68 research outputs found
Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone infusion during late gestation
Glucocorticoids near term are known to upregulate many important enzyme
systems prior to birth. Glutamate dehydrogenase (GDH) is a mitochondrial
enzyme that catalyzes both the reversible conversion of ammonium nitrogen
into organic nitrogen (glutamate production) and the oxidative deamination
of glutamate resulting in 2-oxoglutarate. The activity of this enzyme is
considered to be of major importance in the development of catabolic
conditions leading to gluconeogenesis prior to birth. Ovine hepatic GDH
mRNA expression and activity were determined in near-term (130 days of
gestation, term 147 +/- 4 days) control and acutely dexamethasone-treated
(0.07 mg(-1) hr(-1) for 26 hr) fetuses. Dexamethasone infusion had no
effect on placental or fetal liver weights. Dexamethasone infusion for 26
hr significantly increased hepatic GDH mRNA expression. This increased GDH
mRNA expression was accompanied by an increase in hepatic mitochondrial
GDH activity, from 30.0 +/- 7.4 to 58.2 +/- 8.1 U GDH/U CS (citrate
synthase), and there was a significant correlation between GDH mRNA
expression and GDH activity. The generated ovine GDH sequence displayed
significant similarity with published human, rat, and murine GDH sequence.
These data are consistent with the in vivo studies that have shown a
redirection of glutamine carbon away from net hepatic glutamate release
and into the citric acid cycle through the forward reaction catalyzed by
GDH, i.e., glutamate to oxoglutarate
Fetal hepatic and placental amino acid metabolism : experimental studies in late ovine gestation
For a long time, the study of the metabolism of nutrients by the placenta attracted
much less attention than that by the fetus. This scant interest was probably due to the
commonly held view of the placenta as an organ with minimal metabolic needs, serving
only as a means of transport between the maternal and fetal circulations. This concept
changed when it was demonstrated that in late ovine gestation only about half of the
oxygen taken up from the uterine circulation is actually delivered to the fetus whereas the
other half is used by the placenta itself, which implies a high metabolic rate
approximately equal to that of the brain. Further quantitative in vivo studies on
net substrate fluxes across both fetal and maternal circulations of the uteroplacental unit
demonstrated that placental metabolism plays a significant role in the nutritional demands
of pregnancy.
In obstetrics the main focus of scientific interest has been on the significance of
reduced uteroplacental and lUllbilical perfusion with impaired oxygenation and uptake of
nutrients as the pathophysiological mechanism of fetal growth restriction. But in smallfor-
gestational age (SGA) fetuses, not only total aminonitrogen levels are reduced, there
are also marked differences between adequate-for-gestational age (AGA) and SGA
fetuses with respect to fetal concentrations of leucine, isoleucine and valine.
A possible role for placental amino acid metabolism in fetal growth restriction is apparent
from in vivo experiments in ovine gestation with restriction of fetal growth induced by
heat-stress. These studies showed a significantly reduced uterine uptake of essential
amino acids such as threonine and leucine by the placenta expressed per gram of placenta. This finding is supported by the observation of a significantly reduced amino acid
transport activity by microvillous vesicles from placentas obtained from patients with
fetal growth restriction
Feeding Two Birds With One Scone? The Relationship Between Teaching and Research for Graduate Students Across the Disciplines
We surveyed over 300 graduate students at a Southeastern research university to increase our understanding of their perceptions of (a) the connection between teaching and research, (b) the means by which integration occurs, and (c) the extent to which teaching and research contribute to a shared skill set that is of value in both contexts. We also examined differences across disciplines in the perception of this teaching-research nexus. Overall, findings indicate that graduate students perceive important relationships between teaching and research, and they point toward opportunities for administrators to promote teaching and research integration
Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange
Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a
two- to threefold increase in plasma glutamine and other glucogenic amino
acids and a decrease of plasma glutamate to approximately one-third of
normal. To explore the underlying mechanisms, hepatic amino acid uptake
and conversion of L-[1-(13)C]glutamine to L-[1-(13)C]glutamate and
(13)CO(2) were measured in six sheep fetuses before and in the last 2 h of
a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes
(P < 0.01) and hepatic glutamate output (P < 0.001). Hepatic outputs of
the glutamate (R(Glu,Gln)) and CO(2) formed from plasma glutamine
decreased to 21 (P < 0.001) and 53% (P = 0.009) of control, respectively.
R(Glu,Gln), expressed as a fraction of both outputs, decreased (P < 0.001)
from 0.36 +/- 0.02 to 0.18 +/- 0.04. Hepatic glucose output remained
virtually zero throughout the experiment. We conclude that Dex decreases
fetal hepatic glutamate output by increasing the routing of glutamate
carbon into the citric acid cycle and by decreasing the hepatic uptake of
glucogenic amino acids
Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration
Uterine and umbilical uptakes of alanine (Ala) were measured in 10 ewes
before (control) and during intravenous infusion of Ala, which increased
maternal arterial Ala concentration from 115 +/- 14 to 629 +/- 78 microM
(P < 0.001). In 8 of these ewes, placental Ala fluxes were traced by
constant intravenous infusion of L-[3,3,3-2H3]Ala in the mother and
L-[1-13C]Ala in the fetus. Rates are reported as micromoles per minute per
kilogram fetus. Ala infusion increased uterine uptake (2.5 +/- 0.6 to 15.6
+/- 3.1, P < 0.001), umbilical uptake (3.1 +/- 0.5 to 6.9 +/- 0.8, P <
0.001), and net uteroplacental utilization (-0.7 +/- 0.8 to 8.6 +/- 2.7, P
< 0.01) of Ala. Control Ala flux to fetus from mother (Rf,m) was much less
than the Ala flux to fetus from placenta (Rf,p) (0.17 +/- 0.04 vs. 5. 0
+/- 0.6). Two additional studies utilizing L-[U-13C]Ala as the maternal
tracer confirmed the small relative contribution of Rf,m to Rf,p. During
maternal Ala infusion, Rf,m increased significantly (P < 0.02) but
remained a small fraction of Rf,p (0.71 +/- 0.2 vs. 7.3 +/- 1.3). We
conclude that maternal Ala entering the placenta is metabolized and
exchanged for placental Ala, so that most of the Ala delivered to the
fetus is produced within the placenta. An increase in maternal Ala
concentration increases placental Ala utilization and the fetal uptake of
both maternal and placental Ala
Graduate students\u27 teaching experiences improve their methodological research skills
Science, technology, engineering, and mathematics (STEM) graduate students are often encouraged to maximize their engagement with supervised research and minimize teaching obligations. However, the process of teaching students engaged in inquiry provides practice in the application of important research skills. Using a performance rubric, we compared the quality of methodological skills demonstrated in written research proposals for two groups of early career graduate students (those with both teaching and research responsibilities and those with only research responsibilities) at the beginning and end of an academic year. After statistically controlling for preexisting differences between groups, students who both taught and conducted research demonstrate significantly greater improvement in their abilities to generate testable hypotheses and design valid experiments. These results indicate that teaching experience can contribute substantially to the improvement of essential research skills
Facilitating Recovery of Daily Functioning in People With a Severe Mental Illness Who Need Longer-Term Intensive Psychiatric Services:Results From a Cluster Randomized Controlled Trial on Cognitive Adaptation Training Delivered by Nurses
Background: Feasible and effective interventions to improve daily functioning in people with a severe mental illness (SMI), such as schizophrenia, in need of longer-term rehabilitation are scarce. Aims: We assessed the effectiveness of Cognitive Adaptation Training (CAT), a compensatory intervention to improve daily functioning, modified into a nursing intervention. Method: In this cluster randomized controlled trial, 12 nursing teams were randomized to CAT in addition to treatment as usual (CAT; n = 42) or TAU (n = 47). Daily functioning (primary outcome) was assessed every 3 months for 1 year. Additional follow-up assessments were performed for the CAT group in the second year. Secondary outcomes were assessed every 6 months. Data were analyzed using multilevel modeling. Results: CAT participants improved significantly on daily functioning, executive functioning, and visual attention after 12 months compared to TAU. Improvements were maintained after 24 months. Improved executive functioning was related to improved daily functioning. Other secondary outcomes (quality of life, empowerment, negative symptoms) showed no significant effects. Conclusions: As a nursing intervention, CAT leads to maintained improvements in daily functioning, and may improve executive functioning and visual attention in people with SMI in need of longer-term intensive psychiatric care. Given the paucity of evidence-based interventions in this population, CAT can become a valuable addition to recovery-oriented care
Analysis of a mouse germ cell tumor model establishes pluripotency-associated miRNAs as conserved serum biomarkers for germ cell cancer detection
Malignant testicular germ cells tumors (TGCTs) are the most common solid cancers in young men. Current TGCT diagnostics include conventional serum protein markers, but these lack the sensitivity and specificity to serve as accurate markers across all TGCT subtypes. MicroRNAs (miRNAs) are small non-coding regulatory RNAs and informative biomarkers for several diseases. In humans, miRNAs of the miR-371-373 cluster are detectable in the serum of patients with malignant TGCTs and outperform existing serum protein markers for both initial diagnosis and subsequent disease monitoring. We previously developed a genetically engineered mouse model featuring malignant mixed TGCTs consisting of pluripotent embryonal carcinoma (EC) and differentiated teratoma that, like the corresponding human malignancies, originate in utero and are highly chemosensitive. Here, we report that miRNAs in the mouse miR-290-295 cluster, homologs of the human miR-371-373 cluster, were detectable in serum from mice with malignant TGCTs but not from tumor-free control mice or mice with benign teratomas. miR-291-293 were expressed and secreted specifically by pluripotent EC cells, and expression was lost following differentiation induced by the drug thioridazine. Notably, miR-291-293 levels were significantly higher in the serum of pregnant dams carrying tumor-bearing fetuses compared to that of control dams. These findings reveal that expression of the miR-290-295 and miR-371-373 clusters in mice and humans, respectively, is a conserved feature of malignant TGCTs, further validating the mouse model as representative of the human disease. These data also highlight the potential of serum miR-371-373 assays to improve patient outcomes through early TGCT detection, possibly even prenatally
Erratum to: Methods for evaluating medical tests and biomarkers
[This corrects the article DOI: 10.1186/s41512-016-0001-y.]
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