Standard two-dimensional ultrasound has been used to aid prenatal visualization and detection of anomalies for the past 60 years. Three-dimensional ultrasound, introduced in the 1980s, provides the ...additional capability of examining the in utero environment from a variety of different angles. Use of this technology in conjunction with standard two-dimensional ultrasound can lead to a more thorough evaluation of structural defects and a greater patient understanding of genetic conditions.
Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive condition having significant clinical overlap with trisomy 18. Though rare in the general population, it is quite common in the Hutterites ...of the United States and Canada. The carrier frequency in the Hutterite population is estimated to be one in 10, making BCS one of the most commonly inherited genetic diseases in any human group studied to date. We describe two infant patients who were initially thought to have trisomy 18, but for whom chromosome studies were normal. Additionally, we briefly review the historical background of the Anabaptist Hutterite populations in South Dakota, compare the clinical findings in BCS and trisomy 18 and discuss the importance of genetic counseling for couples of Hutterite descent.
A first-trimester screen consists of a nuchal translucency (NT) ultrasound measurement as well as maternal serum testing for pregnancy-associated plasma protein-A (PAPP-A) and human chorionic ...gonadotropin (hCG). An increased nuchal translucency (NT) thickness at 11 to 14 weeks gestational age is a common finding for Down syndrome, Trisomy 18 and cardiac defects. We present a series of six patients, four with NT measurements greater than the 95th centile, and two additional cases where the NT was normal, but maternal serum biochemical markers were unusual. All six of these cases had a chromosome anomaly or another genetic condition: Noonan syndrome, triploidy, Down syndrome, Trisomy 18, Turner syndrome and a rare chromosome abnormality known as Ring 18-Monosomy 18. Our series underlines the fact that it is important to explore other genetic and chromosome abnormalities, in addition to Down syndrome and Trisomy 18, when there is an abnormality on a first-trimester screen.
Obesity risk is amplified in the presence of obese relatives yet does not usually follow classic Mendelian inheritance patterns. A combination of gene mutations, deletions and single nucleotide ...polymorphisms are all known to contribute to obesity. Most cases are polygenic, the result of multiple genes interacting with a changing environment. Each "obesity gene" only makes a small contribution to phenotype, but collectively, inherited genetic variations play a major role in determining body mass and how the body responds to physical activity and nutrition. While obesity is most commonly associated with polygenic inheritance, there are other instances in which the cause is monogenic or syndromic. Monogenic obesity typically is caused by a single gene mutation with severe obesity as the main symptom. Syndromic obesity, on the other hand, has many characteristics, of which obesity is one symptom.
The first-trimester screen combines nuchal translucency measurement and serum levels ot PAPP-A and beta-hCG between 11 and 13 weeks gestational age which can be used to calculate the risk of fetal ...Trisomy 21 and 18. Although these trisomies are the most common conditions detected, recognition of increased risk for several other fetal conditions and maternal complications have also been documented. A common misconception is that requesting this test implies that the patient will automatically terminate an affected fetus. Although termination may be one option, it is not the primary goal of this screen. If this screen results in the discovery of an abnormal fetus, the patient is allowed maximal time for privacy, formulation of a medical management plan, preparation for caring for a child with special needs, personal research and consultation with appropriate pediatric subspecialists. This test also decreases maternal anxiety throughout pregnancy. The American College of Obstetricians and Gynecologists (ACOG) recommends that all women, regardless of maternal age and risk factors, be offered this screening test. This paper addresses how the test is performed, management of abnormal findings, risk factors and detection rates.
A Methodology for Flash Drought Identification Christian, Jordan I.; Basara, Jeffrey B.; Otkin, Jason A. ...
Journal of hydrometeorology,
05/2019, Letnik:
20, Številka:
5
Journal Article
Recenzirano
Odprti dostop
With the increasing use of the term “flash drought” within the scientific community, Otkin et al. provide a general definition that identifies flash droughts based on their unusually rapid rate of ...intensification. This study presents an objective percentile-based methodology that builds upon that work by identifying flash droughts using standardized evaporative stress ratio (SESR) values and changes in SESR over some period of time. Four criteria are specified to identify flash droughts: two that emphasize the vegetative impacts of flash drought and two that focus on the rapid rate of intensification. The methodology was applied to the North American Regional Reanalysis (NARR) to develop a 38-yr flash drought climatology (1979–2016) across the United States. It was found that SESR derived from NARR data compared well with the satellite-based evaporative stress index for four previously identified flash drought events. Furthermore, four additional flash drought cases were compared with the U.S. Drought Monitor (USDM), and SESR rapidly declined 1–2 weeks before a response was evident with the USDM. From the climatological analysis, a hot spot of flash drought occurrence was revealed over the Great Plains, the Corn Belt, and the western Great Lakes region. Relatively few flash drought events occurred over mountainous and arid regions. Flash droughts were categorized based on their rate of intensification, and it was found that the most intense flash droughts occurred over the central Great Plains, Corn Belt, and western Great Lakes region.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Voltage-gated calcium channels mediate excitationcontraction coupling in the skeletal muscle. Their molecular composition, similar to neuronal channels, includes the pore-forming alpha(1) and ...auxiliary alpha(2)delta, beta, and gamma subunits. The gamma subunits are the least characterized, and their subunit interactions are unclear. The physiological importance of the neuronal gamma is emphasized by epileptic stargazer mice that lack gamma(2). In this study, we examined the molecular basis of interaction between skeletal gamma(1) and the calcium channel. Our data show that the alpha(1)1.1, beta(1a), and alpha(2)delta subunits are still associated in gamma(1) null mice. Reexpression of gamma(1) and gamma(2) showed that gamma(1), but not gamma(2), incorporates into gamma(1) null channels. By using chimeric constructs, we demonstrate that the first half of the gamma(1) subunit, including the first two transmembrane domains, is important for subunit interaction. Interestingly, this chimera also restores calcium conductance in gamma(1) null myotubes, indicating that the domain mediates both subunit interaction and current modulation. To determine the subunit of the channel that interacts with gamma(1), we examined the channel in muscular dysgenesis mice. Cosedimentation experiments showed that gamma(1) and alpha(2)delta are not associated. Moreover, alpha(1)1.1 and gamma(1) subunits form a complex in transiently transfected cells, indicating direct interaction between the gamma(1) and alpha(1)1.1 subunits. Our data demonstrate that the first half of gamma(1) subunit is required for association with the channel through alpha(1)1.1. Because subunit interactions are conserved, these studies have broad implications for gamma heterogeneity, function and subunit association with voltage-gated calcium channels.
Voltage-gated calcium channels mediate excitationcontraction coupling in the skeletal muscle. Their molecular composition,
similar to neuronal channels, includes the pore-forming α 1 and auxiliary ...α 2 δ, β, and γ subunits. The γ subunits are the least characterized, and their subunit interactions are unclear. The physiological
importance of the neuronal γ is emphasized by epileptic stargazer mice that lack γ 2 . In this study, we examined the molecular basis of interaction between skeletal γ 1 and the calcium channel. Our data show that the α 1 1.1, β 1a , and α 2 δ subunits are still associated in γ 1 null mice. Reexpression of γ 1 and γ 2 showed that γ 1 , but not γ 2 , incorporates into γ 1 null channels. By using chimeric constructs, we demonstrate that the first half of the γ 1 subunit, including the first two transmembrane domains, is important for subunit interaction. Interestingly, this chimera
also restores calcium conductance in γ 1 null myotubes, indicating that the domain mediates both subunit interaction and current modulation. To determine the subunit
of the channel that interacts with γ 1 , we examined the channel in muscular dysgenesis mice. Cosedimentation experiments showed that γ 1 and α 2 δ are not associated. Moreover, α 1 1.1 and γ 1 subunits form a complex in transiently transfected cells, indicating direct interaction between the γ 1 and α 1 1.1 subunits. Our data demonstrate that the first half of γ 1 subunit is required for association with the channel through α 1 1.1. Because subunit interactions are conserved, these studies have broad implications for γ heterogeneity, function and subunit
association with voltage-gated calcium channels.
Identifying new targeted therapies that kill tumor cells while sparing normal tissue is a major challenge of cancer research. Using a high-throughput chemical synthetic lethal screen, we sought to ...identify compounds that exploit the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in about 80% of renal cell carcinomas (RCCs). RCCs, like many other cancers, are dependent on aerobic glycolysis for ATP production, a phenomenon known as the Warburg effect. The dependence of RCCs on glycolysis is in part a result of induction of glucose transporter 1 (GLUT1). Here, we report the identification of a class of compounds, the 3-series, exemplified by STF-31, which selectively kills RCCs by specifically targeting glucose uptake through GLUT1 and exploiting the unique dependence of these cells on GLUT1 for survival. Treatment with these agents inhibits the growth of RCCs by binding GLUT1 directly and impeding glucose uptake in vivo without toxicity to normal tissue. Activity of STF-31 in these experimental renal tumors can be monitored by (18)Ffluorodeoxyglucose uptake by micro-positron emission tomography imaging, and therefore, these agents may be readily tested clinically in human tumors. Our results show that the Warburg effect confers distinct characteristics on tumor cells that can be selectively targeted for therapy.
We report on a 20-month-old male, diagnosed prenatally with de novo mosaic ring chromosome 18 and low level monosomy 18, who also exhibited an inherited and apparently balanced translocation between ...chromosomes 3 and 6. We believe this to be the first reported case of prenatally diagnosed mosaic ring chromosome 18 and monosomy 18 in which the child was carried to term. Ring chromosomes are associated with an abnormal phenotype that is dependent on the amount of material that is deleted from the p and q arms. This child has a 22.5 Mb deletion of 18q and a 2.8 Mb deletion of 18p as a result of ring formation. Although the large deletion has resulted in some developmental delays and health problems, the child is making more developmental progress than was anticipated prenatally. We present his clinical course and the genetic counseling challenges associated with this case.
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