Characterization of chemokine receptors expressed in primitive blood cells during human hematopoietic ontogeny

Chemokines are capable of regulating a variety of fundamental processes of hematopoietic cells that include proliferation, differentiation, and migration. To evaluate potential chemokine signaling pathways important to the regulation of primitive human hematopoietic cells, we examined chemokine receptor expression of highly purified subpopulations of uncommitted human blood cells. CXCR1-, CXCR2-, CXCR4-, and CCR5-expressing cells were detected by flow cytometry among human blood subsets depleted of lineage-restricted cells (Lin(-)) derived from adult bone marrow, mobilized peripheral blood, cord blood (CB), and circulating fetal blood. Although these chemokine receptors could be detected on Lin(-) cells throughout human development, only CXCR4 could be detected in CD34(-)CD38(-)Lin(-) and CD34(+)CD38(-)Lin(-) subfractions enriched for stem cell function, suggesting that independent of ontogeny, CXCR4-mediated signals are critical to primitive hematopoiesis. Distinct to other stages of human hematopoietic development, primitive CB cells expressed higher levels of CXCR1, CXCR2, CCR5, and CXCR4 on both CD34(-)CD38(-)Lin(-) and CD34(+)CD38(-)Lin(-) subsets. Isolation of these fractions revealed expression of additional chemokine receptors CCR7, CCR8, and Bonzo (STRL133), whereas BOB (GPR15) could not be detected. Our study illustrates that rare uncommitted hematopoietic cells express chemokine receptors not previously associated with primitive human blood cells. Based on these results, we suggest that signaling pathways mediated by chemokine receptors identified here may play a fundamental role in hematopoietic stem cell regulation and provide alternative receptor targets for retroviral pseudotyping for genetic modification of repopulating cells.     

Molecular evolution of the hemagglutinin and neuraminidase genes of pandemic (H1N1) 2009 influenza viruses in Sendai, Japan, during 2009–2011

Analyzing the evolutionary pattern of the influenza A(H1N1)pdm09 strain in different regions is important for understanding its diversification. We therefore conducted this study to elucidate the genetic variability and molecular evolution of the influenza A(H1N1)pdm09 strains that circulated during the 2009–2010 and 2010–2011 influenza seasons in Sendai, Japan. Nasopharyngeal swab specimens were collected from patients with influenza-like illnesses who visited outpatient clinics in Sendai City, Japan, from September 2009 to April 2011. A total of 75 isolates were selected from September 2009 to April 2011 to analyze the genetic changes in the entire hemagglutinin 1 (HA1) segment of the HA gene and the neuraminidase (NA) gene based on sequence analysis. Bayesian coalescent Markov chain Monte Carlo analyses of HA1 and NA gene sequences were performed for further analysis. High sequence identities were observed for HA1 and NA in influenza A(H1N1)pdm09, displaying 99.06 and 99.33 % nucleotide identities, respectively, with the A(H1N1)pdm09 vaccine strain A/California/07/2009. The substitution rates of nucleotides for HA1 in the 2009–2010 and 2010–2011 were 1.5 × 10^?3 and 1.6 × 10^?3 substitutions per site per year, respectively. Phylogenetic tree analysis demonstrated that Sendai isolates were clustered into global clade 7, which is characterized by an S203T mutation in the HA1 gene. Moreover, two distinct circulation clusters were present in the 2010–2011 season. Mutations were present in antigenic or receptor-binding domains of the HA1 segment, including A141V, S143G, S183P, S185T, and S203T. The Bayesian skyline plot model illustrated a steady rate for the maintenance of genetic diversity, followed by a slight increase in the later part of the 2010–2011 season. Selection analysis revealed that the HA1 (position 197) and NA (position 46) sites were under positive selection; however, no known mutation conferring resistance to NA inhibitors such as H275Y was observed. The effect on control of the influenza A(H1N1)pdm09 virus, including vaccine strain selection, requires continuous monitoring of the strain by genetic surveillance.     

An advanced and efficient Co3O4/C nanocomposite for the oxygen evolution reaction in alkaline media

The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy. In this study, we developed a facile approach to produce porous carbon from the dehydration of sucrose and use it for the preparation of nanocomposites with cobalt oxide (Co₃O₄). The nanocomposites were studied by the powder X-ray diffraction and scanning electron microscopy techniques, and they exhibited the cubic phase of cobalt oxide and porous structure of carbon. The nanocomposites showed significant OER activity in alkaline media, and the current densities of 10 and 20 mA cm⁻² could be obtained at 1.49 and 1.51 V versus reversible hydrogen electrode (RHE), respectively. The impedance study confirms favorable OER activity on the surface of the prepared nanocomposites. The nanocomposite is cost-effective and can be capitalized in various energy storage technologies.

The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy.     

Effects of early life adversity on immune function and cognitive performance: results from the ALSPAC cohort

Social Psychiatry and Psychiatric Epidemiology - Early life adversity (ELA) is a significant risk factor for mental health disorders. One hypothesised mechanism by which this occurs is via an...     

Cytotoxic and photocatalytic studies of hexagonal boron nitride nanotubes: a potential candidate for wastewater and air treatment

Boron nitride (BN) nanomaterials are rapidly being investigated for potential applications in biomedical sciences due to their exceptional physico-chemical characteristics. However, their safe use demands a thorough understanding of their possible environmental and toxicological effects. The cytotoxicity of boron nitride nanotubes (BNNTs) was explored to see if they could be used in living cell imaging. It was observed that the cytotoxicity of BNNTs is higher in cancer cells (65 and 80%) than in normal cell lines (40 and 60%) for 24 h and 48 h respectively. The influence of multiple experimental parameters such as pH, time, amount of catalyst, and initial dye concentration on percentage degradation efficiency was also examined for both catalyst and dye. The degradation effectiveness decreases (92 to 25%) as the original concentration of dye increases (5–50 ppm) due to a decrease in the availability of adsorption sites. Similarly, the degradation efficiency improves up to 90% as the concentration of catalyst increases (0.01–0.05 g) due to an increase in the adsorption sites. The influence of pH was also investigated, the highest degradation efficiency for MO dye was observed at pH 4. Our results show that lower concentrations of BNNTs can be employed in biomedical applications. Dye degradation properties of BNNTs suggest that it can be a potential candidate as a wastewater and air treatment material.

Photocatalytic degradation studies of methyl orange using BNNTs.     

Investigation of Self-Healing Mortars with and without Bagasse Ash at Pre- and Post-Crack Times

Cracks in typical mortar constructions enhance water permeability and degrade ions into the structure, resulting in decreased mortar durability and strength. In this study, mortar samples are created that self-healed their cracks by precipitating calcium carbonate into them. Bacillus subtilus bacterium (10⁻⁷, 10⁻⁹ cells/mL), calcium lactate, fine aggregate, OPC-cement, water, and bagasse ash were used to make self-healing mortar samples. Calcium lactates were prepared from discarded eggshells and lactic acid to reduce the cost of self-healing mortars, and 5% control burnt bagasse ash was also employed as an OPC-cement alternative. In the presence of moisture, the bacterial spores in mortars become active and begin to feed the nutrient (calcium lactate). The calcium carbonate precipitates and plugs the fracture. Our experimental results demonstrated that cracks in self-healing mortars containing bagasse ash were largely healed after 3 days of curing, but this did not occur in conventional mortar samples. Cracks up to 0.6 mm in self-healing mortars were filled with calcite using 10⁻⁷ and 10⁻⁹ cell/mL bacteria concentrations. Images from an optical microscope, X-ray Diffraction (XRD), and a scanning electron microscope (SEM) were used to confirm the production of calcite in fractures. Furthermore, throughout the pre- and post-crack-development stages, self-healing mortars have higher compressive strength than conventional mortars. The precipitated calcium carbonates were primed to compact the samples by filling the void spaces in hardened mortar samples. When fissures developed in hardened mortars, bacteria became active in the presence of moisture, causing calcite to precipitate and fill the cracks. The compressive strength and flexural strength of self-healing mortar samples are higher than conventional mortars before cracks develop in the samples. After the healing process of the broken mortar parts (due to cracking), self-healing mortars containing 5% bagasse ash withstand a certain load and have greater flexural strength (100 kPa) than conventional mortars (zero kPa) at 28 days of cure. Self-healing mortars absorb less water than typical mortar samples. Mortar samples containing 10⁻⁷ bacteria cells/mL exhibit greater compressive strength, flexural strength, and self-healing ability. XRD and SEM were used to analyze mortar samples with healed fractures. XRD, FTIR, and SEM images were also used to validate the produced calcium lactate. Furthermore, the durability of mortars was evaluated using DTA-TGA analysis and water absorption tests.     

Endoplasmic reticulum (ER) stress: hepatitis C virus induces an ER-nucleus signal transduction pathway and activates NF-kappaB and STAT-3

Human hepatitis C virus (HCV) is the leading cause of chronic hepatitis, which often results in liver cirrhosis and hepatocellular carcinoma. The HCV RNA genome codes for at least ten proteins. The HCV non-structural protein 5A (NS5A) has generated considerable interest due to its effect on interferon sensitivity via binding and inactivating the cellular protein kinase, PKR. It has been shown that NS5A engages in the endoplasmic reticulum (ER)-nucleus signal transduction pathway. The expression of NS5A in the ER induces an ER stress ultimately leading to the activation of STAT-3 and NF-kappaB. This pathway is sensitive to inhibitors of Ca(2+) uptake in the mitochondria (ruthenium red), Ca(2+) chelators (TMB-8, EGTA-AM), and antioxidants (PDTC, NAC, Mn-SOD). The inhibitory effect of protein tyrosine kinase (PTK) inhibitors indicates the involvement of PTK in NF-kappaB activation by NS5A. This implicates an alternate pathway of NF-kappaB activation by NS5A. The actions of NS5A have also been studied in the context of an HCV subgenomic replicon inducing a similar intracellular event. Thus, activation of NF-kappaB leads to the induction of cellular genes, which are largely antiapoptotic in function. These studies suggest a potential function of NS5A in inducing chronic liver disease and hepatocellular carcinoma associated with HCV infection.     

Bone mineral measurement of phalanges: comparison of radiographic absorptiometry and area dual X-ray absorptiometry

With a standard, image-intensifier-based, digital radiographic system, high-spatial-resolution images of the hand were acquired for analysis of phalangeal bone mineral density with dual x-ray absorptiometry (DXA). Results with phalangeal DXA had precision of plus or minus 0.67% and accuracy of 4.1% and correlated well with those with radiographic absorptiometry. This phalangeal DXA technique is potentially useful for clinical diagnosis of osteoporosis.