Evaluation of Stockpiled Berseem Clover and Brown Midrib Sorghum x Sudangrass as Supplements for Grazed Cornstalks in Beef Cow Wintering Systems

Berseem clover and oats were incorporated into a corncorn- oat/berseem clover rotation in 1994 and 1995. Two cuttings of oat-berseem clover hay were harvested during the summer before forage was allowed to stockpile for winter grazing. In 1995, a brown midrib sorghum x sudangrass hybrid was seeded into a field adjacent to a corn field. After corn grain harvest in 1994 and 1995, Charolais x Angus x Simmental cows in midgestation were allotted to replicated fields containing corn crop residues with no complementary forages at 2.5 acres/cow, or corn crop residues and stockpiled berseem clover (2:1) at 2.5 acres/cow to simultaneously graze, or to a drylot. In 1995, cows were allotted to fields containing corn crop residues and brown midrib sorghum x sudangrass (7:3) at 2.5 acres/cow. Berseem clover had greater concentrations of digestible organic matter and crude protein than corn crop residues at the initiation of grazing, but had a more rapid decrease in digestible organic matter concentration than corn crop residues. Brown midrib sorghum x sudangrass forage also had a higher initial concentration of digestible organic matter, but an equal rate of decrease in digestible organic matter concentration to corn crop residues in ungrazed areas of the field. Cows grazing berseem clover with corn crop residues had greater body condition score increases during the first half of the grazing season than cows grazing corn crop residues without complementary forages. Cows grazing corn crop residues without complementary forages required 2,786 and 1,412 less lb hay per cow than cows maintained in a drylot in 1994 and 1995. In 1994, simultaneous grazing of berseem clover with corn crop residues did not reduce hay feeding more than feeding corn crop residues alone. However, in 1995, grazing berseem clover or brown midrib sorghum x sudangrass with corn crop residues reduced the amount of hay required to maintain cows by 358 and 376 lb hay per cow compared with grazing corn crop residues without complementary forage.

Changes in Chemical Composition and Digestion Kinetics of Stockpiled Kura Clover in Late Fall

Stockpiled kura clover samples harvested on three different winter dates were used to determine changes in chemical composition and N digestion kinetics. Kura clover was harvested from four different plots at 14 d intervals and analyzed for neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), acid detergent insoluble nitrogen (ADIN), and in vitro digestible dry matter (IVDMD), and in situ digestion kinetics of N. Crude protein concentrations decreased, but ADIN concentrations increased with later date of harvest. Digestible N pool-size and the rate of digestion was the lowest in third-harvest kura clover. Although the proportion of protein that is soluble or nondigestible increased, proportion of protein that is potentially digestible decreased with maturity.

Proceedings of the Third Biochemical Engineering Symposium (April 28, 1973)

This report presents the proceedings of the Biochemical Engineering Symposium held at Kansas State University, April 28, 1973. Since a number of the contributions will be published in detail elsewhere, only brief summaries of each contribution are included here. Requests for additional information on projects conducted at The University of Nebraska should be directed to Dr. Peter J. Reilly, and those at Kansas State University to the editors. ContentsKenneth J. Jacobson, Andrew H.C. Chan, and Raymond C. Eliason, "Properties and Utilization of Small Particulates in Cattle Manure" Cady R. Engler and James S. Yohn, "Protein from Manure" Robert J. Williams, "Kinetics of Sucrose Inversion Using Invertase Immobilized on Hollow Fibers of Cellulose Acetate" David F. Aldis and Thomas A. Carlisle, "Study of a Triiodide-Resin Complex Disinfection System" John C. Heydweiller, "Modeling and Analysis of Symbiotic Growth" Kenneth J. Jacobson, "Synchronized Growth of the Blue Green Alga Microcystis aeruginosa" Clarence C. Y. Ron arui Lincoln L. S. Yang, "Computer Modeling of the Reductive Pentose Phosphate Cycle" Ming-ching T. Kuo, "Application of a Parallel Biochemical Oxidation Kinetic Model to the Design of an Activated Sludge System Including a Primary Clarifier" Prakash N. Mishra, "Optimal Synthesis of Water Renovation Systems"

Proceedings of the Fourth Annual Kansas State–Nebraska Biochemical Engineering Symposium

The symposium whose papers are abstracted here was the fourth in a series held alternately at Kansas State University and the University of Nebraska–Lincoln. Requests for further information on projects conducted at Kansas State should be directed to Professor L.E. Erickson and on those at Nebraska to the editor. ContentsJohn C. Heydweiller, "Estimating Sedimentation of Organisms in a Tower-Type Activated Sludge System" Raymond C. Eliason, "Properties and Utilization of Small Particulates in Cattle Manure" Kenneth H. Hsu, "Oxygen Transfer in Tower Systems with Motionless Mixers" Raymond C. Eliason, "Hydrolysis of Sucrose by 20 Invertase Immobilized on Hollow Fibers" Robert Shipman, "Single Cell Protein from Photosynthetic 26 Bacteria" Peter J. Reilly, "Stability of Commensalistic Systems"

Stent thrombosis with ticagrelor versus clopidogrel in patients with acute coronary syndromes: an analysis from the prospective, randomized PLATO trial

BACKGROUND We aimed to describe the effects of ticagrelor versus clopidogrel on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial. METHODS AND RESULTS Of 18 624 patients hospitalized for acute coronary syndromes, 11 289 (61%) had at least 1 intracoronary stent. Ticagrelor reduced stent thrombosis compared with clopidogrel across all definitions: definite, 1.37% (n=71) versus 1.93% (n=105; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50-0.90; P=0.0091); definite or probable, 2.21% (n=118) versus 2.87% (n=157; HR, 0.75; 95% CI, 0.59-0.95; P=0.017); and definite, probable, and possible, 2.94% (n=154) versus 3.77 (n=201; HR, 0.77; 95% CI, 0.62-0.95). The reduction in definite stent thrombosis was consistent regardless of acute coronary syndrome type, presence of diabetes mellitus, stent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel before randomization, and use of glycoprotein IIb/IIIa inhibitors at randomization. The reduction in stent thrombosis with ticagrelor was numerically greater for late (>30 days; HR, 0.48; 95% CI, 0.24-0.96) and subacute (4 hours-30 days; HR, 0.60; 95% CI, 0.39-0.93) compared with acute (<24 hours; HR, 0.94; 95% CI, 0.43-2.05) stent thrombosis or for patients compliant to therapy (ie, taking blinded study treatment ≥80% of the time) compared with less compliant patients. Randomization to ticagrelor was a strong independent inverse predictor of definite stent thrombosis (HR, 0.65; 95% CI, 0.48-0.88). CONCLUSION Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with acute coronary syndromes, with consistent benefit across a broad range of patient, stent, and treatment characteristics.

Computerized provider order entry adoption: implications for clinical workflow.

OBJECTIVE: To identify and describe unintended adverse consequences related to clinical workflow when implementing or using computerized provider order entry (CPOE) systems. METHODS: We analyzed qualitative data from field observations and formal interviews gathered over a three-year period at five hospitals in three organizations. Five multidisciplinary researchers worked together to identify themes related to the impacts of CPOE systems on clinical workflow. RESULTS: CPOE systems can affect clinical work by 1) introducing or exposing human/computer interaction problems, 2) altering the pace, sequencing, and dynamics of clinical activities, 3) providing only partial support for the work activities of all types of clinical personnel, 4) reducing clinical situation awareness, and 5) poorly reflecting organizational policy and procedure. CONCLUSIONS: As CPOE systems evolve, those involved must take care to mitigate the many unintended adverse effects these systems have on clinical workflow. Workflow issues resulting from CPOE can be mitigated by iteratively altering both clinical workflow and the CPOE system until a satisfactory fit is achieved.

Conversion of myoblasts to physiologically active neuronal phenotype.

Repressor element 1 (RE1)-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress several terminal neuronal differentiation genes by binding to a specific DNA sequence (RE1/neuron-restrictive silencer element [NRSE]) present in their regulatory regions. REST-VP16 binds to the same RE1/NRSE, but activates these REST/NRSF target genes. However, it is unclear whether REST-VP16 expression is sufficient to cause formation of functional neurons either from neural stem cells or from heterologous stem cells. Here we show that the expression of REST-VP16 in myoblasts grown under muscle differentiation conditions blocked entry into the muscle differentiation pathway, countered endogenous REST/NRSF-dependent repression, activated the REST/NRSF target genes, and, surprisingly, activated other neuronal differentiation genes and converted the myoblasts to a physiologically active neuronal phenotype. Furthermore, in vitro differentiated neurons produced by REST-VP16-expressing myoblasts, when injected into mouse brain, survived, incorporated into the normal brain, and did not form tumors. This is the first instance in which myoblasts were converted to a neuronal phenotype. Our results suggest that direct activation of REST/NRSF target genes with a single transgene, REST-VP16, is sufficient to activate other terminal neuronal differentiation genes and to override the muscle differentiation pathways, and they suggest that this approach provides an efficient way of triggering neuronal differentiation in myoblasts and possibly other stem cells.

Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation.

Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes. Previous studies have shown that neither c-Myc nor REST/NRSF alone could cause tumor formation. To determine whether c-Myc and REST/NRSF act together to cause medulloblastomas, we used a previously established cell line derived from external granule layer stem cells transduced with activated c-myc (NSC-M). These immortalized NSCs were able to differentiate into neurons in vitro. In contrast, when the cells were engineered to express a doxycycline-regulated REST/NRSF transgene (NSC-M-R), they no longer underwent terminal neuronal differentiation in vitro. When injected into intracranial locations in mice, the NSC-M cells did not form tumors either in the cerebellum or in the cerebral cortex. In contrast, the NSC-M-R cells did produce tumors in the cerebellum, the site of human medulloblastoma formation, but not when injected into the cerebral cortex. Furthermore, the NSC-M-R tumors were blocked from terminal neuronal differentiation. In addition, countering REST/NRSF function blocked the tumorigenic potential of NSC-M-R cells. To our knowledge, this is the first study in which abnormal expression of a sequence-specific DNA-binding transcriptional repressor has been shown to contribute directly to brain tumor formation. Our findings indicate that abnormal expression of REST/NRSF and Myc in NSCs causes cerebellum-specific tumors by blocking neuronal differentiation and thus maintaining the "stemness" of these cells. Furthermore, these results suggest that such a mechanism plays a role in the formation of human medulloblastoma.

FoxM1B regulates NEDD4-1 expression, leading to cellular transformation and full malignant phenotype in immortalized human astrocytes.

Our recent studies have shown that the FoxM1B transcription factor is overexpressed in human glioma tissues and that the level of its expression correlates directly with glioma grade. However, whether FoxM1B plays a role in the early development of glioma (i.e., in transformation) is unknown. In this study, we found that the FoxM1B molecule causes cellular transformation and tumor formation in normal human astrocytes (NHA) immortalized by p53 and pRB inhibition. Moreover, brain tumors that arose from intracranial injection of FoxM1B-expressing immortalized NHAs displayed glioblastoma multiforme (GBM) phenotypes, suggesting that FoxM1B overexpression in immortalized NHAs not only transforms the cells but also leads to GBM formation. Mechanistically, our results showed that overexpression of FoxM1B upregulated NEDD4-1, an E3 ligase that mediates the degradation and downregulation of phosphatase and tensin homologue (PTEN) in multiple cell lines. Decreased PTEN in turn resulted in the hyperactivation of Akt, which led to phosphorylation and cytoplasmic retention of FoxO3a. Blocking Akt activation with phosphoinositide 3-kinase/Akt inhibitors inhibited the FoxM1B-induced transformation of immortalized NHAs. Furthermore, overexpression of FoxM1B in immortalized NHAs increased the expression of survivin, cyclin D1, and cyclin E, which are important molecules for tumor growth. Collectively, these results indicate that overexpression of FoxM1B, in cooperation with p53 and pRB inhibition in NHA cells, promotes astrocyte transformation and GBM formation through multiple mechanisms.

Active water in protein-protein communication within the membrane: the case of SRII-HtrII signal relay.

We detect internal water molecules in a membrane-embedded receptor-transducer complex and demonstrate water structure changes during formation of the signaling state. Time-resolved FTIR spectroscopy reveals stimulus-induced repositioning of one or more structurally active water molecules to a significantly more hydrophobic environment in the signaling state of the sensory rhodopsin II (SRII)-transducer (HtrII) complex. These waters, distinct from bound water molecules within the SRII receptor, appear to be in the middle of the transmembrane interface region near the Tyr199(SRII)-Asn74(HtrII) hydrogen bond. We conclude that water potentially plays an important role in the SRII --> HtrII signal transfer mechanism in the membrane's hydrophobic core.

Genetic networks controlling retinal injury.

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury. METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases. RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription factors. Three genomic loci control transcript expression of acute phase genes in brains of BXD RI mouse strains. One locus was identified on chromosome 12 and was highly correlated with the expression of classic acute phase genes. Within the locus we identified the inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was upregulated as an acute phase transcript in injury models of rat retina, brain, and spinal cord. CONCLUSIONS: We defined a group of transcriptional changes associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate regulators that control transcript levels of acute phase genes.