The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus)

We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat (Myrmecobius fasciatus). Surprisingly, both of our thylacine sequences differ by 11%–15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples’ heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes.     

Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugates

The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement (18)F-FDG. Copper-64 ((64)Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-N-(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6] eicosane-1,8-diamine) for use in developing a new class of tumor-specific (64)Cu radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with (64)Cu resulted in >95% of the (64)Cu being chelated by the immunoconjugate. Specific activities of at least 10 microCi/microg (1 Ci = 37 GBq) were routinely achieved, and no additional purification was required after (64)Cu labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15-20% of the injected dose per gram accumulated in the tumor at 24 hours after injection, and only 5-10% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (<5% injected dose per gram). MicroPET imaging confirmed significant uptake of the tracer in GD-2-positive tumors, with minimal uptake in GD-2-negative tumors and nontarget tissues such as liver. The (64)Cu-SarAr-mAb system described here is potentially applicable to (64)Cu-PET imaging with a broad range of antibody or peptide-based imaging agents.     

Serial metabolic measurements and conversion to type 2 diabetes in the west of Scotland coronary prevention study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor

To examine metabolic changes (lipids, liver enzymes, blood pressure, and weight) potentially associated with conversion to diabetes, we analyzed serial glucose and other metabolic measures obtained every 6 months within the West of Scotland Coronary Prevention Study trial. Changes in parameters for 86 men who converted to new-onset diabetes ("converters": two consecutive glucose levels > or =7 mmol/l) were compared with 860 "nonconverters" matched for age and treatment allocation. Eighteen months before the diagnosis, converters to diabetes had elevated (P < 0.01) fasting glucose, weight, triglyceride, alanine aminotransferase (ALT), blood pressure, and white cell count and lower HDL cholesterol compared with nonconverters. The mean (SD) increase in fasting glucose over 18 months in converters was 1.80 (1.52) mmol/l, compared with 0.10 (0.57) in nonconverters. Of parameters measured, only ALT (P = 0.0005) and triglyceride (P = 0.030) increased significantly more over the 18 months in converters compared with nonconverters, but neither parameter increased significantly in nonconverters with high baseline glucose concentrations (>6.1 mmol/l). Finally, only sustained increases in ALT predicted a higher risk for diabetes. We conclude that a relatively rapid rise in fasting glucose levels is frequent in converters to diabetes and that associated increases over time in ALT and potentially triglyceride suggest hepatic fat accumulation as a contributing factor for conversion to diabetes in men at risk.     

生活方式改善对预防糖尿病的重要作用

营养过剩、肥胖．缺少运动是糖尿病发病的重要原因。本文针对这些原因阐述了防止肥胖、控制饮食和增加运动等生活方式的改善对预防糖尿病的重要作用。     

呼和浩特市区餐饮单位的餐具消毒效果

目的了解呼和浩特市餐饮单位餐具消毒状况,分析不同规模餐饮单位餐具消毒效果。方法采用大肠菌群快速检测纸片法,抽取2005-2007年本市餐饮单位消毒后备用餐具进行检测。结果3年共检测餐具7957份,合格率为64.28％;大、中、小型餐饮单位合格率分别为74.59％、65.32％和36.33％;大中专院校食堂合格率为68.21％。结论呼和浩特市餐具消毒总体合格率较低,应加大执法力度,加强监测频率,尤其要督促搞好学校食堂餐具消毒工作。     

Association between apolipoprotein E4 and cognitive decline in elderly adults

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2‐year (range 0.7–4.2) follow‐up for memory (Picture‐Word Recall), speed of information processing (Stroop and Letter‐Digit Coding), global cognitive function (Mini‐Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E₄ versus those without E₄ had poorer memory performance (mean score difference ?0.20 (95% confidence interval (CI)=?0.31 to ?0.09) for immediate recall and ?0.32 (95% CI=?0.48 to ?0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20–4.28); Letter‐Digit score, ?0.36, (95% CI=?0.77–0.05). Subjects with apolipoprotein E₄ showed a greater decline in immediate (?0.22, 95% CI=?0.33 to ?0.11) and delayed (?0.30, 95% CI=?0.46 to ?0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter‐Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E₄, 4.3% in E₄ heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E₄) and 8.9% to 13.8% in E₄ homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E₄ was associated with greater decline in instrumental activities of daily living (P<.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E₄ is associated with more‐rapid cognitive decline and may, therefore, predispose to dementia.     

Management of resistant halo nevi

Background: Halo nevus (HN) is a rare dermatologic disorder characterized by typical whitish rim surrounding an existing melanocytic nevus resembling halo. It is a cosmetic problem that may be linked to vitiligo, and it is advised to remove these nevi in order to avoid development of vitiligo.

Objectives: The aim of the present study is to evaluate the cosmetic outcome after nevus removal and leukoderma dermabrasion with epithelial graft followed by narrow-band ultraviolet B (NB-UVB) phototherapy as management of resistant halo nevi and avoidance of development of vitiligo.

Patients and Methods: Ten patients with persisting halo nevi were selected as candidates in this study. Superficial dermabrasion was carried out using proper diamond fraises on depigmented rim and then punch biopsy probes with suitable size were used to harvest the nevus. Thiersch graft was prepared and applied on the dermabraded depigmented area. After 1 week of the procedure, patients were exposed to NB-UVB twice weekly and were followed up for 3 months.

Results: Repigmentation was noticed in 2 weeks and was nearly fully accomplished in all 10 patients within the 3-month period. No other vitiligo lesions developed during this period in all patients except for one case.

Conclusion: Excision of Sutton’s nevus with combined dermabrasion and Thiersch grafting followed by phototherapy is a good aesthetic maneuver in treating halo nevi and helps in avoiding further vitiligo depigmentation.