378 research outputs found

    An Economic Comparison Of Year Round vs Conventional Grazing Systems In Iowa

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    Year round grazing systems that utilize stockpiled forage and/or crop residue are often promoted as a way for Northern and Western cow-calf producers to reduce winter feeding costs and improve overall profitability. This study compared the profitability of a conventional spring calving/summer grazing- winter drylot herd to a year round system that utilized both spring- and fall-calving herds with weaned calves retained as stockers. Forage supplies in the year round system were derived from stockpiled forage and corn crop residues. We developed a model that randomly generated production values with parameters based on the results of a 3-year study conducted at the Iowa State University McNay Research and Demonstration farm near Chariton, Iowa. The simulated production values were combined with livestock and forage prices prevailing from 1993-2001 to estimate income per head generated by each system. Average income over the nine- year period was equal. However, the year round system was economically superior in 3 years, equivalent in 1 year, and inferior in 5 years.

    Gonadotropin and Gonadal Steroid Release in Response to a Gonadotropin-Releasing Hormone Agonist in G_q^ɑ and G_(11)^ɑ Knockout Mice

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    In this study, we used mice lacking the G_(11)^α[ G_(11) knockout (KO)] or G_q^α gene (G_q KO) to examine LH release in response to a metabolically stable GnRH agonist (Buserelin). Mice homozygous for the absence of G_(11)^α and G_q^α appear to breed normally. Treatment of (5 wk old) female KO mice with the GnRH agonist Buserelin (2 μg/100 μl, sc) resulted in a rapid increase of serum LH levels (reaching 328 ± 58 pg/25 μl for G_(11) KO; 739 ± 95 pg/25 μl for G_q KO) at 75 min. Similar treatment of the control strain, 129SvEvTacfBr for G_(11) KO or the heterozygous mice for G_q KO, resulted in an increase in serum LH levels (428 ± 57 pg/25 μl for G_(11) KO; 884 ± 31 pg/25 μl for G_q KO) at 75 min. Both G_(11) KO and G_q KO male mice released LH in response to Buserelin (2 μg/100 μl of vehicle; 363 ± 53 pg/25μ l and 749 ± 50 pg/25 μl 1 h after treatment, respectively). These values were not significantly different from the control strain. In a long-term experiment, Buserelin was administered every 12 h, and LH release was assayed 1 h later. In female G11 KO mice and control strain, serum LH levels reached approximately 500 pg/25 μl within the first hour, then subsided to a steady level (∼100 pg/25 μl) for 109 h. In male G_(11) KO mice and in control strain, elevated LH release lasted for 13 h; however, LH levels in the G_(11) KO male mice did not reach control levels for approximately 49 h. In a similar experimental protocol, the G_q KO male mice released less LH (531 ± 95 pg/25 μl) after 13 h from the start of treatment than the heterozygous male mice (865 ± 57 pg/25 μl), but the female KO mice released more LH (634 ± 56 pg/25 μl) after 1 h from the start of treatment than the heterozygous female mice (346 ± 63 pg/25 μl). However, after the initial LH flare, the LH levels in the heterozygous mice never reached the basal levels achieved by the KO mice. G_(11) KO mice were less sensitive to low doses (5 ng/per animal) of Buserelin than the respective control mice. Male G_(11) KO mice produced more testosterone than the control mice after 1 h of stimulation by 2 μg of Buserelin, whereas there was no significant difference in Buserelin stimulated testosterone levels between G_q KO and heterozygous control mice. There was no significant difference in Buserelin stimulated estradiol production in the female G_q KO mice compared with control groups of mice. However, female G_(11) KO mice produced less estradiol in response to Buserelin (2 μg) compared with control strain. Although there were differences in the dynamics of LH release and steroid production in response to Buserelin treatment compared with control groups of mice, the lack of complete abolition of these processes, such as stimulated LH release, and steroid production, suggests that these G proteins are either not absolutely required or are able to functionally compensate for each other

    Detection of Semi-polar Vitamins and Nutrients in Biological Samples

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    Metabolomics is used to examine metabolite fluctuations in biological systems and enables the diagnosis of metabolic disorders and the identification of new therapeutic targets.1 Liquid chromatography-mass spectrometry (LC-MS) was utilized to develop a new method using a T3 column to separate small molecule nutrients and vitamins in a tissue sample. Initial tests of column performance used standard solutions; the amount of metabolites identified and the elution profile of these metabolites was examined. Both the standard solution and sample of brain tissue were tested with the final method developed. Six metabolites were identified in the standard and 31 were identified in the tissue sample. Two of these metabolites were the same: creatine and pyridoxine. However, broad peaks for some metabolites were observed in the chromatography. The method developed was able to separate and identify metabolites from a biological sample, however, based on the multiple elution points of certain compounds during both the standard and the tissue sample, it was determined that the method should be further modified

    Wavelet Transform of Optical Conductivity of Bi2Sr2CaCu2O8+x in the Normal and Superconducting State

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    This paper compares the wavelet transform of the optical conductivity of Bi2Sr2CaCu2O8+x in both the normal and the superconducting state. The wavelet transforms of the normal and superconducting state are also compared with wavelet transforms of the Drude model as well as the Lorentz model. The wavelet transform of the collected data for Bi2Sr2CaCu2O8+x is similar in shape to the Drude model. The wavelet transform of the collected data in the normal state corresponds to the Drude model with a high scattering rate and the collected data in the superconducting state corresponds to the Drude model with a low scattering rate

    Evaluation of year-round grazing systems for fall- and spring-calving beef cows

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    Two grazing systems were evaluated over three years to compare the amounts of hay fed, cow weight and condition score changes, growing animal production, and effects of management systems on the mass and nutritive value of forages. In a minimal land (ML) grazing system, replicated 8.1-ha smooth bromegrass-orchardgrass-birdsfoot trefoil (SB-OG-BFT) pastures were rotationally stocked with six spring-calving cows and calves. Excess forage was harvested as first-cutting hay, then the entire area was rotationally stocked the rest of the season. At termination of summer grazing, cows were fed hay in a drylot. In the year-round (YR) grazing system, 8.1-ha SB-OG-BFT, 6.1-ha smooth bromegrass-red clover (SB-RC), and 6.1-ha tall fescue-red clover (TF-RC) pastures were stocked with six spring-calving cows and calves, 12 stocker animals (previous season\u27s calf crop) and six fall-calving cows. First-cutting hay was harvested from TF-RC and SB-RC pastures simultaneous to the ML system. Second-cutting forage was strip-grazed by cows, while stocker animals remained in SB-OG-BFT pastures. Stocker animals were removed from pastures and finished and cows were again stocked in SB-OG-BFT pastures, while forage was allowed to accumulate in TF-RC and SB-RC pastures. During winter, spring-calving cows sequentially strip-grazed corn crop residue fields and stockpiled SB-RC pastures. Simultaneous to initiation of corn crop residue grazing, fall-calving cows with calves strip-grazed stockpiled TF-RC pastures. Hay was supplemented during winter when weather conditions limited grazing. Fall-calving cows had greater (P [Less than or equal to symbol] 0.03) body condition scores at all production stages except post-breeding (P = 0.13) and post-weaning (P = 0.53) compared to either group of spring-calving cows. Total growing animal production was 27 kg/cow greater (P = 0.01) from the YR grazing system than the ML grazing system. The amount of hay fed in the ML grazing system was 896 kg DM/cow-stocker pair greater (P \u3c 0.01) than the YR grazing system. Over summer, concentration of CP or IVDMD in forage in SB-OG-BFT pastures was similar in the ML and YR grazing systems. Forage management in the YR grazing system produced 1.4 Mg DM/cow more perennial forage as hay and stockpiled forage for winter than the hay harvest in the ML system

    Pharmacoperone Identification for Therapeutic Rescue of Misfolded Mutant Proteins

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    G protein-coupled receptors (GPCRs), which includes the gonadotropin-releasing hormone (GnRH) receptor (GnRHR), comprises the largest family of validated drug targets – more than half of all approved drugs derive their benefits by selective targeting of GPCRs. Most drugs in this class are either agonists or antagonists of GPCRs and high throughput screens have typically been designed and performed with a view toward identification of such compounds as lead drug candidates. This manuscript presents the case that valuable drugs which effect the trafficking of GPCRs may have been overlooked because pharmacoperones have been selected from existing screens that identify agonists and antagonists. A “gain of activity assay” is proposed; this assay relies on the expression of a mutant of the GnRHR that is known to be rescuable by pharmacoperone drugs, and which is restored to activity in their presence. Accordingly, “hits” are identified by the appearance of activity. The gene for the mutant is under control of tetracycline and may be prevented from being expressed. This is a valuable feature since it allows false positives to be identified. Such drugs will show apparent activity whether or not the mutant is expressed. This assay will enable identification of these drugs from chemical libraries and does not rely on their activity as agonists or antagonists

    Evaluation of Year-round Forage Management Systems for Spring- and Fall-Calving Beef Cows

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    Stored feeds make up almost half the cost of production for cow–calf enterprises in Iowa. Therefore, any reduction in the amount of stored feeds needed to maintain cows through the winter can have an impact on overall costs of maintaining the herd. Two resources that may be used to reduce the use of stored feeds are corn-crop residues and stockpiled perennial forages, which may be grazed during the winter. The objective of this experiment was to design and evaluate grazing systems to utilize such resources

    Therapeutic Rescue of Misfolded Mutants: Validation of Primary High Throughput Screens for Identification of Pharmacoperone Drugs

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    Functional rescue of misfolded mutant receptors by small non-peptide molecules has been demonstrated. These small, target-specific molecules (pharmacological chaperones or "pharmacoperones") serve as molecular templates, promote correct folding and allow otherwise misfolded mutants to pass the scrutiny of the cellular quality control system (QCS) and be expressed at the plasma membrane (PM) where they function similarly to wild type (WT) proteins. In the case of the gonadotropin releasing hormone receptor (GnRHR), drugs that rescue one mutant typically rescue many mutants, even if the mutations are located at distant sites (extracellular loops, intracellular loops, transmembrane helices). This increases the value of these drugs. These drugs are typically identified, post hoc, from "hits" in screens designed to detect antagonists or agonists. The therapeutic utility of pharmacoperones has been limited due to the absence of screens that enable identification of pharmacoperones per se.We describe a generalizable primary screening approach for pharmacoperone drugs based on measurement of gain of activity in stable HeLa cells stably expressing the mutants of two different model G-protein coupled receptors (GPCRs) (hGnRHR[E(90)K] or hV2R[L(83)Q]). These cells turn off expression of the receptor mutant gene of interest in the presence of tetracycline and its analogs, which provides a convenient means to identify false positives.The methods described and characterized here provide the basis of novel primary screens for pharmacoperones that detect drugs that rescue GPCR mutants of specific receptors. This approach will identify structures that would have been missed in screens that were designed to select only agonists or antagonists. Non-antagonistic pharmacoperones have a therapeutic advantage since they will not compete for endogenous agonists and may not have to be washed out once rescue has occurred and before activation by endogenous or exogenous agonists

    Assessment of a pharmacist-led comprehensive medication management and wellness program

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    Background: Pharmacists are currently providing comprehensive medication management in the outpatient setting. However, there is little documented evidence demonstrating pharmacists are generating further improved health outcomes utilizing non-pharmacologic support, such as fitness and nutrition counseling. The objective of this study is to determine if a pharmacist-led wellness program with medication management and lifestyle modifications through fitness and nutrition coaching can lead to improved biometric markers. Methods: The wellness program targeted corporate employees and was offered in a corporate headquarters' setting with an on-site workout facility. The program was expected to recruit approximately 15 patients into the wellness program consisting of two treatment arms. The standard group featured nutrition-based classes, medication therapy management and fitness education. The intervention group performed the standard group's activities plus direct, supervised fitness training once weekly. Measured biometric markers were assessed at baseline, 3.5 months, and 7 months and included body mass index (BMI), waist circumference (WC), fasting blood glucose (FBG), systolic and diastolic blood pressure (SBP and DBP), and full lipid panel (TC, TG, HDL, and LDL). Results: Seventeen patients were enrolled in the study. The standard group (n = 11) and intervention group (n = 6) had relatively similar biometric markers at baseline. Seven total patients completed the study (4 from standard group, 3 from intervention group). The majority of biometric markers improved in both groups, and BP and LDL control was maintained for all who completed the study. Conclusion: These data suggest that a licensed pharmacist with certified personal trainer credentials may be capable of maintaining biometric markers at healthy levels and improving where necessary in an employee wellness program through one-on-one medication, fitness and nutrition support. Additional, large-scale research is needed to verify the clinical outcomes and feasibility in a larger group setting.   Type: Clinical Experienc

    Receptor antagonism/agonism can be uncoupled from pharmacoperone activity

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    Pharmacoperones rescue misrouted mutants of the vasopressin receptor type 2 (V2R) and enable them to traffic to the correct biological locus where they function. Previously, a library of nearly 645,000 structures was interrogated with a high throughput screen; pharmacoperones were identified for V2R mutants with a view toward correcting the underlying mutational defects in nephrogenic diabetes insipidus. In the present study, an orthologous assay was used to evaluate hits from the earlier study. We found no consistent relation between antagonism or agonism and pharmacoperone activity. Active pharmacoperones were identified which had minimal antagonistic activity. This increases the therapeutic reach of these drugs, since virtually all pharmacoperone drugs reported to date were selected from peptidomimetic antagonists. Such mixed-activity drugs have a complex pharmacology limiting their therapeutic utility and requiring their removal prior to stimulation of the receptor with agonist
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