Analyzing the effects of lactose on calcium absorption in premature infants using HR-ICP-Mass Spectrometry

Abstract only availableWith advances in neonatal care, premature infants are surviving at increasing rates. During the third trimester of pregnancy, the bone mineral content of infants rapidly increases. It is therefore becoming essential to accurately mimic the womb environment to maintain growth and sustain the health of premature infants as if they were in utero. Regulating calcium absorption in premature infants is crucial primarily for bone formation, as 99% of the calcium in the human body is found in the bones and the teeth. The effect of lactose containing formulas on calcium absorption in premature infants has not been well established. Concerns have been noted in the scientific community regarding lactose intolerance especially in premature infants, as lactase, the enzyme responsible for lactose digestion, is most readily detectible during the third trimester of pregnancy. In this study, in conjunction with Dr. Laura Hillman of the University of Missouri Hospital, each infant was fed lactose and maltose formulas during different weeks using a dual tracer method in which two calcium isotopes were administered, 44Ca orally and 46Ca intravenously. Urine samples were collected after 24 hours. Analysis related natural abundances of calcium isotopes to the measured values in the urine. Polyatomic ion interferences were differentiated from the calcium peaks by analyzing the samples at a resolution of 4000. Mathematical corrections for interferences caused by titanium and doubly charged strontium were determined by measuring the specific isotopes 47Ti and 87Sr++ and using known natural abundances of the interfering isotopes to correct each calcium count rate. Mathematical calculations relate the enriched isotope ratio measurements of 44Ca and 46Ca to calcium absorption. Analysis regarding the effect of lactose on calcium absorption is ongoing. Our data precision on the ICP-MS was acceptable with percent relative standard deviations (%RSD) for external precision over the course of a week at 1.4, 2.2, 0.71, and 1.4 for isotope ratios 42Ca: 43Ca, 42Ca: 44Ca, 42Ca: 46Ca, and 42Ca: 48Ca respectively. Daily internal precision (%RSD) values were .37, 1.3, .69, and 1.5. The precision shows the viability of utilizing HR-ICP-MS analysis for calcium isotope ratios.NSF-REU/NIH Program in Radiochemistr

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.11Nsciescopu

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies