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Hadil A. Alkathiry Samia Q. Alghamdi Holly E.J. Morgan Madeleine E. Noll Jing J. Khoo Abdulaziz N. Alagaili Benjamin L. Makepeace 《Emerging infectious diseases》2023,29(2):402
Scrub typhus is a zoonosis caused by 3 species of Orientia bacteria, including Candidatus Orientia chuto. This species is known only from a human case in Dubai and infections in wildlife in Kenya. We report molecular detection of Candidatus O. chuto in 2 wild rodent species from Saudi Arabia. 相似文献
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Peter Gennemark Rasmus Jansson-Löfmark Gina Hyberg Maria Wigstrand Dorota Kakol-Palm Pernilla Håkansson Daniel Hovdal Peter Brodin Maria Fritsch-Fredin Madeleine Antonsson Karolina Ploj Johan Gabrielsson 《Journal of pharmacokinetics and pharmacodynamics》2013,40(6):651-667
Body composition and body mass are pivotal clinical endpoints in studies of welfare diseases. We present a combined effort of established and new mathematical models based on rigorous monitoring of energy intake (EI) and body mass in mice. Specifically, we parameterize a mechanistic turnover model based on the law of energy conservation coupled to a drug mechanism model. Key model variables are fat-free mass (FFM) and fat mass (FM), governed by EI and energy expenditure (EE). An empirical Forbes curve relating FFM to FM was derived experimentally for female C57BL/6 mice. The Forbes curve differs from a previously reported curve for male C57BL/6 mice, and we thoroughly analyse how the choice of Forbes curve impacts model predictions. The drug mechanism function acts on EI or EE, or both. Drug mechanism parameters (two to three parameters) and system parameters (up to six free parameters) could be estimated with good precision (coefficients of variation typically <20 % and not greater than 40 % in our analyses). Model simulations were done to predict the EE and FM change at different drug provocations in mice. In addition, we simulated body mass and FM changes at different drug provocations using a similar model for man. Surprisingly, model simulations indicate that an increase in EI (e.g. 10 %) was more efficient than an equal lowering of EI. Also, the relative change in body mass and FM is greater in man than in mouse at the same relative change in either EI or EE. We acknowledge that this assumes the same drug mechanism impact across the two species. A set of recommendations regarding the Forbes curve, vehicle control groups, dual action on EI and loss, and translational aspects are discussed. This quantitative approach significantly improves data interpretation, disease system understanding, safety assessment and translation across species. 相似文献
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Matteo Morotti Christos E. Zois Rokaya El-Ansari Madeleine L. Craze Emad A. Rakha Shih-Jung Fan Alessandro Valli Syed Haider Deborah C. I. Goberdhan Andrew R. Green Adrian L. Harris 《British journal of cancer》2021,124(2):494
Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism 相似文献
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Paola Bianchi Elisa Fermo Kimberly Lezon-Geyda Eduard J. van Beers Holmes D. Morton Wilma Barcellini Bertil Glader Satheesh Chonat Yaddanapudi Ravindranath Peter E. Newburger Nina Kollmar Jenny M. Despotovic Madeleine Verhovsek Mukta Sharma Janet L. Kwiatkowski Kevin H. M. Kuo Marcin W. Wlodarski Hassan M. Yaish Susanne Holzhauer Heng Wang Joachim Kunz Kathryn Addonizio Hasan Al-Sayegh Wendy B. London Oliver Andres Richard van Wijk Patrick G. Gallagher Rachael F. F. Grace 《American journal of hematology》2020,95(5):472-482
Pyruvate kinase (PK) deficiency is a rare recessive congenital hemolytic anemia caused by mutations in the PKLR gene. This study reports the molecular features of 257 patients enrolled in the PKD Natural History Study. Of the 127 different pathogenic variants detected, 84 were missense and 43 non-missense, including 20 stop-gain, 11 affecting splicing, five large deletions, four in-frame indels, and three promoter variants. Within the 177 unrelated patients, 35 were homozygous and 142 compound heterozygous (77 for two missense, 48 for one missense and one non-missense, and 17 for two non-missense variants); the two most frequent mutations were p.R510Q in 23% and p.R486W in 9% of mutated alleles. Fifty-five (21%) patients were found to have at least one previously unreported variant with 45 newly described mutations. Patients with two non-missense mutations had lower hemoglobin levels, higher numbers of lifetime transfusions, and higher rates of complications including iron overload, extramedullary hematopoiesis, and pulmonary hypertension. Rare severe complications, including lower extremity ulcerations and hepatic failure, were seen more frequently in patients with non-missense mutations or with missense mutations characterized by severe protein instability. The PKLR genotype did not correlate with the frequency of complications in utero or in the newborn period. With ICCs ranging from 0.4 to 0.61, about the same degree of clinical similarity exists within siblings as it does between siblings, in terms of hemoglobin, total bilirubin, splenectomy status, and cholecystectomy status. Pregnancy outcomes were similar across genotypes in PK deficient women. This report confirms the wide genetic heterogeneity of PK deficiency. 相似文献