bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmable materials and the nature of the DNA bond
Authors: Jones Matthew R. , Seeman Nadrian C. , Mirkin Chad A.
Published: February 2015

Valency and bonding on a larger scale

In molecular systems, valency describes the number of bonds an atom can make with its neighbors. Larger objects such as colloids can be linked together to make connected structures in which the number of connections, or valency, is controlled by the central object. Jones
et al.
review the two main approaches to creating stiff bonds, based on DNA-based materials synthesis. These approaches allow the construction of molecular-like objects from building blocks much larger than single atoms.

Science
, this issue
10.1126/science.1260901
NIH plots million-person megastudy
Authors: Kaiser Jocelyn
Published: February 2015

Questions abound as researchers discuss personalized medicine project.
Understanding particle acceleration in astrophysical plasmas
Authors: Ji Hantao , Zweibel Ellen
Published: February 2015

Simulations reveal new scenarios to accelerate electrons to extremely high energies

[Also see Report by

Matsumoto
et al.

]
Physicist. Defector. Spy?
Half-Life The Divided Life of Bruno Pontecorvo, Physicist or Spy
Frank Close
Basic Books, 2015. 398 pp.
Authors: Wellerstein Alex
Published: February 2015

A closer look at the enigmatic life of Bruno Pontecorvo
Structured photons take it slow
Authors: Sambles J. R.
Published: February 2015

Specially prepared single photons travel below the “speed of light,” even in vacuum

[Also see Report by

Giovannini
et al.

]
Insecticidal RNA, the long and short of it
Authors: Whyard Steve
Published: February 2015

Transgenic plants that express insect-specific RNA in chloroplasts kill pests through RNA interference

[Also see Report by

Zhang
et al.

]
Can oxytocin treat autism?
Authors: Young Larry J. , Barrett Catherine E.
Published: February 2015

We are still at an early stage of assessing oxytocin-based therapy for autism spectrum disorders
Genome Sequence of Salmonella Phage χ
Authors: Hendrix Roger W. , Ko Ching-Chung , Jacobs-Sera Deborah , Hatfull Graham F. , Erhardt Marc , Hughes Kelly T. , Casjens Sherwood R.
Published: February 2015

Salmonella bacteriophage χ is a member of the
Siphoviridae
family that gains entry into its host cells by adsorbing to their flagella. We report the complete 59,578-bp sequence of the genome of phage χ, which together with its relatives, exemplifies a largely unexplored type of tailed bacteriophage.
HIERARCHICAL MAPPING AS A TOOL TO EXAMINE THE NETWORKS OF THOSE AT END OF LIFE
Authors: Canaway A , Coast J , Al-janabi H , Kinghorn P , Bailey C
Published: February 2015

Introduction

End of life care (EoLC) concerns the needs of both patients and those close to them. Current methods of economic evaluation typically focus on the patient and, only infrequently, the health of the carer. There are strong arguments that impacts on those close to the patient should also be included within economic evaluation. It is therefore important to know who, and how many people may be eligible for inclusion within the evaluation.

Aim(s) and method(s)

The aim was to examine the scale of decedents' social networks and explore factors that impact closeness at the end of life (EoL). Hierarchical mapping alongside in-depth interviews was used to examine the networks. Interviews took place with the bereaved, and those with somebody ‘close’ to them receiving EoLC. In total, the networks of 24 decedents were explored.

Results

The median number of individuals included within the close-person network at EoL was eight. Over 60% of the hierarchical maps included individuals who were not family members and many included those who were not geographically close. Family size and death trajectory appeared to play key roles in determining the size of network at the EoL.

Conclusion(s)

The hierarchical mapping task was a quick and easy method of establishing the scale of close-person networks. Results suggest that if economists are to assess the full (true) impact of EoLC, assessment will need to extend beyond those providing informal care. This work aligns with the normative stance that evaluation of EoLC should not be limited solely to health outcomes.
THE FUTURE OF DATA COLLECTION IN PALLIATIVE CARE PRACTICE
Authors: Witt J , Brown A , Kaler P , Pannell C , Murtagh FEM
Published: February 2015

Introduction

Patient-reported outcome measures (PROMs) are usually completed on paper. Laptops, electronic (e/)tablets and smartphones are rarely used with palliative care patients and it is not known whether their use is feasible and acceptable in this population.

Aim(s) and method(s)

We explored whether palliative care patients find the use of e/tablets for PROMs data collection feasible and acceptable. To do this, we embedded a qualitative component within a larger study in two urban UK hospitals. We asked patients who completed PROMs on e/tablets or paper to complete a brief structured telephone survey followed by a semi-structured discussion of any issues experienced. Additionally, research nurses who supported patients during completion were interviewed.

Results

Ten patients (70% male; age range 33–87; 30% non-cancer diagnosis) and two research nurses took part. Satisfaction with either format was high, and most found both easy to read, use and navigate. Emerging themes highlighted advantages and drawbacks of each format: Those who used paper valued the simplicity and familiarity of this format. Those who used e/tablets particularly liked the immediate transfer of their responses to electronic records and their clinician. However, several issues with e/tablets were also raised, including poor responsiveness to touch, connectivity problems and weight.

Conclusion(s)

E/tablet use is feasible and has potential to improve collection and use of PROMs by clinicians. However, for maximum utility, e/tablets need to be touch responsive, well connected, and lightweight, and integrated into clinical databases with real time feedback.

Funder: the National Institute for Health Research—Programme.
A SUMMARY OF THE NATIONAL CARE OF THE DYING AUDIT FOR HOSPITALS, ENGLAND (NCDAH) 2013/14 AUDIT RESULTS
Authors: Mulholland Helen , Gambles Maureen , Lowe Derek , Husk Janet , Stewart Kevin , Ellershaw John
Published: February 2015

Introduction

The quality of end of life services is suggested as an indicator of the quality of all health care provision. NCDAH provides data regarding the standard of care delivered to imminently dying patients.

Aim(s) and method(s)

To report on the care provided to dying patients and their relatives to highlight areas for improvement in clinical practice and influence policy/funding/research agendas.

Retrospective audit of organisational aspects of care & clinical data from 6580 patient records for May 2013 from 131 Hospitals (H).

36H (27%) captured 858/2313 (37% response) bereaved relatives' (BR) views via the Care of the Dying Evaluation questionnaire.

Results

Median age 82; cancer diagnosis 23% (1546); female 51% (3332).

Organisational

7-day-access to specialist palliative care service (SPCS) in 28H (21%).

No education/training provision in 24H (18%).

No Trust Board (TB) representation in 61H (47%).

No Audit in 57H (44%).

Clinical

Decisions and assessments routinely recorded (eg.Recognition of dying recorded in 87% (5722) cases). Exceptions-Clinically Assisted Nutrition 45% (2563)/Hydration 59% (3351).

Communication of decisions more likely undertaken with relatives than patients.

Least routinely recorded:Spiritual needs assessment(Capable patients 21% (715/3391)*/Relatives 25% (1623/6575*)).

Care after death 46% (3037)

BR Views

Most reported that patients were ‘always’ treated with dignity & respect by doctors (66%/535*) and nurses (70%/577*)

BR felt adequately supported (76%/610*)

*Reduced sample

Conclusion(s)

Organisational processes should include: 7 day access to SPCS; staff education; Trust Board representation/audit. Clinical decision documentation & communication to patients & relatives could be improved. Whilst bereaved relatives views were generally positive, a significant minority reported negative perceptions of care.
IS SOCIAL MEDIA SHAPING THE FUTURE OF PALLIATIVE CARE RESEARCH: EXPERIENCE OF THE EVOLUTION AND REVOLUTION OF NEW TECHNOLOGIES
Authors: Ngwenya N
Published: February 2015

Introduction

Research in palliative care faces many ethical and practical challenges which call for the exploration of new methodologies to help overcome these barriers. With an awareness of how the internet has revolutionised the world, social media techniques are a feasible option as they have been successfully implemented and used in other research disciplines.

Aim(s) and method(s)

This paper discusses various ways that social media can be adopted in palliative care research and the methodological implications of their use. Two case studies based on our experience of using social media in research will be presented.

Results

Both quantitative and qualitative research can use the internet as an additional modality that complements research objectives. Within the two case studies social media was successfully used to facilitate patient identification and access hard to reach participants improving recruitment and attrition rates; afforded the possibility of innovative data collection methods that consider issues such as low tolerance for burden with palliative care patients, thus enriching the data. Data analysis and dissemination were improved with the possibility of informing the general public thus promoting palliative care as a public health issue.

Conclusion(s)

Based on our experience, recommendations are given for those planning to use social media for research in palliative care. Techniques for improving patient recruitment and quality data collection are suggested, stressing the need to use these methods appropriately and not simple as a replacement of traditional approaches. Timeframe processes of online methods vary and the objectives of the study should be considered to ensure that relevant data are collected.
INTERNATIONAL PALLIATIVE CARE JOURNAL CLUB ON TWITTER: EXPERIENCE SO FAR
Authors: Whitburn T , Walshe C , Sleeman KE
Published: February 2015

Introduction

@hpmJC (hospice and palliative medicine Journal Club, #hpmJC) was launched in February 2014 on the social networking service Twitter, as a regular international journal club for palliative care. The journal club aims to encourage critical analysis of research methods and findings, and to promote evidence based practice, by providing a forum to discuss latest research findings.

Aim(s) and method(s)

To analyse the use and reach of #hpmJC, from the first journal club in February 2014, to date.

All data on Twitter posts (tweets) using #hpmJC were extracted from Twitter using analytic tools Sysomos and Symplur. Outcomes included number of tweets, number of unique users, users' designated country, and impressions (potential number of accounts reached).

Results

7 journal clubs have taken place. 2360 tweets were sent, from 230 individual Twitter accounts and with contributions from people in 17 countries. For contributors whose country of origin is known (59%), most were based in the UK (41%) or USA (26%).Tweets from resource-poor countries were initially uncommon but increased over the time period. The mean number of contributors at each journal club was 32. The potential reach of #hpmJC varied, but for the most recent journal club was 290,802 unique users.

Conclusion(s)

Social media provides opportunities to share expertise and disseminate information globally, transcending geographical boundaries.

@hpmJC has been used to start a viable and sustainable online multidisciplinary journal club with wider geographical spread and potential reach than a traditional journal club. Strategies to increase participation in resource-poor countries are being developed.
Finding a home in shelter medicine
Authors: Litster Annette
Published: February 2015

Inspired by a life‐changing sabbatical in the USA, Annette Litster found her way into shelter medicine. An openness to change has fuelled a career full of twists and turns
Study of ground collapse induced by large-diameter horizontal directional drilling in a sand layer using numerical modeling
Authors: Shu Biao , Ma Baosong
Published: February 2015

With large-diameter horizontal directional drilling (HDD) becoming the preferred method to construct oil and gas pipelines and utility pipelines beneath rivers, the issue of potential ground collapse arises when drilling in loose geological layers such as sand. Ground collapse is a result of borehole collapse and may cause significant damage to the topography and nearby facilities. The present investigation considered the potential causes of ground collapse induced by an actual 1.219 m diameter HDD river-crossing project, using the FLAC3D numerical modeling tool. The analysis showed that the failure zone first developed at the crown of the borehole, resulting in subsequent borehole collapse due to instability of the sand above, and eventually leading to ground collapse. Sequential reaming cycles have been simulated and the results indicate very little effect in comparison with a single reaming cycle. The risk of borehole collapse, and consequent ground collapse, increases with borehole diameter. Parametric numerical modelling has also been conducted to study the influence of soil parameters and drilling mud pressure on the stability of the ground surface above the borehole. The results show that soil cohesion and friction angle have a large influence on stability of the borehole and ground surface, while elastic modulus and Poisson’s ratio have relatively little effect. It was also determined that mud pressure is a very important factor in maintaining stability of the borehole, and therefore the ground surface as well.
Combining aerial LiDAR and multispectral imagery to assess postfire regeneration types in a Mediterranean forest
Authors: Martín-Alcón Santiago , Coll Lluís , De Cáceres Miquel , Guitart Lídia , Cabré Mariló , Just Ariadna , González-Olabarría José Ramón
Published: February 2015

Wildfires play a major role in driving vegetation changes and can cause important environmental and economic losses in Mediterranean forests, especially where the dominant species lacks efficient postfire regeneration mechanisms. In these areas, postdisturbance vegetation management strategies need to be based on detailed, spatially continuous inventories of the burned area. Here, we present a methodology in which we combine airborne LiDAR and multispectral imagery to assess postfire regeneration types in a spatially continuous way, using a Mediterranean black pine (Pinus nigra Arn ssp. salzmannii) forest that burned in 1998 as a case study. Five postfire regeneration types were obtained by clustering field-plot data using Ward’s method. Two of the five regeneration types presented high tree cover (one clearly dominated by hardwoods and the other dominated by pines), a third type presented low to moderate tree cover, being dominated by hardwoods, and the remaining two types matched to areas dominated by soil–herbaceous or shrub layers with very low or no tree cover (i.e., very low to no tree species regeneration). These five types of regeneration were used to conduct a supervised classification of remote sensing data using a nonparametric supervised classification technique. Compared with independent field validation points, the remote sensing based assessment method resulted in a global classification accuracy of 82.7%. Proportions of regeneration types in the study area indicated a general shift from the former pine-dominated forest toward hardwood dominance and showed no serious problems of regeneration failure. Our methodological approach appears to be appropriate for informing postdisturbance vegetation management strategies over large areas.
Bistable behaviors of weak probe light via coherent and incoherent fields
Authors: Jafarzadeh H. , Sangachin E. Ahmadi , Asadpour Seyyed Hossein
Published: February 2015

In this paper, the bistable behaviors of weak probe light in a unidirectional ring cavity with a four-level atomic system are discussed. We find that in the presence of spontaneously generated coherence (SGC), the medium is completely phase dependent and the intensity threshold of optical bistability can be controlled. The effect of an incoherent pumping field on optical bistability in the presence and absence of SGC is also analyzed. Moreover, the group index behavior of weak probe light is investigated. We show that the intensity threshold of optical bistability can be controlled by light propagation switching from slow to fast by different parameters of the atomic medium.
Realistic f(T) model describing the de Sitter epoch of the dark energy dominated universe
Authors: Nassur S.B. , Kpadonou A.V. , Rodrigues M.E. , Houndjo M.J.S. , Tossa J.
Published: February 2015

We consider an exponential model within the so-called f(T) theory of gravity, where T denotes the torsion scalar. We focus our attention on a cosmological feature of a f(T) model, checking whether it may describe the de Sitter stage of the current universe according to the evolution of the redshift, z. Our results show that the model reproduces the de Sitter stage only for low redshifts, where the perturbation function approached zero, whereas the effective parameter of the equation of state goes to –1, which is the expected behavior for any model able to reproduce the de Sitter stage.
Hypersurface-homogeneous cosmological models with dynamical equation of state parameter in Lyra geometry
Authors: Ram Shri , Chandel S. , Verma M.K.
Published: February 2015

The hypersurface homogeneous cosmological models are investigated in the presence of an anisotropic fluid in the framework of Lyra geometry. Exact solutions of field equations are obtained by applying a special law of variation for mean Hubble parameter that gives a negative constant value of the deceleration parameter. These solutions correspond to anisotropic accelerated expanding cosmological models that isotropize for late time even in the presence of anisotropic fluid. The anisotropy of the fluid also isotropizes at late time. Some physical and kinematical properties of the model are also discussed.
An asymptotic method for selection of inflationary modes
Authors: Yusofi E. , Mohsenzadeh M.
Published: February 2015

We present some features of early universe cosmology in terms of Hankel functions index (ν). Actually, the recent data from observational cosmology indicate that our universe was nearly de Sitter spacetime in the early times which results in an approximate scale-invariant spectrum. This imposes some constrains on index ν [E. Yusofi and M. Mohsenzadeh, JHEP 09, 020 (2014)]. These constrains stimulate us to use general solution of inflaton field equation for [Formula: see text]. To obtain the general solution for the inflationary background, we use asymptotic expansion of Hankel functions up to nonlinear order of [Formula: see text]. We consider the nonlinear modes as the fundamental modes for early universe during the inflation. In this paper, we obtain the general form of the inflationary modes, scale factor expansion, equation of state and some nonlinear corrections of power spectrum in terms of index ν. These results are general and in quasi-de Sitter and de Sitter limit confirm the conventional results.
An extended lattice model for two-lane traffic flow with consideration of the slope effect
Authors: Chen Jianzhong , Peng Zhiyuan , Fang Yuan
Published: February 2015

An extended two-lane lattice model of traffic flow with consideration of the slope effect is proposed. The slope effect is reflected in both the maximal velocity and the relative current. The stability condition of the model is derived by applying the linear stability method. By using the nonlinear analysis method, we obtain the Korteweg–de Vries (KdV) equation near the neutral stability line and the modified Korteweg–de Vries (mKdV) equation near the critical point. The analytical and numerical results demonstrate that the stability of traffic flow is enhanced on the uphill but is weakened on the downhill when the slope angle increases.
Minimum remote state preparation of an arbitrary two-level one-atom state via cavity QED
Authors: Wang Yahong , Yu Changshui
Published: February 2015

In this paper, we propose three schemes for remotely state preparation (RSP) an arbitrary two-level one-atom state via cavity quantum electro dynamics (QED) with minimal resources consumption. In the first case, a Greenberger–Horne–Zeilinger (GHZ) state is used as quantum channel; in the second case, the sender needs to construct an quantum channel with both of the assistant of cavity QED and the knowledge about the state to be remotely prepared. In each scheme, only 1 cbit and 1 ebit are needed with the aid of cavity QED. In the third case, we combine the first two protocols and give a theoretical proposal for controlled RSP with only 2 cbits and 1 ebit resources consumption.
Investigations on Fe-doped strontium barium niobate, single phase ferroelectric and magnetodielectric compounds
Authors: Kshirsagar S. H. , Jigajeni S. R. , Tarale A. N. , Salunkhe D. J. , Joshi P. B.
Published: February 2015

To understand possible interaction between magnetic and electric order parameters of Fe -doped Sr x Ba 1-x Nb 2 O 6 (SBN), Fe -doped Sr 0.5 Ba 0.5 Nb 2 O 6 (SBN50) and Sr 0.4 Ba 0.6 Nb 2 O 6 (SBN40) are synthesized and investigated. Synthesis has been carried out via ceramic route. The paper reports synthesis, crystal structure, dielectric properties, P–E hysteresis loops, M–H hysteresis loops and magneto-capacitance of the Fe -doped SBN compositions. All the compositions are observed to exhibit a useful value of magneto-capacitance, especially at frequencies less than 10 kHz.
Natural hazards and geological heritage in Earth science education projects
Authors: Ferrero Elena , Magagna Alessandra
Published: February 2015

To the non-specialist, the concept of geological natural hazard usually refers to natural processes affecting the geosphere that produce far-reaching and intense effects, involving significant transfers of matter and energy, in a relatively short time when compared to the human timescale. Usually, these processes are also associated with abrupt and destructive effects involving human activities and lives.

From the geoscientific point of view, slower and more gradual processes, which produce small scale effects, can also pose a hazard, for example when the process results in the loss of scientific information or in the destruction of evidence of past events that cannot be reproduced, such as those related to the history of life, or when spectacular examples of particular aesthetic value are destroyed.

Only widespread education and good quality communication, both rigorous and effective, can increase people's awareness and sensitivity to the need for protection of the geological heritage and for adopting geoethic attitudes.

This paper presents some case studies in the Piedmont region (NW Italy) that involved students of primary and secondary schools in an active and participatory way and that represented a training opportunity for their teachers.
USING A COURSE-LONG THEME FOR INQUIRY-BASED LABORATORIES IN A COMPARATIVE PHYSIOLOGY COURSE
Authors: Rivers David B.
Published: February 2015

I developed an inquiry-based laboratory model that uses a central theme throughout the semester to develop in undergraduate biology majors the skills required for conducting science while introducing them to modern and classical physiological techniques. The physiology laboratory uses a goal-oriented approach, with students working cooperatively in small groups to answer basic biological questions. The student teams work to develop skills associated with experimental design, data analysis, written and oral communication, science literacy, and critical thinking. The laboratory curriculum is a research-based model that offers the advantage of students asking open-ended questions by use of a variety of techniques. For the students and instructor alike, this presents an exciting and challenging approach for learning physiology and basic biological principles. Another advantage of this laboratory model is that it is flexible and adaptable; the central theme can be any that the instructor chooses, and the goals and techniques developed are based on student and instructor needs and interests. Students who have completed this model at Loyola College in Maryland have become equipped with the skills essential for any area of the biological sciences and, most importantly, showed elevated excitement and commitment to learning.
Hypothesis testing as a laboratory exercise: a simple analysis of human walking, with a physiological surprise
Authors: Bertram John E. A.
Published: February 2015

This paper describes a laboratory exercise designed to provide students with experience testing a hypothesis by systematically isolating and controlling determinant variables. The study involves an analysis of walking and is performed by the students on a subject from within their lab group. The study requires use of a motorized treadmill, tape measure, stop watch, metronome, personal cassette player, and calculator. The exercise is designed to include factors that the students are familiar with, so they can focus on the isolation of variables without being confused about the process they are investigating. However, the exercise will not turn out as the students anticipate, meaning they will be forced to reevaluate the assumptions that formed the basis of their original hypothesis. This exercise is designed for a college-level course in exercise science, physiology, or biology but could easily be managed by a high school honors class with appropriate guidance.
Submitting illuminations for review
Authors: Richardson Daniel
Published: February 2015

As educators, we are continually designing new methods and procedures to enhance learning. During this process, good ideas are frequently generated and tested, but the extent of such activities may not be adequate for a full manuscript. Nonetheless, the ideas may be quite beneficial in improving the teaching and learning of physiology. Illuminations is a column designed to facilitate the sharing of these ideas (illuminations). The format of submissions is quite simple: a succinct description of about one or two double-spaced pages (less title and authorship) of something you have used for the classroom, teaching, lab, conference room, etc. You may include one or two simple figures or references. Submit ideas for inclusion in Illuminations directly to the Associate Editor in charge, Stephen DiCarlo ( dicarlo@med.wayne.edu ).
An intensive hands-on course designed to teach molecular biology techniques to physiology graduate students
Authors: Weston Andrea D. , Stasko Sasha , Kidder Gerald M.
Published: February 2015

To address a growing need to make research trainees in physiology comfortable with the tools of molecular biology, we have developed a laboratory-intensive course designed for graduate students. This course is offered to a small group of students over a three-week period and is organized such that comprehensive background lectures are coupled with extensive hands-on experience. The course is divided into seven modules, each organized by a faculty member who has particular expertise in the area covered by that module. The modules focus on basic methods such as cDNA subcloning, sequencing, gene transfer, polymerase chain reaction, and protein and RNA expression analysis. Each module begins with a lecture that introduces the technique in detail by providing a historical perspective, describing both the uses and limitations of that technique, and comparing the method with others that yield similar information. Most of the lectures are followed by a laboratory session during which students follow protocols that were carefully designed to avoid pitfalls. Throughout these laboratory sessions, students are given an appreciation of the importance of proper technique and accuracy. Communication among the students, faculty, and the assistant coordinator is focused on when and why each procedure would be used, the importance of each step in the procedure, and approaches to troubleshooting. The course ends with an exam that is designed to test the students’ general understanding of each module and their ability to apply the various techniques to physiological questions.
A simple water-filled plethysmograph for measurement of limb blood flow in humans
Authors: Raine Neil M. , Sneddon Jennifer C.
Published: February 2015

Fundamental principles underpinning the study of cardiovascular physiology can be emphasized by measuring blood flow. Plethysmography is an appropriate, noninvasive technique to use but may not be available to some institutions. Therefore, for measurement of blood flow in human limbs, we developed a simple water-filled plethysmograph that may be built with minimal technical support. The device is formed from a plastic cylinder and houses a latex sleeve sealed at either end by means of circular flanges and rubber O-ring seals. Limb volume changes are transcribed using an air-filled piston recorder. This instrument proves to be sensitive and accurately determines limb volume changes over time. Utilizing an appropriate venous occlusion protocol, predicted vascular responses to postural challenge and physical exercise may be followed. In response to a questionnaire, a majority of students ( n = 33) agreed that performing blood flow measurements succeeded in relating theory to practice, improved technical and observational skills, and made the learning experience real. This modified plethysmograph proves to be a valuable teaching tool in human physiology classes.
IGF-I attenuates diabetes-induced cardiac contractile dysfunction in ventricular myocytes
Authors: Norby Faye L. , Wold Loren E. , Duan Jinhong , Hintz Kadon K. , Ren Jun
Published: February 2015

Diabetic cardiomyopathy is characterized by impaired ventricular contraction and altered function of insulin-like growth factor I (IGF-I), a key factor for cardiac growth and function. Endogenous IGF-I has been shown to alleviate diabetic cardiomyopathy. This study was designed to evaluate exogenous IGF-I treatment on the development of diabetic cardiomyopathy. Adult rats were divided into four groups: control, control + IGF-I, diabetic, and diabetic + IGF-I. Streptozotocin (STZ; 55 mg/kg) was used to induce experimental diabetes immediately followed by a 7-wk IGF-I (3 mg · kg−1 · day−1 ip) treatment. Mechanical properties were assessed in ventricular myocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (±dL/d t). Intracellular Ca2+ transients were evaluated as Ca2+-induced Ca2+ release and Ca2+ clearing constant. Levels of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and glucose transporter (GLUT4) were assessed by Western blot. STZ caused significant weight loss and elevated blood glucose, demonstrating the diabetic status. The diabetic state is associated with reduced serum IGF-I levels, which were restored by IGF-I treatment. Diabetic myocytes showed reduced PS and ±dL/d t as well as prolonged TPS, TR90, and intracellular Ca2+ clearing compared with control. IGF-I treatment prevented the diabetes-induced abnormalities in PS, ±dL/d t, TR90, and Ca2+ clearing but not TPS. The levels of SERCA and GLUT4, but not PLB, were significantly reduced in diabetic hearts compared with controls. IGF-I treatment restored the diabetes-induced decline in SERCA, whereas it had no effect on GLUT4 and PLB levels. These results suggest that exogenous IGF-I treatment may ameliorate contractile disturbances in cardiomyocytes from diabetic animals and could provide therapeutic potential in the treatment of diabetic cardiomyopathy.
Changes in fatty acid transport and transporters are related to the severity of insulin deficiency
Authors: Luiken Joost J. F. P. , Arumugam Yoga , Bell Rhonda C. , Calles-Escandon Jorge , Tandon Narendra N. , Glatz Jan F. C. , Bonen Arend
Published: February 2015

We have examined the effects of streptozotocin (STZ)-induced diabetes (moderate and severe) on fatty acid transport and fatty acid transporter (FAT/CD36) and plasma membrane-bound fatty acid binding protein (FABPpm) expression, at the mRNA and protein level, as well as their plasmalemmal localization. These studies have shown that, with STZ-induced diabetes, 1) fatty acid transport across the plasma membrane is increased in heart, skeletal muscle, and adipose tissue and is reduced in liver; 2) changes in fatty acid transport are generally not associated with changes in fatty acid transporter mRNAs, except in the heart; 3) increases in fatty acid transport in heart and skeletal muscle occurred with concomitant increases in plasma membrane FAT/CD36, whereas in contrast, the increase and decrease in fatty acid transport in adipose tissue and liver, respectively, were accompanied by concomitant increments and reductions in plasma membrane FABPpm; and finally, 4) the increases in plasma membrane transporters (FAT/CD36 in heart and skeletal muscle; FABPpm in adipose tissue) were attributable to their increased expression, whereas in liver, the reduced plasma membrane FABPpm appeared to be due to its relocation within the cell in the face of slightly increased expression. Taken together, STZ-induced changes in fatty acid uptake demonstrate a complex and tissue-specific pattern, involving different fatty acid transporters in different tissues, in combination with different underlying mechanisms to alter their surface abundance.
Cardiac gene expression profile and lipid accumulation in response to starvation
Authors: Suzuki Jinya , Shen Wen-Jun , Nelson Brett D. , Selwood Simon P. , Murphy Greer M. , Kanefara Hideo , Takahashi Sadao , Oida Koji , Miyamori Isamu , Kraemer Fredric B.
Published: February 2015

Starvation induces many biochemical and histological changes in the heart; however, the molecular events underlying these changes have not been fully elucidated. To explore the molecular response of the heart to starvation, microarray analysis was performed together with biochemical and histological investigations. Serum free fatty acids increased twofold in both 16- and 48-h-fasted mice, and cardiac triglyceride content increased threefold and sixfold in 16- and 48-h-fasted mice, respectively. Electron microscopy showed numerous lipid droplets in hearts of 48-h-fasted mice, whereas fewer numbers of droplets were seen in hearts from 16-h-fasted mice. Expression of 11,000 cardiac genes was screened by microarrays. More than 50 and 150 known genes were detected by differential expression analysis after 16- and 48-h-fasts, respectively. Genes for fatty acid oxidation and gluconeogenesis were increased, and genes for glycolysis were decreased. Many other genes for metabolism, signaling/cell cycle, cytoskeleton, and tissue antigens were affected by fasting. These data provide a broad perspective of the molecular events occurring physiologically in the heart in response to starvation.
The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases β-cell mass in diabetic mice
Authors: Rolin Bidda , Larsen Marianne O. , Gotfredsen Carsten F. , Deacon Carolyn F. , Carr Richard D. , Wilken Michael , Knudsen Lotte Bjerre
Published: February 2015

NN2211 is a long-acting, metabolically stable glucagon-like peptide-1 (GLP-1) derivative designed for once daily administration in humans. NN2211 dose dependently reduced the glycemic levels in ob/ob mice, with antihyperglycemic activity still evident 24 h postdose. Apart from an initial reduction in food intake, there were no significant differences between NN2211 and vehicle treatment, and body weight was not affected. Histological examination revealed that β-cell proliferation and mass were not increased significantly in ob/ob mice with NN2211, although there was a strong tendency for increased proliferation. In db/db mice, exendin-4 and NN2211 decreased blood glucose compared with vehicle, but NN2211 had a longer duration of action. Food intake was lowered only on day 1 with both compounds, and body weight was unaffected. β-Cell proliferation rate and mass were significantly increased with NN2211, but with exendin-4, only the β-cell proliferation rate was significantly increased. In conclusion, NN2211 reduced blood glucose after acute and chronic treatment in ob/ob and db/db mice and was associated with increased β-cell mass and proliferation in db/db mice. NN2211 is currently in phase 2 clinical development.
Correlation between GABA release from rat islet β-cells and their metabolic state
Authors: Winnock Frederic , Ling Zhidong , De Proft Rene , Dejonghe Sandra , Schuit Frans , Gorus Frans , Pipeleers Daniel
Published: February 2015

Pancreatic β-cells express glutamate decarboxylase (GAD), which is responsible for the production and release of γ-aminobutyric acid (GABA). Over a 24-h culture period, total GABA release by purified rat β-cells is eightfold higher than the cellular GABA content and can thus be used as an index of cellular GAD activity. GABA release is 40% reduced by glucose (58 pmol/103cells at 10 mM glucose vs. 94 pmol at 3 mM glucose, P < 0.05). This suppressive effect of glucose was not observed when glucose metabolism was blocked by mannoheptulose or 2,4-dinitrophenol; it was amplified when ATP-dependent β-cell activities were inhibited by addition of diazoxide, verapamil, or cycloheximide or by reduction of extracellular calcium levels; it was counteracted when β-cell functions were activated by nonmetabolized agents, such as glibenclamide, IBMX, glucagon, or glucacon-like peptide-1 (GLP-1), which are known to stimulate calcium-dependent activities, such as hormone release and calcium-dependent ATPases. These observations suggest that GABA release from β-cells varies with the balance between ATP-producing and ATP-consuming activities in the cells. Less GABA is released in conditions of elevated glucose metabolism, and hence ATP production, but this effect is counteracted by ATP-dependent activities. The notion that increased cytoplasmic ATP levels can suppress GAD activity in β-cells, and hence GABA production and release, is compatible with previous findings on ATP suppression of brain GAD activity.
Myocellular triacylglycerol breakdown in females but not in males during exercise
Authors: Steffensen Charlotte H. , Roepstorff Carsten , Madsen Marianne , Kiens Bente
Published: February 2015

The resting content and use of myocellular triacylglycerol (MCTG) during 90 min of submaximal exercise [60% of peak oxygen uptake (V˙o 2 peak)] were studied in 21 eumenorrheic female and 21 male subjects at different training levels [untrained (UT), moderately trained (MT), and endurance trained (END)]. Males and females were matched according to theirV˙o 2 peak expressed relative to lean body mass, physical activity level, and training history. All subjects ingested the same controlled diet for 8 days, and all females were tested in the midfollicular phase of the menstrual cycle. Resting MCTG, measured with the muscle biopsy technique, averaged 48.4 ± 4.2, 48.5 ± 8.4, and 52.2 ± 5.8 mmol/kg dry wt in UT, MT, and END females, respectively, and 34.1 ± 4.9, 31.6 ± 3.3, and 38.4 ± 3.0 mmol/kg dry wt in UT, MT, and END males, respectively ( P < 0.001, females vs. males in all groups). Exercise decreased MCTG content in the female subjects by an average of 25%, regardless of training status, whereas in the male groups MCTG content was unaffected by exercise. The arterial plasma insulin concentration was higher ( P < 0.05) and the arterial plasma epinephrine concentration was lower ( P < 0.05) in the females than in the males at rest and during exercise. MCTG use was correlated to the resting concentration of MCTG ( P < 0.001). We conclude that resting content and use of MCTG during exercise are related to gender and furthermore are independent of training status.
Isolation and characterization of human thyroid endothelial cells
Authors: Patel Vimal A. , Logan Ann , Watkinson John C. , Uz-Zaman Saad , Sheppard Michael C. , Ramsden James D. , Eggo Margaret C.
Published: February 2015

From collagenase digests of human thyroid, endothelial cells were separated from follicular cells by their greater adherence to gelatin-coated plates. Endothelial cells were further purified using fluorescence-activated cell sorting, selecting for cells expressing factor VIII-related antigen. Isolated cells were negative for thyroglobulin and calcitonin when examined by immunostaining. The receptor for the angiopoietins, Tie-2, was expressed by the cells, and expression was increased by agents that elevate cAMP. Nitric oxide synthase (NOS) 3, the endothelial form of NOS, was expressed by the cells and similarly regulated. Cells responded strongly to the mitogen fibroblast growth factor (FGF)-2 in growth assays but only weakly to vascular endothelial growth factor (VEGF). VEGF was, however, able to stimulate nitric oxide release from the cells consistent with their endothelial origin. The FGF receptor (FGFR1) was full length (120 kDa) and immunolocalized to the cytosol and nucleus. Thyrotropin (TSH) did not regulate FGFR1, but its expression was increased by VEGF. Thrombospondin, a product of follicular cells, was a growth inhibitor, but neither TSH nor 3,5,3′-triiodothyronine had direct mitogenic effects. Thyroid follicular cell conditioned medium contained plasminogen activator activity and stimulated the growth of the endothelial cells, but when treated with plasminogen to produce the endothelial-specific inhibitor, angiostatin, growth was inhibited. Human thyroid endothelial cell cultures will be invaluable in determining the cross talk between endothelial and follicular cells during goitrogenesis.
In vivo rat assay: bone remodeling and steroid effects on juvenile bone by pQCT quantification in 7 days
Authors: McHugh Nansie A. , Vercesi Haydee M. , Egan Robert W. , Hey John A.
Published: February 2015

Anesthetized Sprague-Dawley weanling rats were scanned for bone mineral density (BMD) values after 7 days of treatment to determine whether resorption/growth at the proximal tibia can be quantified by peripheral quantitative computed tomography scanning techniques. Because the weanling rat is in a rapid growth stage, all groups showed significant increases in change from baseline values of BMD. Bisphosphonate treatment produced significant dose-related changes in BMD with average increases of 195 and 241% (10 and 20 μg/kg) vs. 86% in control rats. We further characterized this model to determine effects of steroids on growing bone. Graded doses of glucocorticoid (3.5, 7.0, 10.5, 14.0, 28.0, and 42.0 mg · kg−1· wk−1) caused no significant differences in trabecular BMD in 7 days between control and treated rats. Significant decreases in growth (weights) and increases in cortical bone area were observed, indicating that this model may be useful in comparing effects of nonsteroid, anti-inflammatory alternatives on juvenile bone. Although the relevance of this model to adult disease remains to be elucidated, it also provides a tool for mechanistic evaluation of therapeutic modalities or efficacy assessment for dose selection for longerterm models.
Effect of enteral vs. parenteral glucose delivery on initial splanchnic glucose uptake in nondiabetic humans
Authors: Vella Adrian , Shah Pankaj , Basu Rita , Basu Ananda , Camilleri Michael , Schwenk W. Frederick , Rizza Robert A.
Published: February 2015

To determine if enteral delivery of glucose influences splanchnic glucose metabolism, 10 subjects were studied when glucose was either infused into the duodenum at a rate of 22 μmol · kg−1 · min−1 and supplemental glucose given intravenously or when all glucose was infused intravenously while saline was infused intraduodenally. Hormone secretion was inhibited with somatostatin, and glucose (∼8.5 mmol/l) and insulin (∼450 pmol/l) were maintained at constant but elevated levels. Intravenously infused [6,6-2H2]glucose was used to trace the systemic appearance of intraduodenally infused [3-3H]glucose, whereas UDP-glucose flux (an index of hepatic glycogen synthesis) was measured using the acetaminophen glucuronide method. Despite differences in the route of glucose delivery, glucose production (3.5 ± 1.0 vs. 3.3 ± 1.0 μmol · kg−1 · min−1) and glucose disappearance (78.9 ± 5.7 vs. 85.0 ± 7.2 μmol · kg−1 · min−1) were comparable on intraduodenal and intravenous study days. Initial splanchnic glucose extraction (17.5 ± 4.4 vs. 14.5 ± 2.9%) and hepatic UDP-glucose flux (9.0 ± 2.0 vs. 10.3 ± 1.5 μmol · kg−1 · min−1) also did not differ on the intraduodenal and intravenous study days. These data argue against the existence of an “enteric” factor that directly (i.e., independently of circulating hormone concentrations) enhances splanchnic glucose uptake or hepatic glycogen synthesis in nondiabetic humans.
β-Adrenoceptors mediate inhibition of lipolysis in adipocytes of tilapia (Oreochromis mossambicus)
Authors: Vianen Gerjanne J. , Obels Peter P. , van den Thillart Guido E. E. J. M. , Zaagsma Johan
Published: February 2015

The regulation of triglyceride mobilization by catecholamines was investigated in the teleost fish Oreochromis mossambicus (tilapia) in vivo and in vitro. In vitro experiments were carried out with adipocytes that were isolated for the first time from fish adipose tissue. For the in vivo experiments, cannulated tilapia were exposed to stepwise decreasing oxygen levels (20, 10, and 5% air saturation; 3.9, 1.9, and 1.0 kPa Po2, respectively), each level being maintained for 2 h. Blood samples were taken at timed intervals and analyzed for plasma lactate, glucose, free fatty acids, epinephrine, norepinephrine, and cortisol. Hypoxia exposure did not change plasma epinephrine levels. In contrast, the plasma norepinephrine concentration markedly increased at all hypoxia levels. Over the same period, plasma free fatty acid levels showed a significant continuous decrease, suggesting that norepinephrine is responsible for the reduced plasma free fatty acid concentration, presumably through inhibition of lipolysis in adipose tissue. To elucidate the mechanism, adipocytes were isolated from mesenteric adipose tissue of tilapia and incubated with 1) norepinephrine, 2) norepinephrine + phentolamine (α1,α2-antagonist), 3) isoproterenol (nonselective β-agonist), 4) isoproterenol + timolol (β1,β2-antagonist), 5) norepinephrine + timolol, and 6) BRL-35135A (β3-agonist). The results demonstrate for the first time that norepinephrine and isoproterenol suppress lipolysis in isolated adipocytes of tilapia. The effect of norepinephrine is not mediated through α2-adrenoceptors but, like isoproterenol, via β-adrenoceptors. Furthermore, this study provides strong indications that β3-adrenoceptors are involved.