抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61766-8.pdf

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010

Free radicals, metals and antioxidants in oxidative stress-induced cancer

How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media. How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a working family, the effect of politics on programs for children, the costs and benefits of intervention, and other issues. The committee issues a series of challenges to decision makers regarding the quality of child care, issues of racial and ethnic diversity, the integration of children's cognitive and emotional development, and more. Authoritative yet accessible, From Neurons to Neighborhoods presents the evidence about "brain wiring" and how kids learn to speak, think, and regulate their behavior. It examines the effect of the climate-family, child care, community-within which the child grows.

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From Neurons to Neighborhoods: The Science of Early Childhood Development

Patients with sickle cell disease (SCD) are at risk for bone fragility from multiple factors including vitamin D deficiency. To date, no studies have evaluated the efficacy and safety of long-term vitamin D therapy for bone disease in children with SCD. We report a cohort of 4 children with SCD found to have severe vitamin D deficiency, secondary hyperparathyroidism, and abnormal bone mineral density treated with monthly high-dose oral cholecalciferol over 2 years. All patients exhibited a positive response to therapy without hypervitaminosis D or hypercalcemia. Further studies are needed to standardize guidelines for optimal vitamin D dosing and prevention of toxicity.

/pdf/response-to-long-term-vitamin-d-therapy-for-bone-disease-in-q3ms8ax9ch.pdf

Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease.

Background: After the oral administration of iron, the production of circulating non–transferrin-bound iron may contribute to an increased risk of illness in malaria-endemic areas that lack effective medical services. Objective: In healthy women with a range of body iron stores, we aimed to determine effects on the production of circulating non– transferrin-bound iron resulting from the oral administration of 1) a supplemental dose of iron (60 mg) with water, 2) a supplemental dose of iron (60 mg) with a standard test meal, and 3) a fortification dose of iron (6 mg) with a standard test meal. Design: With the use of serum ferritin as the indicator, healthy women with replete iron stores (ferritin concentration .25 mg/L; n = 16) and reduced iron stores (ferritin concentration #25 mg/L; n = 16) were enrolled in a prospective, randomized, crossover study. After the oral administration of aqueous solutions of ferrous sulfate isotopically labeled with 54 Fe, 57 Fe, or 58 Fe, blood samples were collected for 8 h, and iron absorption was estimated by erythrocyte incorporation at 14 d. Results: At 4 h, serum non–transferrin-bound iron reached peaks with geometric mean (95% CI) concentrations of 0.81 mmol/L (0.56, 1.1 mmol/L) for 60 mg Fe with water and 0.26 mmol/L (0.15, 0.38 mmol/L) for 60 mg Fe with food but was at assay limits of detection (0.1 mmol Fe/L) for 6 mg Fe with food. For the 60 mg Fe without food, the area under the curve over 8 h for serum non– transferrin-bound iron was positively correlated with the amount of iron absorbed (R = 0.49, P , 0.01) and negatively correlated with serum ferritin (R = 20.39, P , 0.05). Conclusions: In healthy women, the production of circulating non– transferrin-bound iron is determined by the rate and amount of iron absorbed. The highest concentrations of non–transferrin-bound iron resulted from the administration of supplemental doses of iron without food. Little or no circulating non–transferrin-bound iron resulted from the consumption of a meal with a fortification dose of iron. This trial was registered at clinicaltrials.gov as NCT0140453. Am J Clin Nutr doi: 10.3945/ajcn.113.081505.

Circulating non-transferrin-bound iron after oral administration of supplemental and fortification doses of iron to healthy women:

J. S. Cheung, W-Y. Au, S-Y. Ha, J. H. Jensen, D. Kim, A. Y. Ding, I. Y. Zhou, H. Guo, T. R. Brown, W. C. Chu, D. D. Rasalkar, P-L. Khong, G. M. Brittenham, and E. X. Wu Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of, Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of, Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of, Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of, Department of Radiology, New York University School of Medicine, New York, United States, Department of Radiology, Columbia University, New York, United States, Department of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Hong Kong SAR, China, People's Republic of, Department of Diagnostic Radiology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of, Department of Pediatrics, Columbia University, New York, United States

/pdf/monitoring-iron-chelation-effect-in-hearts-of-thalassaemia-4qb1bpege3.pdf

Monitoring iron chelation effect in hearts of thalassaemia patients with improved sensitivity using reduced transverse relaxation rate (RR2)

Two families from southern India with members having the clinical manifestations of thalassemia intermedia are presented. Hematologic and globin chain synthesis data indicated that in one family the a

Gary M. Brittenham

Papers

Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease.

Circulating non-transferrin-bound iron after oral administration of supplemental and fortification doses of iron to healthy women:

Monitoring iron chelation effect in hearts of thalassaemia patients with improved sensitivity using reduced transverse relaxation rate (RR2)

Thalassemia in Southern India Interaction of Genes for β+-, β°-, and δ° β°-ThaIassemia

Short-term periods of strenuous physical activity lower iron absorption