bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversification, sympatry, and the emergence of mega-diverse tropical assemblages
Authors: Socolar Jacob B. , Lees Alexander C.
Published: December 2017

Geographic gradients in species richness, including latitudinal gradients, can arise from geographic variation in any of three mechanisms: the geologic age of habitats, net rates of evolutionary diversification, or rates of sympatry among diversifying lineages. Here we show that variation in rates of sympatry is a dominant force structuring geographic richness gradients in birds. Species-rich sites contain disproportionately high numbers of recently diverged sympatric species but contain lineages with slower-than-average diversification rates. The positive sympatry-diversity relationship consistently overwhelms the negative diversification-diversity relationship, particularly among high-diversity sites (>250 species). These patterns repeat across biomes and continents with striking regularity, and remain consistent across multiple timescales, including the recent evolutionary past. Biogeographic and evolutionary patterns in birds are consistent with a role for ecological conditions in promoting species coexistence, which allows sister species to co-occur and potentially lowers extinction rates.
Crystal structure of peroxiredoxin 3 from Vibrio vulnificus and its implications for scavenging peroxides and nitric oxide
Authors: Ahn Jinsook , Jang Kyung Ku , Jo Inseong , Nurhasni Hasan , Lim Jong Gyu , Yoo Jin-Wook , Choi Sang Ho , Ha Nam-Chul
Published: December 2017

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidase enzymes. Recently, a new type of Prx, VvPrx3, was identified in the pathogenic bacterium Vibrio vulnificus as being important for survival in macrophages. It employs only one catalytic cysteine residue to decompose peroxides. Here, crystal structures of VvPrx3 representing its reduced and oxidized states have been determined, together with an H2O2-bound structure, at high resolution. The crystal structure representing the reduced Prx3 showed a typical dimeric interface, called the A-type interface. However, VvPrx3 forms an oligomeric interface mediated by a disulfide bond between two catalytic cysteine residues from two adjacent dimers, which differs from the doughnut-like oligomers that appear in most Prxs. Subsequent biochemical studies showed that this disulfide bond was induced by treatment with nitric oxide (NO) as well as with peroxides. Consistently, NO treatment induced expression of the prx3 gene in V. vulnificus, and VvPrx3 was crucial for the survival of bacteria in the presence of NO. Taken together, the function and mechanism of VvPrx3 in scavenging peroxides and NO stress via oligomerization are proposed. These findings contribute to the understanding of the diverse functions of Prxs during pathogenic processes at the molecular level.
Active-site solvent replenishment observed during human carbonic anhydrase II catalysis
Authors: Kim Jin Kyun , Lomelino Carrie L. , Avvaru Balendu Sankara , Mahon Brian P. , McKenna Robert , Park SangYoun , Kim Chae Un
Published: December 2017

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO2/HCO3
−. Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (WI′) is observed next to the previously observed intermediate water WI, and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH− on CO2. This mechanism explains how the zinc-bound water (WZn) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first `physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.
Production, biophysical characterization and initial crystallization studies of the N- and C-terminal domains of DsbD, an essential enzyme inNeisseria meningitidis
Authors: Smith Roxanne P. , Whitten Andrew E. , Paxman Jason J. , Kahler Charlene M. , Scanlon Martin J. , Heras Begoña
Published: December 2017

The membrane protein DsbD is a reductase that acts as an electron hub, translocating reducing equivalents from cytoplasmic thioredoxin to a number of periplasmic substrates involved in oxidative protein folding, cytochromecmaturation and oxidative stress defence. DsbD is a multi-domain protein consisting of a transmembrane domain (t-DsbD) flanked by two periplasmic domains (n-DsbD and c-DsbD). Previous studies have shown that DsbD is required for the survival of the obligate human pathogenNeisseria meningitidis. To help understand the structural and functional aspects ofN. meningitidisDsbD, the two periplasmic domains which are required for electron transfer are being studied. Here, the expression, purification and biophysical properties of n-NmDsbD and c-NmDsbD are described. The crystallization and crystallographic analysis of n-NmDsbD and c-NmDsbD are also described in both redox states, which differ only in the presence or absence of a disulfide bond but which crystallized in completely different conditions. Crystals of n-NmDsbDOx, n-NmDsbDRed, c-NmDsbDOxand c-NmDsbDReddiffracted to 2.3, 1.6, 2.3 and 1.7 Å resolution and belonged to space groupsP213,P321,P41andP1211, respectively.
Structure of the mouse acidic amino acid decarboxylase GADL1
Authors: Raasakka Arne , Mahootchi Elaheh , Winge Ingeborg , Luan Weisha , Kursula Petri , Haavik Jan
Published: December 2017

Pyridoxal 5′-phosphate (PLP) is a ubiquitous cofactor in various enzyme classes, including PLP-dependent decarboxylases. A recently discovered member of this class is glutamic acid decarboxylase-like protein 1 (GADL1), which lacks the activity to decarboxylate glutamate to γ-aminobutyrate, despite its homology to glutamic acid decarboxylase. Among the acidic amino acid decarboxylases, GADL1 is most similar to cysteine sulfinic acid decarboxylase (CSAD), but the physiological function of GADL1 is unclear, although its expression pattern and activity suggest a role in neurotransmitter and neuroprotectant metabolism. The crystal structure of mouse GADL1 is described, together with a solution model based on small-angle X-ray scattering data. While the overall fold and the conformation of the bound PLP are similar to those in other PLP-dependent decarboxylases, GADL1 adopts a more loose conformation in solution, which might have functional relevance in ligand binding and catalysis. The structural data raise new questions about the compactness, flexibility and conformational dynamics of PLP-dependent decarboxylases, including GADL1.
Crystal structure of 4′-allyl-4,5,6,7,2′,7′-hexachlorofluorescein allyl ester unknown solvate
Authors: Wang Lili , Filatov Alexander S. , Engel Gregory S.
Published: December 2017

In the title compound, 4′-allyl-4,5,6,7,2′,7′-hexachlorofluorescein allyl ester {systematic name: prop-2-en-1-yl 2,3,4,5-tetrachloro-6-[2,7-dichloro-6-hydroxy-3-oxo-4-(prop-2-en-1-yl)-3H-xanthen-9-yl]benzoate}, C26H14Cl6O5, accompanied by unknown solvate molecules, the dihedral angle between the xanthene ring system (r.m.s. deviation = 0.046 Å) and the pentasubstituted benzene ring is 71.67 (9)°. Both allyl groups are disordered over two sets of sites in statistical ratios. The scattering contributions of the disordered solvent molecules (both Ph2O and CHCl3, as identified by NMR) were removed with thePLATONSQUEEZE algorithm [Spek (2015).Acta Cryst.C71, 9–18]. In the crystal, tetrameric supramolecular aggregates linked by O—H...O hydrogen bonds occur; these further interact with neighboring aggregates through C—Cl...π interactions arising from the benzene rings, forming infinite two-dimensional sheets. Each C6Cl4ring shifts in the direction perpendicular to the two-dimensional sheet, exhibiting a helical chain in which every C6Cl4ring is utilized as both a donor and an acceptor of Cl...π contacts. Thus, these two-dimensional sheets pack in a helical fashion, constructing a three-dimensional network.
Variations in disability and quality of life with age and sex between eight lower income and middle-income countries: data from the INDEPTH WHO-SAGE collaboration
Authors: Gomez-Olive Francesc Xavier , Schröders Julia , Aboderin Isabella , Byass Peter , Chatterji Somnath , Davies Justine I , Debpuur Cornelius , Hirve Siddhivinayak , Hodgson Abraham , Juvekar Sanjay , Kahn Kathleen , Kowal Paul , Nathan Rose , Ng Nawi , Razzaque Abdur , Sankoh Osman , Streatfield Peter K , Tollman Stephen M , Wilopo Siswanto A , Witham Miles D
Published: December 2017

Background

Disability and quality of life are key outcomes for older people. Little is known about how these measures vary with age and gender across lower income and middle-income countries; such information is necessary to tailor health and social care policy to promote healthy ageing and minimise disability.

Methods

We analysed data from participants aged 50 years and over from health and demographic surveillance system sites of the International Network for the Demographic Evaluation of Populations and their Health Network in Ghana, Kenya, Tanzania, South Africa, Vietnam, India, Indonesia and Bangladesh, using an abbreviated version of the WHO Study on global AGEing survey instrument. We used the eight-item WHO Quality of Life (WHOQoL) tool to measure quality of life and theWHO Disability Assessment Schedule, version 2 (WHODAS-II) tool to measure disability. We collected selected health status measures via the survey instrument and collected demographic and socioeconomic data from linked surveillance site information. We performed regression analyses to quantify differences between countries in the relationship between age, gender and both quality of life and disability, and we used anchoring vignettes to account for differences in interpretation of disability severity.

Results

We included 43 935 individuals in the analysis. Mean age was 63.7 years (SD 9.7) and 24 434 (55.6%) were women. In unadjusted analyses across all countries, WHOQoL scores worsened by 0.13 points (95% CI 0.12 to 0.14) per year increase in age and WHODAS scores worsened by 0.60 points (95% CI 0.57 to 0.64). WHODAS-II and WHOQoL scores varied markedly between countries, as did the gradient of scores with increasing age. In regression analyses, differences were not fully explained by age, socioeconomic status, marital status, education or health factors. Differences in disability scores between countries were not explained by differences in anchoring vignette responses.

Conclusions

The relationship between age, sex and both disability and quality of life varies between countries. The findings may guide tailoring of interventions to individual country needs, although these associations require further study.
Politics, policies and processes: a multidisciplinary and multimethods research programme on policies on the social determinants of health inequity in Australia
Authors: Baum Fran , Friel Sharon
Published: December 2017

Introduction

The development and implementation of multisectoral policy to improve health and reduce health inequities has been slow and uneven. Evidence is largely focused on the facts of health inequities rather than understanding the political and policy processes. This 5-year funded programme of research investigates how these processes could function more effectively to improve equitable population health.

Methods and analysis

The programme of work is organised in four work packages using four themes (macroeconomics and infrastructure, land use and urban environments, health systems and racism) related to the structural drivers shaping the distribution of power, money and resources and daily living conditions. Policy case studies will use publicly available documents (policy documents, published evaluations, media coverage) and interviews with informants (policy-makers, former politicians, civil society, private sector) (~25 per case). NVIVO software will be used to analyse the documents to see how ‘social and health equity’ is included and conceptualised. The interview data will include qualitative descriptive and theory-driven critical discourse analysis. Our quantitative methodological work assessing the impact of public policy on health equity is experimental that is in its infancy but promises to provide the type of evidence demanded by policy-makers.

Ethics and dissemination

Our programme is recognising the inherently political nature of the uptake, formulation and implementation of policy. The early stages of our work indicate its feasibility. Our work is aided by a Critical Policy Reference Group. Multiple ethics approvals have been obtained with the foundation approval from the Social and Behavioural Ethics Committee, Flinders University (Project No: 6786).

The theoretical, methodological and policy engagement processes established will provide improved evidence for policy-makers who wish to reduce health inequities and inform a new generation of policy savvy knowledge on social determinants.
Healthcare to parents of young terrorism survivors: a registry-based study in Norway
Authors: Haga Jon Magnus , Thoresen Siri , Stene Lise Eilin , Wentzel-Larsen Tore , Dyb Grete
Published: December 2017

Objectives

To assess changes in parents’ short-term and long-term primary and specialised healthcare consumption following a terrorist attack threatening the lives of their children.

Design

Registry-based study comparing parental healthcare service consumption in the 3 years before and the 3 years after a terrorist attack.

Setting

The aftermath of the Utøya terrorist attack. The regular, publicly funded, universal healthcare system in Norway. Parents learning of a terrorist attack on their adolescent and young adult child ren.

Participants

Mothers (n=226) and fathers (n=141) of a total of 263 survivors of the Utøya terrorist attack (54.6% of all survivors 13–33 years, n=482).

Main outcome measures

We report primary and specialised somatic and mental healthcare service consumption in the early (0–6 months) and delayed (>6–36 months) aftermath of the attack, both in terms of frequency of services consumed (assessed by age-adjusted negative binomial hurdle regression) and proportions of mothers and fathers provided for (mean semiannual values). The predisaster and postdisaster rates were compared by rate ratios (RRs), and 95% CI were generated through bootstrap replications.

Results

Frequency of primary healthcare service consumption increased significantly in both mothers and fathers in the early aftermath of the attack (mothers: RR=1.97, 95% CI 1.76 to 2.23; fathers: RR=1.73, 95% CI 1.36 to 2.29) and remained significantly elevated throughout the delayed aftermath. In the specialised mental healthcare services, a significant increase in the frequency of service consumption was observed in mothers only (early: RR=7.00, 95% CI 3.86 to 19.02; delayed: RR=3.20, 95% CI 1.49 to 9.49). In specialised somatic healthcare, no significant change was found.

Conclusion

Following terrorist attacks, healthcare providers must prepare for increased healthcare needs in survivors and their close family members, such as parents. Needs may present shortly after the attack and require long-term follow-up.
User involvement in adolescents’ mental healthcare: protocol for a systematic review
Authors: Viksveen Petter , Bjønness Stig Erlend , Berg Siv Hilde , Cardenas Nicole Elizabeth , Game Julia Rose , Aase Karina , Storm Marianne
Published: December 2017

Introduction

User involvement has become a growing importance in healthcare. The United Nations state that adolescents have a right to be heard, and user involvement in healthcare is a legal right in many countries. Some research provides an insight into the field of user involvement in somatic and mental healthcare for adults, but little is known about user involvement in adolescents’ mental healthcare, and no overview of the existing research evidence exists.

Methods and analysis

The aim of this systematic review is to provide an overview of existing research reporting on experiences with and the effectiveness and safety issues associated with user involvement for adolescents’ mental healthcare at the individual and organisational level. A systematic literature search and assessment of published research in the field of user involvement in adolescents’ mental healthcare will be carried out. Established guidelines will be used for data extraction (Cochrane Collaboration guidelines, Strengthening the Reporting of Observational studies in Epidemiology and Critical Appraisal Skills Programme (CASP)), critical appraisal (Cochrane Collaboration guidelines and Pragmatic-Explanatory Continuum Indicator Summary) and reporting of results (Preferred Reporting Items for Systematic reviews and Meta-Analyses, Consolidated Standards of Reporting Trials and CASP). Confidence in the research evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Adolescents are included as coresearchers for the planning and carrying out of this systematic review. This systematic review will provide an overview of the existing research literature and thereby fill a knowledge gap. It may provide various stakeholders, including decision-makers, professionals, individuals and their families, with an overview of existing knowledge in an underexplored field of research.

Ethics and dissemination

Ethics approval is not required for this systematic review as we are not collecting primary data. The results will be published in a peer-reviewed journal and at conference presentations and will be shared with stakeholder groups.
Investigating fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) and asthma–COPD overlap (ACO): a scoping review protocol
Authors: Mostafavi-Pour-Manshadi Seyed-Mohammad-Yousof , Naderi Nafiseh , Barrecheguren Miriam , Dehghan Abolfazl , Bourbeau Jean
Published: December 2017

Introduction

During the last decade, many articles have been published, including reviews on fractional exhaled nitric oxide (FeNO) use and utility in clinical practice and for monitoring and identifying eosinophilic airway inflammation, especially in asthma, and evaluating corticosteroid responsiveness. However, the exact role of FeNO in patients with chronic obstructive pulmonary disease (COPD) and its ability to distinguish patients with COPD and those having concomitant asthma, that is, asthma–COPD overlap (ACO) is still unclear and needs to be defined. Due to the broad topics of FeNO in chronic airway disease, we undertook a scoping review. The present article describes the protocol of a scoping review of peer-reviewed published literature specific to FeNO in COPD/ACO over the last decade.

Methods and analysis

We used Joanna Briggs Institute Reviewers’ Manual scoping review methodology as well as Levacet al’s and Arkseyet al’s framework as guides. We searched a variety of databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and BioSciences Information Service (BIOSIS) on 29 June 2016. Additional studies will be recognised by exploring the reference list of identified eligible studies. Screening of eligible studies will be independently performed by two reviewers and any disagreement will be solved by the third reviewer. We will analyse the gathered data from article bibliographies and abstracts.

Ethics and dissemination

To investigate the body of published studies regarding the role of FeNO in patients with COPD and its usefulness in the clinical setting, a scoping review can be used as a modern and pioneer model, which does not need ethics approval. By this review, new insights for conducting new research specific to FeNO in COPD/ACO population will emerge. The results of this study will be reported in the scientific meetings and conferences, which aim to provide information to the clinicians, primary care providers and basic science researchers.
Recognition of mental disorders: findings from a cross-sectional study among medical students in Singapore
Authors: Picco Louisa , Seow Esmond , Chua Boon Yiang , Mahendran Rathi , Verma Swapna , Chong Siow Ann , Subramaniam Mythily
Published: December 2017

Objectives

To assess recognition of five mental disorders (alcohol abuse, dementia, depression, obsessive–compulsive disorder (OCD) and schizophrenia) among a sample of medical students using a vignette-based approach. Socio-demographic predictors of correct recognition were also explored.

Design

Cross-sectional online survey.

Participants

Medical students studying in Singapore.

Methods

This was a cross-sectional online study among medical students (n=502) who were randomly assigned one of the five vignettes. Students were instructed to read the vignette, then answer the open text question, ‘What do you think the person in the vignette is suffering from?’ Multiple logistic regression was performed to determine the predictors of correct recognition.

Results

81.7% could correctly recognise the condition described in the vignette. Depression was most well recognised (93.0%), followed by alcohol abuse (89.0%), OCD (87.1%) and dementia (79.2%), while only 60.0% of students correctly recognised schizophrenia. Females were significantly more likely to correctly recognise the disorders, while the odds of correct recognition were significantly higher among fourth-year and fifth-year students compared with first-year students. Compared with depression, dementia and schizophrenia were significantly more likely to be mislabelled.

Conclusion

While overall correct recognition was high (81.7%), this did vary by disorder, where schizophrenia (60%) was the most poorly recognised condition. Given that primary care providers are often the first professional help-seeking source for people with mental health problems, medical students should be equipped with the skills and ability to recognise signs and symptoms of various mental illnesses.
Results of a community-based screening programme for diabetic retinopathy and childhood blindness in district Hyderabad, Pakistan
Authors: Nizamani Noor Bakht , Talpur Khalid Iqbal , Awan Farooq , Khanzada Mahtab Alam , Memon Mariya Nazish
Published: December 2017

Purpose

To present the results of a community-based screening programme for diabetes, diabetic retinopathy (DR) and childhood blindness (CB) in District Hyderabad, Pakistan

Methods

Prospective cross-sectional data collection from January 2014 to December 2015 of screening for diabetes, DR and CB in Hyderabad District. Female health workers were trained to identify high-risk (potential) patients for diabetes and childhood eye disorders to undertake preliminary screening and refer patients to basic health units. The patients were further assessed by medical officers with the support of qualified optometrist, after which they were referred to Sindh Institute of Ophthalmology and Visual Sciences, Hyderabad, Pakistan for management.

Results

A total of 995 244 population was covered in this screening programme during which 2622 children (0–≤15 years) were screened for CB while 16 760 adult patients (>15 years) were screened for diabetes. Random blood glucose level of 3075 patients was >140 mg/dL. Out of these patients, 17% were diagnosed with DR. Refractive error (42%) was the most common cause of childhood visual impairment.

Conclusion

The diabetic screening programme detected a high prevalence (17%) of retinopathy in patients with diabetes living in Hyderabad District. The most common cause of childhood visual impairment was refractive error (42%), which was successfully managed due to timely diagnosis. A large number of patients benefited from this community-based screening programme.
Thromboembolism Peaking 3 Months after Starting Testosterone Therapy: Testosterone–Thrombophilia Interactions
Authors: Glueck Charles J , Goldenberg Naila , Wang Ping
Published: December 2017

We assessed time of thrombotic events (venous thromboembolism (VTE)) after starting testosterone therapy (TT) in 21 men who sustained 23 VTE. The density of thrombotic events was greatest at 3 months after starting TT, with a rapid decline in events by 10 months. The 21 cases with VTE on TT differed from 110 patient controls with unprovoked VTE, not taking TT (VTE-no TT) for Factor V Leiden heterozygosity (FVL) (33 per cent vs 13 per cent, P=0.037), for high lipoprotein (a) (Lp(a)) (55 per cent vs 17 per cent, P=0.012), and for the lupus anticoagulant (33 per cent vs 4 per cent, P=0.003). These differences between cases and VTE-no TT controls were independent of age and gender. TT can interact with underlying thrombophilia–hypofibrinolysis promoting VTE. We suggest that TT should not be started in subjects with known thrombophilia. Coagulation screening, particularly for the FVL, Lp(a), and the lupus anticoagulant should be considered before starting TT, to identify men at high VTE risk who have an adverse risk/benefit ratio for TT.
REBOA at Role 2 Afloat: resuscitative endovascular balloon occlusion of the aorta as a bridge to damage control surgery in the military maritime setting
Authors: Rees Paul , Waller B , Buckley A M , Doran C , Bland S , Scott T , Matthews J
Published: December 2017

Role 2 Afloat provides a damage control resuscitation and surgery facility in support of maritime, littoral and aviation operations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) offers a rapid, effective solution to exsanguinating haemorrhage from pelvic and non-compressible torso haemorrhage. It should be considered when the patient presents in a peri-arrest state, if surgery is likely to be delayed, or where the single operating table is occupied by another case. This paper will outline the data in support of endovascular haemorrhage control, describe the technique and explore how REBOA could be delivered using equipment currently available in the Royal Navy Role 2 Afloat equipment module. Also discussed are potential future directions in endovascular resuscitation.
Detection of Properties and Capacities of Quantum Channels
Authors: Macchiavello Chiara , Sacchi Massimiliano F.
Published: December 2017

We review in a unified way a recently proposed method to detect properties of unknown quantum channels and lower bounds to quantum capacities, without resorting to full quantum process tomography. The method is based on the preparation of a fixed bipartite entangled state at the channel input or, equivalently, an ensemble of an overcomplete set of single-system states, along with few local measurements at the channel output.
Fast Convergence in the Double Oral Auction
Authors: Assadi Sepehr , Khanna Sanjeev , Li Yang , Vohra Rakesh
Published: December 2017

A classical trading experiment consists of a set of unit demand buyers and unit supply sellers with identical items. Each agent’s value or opportunity cost for the item is his private information, and preferences are quasilinear. Trade between agents employs a double oral auction (DOA) in which both buyers and sellers call out bids or offers that an auctioneer recognizes. Transactions resulting from accepted bids and offers are recorded. This continues until there are no more acceptable bids or offers. Remarkably, the experiment consistently terminates in a Walrasian price. The main result of this article is a mechanism in the spirit of the DOA that converges to a Walrasian equilibrium in a polynomial number of steps, thus providing a theoretical basis for the empirical phenomenon described previously. It is well known that computation of a Walrasian equilibrium for this market corresponds to solving a maximum weight bipartite matching problem. The uncoordinated but mildly rational responses of agents thus solve in a distributed fashion a maximum weight bipartite matching problem that is encoded by their private valuations. We show, furthermore, that every Walrasian equilibrium is reachable by some sequence of responses. This is in contrast to the well-known auction algorithms for this problem that only allow one side to make offers and thus essentially choose an equilibrium that maximizes the surplus for the side making offers. Our results extend to the setting where not every agent pair is allowed to trade with each other.
Applications of α-Strongly Regular Distributions to Bayesian Auctions
Authors: Cole Richard , Rao Shravas
Published: December 2017

Two classes of distributions that are widely used in the analysis of Bayesian auctions are the monotone hazard rate (MHR) and regular distributions. They can both be characterized in terms of the rate of change of the associated virtual value functions: for MHR distributions, the condition is that for values
v
<
v
′
, ϕ (
v
′
) - ϕ (
v
) ≥
v
′
-
v
, and for regular distributions, ϕ (
v
′
) - ϕ (
v
) ≥ 0. Cole and Roughgarden introduced the interpolating class of α-strongly regular distributions (α-SR distributions for short), for which ϕ (
v
′
) - ϕ (
v
) ≥ α (
v
′
-
v
), for 0 ≤ α ≤ 1.

In this article, we investigate five distinct auction settings for which good expected revenue bounds are known when the bidders’ valuations are given by MHR distributions. In every case, we show that these bounds degrade gracefully when extended to α-SR distributions. For four of these settings, the auction mechanism requires knowledge of these distributions (in the remaining setting, the distributions are needed only to ensure good bounds on the expected revenue). In these cases, we also investigate what happens when the distributions are known only approximately via samples, specifically how to modify the mechanisms so that they remain effective and how the expected revenue depends on the number of samples.
Appraising the nature of luteinizing hormone secretory events in men
Authors: Veldhuis J. D. , Guardabasso V. , Rogol A. D. , Evans W. S. , Oerter K. E. , Johnson M. L. , Rodbard D.
Published: December 2017

We have appraised the nature of spontaneous luteinizing hormone (LH) secretory events in normal men by analyzing immunoactive LH concentrations in blood samples withdrawn at 5-min intervals for 24 h in eight healthy individuals. A novel discrete deconvolution algorithm was applied to determine apparent instantaneous LH secretory rates from these LH concentration series. These analyses unmasked unique attributes of spontaneous LH secretory events, which were represented as delimited momentary augmentations in endogenous LH secretory rates interspersed among intervals of relative secretory quiescence. For three different peak-detection thresholds (P = 0.02, = 0.01, and = 0.005), the frequency of LH secretory episodes was significantly greater than that of LH "pulses" judged from concentration data alone. Moreover, the total mass of LH released within discrete secretory episodes could account for approximately 90% of LH secreted during the day. This model of distinct, short-lived, burst-like secretion of LH has important implications for further investigations of the neuroendocrine regulation of gonadotropin secretion in humans.
Two daily glucagon injections induce nonshivering thermogenesis in Muscovy ducklings
Authors: Barre H. , Cohen-Adad F. , Rouanet J. L.
Published: December 2017

In 6-wk-old chronically glucagon-treated (GT) ducklings, the calorigenic effect of intraperitoneal test injection of glucagon was measured at 25 and 4 degrees C ambient temperature (Ta). At 25 degrees C Ta, the increase in metabolic rate (MR) due to test injection of glucagon (360 micrograms/kg) reached 5.3 W/kg (i.e., 98% above the saline control value) in GT ducklings and only 1.7 W/kg (i.e., 29% above the control value) in control (TN) ducklings. After the injection, GT ducklings developed a hyperthermia, reaching 2.4 degrees C, accompanied by intense panting, whereas thermal body temperature did not change in TN ducklings. At 4 degrees C Ta for the same dose of glucagon, no significant change in MR was observed in GT ducklings during 180 min of exposure, whereas a 25% decrease in MR occurred in the same conditions in TN ducklings. In the cold, glucagon injection inhibited shivering in both groups of ducklings but thermogenesis was not suppressed in GT ducklings, showing a true nonshivering thermogenesis in these birds. This nonshivering thermogenesis was estimated to be 3 W/kg (i.e., 55% above resting MR). Such changes produced by chronic glucagon treatment resemble the artificial cold acclimation of rats chronically treated by norepinephrine.
Multiple effects of phorbol esters on hormone-sensitive adenylate cyclase activity in S49 lymphoma cells
Authors: Bell J. D. , Brunton L. L.
Published: December 2017

In S49 lymphoma cells, 12-O-tetradecanoyl phorbol-13-acetate (TPA) enhances adenylate cyclase activity and doubles cAMP accumulation in response to beta-adrenergic stimulation at 37 degrees C, putatively via the action of protein kinase C. At 27 degrees C, TPA has the opposite effect, inhibiting cAMP production in response to isoproterenol by approximately 25%. TPA also inhibits the response to prostaglandin E1 (PGE1), another stimulant of hormone-sensitive adenylate cyclase in these cells, by 30% at 37 degrees C and almost 50% at 27 degrees C. In contrast, TPA enhances responses to forskolin and cholera toxin at both 27 and 37 degrees C. In membranes from cells treated with TPA, PGE1-stimulated adenylate cyclase activity is inhibited by 50%, whereas the catalytic activity stimulated by NaF or forskolin is enhanced. TPA reduces the potency of both PGE1 and isoproterenol for cAMP generation by 50%. TPA causes a similar decrease in beta-adrenergic agonist affinity with no reduction in the density of either antagonist or agonist binding sites in wild type cells and in cells lacking the alpha-subunit of the stimulatory transducer protein (Gs) (cyc-) or lacking functional receptor Gs coupling (UNC). Therefore, TPA has at least three functionally distinct effects on hormone-sensitive adenylate cyclase in S49 cells: a 50% reduction in agonist affinity, attenuation of receptor-transducer coupling, and enhancement of GTP-dependent catalytic activity. We conclude that multiple and opposing effects of TPA on hormone-sensitive adenylate cyclase occur simultaneously within the same cell, affecting the responses to several agonists differently.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin resistance during suckling period in rats
Authors: Issad T. , Coupe C. , Ferre P. , Girard J.
Published: December 2017

Glucose metabolism was studied in 13- to 15-day-old suckling rats and 28- to 30-day-old rats weaned at 19 days on a high-carbohydrate, low-fat diet. The glucose turnover rate in the basal state was similar in suckling and weaned rats (14 mg X min-1 X kg-1). Glucose infusion (20 mg X min-1 X kg-1) produced a moderate hyperglycemia in weaned rats (150 mg/dl), whereas the suckling rats developed a high hyperglycemia (280 mg/dl), despite a large increase of plasma insulin concentration. The effect of insulin on glucose kinetics was then assessed by the euglycemic-hyperinsulinemic clamp technique. The plasma insulin levels reached were 736 +/- 87 microU/ml in the suckling and 444 +/- 34 microU/ml in the weaned rats, despite similar insulin infusion rates. Hepatic glucose production was suppressed by 90% in the weaned rats, whereas it remained at 40% of basal value in the suckling rats. The increase of glucose utilization above basal was fourfold higher in the weaned than in the suckling rats. Thus an insulin resistance state is present in the suckling rats and disappears after weaning onto a high-carbohydrate diet.
Pathophysiology of type A hypoxic lactic acidosis in dogs
Authors: Arieff A. I. , Graf H.
Published: December 2017

Hypoxic lactic acidosis (HLA) was induced in dogs by ventilating them with a hypoxic gas mixture of 8% O2-92% N2. The animals were studied both in the control state and after development of HLA, where arterial lactate was above 5 mM, pH was below 7.2, bicarbonate was below 12 mM, and arterial PO2 was between 26 and 30 Torr. After hypoxia had been present for 90 min, most of the increase in arterial lactate vs. control was due to increased lactate production from gut and carcass in the presence of a decreased capacity of the liver to extract lactate. The capacity of the liver to extract lactate in the normoxic state was evaluated in another group of six dogs after infusion of L-lactic acid such that arterial pH, lactate, and bicarbonate were similar to hypoxic values. In these experiments it was found that the capacity of the liver to extract lactate was 14.8 +/- 1.7% of the delivered load vs. 4.9 +/- 1.3% observed in hypoxic animals. The decreased liver lactate extraction in HLA was probably secondary to both a decrease in liver oxygen uptake and a decrease in liver intracellular pH and was paralleled by an increase in liver tissue lactate levels. Cardiac output, in contrast to other forms of lactic acidosis, was increased by 40% vs. control and femoral artery flow by 35%, whereas liver blood flow was unchanged and renal blood flow decreased. Hypoxic lactic acidosis thus is the consequence of overproduction of lactate by both gut and carcass, in the presence of impaired utilization of lactate by the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of free and sulfate-conjugated catecholamines in human platelets
Authors: McCulloch R. K. , Vandongen R. , Tunney A. M. , Beilin L. J. , Rogers P. B.
Published: December 2017

Sulfate conjugation represents a major pathway for the inactivation of catecholamines and is presumed to occur at sites, including platelets, where phenylsulfotransferase activity has been identified. This study examines the relative distribution of free and conjugated norepinephrine, epinephrine, and dopamine in the platelets and plasma of resting subjects. As active uptake of free catecholamines into platelets has been reported in vitro; the possibility of a similar mechanism, operating for sulfate conjugates, was also investigated. The presence of sulfated catecholamines in platelets is confirmed. The proportion of total catecholamines existing in the free form was 78 +/- 4% (mean +/- SE) for norepinephrine, 52 +/- 5% for epinephrine, and 50 +/- 10% for dopamine, which was considerably higher than for plasma. Increases in plasma free and conjugated catecholamines achieved by bicycle exercise and oral administration of amines, respectively, were not accompanied by corresponding increases in platelet levels. The origin of platelet conjugates would appear to be the result of intraplatelet sulfation of free amines rather than direct uptake from plasma. Because acute elevation of plasma free and conjugated amines are not reflected in increased platelet levels, it is unlikely that platelet uptake mechanisms play a significantly role in the disposal of circulating catecholamines.
Effects of leucine, isoleucine, or threonine infusion on leucine metabolism in humans
Authors: Schwenk W. F. , Haymond M. W.
Published: December 2017

Leucine and/or its alpha-keto acid, alpha-ketoisocaproate (KIC), have been reported to spare protein in humans. To determine whether specific amino acid infusions affect whole-body protein metabolism as estimated by changes in leucine flux and oxidation, five groups of normal subjects were infused with saline, leucine (0.47 and 0.94 mumol . kg-1 . min-1), isoleucine (0.47 mumol . kg-1 . min-1), or threonine (0.47 mumol . kg-1 . min-1). Independent estimates of leucine metabolism were obtained using simultaneous infusions of [3H]-leucine and alpha-[14C]ketoisocaproate. Nearly identical results were obtained using either tracer compared with the saline controls. Compared with the saline controls, leucine infusion 1) had no effect on estimated rates of appearance of endogenous leucine, 2) stimulated leucine oxidation, 3) decreased plasma concentrations of other amino acids, and 4) stimulated non-oxidized leucine disappearance in a dose-dependent fashion. In contrast, isoleucine and threonine infusions had no effect on leucine metabolism. Assuming the validity of the isotope model employed, these data suggest that the purported anabolic effect of leucine infusion on whole-body protein metabolism is mediated via stimulation of protein synthesis rather than decreased proteolysis.
GRF elevates cytosolic free calcium concentration in rat anterior pituitary cells
Authors: Schofl C. , Sandow J. , Knepel W.
Published: December 2017

The effect of human growth hormone-releasing factor (GRF) on intracellular free calcium concentration ([Ca2+]i) was examined in rat anterior pituitary cells. The [Ca2+]i was monitored directly by means of the intracellularly trapped fluorescent indicator, fura-2. GRF rapidly elevated [Ca2+]i, reaching a new plateau within approximately 30 s. The half-maximally effective concentration of GRF was approximately 130 pM. GRF produced a maximal increase in [Ca2+]i by approximately 120 nM. The GRF (2 nM)-induced elevation of [Ca2+]i was abolished by removal of extracellular calcium (Ca2+ omitted, 2 mM EGTA). The GRF (2 nM)-caused rise in [Ca2+]i was largely reduced in the presence of the calcium channel blockers Mg2+ (31.2 mM) or nifedipine (1 microM). An increase in [Ca2+]i by approximately 60 nM was elicited by the addition of prostaglandin E2 (1 microM), which can stimulate growth hormone secretion independent of GRF receptors. These data indicate that GRF elevates the [Ca2+]i, possibly in somatotrophs; this GRF-induced increase in [Ca2+]i may depend on an influx of extracellular Ca2+, largely through Mg2+- and nifedipine-sensitive calcium channels.
Effect of endurance training on leucine metabolism in perfused rat skeletal muscle
Authors: Hood D. A. , Terjung R. L.
Published: December 2017

An isolated single rat hindlimb muscle preparation was used to examine the influence of exercise training on leucine metabolism during steady-state conditions at rest and during isometric contractions. Treadmill training increased the activity of citrate synthase in the hindlimb muscle by 40-45%. Leucine oxidation, measured as the rate of alpha-decarboxylation, was not different between trained (2.28 +/- 0.15 nmol.min-1.g-1, n = 9) and control (2.57 +/- 0.20, n = 9) muscle at rest. In addition, successive 40-min contraction periods at 15 and 45 tetani/min induced similar increases (50 and 100%, respectively) in leucine oxidation in both groups. However, trained muscle maintained a greater tension output (P less than 0.05) during contractions and exhibited a greater oxygen consumption (VO2) (P less than 0.05) during 45 tetani/min. Thus the rate of leucine oxidation, relative to VO2, was less (P less than 0.05) in the trained group. This response was probably related to differences in intracellular factors modulating branched-chain alpha-keto acid dehydrogenase, the rate-limiting step in leucine oxidation. Although our observed rates of muscle leucine alpha-decarboxylation can reasonably account for the rates of whole-body leucine alpha-decarboxylation of nontrained individuals found during steady-state tracer studies in vivo, this is less reasonably the case for the trained group. This suggests that a greater rate of leucine oxidation by nonmuscle tissues (e.g., liver) may occur in trained compared with nontrained individuals.
Carbonic anhydrase activity of chick osteoclasts is increased by parathyroid hormone
Authors: Silverton S. F. , Dodgson S. J. , Fallon M. D. , Forster R. E.
Published: December 2017

Embryonic chick osteoclasts were harvested, cultured for 18 h, and separated from erythrocytes, and carbonic anhydrase (CA) activity was assayed. Cultures contained 75-85% osteoclasts by acid phosphatase stain. CA activity was also determined after exposure to parathyroid hormone (PTH). Two methods of measurement were used: a delta pH method, which detects the generation of hydrogen ion by carbonic anhydrase, and a mass spectrometric method, which follows the disappearance of 18O-enriched CO2. Unstimulated osteoclasts showed CA activity that was one-third that of erythrocytes but was comparable with macrophages and chondrocytes. Osteoclasts exposed to PTH showed a twofold increase in activity, which occurred after 30 min. Ethoxzolamide (10(-8) M) inhibited enzyme activity by 90%. Treatment of osteoclasts with calcitonin did not prevent the PTH-associated increase in CA activity. The doubling of CA activity with PTH stimulation supports the hypothesis that osteoclastic CA is intimately involved in bone resorption.
Regional lactate production in early canine endotoxin shock
Authors: van Lambalgen A. A. , Runge H. C. , van den Bos G. C. , Thijs L. G.
Published: December 2017

High serum lactate may not reflect the severity of endotoxin shock: the lactate load could even be formed immediately after the endotoxin challenge. During the first 30 min after endotoxin injection (Escherichia coli; 1.5 mg/kg iv) into anesthetized dogs (4 mg.kg-1.h-1 etomidate, n = 19) we studied arterial lactate concentration; contributions of portal and splanchnic (n = 6), renal and pulmonary (n = 7), and femoral (n = 6) vascular beds to the early lactate rise; and regional O2 extraction and blood flow (microspheres). In control dogs (n = 5, no endotoxin), we found no significant hemodynamic and biochemical changes. Endotoxin caused an immediate decrease in blood pressure, cardiac output, and organ perfusion, followed by recovery after approximately 5 min to approximately 75% of preshock values at t = 30 min (except for renal blood flow, which remained low). Arterial lactate concentration started to increase almost immediately after endotoxin and increased rapidly until t = 15 min (to 300%) and then leveled off, but in spite of the hemodynamic recovery it remained elevated. A major part of the early increase in lactate concentration can be explained by splanchnic lactate production. The total splanchnic bed released more lactate than the portal bed, indicating that the liver produces lactate. We conclude that the lactate concentration later in canine endotoxin shock depends on events that occur during early shock in which the liver may play a crucial role.
Normalization of carbohydrate-induced thermogenesis by fructose in insulin-resistant states
Authors: Simonson D. C. , Tappy L. , Jequier E. , Felber J. P. , DeFronzo R. A.
Published: December 2017

To examine whether defects in carbohydrate oxidation and thermogenesis in aging, obesity, and diabetes are secondary to impaired insulin action or to a primary defect in intracellular metabolism, we compared substrate oxidation and energy expenditure in 9 younger, 9 older, 9 obese, and 10 non-insulin-dependent diabetic subjects after the ingestion of 75 g of glucose or fructose (a monosaccharide whose transport into the cell and subsequent metabolism are independent of insulin). In young control subjects fructose produced a significantly greater increase in carbohydrate oxidation and energy expenditure than glucose despite significantly lower plasma glucose and insulin levels. In aged, obese, and diabetic individuals the increments in carbohydrate oxidation and energy expenditure after glucose ingestion were significantly imparied versus the younger controls. After fructose ingestion the increase in carbohydrate oxidation in the three insulin-resistant groups remained below that observed in the younger volunteers, whereas carbohydrate-induced thermogenesis was enhanced to levels that were comparable with those seen in the younger group. These data suggest that 1) the stimulation of thermogenesis after fructose ingestion is related to an augmentation of intracellular metabolism rather than an increase in the plasma insulin concentration per se, 2) the insulin resistance of aging, obesity, and diabetes is associated with a defect in intracellular carbohydrate oxidation, and 3) the cellular mechanisms involved in carbohydrate-induced thermogenesis are not primarily impaired in insulin-resistant states.