The generation of an adaptive immune response against intracellular pathogens requires the recrui... more The generation of an adaptive immune response against intracellular pathogens requires the recruitment of effector T cells to sites of infection. Here we show that the chemokine IP-10, a specific chemoattractant for activated T cells, controls this process in mice naturally infected with Toxoplasma gondii. Neutralization of IP-10 in infected mice inhibited the massive influx of T cells into tissues and impaired antigen-specific T cell effector functions. This resulted in >1000-fold increase in tissue parasite burden and a marked increase in mortality compared to control antibody-treated mice. These observations suggest that IP-10 may play a broader role in the localization and function of effector T cells at sites of Th1 inflammation.
Peste des petits ruminants (PPR), an economically important viral transboundary disease of small ... more Peste des petits ruminants (PPR), an economically important viral transboundary disease of small ruminants is not only prevalent in Pakistan but also in other countries where people rely on agriculture and animal products. The present study was aimed at describing the pathology and antigen localization in natural PPR infections in local (Kajli sheep; Beetal goats) as well as imported small ruminant breeds (Dorper sheep; Australian Boer goat). Morbidity and mortality rates were significantly (P < 0.001) higher in indigenous Kajli sheep (75.37 and 32.80%) and Beetal goats (81.10 and 37.24%) as compared to Dorper sheep (6.99 and 1.48%) and Australian Boer goat (5.01 and 2.23%). Affected animals exhibited high fever, severe diarrhea, abdominal pain, respiratory distress and nodular lesions on lips and nostrils. Thick mucous discharge was oozing out from nostrils. On postmortem examination, lungs were congested and pneumonic, with nodular and cystic appearance and intestines were hemo...
Phosphate-solubilizing bacteria (PSB) reduce the negative effects of soil calcification on soil p... more Phosphate-solubilizing bacteria (PSB) reduce the negative effects of soil calcification on soil phosphorus (P) nutrition. In this incubation study, we explored the ability of PSB (control and inoculated) to release P from different P sources [single super phosphate (SSP), rock phosphate (RP), poultry manure (PM) and farm yard manure (FYM)] with various soil lime contents (4.78, 10, 15 and 20%) in alkaline soil. PSB inoculation progressively enriched Olsen extractable P from all sources compared to the control over the course of 56 days; however, this increase was greater from organic sources (PM and FYM) than from mineral P sources (SSP and RP). Lime addition to the soil decreased bioavailable P, but this effect was largely neutralized by PSB inoculation. PSB were the most viable in soil inoculated with PSB and amended with organic sources, while lime addition decreased PSB survival. Our findings imply that PSB inoculation can counteract the antagonistic effect of soil calcification...
A series of iminothiazolines (4a-j) featuring 2,4,5-trichlorophenyl moiety and aroyl/heteroaroyl ... more A series of iminothiazolines (4a-j) featuring 2,4,5-trichlorophenyl moiety and aroyl/heteroaroyl substituents has been prepared from readily accessible thioureas. In-vitro screening against glucosidase enzymes showed highly specific inhibition of α-glucosidase with a marked dependence of the potency upon the nature of the aroyl/heteroaroyl substituents. The most potent representatives, bearing ortho-tolyl and bulky naphthyl groups displayed the highest inhibitory potential with IC50 value of 0.15±0.01µM compared to standard drug acarbose (IC50=38.2±0.12µM). Several other derivatives (4c, 4d, 4i and 4j) were also significantly powerful and selective inhibitors of α-glucosidase. Binding interactions of potent compounds 4b, 4c, 4h and 4i with α-glucosidase were explored by molecular docking simulation. These results clearly identified a new class of structural leads which can be further investigated for the development of promising α-glucosidase inhibitors for the prevention of diabetes mellitus.
Rapid increase in bacterial resistance has become a major public concern by escalating alongside ... more Rapid increase in bacterial resistance has become a major public concern by escalating alongside a lack of development of new anti-infective drugs. Novel remedies in the battle against multidrug-resistant bacterial strains are urgently needed. So, in this context, the present work is towards the investigation of antimicrobial efficacy of some novel keto ester derivatives, which are prepared by the condensation of substituted benzoic acids with various substituted phenacyl bromides in dimethylformamide at room temperature using triethylamine as a catalyst. The structural build-up of the target compounds was accomplished by spectroscopic techniques including FTIR, (1)H and (13)C NMR spectroscopy and mass spectrometry. The purity of the synthesized compounds was ascertained by elemental analysis. The molecular structures of compounds (4b) and (4l) were established by X-ray crystallographic analysis. The prepared analogues were evaluated for their antimicrobial activity against Gram-pos...
Angewandte Chemie (International ed. in English), Jan 25, 2015
Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp(2) )... more Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp(2) )-H functionalization and oxidative annulation with alkynes to give spiroindenes containing all-carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O-bound rhodium enolate into the C-bound isomer, appear to be critical for high enantiomeric excesses.
6th IFAC Symposium on Modeling and Control in Biomedical Systems, 2006, 2006
... 3Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, CF14 4X, UK ... more ... 3Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, CF14 4X, UK ... Critical to realizing this aim is the development of bioinformatics and visualisation tools to address problems of cellular heterogeneity, stochasticity and scaling for the impact of drugs ...
Slurry bubble columns, for use in Fisher-Tropsch synthesis, have been investigated. Two bubble co... more Slurry bubble columns, for use in Fisher-Tropsch synthesis, have been investigated. Two bubble columns (0.108 and 0.305 m internal diameter) were set up and experiments were conducted to determine gas holdup and heat transfer coefficients. These columns were equipped with either single heat transfer probes of different diameters, or bundles of five-, seven- or thirty-seven tubes. The experiments were conducted
Toxoplasma gondii remains a serious cause of morbidity and mortality in individuals that are immu... more Toxoplasma gondii remains a serious cause of morbidity and mortality in individuals that are immunosuppressed, patients with AIDS in particular. The cellular immune response, especially by gamma interferon (IFN-gamma)-producing CD8(+) T cells, is an essential component of protective immunity against the parasite. In the present study the role of CD8(+) T cells during the reactivation of Toxoplasma infection in an immunocompromised murine model was evaluated. Chronically infected mice were challenged with LP-BM5 virus, and the kinetics of CD8(+) T-cell function was studied. At 10 weeks after viral infection, mice showed obvious signs of systemic illness and began to die. At this stage, CD8(+) T cells were unresponsive to antigenic stimulation and unable to kill Toxoplasma-infected targets. IFN-gamma production by the CD8(+) T cells from dual-infected animals reached background levels, and a dramatic fall in the frequency of precursor cytotoxic T lymphocytes was observed. Histopatholo...
To study the indication for reoperations after lumbar decompression, the factors predisposing to ... more To study the indication for reoperations after lumbar decompression, the factors predisposing to redo operations, and the effect of prior instrumentation on developing adjacent level stenosis requiring reoperation. Kaplan-Meier analysis was used to compare the median interval to first reoperation. Cox regression was used for multivariate analysis of time to first reoperation. Of 335 patients who underwent surgery for lumbar spinal stenosis, 63 (18%) underwent instrumentation in addition to decompression. There were 50 reoperations performed in 44 patients (13%). Of these 50 reoperations, 26 were at the same level, 14 were at the same level plus an adjacent level, and 10 were at an adjacent level. In 21 reoperations, the indication was adjacent level spinal stenosis; in 16, adjacent level spinal stenosis plus instability; in 9, instability alone; and in 4, disc problem. The risk of reoperation was higher among male patients (hazard ratio [HR] 1.2, 95% confidence interval [CI] 0.586-2.635) and in patients with prior instrumentation (HR 1.7, 95% CI 0.684-4.640). There was no statistical association between prior instrumentation and subsequent risk of reoperation (P = 0.12). There was no association between prior instrumentation and development of adjacent level stenosis requiring reoperation (P = 0.473). Many patients with spinal stenosis undergo instrumentation because of instability. Most patients in this study underwent reoperation at the same level, and the most common pathology was spinal stenosis. The risk of reoperation was lower in older patients (≥65 years old). Although there was a trend that the risk of reoperation was higher among patients with prior instrumentation, it did not reach statistical significance. In this study, there was no association between prior instrumentation and adjacent level stenosis requiring reoperation. These findings need to be evaluated further in randomized trials.
The generation of an adaptive immune response against intracellular pathogens requires the recrui... more The generation of an adaptive immune response against intracellular pathogens requires the recruitment of effector T cells to sites of infection. Here we show that the chemokine IP-10, a specific chemoattractant for activated T cells, controls this process in mice naturally infected with Toxoplasma gondii. Neutralization of IP-10 in infected mice inhibited the massive influx of T cells into tissues and impaired antigen-specific T cell effector functions. This resulted in >1000-fold increase in tissue parasite burden and a marked increase in mortality compared to control antibody-treated mice. These observations suggest that IP-10 may play a broader role in the localization and function of effector T cells at sites of Th1 inflammation.
Peste des petits ruminants (PPR), an economically important viral transboundary disease of small ... more Peste des petits ruminants (PPR), an economically important viral transboundary disease of small ruminants is not only prevalent in Pakistan but also in other countries where people rely on agriculture and animal products. The present study was aimed at describing the pathology and antigen localization in natural PPR infections in local (Kajli sheep; Beetal goats) as well as imported small ruminant breeds (Dorper sheep; Australian Boer goat). Morbidity and mortality rates were significantly (P < 0.001) higher in indigenous Kajli sheep (75.37 and 32.80%) and Beetal goats (81.10 and 37.24%) as compared to Dorper sheep (6.99 and 1.48%) and Australian Boer goat (5.01 and 2.23%). Affected animals exhibited high fever, severe diarrhea, abdominal pain, respiratory distress and nodular lesions on lips and nostrils. Thick mucous discharge was oozing out from nostrils. On postmortem examination, lungs were congested and pneumonic, with nodular and cystic appearance and intestines were hemo...
Phosphate-solubilizing bacteria (PSB) reduce the negative effects of soil calcification on soil p... more Phosphate-solubilizing bacteria (PSB) reduce the negative effects of soil calcification on soil phosphorus (P) nutrition. In this incubation study, we explored the ability of PSB (control and inoculated) to release P from different P sources [single super phosphate (SSP), rock phosphate (RP), poultry manure (PM) and farm yard manure (FYM)] with various soil lime contents (4.78, 10, 15 and 20%) in alkaline soil. PSB inoculation progressively enriched Olsen extractable P from all sources compared to the control over the course of 56 days; however, this increase was greater from organic sources (PM and FYM) than from mineral P sources (SSP and RP). Lime addition to the soil decreased bioavailable P, but this effect was largely neutralized by PSB inoculation. PSB were the most viable in soil inoculated with PSB and amended with organic sources, while lime addition decreased PSB survival. Our findings imply that PSB inoculation can counteract the antagonistic effect of soil calcification...
A series of iminothiazolines (4a-j) featuring 2,4,5-trichlorophenyl moiety and aroyl/heteroaroyl ... more A series of iminothiazolines (4a-j) featuring 2,4,5-trichlorophenyl moiety and aroyl/heteroaroyl substituents has been prepared from readily accessible thioureas. In-vitro screening against glucosidase enzymes showed highly specific inhibition of α-glucosidase with a marked dependence of the potency upon the nature of the aroyl/heteroaroyl substituents. The most potent representatives, bearing ortho-tolyl and bulky naphthyl groups displayed the highest inhibitory potential with IC50 value of 0.15±0.01µM compared to standard drug acarbose (IC50=38.2±0.12µM). Several other derivatives (4c, 4d, 4i and 4j) were also significantly powerful and selective inhibitors of α-glucosidase. Binding interactions of potent compounds 4b, 4c, 4h and 4i with α-glucosidase were explored by molecular docking simulation. These results clearly identified a new class of structural leads which can be further investigated for the development of promising α-glucosidase inhibitors for the prevention of diabetes mellitus.
Rapid increase in bacterial resistance has become a major public concern by escalating alongside ... more Rapid increase in bacterial resistance has become a major public concern by escalating alongside a lack of development of new anti-infective drugs. Novel remedies in the battle against multidrug-resistant bacterial strains are urgently needed. So, in this context, the present work is towards the investigation of antimicrobial efficacy of some novel keto ester derivatives, which are prepared by the condensation of substituted benzoic acids with various substituted phenacyl bromides in dimethylformamide at room temperature using triethylamine as a catalyst. The structural build-up of the target compounds was accomplished by spectroscopic techniques including FTIR, (1)H and (13)C NMR spectroscopy and mass spectrometry. The purity of the synthesized compounds was ascertained by elemental analysis. The molecular structures of compounds (4b) and (4l) were established by X-ray crystallographic analysis. The prepared analogues were evaluated for their antimicrobial activity against Gram-pos...
Angewandte Chemie (International ed. in English), Jan 25, 2015
Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp(2) )... more Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp(2) )-H functionalization and oxidative annulation with alkynes to give spiroindenes containing all-carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O-bound rhodium enolate into the C-bound isomer, appear to be critical for high enantiomeric excesses.
6th IFAC Symposium on Modeling and Control in Biomedical Systems, 2006, 2006
... 3Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, CF14 4X, UK ... more ... 3Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, CF14 4X, UK ... Critical to realizing this aim is the development of bioinformatics and visualisation tools to address problems of cellular heterogeneity, stochasticity and scaling for the impact of drugs ...
Slurry bubble columns, for use in Fisher-Tropsch synthesis, have been investigated. Two bubble co... more Slurry bubble columns, for use in Fisher-Tropsch synthesis, have been investigated. Two bubble columns (0.108 and 0.305 m internal diameter) were set up and experiments were conducted to determine gas holdup and heat transfer coefficients. These columns were equipped with either single heat transfer probes of different diameters, or bundles of five-, seven- or thirty-seven tubes. The experiments were conducted
Toxoplasma gondii remains a serious cause of morbidity and mortality in individuals that are immu... more Toxoplasma gondii remains a serious cause of morbidity and mortality in individuals that are immunosuppressed, patients with AIDS in particular. The cellular immune response, especially by gamma interferon (IFN-gamma)-producing CD8(+) T cells, is an essential component of protective immunity against the parasite. In the present study the role of CD8(+) T cells during the reactivation of Toxoplasma infection in an immunocompromised murine model was evaluated. Chronically infected mice were challenged with LP-BM5 virus, and the kinetics of CD8(+) T-cell function was studied. At 10 weeks after viral infection, mice showed obvious signs of systemic illness and began to die. At this stage, CD8(+) T cells were unresponsive to antigenic stimulation and unable to kill Toxoplasma-infected targets. IFN-gamma production by the CD8(+) T cells from dual-infected animals reached background levels, and a dramatic fall in the frequency of precursor cytotoxic T lymphocytes was observed. Histopatholo...
To study the indication for reoperations after lumbar decompression, the factors predisposing to ... more To study the indication for reoperations after lumbar decompression, the factors predisposing to redo operations, and the effect of prior instrumentation on developing adjacent level stenosis requiring reoperation. Kaplan-Meier analysis was used to compare the median interval to first reoperation. Cox regression was used for multivariate analysis of time to first reoperation. Of 335 patients who underwent surgery for lumbar spinal stenosis, 63 (18%) underwent instrumentation in addition to decompression. There were 50 reoperations performed in 44 patients (13%). Of these 50 reoperations, 26 were at the same level, 14 were at the same level plus an adjacent level, and 10 were at an adjacent level. In 21 reoperations, the indication was adjacent level spinal stenosis; in 16, adjacent level spinal stenosis plus instability; in 9, instability alone; and in 4, disc problem. The risk of reoperation was higher among male patients (hazard ratio [HR] 1.2, 95% confidence interval [CI] 0.586-2.635) and in patients with prior instrumentation (HR 1.7, 95% CI 0.684-4.640). There was no statistical association between prior instrumentation and subsequent risk of reoperation (P = 0.12). There was no association between prior instrumentation and development of adjacent level stenosis requiring reoperation (P = 0.473). Many patients with spinal stenosis undergo instrumentation because of instability. Most patients in this study underwent reoperation at the same level, and the most common pathology was spinal stenosis. The risk of reoperation was lower in older patients (≥65 years old). Although there was a trend that the risk of reoperation was higher among patients with prior instrumentation, it did not reach statistical significance. In this study, there was no association between prior instrumentation and adjacent level stenosis requiring reoperation. These findings need to be evaluated further in randomized trials.
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