Uncovering nano-bonechar for attenuating fluoride in naturally contaminated soil.

Fluoride ion (F-) is one of the major geogenic contaminants in water and soil. Excessive consumption of these geogenic contaminants poses serious health impacts on humans and plants. In this study, a novel carbonaceous material, nano-bonechar, was synthesized from cow bones and applied as a soil amendment at rates of 0, 0.5, 1, and 2% to remediate and revitalize naturally F--contaminated soil. The results revealed that the nano-bonechar significantly reduced the mobility and bioavailability of F- by 90% in the contaminated soil, and improved the soil quality by increasing the soil water holding capacity, soil organic matter, and the bioavailable contents of PO43-, Ca2+, and Na+. Subsequently, the pot experiment results showed a significant reduction in the uptake of F- by 93% in Zea mays plants. Moreover, the nano-bonechar application improved the plant's growth, as indicated by the higher fresh and dry weights, root and shoot lengths, and total content of PO43-, Ca2+, and K+ than those of un-amended soil. The F-immobilization in soil was mainly due to the presence of the hydroxyapatite [Ca10(PO4)6(OH)2] mineral in the nano-bonechar. Ion exchange between OH- (of nano-bonechar) and F- (of soil), and the formation of insoluble fluorite (CaF2) contributed to the attenuation of F- mobility in the soil. It is concluded that nano-bonechar, due to its size and enrichment in hydroxyapatite, could successfully be utilized for the rapid remediation and revitalization of F--contaminated agricultural soil.

Effect of Ni charge states on structural, electronic, magnetic, and optical properties of InN.

The first-principles study of Ni-doped InN has been carried out to explore the doping effect of various charge states of Ni on the structural, electronic, magnetic, and optical properties of InN using generalized gradient approximation. Structural properties like lattice parameters, aspect ratios, bond lengths, and formation energies of (In, Ni) N are used to determine the stability of each doped system. The formation energies of (In, Ni)N systems decrease with the increase in charge state of nickel, while the bond lengths show an opposite trend. The DOS diagram shows that the introduction of Ni-d states within the bang gap region reduces the band gap for Ni(1+)- and Ni(2+)-doped InN, while the isolated states are generated in the case of Ni(3+)- and Ni(4+)-doped systems. The Ni(1+)-, Ni(3+)-, and Ni(4+)-doped InN systems are ferromagnetic in nature, whereas the (In, Ni(2+))N depicts spin-glass-like behavior. The best possible magnetization is obtained for (In, Ni(4+))N with a total magnet moment of 2.42 µB per supercell. Because of the presence of nickel impurities, the optical properties of InN have been significantly improved. The pure and Ni(3+)- and Ni(4+)-doped InN systems show nearly the same values of absorption edges (∼0.56 eV), in contrast with the Ni(1+)- and Ni(2+)-doped systems, where these values are 0.37 and 0.51 eV, respectively. The shift in absorption edges of Ni(1+)- and Ni(2+)-doped InN to lower energies and increase in the intensity of absorption and broadening of absorption peaks can be attributed to the pronounced band-gap reduction for these systems. A negligible shift of absorption edges in the case of Ni(3+)- and Ni(4+)- doped InN is the characteristic of isolated charge states introduced around the Fermi level, which inhibit the band gap reduction, and hence the optical properties are not improved as expected. This study demonstrates an important fact that for best possible optical device applications Ni(1+)-doped InN system is excellent, while for better magnetic properties the (In, Ni(4+))N is more suitable.

Synthesis and electrochemical properties of stannous oxide clinopinacoid as anode material for lithium ion batteries.

Tin monoxide is a significant functional semiconductor material which employed to a wide area of applications especially optical and energy storage devices. Presently, template free hydrothermal technique has been employing to synthesize stannous oxide (SnO) clinopinacoid type controlled morphology using SnCl2 x 2H2O, NH3, and H2O as raw materials. The crystalline phase, morphology, particle size and component were characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and field-emission scanning electron microscopy (FESEM). FESEM results exhibited the large scale homogeneous growth of clinopinacoid architecture with the obvious size of 5 - 7 micrometers. The XRD results showed that the average crystallite size of the tetragonal phase romarchite SnO was about 29 nm calculated from the FWHM of X-ray diffraction pattern. The dominant Raman active modes A(1g) = 205 cm(-1), B(1g) = 105-107 cm(-1) and about 6 cm(-1) redshift were observed by the Raman spectroscopy, which further confirmed the existence of the nano tetragonal phase SnO. The electrochemical performance of as-synthesized SnO clinopinacoid structure as the anode material for lithium ion batteries was investigated. It was observed that the first discharge capacity of the two samples could reach a very high value of 1502 mA h g(-1) and 1422 mA h g(-1) respectively. The effect of nitrogen concentration on morphology as well as cyclic performance of Li-Ion-batteries was also discussed.

Utilization of CRISPR-Mediated Tools for Studying Functional Genomics in Hematological Malignancies: An Overview on the Current Perspectives, Challenges, and Clinical Implications.

Hematological malignancies (HM) are a group of neoplastic diseases that are usually heterogenous in nature due to the complex underlying genetic aberrations in which collaborating mutations enable cells to evade checkpoints that normally safeguard it against DNA damage and other disruptions of healthy cell growth. Research regarding chromosomal structural rearrangements and alterations, gene mutations, and functionality are currently being carried out to understand the genomics of these abnormalities. It is also becoming more evident that cross talk between the functional changes in transcription and proteins gives the characteristics of the disease although specific mutations may induce unique phenotypes. Functional genomics is vital in this aspect as it measures the complete genetic change in cancerous cells and seeks to integrate the dynamic changes in these networks to elucidate various cancer phenotypes. The advent of CRISPR technology has indeed provided a superfluity of benefits to mankind, as this versatile technology enables DNA editing in the genome. The CRISPR-Cas9 system is a precise genome editing tool, and it has revolutionized methodologies in the field of hematology. Currently, there are various CRISPR systems that are used to perform robust site-specific gene editing to study HM. Furthermore, experimental approaches that are based on CRISPR technology have created promising tools for developing effective hematological therapeutics. Therefore, this review will focus on diverse applications of CRISPR-based gene-editing tools in HM and its potential future trajectory. Collectively, this review will demonstrate the key roles of different CRISPR systems that are being used in HM, and the literature will be a representation of a critical step toward further understanding the biology of HM and the development of potential therapeutic approaches.

Interplay of protein misfolding pathway and unfolded-protein response in acute promyelocytic leukemia.

Protein misfolding has traditionally been linked to the pathogenesis of various neurodegenerative diseases. However, emerging evidence from various laboratories, including ours, suggests that protein misfolding may also play a fundamental role in some malignancies, particularly those caused by fusion oncoprotein generated from chromosomal translocation. Promyelocytic leukemia (PML) fused to the retinoic acid receptor (RAR) is a fusion oncoprotein linked to the transformation of acute promyelocytic leukemia (APL), and is not only a misfolded protein itself, but also promotes misfolding of nuclear receptor corepressor (N-CoR) protein, a corepressor essential for the growth-suppressive function of several tumor-suppressor proteins. PML-RAR promotes misfolding of N-CoR by inducing aberrant post-translational modification, which destabilizes its core and promotes instability. Misfolded N-CoR, thus, contributes to differentiation arrest and survival of APL cells through loss-of-function and aberrant gain-of-function properties. Therapeutic restoration of N-CoR conformation and function with conformation-modifying agents not only releases this differentiation arrest but also sensitizes APL cells to programmed cell death. These findings illustrate the potential of the misfolded N-CoR protein as a conformation-based drugable molecular target for APL, and highlights the promise of various conformation-modifying agents as novel therapeutics for APL. Protein conformational rearrangement, resulting from an inherited or acquired genetic alteration, could be a common pathological phenomenon contributing to transformation in different types of leukemias and solid tumors and, therefore, could serve as a common ground for designing a unifying diagnostic as well as therapeutic approach for a widely diverse disease such as cancer. To that end, APL could serve as a model for the development of a novel conformation-based therapeutic approach for other malignant diseases.

Frequency And Predictors Of Radial Artery Spasm During Coronary Angiography/Percutaneous Coronary Intervention.

BACKGROUND: Coronary angiography is the gold standard test for diagnosis coronary artery disease. It can be performed via various intra-arterial routes, i.e., femoral, radial, brachial, ulnar, or axillary arteries. Trans-Radial access for coronary angiography is a good approach with less major vascular complications, increased patient comfort and early mobilization and less hospital stay but is associated with radial artery spasm as the major complication affecting the success of the procedure. METHODS: This study was a descriptive cross-sectional study. It enrolled one hundred and thirty-six (136) consecutive patients who underwent the procedure of coronary angiography/PCI over a 6-month period. The study included both in and outpatients undergoing coronary angiography/PCI. Coronary angiography/Percutaneous coronary intervention was done via trans radial approach and the study participants were observed for development of radial artery spasm using clinical and angiographic parameters. Data was entered and analysed using SPSS-19. RESULTS: The frequency of radial artery spasm was 13.24% (n=18). Radial artery spasm was statistically significant in females (p<0.05), those who had severe pain during radial artery puncture (p<0.001) and those who had unsuccessful first attempt during radial artery puncture (p<0.001). No statistically significant association was found between radial artery spasm and other predictors such as age, hypertension and diabetes mellitus. CONCLUSIONS: Radial artery spasm is a common complication during trans radial approach for coronary angiography/percutaneous coronary intervention particularly in females, those who have unsuccessful first attempt and those who have severe pain during radial artery puncture.

Autophagic Degradation of Misfolded Nuclear Receptor Co-repressor (NCoR) Is Linked to the Growth of Tumor Cells in HBX Positive Hepatocellular Carcinoma (HCC).

Hepatitis B virus (HBV) is causally linked to hepatocellular injury and cell death, which are followed by hepatocellular carcinoma (HCC) after a long latent period. The HBV derived X protein (HBX) is the most potent carcinogenic factor for HCC, however, the molecular mechanism of HBX-induced transformation of hepatic cells in HCC is poorly understood. We have shown that nuclear receptor co-repressor (NCoR) is essential for the spatial repression of global transcription by the promyelocytic leukemia oncogenic domains (PODs), a frequent target of viral oncoproteins like HBX and that disintegration of PODs due to misfolded conformation dependent loss (MCDL) of NCoR is linked to promyelocytic and monocytic acute myeloid leukemia (AML). Given the key role of NCoR in cellular homeostasis across various tissue subtypes, we hypothesized that HBX-induced MCDL of NCoR might be linked to HCC through similar mechanism. Based on this hypothesis, the conformation of NCoR in HCC derived tumor cells and primary human tissue sections were analyzed and a selective MCDL of NCoR in HBX positive HCC cells was identified. HBX triggered the misfolding of NCoR through ubiquitination, followed by its degradation by autophagy, thus suggesting a cross talk between ubiquitin proteasome system (UPS) and autophagy lysosomal pathway (ALP) in MCDL of NCoR in HBX positive HCC cells. SiRNA-induced NCoR ablation selectively impaired the growth and survival of HBX positive HCC cells, suggesting a role of MCDL in the growth and survival of HBX positive HCC cells. These finding identify a possible crosstalk between UPS and ALP in the misfolding and loss of NCoR in HBX positive HCC cells and suggest a role of autophagic recycling of misfolded NCoR in the activation of oncogenic metabolic signaling in HCC. The misfolded NCoR reported in this study represents a novel conformation based molecular target which could be valuable in the design and development of tumor cell specific diagnostic and therapeutic approach for HBX positive HCC.

An overview of radioactivity measurement studies in Pakistan.

In our environment, various naturally occurring radionuclides are present (both underground and overground) in several places, which results in lifelong human exposure. The radiation dose received by human beings from the radiation emitted by these naturally occurring radionuclides is approximately 87%. Exposure to radiation poses radiological health hazards. To assess the human health hazards from radiation, the concentration of these naturally occurring radionuclides are measured in soil (used for cultivation), building materials (soil, bricks, sand, marble, etc.), water and dietary items, worldwide. The available literature revealed that numerous studies related to the subject have been carried out in Pakistan. Most of these studies measured the radioactivity concentrations of primordial [uranium (238U), thorium (232Th), radium (226Ra) and potassium (40K)] and anthropogenic [cesium (137Cs)] radionuclide in soil samples (used for cultivation), fertilizers, building materials (i.e. bricks, rocks, sand, soil, marble, etc.), as well as water and dietary items, using a sodium iodide detector or high purity germanium. An effort was made in 2008 to compile these studies as a review article. However, since then, considerable studies have been undertaken and reported in the literature. Therefore, the main objective of the present article is to provide a countrywide baseline data on radionuclide levels, by overviewing and compiling the relevant studies carried out in Pakistan.

Usefulness Of Neutrophils To Lymphocytes Ratio For Predicting Troponin-I Elevation In Patients Presenting With Suspected Nste-Acute Coronary Syndrome.

BACKGROUND: Most of the admissions to the coronary care unit are patients who are having Non- ST-segment elevation acute coronary syndrome (NSTE-ACS). Inflammation has an important role in the pathogenesis of the acute coronary syndrome. Inflammatory marker such as Leukocyte counts & most importantly Neutrophils to Lymphocyte Ratio (NLR) has been found an important predictor of cardiovascular events. Few studies show the diagnostic role of Neutrophils to Lymphocyte ratio in the patient presenting with NSTE-ACS. The objective of this study was to determine the diagnostic role of Neutrophils to Lymphocytes ratio to predict the elevation of Troponin-I in patients presenting with suspected NSTE-acute coronary syndrome. METHODS: This was a Descriptive Case Series study, conducted in Cardiology department Ayub Teaching Hospital/Ayub Medical College Abbottabad, from 15th May 2017 to30th December 2018. A total of 203 patients with suspected NSTE-ACS were inducted in the study by non-probability, consecutive sampling. RESULTS: Results of this study shown a strong correlation between Neutrophils to Lymphocyte ratio (NLR) & rise in Troponin-I levels. Furthermore, results shown that at 4th quartile of Neutrophils to Lymphocyte ratio (NLR) there is high Specificity (97.8%) and very high positive predictive of value 96.7% for predicting the rise in Troponin-I levels. CONCLUSION: We concluded that there is a strong correlation between rising Neutrophils to Lymphocyte ratio (NLR) and cardiac Troponin-I elevation in patients presenting with suspected NSTE-acute coronary syndrome. Therefore, this parameter can be used to predict the rise in troponin level in patients presenting with suspected NSTE-ACS.

Association Of Degree Of St Segment Depression With Inhospital Mortality In Patients With Non-St Elevation Myocardial Infarction.

BACKGROUND: Ischemic heart disease is responsible for approximately 1/3 of all global deaths, making it a leading cause of cardiovascular mortality. Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) which is an acute event in spectrum of coronary artery disease is a potentially lifethreatening emergency, makes up for the majority of admissions to a cardiac unit with one-year mortality rate of 23.5%. The objective of this study was to determine the association of degree of ST segment depression on hospital mortality in patients presenting with Non-ST segment elevation myocardial infarction (NSTEMI). METHODS: This descriptive case-series was carried out in the department of Cardiology, Punjab Institute of Cardiology Lahore. Using Non-probability purposive sampling technique, a total of 250 patients of age between 30-75 years of either gender, who reported during the study period, with NSTEMI were inducted in this study.. RESULTS: In our study, 33.2% (n=83) patients were between 30-50 years and 66.8% (n=167) patients were between 51-75 years of the age. Mean age was 54.64±9.69 years. 43.2% (n=108) patients were male and 56.8% (n=142) were females. Frequency of in-hospital mortality was 4.4% (n=11). Mortality increased with increasing degree of ST segment depression on admission Electrocardiogram (ECG).. CONCLUSIONS: In patients admitted with Non-ST segment elevation myocardial infarction (NSTEMI), degree of ST segment depression on admission ECG predicts In-Hospital mortality.

Cleavage of misfolded nuclear receptor corepressor confers resistance to unfolded protein response-induced apoptosis.

We have recently reported that accumulation of misfolded nuclear hormone receptor corepressor (N-CoR) as insoluble protein aggregates in acute promyelocytic leukemia (APL) cells induces endoplasmic reticulum (ER) stress and activates unfolded protein response (UPR). Although accumulation of misfolded proteins is known to trigger UPR-induced cytotoxic cell death in several neurodegenerative disorders, APL cells are notably resistant to UPR-induced apoptosis. The molecular basis for the paradoxical response of APL cells to UPR is not known. Here, we report that a glycoprotease, selectively expressed in APL cells, regulates the response of APL cells to UPR-induced apoptosis through processing of misfolded N-CoR protein. Results show that misfolded N-CoR is cleaved selectively in APL cells, and cellular extracts of APL cells and human primary APL cells contain activity that cleaves N-CoR protein. Purification and spectrometric analysis of N-CoR cleaving activity from an APL cell line reveals that it is a glycoprotein endopeptidase known as OSGEP. Furthermore, the cleavage of N-CoR in APL cells could be blocked by the broad-spectrum protease inhibitor AEBSF and by RNA interference-mediated down-regulation of OSGEP expression. AEBSF selectively inhibits growth and promotes apoptosis of APL cells possibly through a mechanism involving AEBSF-induced accumulation of insoluble N-CoR protein and by triggering ER stress. Taken together, these findings suggest that selective induction of protease activity in APL cells may represent a novel cytoprotective component of UPR, which could be exploited by tumor cells to survive the toxic insult of misfolded protein(s).

Synergistic antileukemia effect of genistein and chemotherapy in mouse xenograft model and potential mechanism through MAPK signaling.

We investigated the antiproliferative effect of genistein, and its antileukemia effect in combination with cytosine arabinoside (ara-C) in acute myeloid leukemia (AML). Optimal dosage of genistein as single agent and in combination with ara-C was first determined in vitro. Genistein demonstrated a dose- and time-dependent inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest at G(2)/M phase. Gene-expression profiles revealed mitogen-activated protein kinase (MAPK) signaling as one of the most affected biological pathways. Phosphatidylinositol 3 kinase, protein kinase A, protein kinase C, MAPK kinase 4, KIT, PIM1, and transforming growth factor-beta receptor 1, were significantly downregulated by genistein. To test whether genistein could augment the antiproliferation activity of ara-C, two groups of severe combined immunodeficient mice were inoculated with NB4 and HL-60 cells, respectively, followed by treatment with either genistein or combination of genistein and ara-C. The combination treatment significantly inhibited tumor growth, and improved survival of NB4 (p = 0.0031) and HL-60 (p = 0.0007) xenograft mice. Our present study highlighted the schedule-dependent synergistic antileukemia effect of genistein with chemotherapy in both in vitro and in vivo models. This novel combination could potentially be a promising regimen for treatment of AML.

Therapeutic targeting of nuclear receptor corepressor misfolding in acute promyelocytic leukemia cells with genistein.

We have recently reported that PML-RAR-induced misfolding of the N-CoR protein could be reversed by retinoic acid (RA), a therapeutic agent that promotes differentiation of acute promyelocytic leukemia (APL) cells. This finding suggests a role of misfolded N-CoR in the differentiation arrest of APL cells and highlights its significance as a potential molecular target in protein conformation-based therapy for APL. Based on this hypothesis, we investigated the therapeutic potential of several protein conformation modifiers on APL-derived cell lines NB4 and NB4-R1. Through a small-scale screening of these selected compounds, we identified genistein as a potent inhibitor of growth of both RA-sensitive and RA-resistant APL cells. Genistein inhibited the growth of NB4 cells through its collective regulatory effects on cell cycle progression, differentiation, and apoptosis. Genistein-induced apoptosis of NB4 cells was mediated by activation of caspase-9 and caspase-3 and was associated with a decrease in mitochondrial transmembrane potential and cytosolic release of cytochrome c. Genistein promoted differentiation of both RA-sensitive and RA-resistant NB4 cells and induced cell cycle arrest by blocking the G(2)-M transition. Genistein up-regulated the expression of PML and N-CoR proteins, promoted degradation of PML-RAR, and reorganized the microspeckled distribution of PML oncogenic domains to a normal dot-like pattern in NB4 cells. Moreover, genistein significantly reversed the PML-RAR-induced misfolding of N-CoR protein by possibly inhibiting the selective phosphorylation-dependent binding of N-CoR to PML-RAR. These findings identify genistein as a potent modifier of N-CoR protein conformation and highlights its therapeutic potential in both RA-sensitive and RA-resistant APL cells.

Analysis of Indium Oxidation State on the Electronic Structure and Optical Properties of TiO2.

Due to the high formation energy of Indium interstitial defect in the TiO2 lattice, the most probable location for Indium dopant is substitutional sites. Replacing Ti by In atom in the anatase TiO2 shifted the absorption edge of TiO2 towards visible regime. Indium doping tuned the band structure of TiO2 via creating In 5p states. The In 5p states are successfully coupled with the O 2p states reducing the band gap. Increasing In doping level in TiO2 improved the visible light absorption. Compensating the charge imbalance by oxygen vacancy provided compensated Indium doped TiO2 model. The creation of oxygen vacancy widened the band gap, blue shifted the absorption edge of TiO2 and declined the UV light absorption. The 2.08% In in TiO2 is the optimal Indium doping concentration, providing suitable band structure for the photoelectrochemical applications and stable geometrical configuration among the simulated models. Our results provide a reasonable explanation for the improved photoactivity of Indium doped TiO2.

DFT Insights into the Role of Relative Positions of Fe and N Dopants on the Structure and Properties of TiO2.

The location and nature of the doped elements strongly affect the structural, electronic and optical properties of TiO2. To tailor the band structure and modify the photoelectrochemical properties of TiO2, a pair of dopants is selected. Fe and N atoms are inserted in the TiO2 network at substitutional and interstitial sites with different relative distances. The main objective behind the different locations and sites of the doped elements is to banish the isolated unoccupied states from the forbidden region that normally annihilates the photogenerated carriers. Fe at the Ti site and N at the O site doped in the TiO2 network separated at a distance of 7.805 Å provided a suitable configuration of dopant atoms in terms of geometry and band structure. Moreover, the optical properties showed a notable shift to the visible regime. Individual dopants either introduced isolated unoccupied states in the band gap or disturbed the fermi level and structural properties. Furthermore, the other co-doped configurations showed no remarkable band shift, as well as exhibiting a suitable band structure. Resultantly, comparing the band structure and optical properties, it is argued that Fe (at Ti) and N (at O) doped at a distance of 7.805 Å would strongly improve the photoelectrochemical properties of TiO2.

Determining E1 and E2 values for yttrium aluminum garnet ceramics using the Duane-Hunt limit.

A major challenge when performing scanning electron microscopy and X-ray analysis on many ceramic materials is their electrical insulation properties, which leads to buildup of the surface charge and reduced contrast in the secondary electron image. A new procedure was established to quantitatively determine the neutral state values, E1 and E2 , of yttrium aluminum garnet (YAG) ceramics using the Duane-Hunt limit (EDHL ) of Bremsstrahlung, in order to eliminate this charge effect. Thirty-eight EDHL values were linearly fitted with the last portion of X-ray spectra acquired under the incident energy, E0 , from 0.35 to 5.0 kV. According to the distribution of EDHL , two piecewise linear fitting was first employed with a breakpoint of 1.0 kV. Consequently, two intersection points of 0.54 and 2.48 kV, which correspond to E1 and E2 for YAG ceramics, were directly determined using a theoretical curve (EDHL = E0 ). As a result, the high-resolution images of the YAG ceramic grain structure were successfully obtained using the calculated E1 and E2 values.

Procedural Outcomes Of Primary Percutaneous Coronary Intervention In Elderly Patients With Stemi.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide, and coronary artery disease (CAD) is the most prevalent manifestation associated with high mortality and morbidity. Older age is independent predictor of cardiovascular mortality and death. Elderly may experience high rates of complications following acute STEMI. Optimal reperfusion strategy in elderly following STEMI remains under debate due to their exclusion from trials evaluating various treatment modalities. Primary PCI has emerged as treatment of choice in patients presenting with acute STEMI in a certain window period. The rationale of this study is to help us determine the outcome of primary PCI in the local elderly population. METHODS: The study was designed as descriptive cross-sectional study and was carried out at AFIC, NIHD hospital Rawalpindi over a six months period. A total of 105 adults with STEMI were included in study. Data was analysed using SPSS-19.0. RESULTS: Total 105 patients were included in the study according to the inclusion criteria of the study. There were 102 (97.1%) patients who successfully achieved TIMI II flow post Primary PCI.. CONCLUSIONS: We concluded that outcome of primary PCI in local elderly population is favourable which leads to a consensus that primary PCI should be offered to every elderly patient presenting to tertiary care hospital with well-equipped Cath lab and experienced staff.

Electronic Band Structure Variations in the Ceria Doped Zirconia: A First Principles Study.

Using first principle calculations, the effect of Ce with different doping concentrations in the network of Zirconium dioxide (ZrO2) is studied. The ZrO2 cell volume linearly increases with the increasing Ce doping concentration. The intrinsic band gap of ZrO2 of 5.70 eV reduces to 4.67 eV with the 2.08% Ce doping. In 4.16% cerium doped ZrO2, the valence band maximum and conduction band minimum come closer to each other, about 1.1 eV, compared to ZrO2. The maximum band gap reduction of ZrO2 is observed at 6.25% Ce doping concentration, having the value of 4.38 eV. No considerable shift in the band structure is found with further increase in the doping level. The photo-response of the ZrO2 is modulated with Ce insertion, and two distinct modifications are observed in the absorption coefficient: an imaginary part of the dielectric function and conductivity. A 2.08% Ce-doped ZrO2 modeled system reduces the intensities of peaks in the optical spectra while keeping the peaks of intrinsic ZrO2. However, the intrinsic peaks related to ZrO2 completely vanish in 4.16%, 6.25%, 8.33%, and 12.5% Ce doped ZrO2, and a new absorption hump is created.

Induction of Th1 type-oriented humoral response through intranasal immunization of mice with SAG1-Toxoplasma gondii polymeric nanospheres.

About one-third of the world population is prone to have infection with T. gondii, which can cause toxoplasmosis in the developing fetus and in people whose immune system is compromised through disease or chemotherapy. Surface antigen-1 (SAG1) is the candidate of vaccine against toxoplasmosis. Recent advances in biotechnology and nano-pharmaceuticals have made possible to formulate nanospheres of recombinant protein, which are suitable for sub-unit vaccine delivery. In current study, the local strain was obtained from cat feces as toxoplasma oocysts. Amplified 957 bp of SAG1 was cloned into pGEM-T and further sub-cloned into pET28-SAG1. BL21 bacteria were induced at different concentrations of isopropyl ß-d-1-thiogalactopyranoside for the expression of rSAG1 protein. An immunoblot was developed for the confirmation of recombinant protein expression at 35 kDa that was actually recognized by anti-HIS antibodies and sera were collected from infected mice. PLGA encapsulated nanospheres of recombinant SAG1 were characterized through scanning electron microscopy. Experimental mice were intraperitoneally immunized with rSAG1 protein and intra-nasally immunized with nanosphere. The immune response was evaluated by indirect ELISA. In results intra-nasally administered rSAG1 in nanospheres appeared to elicit elevated responses of specific IgA and IgG2a than in control. Nanospheres of rSAG1 are found to be a bio-compatible candidate for the development of vaccine against T. gondii.

Misfolded N-CoR is Linked to the Ectopic Reactivation of CD34/Flt3-Based Stem-Cell Phenotype in Promyelocytic and Monocytic Acute Myeloid Leukemia.

Nuclear receptor co-repressor (N-CoR) is the key component of generic co-repressor complex essential for the transcriptional control of genes involved in cellular hemostasis. We have recently reported that N-CoR actively represses Flt3, a key factor of hematopoietic stem cells (HSC) self-renewal and growth, and that de-repression of Flt3 by the misfolded N-CoR plays an important role in the pathogenesis of promyelocytic and monocytic acute myeloid leukemia (AML). The leukemic cells derived from the promyelocytic and monocytic AML are distinctly characterized by the ectopic reactivation of stem cell phenotypes in relatively committed myeloid compartment. However, the molecular mechanism underlying this phenomenon is not known. Here, we report that N-CoR function is essential for the commitment of primitive hematopoietic cells to the cells of myeloid lineage and that loss of N-CoR function due to misfolding is linked to the ectopic reactivation of generic stem cell phenotypes in promyelocytic and monocytic AML. Analysis of N-CoR and Flt3 transcripts in mouse hematopoietic cells revealed a positive correlation between N-CoR level and the commitment of myeloid cells and an inverse correlation between N-CoR and Flt3 levels in primitive as well as committed myeloid cells. Enforced N-CoR expression in mouse HSCs inhibited their growth and self-renewal potentials and promoted maturation toward cells of myeloid lineage, suggesting a role of N-CoR in the commitment of cells of myeloid lineage. In contrast to AML cells with natively folded N-CoR, primary and secondary promyelocytic and monocytic AML cells harboring the misfolded N-CoR were highly positive for Flt3 and myeloid antigen-based HSC marker CD34. Genetic and therapeutic restoration of N-CoR conformation significantly down-regulated the CD34 levels in monocytic AML cells, suggesting an important role of N-CoR in the suppression of CD34-based HSC phenotypes. These findings collectively suggest that N-CoR is crucial for the commitment of primitive hematopoietic cells to cells of myeloid lineage and that misfolded N-CoR may contribute to transformation of committed myeloid cells through the ectopic reactivation of Flt3/CD34-based stem cell phenotypes in promyelocytic and monocytic AML. Moreover, these findings provide novel mechanistic insights into the formation of leukemic stem cells in subsets of AML and identify the misfolded N-CoR as a subtype-specific biomarker of AML.