Molecular therapy : the journal of the American Society of Gene Therapy, Apr 8, 2017
The liver continuously receives antigens from circulation and the gastrointestinal tract. A compl... more The liver continuously receives antigens from circulation and the gastrointestinal tract. A complex immune regulatory system has evolved in order to both limit inflammation and promote tolerance in the liver. Although in situ immune tolerance mechanisms enable successful gene therapy and liver transplantation, at the same time they facilitate chronic infections by pathogens such as hepatitis viruses. It is, however, poorly understood why hepatocytes infected with hepatitis viruses or transduced with adeno-associated virus (AAV)-based vectors may be rejected by CD8(+) T cells several months later. We found that hepatic transfer of limited doses of an AAV-ovalbumin vector rapidly induced antigen-specific CD8(+) T cells that only became functionally competent after >2 months. At this time, CD8(+) T cells had downregulated negative checkpoint markers, e.g., the programmed death 1 [PD-1] receptor, and upregulated expression of relevant cytokines. At further reduced vector dose, only i...
Around 2 billion people are suffering from chronic malnutrition or “hidden hunger”, which is the ... more Around 2 billion people are suffering from chronic malnutrition or “hidden hunger”, which is the result of many diseases and disorders, including cognitive degeneration, stunting growth, and mortality. Thus, biofortification of staple food crops enriched with micronutrients is a more sustainable option for providing nutritional supplements and managing malnutrition in a society. Since 2001, when the concept of biofortification came to light, different research activities have been carried out, like the development of target populations, breeding or genetic engineering, and the release of biofortified cultivars, in addition to conducting nutritional efficacy trials and delivery plan development. Although, being a cost-effective intervention, it still faces many challenges, like easy accessibility of biofortified cultivars, stakeholders’ acceptance, and the availability of biofortified germplasm in the public domain, which varies from region to region. Hence, this review is focused on...
Solid-state sodium ion batteries are frequently referred to as the most promising technology for ... more Solid-state sodium ion batteries are frequently referred to as the most promising technology for next-generation energy storage applications. However, developing a suitable solid electrolyte with high ionic conductivity, excellent electrolyte–electrode interfaces, and a wide electrochemical stability window, remains a major challenge. Although solid-polymer electrolytes have attracted great interest due to their low cost, low density and very good processability, they generally have significantly lower ionic conductivity and poor mechanical strength. Here, we report on the development of a low-cost composite solid polymer electrolyte comprised of poly(ethylene oxide), poly(vinylpyrrolidone) and sodium hexafluorophosphate, mixed with indium arsenide nanowires. We show that the addition of 1.0% by weight of indium arsenide nanowires increases the sodium ion conductivity in the polymer to 1.50 × 10−4 Scm−1 at 40 °C. In order to explain this remarkable characteristic, we propose a new t...
The aim of present investigation pertains to study the impact of different culture media on the m... more The aim of present investigation pertains to study the impact of different culture media on the mycelial growth and dry weight of Pleurotus spp. Grains generally contains high nutritional content thereby decreases the harvesting period of mycelium and enhances dry weight. The study was conducted at Mushroom Laboratory Department Plant Pathology, S. V. P. University of Agriculture and Technology, Meerut, UP, India. Different crop grains were used as source of nutrition for fungus and added in PDA (media) in separate amount. Experiment was conducted in seven treatments with four replications. All the extracts observed varied mycelial growth of Pleurotus spp. After nine days maximum radial growth (90.00 mm) in both species (P. sapidus and P. flabellatus) was observed in barley extract media. The maximum growth rate (10.00 mm/day) of mycelium in P. sapidus and P. flabellatus was recorded in barley extract agar. Maximum dry mycelium weight (7.98 mg/100 ml & 8.35 mg/100 ml) of P. sapidus ...
The integration of transgenes into a plant host genome following Agrobacterium tumefaciens-mediat... more The integration of transgenes into a plant host genome following Agrobacterium tumefaciens-mediated or direct transformation may occur as a single copy or in the form of tandem repeats. The latter has been associated with promoter methylation and silencing of transgenes. Thus, the early screening of such transgenic plants is desirable for ruling out future repeat-dependent transgene instability. We developed a simple PCR-based method in which primer pairs were specifically designed so that amplifications could only be obtained if the transgene was present in the form of multiple inserts in a transgenic line. The method was established using 35S-rolC transgenic aspen lines showing morphologically visible transgenic silencing. Later, it was possible to screen independent transgenic lines showing no visible marker gene expression. Furthermore, a method was developed in which positive PCR amplification was indicative of promoter methylation. The results were consistent and reproducible ...
Gene therapy aims to replace a defective or a deficient protein at therapeutic or curative levels... more Gene therapy aims to replace a defective or a deficient protein at therapeutic or curative levels. Improved vector designs have enhanced safety, efficacy, and delivery, with potential for lasting treatment. However, innate and adaptive immune responses to the viral vector and transgene product remain obstacles to the establishment of therapeutic efficacy. It is widely accepted that endogenous regulatory T cells (Tregs) are critical for tolerance induction to the transgene product and in some cases the viral vector. There are two basic strategies to harness the suppressive ability of Tregs:induction of adaptive Tregs specific to the introduced gene product and concurrent administration of autologous,expanded Tregs. The latter may be polyclonal or engineered to direct specificity to the therapeutic antigen. Recent clinical trials have advanced adoptive immunotherapy with Tregs for the treatment of autoimmune disease and in patients receiving cell transplants. Here, we highlight the po...
Molecular therapy. Methods & clinical development, Jan 16, 2017
Gene-modified B cells expressing immunoglobulin G (IgG) fusion proteins have been shown to induce... more Gene-modified B cells expressing immunoglobulin G (IgG) fusion proteins have been shown to induce tolerance in several autoimmune and other disease models. However, lack of a vector suitable for gene transfer to human B cells has been an obstacle for translation of this approach. To overcome this hurdle, we developed an IgG-human factor IX (hFIX) lentiviral fusion construct that was targeted to specifically transduce cells expressing human CD20 (hCD20). Receptor-specific retargeting by mutating envelope glycoproteins of measles virus (MV)-lentiviral vector (LV) and addition of a single-chain variable fragment specific for hCD20 resulted in gene delivery into primary human and transgenic hCD20 mouse B cells with high specificity. Notably, this protocol neither required nor induced activation of the B cells, as confirmed by minimal activation of inflammatory cytokines. Using this strategy, we were able to demonstrate induction of humoral tolerance, resulting in suppression of antibody...
CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) are critical elements for maintaining immune tole... more CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) are critical elements for maintaining immune tolerance, for instance to exogenous antigens that are introduced during therapeutic interventions such as cell/organ transplant or gene/protein replacement therapy. Co-administration of antigen with rapamycin simultaneously promotes deletion of conventional CD4(+) T cells and induction of Treg. Here, we report that the cytokine FMS-like receptor tyrosine kinase ligand (Flt3L) enhances the in vivo effect of rapamycin. This occurs via selective expansion of plasmacytoid dendritic cells (pDC), which further augments the number of Treg. Whereas in conventional DC, rapamycin effectively blocks mTOR1 signaling induced by Flt3L, increased mTOR1 activity renders pDC more resistant to inhibition by rapamycin. Consequently, Flt3L and rapamycin synergistically promote induction of antigen-specific Treg via selective expansion of pDC. This concept is supported by the finding that Treg induction is abro...
Indian journal of virology : an official organ of Indian Virological Society, 2010
Reduced seed production in onion is associated with Onion yellow dwarf virus (OYDV), a filamentou... more Reduced seed production in onion is associated with Onion yellow dwarf virus (OYDV), a filamentous Potyvirus. Onion is also infected with other filamentous virus particles suspected to be Allexivirus. RT-PCR was used to detect mixed infection of both the viruses in leaves and bulbs. A duplex RT-PCR was developed, which simultaneously detected the presence of these two viruses in winter (Rabi) onion bulb. In summer (Kharif) onion bulbs only Allexivirus was detected. The absence of OYDV in summer crop is discussed. The sequencing of RT-PCR amplified products confirmed the identity of OYDV and Allexivirus, the latter showing closer identity to Garlic virus C (GVC)/Garlic mite-borne mosaic virus. This makes the first detection of an Allexivirus in onion crop in India. The duplex RT-PCR to detect these viruses (OYDV and Allexivirus) would be an improvement for indexing of viruses in onion bulbs for seed production.
A Polyethylene (PE) pipe reinforced by a cross-winding steel wire (PSP) is a new type of plastic-... more A Polyethylene (PE) pipe reinforced by a cross-winding steel wire (PSP) is a new type of plastic-matrix steel composite pipe, which has excellent performance. Its short-time burst pressure, strain, critical buckling pressure, and failure mode under various temperatures were investigated. Experimental results show that PSP has an increase of short-time burst pressure at room temperature up to 129%, ring stiffness up to 19%, and critical buckling pressure up to 57% in comparison with a comparable PE pipe. Failure modes of PSP subjected to internal pressure under various temperatures are found to be ductile burst and excessive deformation, and their transition temperature is about 45°C. Moreover, at the same pressure, the radial expansion ratio of PSP only bearing radial force is much larger than that of PSP bearing both radial and axial forces.
Biochar produced from switchgrass via hydrothermal carbonization (HTC) was used as a sorbent for ... more Biochar produced from switchgrass via hydrothermal carbonization (HTC) was used as a sorbent for the removal of copper and cadmium from aqueous solution. The cold activation process using KOH at room temperature was developed to enhance the porous structure and sorption properties of the HTC biochar. The sorption efficiency of HTC biochar and alkali activated HTC biochar (HTCB) for removing copper and cadmium from aqueous solution were compared with commercially available powdered activated carbon (PAC). The present batch adsorption study describes the effects of solution pH, biochar dose, and contact time on copper and cadmium removal efficiency from single metal ion aqueous solutions. The activated HTCB exhibited a higher adsorption potential for copper and cadmium than HTC biochar and PAC. Experiments conducted with an initial metal concentration of 40 mg/L at pH 5.0 and contact time of 24 h resulted in close to 100% copper and cadmium removal by activated HTCB at 2 g/L, far greater than what was observed for HTC biochar (16% and 5.6%) and PAC (4% and 7.7%). The adsorption capacities of activated HTCB for cadmium removal were 34 mg/g (0.313 mmol/g) and copper removal was 31 mg/g (0.503 mmol/g).
Molecular therapy : the journal of the American Society of Gene Therapy, Apr 8, 2017
The liver continuously receives antigens from circulation and the gastrointestinal tract. A compl... more The liver continuously receives antigens from circulation and the gastrointestinal tract. A complex immune regulatory system has evolved in order to both limit inflammation and promote tolerance in the liver. Although in situ immune tolerance mechanisms enable successful gene therapy and liver transplantation, at the same time they facilitate chronic infections by pathogens such as hepatitis viruses. It is, however, poorly understood why hepatocytes infected with hepatitis viruses or transduced with adeno-associated virus (AAV)-based vectors may be rejected by CD8(+) T cells several months later. We found that hepatic transfer of limited doses of an AAV-ovalbumin vector rapidly induced antigen-specific CD8(+) T cells that only became functionally competent after >2 months. At this time, CD8(+) T cells had downregulated negative checkpoint markers, e.g., the programmed death 1 [PD-1] receptor, and upregulated expression of relevant cytokines. At further reduced vector dose, only i...
Around 2 billion people are suffering from chronic malnutrition or “hidden hunger”, which is the ... more Around 2 billion people are suffering from chronic malnutrition or “hidden hunger”, which is the result of many diseases and disorders, including cognitive degeneration, stunting growth, and mortality. Thus, biofortification of staple food crops enriched with micronutrients is a more sustainable option for providing nutritional supplements and managing malnutrition in a society. Since 2001, when the concept of biofortification came to light, different research activities have been carried out, like the development of target populations, breeding or genetic engineering, and the release of biofortified cultivars, in addition to conducting nutritional efficacy trials and delivery plan development. Although, being a cost-effective intervention, it still faces many challenges, like easy accessibility of biofortified cultivars, stakeholders’ acceptance, and the availability of biofortified germplasm in the public domain, which varies from region to region. Hence, this review is focused on...
Solid-state sodium ion batteries are frequently referred to as the most promising technology for ... more Solid-state sodium ion batteries are frequently referred to as the most promising technology for next-generation energy storage applications. However, developing a suitable solid electrolyte with high ionic conductivity, excellent electrolyte–electrode interfaces, and a wide electrochemical stability window, remains a major challenge. Although solid-polymer electrolytes have attracted great interest due to their low cost, low density and very good processability, they generally have significantly lower ionic conductivity and poor mechanical strength. Here, we report on the development of a low-cost composite solid polymer electrolyte comprised of poly(ethylene oxide), poly(vinylpyrrolidone) and sodium hexafluorophosphate, mixed with indium arsenide nanowires. We show that the addition of 1.0% by weight of indium arsenide nanowires increases the sodium ion conductivity in the polymer to 1.50 × 10−4 Scm−1 at 40 °C. In order to explain this remarkable characteristic, we propose a new t...
The aim of present investigation pertains to study the impact of different culture media on the m... more The aim of present investigation pertains to study the impact of different culture media on the mycelial growth and dry weight of Pleurotus spp. Grains generally contains high nutritional content thereby decreases the harvesting period of mycelium and enhances dry weight. The study was conducted at Mushroom Laboratory Department Plant Pathology, S. V. P. University of Agriculture and Technology, Meerut, UP, India. Different crop grains were used as source of nutrition for fungus and added in PDA (media) in separate amount. Experiment was conducted in seven treatments with four replications. All the extracts observed varied mycelial growth of Pleurotus spp. After nine days maximum radial growth (90.00 mm) in both species (P. sapidus and P. flabellatus) was observed in barley extract media. The maximum growth rate (10.00 mm/day) of mycelium in P. sapidus and P. flabellatus was recorded in barley extract agar. Maximum dry mycelium weight (7.98 mg/100 ml & 8.35 mg/100 ml) of P. sapidus ...
The integration of transgenes into a plant host genome following Agrobacterium tumefaciens-mediat... more The integration of transgenes into a plant host genome following Agrobacterium tumefaciens-mediated or direct transformation may occur as a single copy or in the form of tandem repeats. The latter has been associated with promoter methylation and silencing of transgenes. Thus, the early screening of such transgenic plants is desirable for ruling out future repeat-dependent transgene instability. We developed a simple PCR-based method in which primer pairs were specifically designed so that amplifications could only be obtained if the transgene was present in the form of multiple inserts in a transgenic line. The method was established using 35S-rolC transgenic aspen lines showing morphologically visible transgenic silencing. Later, it was possible to screen independent transgenic lines showing no visible marker gene expression. Furthermore, a method was developed in which positive PCR amplification was indicative of promoter methylation. The results were consistent and reproducible ...
Gene therapy aims to replace a defective or a deficient protein at therapeutic or curative levels... more Gene therapy aims to replace a defective or a deficient protein at therapeutic or curative levels. Improved vector designs have enhanced safety, efficacy, and delivery, with potential for lasting treatment. However, innate and adaptive immune responses to the viral vector and transgene product remain obstacles to the establishment of therapeutic efficacy. It is widely accepted that endogenous regulatory T cells (Tregs) are critical for tolerance induction to the transgene product and in some cases the viral vector. There are two basic strategies to harness the suppressive ability of Tregs:induction of adaptive Tregs specific to the introduced gene product and concurrent administration of autologous,expanded Tregs. The latter may be polyclonal or engineered to direct specificity to the therapeutic antigen. Recent clinical trials have advanced adoptive immunotherapy with Tregs for the treatment of autoimmune disease and in patients receiving cell transplants. Here, we highlight the po...
Molecular therapy. Methods & clinical development, Jan 16, 2017
Gene-modified B cells expressing immunoglobulin G (IgG) fusion proteins have been shown to induce... more Gene-modified B cells expressing immunoglobulin G (IgG) fusion proteins have been shown to induce tolerance in several autoimmune and other disease models. However, lack of a vector suitable for gene transfer to human B cells has been an obstacle for translation of this approach. To overcome this hurdle, we developed an IgG-human factor IX (hFIX) lentiviral fusion construct that was targeted to specifically transduce cells expressing human CD20 (hCD20). Receptor-specific retargeting by mutating envelope glycoproteins of measles virus (MV)-lentiviral vector (LV) and addition of a single-chain variable fragment specific for hCD20 resulted in gene delivery into primary human and transgenic hCD20 mouse B cells with high specificity. Notably, this protocol neither required nor induced activation of the B cells, as confirmed by minimal activation of inflammatory cytokines. Using this strategy, we were able to demonstrate induction of humoral tolerance, resulting in suppression of antibody...
CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) are critical elements for maintaining immune tole... more CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) are critical elements for maintaining immune tolerance, for instance to exogenous antigens that are introduced during therapeutic interventions such as cell/organ transplant or gene/protein replacement therapy. Co-administration of antigen with rapamycin simultaneously promotes deletion of conventional CD4(+) T cells and induction of Treg. Here, we report that the cytokine FMS-like receptor tyrosine kinase ligand (Flt3L) enhances the in vivo effect of rapamycin. This occurs via selective expansion of plasmacytoid dendritic cells (pDC), which further augments the number of Treg. Whereas in conventional DC, rapamycin effectively blocks mTOR1 signaling induced by Flt3L, increased mTOR1 activity renders pDC more resistant to inhibition by rapamycin. Consequently, Flt3L and rapamycin synergistically promote induction of antigen-specific Treg via selective expansion of pDC. This concept is supported by the finding that Treg induction is abro...
Indian journal of virology : an official organ of Indian Virological Society, 2010
Reduced seed production in onion is associated with Onion yellow dwarf virus (OYDV), a filamentou... more Reduced seed production in onion is associated with Onion yellow dwarf virus (OYDV), a filamentous Potyvirus. Onion is also infected with other filamentous virus particles suspected to be Allexivirus. RT-PCR was used to detect mixed infection of both the viruses in leaves and bulbs. A duplex RT-PCR was developed, which simultaneously detected the presence of these two viruses in winter (Rabi) onion bulb. In summer (Kharif) onion bulbs only Allexivirus was detected. The absence of OYDV in summer crop is discussed. The sequencing of RT-PCR amplified products confirmed the identity of OYDV and Allexivirus, the latter showing closer identity to Garlic virus C (GVC)/Garlic mite-borne mosaic virus. This makes the first detection of an Allexivirus in onion crop in India. The duplex RT-PCR to detect these viruses (OYDV and Allexivirus) would be an improvement for indexing of viruses in onion bulbs for seed production.
A Polyethylene (PE) pipe reinforced by a cross-winding steel wire (PSP) is a new type of plastic-... more A Polyethylene (PE) pipe reinforced by a cross-winding steel wire (PSP) is a new type of plastic-matrix steel composite pipe, which has excellent performance. Its short-time burst pressure, strain, critical buckling pressure, and failure mode under various temperatures were investigated. Experimental results show that PSP has an increase of short-time burst pressure at room temperature up to 129%, ring stiffness up to 19%, and critical buckling pressure up to 57% in comparison with a comparable PE pipe. Failure modes of PSP subjected to internal pressure under various temperatures are found to be ductile burst and excessive deformation, and their transition temperature is about 45°C. Moreover, at the same pressure, the radial expansion ratio of PSP only bearing radial force is much larger than that of PSP bearing both radial and axial forces.
Biochar produced from switchgrass via hydrothermal carbonization (HTC) was used as a sorbent for ... more Biochar produced from switchgrass via hydrothermal carbonization (HTC) was used as a sorbent for the removal of copper and cadmium from aqueous solution. The cold activation process using KOH at room temperature was developed to enhance the porous structure and sorption properties of the HTC biochar. The sorption efficiency of HTC biochar and alkali activated HTC biochar (HTCB) for removing copper and cadmium from aqueous solution were compared with commercially available powdered activated carbon (PAC). The present batch adsorption study describes the effects of solution pH, biochar dose, and contact time on copper and cadmium removal efficiency from single metal ion aqueous solutions. The activated HTCB exhibited a higher adsorption potential for copper and cadmium than HTC biochar and PAC. Experiments conducted with an initial metal concentration of 40 mg/L at pH 5.0 and contact time of 24 h resulted in close to 100% copper and cadmium removal by activated HTCB at 2 g/L, far greater than what was observed for HTC biochar (16% and 5.6%) and PAC (4% and 7.7%). The adsorption capacities of activated HTCB for cadmium removal were 34 mg/g (0.313 mmol/g) and copper removal was 31 mg/g (0.503 mmol/g).
Uploads
Papers by SANDEEP Kumar