AP endonuclease 1 prevents trinucleotide repeat expansion via a novel mechanism during base excision repair

Base excision repair (BER) of an oxidized base within a trinucleotide repeat (TNR) tract can lead to TNR expansions that are associated with over 40 human neurodegenerative diseases. This occurs as a result of DNA secondary structures such as hairpins formed during repair. We have previously shown that BER in a TNR hairpin loop can lead to removal of the hairpin, attenuating or preventing TNR expansions. Here, we further provide the first evidence that AP endonuclease 1 (APE1) prevented TNR expansions via its 3′-5′ exonuclease activity and stimulatory effect on DNA ligation during BER in a hairpin loop. Coordinating with flap endonuclease 1, the APE1 3′-5′ exonuclease activity cleaves the annealed upstream 3′-flap of a double-flap intermediate resulting from 5′-incision of an abasic site in the hairpin loop. Furthermore, APE1 stimulated DNA ligase I to resolve a long double-flap intermediate, thereby promoting hairpin removal and preventing TNR expansions

Evidence for spin-triplet superconducting correlations in metal-oxide heterostructures with non-collinear magnetization

Heterostructures composed of ferromagnetic La0.7Sr0.3MnO3, ferromagnetic SrRuO3, and superconducting YBa2Cu3Ox were studied experimentally. Structures of composition Au/La0.7Sr0.3MnO3/SrRuO3/YBa2Cu3Ox were prepared by pulsed laser deposition, and their high quality was confirmed by X-ray diffraction and reflectometry. A non-collinear magnetic state of the heterostructures was revealed by means of SQUID magnetometry and polarized neutron reflectometry. We have further observed superconducting currents in mesa-structures fabricated by deposition of a second superconducting Nb layer on top of the heterostructure, followed by patterning with photolithography and ion-beam etching. Josephson effects observed in these mesa-structures can be explained by the penetration of a triplet component of the superconducting order parameter into the magnetic layers.Comment: 10 pages, 6 figure

X-ray absorption study of the ferromagnetic Cu moment at the YBa2Cu3O7/La2/3Ca1/3MnO3\mathbf{{YBa_2Cu_3O_7}/{La_{2/3}Ca_{1/3}MnO_3}} interface and the variation of its exchange interaction with the Mn moment

With x-ray absorption spectroscopy and polarized neutron reflectometry we studied how the magnetic proximity effect at the interface between the cuprate high-$T_C$ superconductor $\mathrm{YBa_2Cu_3O_7}$ (YBCO) and the ferromagnet $\mathrm{La_{2/3}Ca_{1/3}MnO_3}$ (LCMO) is related to the electronic and magnetic properties of the LCMO layers. In particular, we explored how the magnitude of the ferromagnetic Cu moment on the YBCO side depends on the strength of the antiferromagnetic (AF) exchange coupling with the Mn moment on the LCMO side. We found that the Cu moment remains sizeable if the AF coupling with the Mn moments is strongly reduced or even entirely suppressed. The ferromagnetic order of the Cu moments thus seems to be intrinsic to the interfacial CuO$_2$ planes and related to a weakly ferromagnetic intra-planar exchange interaction. The latter is discussed in terms of the partial occupation of the Cu $3d_{3z^2-r^2}$ orbitals, which occurs in the context of the so-called orbital reconstruction of the interfacial Cu ions

DNA Base Excision Repair Modulates DNA Repeat Instability and Non-B Form DNA Structures

The human genome is constantly attacked by endogenous and exogenous sources of DNA damage that generates DNA base lesions and strand breaks leading to genome instability, cell death, and diseases. To combat these adverse effects, cells have evolved a robust DNA repair mechanism called “the DNA base excision repair (BER),” which efficiently removes DNA lesions maintaining genome stability. However, its underlying molecular mechanisms remain to be elucidated. In my dissertation research, I explored the molecular mechanism by which BER modulates trinucleotide repeats (TNR) by processing non-B form structures such as hairpins and R-loops through the coordination among BER enzymes and cofactors and the proteins from other DNA repair pathways. For the first time, we discovered that Fanconi anemia-associated nuclease 1 (FAN1) coordinated with a key BER enzyme, flap endonuclease 1 (FEN1), to prevent repeat expansion by promoting CAG repeat deletion during BER of oxidative DNA damage. We further demonstrated that the BER cofactor, PCNA/ubPCNA, coordinated with FAN1 to attenuate CAG repeat expansion during BER in a CAG repeat hairpin. Exploring the mechanisms by which BER regulates TNR instability by processing bulky non-B form structures, R-loops. We found that an abasic lesion on the non-template strand of a CAG repeat R-loop was incised by AP endonuclease 1 (APE1), converting the R-loop into a double-flap intermediate containing an RNA:DNA hybrid. This inhibited DNA polymerase β (pol β) DNA synthesis and stimulated FEN1 cleavage of the repeats leading to repeat deletion. We showed that FEN1 partially cleaved the RNA strand on a CAG repeat R-loop to facilitate pol β skip-over of a hairpin leading to repeat deletion. We further identified a new role of FEN1 of resolving R-loops through the BER pathway. We found that FEN1 efficiently cleaved RNA during the processing of DNA lagging strand and R-loops and demonstrated that FEN1 also used its flap tracking to track down to the DNA region to make a cleavage removing the RNA leading to the lagging strand maturation and R-loop resolution via BER. Our study provides new insights into the molecular mechanism by which BER maintains genome stability and integrity

X-ray absorption spectroscopy study of the electronic and magnetic proximity effects in YBa2Cu3O7/La2/3Ca1/3MnO3{\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{7}/{\mathrm{La}}_{2/3}{\mathrm{Ca}}_{1/3}{\mathrm{MnO}}_{3} and {\mathrm{La}}_{2-{}x}{\mathrm{Sr}}_{x}{\mathrm{CuO}}_{4}/{\mathrm{La}}_{2/3}{\mathrm{Ca}}_{1/3}{\mathrm{MnO}}_{3} multilayers

With x-ray absorption spectroscopy we investigated the orbital reconstruction and the induced ferromagnetic moment of the interfacial Cu atoms in YBa2Cu3O7/La2/3Ca1/3MnO3 (YBCO/LCMO) and La2−xSrxCuO4/La2/3Ca1/3MnO3 (LSCO/LCMO) multilayers. We demonstrate that these electronic and magnetic proximity effects are coupled and are common to these cuprate/manganite multilayers. Moreover, we show that they are closely linked to a specific interface termination with a direct Cu-O-Mn bond. We furthermore show that the intrinsic hole doping of the cuprate layers and the local strain due to the lattice mismatch between the cuprate and manganite layers are not of primary importance. These findings underline the central role of the covalent bonding at the cuprate/manganite interface in defining the spin-electronic properties

Magnetic Proximity Effect in YBa₂Cu₃O₇/La_2/3Ca_1/3MnO₃ and YBa₂Cu₃O₇/LaMnO₃₊ Superlattices

Using neutron reflectometry and resonant x-ray techniques we studied the magnetic proximity effect (MPE) in superlattices composed of superconducting YBa₂Cu₃O₇ and ferromagnetic-metallic La0.67Ca0.33MnO₃ or ferromagnetic-insulating LaMnO₃₊. We find that the MPE strongly depends on the electronic state of the manganite layers, being pronounced for the ferromagnetic-metallic La0.67Ca0.33MnO₃ and almost absent for ferromagnetic-insulating LaMnO₃₊. We also detail the change of the magnetic depth profile due to the MPE and provide evidence for its intrinsic nature

Preclinical evaluation of collagen type I scaffolds, including gelatin-collagen microparticles and loaded with a hydroglycolic Calendula officinalis extract in a lagomorph model of full-thickness skin wound

Previously, we have developed collagen type I scaffolds including microparticles of gelatin-collagen type I (SGC) that are able to control the release of a hydroglycolic extract of the Calendula officinalis flower. The main goal of the present work was to carry out the preclinical evaluation of SGC alone or loaded with the C. officinalis extract (SGC-E) in a lagomorph model of full-thickness skin wound. A total of 39 rabbits were distributed in three groups, of 13 animals each. The first group was used to compare wound healing by secondary intention (control) with wound healing observed when wounds were grafted with SGC alone. Comparison of control wounds with wounds grafted with SGC-E was performed in the second group, and comparison of wounds grafted with SGC with wounds grafted with SGC-E was performed in the third group. Clinical follow-ups were carried in all animals after surgery, and histological and histomorphometric analyses were performed on tissues taken from the healed area and healthy surrounding tissue. Histological and histomorphometric results indicate that grafting of SGC alone favors wound healing and brings a better clinical outcome than grafting SGC-E. In vitro collagenase digestion data suggested that the association of the C. officinalis extract to SGC increased the SGC-E cross-linking, making it difficult to degrade and affecting its biocompatibility.http://unidadinvestigacion.usta.edu.c

ENTRE LAÇOS, CACHOS E TRANÇAS: O EMPODERAMENTO DAS MENINAS NEGRAS ATRAVÉS DA LITERATURA

Neste artigo reunimos quatro obras da literatura infanto-juvenil que têm em comum meninas negras, com cabelos crespos, como protagonistas. Essas meninas são conscientes e orgulhosas de sua cultura e de seu pertencimento. Nosso objetivo é demonstrar como as autoras dessas obras utilizam essas narrativas para promover e valorizar a cultura africana e afro-brasileira. Acreditamos que trabalhar com essas literaturas em sala de aula permite que as crianças tenham contato com literaturas desconhecidas ou marginalizadas pelos cânones oficializados. Possibilita ainda a construção afirmativa da identidade racial e a valorização da contribuição cultural africana e afrodescendente. Também reforça a beleza negra, uma vez que tais textos discutem não só aspectos culturais e históricos brasileiros e africanos, mas também tratam de questões ligadas à imagem e à autoestima, que são muito comuns ao cotidiano de crianças negras, o que possibilita uma visão crítica a respeito da diversidade cultural e racial de nosso contexto

Sertolinoma maligno en un canino criptórquido con hiperplasia prostática benigna quística: reporte de caso

The case of an 8-year-old Beagle canine, who was attended at the ASMEVET veterinary hospital in the city of Tunja, Colombia, is presented. The owner reported that in recent months he has been losing hair, has increased water consumption, has not been neutered, and more recently is depressed, lack of appetite and with signs of dysuria. On physical examination, generalized alopecia and gynecomastia were observed, and the prostate was enlarged and asymmetric. Transabdominal ultrasonography revealed an enlarged prostate, with heteroechogenic parenchyma and microcysts, and the testicles were retained at the level of the apex of the bladder. Enrofloxacin was administered for 5 days, and meloxicam for 4 days, and then the patient underwent celiotomy to remove the retained testicles. The histopathological study reported malignant sertolinoma. Fine needle aspiration of prostate tissue revealed cells consistent with benign prostatic hyperplasia. After 90 days of bilateral orchiectomy, remission of alopecia was observed and ultrasound evaluation showed a decrease in the size of the prostate.Se presenta el caso de un canino de 8 años, raza Beagle, que fue atendido en el hospital veterinario ASMEVET de la ciudad de Tunja, Colombia. El propietario informó que en los últimos meses ha estado perdiendo, ha aumentado el consumo de agua, no ha sido castrado, y que recientemente se encuentra deprimido, inapetente y con signos de disuria. Al examen físico se observa alopecia generalizada y ginecomastia, y la próstata se encuentra aumentada de tamaño y asimétrica. La ultrasonografía transabdominal revela próstata aumentada de tamaño, con parénquima heteroecogénico y microquistes, y los testículos se encontraban retenidos a la altura del vértice de la vejiga. Se administró enrofloxacina por 5 días, y meloxicam por 4 días, y luego se sometió a celiotomía para extirpar los testículos retenidos. El estudio histopatológico reportó sertolinoma maligno. La muestra del tejido prostático mediante aspiración con aguja fina reveló células compatibles con hiperplasia prostática benigna. Después de los 90 días de la orquiectomía bilateral se observó la remisión de la alopecia y la ecografía control mostró disminución del tamaño de la próstata