Genetic instability in EBV-transformed lymphoblastoid cell lines

Epstein Barr virus (EBV)-transformed lymphoblastoid cell lines are commonly used to provide an inexhaustible supply of DNA. We examined microsatellite instability in these cell lines in 35 individuals where DNA was available from the original blood samples and from cultured cell lines. Mutations were observed in 0.3% of the analyses, thus providing a quantitative measure of somatic mutation rate.     

The genetic legacy of the Mongols

We have identified a Y-chromosomal lineage with several unusual features. It was found in 16 populations throughout a large region of Asia, stretching from the Pacific to the Caspian Sea, and was present at high frequency: approximately 8% of the men in this region carry it, and it thus makes up approximately 0.5% of the world total. The pattern of variation within the lineage suggested that it originated in Mongolia approximately 1,000 years ago. Such a rapid spread cannot have occurred by chance; it must have been a result of selection. The lineage is carried by likely male-line descendants of Genghis Khan, and we therefore propose that it has spread by a novel form of social selection resulting from their behavior.     

Interleukin-10 and sudden infant death syndrome

Uncontrolled pro-inflammatory responses to infections or bacterial toxins have been suggested to play a role in triggering the physiological events leading to sudden infant death syndrome (SIDS). We tested the hypothesis that these uncontrolled responses might be due to interactions between the gene polymorphisms inducing low levels of IL-10 and exposure to cigarette smoke. In vitro, the IL-10 (G-1082A) polymorphism was associated with low IL-10 levels and the -1082G allele was associated with high levels. The first objective was to assess the distribution of this polymorphism among SIDS infants, parents of SIDS infants and controls, and two ethnic groups: Aboriginal Australians who have a high incidence of SIDS; and Bangladeshis who in Britain have a low incidence of SIDS compared with Europeans. The second objective was to assess effects of human recombinant IL-10 on interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) responses of human leukocytes to staphylococcal toxins implicated in SIDS. The third objective was to assess IL-10 responses to endotoxin and toxic shock syndrome toxin (TSST) from leukocytes of smokers and non-smokers in relation to the IL-10 (G-1082A) polymorphism. There were major differences in the distributions of these polymorphisms between Europeans and Bangladeshis (p=0.00) and between Europeans and Aboriginal Australians (p=0.00); however, they were similar for the Bangladeshi and Aboriginal Australian subjects. There were no significant differences in the distribution of these polymorphisms among SIDS infants or parents of SIDS infants compared to control groups. IL-10 significantly reduced IL-6 and TNF-alpha responses to TSST and staphylococcal enterotoxins A and C. At 50 ng ml(-1), IL-10 significantly increased TNF-alpha but not IL-6 responses to TSST and enterotoxin A. Although IL-10 responses to endotoxin were lower from leukocytes of smokers who were homozygous for the G allele, the differences were not significant; however, significantly lower IL-10 responses were found for smokers who were homozygous for the A allele (p=0.01) and heterozygotes (p=0.04). The pooled data found smokers had significantly lower levels of IL-10 responses to TSST, but there were no significant differences for smokers compared with non-smokers for the three genotypes. The high incidence of SIDS and serious respiratory infections among Aboriginal Australian infants and the low incidence of these conditions among Bangladeshi infants might be explained in part by our findings of differences in IL-10 responses between smokers and non-smokers. The lowest levels of IL-10 responses were observed among smokers who were homozygous for the A allele which is most prevalent among the Aboriginal Australians (83%) and Bangladeshis (84%). The major difference between the risk factors for SIDS in these two groups is the level of exposure of infants to cigarette smoke associated with maternal smoking.     

Heparan sulfate-independent infection attenuates high-neurovirulence GDVII virus-induced encephalitis

The high-neurovirulence Theiler's murine encephalomyelitis virus (TMEV) strain GDVII uses heparan sulfate (HS) as a coreceptor to enter target cells. We report here that GDVII virus adapted to growth in HS-deficient cells exhibited two amino acid substitutions (R3126L and N1051S) in the capsid and no longer used HS as a coreceptor. Infectious-virus yields in CHO cells were 25-fold higher for the adapted virus than for the parental GDVII virus, and the neurovirulence of the adapted virus in intracerebrally inoculated mice was substantially attenuated. The adapted virus showed altered cell tropism in the central nervous systems of mice, shifting from cerebral and brainstem neurons to spinal cord anterior horn cells; thus, severe poliomyelitis, but not acute encephalitis, was observed in infected mice. These data indicate that the use of HS as a coreceptor by GDVII virus facilitates cell entry and plays an important role in cell tropism and neurovirulence in vivo.     

Fine needle aspiration cytology of the thyroid: a cytohistologic study with evaluation of discordant cases

OBJECTIVE: To analyze the diagnostic efficacy of fine needle aspiration cytology (FNAC) in the initial evaluation of thyroid nodules, with special emphasis on discrepant cytologic diagnoses. STUDY DESIGN: A total of 192 thyroid fine needle aspirates with subsequent histopathologic follow-up were analyzed. The cytologic diagnoses were divided into 4 categories: positive for malignancy, negative for malignancy, indeterminate for diagnosis and nondiagnostic. The detailed cytologic features were studied along with histopathology sections in all these cases by 2 observers (S.J. and P.D) independently. RESULTS: Cytohistologic correlation was seen in 78.1% of cases and discordance in 21.9%. Indeterminate diagnoses accounted for 15.1% of cases. The majority of these were "follicular neoplasms." The overall sensitivity was 84.44% and specificity 99.11 %. A false positive diagnosis was made in 1 case (0.5%), proven a follicular adenoma on histopathologic examination. A false negative diagnosis was seen in 3.6% of cases. These were cases of papillary microcarcinoma. CONCLUSION: FNAC is a safe, sensitive and specific technique in the initial evaluation of thyroid nodules. A correct cytologic diagnosis can be achieved in a majority of cases, thus obviating the need for a second surgical intervention. A careful and diligent search for various cytologic features and accurate sampling can help in reducing the number of indeterminate, false positive and false negative diagnoses.     

Diel timing of nest predation changes across breeding season in a subtropical shorebird

Predation is the most common cause of nest failure in birds. While nest predation is relatively well studied in general, our knowledge is unevenly distributed across the globe and taxa, with, for example, limited information on shorebirds breeding in subtropics. Importantly, we know fairly little about the timing of predation within a day. Here, we followed 444 nests of the red‐wattled lapwing (Vanellus indicus), a ground‐nesting shorebird, for a sum of 7,828 days to estimate a nest predation rate, and continuously monitored 230 of these nests for a sum of 2,779 days to reveal how the timing of predation changes over the day and season in a subtropical desert. We found that 312 nests (70%) hatched, 76 nests (17%) were predated, 23 (5%) failed for other reasons, and 33 (7%) had an unknown fate. Daily predation rate was 0.95% (95%CrI: 0.76% – 1.19%), which for a 30‐day long incubation period translates into ~25% (20% – 30%) chance of nest being predated. Such a predation rate is low compared to most other avian species. Predation events (N = 25) were evenly distributed across day and night, with a tendency for increased predation around sunrise, and evenly distributed also across the season, although night predation was more common later in the season, perhaps because predators reduce their activity during daylight to avoid extreme heat. Indeed, nests were never predated when midday ground temperatures exceeded 45℃. Whether the diel activity pattern of resident predators undeniably changes across the breeding season and whether the described predation patterns hold for other populations, species, and geographical regions await future investigations.     

Découverte de charophytes et ostracodes de l’Yprésien inférieur dans les Monts des Ksour (Algérie) : biostratigraphie et paléoécologie

A stratigraphic, palaeontological and sedimentological study was carried out in the red beds cropping out on the left side of Oued Tafarahit, south-east of the Ksour Mountains (Algeria). The studied succession consists of a non-marine fining-upward detrital formation, including microconglomerate, sandstone and clay beds, which were previously attributed to the Cenozoic sensu lato, since no palaeontological evidence was available. Sedimentology suggests deposition in a fluvial environment. The clayey levels yielded the assemblage formed by the charophytes Peckichara atlasensis, Maedleriella cristellata, Nitellopsis (Tectochara) thaleri, Grovesichara sp., and Lamprothamnium papulosum and the ostracods Neocyprideis meguerchiensis, Herpetocypris? sp. and Cyprinotus? sp. This assemblage allows constraining the age of the detrital series from Oued Tafarahit to the Ypresian. Ostracods are typical of freshwater to euryhaline environments. The freshwater taxa (Herpetocypris? sp. and Cyprinotus? sp.) would indicate phases of desalinisation during periods of flood. However, the brackish water species (Neocyprideis meguerchiensis) is characteristic of saline phases related to low water table periods. Moreover the charophyte and ostracod assemblage confirms a close palaeobiogeographic relationship between North Africa and Southern Europe during the Lower Eocene.     

Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy

In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR).