Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy

The condensin protein complex compacts chromatin during mitosis using its DNA-loop extrusion activity. Previous studies proposed scrunching and loop-capture models as molecular mechanisms for the loop extrusion process, both of which assume the binding of double-strand (ds) DNA to the hinge domain formed at the interface of the condensin subunits Smc2 and Smc4. However, how the hinge domain contacts dsDNA has remained unknown. Here, we conducted atomic force microscopy imaging of the budding yeast condensin holo-complex and used this data as basis for coarse-grained molecular dynamics simulations to model the hinge structure in a transient open conformation. We then simulated the dsDNA binding to open and closed hinge conformations, predicting that dsDNA binds to the outside surface when closed and to the outside and inside surfaces when open. Our simulations also suggested that the hinge can close around dsDNA bound to the inside surface. Based on these simulation results, we speculate that the conformational change of the hinge domain might be essential for the dsDNA binding regulation and play roles in condensin-mediated DNA-loop extrusion

Extracting and Mathematical Identifying Form of Stationary Noise in X-ray Images

Image noise may prevent proper diagnostic X-ray imaging. This study is aimed at developing new noise rejection methods using a mathematical model that describes the form of X-ray image noise. Stationary noise is one type of noise found in X-ray images. Stationary noise is nonstochastic and appears independent of the radiographic factors. In this paper, we verify methods for identifying stationary noise using a polynomial regression model, and extracting such noise from X-ray images obtained from a CR system. The results of this study demonstrate that stationary noise can be extracted with high precision using a particular low-pass filter frequency. We found that a regression model for greater than second-degree polynomials can be applied for roughly identifying stationary noise. However, the fitting accuracy of the regression curve is not significantly improved in terms of the amount of multiplication required when increasing the degree of the polynomial regression model

Seismic refraction and wide-angle reflection exploration by JARE-43 on Mizuho Plateau, East Antarctica

The 43rd Japanese Antarctic Research Expedition (JARE-43) carried out seismic exploration experiments on Mizuho Plateau,East Antarctica,in the austral summer season of ,2001-2002. The exploration was composed of seven large explosions and 161seismic stations distributed along the 151 km-long seismic line.The first arrival time data are analyzed by a refraction method.It is found that the ice sheet is composed of two layers:the upper layer with P wave velocity of 2.7-2.9 km/s has thickness of 35-45 m,and the lower layer with P wave velocity of 3.7-3.9 km/s continues to the bedrock.Lateral velocity variation in the upper-most crust is revealed:P wave velocity for the upper-most crust in the southern and central parts is 6.1-6.2 km/s and that in the northern part is5.9 km/s. This result implies that the geological boundary observed along the coast in the Lu tzow-Holm Bay and Prince Olav Coast regions possibly continues to the inland area.The S wave velocity is also obtained to be roughly 3.5km/s for the whole upper-most crust.Travel time analysis of two distinct reflection phases shows two horizontal reflecting planes located at 19 and 40km depth; the latter corresponds to the Moho discontinuity

The role of digital rectal examination for diagnosis of acute appendicitis: A systematic review and meta-analysis

Background: Digital rectal examination (DRE) has been traditionally recommendedto evaluate acute appendicitis, although several reports indicate its lack of utility for this diagnosis. No metaanalysis has examined DRE for diagnosis of acute appendicitis. Objectives: To assess the role of DRE for diagnosis of acute appendicitis. Data Sources: Cochrane Library, PubMed, and SCOPUS from the earliest available date of indexing through November 23, 2014, with no language restrictions. Study Selection: Clinical studies assessing DRE as an index test for diagnosis of acute appendicitis. Data Extraction and Synthesis: Two independent reviewers extracted study data and assessed the quality, using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Bivariate random-effects models were used for the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) as point estimates with 95% confidence intervals (CI). Main Outcomes and Measures: The main outcome measure was the diagnostic performance of DRE for diagnosis of acute appendicitis. Results: We identified 19 studies with a total of 7511 patients. The pooled sensitivity and specificity were 0.49 (95% CI 0.42-0.56) and 0.61 (95% CI 0.53-0.67), respectively. The positive and negative likelihood ratios were 1.24 (95% CI 0.97-1.58) and 0.85 (95% CI 0.70-1.02), respectively. The DOR was 1.46 (0.95-2.26). Conclusion and Relevance: Acute appendicitis cannot be ruled in or out through the result of DRE. Reconsideration is needed for the traditional teaching that rectal examination should be performed routinely in all patients with suspected appendicitis

Pyoderma gangrenosum after breast cancer resection: A less-invasive and early treatment using the skin around ulcers

Surgical invasion is a risk factor of pyoderma gangrenosum (PG). A total of 25% of postoperative PG cases were reported to occur after breast surgeries, including bilateral breast reduction and breast reconstruction following cancer resection. Immunosuppressive therapy and less-invasive wound therapy are necessary; however, the complete healing of ulcers takes 5.1 months on average. We herein report a case of skin grafting under a surgical concept of less-invasive and short-term treatment. An 82-year-old woman complained of a high fever and severe pain at her breast wounds after bilateral breast cancer resection. Although we performed emergency debridement surgery to remove the necrotic tissue, suspecting surgical site infection and inflammation, her high fever persisted. She was diagnosed with PG because of the physical findings of characteristic painful, sterile ulcerations, bullae and pustules, and the pathological abundance of neutrophils in the absence of infection and vasculitis. Oral administration of prednisolone 30 mg/day improved the symptoms, and we applied negative-pressure wound therapy (NPWT) from day 16 following debridement surgery. After the gradual reduction of oral steroid intake to 12.5 mg/day, we performed skin grafting surgery. To limit the surgical invasion, we used the surplus skin around the ulcers. Split-thickness mesh skin grafts were fixed by NPWT to avoid the use of tie-over sutures. We achieved short-term treatment of PG with a less-invasive surgical strategy using skin around the ulcers and NPWT

Unexpected Instability of Family of Repeats (FR), the Critical cis-Acting Sequence Required for EBV Latent Infection, in EBV-BAC Systems

A group of repetitive sequences, known as the Family of Repeats (FR), is a critical cis-acting sequence required for EBV latent infection. The FR sequences are heterogeneous among EBV strains, and they are sometimes subject to partial deletion when subcloned in E. coli-based cloning vectors. However, the FR stability in EBV-BAC (bacterial artificial chromosome) system has never been investigated. We found that the full length FR of the Akata strain EBV was not stably maintained in a BAC vector. By contrast, newly obtained BAC clones of the B95-8 strain of EBV stably maintained the full length FR during recombinant virus production and B-cell transformation. Investigation of primary DNA sequences of Akata–derived EBV-BAC clones indicates that the FR instability is most likely due to a putative secondary structure of the FR region. We conclude that the FR instability in EBV-BAC clones can be a pitfall in E. coli-mediated EBV genetics