Mild gestational diabetes in pregnancy and the adipoinsular axis in babies born to mothers in the ACHOIS randomised controlled trial

BACKGROUND: Mild gestational diabetes is a common complication of pregnancy, affecting up to 9% of pregnant women. Treatment of mild GDM is known to reduce adverse perinatal outcomes such as macrosomia and associated birth injuries, such as shoulder dystocia, bone fractures and nerve palsies. This study aimed to compare the plasma glucose concentrations and serum insulin, leptin and adiponectin in cord blood of babies of women (a) without gestational diabetes mellitus (GDM), (b) with mild GDM under routine care, or (c) mild GDM with treatment. METHODS: 95 women with mild GDM on oral glucose tolerance testing (OGTT) at one tertiary level maternity hospital who had been recruited to the ACHOIS trial at one of the collaborating hospitals and randomised to either Treatment (n = 46) or Routine Care (n = 49) and Control women with a normal OGTT (n = 133) were included in the study. Women with mild GDM (treatment or routine care group) and OGTT normal women received routine pregnancy care. In addition, women with treated mild GDM received dietary advice, blood glucose monitoring and insulin if necessary. The primary outcome measures were cord blood concentrations of glucose, insulin, adiponectin and leptin. RESULTS: Cord plasma glucose was higher in women receiving routine care compared with control, but was normalized by treatment for mild GDM (p = 0.01). Cord serum insulin and insulin to glucose ratio were similar between the three groups. Leptin concentration in cord serum was lower in GDM treated women compared with routine care (p = 0.02) and not different to control (p = 0.11). Adiponectin was lower in both mild GDM groups compared with control (Treatment p = 0.02 and Routine Care p = 0.07), while the adiponectin to leptin ratio was lower for women receiving routine care compared with treatment (p = 0.08) and control (p = 0.05). CONCLUSION: Treatment of women with mild GDM using diet, blood glucose monitoring and insulin if necessary, influences the altered fetal adipoinsular axis characteristic of mild GDM in pregnancy

Genome-wide analysis of PDX1 target genes in human pancreatic progenitors

Objective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing beta-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult beta-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs) and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. Methods: In this study, we have generated a novel induced pluripotent stem cell (iPSC) line that efficiently differentiates into human pancreatic progenitors (PPs). Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. Results: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and ME1S1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation maintains PDX1 expression and initiates a pancreatic TF program. Remarkably, we identified several PDX1 target genes that have not been reported in the literature in human so far, including RFX3, required for ciliogenesis and endocrine differentiation in mouse, and the ligand of the Notch receptor DLL1, which is important for endocrine induction and tip-trunk patterning. The comparison of PDX1 profiles from PPs and adult human islets identified sets of stage-specific target genes, associated with early pancreas development and adult beta-cell function, respectively. Furthermore, we found an enrichment of T2DM-associated SNPs in active chromatin regions from iPSC-derived PPs. Two of these SNPs fall into PDX1 occupied sites that are located in the intronic regions of TCF7L2 and HNF1B. Both of these genes are key transcriptional regulators of endocrine induction and mutations in cis-regulatory regions predispose to diabetes. Conclusions: Our data provide stage-specific target genes of PDX1 during in vitro differentiation of stem cells into pancreatic progenitors that could be useful to identify pathways and molecular targets that predispose for diabetes. In addition, we show that T2DM-associated SNPs are enriched in active chromatin regions at the pancreatic progenitor stage, suggesting that the susceptibility to T2DM might originate from imperfect execution of a beta-cell developmental program

The consumption of work: representations and interpretations of the meaning of work at a UK university

This paper focuses on representations of the nexus of work, meaning and consumption as experienced by university students. We develop an empirically based argument that the meaning of work is being constructed as an object of consumption on a British university campus. We suggest that this indicates two key changes in representations of the meaning of work. First, there is a significant shift in the social construction of orientations to work towards what we term ‘consumption of work’. Second, we argue that this new social construction is made up of three dimensions: consumption of an idealised image of work, consumption through specific work processes and consumption of self-development opportunities at work. We conclude by suggesting ways in which this argument could be researched further

PEMBUATAN SISTEM INFORMASI OBYEK WISATA BERBASIS WEB MENGGUNAKAN MAPSERVER ( Studi Kasus : Kota Batu )

Kota Batu merupakan salah satu wilayah di Jawa Timur yang memiliki potensi obyek wisata yang besar. Namun potensi obyek wisata ini tidak dapat diketahui oleh wisatawan, dikarenakan kurangnya informasi tentang obyek wisata di Kota Batu. Disamping itu, informasi yang disediakan selama ini hanya bersifat statis. Mengacu pada pemahaman tersebut maka penelitian ini mengkaji sebuah penyajian informasi untuk Obyek Wisata Kota Batu memanfaatkan WEBGIS dengan menggunakan MapServer OpenSource, MySQL, PHP/Mapscript dan ArcGIS. Penelitian ini menghasilkan sebuah sistem informasi tentang obyek wisata di Kota Batu yang berbasis web yang didalamnya juga terdapat informasi jenis wisata, lokasi obyek wisata,dan deskripsi obyek wisata serta foto obyek wisata. Kata Kunci : Kota batu, Obyek Wisata, WebGI

Implementasi Penilaian Otentik oleh Guru Bahasa Inggris di Flores

Kegiatan pembelajaran yang baik dan bermakna juga memerlukan sebuah penilaian yang baik. Perencanaan dan proses pembelajaran harus diakhiri dengan sebuah tahapan penilaian yang berkualitas. Penelitian desain kualitatif ini bertujuan untuk mengetahui praktik, masalah, dan kendala guru dalam kegiatan penilaian otentik. Penelitian melibatkan guru bahasa Inggris yang tergabung dalam Musyawarah Guru Mata Pelajaran Sekolah Bahasa Inggris di Flores. Data diambil dengan teknik observasi, wawancara, dan studi dokumentasi. Hasil penelitian menemukan bahwa implementasi penilaian otentik untuk mata pelajaran bahasa Inggris belum berjalan dengan baik. Kesiapan guru terkait instrumen, penentuan tipe penilaian, dan prosedur penilaian menjadi masalah dalam penerapannya. Selain itu, alokasi waktu dan kemampuan siswa merupakan tantangan yang dihadapi guru dalam menjalankan proses penilaian. Oleh karena itu, guru harus menyiapkan sebuah instrumen, penentuan tipe, dan prosedur penilaian dengan baik