bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonization of a host tree by herbivorous insects under a changing climate
Authors: Heimonen Kaisa , Valtonen Anu , Kontunen‐Soppela Sari , Keski‐Saari Sarita , Rousi Matti , Oksanen Elina , Roininen Heikki
Published: December 2014

Climate warming has been predicted to increase the abundance of herbivorous insects. Together with concurrent poleward shifts in many insect species this may increase herbivore pressure on plants. However, the manner in which plants at higher latitudes become colonized by herbivorous insects in the future is unknown. We established a translocation experiment using 26 micropropagated silver birchBetula pendulagenotypes from six populations originating from 60°N to 67°N, to study the susceptibility of the translocated birches to local herbivores. The birches were planted at three different latitudes in Finland (60°N, 62°N and 67°N). We studied the effect of source population and latitudinal translocation on herbivore density, species richness, and community composition among the genotypes growing in the same environmental conditions in two years; 2011 and 2012. The source population explained the variation in the herbivore density only in 2012, whereas latitudinal translocation did not affect herbivore density. Variation in species richness was not explained by the source population or by the latitudinal translocation. At two of the study sites, the similarity of the herbivore communities among the populations decreased with increasing latitudinal distance of the source populations, possibly because birch populations that grow geographically closer to each other are genetically more similar, and therefore support a more similar composition of the arthropod community. All birch genotypes were colonized by local herbivores, suggesting that as herbivores shift their ranges polewards, they are able to colonize novel host‐plant genotypes. This enables compositional changes in insect communities on their host plants in the future, which in turn, might affect total herbivory and eventually, plant growth.
Childhood body mass index and wheezing disorders: a systematic review and meta‐analysis
Authors: Mebrahtu Teumzghi F. , Feltbower Richard G. , Greenwood Darren C. , Parslow Roger C.
Published: December 2014

Background

It has been claimed that overweight/obesity, childhood asthma and wheezing disorders are associated, although the results of observational studies have remained inconsistent. We conducted a systematic review and meta‐analysis to investigate this.

Methods

An online search of published papers linking childhood asthma and wheezing with overweight/obesity up to May 2014 using EMBASE and MEDLINE medical research databases was carried out. Summary odds ratios (OR) were estimated using random‐effects models. Subgroup meta‐analyses were performed to assess the robustness of risk associations and between‐study heterogeneity.

Results

A total of 38 studies comprising 1,411,335 participants were included in our meta‐analysis. The summary ORs of underweight (<5th percentile), overweight (>85th to <95th percentile) and obesity (≥95th percentile) were 0.85 (95% CI: 0.75 to 0.97; p = 0.02), 1.23 (95% CI: 1.17 to 1.29; p < 0.001) and 1.46 (95% CI: 1.36 to 1.57, p < 0.001), respectively. Heterogeneity was significant and substantial in all three weight categories, and not accounted for by pre‐defined study characteristics.

Conclusion

Our results suggest that underweight is associated with a reduced risk of childhood asthma, and overweight and obesity are associated with an increased risk of childhood asthma. Although our findings assert that overweight/obesity and childhood asthma are associated, the causal pathway and temporal aspects of this relationship remain unanswered and deserve further epidemiological investigation.
How membranes organize during seed germination: three patterns of dynamic lipid remodelling define chilling resistance and affect plastid biogenesis
Authors: YU XIAOMEI , LI AIHUA , LI WEIQI
Published: December 2014

Imbibitional chilling injury during germination causes agricultural losses, but this can be overcome by osmopriming. It remains unknown how membranes reorganize during germination. Herein, we comparatively profiled changes of membrane lipids during imbibition under normal and chilling temperatures in chilling‐tolerant and ‐sensitive soybean seeds. We found three patterns of dynamic lipid remodelling during the three phases of germination. Pattern 1 involved a gradual increase in plastidic lipids during phases I and II, with an abrupt increase during phase III. This abrupt increase was associated with initiation of photosynthesis. Pattern 3 involved phosphatidic acid (PA) first decreasing, then increasing, and finally decreasing to a low level. Patterns 1 and 3 were interrupted in chilling‐sensitive seeds under low temperature, which lead a block in plastid biogenesis and accumulation of harmful PA, respectively. However, they were rescued and returned to their status under normal temperature after polyethylene glycol osmopriming. We specifically inhibited phospholipase D (PLD)‐mediated PA formation in chilling‐sensitive seeds of soybean, cucumber, and pea, and found their germination under low temperature was significantly improved. These results indicate that membranes undergo specific and functional reorganization of lipid composition during germination and demonstrate that PLD‐mediated PA causes imibibitional chilling injury.
Who Knows Best? Education, Partisanship, and Contested Facts
Authors: Joslyn Mark R. , Haider‐Markel Donald P.
Published: December 2014

An alert, informed electorate is considered vital to a robust democracy, and the main path to that electorate includes formal education. The educated citizen is politically attentive, knowledgeable, and participatory, and the uneducated citizen is not. However, this fact conceals a less favorable effect of education. Educated citizens possess the cognitive skills to reject facts inconsistent with prior dispositions. And educated citizens are among the most invested partisans. Thus education is indispensable for an ideal democratic citizen, but that same education can create a resistant, insular democratic participant. We examine this duality across several prominent empirical cases where political facts are in dispute and employ goal‐oriented information processing theory to generate hypotheses. In each case, we find that the most educated partisans are furthest apart in their factual understanding. Our primary concern resides with the inability of education to overcome powerful partisan motives; education intensifies those motives.
Critical Perspectives on Digital Health Technologies
Authors: Lupton Deborah
Published: December 2014

Discussions of digital health technologies in the popular media and the medical and public health academic literature frequently comment on how these technologies might offer new or improved ways of delivering health care, conducting health promotion activities and monitoring public health. Following the presentation of an overview of the range of digital health technologies that are currently in use, I review the work of researchers in the field of critical digital health studies who have addressed their broader social, cultural and political dimensions. The discussion focuses on four major topics: health and medical websites and platforms; telemedicine and telehealth; the politics of digital health; and digitised embodiment. I end with identifying some important directions for future research in critical digital health studies.
Slight Expectations: Making Sense of the “Me Me Me” Generation
Authors: Silva Jennifer M.
Published: December 2014

Current scholarship on the transition to adulthood focuses on the declining importance of role transitions, such as school completion or marriage, in subjective definitions of adulthood. Recent research finds that in place of traditional markers, young adults emphasize individualistic or psychological attributes as indicators of achieving adulthood. Some scholars and popular writers have interpreted this shift toward personal markers of growth as a sign of narcissism, self‐absorption, and lack of a collective sense of responsibility. Drawing on 100 interviews with working‐class young men and women, I argue that these characterizations of young adults fail to take into account the larger cultural and social context of declining job security, rising inequality, and falling institutional trust. By situating young adults' individualistic, self‐focused accounts of adulthood within the framework of declining loyalty in work, distrust in institutions, and diminishing social support, I demonstrate that working‐class Millennials' use of individualistic criteria of adulthood can be better understood as a strategy for coming to terms with the impossibility of traditional sources of meaning and self‐worth such as work or family.
Internet and the Political Public Sphere
Authors: Rasmussen Terje
Published: December 2014

The article addresses the main theory of the political public sphere generally, and the role of the Internet and Internet‐based media in the theory specifically. It first reviews briefly the initial social research on the Internet in the 1990s concerning political participation. After a presentation of Jürgen Habermas' theory of the contemporary public sphere, it proceeds to discuss the main problems concerning the Internet as a platform or infrastructure for public debate: segmentation and concentration. It argues that a general conclusion is that the public sphere differentiates and become more complex. A key task for future research, it argues, is to investigate the complex connections between Internet publics and mass media publics.
Social Disputes over GMOs: An Overview
Authors: Motta Renata
Published: December 2014

This review provides an overview of social research on genetically modified crops (GM crops), also known as genetically modified organisms (GMOs). Academic inquiry on the social disputes over the future of agriculture biotechnology has multiplied since the mid‐1990s, when the first seeds were approved for market commercialization. This essay identifies and describes five prominent analytical approaches to explain public controversies over GMOs: the political economy of food and agriculture, social studies on science, democracy theory, research on corporations and hegemony, and social movement and peasant studies. This overview concludes by arguing that these different strains, although each privileging one analytical dimension and one level of analysis, converge in (i) the definition of the relevant explanatory factors, (ii) in the identification of the various levels of analysis – global, transnational, national and local – involved in the issue and (iii) in the prognostic that social disputes over GMOs are likely to remain a topic of public and scholar interest in the near future.
Social Movement Theory and the “Modern Day Tea Party”
Authors: Pullum Amanda
Published: December 2014

The rise of the Tea Party movement took many political observers by surprise, but social movement theory can help us to understand how the Tea Party began. Frustration with the federal government's plans for economic recovery, combined with opposition to President Obama's election, morphed into nationwide protests and a vocal presence in the 2010 midterm elections. This paper uses the Tea Party as an example to illustrate social movement life cycles, explaining relevant theories, their application to the movement in each phase of its development, and areas in which the Tea Party challenges current literature on social movements. Social movement theory is discussed as a tool that is constantly being honed as new research increases our understanding of how movements develop and function.
Cerebral autoregulation index at high altitude assessed by thigh‐cuff and transfer function analysis techniques
Authors: Subudhi Andrew W. , Grajzel Katalin , Langolf Robert J. , Roach Robert C. , Panerai Ronney B. , Davis John E.
Published: December 2014

New Findings

What is the central question of this study?

Whether cerebral autoregulation (CA) is impaired at high altitude and associated with acute mountain sickness remains controversial. We sought to compare two of the most common methods to assess dynamic CA in subjects who ascended to 3424 m and acclimatized.

What is the main finding and its importance?

We found that CA was reduced at 3424 m when assessed by the classic thigh‐cuff inflation–deflation technique, but not when evaluated by transfer function analysis. These findings suggest that the cerebral vasculature of healthy individuals may become less able to buffer a large, abrupt drop in arterial blood pressure, while still maintaining the ability to regulate slow rhythmical oscillations, during periods of moderate hypoxaemia.

The occurrence and implications of changes in cerebral autoregulation (CA) at high altitude are controversial and confounded by differences in methods used to assess CA. To compare two of the most common methods of dynamic CA assessment, we studied 11 young, healthy sea‐level residents (six females and five males; 20.5 ± 2.3 years old) as they ascended to 3424 m and acclimatized over 13 days. A common autoregulation index (ARI) was calculated from the following: (i) transfer function analysis (TFA ARI) of resting oscillations in arterial blood pressure (ABP; finger plethysmography) and middle cerebral artery blood velocity (MCAv; transcranial Doppler); and (ii) MCAv responses following large, abrupt reductions in ABP using the classic thigh‐cuff technique (Cuff ARI). Symptoms of acute mountain sickness (AMS) were monitored using the Lake Louise AMS Questionnaire. Cuff ARI scores decreased (P = 0.021) as subjects ascended from low (4.7 ± 1.5) to high altitude (3.2 ± 1.6) and did not change after 13 days of acclimatization (2.9 ± 1.3). The TFA ARI scores were not affected by ascent or acclimatization to 3424 m. Neither Cuff nor TFA ARI scores were correlated with AMS symptoms. These findings suggest that the cerebral vasculature of healthy individuals may become less able to buffer large step changes in ABP, while still maintaining the ability to regulate slow rhythmical oscillations, during periods of moderate hypoxaemia. Given the inherent differences in the autoregulatory stimulus between methods, multiple assessment techniques may be needed to clarify the implications of changes in cerebrovascular regulation at high altitude.
Refinement of analgesia following thoracotomy and experimental myocardial infarction using the Mouse Grimace Scale
Authors: Faller Kiterie M. E. , McAndrew Debra J. , Schneider Jurgen E. , Lygate Craig A.
Published: December 2014

New Findings

What is the central question of this study?

There is an ethical imperative to optimize analgesia protocols for laboratory animals, but this is impeded by our inability to recognize pain reliably. We examined whether the Mouse Grimace Scale (MGS) provides benefits over a standard welfare scoring system for identifying a low level of pain in the frequently used murine surgical model of myocardial infarction.

What is the main finding and its importance?

Low‐level pain, responsive to analgesia, was detected by MGS but not standard methods. In this model, most of the pain is attributable to the thoracotomy, excepted in mice with very large infarcts. This approach represents a model for assessing postsurgical analgesia in rodents.

The Mouse Grimace Scale (MGS) was developed for assessing pain severity, but the general applicability to complex postsurgical pain has not been established. We sought to determine whether the MGS provides benefits over and above a standard welfare scoring system for identifying pain in mice following experimental myocardial infarction. Female C57BL/6J mice (n = 60), anaesthetized with isoflurane, were subjected to thoracotomy with ligation of a coronary artery or sham procedure. A single s.c. dose of buprenorphine (1.1 mg kg−1) was given at the time of surgery and pain assessed at 24 h by MGS and a procedure‐specific welfare scoring system. In some animals, a second dose of 0.6 mg kg−1 buprenorphine was given and pain assessment repeated after 30 min. The MGS was scored from multiple photographs by two independent blinded observers with good correlation (r = 0.98). Using the average MGS score of both observers, we identified a subset of mice with low scores that were not considered to be in pain by the welfare scoring system or by single observer MGS. These mice showed a significant improvement with additional analgesia, suggesting that this low‐level pain is real. Pain attributable to the myocardial injury, as opposed to thoracotomy, persisted at 24 h only in mice with large infarcts >40%. In conclusion, the use of a multi‐observer, post hoc version of the MGS is a sensitive tool to assess the efficacy of postsurgical analgesic protocols. Following surgical induction of myocardial infarction, we identified a significant proportion of mice that were in low‐level pain at 24 h that were not identified by other assessment methods.
Sleep deprivation alters thyroid hormone economy in rats
Authors: Rodrigues Nayana Coutinho , da Cruz Natália Santos , de Paula Nascimento Cristine , da Conceição Rodrigo Rodrigues , da Silva Alba Cenélia Matos , Olivares Emerson Lopes , Marassi Michelle Porto
Published: December 2014

New Findings

What is the central question of this study?

The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic–pituitary–thyroid axis and thyroid hormone metabolism in sleep‐deprived and sleep‐restricted rats.

What is the main finding and its importance?

Central hypothyroidism and high thyroxine (T4) to 3,5,3′‐triiodothyronine (T3) activation in brown adipose tissue were observed following sleep deprivation. Sleep‐restricted rats exhibited normal thyroid‐stimulating hormone and T4 concentrations despite increased circulating T3. Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation.

Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic–pituitary–thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200–250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3′‐triiodothyronine (T3), thyroxine (T4) and thyroid‐stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50–100%) in all sleep‐deprived and sleep‐restricted rats; rebound restored this parameter in only the PSD24R group. The serum TSH and T4 concentrations decreased, whereas T3 increased in both the PSD24 and PSD96 groups compared with control animals (P < 0.05). Only PSD24R and PSD96R normalized T4 and thyroid‐stimulating hormone concentrations, respectively, independently of the higher circulating T3 concentrations (∼20–30%) noted in all groups compared with control animals (P < 0.05). Brown adipose tissue D2 activity increased in the PSD 24 and 96 h groups (∼10 times), and PSD24R was more effective than PSD96R at restoring basal brown adipose tissue D2 activity. Our data suggest that thyroid hormone metabolism adapts to sleep deprivation‐induced hypothalamic–pituitary–thyroid alterations and increases T4 to T3 activation peripherally, thereby increasing circulating T3 in rats.
Exogenous interleukin‐10 attenuates hyperoxia‐induced acute lung injury in mice
Authors: Li Huai‐Dong , Zhang Qing‐Xiang , Mao Zhi , Xu Xing‐Jie , Li Nai‐Yi , Zhang Hui
Published: December 2014

New Findings

What is the central question of this study?

It is not known whether treatment with interleukin‐10 (IL‐10) attenuates hyperoxia‐induced acute lung injury in mice.

What is the main finding and its importance?

Our results showed that exogenous IL‐10 treatment alleviated hyperoxia‐induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases.

Lung injury caused by breathing air enriched with oxygen continues to be a major problem in clinical medicine. Here, we investigated the therapeutic role of interleukin‐10 (IL‐10) in hyperoxia‐induced acute lung injury in mice. In the first experiment, mice were exposed to room air or 95% O2 and treated with IL‐10 simultaneously. In the second experiment, wild‐type mice and IL‐10−/− mice were exposed to room air or 95% O2. Exogenous IL‐10 treatment attenuated hyperoxia‐induced acute lung injury, evidenced by a reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, cell numbers and protein content in bronchoalveolar lavage fluid and cell death. Interleukin‐10 treatment markedly prolonged the survival of mice during oxygen exposure. Interleukin‐10 treatment reduced the activity of myeloperoxidase and mRNA levels of interleukin‐6, tumour necrosis factor‐α and macrophage inflammatory protein 2, suppressed nuclear factor‐κB activation and decreased inducible nitric oxide synthnase expression and nitric oxide formation in lungs of mice exposed to hyperoxia. Interleukin‐10 treatment suppressed activities of matrix metalloproteinase 2 and matrix metalloproteinase 9 and reduced lung permeability in mice during oxygen exposure. Furthermore, absence of IL‐10 aggravated hyperoxia‐induced acute lung injury and reduced the duration of survival of mice during oxygen exposure, which was attenuated by treatment with IL‐10. In conclusion, our results show that exogenous IL‐10 treatment alleviates hyperoxia‐induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. This suggests that IL‐10 treatment may be a promising therapeutic strategy to reduce lung injury in patients exposed to hyperoxia.
Quantifying inter‐species differences in contractile function through biophysical modelling
Authors: Tøndel Kristin , Land Sander , Niederer Steven A. , Smith Nicolas P.
Published: December 2014

Key points

To facilitate translation of data from animal models into clinical applications, it is important to analyse and quantify the differences and relevance of specific physiological mechanisms between species.

We propose a novel approach for the quantification of inter‐species differences in terms of biophysical model parameters and apply this to elucidate the differences in cardiac contraction mechanisms between mouse, rat and human.

Our results indicate that the parameters related to the sensitivity and cooperativity of calcium binding to troponin C and the activation and relaxation rates of tropomyosin/crossbridge binding kinetics differ most significantly between mouse, rat and human.

Our results predict crossbridge binding to be slowest in human and fastest in mouse.

Animal models and measurements are frequently used to guide and evaluate clinical interventions. In this context, knowledge of inter‐species differences in physiology is crucial for understanding the limitations and relevance of animal experimental assays for informing clinical applications. Extensive effort has been put into studying the structure and function of cardiac contractile proteins and how differences in these translate into the functional properties of muscles. However, integrating this knowledge into a quantitative description, formalising and highlighting inter‐species differences both in the kinetics and in the regulation of physiological mechanisms, remains challenging. In this study we propose and apply a novel approach for the quantification of inter‐species differences between mouse, rat and human. Assuming conservation of the fundamental physiological mechanisms underpinning contraction, biophysically based computational models are fitted to simulate experimentally recorded phenotypes from multiple species. The phenotypic differences between species are then succinctly quantified as differences in the biophysical model parameter values. This provides the potential of quantitatively establishing the human relevance of both animal‐based experimental and computational models for application in a clinical context. Our results indicate that the parameters related to the sensitivity and cooperativity of calcium binding to troponin C and the activation and relaxation rates of tropomyosin/crossbridge binding kinetics differ most significantly between mouse, rat and human, while for example the reference tension, as expected, shows only minor differences between the species. Hence, while confirming expected inter‐species differences in calcium sensitivity due to large differences in the observed calcium transients, our results also indicate more unexpected differences in the cooperativity mechanism. Specifically, the decrease in the unbinding rate of calcium to troponin C with increasing active tension was much lower for mouse than for rat and human. Our results also predicted crossbridge binding to be slowest in human and fastest in mouse.
Disrupted hippocampal sharp‐wave ripple‐associated spike dynamics in a transgenic mouse model of dementia
Authors: Witton Jonathan , Staniaszek Lydia E. , Bartsch Ullrich , Randall Andrew D. , Jones Matthew W. , Brown Jonathan T.
Published: December 2014

Key points

High frequency (100–250 Hz) neuronal oscillations in the hippocampus, known as sharp‐wave ripples (SWRs), synchronise the firing behaviour of groups of neurons and play a key role in memory consolidation.

Learning and memory are severely compromised in dementias such as Alzheimer's disease; however, the effects of dementia‐related pathology on SWRs are unknown.

The frequency and temporal structure of SWRs was disrupted in a transgenic mouse model of tauopathy (one of the major hallmarks of several dementias).

Excitatory pyramidal neurons were more likely to fire action potentials in a phase‐locked manner during SWRs in the mouse model of tauopathy; conversely, inhibitory interneurons were less likely to fire phase‐locked spikes during SWRs.

These findings indicate there is reduced inhibitory control of hippocampal network events and point to a novel mechanism which may underlie the cognitive impairments in this model of dementia.

Neurons within the CA1 region of the hippocampus are co‐activated during high frequency (100–250 Hz) sharp‐wave ripple (SWR) activity in a manner that probably drives synaptic plasticity and promotes memory consolidation. In this study we have used a transgenic mouse model of dementia (rTg4510 mice), which overexpresses a mutant form of tau protein, to examine the effects of tauopathy on hippocampal SWRs and associated neuronal firing. Tetrodes were used to record simultaneous extracellular action potentials and local field potentials from the dorsal CA1 pyramidal cell layer of 7‐ to 8‐month‐old wild‐type and rTg4510 mice at rest in their home cage. At this age point these mice exhibit neurofibrillary tangles, neurodegeneration and cognitive deficits. Epochs of sleep or quiet restfulness were characterised by minimal locomotor activity and a low theta/delta ratio in the local field potential power spectrum. SWRs detected off‐line were significantly lower in amplitude and had an altered temporal structure in rTg4510 mice. Nevertheless, the average frequency profile and duration of the SWRs were relatively unaltered. Putative interneurons displayed significantly less temporal and phase locking to SWRs in rTg4510 mice, whilst putative pyramidal neurons showed increased temporal and phase locking to SWRs. These findings indicate there is reduced inhibitory control of hippocampal network events and point to a novel mechanism which may contribute to impairments in memory consolidation in this model of dementia.
A new window into the molecular physiology of membrane proteins
Authors: Landreh Michael , Robinson Carol V.
Published: December 2014

Integral membrane proteins comprise ∼25% of the human proteome. Yet, our understanding of their molecular physiology is still in its infancy. This can be attributed to two factors: the experimental challenges that arise from the difficult chemical nature of membrane proteins, and the unclear relationship between their activity and their native environment. New approaches are therefore required to address these challenges. Recent developments in mass spectrometry have shown that it is possible to study membrane proteins in a solvent‐free environment and provide detailed insights into complex interactions, ligand binding and folding processes. Interestingly, not only detergent micelles but also lipid bilayer nanodiscs or bicelles can serve as a means for the gentle desolvation of membrane proteins in the gas phase. In this manner, as well as by direct addition of lipids, it is possible to study the effects of different membrane components on the structure and function of the protein components allowing us to add functional data to the least accessible part of the proteome.
Essential amino acid transporter Lat4 (Slc43a2) is required for mouse development
Authors: Guetg Adriano , Mariotta Luca , Bock Lukas , Herzog Brigitte , Fingerhut Ralph , Camargo Simone M. R. , Verrey François
Published: December 2014

Key points

Lat4 (Slc43a2) transports branched‐chain amino acids, phenylalanine and methionine, and is expressed in kidney tubule and small intestine epithelial cells.

Using a new knockout model as a negative control, it is shown that Lat4 is expressed at the basolateral side of small intestine enterocytes and kidney epithelial cells of the proximal tubule, thick ascending limb and distal convoluted tubule.

In the Xenopus oocyte expression system, Lat4 is shown to function as a uniporter with symmetric intracellular and extracellular apparent affinities for phenylalanine.

Mice lacking Lat4 display a slight intrauterine growth restriction, postnatal malnutrition and early death, presumably as a result of defective amino acid (re)absorption.

These results demonstrate the crucial role that the uniporter Lat4 plays for amino acid transport across cellular barriers and mouse development.

Amino acid (AA) uniporter Lat4 (Slc43a2) mediates facilitated diffusion of branched‐chain AAs, methionine and phenylalanine, although its physiological role and subcellular localization are not known. We report that Slc43a2 knockout mice were born at expected Mendelian frequency but displayed an ∼10% intrauterine growth retardation and low amniotic fluid AAs, suggesting defective transplacental transport. Postnatal growth was strongly reduced, with premature death occurring within 9 days such that further investigations were made within 3 days of birth. Lat4 immunofluorescence showed a strong basolateral signal in the small intestine, kidney proximal tubule and thick ascending limb epithelial cells of wild‐type but not Slc43a2 null littermates and no signal in liver and skeletal muscle. Experiments using Xenopus laevis oocytes demonstrated that Lat4 functioned as a symmetrical low affinity uniporter with a K0.5 of ∼5 mm for both in‐ and efflux. Plasma AA concentration was decreased in Slc43a2 null pups, in particular that of non‐essential AAs alanine, serine, histidine and proline. Together with an increased level of plasma long chain acylcarnitines and a strong alteration of liver gene expression, this indicates malnutrition. Attempts to rescue pups by decreasing the litter size or by nutrients injected i.p. did not succeed. Radioactively labelled leucine but not lysine given per os accumulated in the small intestine of Slc43a2null pups, suggesting the defective transcellular transport of Lat4 substrates. In summary, Lat4 is a symmetrical uniporter for neutral essential AAs localizing at the basolateral side of (re)absorbing epithelia and is necessary for early nutrition and development.
Proton transfer unlocks inactivation in cyclic nucleotide‐gated A1 channels
Authors: Marchesi Arin , Arcangeletti Manuel , Mazzolini Monica , Torre Vincent
Published: December 2014

Key points

Desensitization and inactivation provide a form of short‐term memory controlling the firing patterns of excitable cells and adaptation in sensory systems.

Unlike many of their cousin K+ channels, cyclic nucleotide‐gated (CNG) channels are thought not to desensitize or inactivate.

Here we report that CNG channels do inactivate and that inactivation is controlled by extracellular protons.

Titration of a glutamate residue within the selectivity filter destabilizes the pore architecture, which collapses towards a non‐conductive, inactivated state in a process reminiscent of the usual C‐type inactivation observed in many K+ channels.

These results indicate that inactivation in CNG channels represents a regulatory mechanism that has been neglected thus far, with possible implications in several physiological processes ranging from signal transduction to growth cone navigation.

Ion channels control ionic fluxes across biological membranes by residing in any of three functionally distinct states: deactivated (closed), activated (open) or inactivated (closed). Unlike many of their cousin K+ channels, cyclic nucleotide‐gated (CNG) channels do not desensitize or inactivate. Using patch recording techniques, we show that when extracellular pH (pHo) is decreased from 7.4 to 6 or lower, wild‐type CNGA1 channels inactivate in a voltage‐dependent manner. pHo titration experiments show that at pHo < 7 the I–V relationships are outwardly rectifying and that inactivation is coupled to current rectification. Single‐channel recordings indicate that a fast mechanism of proton blockage underlines current rectification while inactivation arises from conformational changes downstream from protonation. Furthermore, mutagenesis and ionic substitution experiments highlight the role of the selectivity filter in current decline, suggesting analogies with the C‐type inactivation observed in K+ channels. Analysis with Markovian models indicates that the non‐independent binding of two protons within the transmembrane electrical field explains both the voltage‐dependent blockage and the inactivation. Low pH, by inhibiting the CNGA1 channels in a state‐dependent manner, may represent an unrecognized endogenous signal regulating CNG physiological functions in diverse tissues.
Study of Insertion Force and Deformation for Suturing With Precurved NiTi Guidewire
Authors: Wang Yancheng , Chen Roland K. , Tai Bruce L. , Xu Kai , Shih Albert J.
Published: December 2014

This research presents an experimental study evaluating stomach suturing using a precurved nickel–titanium (NiTi) guidewire for an endoscopic minimally invasive obesity treatment. Precise path planning is critical for accurate and effective suturing. A position measurement system utilizing a hand-held magnetic sensor was used to measure the shape of a precurved guidewire and to determine the radius of curvature before and after suturing. Ex vivo stomach suturing experiments using four different guidewire tip designs varying the radius of curvature and bevel angles were conducted. The changes in radius of curvature and suturing force during suturing were measured. A model was developed to predict the guidewire radius of curvature based on the measured suturing force. Results show that a small bevel angle and a large radius of curvature reduce the suturing force and the combination of small bevel angle and small radius of curvature can maintain the shape of guidewire for accurate suturing.
A General Method for the Dynamic Modeling of Ball Bearing–Rotor Systems
Authors: Li Yamin , Cao Hongrui , Niu Linkai , Jin Xiaoliang
Published: December 2014

A general dynamic modeling method of ball bearing–rotor systems is proposed. Gupta's bearing model is applied to predict the rigid body motion of the system considering the three-dimensional motions of each part (i.e., outer ring, inner ring, ball, and rotor), lubrication tractions, and bearing clearances. The finite element method is used to model the elastic deformation of the rotor. The dynamic model of the whole ball bearing–rotor system is proposed by integrating the rigid body motion and the elastic vibration of the rotor. An experiment is conducted on a test rig of rotor supported by two angular contact ball bearings. The simulation results are compared with the measured vibration responses to validate the proposed model. Good agreements show the accuracy of the proposed model and its ability to predict the dynamic behavior of ball bearing–rotor systems. Based on the proposed model, vibration responses of a two bearing–rotor system under different bearing clearances were simulated and their characteristics were discussed. The proposed model may provide guidance for structural optimization, fault diagnosis, dynamic balancing, and other applications.
Liquid Metal Based Stretchable Radiation-Shielding Film
Authors: Deng Yueguang , Liu Jing
Published: December 2014

We reported a stretchable and flexible radiation-shielding film based on room-temperature liquid metal. Conceptual experiments showed that the liquid metal based printing technology can achieve an ultrathin flexible radiation-shielding film with a thickness of 0.3 mm. Moreover, the yield strength and ultimate strength of the liquid metal film appear much better than those of a conventional lead-particle-containing radiation-shielding material. In order to evaluate the radiation-shielding performance of the liquid metal material, X-ray radiation experiments to compare the liquid metal film and conventional lead-particle-based shielding material under different stretching conditions were performed. The results indicate that the liquid metal shielding film could achieve a certain radiation-shielding performance. Furthermore, because of the screen-printing properties of liquid metal, a low-cost X-ray mask method using a liquid metal selective radiation-shielding film was also studied, which could serve as a highly efficient and practical method for the medical X-ray shielding applications or semiconductor lithography industry.
A Review on Compliant Joints and Rigid-Body Constant Velocity Universal Joints Toward the Design of Compliant Homokinetic Couplings
Authors: Farhadi Machekposhti D. , Tolou N. , Herder J. L.
Published: December 2014

This paper presents for the first time a literature survey toward the design of compliant homokinetic couplings. The rigid-linkage-based constant velocity universal joints (CV joints) available from literature were studied, classified, their graph representations were presented, and their mechanical efficiencies compared. Similarly, literature is reviewed for different kinds of compliant joints suitable to replace instead of rigid-body joints in rigid-body CV joints. The compliant joints are compared based on analytical data. To provide a common basis for comparison, consistent flexure scales and material selection are used. It was found that existing compliant universal joints are nonconstant in velocity and designed based on rigid-body Hooke's universal joint. It was also discovered that no compliant equivalent exists for cylindrical, planar, spherical fork, and spherical parallelogram quadrilateral joints. We have demonstrated these compliant joints can be designed by combining existing compliant joints. The universal joints found in this survey are rigid-body non-CV joints, rigid-body CV joints, or compliant non-CV joints. A compliant homokinetic coupling is expected to combine the advantages of compliant mechanisms and constant velocity couplings for many applications where maintenance or cleanliness is important, for instance in medical devices and precision instruments.
Redundancy Allocation for Reliability Design of Engineering Systems With Failure Interactions
Authors: Wang Jing , Li Mian
Published: December 2014

Optimal allocation of redundancies is one of the most important ways of improving system reliability. Generally, in these redundancy allocation problems, it is assumed that failures of components are independent. However, under this assumption failure rates can be underestimated since failure interactions can significantly affect the performance of systems. In this paper, we first propose an analytical model to describe the failure rates with failure interactions, followed by a modified analytical hierarchy process (MAHP) which is proposed to solve redundancy allocation problems with failure interactions. MAHP decomposes the system into several blocks and deals with those downsized blocks before diving deep into the most appropriate component for redundancy allocation. Being simple and flexible, MAHP provides an intuitive way to design a complex system and the explicit function of the entire system reliability is not required in the proposed approach. More importantly, with the help of the proposed analytical failure interaction model, MAHP can capture the effect of failure interactions. Results from case studies clearly demonstrate the applicability of the analytical model for failure interactions and MAHP for reliability design.
Study on Minimum Wall Thickness Requirement for Seismic Buckling of Reactor Vessel Based on System Based Code Concept
Authors: Takaya Shigeru , Watanabe Daigo , Yokoi Shinobu , Kamishima Yoshio , Kurisaka Kenichi , Asayama Tai
Published: December 2014

The minimum wall thickness required to prevent seismic buckling of a reactor vessel (RV) in a fast reactor is derived using the system based code (SBC) concept. One of the key features of SBC concept is margin optimization; to implement this concept, the reliability design method is employed, and the target reliability for seismic buckling of the RV is derived from nuclear plant safety goals. Input data for reliability evaluation, such as distribution type, mean value, and standard deviation of random variables, are also prepared. Seismic hazard is considered to evaluate uncertainty of seismic load. Minimum wall thickness required to achieve the target reliability is evaluated, and is found to be less than that determined from a conventional deterministic design method. Furthermore, the influence of each random variable on the evaluation is investigated, and it is found that the seismic load has a significant impact.
Evaluating Compliant Hinge Geometries for Origami-Inspired Mechanisms
Authors: Delimont Isaac L. , Magleby Spencer P. , Howell Larry L.
Published: December 2014

Origami-inspired design is an emerging field capable of producing compact and efficient designs. Compliant hinges are proposed as a way to replicate the folding motion of paper when using nonpaper materials. Compliant hinges function as surrogate folds and can be defined as localized reduction of stiffness. The purpose of this paper is to organize and evaluate selected surrogate folds for use in compliant mechanisms. These surrogate folds are characterized based on the desired motion as well as motions typically considered parasitic. Additionally, the surrogate folds' ability to rotate through large deflections and their stability of center of rotation are evaluated. Existing surrogate folds are reviewed and closed-form solutions presented. A diagram intended as a straightforward design guide is presented. Areas for potential development in the surrogate fold design space are noted.
Time-Dependent Reliability Analysis Using the Total Probability Theorem
Authors: Mourelatos Zissimos P. , Majcher Monica , Pandey Vijitashwa , Baseski Igor
Published: December 2014

A new reliability analysis method is proposed for time-dependent problems with explicit in time limit-state functions of input random variables and input random processes using the total probability theorem and the concept of composite limit state. The input random processes are assumed Gaussian. They are expressed in terms of standard normal variables using a spectral decomposition method. The total probability theorem is employed to calculate the time-dependent probability of failure using time-dependent conditional probabilities which are computed accurately and efficiently in the standard normal space using the first-order reliability method (FORM) and a composite limit state of linear instantaneous limit states. If the dimensionality of the total probability theorem integral is small, we can easily calculate it using Gauss quadrature numerical integration. Otherwise, simple Monte Carlo simulation (MCS) or adaptive importance sampling are used based on a Kriging metamodel of the conditional probabilities. An example from the literature on the design of a hydrokinetic turbine blade under time-dependent river flow load demonstrates all developments.
Development of a Reverse Genetic System for Infectious Salmon Anemia Virus: Rescue of Recombinant Fluorescent Virus by Using Salmon Internal Transcribed Spacer Region 1 as a Novel Promoter
Authors: Toro-Ascuy Daniela , Tambley Carolina , Beltran Carolina , Mascayano Carolina , Sandoval Nicolas , Olivares Eduardo , Medina Rafael A. , Spencer Eugenio , Cortez-San Martín Marcelo
Published: December 2014

Infectious salmon anemia (ISA) is a serious disease of marine-farmed Atlantic salmon (
Salmo salar
) caused by ISA virus (ISAV), belonging to the genus
Isavirus
, family
Orthomyxoviridae
. There is an urgent need to understand the virulence factors and pathogenic mechanisms of ISAV and to develop new vaccine approaches. Using a recombinant molecular biology approach, we report the development of a plasmid-based reverse genetic system for ISAV, which includes the use of a novel fish promoter, the Atlantic salmon internal transcribed spacer region 1 (ITS-1). Salmon cells cotransfected with pSS-URG-based vectors expressing the eight viral RNA segments and four cytomegalovirus (CMV)-based vectors that express the four proteins of the ISAV ribonucleoprotein complex allowed the generation of infectious recombinant ISAV (rISAV). We generated three recombinant viruses, wild-type rISAV
901_09
and rISAVr
S6-NotI-HPR
containing a NotI restriction site and rISAV
S6/EGFP-HPR
harboring the open reading frame of enhanced green fluorescent protein (EGFP), both within the highly polymorphic region (HPR) of segment 6. All rescued viruses showed replication activity and cytopathic effect in Atlantic salmon kidney-infected cells. The fluorescent recombinant viruses also showed a characteristic cytopathic effect in salmon cells, and the viruses replicated to a titer of 6.5 × 10
5
PFU/ml, similar to that of the wild-type virus. This novel reverse genetics system offers a powerful tool to study the molecular biology of ISAV and to develop a new generation of ISAV vaccines to prevent and mitigate ISAV infection, which has had a profound effect on the salmon industry.