Dated molecular phylogenies indicate a Miocene origin for Arabidopsis thaliana

Dated molecular phylogenies are the basis for understanding species diversity and for linking changes in rates of diversification with historical events such as restructuring in developmental pathways, genome doubling, or dispersal onto a new continent. Valid fossil calibration points are essential to the accurate estimation of divergence dates, but for many groups of flowering plants fossil evidence is unavailable or limited. Arabidopsis thaliana, the primary genetic model in plant biology and the first plant to have its entire genome sequenced, belongs to one such group, the plant family Brassicaceae. Thus, the timing of A. thaliana evolution and the history of its genome have been controversial. We bring previously overlooked fossil evidence to bear on these questions and find the split between A. thaliana and Arabidopsis lyrata occurred about 13 Mya, and that the split between Arabidopsis and the Brassica complex (broccoli, cabbage, canola) occurred about 43 Mya. These estimates, which are two- to threefold older than previous estimates, indicate that gene, genomic, and developmental evolution occurred much more slowly than previously hypothesized and that Arabidopsis evolved during a period of warming rather than of cooling. We detected a 2- to 10-fold shift in species diversification rates on the branch uniting Brassicaceae with its sister families. The timing of this shift suggests a possible impact of the Cretaceous-Paleogene mass extinction on their radiation and that Brassicales codiversified with pierid butterflies that specialize on mustard-oil-producing plants.     

Overview of endocrinopathies associated with β‐thalassaemia major

Background: Thalassaemia major is a common and serious medical problem worldwide that is associated with a range of complications, including effects on multiple endocrine pathways. Minimizing or preventing comorbidities is important for these individuals who need life‐long multidisciplinary care and treatment. However, there are limited overviews of the endocrine complications associated with this illness, nor any consensus regarding management guidelines. Method: A retrospective cohort analysis of β‐thalassaemia patients attending an ambulatory transfusion clinic at Royal Prince Alfred Hospital was conducted from June 2008. Results: All of our subjects (n = 29) had at least one endocrinopathy present with 16 patients (55%) having three or more (≥3) endocrinopathies. Hypogonadism was the most prevalent followed by osteoporosis and growth failure (less than 3rd centile) with a frequency of 16/29 (55%), 14/29 (48%) and 10/29 (35%) patients respectively. Those with more endocrinopathies (≥3) had a longer duration of transfusion therapy when compared with those with fewer endocrinopathies. Conclusion: A summary of our clinical guidelines, which have been used to monitor and manage these complications, is presented along with a discussion on the results and pathophysiology of the associated endocrinopathies.     

HIV Prevalence and Risk Behaviours from Three Consecutive Surveys Among Men Who Have Multiple Female Sexual Partners in Cape Town

HIV bio-behavioural surveillance surveys conducted at regular intervals are critical for monitoring of, and informing a targeted response to the HIV pandemic. We used Respondent-driven Sampling in 2006, 2008 and 2010 to recruit men who have multiple female sexual partners. We performed several logistic regression analyses to compare HIV sexual risk behaviours, and HIV infection over time. Decreases in inconsistent condom use with main partners were not sustained in 2010. Inconsistent condom use with non-main partners, partner numbers and having one-time partners continued to decrease over time. Levels of alcohol consumption in 2010 reverted to a level higher than in 2006. Non-significant increases in HIV prevalence and reporting a symptom of a sexually transmitted infection (STI) were found. The decrease in numbers of and one-time sexual partners, and in inconsistent condom use with non-main partners augers well for decreasing HIV incidence among men in the study community, but might be offset by decreases in consistent condom use with main partners, and increases in alcohol consumption and STIs.     

Molecular basis of quantitative fibrinogen disorders in 27 patients from India

Congenital fibrinogen deficiency is an extremely rare (1:1 000 000) hereditary bleeding disorder caused by defects in genes coding for fibrinogen Aα‐, Bβ‐ and γ‐chains, respectively. We report here the molecular basis of fibrinogen deficiency in a large series of patients from India. Twenty‐seven patients with clinical features suggestive of fibrinogen deficiency and with prolonged plasma clotting times and low fibrinogen levels were studied. Genomic DNA was screened for mutations in the fibrinogen alpha (FGA), beta (FGB), gamma (FGG) genes by PCR and conformation sensitive gel electrophoresis. Fourteen different disease‐causing mutations including frameshifts (51.9%), splice site (22.2%), missense (18.5%) and nonsense mutation (7.4%) were identified in 27 patients. Thirteen of them were novel, including seven frameshifts (fibrinogen Aα: p.Asp296 fs*59, p.Thr466 fs*17 and p.Lys575 fs*74; fibrinogen Bβ: p.Gly414 fs*2 and fibrinogen γ: p.Ser81 fs*5, p.Lys185 fs*13 and p.Asp278_279 fs*17), three splice site mutations (FGA gene c.364+1G>A; c.510+2 T>G; FGB gene c.851+1G>A), two missense substitutions (fibrinogen Bβ: p.Gly288Ser; p.Arg445Thr) and a nonsense mutation in fibrinogen Aα (p.Tyr127*). Two common mutations (FGA: c.364+1G>A, n = 6, FGG: p.Lys185 fs*13, n = 7) affecting 13 patients were identified in this series, suggesting that these mutations could be screened first in Indian patients with fibrinogen deficiency. The molecular data presented here is the largest series of patients with fibrinogen deficiency reported so far, adding significantly to the mutation database of this condition. It also helps create an algorithm for its genetic diagnosis in India.