Generative haplotype prediction outperforms statistical methods for small variant detection in next-generation sequencing data.

Motivation: Detection of germline variants in next-generation sequencing data is an essential component of modern genomics analysis. Variant detection tools typically rely on statistical algorithms such as de Bruijn graphs or Hidden Markov models, and are often coupled with heuristic techniques and thresholds to maximize accuracy. Despite significant progress in recent years, current methods still generate thousands of false-positive detections in a typical human whole genome, creating a significant manual review burden.

Ulnocarpal arthrodesis as a new treatment for ectrodactyly in a dog and a cat.

Case History: A 4-month-old male Shih Tzu dog (Case 1) and an 11-month-old female Devon Rex cat (Case 2) were referred to specialist veterinary hospitals for evaluation of right thoracic lameness and growth abnormality in the distal aspect of the forelimb.

Clinical Findings: Non-weight-bearing lameness and decreased range of motion were noted in the affected limbs of both cases. Case 1 had a plantigrade stance, and a cleft separation between the first and second digits extending upwards to the distal third of the antebrachium.

Author Correction: Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

A novel modelling mechanism of PAEL receptor and GABARAPL2 interaction involved in Parkinson's disease.

Parkin associated endothelin like receptor (PAELR) is G-protein coupled and ubiquitinated by parkin, promoting its degradation. In autosomal recessive Parkinson's disease, mutations in parkin lead to PAELR aggregation in the endoplasmic reticulum (ER), ER stress, neurotoxicity and cell death. We have identified previously that the protein kinase C interacting protein (PICK1) interacts with and regulates the expression and cell toxicity of PAELR.

Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.

Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme's ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in plants and their enzymatic properties were investigated.

Transmural coil embolization-alternative technique for management of arterial perforation during subintimal angioplasty.

Subintimal angioplasty of lower limb arterial occlusion carries a relatively higher risk of vessel perforation compared to transluminal angioplasty. Vessel perforation is a potentially life threatening complication which requires prompt recognition and management. They are usually managed by endovascular techniques such as low-pressure balloon tamponade, covered stents, and coil embolization of the ruptured artery.

Adaptive BP-Dock: An Induced Fit Docking Approach for Full Receptor Flexibility.

We present an induced fit docking approach called Adaptive BP-Dock that integrates perturbation response scanning (PRS) with the flexible docking protocol of RosettaLigand in an adaptive manner. We first perturb the binding pocket residues of a receptor and obtain a new conformation based on the residue response fluctuation profile using PRS. Next, we dock a ligand to this new conformation by RosettaLigand, where we repeat these steps for several iterations.

A Rigid Hinge Region Is Necessary for High-Affinity Binding of Dimannose to Cyanovirin and Associated Constructs.

Mutations in the hinge region of cyanovirin-N (CVN) dictate its preferential oligomerization state. Constructs with the Pro51Gly mutation preferentially exist as monomers, whereas wild-type cyanovirin can form domain-swapped dimers under certain conditions. Because the hinge region is an integral part of the high-affinity binding site of CVN, we investigated whether this mutation affects the shape, flexibility, and binding affinity of domain B for dimannose.

Arthroscopic assisted femoral tunnel drilling for the intra-articular anatomic cranial cruciate ligament reconstruction in dogs.

Objective: To develop and test an arthroscopic aiming device for extra- to intra-articular femoral tunnel drilling emerging at the center of the femoral insertion of the cranial cruciate ligament (CrCL) in medium to large breed dogs.

Material And Methods: Hindlimbs (n = 12) of six cadaveric dogs (≥ 20 kg bodyweight). One hindlimb from each cadaver was randomly chosen.

Ultrasonography alone can reliably locate parathyroid tumours and facilitates minimally invasive parathyroidectomy.

Introduction: Minimally invasive parathyroidectomy (MIP) is performed via a short incision (≤3cm). Previous studies have employed multiple imaging modalities including ultrasonography, sestamibi imaging and/or intraoperative parathyroid hormone assay. We present our eight-year experience of MIP using ultrasonography alone.

Radiographic location of the femoral footprint of the cranial cruciate ligament in dogs.

Objective: To describe the radiographic location of the center of the femoral footprint of the cranial cruciate ligament (CrCL) in dogs.

Material And Methods: Using femora from 49 adult, orthopedically sound dogs (bodyweight≥20 kg), a radiopaque marker was placed on the cranial border of the femoral footprint of the CrCL. Computed tomography and threedimensional (3D) reconstruction of each femur was performed subsequently, followed by manual segmentation of the footprint on the 3D models and calculation of its center.

A flexible docking scheme efficiently captures the energetics of glycan-cyanovirin binding.

Cyanovirin-N (CVN), a cyanobacterial lectin, exemplifies a class of antiviral agents that inhibit HIV by binding to the highly glycosylated envelope protein gp120. Here, we investigate the energetics of glycan recognition using a computationally inexpensive flexible docking approach, backbone perturbation docking (BP-Dock). We benchmarked our method using two mutants of CVN: P51G-m4-CVN, which binds dimannose with high affinity through domain B, and CVN((mutDB)), in which binding to domain B has been abolished through mutation of five polar residues to small nonpolar side chains.

BP-Dock: a flexible docking scheme for exploring protein-ligand interactions based on unbound structures.

Molecular docking serves as an important tool in modeling protein-ligand interactions. However, it is still challenging to incorporate overall receptor flexibility, especially backbone flexibility, in docking due to the large conformational space that needs to be sampled. To overcome this problem, we developed a novel flexible docking approach, BP-Dock (Backbone Perturbation-Dock) that can integrate both backbone and side chain conformational changes induced by ligand binding through a multi-scale approach.

The antiviral lectin cyanovirin-N: probing multivalency and glycan recognition through experimental and computational approaches.

CVN (cyanovirin-N), a small lectin isolated from cyanobacteria, exemplifies a novel class of anti-HIV agents that act by binding to the highly glycosylated envelope protein gp120 (glycoprotein 120), resulting in inhibition of the crucial viral entry step. In the present review, we summarize recent work in our laboratory and others towards determining the crucial role of multivalency in the antiviral activity, and we discuss features that contribute to the high specificity and affinity for the glycan ligand observed in CVN. An integrated approach that encompasses structural determination, mutagenesis analysis and computational work holds particular promise to clarify aspects of the interactions between CVN and glycans.

Endovascular treatment of the common femoral artery for limb ischemia.

Objective: To determine the short- and mid-term outcomes of percutaneous endovascular common femoral artery (CFA) revascularization (eCFR) of the CFA.

Methods: A review of patients who underwent eCFR for limb ischemia between 2006 and 2012 was performed. Limb salvage, patient survival, survival free from reintervention, and survival free from amputation rates were determined.

Isolated percutaneous transluminal angioplasty of the profunda femoris artery for limb ischemia.

Objective: To compare the outcome of endovascular profunda femoral artery revascularization (ePFR) with ePFR and concurrent endovascular femoropopliteal revascularization (eFPR).

Methods: A retrospective review of the consecutive patients with PFA and femoropopliteal vaso-occulsive disease who underwent ePFR or ePFR + eFPR for severe limb ischemia was performed.

Results: A total of 18 ePFRs and 26 ePFR + eFPRs were performed; 17 (94%) ePFRs and 22 (85%) ePFR + eFPRs were technically successful.

Retrieval of proximally migrated double J ureteric stents in children using goose neck snare.

Purpose: Proximal migration of the ureteric double J stent is a rare but known complication. We describe three cases where a minimally invasive technique for retrieval of displaced double J stents using Amplatz(™) goose-neck snare was successful.

Materials And Methods: A retrospective review of patients with displaced double J stent was carried out, in whom cystoscopy guided retrieval of double J stent was attempted with the help of Amplatz goose-neck snare under radiological control.

The binding affinities of proteins interacting with the PDZ domain of PICK1.

Protein interacting with C kinase (PICK1) is well conserved throughout evolution and plays a critical role in synaptic plasticity by regulating the trafficking and posttranslational modification of its interacting proteins. PICK1 contains a single PSD95/DlgA/Zo-1 (PDZ) protein-protein interaction domain, which is promiscuous and shown to interact with over 60 proteins, most of which play roles in neuronal function. Several reports have suggested the role of PICK1 in disorders such as epilepsy, pain, brain trauma and stroke, drug abuse and dependence, schizophrenia and psychosis.

Reprinted article "Subintimal angioplasty of femoropopliteal artery occlusions: the long-term results".

The technique of subintimal angioplasty has been attempted on 200 consecutive femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The principle of the technique is to traverse the occlusion in the subintimal plane and recanalise by inflating the angioplasty balloon within the subintimal space. The technical success rate was 159/200 (80%) and was not significantly different for occlusions <10 cm (81%, n = 73), 11-20 cm (83%, n = 63) or >20 cm (68%, n = 23), p = 0.

Subintimal angioplasty for femoro-popliteal occlusive disease.

There has been a longstanding debate about the roles of surgical bypass graft, percutaneous transluminal angioplasty, subintimal angioplasty, and conservative management for femoro-popliteal occlusive disease. Subintimal angioplasty was first described in 1987 as a method of performing an endovascular arterial bypass. The subintimal space at the start of the occlusion is entered with a catheter and a wire loop is used to cross the occlusion and reenter the vessel lumen distally.

Developments in subintimal angioplasty in the infrainguinal segment.

Since it was first described in 1990, subintimal angioplasty (SIA) has become an established percutaneous procedure for the treatment of symptomatic lower limb arterial occlusions. The concept of this technique is to create a dissection in the subintimal plane in order to cross an occluded intraluminal segment, then to re-enter the true lumen of the patent distal artery. Balloon dilatation of this subintimal channel results in a new extraluminal lumen that is free of atheromatous plaque.

Active retropharyngeal hemorrhage from an acute thyrocervical artery injury: a rare complication of hyperextension cervical spine injury.

Background: Acute vascular injury is uncommon after cervical spine injury. We describe a recent case of active retropharyngeal bleeding from the thyrocervical artery after an acute cervical spine injury.

Objectives: The case illustrates an unusual vascular injury diagnosed by 64-slice multidetector computed tomography (MDCT) and managed successfully by emergency transcatheter embolization.

Percutaneous ultrasound-guided thrombin injection for the treatment of iatrogenic femoral artery pseudoaneurysms.

Purpose: To audit our experience with ultrasound-guided thrombin injection for the treatment of iatrogenic femoral artery pseudoaneurysms.

Methods: A retrospective study of 85 consecutive patients undergoing percutaneous ultrasound-guided thrombin injection of post-catheterization femoral pseudoaneurysms during the period January 2002 to May 2007.

Results: Pseudoaneurysms had a mean maximum diameter of 3.