A mathematical modeling technique to understand the role of decoy receptors in ligand-receptor interaction.

The ligand-receptor interaction is fundamental to many cellular processes in eukaryotic cells such as cell migration, proliferation, adhesion, signaling and so on. Cell migration is a central process in the development of organisms. Receptor induced chemo-tactic sensitivity plays an important role in cell migration. However, recently some receptors identified as decoy receptors, obstruct some mechanisms of certain regular receptors. DcR3 is one such important decoy receptor, generally found in glioma cell, RCC cell and many various malignant cells which obstruct some mechanism including apoptosis cell-signaling, cell inflammation, cell migration. The goal of our work is to mathematically formulate ligand-receptor interaction induced cell migration in the presence of decoy receptors. We develop here a novel mathematical model, consisting of four coupled partial differential equations which predict the movement of glioma cells due to the reaction-kinetic mechanism between regular receptors CD95, its ligand CD95L and decoy receptors DcR3 as obtained in experimental results. The aim is to measure the number of cells in the chamber's filter for different concentrations of ligand in presence of decoy receptors and compute the distance travelled by the cells inside filter due to cell migration. Using experimental results, we validate our model which suggests that the concentration of ligands plays an important role in cell migration.

Important signs to check posterior capsule integrity.

For beginner surgeons, it is difficult to recognize the posterior capsule during cataract surgery. In the case of brown cataracts with a thin posterior capsule and in cataracts with asteroid hyalosis, it is difficult to identify the capsule before intraocular lens (IOL) implantation even for expert surgeons. Here we illustrate five important signs, which can be practiced in routine cases to make sure the posterior capsule is intact, before IOL implantation.

Visual outcomes and complications of manual small-incision cataract surgery in patients with pseudoexfoliation.

Purpose: Pseudoexfoliation is an age-related fibrillopathy characterized by the deposition of fibrillar material in the eye with an increased risk of complications during cataract surgery. Aim was to study visual outcomes and complications in patients with pseudoexfoliation undergoing manual small-incision cataract surgery (MSICS). Methods: Prospective observational study was performed on 152 patients with pseudoexfoliation above 50 years undergoing MSICS in a tertiary hospital from December 2016 to November 2017. Intraoperative and postoperative complications were documented with follow-up on postoperative day 1, 1st week, 1st month, and 3rd month. Results: Preoperative small pupil was noted in 49 eyes (32.2%), and 19 (12.5%) required intraoperative measures. Intraocular complications noted were zonular dialysis in five (3.3%), posterior capsular rupture in one (0.7%), and iridodialysis in one (0.7%). On postoperative day 1, the most common complication was corneal edema in 134 patients but clinically significant in only 23 (15.1%). Postoperative complications at 3 months were irregular pupil in 17 cases and decentered IOL in three cases. Intraocular pressure decreased with each visit [preoperative mean: 14.39 (±3.4) and 13.37 (±2.0) 12.53 (±1.4) mm Hg at 1 and 3 months, respectively]. There was a significant improvement in vision from the first day mean pinhole vision of 0.26 (±0.24) to mean best corrected visual acuity (BCVA) of 0.09 (±0.22) and 0.07 (±0.22) at 1 and 3 months, respectively. Mean endothelial cell loss was 193.16 (7.79%) and 266.01 (10.68%) at 1 and 3 months, respectively. Conclusion: Pseudoexfoliation has an increased risk of complications during cataract surgery. MSICS gives good outcomes in terms of visual recovery and postoperative outcomes.

Perfect anterior capsulorhexis using a dented cystitome.

We describe a novel intraoperative technique of measuring and creating an adequate size continuous curvilinear capsulorhexis (CCC) in phacoemulsification, using a dented cystitome as the ruler. A pair of curved tenotomy scissors is used to create a dent on the cystitome at a distance of 2.5 mm length (i.e., half of the desired approximate capsulorhexis diameter). The dented cystitome is used as a guide for making a CCC of approximately 5 mm diameter, which is considered adequate for phacoemulsification. This method of measuring the capsulorhexis helps in achieving a well centered and stable intraocular lens with a 360° overlap of the optic edge by the anterior capsular rim in the postoperative period. Using a dented cystitome for capsulorhexis mandates reliable and consistent results in the hands of the novice as well as the experienced surgeons.

Pediatric leukemia: Moving toward more accurate models.

Leukemia is a complex genetic disease caused by errors in differentiation, growth, and apoptosis of hematopoietic cells in either lymphoid or myeloid lineages. Large-scale genomic characterization of thousands of leukemia patients has produced a tremendous amount of data that have enabled a better understanding of the differences between adult and pediatric patients. For instance, although phenotypically similar, pediatric and adult myeloid leukemia patients differ in their mutational profiles, typically involving either chromosomal translocations or recurrent single-base-pair mutations, respectively. To elucidate the molecular mechanisms underlying the biology of this cancer, continual efforts have been made to develop more contextually and biologically relevant experimental models. Leukemic cell lines, for example, provide an inexpensive and tractable model but often fail to recapitulate critical aspects of tumor biology. Likewise, murine leukemia models of leukemia have been highly informative but also do not entirely reproduce the human disease. More recent advances in the development of patient-derived xenografts (PDXs) or human models of leukemias are poised to provide a more comprehensive, and biologically relevant, approach to directly assess the impact of the in vivo environment on human samples. In this review, the advantages and limitations of the various current models used to functionally define the genetic requirements of leukemogenesis are discussed.

The impact of time from diagnosis to treatment in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that requires treatment. We retrospectively analyzed the impact of time from diagnosis-to-treatment (TDT) on progression-free survival (PFS) and overall survival (OS) in 581 R-CHOP-treated patients. TDT was defined as the interval between diagnostic biopsy date and day 1 R-CHOP. Cox regression showed stage 3-4 disease (p = .01) and longer TDT (HR 1.13, p =.031) were associated with shorter OS. Eastern Cooperative Oncology Group ≥2 (p = .02), stage 3-4 disease (p < .001), and longer TDT (HR 1.12, p = .028) predicted shorter PFS. The significant interactions between TDT with lactate dehydrogenase (LDH) and with disease stage prompted separate analyses in high versus normal LDH, and stage 3-4 versus 1-2 disease. Longer TDT was associated with shortened PFS and OS only with advanced stage, and, if high LDH was present. Treatment should be started as early as possible for high-tumor burden disease. Delaying treatment in patients with early stage or low LDH does not seem harmful.

Characterization of the autophosphorylation property of HflX, a ribosome-binding GTPase from Escherichia coli.

Escherichia coli HflX belongs to the widely distributed but poorly characterized HflX family of translation factor-related GTPases that is conserved from bacteria to humans. A 426-residue polypeptide that binds 50S ribosomes and has both GTPase and ATPase activities, HflX also exhibits autophosphorylation activity. We show that HflX(C), a C-terminal fragment of HflX, has an enhanced autophosphorylation activity compared to the full-length protein. Using a chemical stability assay and thin layer chromatography, we have determined that phosphorylation occurs at a serine residue. Each of the nine serine residues of HflX(C) was mutated to alanine. It was found that all but S211A retained autophosphorylation activity, suggesting that S211, located in the P-loop, was the likely site for autophosphorylation. While the S211A mutant lacked the autophosphorylation site, it possessed strong GTP binding and GTPase activities.