T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1–3. Here we developed a clinical-grade approach based on CRISPR–Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen–HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.
Nanotechnology is the promising field with its wide applications in biotechnology, pharmaceutical science, drug targeting, nano-medicine and other research areas. This review highlights the positive and negative impact of nanoparticles on plants and its wide applications in agricultural sciences. Effect of NPs in terms of seed germination, growth promotion and enhancement of metabolic rate has been evaluated by several scientific researches. However, NPs also exert their negative effects such as suppression of plant growth, inhibition of chlorophyll synthesis, photosynthetic efficiency etc. Effects of NPs can be either positive or negative it depending upon the plant species and type of nanoparticles used & its concentration. Modern nano-biotechnological tools have a great potential to increase food quality, global food production, plant protection, detection of plant and animal diseases, monitoring of plant growth nano-fertilizers, nano-pesticide, nano-herbicides and nano-fungicides.
AimTo develop a simple method to assess the level of anxiety by using children’s drawings and correlating them with Frankl’s behavior rating scale.Materials and methodsA total of 178 patients aged of 3 to 14 years were handed out two-page forms which contained three sections on coloring and drawing, along with general information, and Frankl’s behavior rating scale for the visit. The three types of drawing exercises given to the patients were geometric copy drawings, coloring a nonthreatening figure, and an empty sheet for freehand drawing.ResultsOut of 178 patients, 60 showed definitely positive behavior, 73 exhibited positive behavior, 37 showed negative behavior, and 8 were definitely negative on Frankl’s behavior rating scale; 133 children had none or, 1 stress marker and 45 exhibited 2 or 3 stress markers in their drawings. Chi-square (χ2) analysis was done with a 2 × 2 contingency table. Observed χ2 value was 46.166, which at 1 degree of freedom was much greater than that at 0.995 percentile. Therefore, the result was highly significant.ConclusionChildren requiring specialized behavioral techniques can be identified by the presence of stress markers in their drawings. This nonverbal activity by itself can have an overall positive effect on the behavior displayed in the dental clinic.How to cite this articleMathur J, Diwanji A, Sarvaiya B, Sharma D. Identifying Dental Anxiety in Children’s Drawings and correlating It with Frankl’s Behavior Rating Scale. Int J Clin Pediatr Dent 2017;10(1):24-28.
A . P ES H IN AN D J. M. S . M AT H UR .1999. An extracellular b-glucosidase enzyme was purified from the fungus Aspergillus niger strain 322. The molecular mass of the enzyme was estimated to be 64 kDa by SDS gel electrophoresis. Optimal pH and temperature for b-glucosidase were 5·5 and 50°C, respectively. Purified enzyme was stable up to 50°C and pH between 2·0 and 5·5. The K m was 0·1 mmol l −1 for cellobiose. Enzyme activity was inhibited by several divalent metal ions.
Use of green agronomic techniques for plant development and crop protection is essential for environmental sustainability. The current research investigates a more efficient and long-term technique of manufacturing silica nanoparticles (SiO2 NPs) from agricultural waste (sugarcane bagasse and corn cob). SiO2 NPs were synthesized by calcinations of waste residues in muffle furnace with varying temperatures (400–1000 °C)/2 h in the present of static air. Field emission scanning electron microscopy (FESEM), Fourier transmission infrared spectroscopy (FTIR), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDX) were used to characterize SiO2 NPs and assessed for their antifungal activity simultaneously investigated the effects of various concentrations of produced SiO2 NPs on Eruca sativa (E. sativa) physiological and biochemical. With SiO2 NPs treatment at 1000 µg L−1 concentration, the seed germination rate was found to be up to 95.5%, and growth characteristics were enhanced compared to control. Accordingly, the ones treated with SiO2 NPs grew better than the control ones. The treatment of plant with SiO2 NPs (500 μg L−1) increased the protein content by 14.8 mg g−1, and chlorophyll level was also increased by 4.08 mg g−1 in leaves compared to untreated plant. Disc diffusion experiment was conducted to test the efficiency of SiO2 NPs against Fusarium oxysporum and Aspergillus niger for antifungal activities. Highest mycelia growth inhibition was obtained with 73.42% and 58.92% for F. oxysporum and A. niger, respectively. The result shows that the SiO2 NPs have a favorable effect on E. sativa growth and germination, enhancing plant production which helps to improve the sustainable agriculture farming and acting as a possible antifungal agent against plant pathogenic fungi. Graphical Abstract
Genomic DNA polymorphism and variation in biologically active components of Moringa oleifera were investigated by two different techniques: RAPD-PCR and HPLC analysis. The concentrations of phenolic compounds (cinnamic, caffeic, ferulic, and coumaric acids) and the content of flavonoids (rutin) were quantified by HPLC analysis. Among 20 RAPD primers, 13 were selected to generate polymorphic amplicons producing an average of 5028 bands, of which 83.7% were found to be polymorphic among 57 accessions of M. oleifera (MO 1 to MO 57) and one outgroup (ACB 58) from Banasthali region, India. In total, 57 accessions were clustered into five major groups within the dendrogram. The results of this analysis were further confirmed by principal coordinate analysis (PCoA). There was also high diversity in the concentration of active compounds in the collected samples as revealed by HPLC analysis. The data revealed that the content of polyphenolic compounds varied between 0.06 (sample KVKB) and 210.5 mg/kg (sample BG). The results suggest that there is a strong correlation between phytochemical variables and DNA polymorphism. The study concludes that the results of the genetic, morphological, and phytochemical diversity could be used to select the best accessions of M. oleifera for agricultural cultivation and breeding.
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