766 research outputs found
Helping children understand divorce (2004)
"This guide is a revision and update of two previous guides: Helping Children Understand Divorce, originally written by Sara Gable, state specialist in human development and family studies at the University of Missouri-Columbia, and Kelly Cole, former extension associate at the University of Missouri-Columbia, and The Effects of Divorce on Children, originally written by Karen DeBord, former state specialist in human development and family studies at the University of Missouri-Columbia.""Information from Human Environmental Sciences Extension.""Family relations."Revised 3/04/10M
Putting Quality Functional Assessment into Practice in Schools: A Research Agenda on Behalf of E/BD Students
The discipline provisions of the IDEA place emphasis on gaining an understanding of why the student is motivated to engage in problem behavior and to consider, when appropriate, positive behavioral interventions, strategies, and supports to address the behavior. These legislative mandates bring center stage a range of new duties and responsibilities for the IEP team. This article discusses the problems that school divisions across the country are encountering when implementing these requirements and recommends a course of research to address these issues
Mechanism of sphingolipid homeostasis revealed by structural analysis of \u3ci\u3eArabidopsis\u3c/i\u3e SPT-ORM1 complex
The serine palmitoyltransferase (SPT) complex catalyzes the first and rate-limiting step in sphingolipid biosynthesis in all eukaryotes. ORM/ORMDL proteins are negative regulators of SPT that respond to cellular sphingolipid levels. However, the molecular basis underlying ORM/ORMDL-dependent homeostatic regulation of SPT is not well understood.We determined the cryoâelectron microscopy structure of Arabidopsis SPT-ORM1 complex, composed of LCB1, LCB2a, SPTssa, and ORM1, in an inhibited state. A ceramide molecule is sandwiched between ORM1 and LCB2a in the cytosolic membrane leaflet. Ceramide binding is critical for the ORM1-dependent SPT repression, and dihydroceramides and phytoceramides differentially affect this repression. A hybrid ÎČ sheet, formed by the amino termini of ORM1 and LCB2a and induced by ceramide binding, stabilizes the amino terminus of ORM1 in an inhibitory conformation. Our findings provide mechanistic insights into sphingolipid homeostatic regulation via the binding of ceramide to the SPT-ORM/ORMDL complex that may have implications for plant-specific processes such as the hypersensitive response for microbial pathogen resistance
Sphingolipids in the Root Play an Important Role in Regulating the Leaf Ionome in \u3ci\u3eArabidopsis thaliana\u3c/i\u3e
Sphingolipid synthesis is initiated by condensation of Ser with palmitoyl-CoA producing 3-ketodihydrosphinganine (3-KDS), which is reduced by a 3-KDS reductase to dihydrosphinganine. Ser palmitoyltransferase is essential for plant viability. Arabidopsis thaliana contains two genes (At3g06060/TSC10A and At5g19200/TSC10B) encoding proteins with significant similarity to the yeast 3-KDS reductase, Tsc10p. Heterologous expression in yeast of either Arabidopsis gene restored 3-KDS reductase activity to the yeast tsc10D mutant, confirming both as bona fide 3-KDS reductase genes. Consistent with sphingolipids having essential functions in plants, double mutant progeny lacking both genes were not recovered from crosses of single tsc10A and tsc10B mutants. Although the 3-KDS reductase genes are functionally redundant and ubiquitously expressed in Arabidopsis, 3-KDS reductase activity was reduced to 10% of wild-type levels in the loss-of-function tsc10a mutant, leading to an altered sphingolipid profile. This perturbation of sphingolipid biosynthesis in the Arabidopsis tsc10a mutant leads an altered leaf ionome, including increases in Na, K, and Rb and decreases in Mg, Ca, Fe, and Mo. Reciprocal grafting revealed that these changes in the leaf ionome are driven by the root and are associated with increases in root suberin and alterations in Fe homeostasis
Motives for the social sharing of an emotional experience
International audienc
Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. METHODS: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed. RESULTS: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS. CONCLUSIONS: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further
Costa Rica Rift hole deepened and logged
During Leg 111 of the Ocean Drilling
Program, scientists on the
drilling vessel JOIDES Resolution
studied crustal structure and hydrothermal
processes in the eastern
equatorial Pacific. Leg 111 spent 43
days on its primary objective, deepening
and logging Hole 5048, a deep
reference hole in 5.9-million-year-old
crust 200 km south of the spreading
axis of the Costa Rica Rift. Even before
Leg 111 , Hole 5048 was the deepest
hole drilled into the oceanic crust,
penetrating 274.5 m of sediments and
1,075.5 m of pillow lavas and sheeted
dikes to a total depth of 1,350 m
below sea floor (mbsf). Leg 111 deepened
the hole by 212.3 m to a total
depth of 1,562.3 mbsf (1,287.8 m into
basement), and completed a highly successful suite of geophysical logs
and experiments, including sampling
of borehole waters
Semaglutide improves postprandial glucose and lipid metabolism, and delays firstâhour gastric emptying in subjects with obesity
Aim: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. Materials and Methods: This was a randomised, double-blind, placebo-controlled, two-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardised meals. Gastric emptying (paracetamol absorption test) and peptide YY (PYY) response were also assessed. Results: Semaglutide treatment significantly lowered fasting concentrations of glucose and glucagon, and increased insulin versus placebo (estimated treatment ratio: 0.95 [95% confidence interval: 0.91, 0.98]; 0.86 [0.75, 0.98]; 1.45 [1.20, 1.75], respectively). Postprandial glucose metabolism significantly improved with semaglutide versus placebo (incremental area under the curve 0â5 hours [iAUC0-5h]; estimated treatment difference: glucose â1.34 mmol*h/L [â2.42, â0.27]; insulin â921 pmol*h/L [â1461, â381]; C-peptide â1.42 nmol*h/L [â2.33, â0.51]). Fasting and postprandial lipid metabolism improved with semaglutide versus placebo. First-hour gastric emptying after the meal was delayed versus placebo (AUC0-1h; estimated treatment ratio: 0.73 [0.61, 0.87]); this may have contributed to the lower postprandial glucose increase in semaglutide-treated subjects. Overall gastric emptying (AUC0-5h) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide versus placebo (p=0.0397 and p=0.0097, respectively). Conclusion: Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to placebo; however, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation
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