Three-dimensional binding sites volume assessment during cardiac pacing lead extraction

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

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Physiological Pacing: A New Road to Future

Indian Journal of Clinical Cardiology ◽

10.1177/2632463620978045 ◽

2021 ◽

pp. 263246362097804

Author(s):

Vanita Arora ◽

Pawan Suri

Keyword(s):

Side Effects ◽

Fibrous Tissue ◽

Cardiac Pacing ◽

His Bundle ◽

Anatomy And Physiology ◽

Long Term Follow Up ◽

Pacing Lead ◽

The Right

Anatomy and physiology are the basis of human body functioning and as we have progressed in management of various diseases, we have understood that physiological intervention is always better than an anatomical one. For more than 50 years, a standard approach to permanent cardiac pacing has been an anatomical placement of transvenous pacing lead at the right ventricular apex with a proven benefit of restoring the rhythm. However, the resultant ventricular dyssynchrony on the long-term follow-up in patients requiring more than 40% ventricular pacing led to untoward side effects in the form of heart failure and arrhythmias. To counter such adverse side effects, a need for physiological cardiac pacing wherein the electrical impulse be transmitted directly through the normal conduction system was sought. His bundle pacing (HBP) with an intriguing alternative of left bundle branch pacing (LBBP) is aimed at restoring such physiological activation of ventricles. HBP is safe, efficacious, and feasible; however, localization and placement of a pacing lead at the His bundle is challenging with existing transvenous systems due to its small anatomic size, surrounding fibrous tissue, long-learning curve, and the concern remains about lead dislodgement and progressive electrical block distal to the HBP lead. In this article, we aim to take the reader through the challenging journey of HBP with focus upon the hardware and technique, selective versus nonselective HBP, indications and potential disadvantages, and finally the future prospects.

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Androgen receptor: acting in the three-dimensional chromatin landscape of prostate cancer cells

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci.2010.055 ◽

2011 ◽

Vol 5 (1) ◽

Author(s):

Harri Makkonen ◽

Jorma J. Palvimo

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Binding Sites ◽

Target Genes ◽

Three Dimensional ◽

Regulatory Elements ◽

Gene Promoters ◽

Loop Formation ◽

Prostate Cancer Cells

AbstractAndrogen receptor (AR) acts as a hormone-controlled transcription factor that conveys the messages of both natural and synthetic androgens to the level of genes and gene programs. Defective AR signaling leads to a wide array of androgen insensitivity disorders, and deregulated AR function, in particular overexpression of AR, is involved in the growth and progression of prostate cancer. Classic models of AR action view AR-binding sites as upstream regulatory elements in gene promoters or their proximity. However, recent wider genomic screens indicate that AR target genes are commonly activated through very distal chromatin-binding sites. This highlights the importance of long-range chromatin regulation of transcription by the AR, shifting the focus from the linear gene models to three-dimensional models of AR target genes and gene programs. The capability of AR to regulate promoters from long distances in the chromatin is particularly important when evaluating the role of AR in the regulation of genes in malignant prostate cells that frequently show striking genomic aberrations, especially gene fusions. Therefore, in addition to the mechanisms of DNA loop formation between the enhancer bound ARs and the transcription apparatus at the target core promoter, the mechanisms insulating distally bound ARs from promiscuously making contacts and activating other than their normal target gene promoters are critical for proper physiological regulation and thus currently under intense investigation. This review discusses the current knowledge about the AR action in the context of gene aberrations and the three-dimensional chromatin landscape of prostate cancer cells.

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Determination of the alpha-actinin-binding site on actin filaments by cryoelectron microscopy and image analysis.

The Journal of Cell Biology ◽

10.1083/jcb.126.2.433 ◽

1994 ◽

Vol 126 (2) ◽

pp. 433-443 ◽

Cited By ~ 124

Author(s):

A McGough ◽

M Way ◽

D DeRosier

Keyword(s):

Image Analysis ◽

Smooth Muscle ◽

Binding Sites ◽

Actin Filaments ◽

Three Dimensional ◽

Actin Binding ◽

Dimensional Structure ◽

Outer Face ◽

Actin Binding Domain

The three-dimensional structure of actin filaments decorated with the actin-binding domain of chick smooth muscle alpha-actinin (alpha A1-2) has been determined to 21-A resolution. The shape and location of alpha A1-2 was determined by subtracting maps of F-actin from the reconstruction of decorated filaments. alpha A1-2 resembles a bell that measures approximately 38 A at its base and extends 42 A from its base to its tip. In decorated filaments, the base of alpha A1-2 is centered about the outer face of subdomain 2 of actin and contacts subdomain 1 of two neighboring monomers along the long-pitch (two-start) helical strands. Using the atomic model of F-actin (Lorenz, M., D. Popp, and K. C. Holmes. 1993. J. Mol. Biol. 234:826-836.), we have been able to test directly the likelihood that specific actin residues, which have been previously identified by others, interact with alpha A1-2. Our results indicate that residues 86-117 and 350-375 comprise distinct binding sites for alpha-actinin on adjacent actin monomers.

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Abstract 11945: Indications and Outcomes Following Transvenous Extraction of ICD versus Pacemaker Leads

Circulation ◽

10.1161/circ.132.suppl_3.11945 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Eric W Black-Maier ◽

Sean D Pokorney ◽

Robert K Lewis ◽

Alexander Christian ◽

Ruth A Greenfield ◽

...

Keyword(s):

Adverse Events ◽

Dwell Time ◽

Clinical Success ◽

Lead Extraction ◽

Index Hospitalization ◽

Lead Failure ◽

Icd Leads ◽

Pacemaker Leads ◽

Pacing Lead ◽

Major Adverse Events

Introduction: Percutaneous transvenous lead extraction of cardiovascular implantable electronic devices (CIEDs) is increasingly common. Although ICD leads are widely considered to be more difficult to extract than pacemaker leads, there are few direct comparisons. Methods/Results: Using a cohort of 368 consecutive patients undergoing lead extraction (dwell time >1 year) between 2005-2012, we compared baseline characteristics/outcomes in extractions involving pacing versus ICD leads. We defined major adverse events (MAE) as any events/complications that required procedural intervention, transfusion, or that resulted in death or serious harm during index hospitalization. Median age was 60.6 yrs and 29.6% were women. There were 136 (37%) pacing lead extractions and 232 (63%) ICD lead extractions. Pacing leads had a longer dwell time (6.14 yrs [IQR 1.2-10.9 ] versus 4.4 yrs [IQR 1.1-6.4], p<0.001) and higher median LVEF (55% [IQR 35-55] vs. 30% [IQR 20-40], p<0.001) compared with ICD lead patients. Indications for pacing and ICD lead extractions included sepsis/endocarditis (21.3% vs. 24.6%, p=0.48), pocket infection (40.4% vs. 34.9%, p=0.29), and lead failure (15.4% vs. 38.8%, p<0.001). There were no significant differences between pacing and ICD lead extractions in median fluoroscopy time (5.5 vs. 8.5 minutes, p=0.86) or femoral bailout rate (4.4% vs. 5.2%, p=0.73). There were similar rates of all-cause MAE during index hospitalization (5.1% vs. 5.6%), death (2.2% vs 3.2%) and clinical success (97.0% vs. 97.0%, p=0.55) in pacemaker and ICD extractions, respectively. Conclusions: ICD leads are more commonly extracted relative to pacemaker leads, and this difference is driven by larger numbers of lead failure within ICD leads. Despite much longer dwell times, major adverse events were similar in pacing lead cases compared with ICD extractions.

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Supporting Binding-Sites Discovery via Iterative Database Processing

International Journal of Systems Biology and Biomedical Technologies ◽

10.4018/ijsbbt.2013070102 ◽

2013 ◽

Vol 2 (3) ◽

pp. 19-41

Author(s):

Ran Tel-Nir ◽

Roy Gelbard ◽

Israel Spiegler

Keyword(s):

Information Extraction ◽

Binding Site ◽

Iterative Algorithm ◽

Spatial Data ◽

Binding Sites ◽

Heuristic Algorithms ◽

Protein Structures ◽

Three Dimensional ◽

Extraction Process ◽

Binary Representation

Recognition of binding sites common to a set of protein structures is important for applications such as drug design. Common methods of binding-sites are based on heuristic algorithms that use summarized spatial data and superimposition techniques. However, computational operations generally do not store intermediate data for further calculation and information extraction. The current study presents an alternative approach to binding calculation by introducing a binary representation scheme for three dimensional molecule data and a fast iterative algorithm which obviates the need to calculate and resolve spatial transformations in the binding site extraction process. This is achieved by using relational database indexing methods and an efficient iterative model. This general-purpose iterative algorithm was tested for binding small molecules. The results show that the method can be applied efficiently for binding site extraction, and bio-information extraction. This binary representation improves performance by reducing processing time by 31% compared to typical representations.

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