SUMO Modification Regulates BLM and RAD51 Interaction at Damaged Replication Forks

The gene mutated in Bloom's syndrome, BLM, is important in the repair of damaged replication forks, and it has both pro- and anti-recombinogenic roles in homologous recombination (HR). At damaged forks, BLM interacts with RAD51 recombinase, the essential enzyme in HR that catalyzes homology-dependent strand invasion. We have previously shown that defects in BLM modification by the small ubiquitin-related modifier (SUMO) cause increased γ-H2AX foci. Because the increased γ-H2AX could result from defective repair of spontaneous DNA damage, we hypothesized that SUMO modification regulates BLM's function in HR repair at damaged forks. To test this hypothesis, we treated cells that stably expressed a normal BLM (BLM+) or a SUMO-mutant BLM (SM-BLM) with hydroxyurea (HU) and examined the effects of stalled replication forks on RAD51 and its DNA repair functions. HU treatment generated excess γ-H2AX in SM-BLM compared to BLM+ cells, consistent with a defect in replication-fork repair. SM-BLM cells accumulated increased numbers of DNA breaks and were hypersensitive to DNA damage. Importantly, HU treatment failed to induce sister-chromatid exchanges in SM-BLM cells compared to BLM+ cells, indicating a specific defect in HR repair and suggesting that RAD51 function could be compromised. Consistent with this hypothesis, RAD51 localization to HU-induced repair foci was impaired in SM-BLM cells. These data suggested that RAD51 might interact noncovalently with SUMO. We found that in vitro RAD51 interacts noncovalently with SUMO and that it interacts more efficiently with SUMO-modified BLM compared to unmodified BLM. These data suggest that SUMOylation controls the switch between BLM's pro- and anti-recombinogenic roles in HR. In the absence of BLM SUMOylation, BLM perturbs RAD51 localization at damaged replication forks and inhibits fork repair by HR. Conversely, BLM SUMOylation relieves its inhibitory effects on HR, and it promotes RAD51 function.</p

SUMO Modification Regulates BLM and RAD51 Interaction at Damaged Replication Forks

SUMO modification of BLM controls the switch between BLM's pro- and anti-recombinogenic roles in homologous recombination following DNA damage during replication

The immune response after hypoxia-ischemia in a mouse model of preterm brain injury

Background: Preterm brain injury consists primarily of periventricular leukomalacia accompanied by elements of gray-matter injury, and these injuries are associated with cerebral palsy and cognitive impairments. Inflammation is believed to be an important contributing factor to these injuries. The aim of this study was to examine the immune response in a postnatal day (PND) 5 mouse model of preterm brain injury induced by hypoxia-ischemia (HI) that is characterized by focal white and gray-matter injury. Methods: C57Bl/6 mice at PND 5 were subjected to unilateral HI induced by left carotid artery ligation and subsequent exposure to 10% O2 for 50 minutes, 70 minutes, or 80 minutes. At seven days post-HI, the white/gray-matter injury was examined. The immune responses in the brain after HI were examined at different time points after HI using RT-PCR and immunohistochemical staining. Results: HI for 70 minutes in PND 5 mice induced local white-matter injury with focal cortical injury and hippocampal atrophy, features that are similar to those seen in preterm brain injury in human infants. HI for 50 minutes resulted in a small percentage of animals being injured, and HI for 80 minutes produced extensive infarction in multiple brain areas. Various immune responses, including changes in transcription factors and cytokines that are associated with a T-helper (Th)1/Th17-type response, an increased number of CD4+ T-cells, and elevated levels of triggering receptor expressed on myeloid cells 2 (TREM-2) and its adaptor protein DNAX activation protein of 12 kDa (DAP12) were observed using the HI 70 minute preterm brain injury model. Conclusions: We have established a reproducible model of HI in PND 5 mice that produces consistent local white/gray-matter brain damage that is relevant to preterm brain injury in human infants. This model provides a useful tool for studying preterm brain injury. Both innate and adaptive immune responses are observed after HI, and these show a strong pro-inflammatory Th1/Th17-type bias. Such findings provide a critical foundation for future studies on the mechanism of preterm brain injury and suggest that blocking the Th1/Th17-type immune response might provide neuroprotection after preterm brain injury

Experimental study on thermochemical composite flooding mechanism of extra heavy oil reservoirs with erosion channels

During the steam flooding of extra heavy oil, expansion of steam chamber is difficult and erosion channels appear, which is different from conventional heavy oil. The thermochemical composite system composed of steam, foam and viscosity reducer can effectively improve the development effect of extra heavy oil reservoirs. However, during the thermochemical composite flooding, the rheological characteristics of extra heavy oil and the influence of erosion channels on oil displacement mechanism are not yet researched. Taking the extra heavy oil reservoir in Block X of the Chunfeng Oilfield as an example, experimental research on the rheological properties and thermochemical composite flooding of extra heavy oil model with erosion channel is conducted. Firstly, the influence of thermochemical composite system on the rheological properties of extra heavy oil is evaluated. Then, a one-dimensional (1D) sand-pack model with erosion channel is used to conduct thermochemical composite flooding experiments, comparing the recovery of steam flooding, foam assisted steam flooding, viscosity reducer assisted steam flooding, and composite flooding (foam and viscosity reducer assisted steam flooding). Finally, a two-dimensional (2D) sand-pack model with erosion channel is used to conduct thermochemical composite flooding experiments, comparing the recovery of viscosity reducer assisted flooding and composite flooding. The results show that viscosity reducer reduces the viscosity of extra heavy oil greatly, and the extra heavy oil is not sensitive to the change of temperature after viscosity reduction. When the concentration of viscosity reducer is 0.4% or more, good viscosity reduction effect can be achieved at different oil-water ratio. In the 1D sand-pack model experiments, compared to steam flooding, foam assisted steam flooding, viscosity reducer assisted steam flooding, and composite flooding, the recovery increased by 4.38%, 17.38%, and 30.46%, respectively. In the 2D sand-pack model experiments, compared to steam flooding, the viscosity reducer assisted steam flooding and composite flooding increase the oil recovery by 12.49% and 16.61%, respectively. The thermochemical composite flooding of extra heavy oil is dominated by erosion, supplemented by displacement. There is a synergistic effect between chemicals in the process of composite flooding. At the same time, the purpose of “enhanced erosion and expanded sweep” is achieved

An Electrostatic Self-Excited Resonator with Pre-Tension/Pre-Compression Constraint for Active Rotation Control

We report a novel electrostatic self-excited resonator driven by DC voltage that achieves variable velocity-position characteristics via applying the pre-tension/pre-compression constraint. The resonator consists of a simply supported micro-beam, two plate electrodes, and two adjustable constraint bases, and it can be under pre-compression or pre-tension constraint by adjusting the distance L between two constraint bases (when beam length l &gt; L, the resonator is under pre-compression and when l &lt; L, it is under pre-tension). The oscillating velocity of the beam reaches the maximum value in the position around electrodes under the pre-compression constraint and reaches the maximum value in the middle position between two electrodes under the pre-tension condition. By changing the constraint of the microbeam, the position of the maximum velocity output of the oscillating beam can be controlled. The electrostatic self-excited resonator with a simple constraint structure under DC voltage has great potential in the field of propulsion of micro-robots, such as active rotation control of flapping wings

Unmet needs for rehabilitation service of middle-aged and older adult residents in Chengdu, Sichuan, China: A cross-sectional study

Abstract To investigate the unmet needs for rehabilitation services among middle-aged and older adults in Chengdu, Sichuan, China, and identify the associated factors. This cross-sectional study was conducted on middle-aged and older adults in Chengdu, Sichuan, China, between 2015 and 2016. The questionnaire included demographic data and questions about rehabilitation needs. Multivariable logistic regression analysis was used to identify the associated factors of unmet needs for rehabilitation services. Among 663 participants, 91.70% needed medical rehabilitation (608/663), 26.55% of who need auxiliary equipment (176/663), 77.07% of who need daily care and social participation (511/663), and 79.34% of who need recreational therapy activities (526/663), while < 30% required auxiliary equipment. Multivariate logistic regression analysis showed that residents who were married, had annual income < CNY 80,000, had no medical insurance, had three or more health problems, were aged ≥ 60, and the disability status were independently associated with unmet needs for rehabilitation services (all P < 0.05). Marital status, annual income, medical insurance, health problems, and disability might be factors independently associated with the unmet needs for rehabilitation services. Attention should be paid to the financial burden of the population on rehabilitation services, and in addition to the disabled, the slow patients should also be given priority