The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of ...human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
The balance between the concentrations of free ionized Ca2+ and bicarbonate in pancreatic juice is of critical importance in preventing the formation of calcium carbonate stones. How the pancreas ...regulates the ionic composition and the level of Ca2+ saturation in an alkaline environment such as the pancreatic juice is not known. Because of the tight cause-effect relationship between Ca2+ concentration and lithogenicity, and because hypercalcemia is proposed as an etiologic factor for several pancreatic diseases, we have investigated whether pancreatic tissues express a Ca2+-sensing receptor (CaR) similar to that recently identified in parathyroid tissue. Using reverse transcriptase-polymerase chain reaction and immunofluorescence microscopy, we demonstrate the presence of a CaR-like molecule in rat pancreatic acinar cells, pancreatic ducts, and islets of Langerhans. Functional studies, in which intracellular free Ca2+ concentration was measured in isolated acinar cells and interlobular ducts, show that both cell types are responsive to the CaR agonist gadolinium (Gd3+) and to changes in extracellular Ca2+ concentration. We also assessed the effects of CaR stimulation on physiological HCO3- secretion from ducts by making measurements of intracellular pH. Luminal Gd3+ is a potent stimulus for HCO3- secretion, being equally as effective as raising intracellular cAMP with forskolin. These results suggest that the CaR in the exocrine pancreas monitors the Ca2+ concentration in the pancreatic juice, and might therefore be involved in regulating the level of Ca2+ in the lumen, both under basal conditions and during hormonal stimulation. The failure of this mechanism might lead to pancreatic stone formation and even to pancreatitis.
Background: Neuroendocrine tumours of the pancreas (PNETs) represent 1–2% of all pancreatic tumours. The terms ‘islet cell tumours’ and ‘carcinoids’ of the pancreas should be avoided. The aim of this ...review is to offer an overview of the history and diagnosis of PNETs followed by a discussion of the available treatment options. Methods: A search on PubMed using the keywords ‘neuroendocrine’, ‘pancreas’ and ‘carcinoid’ was performed to identify relevant literature over the last 30 years. Results: The introduction of a revised classification of neuroendocrine tumours by the World Health Organisation (WHO) in 2000 significantly changed our understanding of and approach to the management of these tumours. Advances in laboratory and radiological techniques have also led to an increased detection of PNETs. Surgery remains the only treatment that offers a chance of cure with increasing number of non-surgical options serving as beneficial adjuncts. The better understanding of the behaviours of PNETs together with improvements in tumour localisation has resulted in a more aggressive management strategy with a concomitant improvement in symptom palliation and a prolongation of survival. Conclusion: Due to their complex nature and the wide range of therapeutic options, the involvement of specialists from all necessary disciplines in a multidisciplinary team setting is vital to provide optimal treatment of this disease.
The acceptability of satisfaction as a quality indicator is qualified by several well known measurement problems. This study examines the variability in satisfaction evaluations related to different ...measurement methods and the effect of response biases on reported satisfaction. Satisfaction evaluations using seven different, commonly used measures of patient satisfaction were obtained from the same sample of respondents. The seven measures were: 1) a global measure of satisfaction using a visual analogue scale; 2) a multidimensional measure of satisfaction based on the Patient Satisfaction Questionnaire using an evaluation response format (poor, fair, good, very good, excellent); 3) a two-item overall evaluation of quality using the evaluation response format; 4) a six-item attitude measure of general satisfaction using a five-point Likert agree-disagree response format; 5) a four-item attitude measure of satisfaction with physician, using the agree-disagree response format; 6) a four-item measure of behavioral intention; and 7) willingness-to-pay in dollars. The percentage of favorable evaluations of care ranged from 63% to 82% across six of the seven measures. Willingness-to-pay does not appear to be a valid measure of satisfaction. Correlations were highest between measures with similar response formats. Although an oppositional response bias was not found, a very substantial acquiescent response bias was detected. Acquiescence reduced the internal consistency of three multiple-item measures, the general and physician attitude and behavioral intention measures, to levels unacceptable even for group comparisons. Between highly and nonacquiescent respondents, levels of satisfaction were somewhat lower for the multidimensional measure of satisfaction and significantly lower for the two attitude satisfaction measures. Highly acquiescent respondents were older, less well educated, and in poorer health than nonacquiescent subjects. Results of satisfaction evaluations dependent on the measurement method used, and unreliability of measurement may be a significant problem in satisfaction measurement, especially for the oldest and most ill patients.
An SNP map of human chromosome 22 Bentley, D. R; Mullikin, J. C; Hunt, S. E ...
Nature (London),
09/2000, Letnik:
407, Številka:
6803
Journal Article
Recenzirano
Odprti dostop
The human genome sequence will provide a reference for measuring DNA sequence
variation in human populations. Sequence variants are responsible for the
genetic component of individuality, including ...complex characteristics such
as disease susceptibility and drug response. Most sequence variants are single
nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP
per kilobase. A sufficiently dense map of SNPs would allow
the detection of sequence variants responsible for particular characteristics
on the basis that they are associated with a specific SNP allele.
Here we have evaluated large-scale sequencing approaches to obtaining SNPs,
and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the
SNPs are within 25 kilobases of a transcribed exon, and are valuable
for association studies. We have scaled up the process, detecting over 65,000
SNPs in the genome as part of The SNP Consortium programme, which is on target
to build a map of 1 SNP every 5 kilobases that is integrated
with the human genome sequence and that is freely available in the public
domain.
Scientific contributions from remote sensing over the last fifty years have significantly advanced our understanding of urban areas. Key contributions of urban remote sensing include but are not ...limited to characterization of urban areas, urban land cover changes and thermal remote sensing of urban climates. Today, the proliferation of new sensors, long time series of the satellite record, joint analysis of Earth observation data with ancillary data sets, widespread availability of high-performance computing facilities, and slow but increasing use of remote sensing data and methods in non-remote sensing fields together offer new opportunities to generate scientific knowledge for an urbanizing planet. Simultaneously, the scale and pace of contemporary urbanization require new information about urban areas from both the science and policy communities. This paper examines remote sensing contributions to the scientific understanding of urban areas over the last 50 years until today. Based on this assessment and current needs by user communities, we identify four strategic directions for future urban remote sensing research: high temporal frequency analysis, characterization of urban heterogeneity, characterization of urban form and structure in two and three dimensions, and linking remote sensing with emerging urban data. Advances in these four areas are likely to generate significant new insights that will be useful to both science and policy.
•This paper reviews remote sensing contributions to the knowledge of urban areas.•Four strategic directions for future urban remote sensing research are proposed.•Advances in these four areas provide new insights that are useful to science and policy.
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X ...chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
We examined sagittal otoliths from 398 gray angelfish (
Pomacanthus arcuatus) collected from the lower Florida Keys between September 2000 and September 2003. Fish ranged in size from 78 to 442
mm ...total length (TL). Males had a mean TL of 329
mm (
n
=
192), females had a mean TL of 308
mm (
n
=
166), and an additional 56 fish were unsexed (mean TL
=
239
mm). Sectioned otoliths displayed clear increments that were used to estimate fish ages. Marginal increment analysis validated the formation of a single annulus per year.
The relationship between TL and age was described by the von Bertalanffy growth equation
L
t
=
325.11
−
exp(−0.0601(
t
+
0.828)) for females and
L
t
=
388.51
−
exp(−0.383(
t
+
0.923)) for males. Females and males grew rapidly for the first 5 years of life and eventually reached asymptotic lengths of ∼325 and ∼388
mm, respectively, with a maximum estimated age of 24 years. Morphometric parameters evaluated for use in the age model for gray angelfish included fish length and weight and otolith length, width, thickness, and weight. As with fish length, otolith length and width became asymptotic between the ages of 4 and 7. Otolith weight increased throughout the life of the fish, but the rate of increase slowed with age. Only otolith thickness was linear with fish age. Stepwise forward regression resulted in the following equation: ln
(age
+
1)
=
1.157
+
2.542
×
ln(otolith thickness) indicating that otolith thickness, which explained 89% of the variation, was the best predictor of age. Additional variables did not improve the regression, nor did dividing the data into subsets based on growth rate. Once the otolith thickness–age relationship was established, the simple process of measuring otolith thickness was as effective for determining the age of gray angelfish as the far more difficult process of sectioning and reading the otoliths. Use of similar models in ageing other species, along with periodic validation to ensure that the otolith parameter–age relationship has not changed over time, could simplify age data collection for population models. This, in turn, could potentially allow fisheries to be better managed at a significantly reduced cost.
PDF
