Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism

Pan, Youdong,Tian, Tian,Park, Chang Ook,Lofftus, Serena Y.,Mei, Shenglin,Liu, Xing,Luo, Chi,O’Malley, John T.,Gehad, Ahmed,Teague, Jessica E.,Divito, Sherrie J.,Fuhlbrigge, Robert,Puigserver, Pere,Kru Macmillan Publishers Limited, part of Springer Nat 2017 Nature Vol.543 No.7644

Tissue-resident memory T (T<SUB>RM</SUB>) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of T<SUB>RM</SUB> cells are obscure. Here we show that mouse CD8<SUP>+</SUP> T<SUB>RM</SUB> cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8<SUP>+</SUP> T<SUB>RM</SUB> cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (T<SUB>CM</SUB>) cells in lymph nodes. In vitro, CD8<SUP>+</SUP> T<SUB>RM</SUB> cells, but not CD8<SUP>+</SUP> T<SUB>CM</SUB> cells, demonstrated increased mitochondrial oxidative metabolism in the presence of exogenous FFAs; this increase was not seen in Fabp4/Fabp5 double-knockout CD8<SUP>+</SUP> T<SUB>RM</SUB> cells. The persistence of CD8<SUP>+</SUP> T<SUB>RM</SUB> cells in the skin was strongly diminished by inhibition of mitochondrial FFA β-oxidation in vivo. Moreover, skin CD8<SUP>+</SUP> T<SUB>RM</SUB> cells that lacked Fabp4/Fabp5 were less effective at protecting mice from cutaneous viral infection, and lung Fabp4/Fabp5 double-knockout CD8<SUP>+</SUP> T<SUB>RM</SUB> cells generated by skin vaccinia virus (VACV) infection were less effective at protecting mice from a lethal pulmonary challenge with VACV. Consistent with the mouse data, increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8<SUP>+</SUP> T<SUB>RM</SUB> cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8<SUP>+</SUP> T<SUB>RM</SUB> cells, and suggest that CD8<SUP>+</SUP> T<SUB>RM</SUB> cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity.

Comparison of Single and Blend Acidifiers as Alternative to Antibiotics on Growth Performance, Fecal Microflora, and Humoral Immunity in Weaned Piglets

Ahmed, S.T.,Hwang, J.A.,Hoon, J.,Mun, H.S.,Yang, C.J. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.1

The banning of the use of antibiotics as feed additive has accelerated investigations of alternative feed additives in animal production. This experiment investigated the effect of pure citric acid or acidifier blend supplementation as substitute for antibiotic growth promoters on growth performance, fecal microbial count, and humoral immunity in weaned piglets challenged with Salmonella enterica serover Typhimurium and Escherichia coli KCTC 2571. A total of 60 newly weaned piglets (crossbred, 28-d-old; average 8 kg initial weight) were randomly assigned to four dietary treatments in a completely randomized design. Dietary treatments included NC (negative control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.5% pure citric acid), and T2 (basal diet+0.4% acidifier blend). All piglets were orally challenged with 5 mL of culture fluid containing $2.3{\times}10^8$ cfu/mL of E. coli KCTC 2571 and $5.9{\times}10^8$ cfu/mL of S. typhimurium at the beginning of the experiment. The PC group showed the highest ADG and ADFI, whereas gain:feed was improved in the PC and T1 group (p<0.05). All dietary treatments showed significant reduction in fecal counts of Salmonella and E. coli, compared to NC (p<0.05), with PC being better than T1 and T2. Significant elevation in fecal Lactobacillus spp. counts was shown by treatments with T1, T2, and PC, whereas Bacillus spp. counts were increased by treatment with T1 and T2 compared to NC and PC diet (p<0.05). Serum IgG concentration was increased by T1 diet (p<0.05), whereas IgM and IgA were not significantly affected by any of the dietary treatments (p>0.05). From these above results, it can be concluded that, as alternatives to antibiotics dietary acidification with pure citric acid or acidifiers blend did not fully ameliorate the negative effects of microbial challenges in respect of growth performance and microbial environment, however improved immunity suggested further research with different dose levels.

Effects of Resveratrol and Essential Oils on Growth Performance, Immunity, Digestibility and Fecal Microbial Shedding in Challenged Piglets

Ahmed, S.T.,Hossain, M.E.,Kim, G.M.,Hwang, J.A.,Ji, H.,Yang, C.J. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.5

A study was conducted to evaluate the effects of resveratrol and essential oils from medicinal plants on the growth performance, immunity, digestibility, and fecal microbial shedding of weaned piglets. A total of 48 weaned piglets (8 kg initial weight, 28-d-old) were randomly allotted to four dietary treatments with 3 replications of 4 piglets each. The dietary treatments were NC (negative control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.2% resveratrol), and T2 (basal diet+0.0125% essential oil blend). All piglets were orally challenged with 5 ml culture fluid containing $2.3{\times}10^8$ cfu/ml of Escherichia coli KCTC 2571 and $5.9{\times}10^8$ cfu/ml Salmonella enterica serover Typhimurium. The PC group (p<0.05) showed the highest average daily gain (ADG) and average daily feed intake (ADFI) throughout the experimental period, although feed conversion ratio (FCR) was improved in the T1 group (p>0.05). Serum IgG level was increased in the T1 group, whereas TNF-${\alpha}$ levels was reduced in the supplemented groups compared to control (p<0.05). The PC diet improved the dry matter (DM) digestibility, whereas PC and T2 diets improved nitrogen (N) digestibility compared to NC and T1 diets (p<0.05). Fecal Salmonella and E. coli counts were reduced in all treatment groups compared to control (p<0.05). Fecal Lactobacillus spp. count was increased in the T2 group compared to others (p<0.05). Dietary treatments had no significant effect on fecal Bacillus spp. count throughout the entire experimental period. Based on these results, resveratrol showed strong potential as antibiotic alternatives for reversing the adverse effects of weaning stress on growth performance, immunity and microbial environment in E. coli and Salmonella-challenged piglets.

Secreted Phosphoprotein 1 Promoter Genetic Variants Are Associated with the Response to Pegylated Interferon α Plus Ribavirin Combination Therapy in Egyptian Patients with Chronic Hepatitis C Virus Infection

( Fahmy T Ali ),( Mohamed A M Ali ),( Mayada M A Elgizawy ),( Ahmed M Elsawy ) 대한소화기학회 2015 Gut and Liver Vol.9 No.4

Background/Aims: The T-helper 1 (TH1) immune reaction is essential for the eradication of hepatitis C virus (HCV) during pegylated interferon α (PEG-IFN-α)- and ribavirin (RBV)-based therapy in chronic HCV patients. Secreted phosphoprotein 1 (SPP1) was shown to be a crucial cytokine for the initiation of a TH1 immune response. We aimed to investigate whether SPP1 single nucleotide polymorphisms (SNPs) may influence sustained virological response (SVR) rates. Methods: Two SNPs in the promoter region of SPP1 at the .443 C>T and .1748 G>A loci were genotyped in 100 patients with chronic HCV genotype 4 infection using a TaqMan SNP genotyping assay. Results: Sixty-seven patients achieved a SVR, and 33 patients showed no SVR. Patients carrying the T/T genotype at the .443 locus showed a significantly higher SVR rate than those carrying the C/T or C/C genotype (83.67% vs 50.98%, p<0.001). At the .1748 locus, the SVR rate was significantly higher in patients with the G/G genotype than in those with the A/A genotype (88.89% vs 52.63%, p=0.028) and in patients with the G/A genotype than in those with the A/A genotype (85.29% vs 52.63%, p=0.001). Conclusions: SPP1 SNPs at .443 C>T and .1748 G>A loci may be useful markers for predicting the response to PEG-IFN-α-2b plus RBV therapy in Egyptian patients with chronic HCV genotype 4 infection. (Gut Liver 2015;9:516-524)

Enhanced electromechanical properties of (1-x)BiFeO₃-BaTiO₃-xLiNbO₃ ceramics by quenching process

Ahmed Malik, R.,Hussain, A.,Kwon Song, T.,Kim, W.J.,Ahmed, R.,Soo Sung, Y.,Kim, M.H. Elsevier 2017 CERAMICS INTERNATIONAL Vol.43 No.suppl1

A new lead-free piezoelectric ceramics (1-x) (0.67Bi<SUB>1.05</SUB>FeO<SUB>3</SUB> - 0.33BaTiO<SUB>3</SUB>)-x LiNbO<SUB>3</SUB>, abbreviated as BFBT-LNx (x = 0.00-0.030), were fabricated by conventional mixed oxide route following by quenching process and crystal structure and electromechanical properties were discussed. X-ray diffraction pattern showed that LiNbO<SUB>3</SUB> addition into 0.67Bi<SUB>1.05</SUB>FeO<SUB>3</SUB> - 0.33BaTiO<SUB>3</SUB> system did not caused any significant change in crystal structure. However, an obvious variation in electrical properties was observed. It is revealed from electrical properties that the modification of LiNbO<SUB>3</SUB> induces a phase transition from a ferroelectric to relaxor state in the 0.67Bi<SUB>1.05</SUB>FeO<SUB>3</SUB> - 0.33BaTiO<SUB>3</SUB> system. At optimum composition (x = 0.010), enhanced field-induced strain with large dynamic piezoelectric constant S<SUB>max</SUB>/E<SUB>max</SUB> = d<SUP>*</SUP><SUB>33</SUB> = 500pm / V at a relatively low field of 3.5kV / mm with lower hysteresis loss of 40% was recorded. For this composition, a high Curie temperature T<SUB>C</SUB> ~ 390<SUP>o</SUP>C was found. These properties suggests that the synthesized system is promising for high temperature actuator applications.

Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection

Jin, H.-T.,Anderson, A.C.,Tan, W.G.,West, E.E.,Ha, S.-J.,Araki, K.,Freeman, G.J.,Kuchroo, V.K.,Ahmed, R. National Academy of Sciences 2010 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.107 No.33

THE WEIBULL MARSHALL-OLKIN LOMAX DISTRIBUTION WITH APPLICATIONS TO BLADDER AND HEAD CANCER DATA

KUMAR, DEVENDRA,KUMAR, MANEESH,ABD EL-BAR, AHMED M.T.,LIMA, MARIA DO CARMO S. The Korean Society for Computational and Applied M 2021 Journal of applied mathematics & informatics Vol.39 No.5

The proposal of new families has been worked out by many authors over recent years. Many ways to generate new families have been developed as the methods of addition, linear combination, composition and, one of the newer, the T-X family of distributions. Using this latter method, Korkmaz et al. (2018) proposed a new class called Weibull Marshall-Olkin-G (WMO-G) family. In the present work, we propose a new distribution, based on the WMO-G family, using the Lomax distribution as baseline, called Weibull Marshall-Olkin Lomax (WMOL) distribution. The hazard rate function of this distribution can be increasing, decreasing, bathtub-shaped, decreasing-increasing-decreasing and unimodal. Some properties of the proposed model are developed. Besides that, we consider method of maximum likelihood for estimating the unknown parameters of the WMOL distribution. We provide a simulation study in order to verify the asymptotic properties of the maximum likelihood estimates. The applicability of the new distribution to modeling real life data is proved by two real data sets.

Coenzyme Q10, oxidative stress, and male infertility: A review

Ahmed T. Alahmar,Aldo E. Calogero,Rajender Singh,Rossella Cannarella,Pallav Sengupta,Sulagna Dutta 대한생식의학회 2021 Clinical and Experimental Reproductive Medicine Vol.48 No.2

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.

A study on finite element of pre damaged stress concentration factor for a composite laminate member with central circular

T. Ahmed,R. S. Choudhry,Atta Ur Rehman Shah,Hasan Aftab Saeed 대한기계학회 2018 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.32 No.8

The study investigates the pre damaged stress concentration factor (SCF) for a composite laminate member (CLM) with central circular hole subjected to tensile loading. The presence of holes yields high stress concentrations in the structural members termed as stress raiser and often regarded as an important design deriver. The pre damaged SCF refers to the stress concentrations within elastic (undamaged) range of the CLM prior to the failure initiation. The traditional experimental and analytical methods for the estimation of SCF offer macro level behaviour which is not considered appropriate for CLM where lamina by lamina behaviour is more significant. A meso level finite element (FE) model is presented to capture the lamina by lamina influence on the overall SCF for a CLM using commercial software Abaqus. The paper deals with the fundamental influencing factors such as laminae orientation effect, stress distribution effect around periphery of the hole, decaying effect and ligament effect on SCF for CLM. Analytical models have been formulated to validate the FE models. The results of FE models have been found in close agreement with the analytical results.

Coenzyme Q10, oxidative stress markers, and sperm DNA damage in men with idiopathic oligoasthenoteratospermia

Ahmed T Alahmar,Pallav Sengupta,Sulagna Dutta,Aldo E. Calogero 대한생식의학회 2021 Clinical and Experimental Reproductive Medicine Vol.48 No.2

Objective: Oxidative stress (OS) plays a key role in the etiology of unexplained male infertility. Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve semen quality and OS in infertile men with idiopathic oligoasthenoteratospermia (OAT), but the underlying mechanism is unknown. Therefore, the present study was undertaken to investigate the effect of CoQ10 on OS markers and sperm DNA damage in infertile patients with idiopathic OAT. Methods: This prospective controlled study included 50 patients with idiopathic OAT and 50 fertile men who served as controls. All patients underwent a comprehensive medical assessment. Patients and controls received 200 mg of oral CoQ10 once daily for 3 months. Semen and blood were collected and analyzed for sperm parameters, seminal CoQ10 levels, reactive oxygen species (ROS) levels, total antioxidant capacity, catalase, sperm DNA fragmentation (SDF), and serum hormonal profile. Results: The administration of CoQ10 to patients with idiopathic OAT significantly improved sperm quality and seminal antioxidant status and significantly reduced total ROS and SDF levels compared to pre-treatment values. Conclusion: CoQ10, at a dose of 200 mg/day for 3 months, may be a potential therapy for infertile patients with idiopathic OAT, as it improved sperm parameters and reduced OS and SDF in these patients.