Deficiency in interferon type 1 receptor improves definitive erythropoiesis in Klf1 null mice

A key regulatory gene in definitive erythropoiesis is the transcription factor Krüppel-like factor 1 (Klf1). Klf1 null mice die in utero by day 15.5 (E15.5) due to impaired definitive erythropoiesis and severe anemia. Definitive erythropoiesis takes place in erythroblastic islands in mammals. Erythroblastic islands are formed by a central macrophage (Central Macrophage of Erythroblastic Island, CMEI) surrounded by maturating erythroblasts. Interferon-β (IFN-β) is activated in the fetal liver’s CMEI of Klf1 null mice. The inhibitory effect of IFN-β on erythropoiesis is known and, therefore, we speculated that IFN-β could have contributed to the impairment of definitive erythropoiesis in Klf1 knockout (KO) mice fetal liver. To validate this hypothesis, in this work we determined whether the inactivation of type I interferon receptor (Ifnar1) would ameliorate the phenotype of Klf1 KO mice by improving the lethal anemia. Our results show a prolonged survival of Klf1/Ifnar1 double KO embryos, with an improvement of the definitive erythropoiesis and erythroblast enucleation, together with a longer lifespan of CMEI in the fetal liver and also a restoration of the apoptotic program. Our data indicate that the cytotoxic effect of IFN-β activation in CMEI contribute to the impairment of definitive erythropoiesis associated with Klf1 deprivation

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Biological assessment of porous-implant hydroxyapatite combined with periosteal grafting in maxillary defects

Purpose: To investigate the use of porous hydroxyapatite (HA) combined with periosteal graft to repair an induced maxillary bone defect. Materials and Methods: A defect was produced in the premaxillary bone of rats. Four groups were used: 1) those treated with the mucoperiosteal graft from the premaxilla; 2) those treated with HA combined with mucoperiosteal graft from the premaxilla; 3) those treated with HA combined with periosteal graft from the femur; and 4) those treated with periosteal graft from the femur. Results: The radiographic aspects from all groups showed no signs of bone formation after 2 weeks. After 16 weeks, there was evidence of points of radiolucency inside the HA implants. Cell proliferation occurred from the periosteum covering the defect. Bone tissue grew from the defect margin to inside the defect in all cases. Mature bone was seen around the HA implants after 8 and 16 weeks. Conclusion: The periosteal graft provides satisfactory support to the HA implant, allowing the growth of new bone. (C) 2007 American Association of Oral and Maxillofacial Surgeons.65584785

Efeitos do alcoolismo e da desintoxicação alcoólica sobre o reparo e biomecânica óssea Effects of alcoholism and alcoholic detoxication on the repair and biomechanics of bone

OBJETIVO: Avaliar os efeitos do consumo crônico de etanol e da desintoxicação alcoólica sobre a resistência mecânica do osso e neoformação óssea junto a implantes de hidroxiapatita densa (HAD) realizados em ratos. MÉTODOS: Foram utilizados 15 ratos divididos em três grupos, sendo controle (CT), alcoolista crônico (AC) e desintoxicado (DE). Após quatro semanas, foi realizada implantação de HAD na tíbia e produzida falha no osso parietal, em seguida o grupo AC continuaram a consumir etanol e o grupo DE iniciaram a desintoxicação. Ao completar 13 semanas os animais sofreram eutanásia, os ossos foram coletados para o processamento histomorfométrico e os fêmures encaminhados ao teste mecânico de resistência. RESULTADOS: Os animais do grupo AC apresentaram menores valores de neoformação óssea, de calcemia e resistência mecânica, quando comparado aos grupos CT e DE. Os animais dos grupos DE apresentaram valores superiores em todas as variáveis avaliadas em relação ao grupo AC. CONCLUSÃO: O consumo de etanol interferiu na osteogênese ao redor de implante de HAD, nos níveis de cálcio e na resistência mecânica óssea. A desintoxicação alcoólica se mostrou eficaz, pois aumentou à osteogênese e osseointegração da HAD, a calcemia e resistência mecânica óssea. Nivel de Evidência I, estudo terapeutico.<br>OBJECTIVE: To evaluate the effects of chronic ethanol consumption and alcohol detoxication on the mechanical resistance of bone and bone neoformation around dense hydroxyapatite implants (DHA) in rats. METHODS: Fifteen rats were separated into three groups: (1) control group (CT); (2) chronic alcoholic (CA), and (3) disintoxicated (DI). After four weeks, a DHA was implanted in the right tibia of the animals, and the CA group continued consuming ethanol, while the DI group started detoxication. The solid and liquid feeding of the animals was recorded, and a new alcohol dilution was effected every 48 hours. After 13 weeks, the animals were euthanized and their biological material was collected. RESULTS: Bone tissue was found around DHA in all the animals. Group CA showed less bone neoformation, lower levels of ionic and total calcium when compared to the animals of the CT and DI groups. The DI animals showed higher values in all the variables in relation to the CA group. CONCLUSION: Ethanol consumption interfered in osteogenesis around the DHA implants, and in calcium levels and mechanical bone resistance. Alcohol detoxication was effective, as it increased osteogenesis, DHA osteointegration, calcemia, and mechanical resistance of the bone. Level of Evidence: Level I, therapeutic studie