To date, all methods to generate induced pluripotent stem cells (iPSCs) require the use of genetic materials and/or potentially mutagenic molecules. Here we report the generation of stable iPSCs from ...human fibroblasts by directly delivering four reprogramming proteins (Oct4, Sox2, Klf4, and c-Myc) fused with a cell-penetrating peptide (CPP). These protein-induced human iPSCs (p-hiPSCs) exhibited similarity to human embryonic stem cells (hESCs) in morphology, proliferation, and expression of characteristic pluripotency markers. p-hiPSC lines produced with these recombinant proteins were successfully maintained for more than 35 passages and differentiated into derivatives of all three embryonic germ layers both invitro and in teratomas. This system eliminates the potential risks associated with the use of viruses, DNA transfection, and potentially harmful chemicals and in the future could potentially provide a safe source of patient-specific cells for regenerative medicine.
Increasing evidence suggests a role for inflammation in neuropsychiatric conditions including autism spectrum disorder (ASD), a neurodevelopmental syndrome with higher prevalence in males than ...females. Here we examined the effects of early-life immune system activation (EIA)-comprising regimens of prenatal, early postnatal, or combined ("two-hit") immune activation-on the core behavioral features of ASD (decreased social interaction, increased repetitive behavior, and aberrant communication) in C57BL/6J mice. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C) on gestational day 12.5 to produce maternal immune activation (MIA). Some offspring also received lipopolysaccharide (LPS) on postnatal day 9 to produce postnatal immune activation (PIA). EIA produced disruptions in social behavior and increases in repetitive behaviors that were larger in males than in females. Ultrasonic vocalizations (USVs) were altered in both sexes. Molecular studies revealed that EIA also produced prominent sex-specific changes in inflammation-related gene expression in the brain. Whereas both sexes showed increases in pro-inflammatory factors, as reflected by levels of mRNA and protein, expression of anti-inflammatory factors was decreased in males but increased in females. Our findings demonstrate that EIA can produce sex-specific behavioral effects and immune responses in the brain, and identify molecular processes that may contribute to resilience in females.
Abstract
In this study, we report a surfactant-mediated synthesis of ferrites (MFe
2
O
4
: M = Co, Ni, Cu, Zn) using the co-precipitation-oxidation method. The band gap calculated from UV-Visible ...diffuse reflectance spectra were found in the range of 1.11–1.81 eV. These ferrite nanocatalysts were studied for the photocatalytic degradation of multiple organic dyes in a 32 W UV-C/H
2
O
2
system. All the four ferrites showed an excellent dye degradation rate in the range of 2.065–2.417 min
−1
at neutral pH. In the optimized condition, NiF was found to degrade 89%, 92%, 93%, and 78% of methylene blue, methyl orange, bromo green, and methyl red, respectively within 1 min of UV-irradiation. A 40% TOC removal was recorded after 5 min of degradation reaction, which increased to 60% after 50 min. Mechanism elucidated by scavenger studies and fluorescence spectroscopy revealed that
•
OH and holes were the primary reactive radicals responsible for the degradation process. Ferrite photocatalysts showed an insignificant performance loss in seven consecutive cycles. The photocatalyst was found efficient in the presence of a high concentration of salts. Thus, it was concluded that these photocatalysts are highly suitable for the remediation of dye-contaminated wastewater.
The orphan nuclear receptor Nurr1 (also known as NR4A2) is critical for the development and maintenance of midbrain dopaminergic neurons, and is associated with Parkinson's disease. However, an ...association between Nurr1 and Alzheimer's disease (AD)‐related pathology has not previously been reported. Here, we provide evidence that Nurr1 is expressed in a neuron‐specific manner in AD‐related brain regions; specifically, it is selectively expressed in glutamatergic neurons in the subiculum and the cortex of both normal and AD brains. Based on Nurr1’s expression patterns, we investigated potential functional roles of Nurr1 in AD pathology. Nurr1 expression was examined in the hippocampus and cortex of AD mouse model and postmortem human AD subjects. In addition, we performed both gain‐of‐function and loss‐of‐function studies of Nurr1 and its pharmacological activation in 5XFAD mice. We found that knockdown of Nurr1 significantly aggravated AD pathology while its overexpression alleviated it, including effects on Aβ accumulation, neuroinflammation, and neurodegeneration. Importantly, 5XFAD mice treated with amodiaquine, a highly selective synthetic Nurr1 agonist, showed robust reduction in typical AD features including deposition of Aβ plaques, neuronal loss, microgliosis, and impairment of adult hippocampal neurogenesis, leading to significant improvement of cognitive impairment. These in vivo and in vitro findings suggest that Nurr1 critically regulates AD‐related pathophysiology and identify Nurr1 as a novel AD therapeutic target.
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•UV pretreatment of the catalyst activate the surface for oxidation of pollutants.•Complete mineralization of VOC occurred followed by adsorption.•we want to represent (.OH) as ...hydroxyl radical showing with free radical means one dot on the OH group OH and OH we want to present this OH group as Hydroxyl ion with negative charge (OH(-)) are main radicals responsible for the degradation of VOC.•The heterogeneous photo-Fenton process is sustainable for multiple reuse of the catalyst.
In this work, the performance of benzene, toluene, ethylbenzene, and xylene (BTEX) removal and degradation from gas, air streams on UV pretreated Fe-ZSM-5 in a batch reactor at room temperature were studied. The Fe-ZSM-5 zeolite catalyst was prepared by hydrothermal reaction method. The influence of UV pre-irradiation time on the removal of BTEX were assessed by varying the time, ranging from 15min to 60smin. Then, sustainability of the activation of the catalyst resulted by UV pretreatment was studied by the four-cycle experiment with one time UV irradiation and after each cycle irradiation followed by BTEX removal after every cycle respectively. The results of BTEX removal depicted that 30min of UV pretreatment was sufficient for complete organics removal. The UV pretreatment effect on the catalytic oxidation and the stability of the catalyst were studied by modern instrumental techniques. The novelty of the process was the sustainable reuse of catalyst with persistent VOC removal, which works on the -adsorption-oxidation-regeneration-adsorption- cycle, which was confirmed by the characterization studies of the catalyst after four runs. The results revealed that the change in the structure, stability, morphology, and removal efficiency of the catalyst during the experiments was negligible. The VOC degradation mechanism studies showed that the oxidation occurs due to the formation of free radicals as well as hydroxyl ions, so named it heterogeneous photo-Fenton oxidation. The residual materials analysis showed the complete mineralization of VOC except small amount of acetone as oxidation product. Lastly, the kinetics of the VOC removal was studied.
Human induced pluripotent stem cells (hiPSC) have been shown to differentiate into a variety of replacement cell types. Detailed evaluation and comparison with their human embryonic stem cell (hESC) ...counterparts is critical for assessment of their therapeutic potential. Using established methods, we demonstrate here that hiPSCs are capable of generating hemangioblasts/blast cells (BCs), endothelial cells, and hematopoietic cells with phenotypic and morphologic characteristics similar to those derived from hESCs, but with a dramatic decreased efficiency. Furthermore, in distinct contrast with the hESC derivatives, functional differences were observed in BCs derived from hiPSCs, including significantly increased apoptosis, severely limited growth and expansion capability, and a substantially decreased hematopoietic colony‐forming capability. After further differentiation into erythroid cells, >1,000‐fold difference in expansion capability was observed in hiPSC‐BCs versus hESC‐BCs. Although endothelial cells derived from hiPSCs were capable of taking up acetylated low‐density lipoprotein and forming capillary‐vascular‐like structures on Matrigel, these cells also demonstrated early cellular senescence (most of the endothelial cells senesced after one passage). Similarly, retinal pigmented epithelium cells derived from hiPSCs began senescing in the first passage. Before clinical application, it will be necessary to determine the cause and extent of such abnormalities and whether they also occur in hiPSCs generated using different reprogramming methods. STEM CELLS 2010;28:704–712
The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated ...metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 Å resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21° shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function.
•Study about the mechanism of Ca2+ and Mg2+ bonding with aerobic granules.•Ca2+ enhanced settleability while Mg2+ improved dewaterability of granular sludges.•Fate of particular EPS produced depends ...upon its structure and size of the metal.•Larger size Ca2+ made bonding with less crowded hydroxyl groups of polysaccharides.•Mg2+ due to smaller size had strong interactions with amide groups of proteins.
The main objectives of the present study were to investigate the interactions of divalent metals (Ca2+ and Mg2+) with protein and polysaccharide components of extracellular polymeric substances (EPS) and to deduce their role in imparting different physicochemical characteristics to aerobic granules in sequencing batch reactor (SBR) system. Three reactors were run for 60 days; R-1 functioned as a control reactor, whereas R-2 and R-3 were operated by dosing 25mg/L of Ca2+ and Mg2+, respectively, and the other operating conditions were similar in all of the SBRs. The granulation rate, particle size and sludge settleability were rapidly increased by Ca2+ addition, whereas the sludge dewaterability was significantly enhanced by Mg2+ augmentation. During the investigations, R-1, R-2 and R-3 had 1.31, 2.98 and 1.58 times higher quantities of polysaccharides, whereas proteins were 1.28, 1.74 and 2.41 times, respectively, more abundant than seed sludge. The divalent metals profoundly changed the composition of EPS, but their total contents were almost similar. XPS and FTIR results showed that Ca2+ bonded strongly with hydroxyl groups of polysaccharides due to there being less steric hindrance than proteins, and Mg2+ preferably bonded with amide groups of proteins and found no such hindrance due to its smaller size and thus changed the composition of EPS, which eventually altered the granular sludge characteristics.
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