The Five AhMTP1 Zinc Transporters Undergo Different Evolutionary Fates towards Adaptive Evolution to Zinc Tolerance in Arabidopsis halleri

Gene duplication is a major mechanism facilitating adaptation to changing environments. From recent genomic analyses, the acquisition of zinc hypertolerance and hyperaccumulation characters discriminating Arabidopsis halleri from its zinc sensitive/non-accumulator closest relatives Arabidopsis lyrata and Arabidopsis thaliana was proposed to rely on duplication of genes controlling zinc transport or zinc tolerance. Metal Tolerance Protein 1 (MTP1) is one of these genes. It encodes a Zn2+/H+ antiporter involved in cytoplasmic zinc detoxification and thus in zinc tolerance. MTP1 was proposed to be triplicated in A. halleri, while it is present in single copy in A. thaliana and A. lyrata. Two of the three AhMTP1 paralogues were shown to co-segregate with zinc tolerance in a BC1 progeny from a cross between A. halleri and A. lyrata. In this work, the MTP1 family was characterized at both the genomic and functional levels in A. halleri. Five MTP1 paralogues were found to be present in A. halleri, AhMTP1-A1, -A2, -B, -C, and -D. Interestingly, one of the two newly identified AhMTP1 paralogues was not fixed at least in one A. halleri population. All MTP1s were expressed, but transcript accumulation of the paralogues co-segregating with zinc tolerance in the A. halleri X A. lyrata BC1 progeny was markedly higher than that of the other paralogues. All MTP1s displayed the ability to functionally complement a Saccharomyces cerevisiæ zinc hypersensitive mutant. However, the paralogue showing the least complementation of the yeast mutant phenotype was one of the paralogues co-segregating with zinc tolerance. From our results, the hypothesis that pentaplication of MTP1 could be a major basis of the zinc tolerance character in A. halleri is strongly counter-balanced by the fact that members of the MTP1 family are likely to experience different evolutionary fates, some of which not concurring to increase zinc tolerance

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials

Perioperative Care of the Infant With Single Ventricle Physiology

Opinion statement Among patients with congenital heart defects, neonates with single ventricle disease continue to challenge clinicians despite significant improvements in survival over the past 30 years. The cardiac anatomical variants associated with the term “single ventricle” are characterized by severe hypoplasia (or absence) of either ventricle, typically in association with obstruction or atresia of either the pulmonary or systemic outflow tracts. Physiologically, the single ventricle receives both pulmonary and systemic venous blood and ejects simultaneously into the pulmonary and systemic circulations, a pattern commonly referred to as single ventricle physiology. Medical and surgical management strategies, though palliative, are aimed at achieving the optimal balance of systemic blood flow and pulmonary blood flow to maximize oxygen delivery. Patients with single ventricle physiology have a greater risk of dying than those with biventricular circulations and are generally committed to multiple palliative interventions throughout childhood with considerable risk. Surgical intervention in the newborn period involves Norwood Stage I palliation, placement of a systemic-to-pulmonary artery shunt, or banding of the pulmonary artery, depending on the status of the outflow tracts. Heart transplantation is offered as the initial approach in some centers. The management strategy and the actual delivery of care from the time of birth (or at time of diagnosis) through the postoperative period is crucial to optimize the short-term and long-term outcomes. Whereas survival following initial palliation in experienced centers is as high as 95%, emphasis is now appropriately shifting toward the control of in-hospital morbidity and optimizing long-term functional outcome. Centers are continually striving to gather and apply new knowledge related to the underlying anatomical and physiologic problems while seeking to improve decision making and care of the patient with single ventricle physiology