Outcomes of descemet stripping automated endothelial keratoplasty in patients with an anterior chamber versus posterior chamber intraocular lens.

Purpose: The aim of this study was to assess the implications of a retained anterior chamber intraocular lens (ACIOL) during Descemet stripping automated endothelial keratoplasty (DSAEK) and to compare the outcomes in this group with those in patients who underwent DSAEK and had a posterior chamber intraocular lens (PCIOL).

Methods: This is a retrospective cohort study conducted in a tertiary medical center, which compares patients who underwent DSAEK and had a retained ACIOL with patients who underwent DSAEK and had a PCIOL regarding operative and postoperative complications, visual acuity, endothelial cell density, and long-term graft survival.

Results: Eleven eyes with an ACIOL and 50 eyes with a PCIOL met the study criteria.

ATPase subdomain IA is a mediator of interdomain allostery in Hsp70 molecular chaperones.

The versatile functions of the heat shock protein 70 (Hsp70) family of molecular chaperones rely on allosteric interactions between their nucleotide-binding and substrate-binding domains, NBD and SBD. Understanding the mechanism of interdomain allostery is essential to rational design of Hsp70 modulators. Yet, despite significant progress in recent years, how the two Hsp70 domains regulate each other's activity remains elusive.

Exploring the conformational transitions of biomolecular systems using a simple two-state anisotropic network model.

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally.

Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids.

Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14).

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer.

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs).

Predicting drug-target interactions using probabilistic matrix factorization.

Quantitative analysis of known drug-target interactions emerged in recent years as a useful approach for drug repurposing and assessing side effects. In the present study, we present a method that uses probabilistic matrix factorization (PMF) for this purpose, which is particularly useful for analyzing large interaction networks. DrugBank drugs clustered based on PMF latent variables show phenotypic similarity even in the absence of 3D shape similarity.

Comparison between femtosecond laser mushroom configuration and manual trephine straight-edge configuration deep anterior lamellar keratoplasty.

Aim: To compare outcomes and complications of femtosecond laser (FSL) mushroom configuration and manual trephine (MT) straight-edge configuration deep anterior lamellar keratoplasty (DALK).

Methods: A cohort of 19 consecutive eyes that underwent FSL DALK was compared with 19 consecutive eyes that underwent MT DALK. Surgery was performed for eyes with keratoconus, corneal ectasia and scarring.

Global transitions of proteins explored by a multiscale hybrid methodology: application to adenylate kinase.

Efficient and accurate mapping of transition pathways is a challenging problem in allosteric proteins. We propose here a to our knowledge new methodology called collective molecular dynamics (coMD). coMD takes advantage of the collective modes of motions encoded by the fold, simultaneously evaluating the interactions and energetics via a full-atomic MD simulation protocol.

Global motions exhibited by proteins in micro- to milliseconds simulations concur with anisotropic network model predictions.

The Anton supercomputing technology recently developed for efficient molecular dynamics simulations permits us to examine micro- to milli-second events at full atomic resolution for proteins in explicit water and lipid bilayer. It also permits us to investigate to what extent the collective motions predicted by network models (that have found broad use in molecular biophysics) agree with those exhibited by full-atomic long simulations. The present study focuses on Anton trajectories generated for two systems: the bovine pancreatic trypsin inhibitor, and an archaeal aspartate transporter, GltPh.

Zig Zag versus Top Hat configuration in IntraLase-enabled penetrating keratoplasty.

Aim: To compare the outcomes with IntraLase-enabled keratoplasty using (IEK) Top Hat (TH) versus Zig Zag (ZZ) configuration.

Methods: Retrospective comparative series of 24 eyes that underwent TH and 10 eyes that underwent ZZ IEK.

Results: There were no significant differences in LogMar Best-spectacle corrected visual acuity (TH- IEK=0.

Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells.

Recognition of injured mitochondria for degradation by macroautophagy is essential for cellular health, but the mechanisms remain poorly understood. Cardiolipin is an inner mitochondrial membrane phospholipid. We found that rotenone, staurosporine, 6-hydroxydopamine and other pro-mitophagy stimuli caused externalization of cardiolipin to the mitochondrial surface in primary cortical neurons and SH-SY5Y cells.

Effect of erythropoietin on healing of corneal epithelial defects in rabbits.

Background/aim: Corneal epithelial defects may heal slowly in patients with diabetes, limbal stem cell deficiency, extensive chemical burns or anesthetized corneas. Studies have shown that erythropoietin, a glycoprotein hormone that promotes red blood cell proliferation and inhibits apoptosis of erythroid progenitors, may also exert a cytoprotective, antiapoptotic effect on nonhematopoietic cells. The aim of the study was to examine the effect of erythropoietin on the healing process of corneal epithelial erosions in rabbit eyes.

Coupled global and local changes direct substrate translocation by neurotransmitter-sodium symporter ortholog LeuT.

Significant advances have been made in recent years in characterizing neurotransmitter:sodium symporter (NSS) family structure and function. Yet, many time-resolved events and intermediates that control the various stages of transport cycle remain to be elucidated. Whether NSSs harbor one or two sites for binding their substrates (neurotransmitters or amino acids), and what the role of the secondary site S2 is, if any, are still unresolved.

First 100: learning curve for Descemet stripping automated endothelial keratoplasty.

Purpose: Endothelial keratoplasty is largely replacing penetrating keratoplasty for the routine treatment of corneal endothelial failure. The aim of the study was to describe the performance, complications, and outcome of the first 100 Descemet stripping automated endothelial keratoplasty (DSAEK) procedures performed at a major medical center, with an emphasis on the learning curve. 


Methods: A retrospective, comparative case series study was conducted by a single surgeon at a tertiary, university-affiliated medical center.

Remote manipulation of posterior lamellar corneal grafts using a magnetic field.

Purpose: In posterior lamellar keratoplasty procedures such as Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty, the lamellar graft is manipulated directly or by injecting an air bubble. This preliminary study sought to evaluate the feasibility of guiding lamellar corneal grafts by generating a magnetic field.

Methods: Rabbit and porcine Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty grafts were manually produced and immersed in a ferromagnetic solution containing nanomagnetic particles conjugated to streptavidin or in gadoteric acid.

[Effects of Imipenem, Tobramycin and Curcumin on Biofilm Formation of Pseudomonas aeruginosa Strains].

Aminoglycoside antibiotics and imipenem are reported to stimulate exopolysaccharide alginate production and cause an increased biofilm volume in Pseudomonas aeruginosa. Recently, some remarkable studies have been conducted on the effects of curcumin (Turmeric), which is the fenolic form of Curcuma longa plant, on virulence factors of P.aeruginosa.

[Evaluation of the Relationship Between Microenvironment and Biofilm and Coagulase Responses of Staphylococcus aureus Strains Under the Effect of Gentamicin].

The frequency of infections caused by Staphylococcus aureus strains and the rate of antibiotic resistance among these strains are gradually increasing. Accordingly, serious problems emerge in the treatment of community or hospital acquired S.aureus infections.

Intracellular gating in an inward-facing state of aspartate transporter Glt(Ph) is regulated by the movements of the helical hairpin HP2.

Sodium-coupled neurotransmitter transporters play a key role in neuronal signaling by clearing excess transmitter from the synapse. Structural data on a trimeric archaeal aspartate transporter, Glt(Ph), have provided valuable insights into structural features of human excitatory amino acid transporters. However, the time-resolved mechanisms of substrate binding and release, as well as that of coupling to sodium co-transport, remain largely unknown for this important family.

Descemet's stripping automated endothelial keratoplasty for posterior polymorphous corneal dystrophy in an 8-month-old boy.

Descemet's stripping automated endothelial keratoplasty (DSAEK) has recently become the preferred treatment for corneal endothelial dystrophies in adults. We describe the case of an 8-month-old boy with congenital corneal epithelial edema due to posterior polymorphous corneal dystrophy who was treated successfully with bilateral DSAEK. This case shows that DSAEK is a treatment option for endothelial dysfunction secondary to posterior polymorphous corneal dystrophy even in very young patients.

FlexE: Using elastic network models to compare models of protein structure.

It is often valuable to compare protein structures to determine how similar they are. Structure comparison methods such as RMSD and GDT-TS are based solely on fixed geometry and do not take into account the intrinsic flexibility or energy landscape of the protein. We propose a method, which we call FlexE, that is based on a simple elastic network model and uses the deformation energy as measure of the similarity between two structures.

Coupling between catalytic loop motions and enzyme global dynamics.

Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these motions appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role in selecting particular mechanisms of motions. We performed an extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops.

An adaptive weighted ensemble procedure for efficient computation of free energies and first passage rates.

We introduce an adaptive weighted-ensemble procedure (aWEP) for efficient and accurate evaluation of first-passage rates between states for two-state systems. The basic idea that distinguishes aWEP from conventional weighted-ensemble (WE) methodology is the division of the configuration space into smaller regions and equilibration of the trajectories within each region upon adaptive partitioning of the regions themselves into small grids. The equilibrated conditional∕transition probabilities between each pair of regions lead to the determination of populations of the regions and the first-passage times between regions, which in turn are combined to evaluate the first passage times for the forward and backward transitions between the two states.

Identification of motions in membrane proteins by elastic network models and their experimental validation.

Identifying the functional motions of membrane proteins is difficult because they range from large-scale collective dynamics to local small atomic fluctuations at different timescales that are difficult to measure experimentally due to the hydrophobic nature of these proteins. Elastic Network Models, and in particular their most widely used implementation, the Anisotropic Network Model (ANM), have proven to be useful computational methods in many recent applications to predict membrane protein dynamics. These models are based on the premise that biomolecules possess intrinsic mechanical characteristics uniquely defined by their particular architectures.