A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine

Background: p53 is an important tumour suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated. Methods: We have conditionally deleted the Adenomatous Polyposis coli gene (Apc) from the adult murine intestine in wild type and p53 deficient environments and subsequently compared the phenotype and transcriptome profiles in both genotypes. Results: Expression of p53 was shown to be elevated following the conditional deletion of Apc in the adult small intestine. Furthermore, p53 status was shown to impact on the transcription profile observed following Apc loss. A number of key Wnt pathway components and targets were altered in the p53 deficient environment. However, the aberrant phenotype observed following loss of Apc (rapid nuclear localisation of β-catenin, increased levels of DNA damage, nuclear atypia, perturbed cell death, proliferation, differentiation and migration) was not significantly altered by the absence of p53. Conclusion: p53 related feedback mechanisms regulating Wnt signalling activity are present in the intestine, and become activated following loss of Apc. However, the physiological Wnt pathway regulation by p53 appears to be overwhelmed by Apc loss and consequently the activity of these regulatory mechanisms is not sufficient to modulate the immediate phenotypes seen following Apc loss. Thus we are able to provide an explanation to the apparent contradiction that, despite having a Wnt regulatory capacity, p53 loss is not associated with early lesion development

Macrosomia and large for gestational age in Asia:One size does not fit all

Macrosomia, usually defined as infant birth weight of >= 4000 g, does not consider gestational age, sex, or country/region-specific differences in mean birth weight and maternal body weight. This issue is particularly relevant for Asia, where 60% of the world's population lives, due to variations in maternal size and birth weights across populations. Large for gestational age (LGA), defined as birth weight > 90th centile, is a more sensitive measure as it considers gestational age and sex, though it is dependent on the choice of growth charts. We aimed to review reporting of macrosomia and LGA in Asia. We reviewed the literature on prevalence and risk of macrosomia and LGA in Asia over the last 29 years. Prevalence of macrosomia ranged from 0.5% (India) to 13.9% (China) while prevalence of LGA ranged from 4.3% (Korea) to 22.1% (China), indicating substantial variation in prevalence within and between Asian countries. High pre-pregnancy body mass index, excessive gestational weight gain, and impaired glucose tolerance conferred risk of macrosomia/LGA. Incidence of macrosomia and LGA varies substantially within and between Asian countries, as do the growth charts and definitions. The latter makes it impossible to make comparisons but suggests differences in intrauterine growth between populations. Reporting LGA, using standardized country/regional growth charts, would better capture the incidence of high birth weight and allow for comparison and identification of contributing factors. Better understanding of local drivers of excessive intrauterine growth could enable development of improved strategies for prevention and management of LGA

EFFECT OF DIFFERENT SOWING DATES ON YIELD OF TOMATO GENOTYPES

The experiment was conducted at Agricultural Research Station, Thakurgaon, Bangladesh during October 2009 to March 2010 to observe the effect of sowing dates on yield of tomato genotypes. Three sowing dates viz. October 1, October 15 and October 30 were considered as factor A and tomato variety viz., BARI Tomato-2, BARI Tomato-3, BARI Tomato-4, BARI Tomato-9 and BARI Hybrid Tomato-4 considered as factor B. The experiment was laid out in RCBD (Factorial) with three replications. Early flowering (52.40 days) as well as early fruit harvesting (119.13 days) was occurred in October 1 sowing, where as sowing on October 30 resulted in delayed flowering (71.73 days) and fruit harvesting (140.67 days), respectively. Number of fruits per plant was also the highest (27.40) in October 1 sowing and the lowest (13.73) was in October 30 sowing. Seed sowing of October 1 was found better in respect of yield (74.75 tha-1) compared to October 15 (58.55 tha-1) and October 30 (24.60 tha1) sowing. Among the variety, BARI Tomat-2 produced the highest (68.12 tha-1) marketable yield followed by BARI Tomato-9 (56.16 tha-1) and BARI Tomato-3 while BARI Tomato-4 gave the lowest (36.91 tha-1) marketable yield

Snm1-Deficient Mice Exhibit Accelerated Tumorigenesis and Susceptibility to Infection

The eukaryotic SNM1 gene family has been implicated in a number of cellular pathways, including repair of DNA interstrand cross-links, involvement in VDJ recombination, repair of DNA double-strand breaks, and participation in cell cycle checkpoint pathways. In particular, mammalian SNM1 has been shown to be required in a mitotic checkpoint that causes arrest of cells in prophase prior to chromosome condensation in response to spindle poisons. Here, we report on the phenotype of a knockout of Snm1 in the mouse. Snm1(−)(/)(−) mice are viable and fertile but exhibit a complex phenotype. Both homozygous and heterozygous mice show a decline in survival compared to wild-type littermates. In homozygous mutant males, this reduction in survival is principally due to bacterial infections in the preputial and mandibular glands and to a lesser extent to tumorigenesis, while in homozygous and heterozygous females, it is due almost solely to tumorigenesis. The high incidence of bacterial infections in the homozygous mutant males suggests an immune dysfunction; however, examinations of T- and B-cell development and immunoglobulin class switching did not reveal a defect in these pathways. Crossing of Snm1 mutant mice with a Trp53 null mutant resulted in an increase in mortality and a restriction of the tumor type to lymphomas, particularly those of the thymus. Taken together, these findings demonstrate that Snm1 is a tumor suppressor in mice that in addition has a role in immunity

Diabetes in pregnancy in Pakistani women: prevalence and complications in an indigenous south Asian community

The aim of this study was to determine the prevalence and complications as well as to correlate maternal and fetal outcome with glycaemic control, in a community of Pakistani women. This was a retrospective study of 6830 deliveries over a 5-year period in a tertiary care hospital in Karachi. Either a 75 g glucose tolerance test or a screening 50 g glucose challenge was administered depending on risk factors for Gestational Diabetes Mellitus (GDM). Case records of deliveries during this period were analysed for presence of GDM or pre-existing diabetes; glycaemic control and complications were ascertained for those with diabetes. During this period 267 (3.9%) of the 6380 deliveries were identified as diabetic pregnancies. Of these 223 (3.3%) had GDM and 44 (0.6%) women had pre-existing diabetes mellitus. Overall maternal complications were high; pre-eclampsia (19%), polyhydramnios (4.6%), and threatened abortion (3.4%). Fetal complications of macrosomia (13.1%), intrauterine growth retardation (7.1%), intrauterine deaths (5.3%) were noted. Complications were higher in poorly controlled groups. We conclude that the prevalence of GDM in Pakistani women in our study was comparable to their Western counterparts but complication rates were higher, possibly due to poorer glycaemic control