or other secondary causes of nephrotic syndrome. DISCUSSION: Individuals with FMF are at greater risk for developing nephrotic syndrome. The most serious etiology is amyloidosis (AA variant) with renal involvement, ultimately progressing to end-stage renal disease. Other known renal diseases in the FMF population include IgA nephropathy, IgM nephropathy, Henoch-Schönlein purpura as well as polyarteritis nodosa. CONCLUSION: To our knowledge, this is the first association between FMF and the M680I mutation later complicated by nephrotic syndrome and fibrillary glomerulonephritis

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