Fgf10 regulates hepatopancreatic ductal system patterning and differentiation

During organogenesis, the foregut endoderm gives rise to the many different cell types that comprise the hepatopancreatic system, including hepatic, pancreatic and gallbladder cells, as well as the epithelial cells of the hepatopancreatic ductal system that connects these organs together and with the intestine. However, the mechanisms responsible for demarcating ducts versus organs are poorly understood. Here, we show that Fgf10 signaling from the adjacent mesenchyme is responsible for refining the boundaries between the hepatopancreatic duct and organs. In zebrafish fgf10 mutants, the hepatopancreatic ductal epithelium is severely dysmorphic, and cells of the hepatopancreatic ductal system and adjacent intestine misdifferentiate toward hepatic and pancreatic fates. Furthermore, Fgf10 also functions to prevent the differentiation of the proximal pancreas and liver into hepatic and pancreatic cells, respectively. These data shed light onto how the multipotent cells of the foregut endoderm, and subsequently those of the hepatopancreatic duct, are directed toward different organ fates.     

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10??). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.     

Autumnal migration of Eared Grebes ( Podiceps nigricollis ) through southwestern Wyoming: a key to assessing the size of the North American population

In autumn the vast majority of the North American population of Eared Grebes ( Podiceps nigricollis ) congregates for several months at Great Salt Lake, Utah, and Mono Lake, California. Because the lakes are so large, it has not been possible to monitor grebe migration with sufficient accuracy to determine when peak numbers are reached. To clarify migration phenology, we analyzed data from 2 isolated wetland areas in southwestern Wyoming where grebes land en route between breeding areas in the interior and Great Salt Lake. Occasional birds, probably nonbreeders or failed breeders, begin moving southward as early as mid-June. Migration of postbreeding birds starts in late July, peaks in late August and September, and is largely completed by the end of October, with very small numbers arriving into November. The pattern of migration and number of birds encountered varied annually, but 95% of the migration was usually completed by 15 October. As a result, censuses at the major staging lake made on or after 15 October but before the grebes depart for wintering areas can be used to study trends in size of the North American population.     

Mule deer foraging preference among five sagebrush ( Artemisia L.) taxa

The hypothesis that sagebrush taxa are equally utilized by mule deer ( Odocoileus hemionus hemionus ) on winter range was tested. Five taxa were studied for 10 years at 2 locations. The taxa were Artemisia tridentata ssp. tridentata (basin big sagebrush), A. t. ssp. wyomingensis (Wyoming big sagebrush), A. t. ssp. vaseyana (mountain big sagebrush), A. tripartita ssp. tripartita (tall threetip sagebrush), and A. arbuscula ssp. arbuscula (low sagebrush). Possible mule deer preferences were determined each year individually for the 2 sites. Utilization was high enough to conclude all taxa are important forage, but not excessive enough to mask preference. Artemisia tridentata ssp. vaseyana (34.4%) and A. arbuscula ssp. arbuscula (35.6%) were preferred over A. t. ssp. wyomingensis (10.9%) and A. t. ssp. tridentata (6.8%) at the Ashbough site. At the Scudder site there were few differences in preference for A. t. ssp. vaseyana (32.1%), A. t. ssp. wyomingensis (28.8%), and A. tripartita ssp. tripartita (32.0%). While ungulates often demonstrate a preference among taxa, all sagebrush taxa are a potentially valuable forage source.     

Variation in bitterbrush ( Purshia tridentata Pursh) crude protein in southwestern Montana

The objective of this study was to determine if crude protein varies significantly during late summer and midwinter among stands of bitterbrush ( Purshia tridentata Pursh) in southwestern Montana. A secondary objective was to determine if leaves, when present, contribute significant additional protein in the region. Nine sites with different environmental conditions within a radius of 14.5 km were studied. Bitterbrush leaves and leaders collected in August 1990 and 1991 and February 1991 were used for crude protein and leaf-to-leader ratio determinations. Crude protein differed ( P < 0.001) among sites for both leaves and leaders on individual collection dates. Crude protein in leaves was nearly twice the level found in leaders. Because few leaves were present in February, they increased crude protein in total foliage by only 0.3% over twigs alone. February crude protein levels averaged 6.8% for total foliage, which is below the estimated requirement for wintering deer.     

Differential phytosociological interactions involving male and female Atriplex bonnevillensis

Wind-pollinated dioecious plants often exhibit spatial segregation of the sexes. This partial niche separation has most often been explored using abiotic niche axes. However, if the sexes are truly separated in space, then they are apt to encounter different plant species that may heavily affect growth and reproduction. Also, to the extent that their niches differ, the sexes may respond differently to the same co-occurring species. Here we examine interspecific interactions that influence male and female reproductive potential in Atriplex bonnevillensis. Using Emlen&rsquo;s interaction assessment, a technique which assesses species interactions based on cover classes, we show that Salsola species compete significantly with females but not males, while Halogeton glomeratus competes with males but not females. The effect of competition only became apparent when we corrected for site-specific fertility. These results imply that differential competition must be considered when studying dioecious plants that display spatial segregation of the sexes.     

Isozymes of an autopolyploid shrub, Atriplex canescens (Chenopodiaceae)

Diploid, tetraploid, and hexaploid populations of Atriplex canescens ( x =9) were examined for 18 isozyme systems. Of 24 interpretable loci, only one locus (Per 1 ) was polymorphic. Another locus (Per 2 ) showed a dosage effect. Genetic distance values, D, ranged from near 0 to 0.05, which are in the normal range for local species races. Results from clonal ramets gave identical results. The data and analyses support an essentially autopolyploid origin for the polyploid populations examined.     

IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics

Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.     

Nanotechnology: fundamental research to product development

The concept of an integrated "lab on a chip" has long been a goal for the micro-electro-mechanical-systems(MEMS) community.This would entail the integration of not only the sampling and analysis of various functions,but also the ability to transmit this information off the chip to a central repository.This paper describes the initial steps in the fabrication of a "lab on a chip" which would continually analyze blood sampled via microneedles using techniques such as nano plasmonics,specifically,concentrations of glucose.The analysis could then be transmitted off the chip using digital signal processing.This paper describes the analysis and optimization of the microneedle shape and size and the fabrication of the resulting needles in silicon using deep reactive ion etching(DRIE).The paper also describes the opportunities for fabrication of such needles in alternative materials and describes the issues that still have to be overcome before such an integrated device is realized.