Correction to: Designing and Modeling of Multi-epitope Proteins for Diagnosis of Toxocara canis Infection

International Journal of Peptide Research and Therapeutics - The original version of this article unfortunately contained an error in the co-author name and also the Acknowledgement section was not...     

A Comprehensive Study of the Polypropylene Fiber Reinforced Fly Ash Based Geopolymer

As a cementitious material, geopolymers show a high quasi-brittle behavior and a relatively low fracture energy. To overcome such a weakness, incorporation of fibers to a brittle matrix is a well-known technique to enhance the flexural properties. This study comprehensively evaluates the short and long term impacts of different volume percentages of polypropylene fiber (PPF) reinforcement on fly ash based geopolymer composites. Different characteristics of the composite were compared at fresh state by flow measurement and hardened state by variation of shrinkage over time to assess the response of composites under flexural and compressive load conditions. The fiber-matrix interface, fiber surface and toughening mechanisms were assessed using field emission scan electron microscopy (FESEM) and atomic force microscopy (AFM). The results show that incorporation of PPF up to 3 wt % into the geopolymer paste reduces the shrinkage and enhances the energy absorption of the composites. While, it might reduce the ultimate flexural and compressive strength of the material depending on fiber content.     

Age-related changes in climbing behavior and neural circuit physiology in Drosophila

Identifying the cellular and molecular basis for functional decline remains key to understanding aging. To this end, we have characterized age-dependent changes in climbing and the electrophysiology of the giant fiber circuitry in wild type (Wt) and mutant flies with altered lifespan (methuselah and fragile-X). Our data demonstrate a gradual decline in climbing in Wt and methuselah flies aged 5-45 days. In contrast, fragile-X flies climbed poorly even at 5 days and failed completely at 45 days. We then examined whether synaptic transmission to indirect flight muscles along the giant fiber circuit was altered with aging. At 5 days, the dorsal longitudinal muscle (DLM) in Wt flies followed high frequency stimulation well (at 130 Hz or above). At 35 and 45 days, these flies only followed 60-80 Hz. Methuselah flies did not follow stimuli as well as the Wt flies did at 5 and 25 days, but they were similar to Wt flies at older ages. Fragile-X flies responded poorly even at 5 days (40 Hz) and worsened at 35 days (30 Hz). Unlike DLMs, the tergotrochanteral muscle followed high frequency stimuli relatively well in all genotypes, suggesting that the peripheral interneuron along the DLM pathway or the DLM muscular synapse is prone to age-dependent functional decline. These studies reveal subcellular structures as potential targets of aging, indicating that the giant fiber pathway can be used as a model circuit for quantitative studies of aging in flies as well as fly models of age-related human neurological disorders.     

Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis

Mice with targeted deletion of fibrinogen-like protein 2 (fgl2) spontaneously developed autoimmune glomerulonephritis with increasing age, as did wild-type recipients reconstituted with fgl2-/- bone marrow. These data implicate FGL2 as an important immunoregulatory molecule and led us to identify the underlying mechanisms. Deficiency of FGL2, produced by CD4+CD25+ regulatory T cells (Treg), resulted in increased T cell proliferation to lectins and alloantigens, Th 1 polarization, and increased numbers of Ab-producing B cells following immunization with T-independent Ags. Dendritic cells were more abundant in fgl2-/- mice and had increased expression of CD80 and MHCII following LPS stimulation. Treg cells were also more abundant in fgl2-/- mice, but their suppressive activity was significantly impaired. Ab to FGL2 completely inhibited Treg cell activity in vitro. FGL2 inhibited dendritic cell maturation and induced apoptosis of B cells through binding to the low-affinity FcgammaRIIB receptor. Collectively, these data suggest that FGL2 contributes to Treg cell activity and inhibits the development of autoimmune disease.     

In silico biophysics and hemorheology of blood hyperviscosity syndrome

Hyperviscosity syndrome (HVS) is characterized by an increase of the blood viscosity by up to seven times the normal blood viscosity, resulting in disturbances to the circulation in the vasculature system. HVS is commonly associated with an increase of large plasma proteins and abnormalities in the properties of red blood cells, such as cell interactions, cell stiffness, and increased hematocrit. Here, we perform a systematic study of the effect of each biophysical factor on the viscosity of blood by employing the dissipative particle dynamic method. Our in silico platform enables manipulation of each parameter in isolation, providing a unique scheme to quantify and accurately investigate the role of each factor in increasing the blood viscosity. To study the effect of these four factors independently, each factor was elevated more than its values for a healthy blood while the other factors remained constant, and viscosity measurement was performed for different hematocrits and flow rates. Although all four factors were found to increase the overall blood viscosity, these increases were highly dependent on the hematocrit and the flow rates imposed. The effect of cell aggregation and cell concentration on blood viscosity were predominantly observed at low shear rates, in contrast to the more magnified role of cell rigidity and plasma viscosity at high shear rates. Additionally, cell-related factors increase the whole blood viscosity at high hematocrits compared with the relative role of plasma-related factors at lower hematocrits. Our results, mapped onto the flow rates and hematocrits along the circulatory system, provide a correlation to underpinning mechanisms for HVS findings in different blood vessels.     

Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels

Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P < 0.05). In mice with IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P < 0.05). On the basis of these results, we examined whether targeted antibody therapy could improve survival in mice with elevated IL-6 levels. A different cohort of mice (n = 54) had blood drawn 6 h after CLP, and then they were randomized to receive either monoclonal anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either overall survival or outcome in mice with IL-6 levels >14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.     

Sorcin a Potential Molecular Target for Cancer Therapy

Sorcin (Soluble resistance related calcium binding protein) is a small soluble penta EF family (PEF) of calcium (Ca²⁺) binding protein (22,000 Da). It has been reported to play crucial roles in the regulation of calcium homeostasis, apoptosis, vesicle trafficking, cancer development, and multidrug resistance (MDR). Overexpression of sorcin has been reported to be associated with different cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of sorcin has been found to be elevated in cancer cells as compared to normal cells, indicating that it has prominent role in cancer. Moreover, sorcin was found to be the regulator of various proteins that has an association with carcinogenesis including NF-κB, STAT3, Akt, ERK1/2, VEGF, MMPs, caspases, etc. Sorcin was also found to regulate apoptosis, as silencing of the same resulted in increased levels of proapoptotic genes and induced mitochondrial apoptotic pathway in cancer. Interestingly, mutations in the sorcin gene have been closely linked with poor overall survival in bladder cancer, brain lower-grade glioma, glioblastoma, glioblastoma multiforme, kidney renal clear cell carcinoma, and stomach adenocarcinoma. Additionally, overexpression of sorcin was also found to induce MDR against different chemotherapeutic drugs. All these findings mark the importance of sorcin in cancer development and MDR. Therefore, there is urgent need to explore the functional mechanism of sorcin and to analyze whether silencing of sorcin would able to chemosensitize MDR cells. The current review summarizes the structure, expression, and functions of sorcin and its importance in the regulation of various malignancies and MDR.     

Measurements of donor endothelial keratoplasty lenticules prepared from fresh donated whole eyes by using ultrasound and optical coherence tomography

This study was conducted to analyze the profile and thickness of endothelial keratoplasty lenticules prepared from fresh donated whole eyes with Visante optical coherence tomography (V-OCT) compared to measurements obtained from ultrasound pachymetry (USP) at the Central Eye Bank of Iran. Microkeratome-assisted precut corneas were prepared for Descemet stripping automated endothelial keratoplasty by using standard eye bank protocol. Central posterior lenticule thickness (CPLT) on fresh whole eye, before excising corneoscleral disc and transferring to Optisol-GS, was measured by USP. V-OCT was used to measure central, paracentral, and midperipheral thicknesses of lenticules after transferring the tissue to Optisol-GS. Chi Square and Bonferroni tests were respectively used to uncover the differences between the USP and V-OCT measurements and also the thickness profile of lenticules. Postoperative reports for the entire transplanted lenticules were recorded. Accordingly, on evaluation of 312 enrolled precut corneas, CPLT measurements by V-OCT versus USP were statistically different (mean: 136 µm vs 165 µm, respectively; P = 0.008). Thickness profile of the posterior lenticules revealed increased thickness from the central to the peripheral parts of the cornea (mean increase of 16 µm at the pericentral and 64.2 µm at the peripheral locations, respectively); however, the increase in the thickness was relatively symmetrical. Postoperative reports of transplanted lenticules were unremarkable, since there were no posterior flap detachments. In essence, V-OCT measurements of microkeratome-assisted precut lenticules prepared from fresh donated whole eyes averaged 29 μm thinner than USP measurements and revealed a significant but symmetric increase of thickness towards the peripheral parts of the corneas. However, the variation in the thickness profile did not affect the attachment or the clarity of transplanted precut lenticlues.