bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure and hydrogen bonding inN-(1-deoxy-β-D-fructopyranos-1-yl)-2-aminoisobutyric acid
Authors: Mossine Valeri V. , Barnes Charles L. , Mawhinney Thomas P.
Published: December 2017

The title compound, alternatively called D-fructose-2-aminoisobutyric acid (FruAib), C10H19NO7, (I), crystallizes exclusively in the β-pyranose form, with two conformationally non-equivalent molecules [(IA) and (IB)] in the asymmetric unit. In solution, FruAib establishes an equilibrium, with 75.6% of the population consisting of β-pyranose, 10.4% β-furanose, 10.1% α-furanose, 3.0% α-pyranose and <0.7% the acyclic forms. The carbohydrate ring in (I) has the normal2C5chair conformation and the amino acid portion is in the zwitterion form. Bond lengths and valence angles compare well with the average values from related pyranose structures. All carboxyl, hydroxy and ammonium groups are involved in hydrogen bonding and form a three-dimensional network of infinite chains that are connected through homodromic rings and short chains. Intramolecular hydrogen bonds bridge the amino acid and sugar portions in both molecules. A comparative Hirshfeld surfaces analysis of FruAib and four other sugar–amino acids suggests an increasing role of intramolecular heteroatom interactions in crystal structures with an increasing proportion of C—H bonds.
Crystal structures and Hirshfeld surfaces of two 1,3-benzoxathiol-2-one derivatives
Authors: Chazin Eliza de L. , Sanches Paola de S. , Vasconcelos Thatyana R. A. , Gomes Claudia R. B. , Wardell James L. , Harrison William T. A.
Published: December 2017

The crystal structures of 6-methoxy-1,3-benzoxathiol-2-one, C9H8O3S, (I), and 2-oxo-1,3-benzoxathiol-6-yl acetate, C9H6O4S, (II), are described. Compound (I) is almost planar (r.m.s. deviation for the non-H atoms = 0.011 Å), whereas (II) shows a substantial twist between the fused-ring system and the acetate substituent [dihedral angle = 74.42 (3)°]. For both structures, the bond distances in the heterocyclic ring suggest that little if any conjugation occurs. In the crystal of (I), C—H...O hydrogen bonds link the molecules into [1-11] chains incorporating alternatingR22(8) andR22(12) inversion dimers. The extended structure of (II) featuresC(7) [201] chains linked by C—H...O hydrogen bonds, with further C—H...O bonds and weak π–π stacking interactions connecting the chains into a three-dimensional network. Hirshfeld fingerprint analyses for (I) and (II) are presented and discussed.
The importance of the helical structure of a MamC-derived magnetite-interacting peptide for its function in magnetite formation
Authors: Nudelman Hila , Perez Gonzalez Teresa , Kolushiva Sofiya , Widdrat Marc , Reichel Victoria , Peigneux Ana , Davidov Geula , Bitton Ronit , Faivre Damien , Jimenez-Lopez Concepcion , Zarivach Raz
Published: December 2017

Biomineralization is the process of mineral formation by organisms and involves the uptake of ions from the environment in order to produce minerals, with the process generally being mediated by proteins. Most proteins that are involved in mineral interactions are predicted to contain disordered regions containing large numbers of negatively charged amino acids. Magnetotactic bacteria, which are used as a model system for iron biomineralization, are Gram-negative bacteria that can navigate through geomagnetic fields using a specific organelle, the magnetosome. Each organelle comprises a membrane-enveloped magnetic nanoparticle, magnetite, the formation of which is controlled by a specific set of proteins. One of the most abundant of these proteins is MamC, a small magnetosome-associated integral membrane protein that contains two transmembrane α-helices connected by an ∼21-amino-acid peptide.In vitrostudies of this MamC peptide showed that it forms a helical structure that can interact with the magnetite surface and affect the size and shape of the growing crystal. Our results show that a disordered structure of the MamC magnetite-interacting component (MamC-MIC) abolishes its interaction with magnetite particles. Moreover, the size and shape of magnetite crystals grown inin vitromagnetite-precipitation experiments in the presence of this disordered peptide were different from the traits of crystals grown in the presence of other peptides or in the presence of the helical MIC. It is suggested that the helical structure of the MamC-MIC is important for its function during magnetite formation.
5,5-Diphenyl-3-propylimidazolidine-2,4-dione
Authors: Guerrab Walid , Mague Joel T. , Akrad Rachida , Ansar Mhammed , Taoufik Jamal , Ramli Youssef
Published: December 2017

The asymmetric unit of the title compound, C18H18N2O2, consists of two independent molecules differing primarily in the orientation of the propyl substituent. One of the propyl groups is disordered over two positions with an occupancy ratio of 0.859 (2):0.141 (2). The two independent molecules are associated through a C—H...π(ring) interaction and sheets parallel to (011) are formed from further sets of C—H...π(ring) interactions. The sheets are connectedviainversion-related N—H...O hydrogen bonds.
Double moderated mediation models: problems and (part) remedies
Authors: Chryssochoidis George
Published: December 2017

Purpose

Researchers in management regularly face modelling issues that involve double-moderated mediation models. Here, the author illustrates how to conceptualise, specify and empirically estimate mediation effects when having to simultaneously account for continuous (Likert type) and nominal (i.e. group) moderator variables. Researchers’ estimates of the mediation effects suffer serious bias because of the effects of unaccounted confounders. This is an issue that plagues management research, and this study aims to show how to address these valid reservations for its focus models. In aiming to inform a wider management audience, the study deliberately uses the rich context of a focus case as this allows the author to clarify the nuances that management researchers face applying double-moderated mediation models. Specifically, the study’s focus case is on professionals’ willingness to implement a new government policy. The study also combines traditional and Bayesian statistical approaches and explains the differences in estimation and interpretation that are associated with the Bayesian approach. Explaining, and exemplifying the use of, the models, the author focuses on how one can substantially increase the robustness of the methods used in management research and can considerably improve the quality of the generated theoretical insights. The study also clarifies important assumptions and solutions.

Design/methodology/approach

The study uses a doubled moderated mediation Bayesian approach, and draws the sample data from a population of 5,199 professionals, all members of either the Dutch Association of Psychologists or the Dutch Association for Psychiatry. The data collection process resulted in 1,307 questionnaires being returned, a response rate of 25 per cent. All the items were measured using a Likert scale, ranging from “strongly disagree” to “strongly agree”, unless stated otherwise.

Findings

Explaining, and exemplifying the use of, the models the study focuses on how one can substantially increase the robustness of the methods used in management research and can considerably improve the quality of the generated theoretical insights.

Originality/value

This is an original approach exemplified for wider use by management researchers.
Intraspecific aggression and the colony structure of the invasive antMyrmica rubra
Authors: CHEN WEN , O'SULLIVAN ÁINE , ADAMS ELDRIDGE S.
Published: December 2017

1. Patterns of aggression between ants from different nests influence colony and population structure. Several species of invasive ants lack colony boundaries over large expanses, forming ‘supercolonies’ with many nests among which workers can move without encountering aggression.

2. Bioassays of aggression were used to determine the colony structure of the invasive antMyrmica rubra(L.) at eight sites in Massachusetts, the state where the species was first discovered in North America. To improve the ability to distinguish systematic patterns from background variability in aggressiveness, a repeated‐measures design was used and replicate assays for each pair of nests were conducted.

3. Aggressive responses showed that populations at all sites consisted of multiple distinct colonies. Patterns of aggression were repeatable and transitive, with few exceptions. Colonies were identified as clusters of nests whose workers showed little to no aggression towards one another but were aggressive towards conspecifics from more distant nests.

4. The degree of aggression varied considerably among different colony pairs but did not depend in any consistent way on the distance of separation or on whether colonies were neighbours.

5. Territories of neighbouring colonies abutted, indicating that they were restricted by intraspecific competition. Mapped territories ranged in size from 0.03 to 1.2 ha, but colonies at the study sites have not undergone the enormous expansions seen in introduced populations of some other species of invasive ants, and neighbouring colonies compete locally.
Phenomenological Analysis of Teachers’ Organizational Deviance Experiences in a Rural Primary School in Turkey
Authors: Anasız Burcu Türkkaş , Püsküllüoğlu Elif Iliman
Published: December 2017

The purpose of this study was to analyze organizational deviance experiences of teachers. The study was in phenomenological design among qualitative research methods. In the research convenience sampling technique was used. The research was conducted in a rural primary school in Mugla province in Turkey. Nine teachers participated in the study, seven of them were women and two of them were men. The data of the study was collected via semi-structured interviews in 2015-2016 school year. In the exploration of the phenomenon, content analysis was used. According to the findings of the research, teachers experienced deviance on organizational and individual levels. The themes emerged on organizational level were production deviance and property deviance, and on individual level were political deviance and personal aggression. The codes appeared under production deviance were using long breaks and excusing absenteeism, and under property deviance was sabotage. The codes occurred under political deviance were gossip and favoritism in managerial processes, and under personal aggression was stealing colleague’s ideas.
Epidemiology of cancers in Lahore, Pakistan, among children, adolescents and adults, 2010–2012: a cross-sectional study part 2
Authors: Badar Farhana , Mahmood Shahid
Published: December 2017

Objectives

To estimate the cancer incidence by age group for the Lahore district population within the Punjab Cancer Registry (PCR), Pakistan. The average annual population of Lahore was 9.8 million in 2010–2012. This is a sequel to a study published earlier.

Design

A cross-sectional study.

Setting

The registry has 19 centres in Lahore reporting their data to the coordinating office located within the Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC), Lahore, Pakistan.

Participants

Data existing in the PCR database, based on a confirmed diagnosis of cancer from 1 January 2010 to 31 December 2012, among the Lahore residents, were reviewed.

Outcome measures

Cancer counts and the age-standardised incidence rates (ASIR) per 100 000 population were computed by gender, cancer site/type and age group (0–14, 15–19 and ≥20 years).

Results

Between 2010 and 2012, of the 15 840 new cancers diagnosed, 57% were in females. The ASIRs in age groups 0–14, 15–19 and ≥20 years, among females, were: 6.1, 8.4 and 170.7, respectively, and among males, 9.3, 12.2 and 104.5, respectively. The common diagnoses in children, adolescents and adults were: (1) among females: leukaemia: 2.2; bone tumour: 1.4 and breast cancer: 79.2, respectively, and (2) among males: leukaemia: 3.6; bone tumour: 2.4 and prostate cancer: 10.7, respectively.

Conclusions

The ASIR was higher in adult women than in men, but it was lower in girls and young women than their corresponding male counterparts. Leukaemia was the most common diagnosis in children and bone tumour in adolescents, regardless of gender. Among women, breast cancer and, in men, prostate cancer, were the leading cancer types, in adults. These estimates could be used for the expansion of health coverage in the region including setting-up low cost, diagnostic tests for early detection of cancers.
Crowd medical services in the English Football League: remodelling the team for the 21st century using a realist approach
Authors: Leary Alison , Kemp Anthony , Greenwood Peter , Hart Nick , Agnew James , Barrett John , Punshon Geoffrey
Published: December 2017

Objectives

To evaluate the new model of providing care based on demand. This included reconfiguration of the workforce to manage workforce supply challenges and meet demand without compromising the quality of care.

Design

Currently the Sports Ground Safety Authority recommends the provision of crowd medical cover at English Football League stadia. The guidance on provision of services has focused on extreme circumstances such as the Hillsborough disaster in 1989, while the majority of demand on present-day services is from patients with minor injuries, exacerbations of injuries and pre-existing conditions. A new model of care was introduced in the 2009/2010 season to better meet demand. A realist approach was taken. Data on each episode of care were collected over 14 consecutive football league seasons at Millwall FC divided into two periods, preimplementation of changes and postimplementation of changes. Data on workforce retention and volunteer satisfaction were also collected.

Setting

The data were obtained from one professional football league team (Millwall FC) located in London, UK.

Primary and secondary outcomes

The primary outcome was to examine the demand for crowd medical services. The secondary outcome was to remodel the service to meet these demands.

Results

In total, 981 episodes of care were recorded over the evaluation period of 14 years. The groups presenting, demographic and type of presentation did not change over the evaluation. First aiders were involved in 87.7% of episodes of care, nurses in 44.4% and doctors 17.8%. There was a downward trend in referrals to hospital. Workforce feedback was positive.

Conclusions

The new workforce model has met increased service demands while reducing the number of referrals to acute care. It involves the first aid workforce in more complex care and key decision-making and provides a flexible registered healthcare professional team to optimise the skill mix of the team.
Using a retrospective cross-sectional study to analyse unintentional fatal drowning in Australia: ICD-10 coding-based methodologies verses actual deaths
Authors: Peden Amy E , Franklin Richard C , Mahony Alison J , Scarr Justin , Barnsley Paul D
Published: December 2017

Objectives

Fatal drowning estimates using a single underlying cause of death (UCoD) may under-represent the number of drowning deaths. This study explores how data vary by International Classification of Diseases (ICD)-10 coding combinations and the use of multiple underlying causes of death using a national register of drowning deaths.

Design

An analysis of ICD-10 external cause codes of unintentional drowning deaths for the period 2007–2011 as extracted from an Australian total population unintentional drowning database developed by Royal Life Saving Society—Australia (the Database). The study analysed results against three reporting methodologies: primary drowning codes (W65-74), drowning-related codes, plus cases where drowning was identified but not the UCoD.

Setting

Australia, 2007–2011.

Participants

Unintentional fatal drowning cases.

Results

The Database recorded 1428 drowning deaths. 866 (60.6%) had an UCoD of W65-74 (accidental drowning), 249 (17.2%) cases had an UCoD of either T75.1 (0.2%), V90 (5.5%), V92 (3.5%), X38 (2.4%) or Y21 (5.9%) and 53 (3.7%) lacked ICD coding. Children (aged 0–17 years) were closely aligned (73.9%); however, watercraft (29.2%) and non-aquatic transport (13.0%) were not. When the UCoD and all subsequent causes are used, 67.2% of cases include W65-74 codes. 91.6% of all cases had a drowning code (T75.1, V90, V92, W65-74, X38 and Y21) at any level.

Conclusion

Defining drowning with the codes W65-74 and using only the UCoD captures 61% of all drowning deaths in Australia. This is unevenly distributed with adults, watercraft and non-aquatic transport-related drowning deaths under-represented. Using a wider inclusion of ICD codes, which are drowning-related and multiple causes of death minimises this under-representation. A narrow approach to counting drowning deaths will negatively impact the design of policy, advocacy and programme planning for prevention.
How is defensive medicine understood and experienced in a primary care setting? A qualitative focus group study among Danish general practitioners
Authors: Assing Hvidt Elisabeth , Lykkegaard Jesper , Pedersen Line Bjørnskov , Pedersen Kjeld Møller , Munck Anders , Andersen Merethe Kousgaard
Published: December 2017

Objectives

Recent years have witnessed a progressive increase in defensive medicine (DM) in several Western welfare countries. In Danish primary and secondary care, documentation on the extent of DM is lacking. Before investigating the extent of DM, we wanted to explore how the phenomenon is understood and experienced in the context of general practice in Denmark. The objective of the study was to describe the phenomenon of DM as understood and experienced by Danish general practitioners (GPs).

Design

A qualitative methodology was employed and data were generated through six focus group interviews with three to eight GPs per group (n=28) recruited from the Region of Southern Denmark. Data were analysed using a thematic content analysis inspired by a hermeneutic-phenomenological focus on understanding and meaning.

Results

DM is understood as unnecessary and meaningless medical actions, carried out mainly because of external demands that run counter to the GP’s professionalism. Several sources of pressure to act defensively were identified by the GPs: the system’s pressure to meet external regulations, demands from consumerist patients and a culture among GPs and peers of infallibility and zero-risk tolerance.

Conclusions

GPs understand DM as unnecessary and meaningless actions driven by external demands instead of a focus on the patient’s problem. GPs consider defensive actions to be carried out as a result of succumbing to various sources of pressure deriving from the system, the patients, the GPs themselves and peers.
n-Alkane and long-chain alcohol recovery in moose (Alces alces), a browsing herbivore
Authors: Carnahan A.M. , Spalinger D.E. , Collins W.B.
Published: December 2017

Habitat management for herbivores often depends on an understanding of the food habits of animals. Plant cuticular waxes containing nearly indigestible complex mixture of n-alkanes and long-chain alcohols (LCOHs) have recently shown promise for diet analyses, but the accuracy of the technique depends strongly on the efficiency of recovery of the markers in feces. Fecal recovery of n-alkanes and LCOHs from 10 browse stems or leaves and two ensiled grass hays fed to moose (Alces alces (Linnaeus, 1758)) during in vivo digestion trials was investigated. n-Alkanes and LCOHs were extracted using a single-step accelerated solvent extraction technique and the recovery of these cuticular components was calculated from the feces of the animals. n-Alkane recoveries from feces averaged 0.82, ranging from a low of 0.58 (haylage) to a high of 0.95 (browse stems). LCOH recoveries averaged 0.92 across all forages, ranging from 0.80 (haylage) to a high of 1.13 (browse stems). n-Alkane and LCOH fecal recovery increased with increasing chain length, similar to findings in other studies. Although fecal recovery of n-alkanes and LCOHs were variable, we conclude that they are inversely related to forage digestibility, are consistent within forage classes, and are therefore predictable markers for use in assessing herbivore diets.
Updates on theCronobacterGenus
Authors: Forsythe Stephen J.
Published: December 2017

There has been considerable concern related to Cronobacter spp. in foods, especially due to their highlighted association with neonatal infections through the ingestion of reconstituted powdered infant formula (PIF). This concern resulted in improved microbiological criteria recommendations by the Codex Alimentarius Commission and revised WHO advice on the preparation of infant feeds. In recent years, the diversity of the genus has been well described, and various detection and typing methods have been developed. This review considers our current knowledge of the genus and how DNA-sequence-based methods have contributed considerably to research into improved detection methods and more reliable identification procedures, genotyping schemes, and genomic analysis. The broader occurrence of Cronobacter in food ingredients, finished products, and food manufacturing environments is covered. This review also highlights the significance of clonal lineages in microbial source tracking and the use of CRISPR-cas array profiling.
Effect of a protein synthetic inhibitor on in vivo estimates of protein synthesis in dogs
Authors: Schwenk W. F. , Rubanyi E. , Haymond M. W.
Published: December 2017

In vivo estimates of nonoxidative leucine disappearance have frequently been used as estimates of leucine incorporation into protein. To attempt to assess this extrapolation to protein synthesis, seven overnight fasted dogs received primed 4-h infusions of emetine (3 mg/kg, 1 mg X kg-1 X h-1), an alkaloid known to inhibit protein synthesis at the translational level. Protein metabolism was studied using infusions of [1-14C]leucine and alpha-[4,5-3H]ketoisocaproate (KIC) and the steady-state specific activities of the leucine moiety (e.g., [14C]KIC and [3H]leucine) reciprocal to the infused isotopes as estimates of intracellular leucine specific activities. Plasma leucine (157 +/- 13 to 217 +/- 13 microM) and KIC (24 +/- 1 to 41 +/- 4 microM) concentrations increased (P less than 0.001), as did leucine oxidation (0.60 +/- 0.07 to 1.67 +/- 0.15 mumol X kg-1 X min-1, P less than 0.001). Estimates of nonoxidative leucine disappearance decreased (P less than 0.001) by approximately 70%, and estimates of the endogenous leucine rate of appearance decreased (P less than 0.001) by approximately 40% using either the 14C or 3H data. We conclude that, although in vivo estimates of leucine metabolism are not quantitative, rapid changes in whole-body estimates of protein synthesis can be predicted during infusion of labeled leucine.
Sensitivity of myofibrillar proteins to glucocorticoid-induced muscle proteolysis
Authors: Kayali A. G. , Young V. R. , Goodman M. N.
Published: December 2017

Previous studies have reported that prolonged administration of pharmacological doses of glucocorticoids in young rats results in a rise in urinary 3-methyl-L-histidine (3-MH) excretion followed by a fall to initial levels by 8 days. To determine whether this response reflects events in skeletal muscle, protein breakdown in this tissue was evaluated using the perfused hindquarter preparation with rats treated with corticosterone (10 mg X 100 g-1 X day-1) for 2, 4, or 8 days. Myofibrillar and total cell proteolysis were evaluated by measuring the release of 3-MH and tyrosine, respectively, after inhibition of protein synthesis with cycloheximide. Corticosterone treatment resulted in an early increase (1-4 days) followed by a fall (4-8 days) in 3-MH excretion. 3-MH release by the perfused hindquarter of treated rats responded in a similar manner, in that its release increased at days 2 and 4 and decreased to control levels by day 8. On the other hand, corticosterone treatment did not affect the release of tyrosine by the perfused hindquarter. Corticosterone treatment diminished protein synthesis in muscle by 30-50% (P less than 0.01), which unlike 3-MH release by perfused muscle persisted throughout the treatment period. The data indicate that glucocorticoids specifically augment the breakdown of myofibrillar proteins in skeletal muscle. This response is attenuated with prolonged treatment and is unrelated to a loss of metabolic effectiveness of the steroid. Also our findings suggest that the breakdown of myofibrillar and nonmyofibrillar proteins might be regulated independently.
Uptake and processing of glycoproteins by rat hepatic mannose receptor
Authors: Taylor M. E. , Leaning M. S. , Summerfield J. A.
Published: December 2017

A linear compartmental model has been developed for the in vivo metabolism of glycoproteins. The model is applied to the interpretation of dynamic data from the rat on agalactoorosomucoid (AGOR), an N-acetylglucosamine (GlcNAc-)-terminated glycoprotein, and three neoglycoproteins terminating in mannose [mannose36-bovine serum albumin (Man-BSA)] or glucose [maltose29-BSA (Mal29-BSA) and maltose8-BSA (Mal8-BSA)]. All of these proteins are taken up by the Man/GlcNAc receptor on hepatic sinusoidal cells. The rate of uptake was found to be determined by sugar type (Man-BSA, 0.78 min-1 greater than Mal29-BSA, 0.13 min-1), sugar density (Mal29-BSA greater than Mal8-BSA), and the geometry of the sugar display (AGOR, 0.51 min-1 greater than Mal29-BSA). Intracellular transport from the cell membrane to the lysosomes was slower for Man-BSA (approximately 3 min) than for the other ligands (approximately 0 min), suggesting that receptor-ligand uncoupling was slower for Man-BSA for which the receptor had the highest affinity or that extralysosomal catabolism of the other ligands occurred. Catabolism was also determined by the carbohydrate moiety of the ligand; it was greater for Mal29-BSA and Mal8-BSA (greater than or equal to 0.8 min-1) than for Man-BSA (0.27 min-1), and AGOR, with a complex oligosaccharide, was most resistant to degradation (0.14 min-1). An understanding of these structural features of glycoproteins that influence hepatic uptake, transport, and catabolism will be of value in drug targeting and for enzyme replacement in lysosomal storage disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of proteoglycans by IGF I and II in microvessel and large vessel endothelial cells
Authors: Bar R. S. , Dake B. L. , Stueck S.
Published: December 2017

Endothelial cells were cultured from bovine capillaries and pulmonary arteries, and the effect of insulinlike growth factor (IGF) I and II (multiplication-stimulating activity) and insulin on the synthesis of proteoglycans was determined. IGF I and II stimulated 35SO4 incorporation into proteoglycans in a dose-dependent manner in both microvessel and pulmonary artery endothelial cells with maximum threefold increases. In pulmonary artery cells, the IGFs caused a general stimulation of all classes of glycosaminoglycan-containing proteoglycans. In microvessel endothelial cells, the IGFs appeared to preferentially increase heparan sulfate-containing proteoglycans. Insulin, at concentrations up to 10(-6) M, had no effect on the synthesis of proteoglycans in either microvessel or pulmonary arterial endothelial cells. Thus, the IGFs stimulate the synthesis of proteoglycans in both microvessel and large vessel endothelial cells, a property that is not mimicked by insulin. Because vascular endothelial cells are bathed by IGFs in vivo, such IGF-mediated functions are likely to be significant in both the normal physiology of vascular endothelium and in disease states such as diabetes mellitus.
Altered glucose kinetics in diabetic rats during gram-negative infection
Authors: Lang C. H. , Dobrescu C. , Bagby G. J. , Spitzer J. J.
Published: December 2017

The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced "severe" diabetes, whereas the lower dose of streptozotocin produced a milder, "latent" diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6-3H]- and [U-14C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Induction of sepsis produced a slight decrease in the glucose turnover in the severe diabetic group but did not alter turnover in the latent diabetics. The rate of glucose disappearance, used to quantitate the alterations in plasma glucose after an intravenous glucose tolerance test, was decreased in both groups of diabetics and was proportional to the severity of the diabetic state. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Hyperglucagonemia during insulin deficiency accelerates protein catabolism
Authors: Nair K. S. , Halliday D. , Matthews D. E. , Welle S. L.
Published: December 2017

Hyperglucagonemia coexists with insulin deficiency or insulin resistance in many conditions where urinary nitrogen excretion is increased, but the precise role of glucagon in these conditions is controversial. The purpose of this study was to evaluate the effect of hyperglucagonemia on protein metabolism in insulin-deficient subjects. We used the stable isotope of an essential amino acid (L-[1-13C]leucine) as a tracer of in vivo protein metabolism. A combined deficiency of insulin and glucagon was induced by intravenous infusion of somatostatin. Hyperglucagonemia and hypoinsulinemia were induced by infusions of somatostatin and glucagon. When somatostatin alone was infused leucine flux increased, indicating a 6-17% increase in proteolysis. When somatostatin and glucagon were infused, leucine flux increased, indicating a 12-32% increase in proteolysis. The increase in leucine flux during the infusion of somatostatin and glucagon was higher than the increase during infusion of somatostatin alone. Somatostatin alone did not change leucine oxidation, whereas the somatostatin plus glucagon increased leucine oxidation 100%. We conclude that hyperglucagonemia accelerates proteolysis and leucine oxidation in insulin-deficient humans.
Reversal of the exercise-induced increase in muscle permeability to glucose
Authors: Young D. A. , Wallberg-Henriksson H. , Sleeper M. D. , Holloszy J. O.
Published: December 2017

Exercise is associated with an increase in permeability of muscle to glucose that reverses slowly (h) in fasting rats during recovery. Previous studies showed that carbohydrate feeding speeds and carbohydrate restriction slows reversal of the exercise-induced increase in glucose uptake. This study was designed to evaluate the roles of glucose transport, glycogen synthesis, and protein synthesis in the reversal process in rat epitrochlearis muscle. In contrast to recovery in vivo, when muscles were incubated without insulin in vitro, the exercise-induced increase in muscle permeability to sugar reversed rapidly regardless of whether glucose transport or glycogen synthesis occurred. Inhibition of protein synthesis did not prevent the reversal. Addition of 33% rat serum or a low concentration of insulin to the incubation medium markedly slowed reversal in vitro. We conclude that 1) prolonged persistence of the increased permeability of mammalian muscle to glucose after exercise requires a low concentration of insulin, and 2) reversal of the increase in permeability does not require glucose transport, glycogen synthesis, or protein synthesis.
Patterns of glycogen turnover in liver characterized by computer modeling
Authors: Youn J. H. , Bergman R. N.
Published: December 2017

We used a computer model of liver glycogen turnover to reexamine the data of Devos and Hers, who reported the time course of accumulation in and loss from glycogen of label originating in [1-14C]galactose injected at different times after the start of refeeding of 40-h fasted mice or rats. In the present study computer representation of individual glycogen molecules was utilized to account for growth and degradation of glycogen according to specific hypothetical patterns. Using this model we could predict the accumulation and localization within glycogen of labeled glucose residues and compare the predictions with the previously published data. We considered three specific hypotheses of glycogen accumulation during refeeding: 1) simultaneous, 2) sequential, and 3) accelerating growth. Hypothetical patterns of glycogen degradation were 1) ordered and 2) random degradation. The pattern of glycogen synthesis consistent with experimental data was a steadily increasing number of growing glycogen molecules, whereas during degradation glycogen molecules are exposed to degrading enzymes randomly, rather than in a specific reverse order of synthesis. These patterns predict the existence of a specific mechanism for the steadily increasing "seeding" of new glycogen molecules during synthesis.
Myometrial desensitization after ritodrine infusion
Authors: Caritis S. N. , Chiao J. P. , Moore J. J. , Ward S. M.
Published: December 2017

We have developed a model in pregnant sheep to investigate pharmacological agents used for suppression of preterm labor. This model allows repetitive determinations of uterine contractility and simultaneous measurements of myometrial receptor and postreceptor events. We used the model to study the beta-adrenergic agent ritodrine. We infused 11 pregnant sheep with ritodrine and 3 with physiological saline for 24 h. Oxytocin boluses were given before and at 5 and 22 h after onset of the infusion. Myometrial biopsies were obtained before and immediately after the infusion. After 22 h of ritodrine infusion, uterine contractility in response to the same oxytocin bolus was 50% greater than at 5 h (P less than 0.02). Myometrial membrane beta-adrenergic receptor density decreased 49% (P less than 0.005), and catecholamine-stimulated adenylate cyclase activity was reduced 70% (P less than 0.005). The model thus demonstrates that use of the beta-adrenergic agonist ritodrine in a clinically relevant manner results in tachyphylaxis of its effects on both physiological parameters and the receptor cascade system.
Blood Ca2+ modulates responsiveness of renal 25(OH)D3-1 alpha-hydroxylase to PTH in rats
Authors: Matsumoto T. , Ikeda K. , Morita K. , Fukumoto S. , Takahashi H. , Ogata E.
Published: December 2017

To clarify whether extracellular Ca2+ modulates renal 25-hydroxyvitamin D3 [25(OH)D3]-1 alpha-hydroxylase, thyroparathyroidectomized rats were infused with 15 mM CaCl2, 20 mM EGTA, and/or 2.5 U/h parathyroid hormone (PTH), and blood Ca2+, serum 1,25-dihydroxyvitamin D [1,25(OH)2D], and renal 1 alpha-hydroxylase activity were determined. Rats with CaCl2, EGTA, or PTH infusion (group 1) exhibited low blood Ca2+, serum 1,25(OH)2D, and 1 alpha-hydroxylase activities. Infusion of CaCl2 alone (group 2) caused a significant increase in blood Ca2+ and a reduction in serum 1,25(OH)2D and 1 alpha-hydroxylase compared with group 1. Administration of PTH alone (group 3) markedly elevated blood Ca2+, serum 1,25(OH)2D, and 1 alpha-hydroxylase activity. When EGTA was infused along with PTH (group 4), blood Ca2+ was significantly reduced compared with group 3, and serum 1,25(OH)2D and renal 1 alpha-hydroxylase were further elevated. In contrast, when CaCl2 was infused with PTH (group 5), blood Ca2+ was higher than that in group 3, and serum 1,25(OH)2D and 1 alpha-hydroxylase activities were significantly reduced compared with group 3. No significant difference in serum inorganic phosphate or urinary cAMP excretion was observed by CaCl2 or EGTA infusion in both PTH-treated and nontreated rats. These results demonstrate that extracellular Ca2+ modulates the responsiveness of renal 1 alpha-hydroxylase to PTH as well as the base-line activity of the enzyme in the absence of PTH. These effects of extracellular Ca2+ on renal 1 alpha-hydroxylase may serve to offer an efficient way of regulating 1,25(OH)2D production and serum 1,25(OH)2D concentration by altering the responsiveness of 1 alpha-hydroxylase to PTH and possibly other stimulations depending on the demand for Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Periodic interactions of GH-releasing factor and somatostatin can augment GH release in vitro
Authors: Weiss J. , Cronin M. J. , Thorner M. O.
Published: December 2017

Growth hormone (GH) is secreted as pulses in vivo. To understand the signals governing this periodicity, we have established a perifusion-based model of pulsatile GH release. Male rat anterior pituitaries were dispersed and perifused with pulses of human growth hormone-releasing factor-(1--40) (GHRF), with or without a continuous or discontinuous somatostatin tonus. An experiment was composed of a 1-h base-line collection followed by four 3-h cycles; each contained single or paired 10-min infusion(s) of 3 nM GHRF. In testing the impact of somatostatin, the protocol was identical except that 0.3 nM somatostatin was added 30 min into the base-line period and then was either continued throughout the study or withdrawn during the periods of GHRF infusion. GH base lines with somatostatin were lower than vehicle base lines (P less than 0.05). GHRF pulses generated consistent peaks of GH release between 200 and 300 ng. min-1. (10(7) cells)-1, and these peaks were not altered by continuous somatostatin. In contrast, withdrawal of somatostatin during GHRF administration elicited markedly higher GH peaks (P less than 0.05) and more total GH release (P less than 0.05). This response could not be accounted for by the additive effects of GHRF and somatostatin withdrawal.
Alterations in glucose kinetics induced by pentobarbital anesthesia
Authors: Lang C. H. , Bagby G. J. , Hargrove D. M. , Hyde P. M. , Spitzer J. J.
Published: December 2017

Because pentobarbital is often used in investigations related to carbohydrate metabolism, the in vivo effect of this drug on glucose homeostasis was studied. Glucose kinetics, assessed by the constant intravenous infusion of [6-3H]- and [U-14C]glucose, were determined in three groups of catheterized fasted rats: conscious, anesthetized and body temperature maintained, and anesthetized but body temperature not maintained. After induction of anesthesia, marked hypothermia (5 degrees C decrease in core temperature) developed in rats not provided with external heat. Anesthetized rats that developed hypothermia showed a decrease in mean arterial blood pressure (25%) and heart rate (40%), whereas no differences were seen in blood pressure and heart rate of conscious and euthermic anesthetized rats. Likewise, the plasma lactate concentration and the rates of glucose appearance, recycling, and metabolic clearance were reduced by 30-50% in the hypothermic anesthetized rats. Changes in whole-body carbohydrate metabolism were prevented when body temperature was maintained. Because plasma pentobarbital levels were similar between the euthermic and hypothermic rats during the first 2 h of the experiment, the rapid reduction in glucose metabolism in this latter group appears related to the decrease in body temperature. The continuous infusion of epinephrine produced alterations in glucose kinetics that were not different between conscious animals and anesthetized rats with body temperature maintained. However, marked differences were seen in hypothermic rats. Thus pentobarbital-anesthetized rats became hypothermic when kept at room temperature and exhibited marked decreases in glucose metabolism. Such changes were absent when body temperature was maintained during anesthesia.
Effect of carbohydrate intake on de novo lipogenesis in human adipose tissue
Authors: Chascione C. , Elwyn D. H. , Davila M. , Gil K. M. , Askanazi J. , Kinney J. M.
Published: December 2017

Rates of synthesis, from [14C]glucose, of fatty acids (de novo lipogenesis) and glycerol (triglyceride synthesis) were measured in biopsies of adipose tissue from nutritionally depleted patients given low- or high-carbohydrate intravenous nutrition. Simultaneously, energy expenditure and whole-body lipogenesis were measured by indirect calorimetry. Rates of whole-body lipogenesis were zero on the low-carbohydrate diet and averaged 1.6 g.kg-1.day-1 on the high-carbohydrate diet. In vitro rates of triglyceride synthesis increased 3-fold going from the low to the high intake; rates of fatty acid synthesis increased approximately 80-fold. In vitro, lipogenesis accounted for less than 0.1% of triglyceride synthesis on the low intake and 4% on the high intake. On the high-carbohydrate intake, in vitro rates of triglyceride synthesis accounted for 61% of the rates of unidirectional triglyceride synthesis measured by indirect calorimetry. In vitro rates of lipogenesis accounted for 7% of whole-body lipogenesis. Discrepancies between in vitro rates of fatty acid synthesis from glucose, compared with acetate and citrate, as reported by others, suggest that in depleted patients on hypercaloric high-carbohydrate diets, adipose tissue may account for up to 40% of whole-body lipogenesis.
A model of the distribution and metabolism of corticotropin-releasing factor
Authors: Candas B. , Lalonde J. , Normand M.
Published: December 2017

The aim of this study is the selection of the number of compartments required for a model to represent the distribution and metabolism of corticotropin-releasing factor (CRF) in rats. The dynamics of labeled rat CRF were measured in plasma for seven rats after a rapid injection. The sampling schedule resulted from the combination of the two D-optimal sampling sets of times corresponding to both rival models. This protocol improved the numerical identifiability of the parameters and consequently facilitated the selection of the relevant model. A three-compartment model fits adequately to the seven individual dynamics and better represents four of them compared with the lower-order model. It was demonstrated, using simulations in which the measurement errors and the interindividual variability of the parameters are included, that his four-to-seven ratio of data sets is consistent with the relevance of the three-compartment model for every individual kinetic data set. Kinetic and metabolic parameters were then derived for each individual rat, their values being consistent with the prolonged effects of CRF on pituitary-adrenocortical secretion.
Development of the biphasic response to glucose in fetal and neonatal rat pancreas
Authors: Hole R. L. , Pian-Smith M. C. , Sharp G. W.
Published: December 2017

A study on the development of biphasic insulin release and sensitivity to inhibitors has been performed using perifused rat pancreas at 19.5 days of gestation (3 days before birth) and at 3 days after birth. In the fetal pancreas, 16.7 mM glucose caused a marked stimulation of insulin release that did not, however, manifest a biphasic response and was not inhibited by verapamil, a Ca2+ channel blocker. This suggested that the immature response was due to either a lack of voltage-dependent Ca2+ channels or their failure to open in response to glucose. Depolarizing concentrations of KCl stimulated insulin release, which was inhibited by verapamil, demonstrating that functional Ca2+ channels were present. In the presence of 16.7 mM glucose, quinine, which blocks glucose-sensitive k+ channels, potentiated the response of the fetal pancreas that now became sensitive to verapamil, demonstrating that functional K+ channels were also present in the fetal pancreatic beta-cell. The immaturity of the response is not due specifically to a defect in glucose metabolism; rather the metabolism of nutrient secretagogues fails to couple with the K+ channel in the fetal islet and thus fails to depolarize the beta-cell membrane. Three days after birth the pattern of response to high glucose is biphasic. Insulin release in fetal pancreas was inhibited by epinephrine and somatostatin.
Effect of sodium-restricted diet and posture on norepinephrine kinetics in humans
Authors: Linares O. A. , Zech L. A. , Jacquez J. A. , Rosen S. G. , Sanfield J. A. , Morrow L. A. , Supiano M. A. , Halter J. B.
Published: December 2017

We used compartmental analysis to analyze the kinetics of distribution and metabolism of norepinephrine (NE) and to determine whether the increase in plasma norepinephrine concentration (PNE) during sodium restriction in humans is due to sympathetic nervous system (SNS) activation. [3H]-NE infusion and postinfusion decay were measured in young subjects in the supine position and during 60 min of standing during normal sodium (NS) diet and after 7 days of 10 meq/day sodium-restricted (SR) diet. The mean supine PNE was greater during SR diet compared with NS diet (154 +/- 9 vs. 185 +/- 12 pg/ml, P = 0.02, n = 10). During both NS and SR diets, upright PNE increased (163 +/- 4 vs. 359 +/- 38 pg/ml and 182 +/- 8 vs. 401 +/- 26 pg/ml, respectively, multivariate one-way analysis of variance, P less than 0.001, alpha = 0.05). The increases of PNE with both SR diet and upright posture were accompanied by a fall in NE metabolic clearance rate (MCR1). During SR diet this was due to a fall in the volume of distribution of NE (6.1 +/- 0.4 vs. 5.0 +/- 0.4 liters, P = 0.003, n = 10). In contrast to the effect of upright posture to increase NE release into the extra-vascular compartment (NE2), during SR diet there was no change in NE2 (1.63 +/- 0.09 vs. 1.62 +/- 0.1 micrograms.min-1.m-2, P = 0.97, n = 10). Thus the increase in PNE during SR diet in humans can be explained by a fall in the volume of distribution of NE, resulting in a decrease in MCR1.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of the isotopic equilibration between lactate and pyruvate
Authors: Wolfe R. R. , Jahoor F. , Miyoshi H.
Published: December 2017

When an isotopic tracer is infused for the purpose of determining the rate of turnover or oxidation of a substrate, it is assumed that the resulting isotopic enrichment by the tracer will reflect the kinetics of only the pool of interest. However, this may not be the case when carbon-labeled lactate is infused, since rapid isotopic exchange with the intracellular pyruvate and alanine pools could potentially occur. Therefore we have determined the extent of isotopic exchange occurring during the infusion of [3-13C]lactate into six anesthetized dogs. In the steady state, pyruvate enrichment was 91 +/- 2.2% (means +/- SE) of the lactate enrichment, and alanine enrichment was 81 +/- 3.3% of the pyruvate enrichment and 72 +/- 2.6% of the lactate enrichment. In contrast, when [3-13C]alanine was infused (n = 2), pyruvate (and lactate) enrichment was 9.9% of the alanine enrichment. We therefore conclude that there is rapid isotopic equilibration between lactate and pyruvate but that interaction with alanine reflects the true metabolic flux rates, rather than isotopic exchange. Consequently, lactate kinetics, as traditionally determined, more accurately reflect whole body pyruvate kinetics.