bluuebunny/crossref_metadata_2025 huggingface dataset:
Painful neuropathies: the emerging role of sodium channelopathies
Authors: Brouwer Brigitte A. , Merkies Ingemar S. J. , Gerrits Monique M. , Waxman Stephen G. , Hoeijmakers Janneke G. J. , Faber Catharina G.
Published: September 2014

Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδand C) fibers. Voltage‐gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway whereNaV1.7,NaV1.8, andNaV1.9 sodium channels (encoded bySCN9A,SCN10A, andSCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain‐of‐functionSCN9Amutations. Recent studies have expanded this spectrum with gain‐of‐functionSCN9Amutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked toSCN10Amutations. Patch‐clamp studies have shown that the effect ofSCN9Amutations is dependent upon the cell‐type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length‐dependent, as demonstrated in patients with initial facial and scalp pain symptoms withSCN9Amutations showing hyperexcitability in both trigeminal ganglion andDRGneurons. There is some evidence suggesting that gain‐of‐functionSCN9Amutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies.
Upper canine inclination influences the aesthetics of a smile
Authors: Bothung C. , Fischer K. , Schiffer H. , Springer I. , Wolfart S.
Published: September 2014

This current study investigated which angle of canine inclination (angle between canine tooth axis (CA‐line) and the line between the lateral canthus and the ipsilateral labial angle (EM‐line)) is perceived to be most attractive in a smile. The second objective was to determine whether laymen and dental experts share the same opinion. A Q‐sort assessment was performed with 48 posed smile photographs to obtain two models of neutral facial attractiveness. Two sets of images (1 male model set, 1 female model set), each containing seven images with incrementally altered canine and posterior teeth inclinations, were generated. The images were ranked for attractiveness by three groups (61 laymen, 59 orthodontists, 60 dentists). The images with 0° inclination, that is CA‐line (maxillary canine axis) parallel to EM‐line (the line formed by the lateral canthus and the ipsilateral corner of the mouth) (male model set: 54·4%; female model set: 38·9%), or −5° (inward) inclination (male model set: 20%; female model set: 29·4%) were perceived to be most attractive within each set. Images showing inward canine inclinations were regarded to be more attractive than those with outward inclinations. Dental experts and laymen were in accordance with the aesthetics. Smiles were perceived to be most attractive when the upper canine tooth axis was parallel to the EM‐line. In reconstructive or orthodontic therapy, it is thus important to incline canines more inwardly than outwardly.
Factors associated with temporomandibular disorders pain in adolescents
Authors: Fernandes G. , van Selms M. K. A. , Gonçalves D. A. G. , Lobbezoo F. , Camparis C. M.
Published: September 2014

To gain a better understanding of temporomandibular disorders (TMD) pain in adolescents, it is important to study the factors associated with its presence. Therefore, the aim of this study was to investigate potential predictors for TMD pain in adolescents, thereby including a diversity of factors from the biopsychosocial model to determine the strongest predictors. The sample of this cross‐sectional study consisted of 1094 adolescents. The presence of TMD pain was assessed using the RDC/TMD, Axis I. Apart from demographical characteristics, the roles of parafunctional habits, psychosocial aspects, menarche and other bodily pain complaints were evaluated. Single and multiple logistic regression models were used to identify associations between the predictor variables and TMD pain. Painful TMD had a prevalence of 25·5%. Logistic regression analyses showed that TMD pain was associated with sleep bruxism (OR = 1·8 95% CI = 1·34–2·34), awake bruxism (OR = 2·1 95% CI = 1·56–2·83), other parafunctional habits (OR = 2·2 95% CI = 1·17–4·08) and bodily pain complaints (OR = 5·0 95% CI = 3·48–7·28). Parafunctional habits and other bodily pain complaints may play an important role in the presence of TMD pain in adolescents. Of course, it remains unclear whether the observed associations between the investigated factors and the adolescent's TMD pain have a true causal linkage.
Biosynthesis of antifungal and antibacterial polyketides by Burkholderia gladioli in coculture with Rhizopus microsporus
Authors: Ross Claudia , Opel Viktoria , Scherlach Kirstin , Hertweck Christian
Published: September 2014

Fungi–bacteria interactions can impact the course of fungal infection and biotechnological use. The mucoralean fungus Rhizopus microsporus, traditionally used in food fermentations (tempe and sufu), is frequently accompanied by Burkholderia gladioli pv. cocovenenans. When producing tempe bongkrek, the bacterial contamination can lead to lethal food‐related intoxications caused by the respiratory toxin bongkrekic acid. To unveil the metabolic potential of the fungus‐associated bacterium, we sequenced its genome, assigned secondary metabolite biosynthesis gene clusters and monitored the metabolic profile under various growth conditions. In addition to the bongkrekic acid biosynthesis gene cluster we found gene clusters coding for the biosynthesis of toxoflavin and a complex polyketide. The orphan polyketide synthase gene cluster was activated under conditions that emulate tempe production, which enabled isolation and structure elucidation of four members of the enacyloxin family of antibiotics, out of which one is new. Moreover, we found that the fungus positively influences the growth of the bacteria and dramatically increases bongkrekic acid production in stationary culture, which inhibits the growth of the fungus. These results showcase the context‐dependent formation of antifungal and antibacterial agents at the fungal‐bacterial interface, which may also serve as a model for scenarios observed in mixed infections.
Evolution of pollination niches in a generalist plant clade
Authors: Gómez José María , Perfectti Francisco , Abdelaziz Mohamed , Lorite Juan , Muñoz‐Pajares Antonio Jesús , Valverde Javier
Published: September 2014

It is widely assumed that floral diversification occurs by adaptive shifts between pollination niches. In contrast to specialized flowers, identifying pollination niches of generalist flowers is a challenge. Consequently, how generalist pollination niches evolve is largely unknown.

We apply tools from network theory and comparative methods to investigate the evolution of pollination niches among generalist species belonging to the genusErysimum. These species have similar flowers.

We found that the studied species may be grouped in several multidimensional niches separated not by a shift of pollinators, but instead by quantitative variation in the relative abundance of pollinator functional groups. These pollination niches did not vary in generalization degree; we did not find any evolutionary trend toward specialization within the studied clade. Furthermore, the evolution of pollination niche fitted to a Brownian motion model without phylogenetic signal, and was characterized by frequent events of niche convergences and divergences.

We presume that the evolution ofErysimumpollination niches has occurred mostly by recurrent shifts between slightly different generalized pollinator assemblages varying spatially as a mosaic and without any change in specialization degree. Most changes in pollination niches do not prompt floral divergence, a reason why adaptation to pollinators is uncommon in generalist plants.
Traits, properties, and performance: how woody plants combine hydraulic and mechanical functions in a cell, tissue, or whole plant
Authors: Lachenbruch Barbara , McCulloh Katherine A.
Published: September 2014

This review presents a framework for evaluating how cells, tissues, organs, and whole plants perform both hydraulic and mechanical functions. The morphological alterations that affect dual functionality are varied: individual cells can have altered morphology; tissues can have altered partitioning to functions or altered cell alignment; and organs and whole plants can differ in their allocation to different tissues, or in the geometric distribution of the tissues they have. A hierarchical model emphasizes that morphological traits influence the hydraulic or mechanical properties; the properties, combined with the plant unit's environment, then influence the performance of that plant unit. As a special case, we discuss the mechanisms by which the proxy property wood density has strong correlations to performance but without direct causality. Traits and properties influence multiple aspects of performance, and there can be mutual compensations such that similar performance occurs. This compensation emphasizes that natural selection acts on, and a plant's viability is determined by, its performance, rather than its contributing traits and properties. Continued research on the relationships among traits, and on their effects on multiple aspects of performance, will help us better predict, manage, and select plant material for success under multiple stresses in the future.

ContentsSummary747I.Introduction747II.Studying dual functionality in plants: some conceptual approaches749III.Mechanisms influencing dual functionality at different spatial scales753IV.Conclusions760Acknowledgements760References760
INTERPERSONAL EPISTEMIC ENTITLEMENTS
Authors: Goldberg Sanford C.
Published: September 2014

In this paper I argue that the nature of our epistemic entitlement to rely on certain belief‐forming processes—perception, memory, reasoning, and perhaps others—is not restricted to one's own belief‐forming processes. I argue as well that we can have access to the outputs of others’ processes, in the form of their assertions. These two points support the conclusion that epistemic entitlements are “interpersonal.” I then proceed to argue that this opens the way for a non‐standard version of anti‐reductionism in the epistemology of testimony, and a more “extended” epistemology—one that calls into question the epistemic significance that has traditionally been ascribed to the boundaries separating individual subjects.
NON‐CONCEPTUAL KNOWLEDGE
Authors: Hofmann Frank
Published: September 2014

The paper is an investigation into the prospects of an epistemology of non‐conceptual knowledge. According to the orthodox view, knowledge requires concepts and belief. I present several arguments to the effect that there is non‐conceptual, non‐doxastic knowledge, the obvious candidate for such knowledge being non‐conceptual perception. Non‐conceptual perception seems to be allowed for by cognitive scientists and it exhibits the central role features of knowledge—it plays the knowledge role: it respects an anti‐luck condition, it is an achievement, it enables one to act for a reason, and it provides justification. Furthermore, it makes a straightforward and elegant explanation of (doxastic) perceptual knowledge possible: doxastic perceptual knowledge builds on non‐conceptual perception as non‐conceptual knowledge. Three objections that might naturally arise will be discussed and answered. Thus, the prospects of an epistemology without belief seem to be much better than the orthodoxy wants to have it. We can extend knowledge into the non‐conceptual realm.
NEUROMEDIA, EXTENDED KNOWLEDGE AND UNDERSTANDING
Authors: Lynch Michael Patrick
Published: September 2014

Imagine you had the functions of your smartphone miniaturized to a cellular level and accessible by your neural network. Reflection on this possibility suggests that we should not just concern ourselves with whether our knowledge is extending “out” to our devices; our devices are extending in, and with them, possibly the information that they bring. If so, then the question of whether knowledge is “extended” becomes wrapped up with the question of whether knowing is something we do, or something we can share with, or outsource to, instruments. And that in turn raises the two questions of this paper: First, to what extent does such technology put pressure on the idea that we might have more than one conception of knowledge (or types of knowledge)? And second, what is the value of states that fit these conceptions (or types) of knowledge?
Single and combined colonization of Sclerotinia sclerotiorum sclerotia by the fungal mycoparasites Coniothyrium minitans and Microsphaeropsis ochracea
Authors: Bitsadze N. , Siebold M. , Koopmann B. , von Tiedemann A.
Published: September 2014

Potential enhancement of mycoparasitic efficacy of Coniothyrium minitans and Microsphaeropsis ochracea through concomitant colonization of Sclerotinia sclerotiorum sclerotia was investigated, following observation that the two mycoparasites did not exhibit any mutual antagonism in dual culture assays. Simultaneous application of both mycoparasites increased sclerotia mortality in a temperature range from 16 to 26°C compared to single application, indicating a predominantly additive interaction. With increasing temperature the efficacy of M. ochracea decreased, but C. minitans was unaffected. Degradation of sclerotia by C. minitans proceeded slightly faster than with M. ochracea. Simultaneous colonization of sclerotia was studied at the histopathological level with mycoparasite strains transformed via Agrobacterium tumefaciens‐mediated transformation (ATMT) with reporter genes encoding for DsRed and GFP. Sclerotia colonization followed by fluorescence microscopy revealed effective penetration of the sclerotial rind, growth and formation of pycnidia in the cortex and medulla by both antagonists, resulting in complete degradation of sclerotia within 25 days after single inoculation. Upon simultaneous inoculation, both antagonists concomitantly colonized the sclerotial tissue and independently formed pycnidia in the sclerotial medulla and on the sclerotial rind, demonstrating their ability to co‐colonize the same host fungus. Although the individual growth of the two mycoparasites in dual inoculations was slightly delayed, the sclerotia degrading effects were additive, suggesting a complementary antagonistic interaction. The combined application of two different species of mycoparasites cooperating on the same host fungus and differing in temperature requirements may be advantageous for making biocontrol applications in the field less sensitive to varying environmental and host conditions.
Metabolic Profile of Broodmares During Late Pregnancy and Early Post‐Partum
Authors: Bazzano M , Giannetto C , Fazio F , Arfuso F , Giudice E , Piccione G
Published: September 2014

Contents

Pregnancy represents a specific physiological status characterized by continuous adjustments that affect maternal metabolism of all nutrients. In the last trimester of pregnancy, mare's nutrient requirements greatly increase and most pregnancy‐associated diseases are likely to occur. Therefore, we aimed to assess the metabolic profile of broodmares focusing on the last 3 months of pregnancy and the early post‐partum. Fifteen pregnant mares (Group A) were monitored from 263 ± 3 days of pregnancy until 21 days after foaling. Seven non‐pregnant mares (Group B) were used as the control group. Blood samples were collected weekly by jugular venipuncture throughout the experimental period, and additional blood samples were collected within 24 ± 12 h of foaling. Obtained sera were analyzed for urea (Ur), creatinine (Cre), total protein (TP), total, direct and indirect bilirubin (tB, dB, iB), triglycerides (TG), total cholesterol (tChol) and β‐hydroxybutyrate (BHB). During pregnancy, Ur (p = 0.015) and dB (p = 0.028) were higher in Group A than Group B. Serum Cre, tB, iB and TG (p < 0.001) decreased after foaling; furthermore, Group A exhibited lower tChol (p < 0.001) and higher BHB (p < 0.001) than Group B during the study. There were significant interactions of time × peripartum on Ur (p = 0.007), Cre (p < 0.001), tB (p = 0.018), TG (p < 0.001) and tChol (p < 0.001). These results can be used in the interpretation of biochemical studies in late gestation mares which develop systemic disease. The improved understanding of the metabolic profile during the peripartum might assist in monitoring the health status of the broodmares to promote foetal growth and well‐being.
Lung function abnormalities in HIV‐infected adults and children
Authors: Calligaro Gregory L. , Gray Diane M.
Published: September 2014

Despite the advent of antiretroviral therapy (ART), the human immunodeficiency virus (HIV) epidemic remains a global health crisis with a high burden of respiratory disease among infected persons. While the early complications of the epidemic were dominated by opportunistic infections, improved survival has led to the emergence of non‐infectious conditions that are associated with chronic respiratory symptoms and pulmonary disability. Obstructive ventilatory defects and reduced diffusing capacity are common findings in adults, and the association between HIV and chronic obstructive pulmonary disease is increasingly recognized. There is synergism between viral factors, opportunistic infections, conventional influences like tobacco smoke and biomass fuel exposure, and potentially, the immunological effects of ART on the development of HIV‐associated chronic obstructive lung disease. Pulmonary function data for HIV‐infected infants and children are scarce, but shows that bronchiectasis and obliterative bronchiolitis with severe airflow limitation are major problems, particularly in the developing world. However, studies from these regions are sorely lacking. There is thus a major unmet need to understand the influences of chronic HIV infection on the lung in both adults and children, and to devise strategies to manage and prevent these diseases in HIV‐infected individuals. It is important for clinicians working with HIV‐infected individuals to have an appreciation of their effects on measurements of lung function.

This review therefore summarizes the lung function abnormalities described in HIV‐positive adults and children, with an emphasis on obstructive lung disease, and examines potential pathogenic links between HIV and the development of chronic pulmonary disability.
Effect of increasing respiratory rate on airway resistance and reactance in COPD patients
Authors: Nakagawa Misa , Hattori Noboru , Haruta Yoshinori , Sugiyama Aya , Iwamoto Hiroshi , Ishikawa Nobuhisa , Fujitaka Kazunori , Murai Hiroshi , Tanaka Junko , Kohno Nobuoki
Published: September 2014

Background and objective

Airway resistance and reactance measured by forced oscillometry have been used to measure the severity of airway obstruction in chronic obstructive pulmonary disease (COPD) patients. The aims of this study were to assess the effects of tachypnoea on airway resistance and reactance and to correlate these with the severity of dyspnoea. We also evaluated the effects of short‐acting β2‐agonist (SABA) on these measurements.

Methods

Airway resistance and reactance were measured with an impulse oscillation system (IOS) in 20 COPD and 10 control participants during resting respiration and metronome‐paced breathing at 20, 30 and 40 tidal breaths/min. The same measurements were made for COPD patients after SABA inhalation. Dyspnoea was evaluated using the modified Medical Research Council (MRC) scale.

Results

In patients with COPD, higher respiratory rates increased expiratory and inspiratory resistance at 5 Hz (R5), the difference in respiratory resistance at 5 Hz and 20 Hz (R5–R20), resonant frequency and decreased expiratory reactance. The decreases in expiratory reactance from 20 to 40 tidal breaths/min were significantly correlated with MRC scores. SABA inhalation significantly reduced the effect of increased respiratory rate on the reactance measurements.

Conclusions

Characteristic changes in IOS measurements, particularly expiratory reactance, induced by increased respiratory rates, were correlated with severity of dyspnoea in COPD patients during their daily lives. IOS and paced breathing may be useful for assessing breathlessness in COPD.
Bayesian Semiparametric Analysis of Semicompeting Risks Data: Investigating Hospital Readmission After a Pancreatic Cancer Diagnosis
Authors: Lee Kyu Ha , Haneuse Sebastien , Schrag Deborah , Dominici Francesca
Published: September 2014

In the USA, the Centers for Medicare and Medicaid Services use 30-day readmission, following hospitalization, as a proxy outcome to monitor quality of care. These efforts generally focus on treatable health conditions, such as pneumonia and heart failure. Expanding quality-of-care systems to monitor conditions for which treatment options are limited or non-existent, such as pancreatic cancer, is challenging because of the non-trivial force of mortality; 30-day mortality for pancreatic cancer is approximately 30%. In the statistical literature, data that arise when the observation of the time to some non-terminal event is subject to some terminal event are referred to as ‘semicompeting risks data’. Given such data, scientific interest may lie in at least one of three areas: estimation or inference for regression parameters, characterization of dependence between the two events and prediction given a covariate profile. Existing statistical methods focus almost exclusively on the first of these; methods are sparse or non-existent, however, when interest lies with understanding dependence and performing prediction. We propose a Bayesian semiparametric regression framework for analysing semicompeting risks data that permits the simultaneous investigation of all three of the aforementioned scientific goals. Characterization of the induced posterior and posterior predictive distributions is achieved via an efficient Metropolis–Hastings–Green algorithm, which has been implemented in an R package. The framework proposed is applied to data on 16051 individuals who were diagnosed with pancreatic cancer between 2005 and 2008, obtained from Medicare part A. We found that increased risk for readmission is associated with a high comorbidity index, a long hospital stay at initial hospitalization, non-white race, being male and discharge to home care.
Making the invisible visible – operating theatre nurses’ perceptions of caring in perioperative practice
Authors: Blomberg Ann‐Catrin , Bisholt Birgitta , Nilsson Jan , Lindwall Lillemor
Published: September 2014

The aim of this study was to describe operating theatre nurses’ (OTNs’) perceptions of caring in perioperative practice. A qualitative descriptive design was performed. Data were collected with interviews were carried out with fifteen strategically selected operating theatre nurses from different operating theatres in the middle of Sweden. A phenomenographic analysis was used to analyse the interviews. The findings show that operating theatre nurses’ perceptions of caring in perioperative practice can be summarised in one main category: To follow the patient all the way. Two descriptive categories emerged: To ensure continuity of patient care and keeping a watchful eye. The operating theatre nurses got to know the patient and as a result became responsible for the patient. They protected the patient's body and preserved patient dignity in perioperative practice. The findings show different aspects of caring in perioperative practice. OTNs wanted to be more involved in patient care and follow the patient throughout the perioperative nursing process. Although OTNs have the ambition to make the care in perioperative practice visible, there is today a medical technical approach which promotes OTNs continuing to offer care in secret.
Instituting Best Practice for Monitoring for Opioid‐Induced Advancing Sedation in Hospitalized Patients
Authors: Jungquist Carla R. , Pasero Chris , Tripoli Nicole M. , Gorodetsky Rachel , Metersky Mark , Polomano Rosemary C.
Published: September 2014

Background

Adverse events related to opioid‐induced unintended advancing sedation and respiratory depression in hospitalized patients are occurring with increased frequency, and these adverse events can have a negative impact on quality and cost outcomes.

Aim

The goal of this paper is to inform nurses on best practices for preventing opioid‐induced advancing sedation and respiratory depression, and to inform nurse leaders on implementation strategies to guide change in policies and practice.

Methods

This paper presents an evidenced‐based systematic approach for organizations to use in implementing strategies to reduce adverse events secondary to opioid‐induced advancing sedation and respiratory depression in the hospitalized adult patient.

Results

An action‐oriented framework was developed based on the authors’ experiences, strategies recommended by the Institute for Healthcare Improvement (IHI), the National Association of Healthcare Quality (NAHQ), and expert consensus‐based best monitoring practices.

Linking Evidence to Action

Nurse executives and nurse managers assume accountability for ensuring that patient care is aligned with the best evidence, practices, and regulatory mandates. The framework presented in this paper can help prevent opioid‐induced advancing sedation and respiratory depression, and assist nurse leaders in implementation strategies to guide policies and practice.
Angiotensin type 1A receptor expression in C1 neurons of the rostral ventrolateral medulla contributes to the development of angiotensin‐dependent hypertension
Authors: Jancovski Nikola , Carter David A. , Connelly Angela A. , Stevens Elyse , Bassi Jaspreet K. , Menuet Clement , Allen Andrew M.
Published: September 2014

New Findings

What is the central question of this study?

This study addresses the mechanism by which deletion of angiotensin II type 1A receptors from catecholaminergic neurons reduces angiotensin‐dependent hypertension, as well as the identity of the cells involved.

What is the main finding and its importance?

Deletion of angiotensin II type 1A receptors from catecholaminergic neurons results in reduced sympathetic nerve activation and fluid and electrolyte retention during angiotensin infusion. The C1 neurons of the rostral ventrolateral medulla are involved in the later phase of the hypertension. We demonstrate that at least two different populations of catecholaminergic neurons are involved in the sympathetic nerve activation required for the full development of angiotensin‐dependent hypertension.

Chronic low‐dose systemic infusion of angiotensin II induces hypertension via activation of the angiotensin II type 1A receptor (AT1AR). Previously, we have demonstrated that expression of the AT1AR on catecholaminergic neurons is necessary for the full development of angiotensin‐dependent hypertension. In the present study, we examined the mechanism by which selective deletion of the AT1AR from these cells affects the development of hypertension. We also tested the hypothesis that AT1ARs expressed by catecholaminergic C1 neurons in the rostral ventrolateral medulla play an important role in angiotensin‐induced hypertension. A Cre‐lox approach was used to delete the AT1AR from all catecholaminergic cells or from C1 neurons selectively. Subcutaneous administration of angiotensin II induced hypertension in all mice, with delayed onset and reduced maximal response in the global AT1AR catecholaminergic knockout mice. The AT1AR catecholaminergic knockout mice had decreased renal fluid and electrolyte retention and urinary noradrenaline excretion. The blood pressure response was reduced only during the second week of angiotensin II infusion in the mice with selective C1 AT1AR deletion, demonstrating that AT1AR expression by C1 neurons plays a moderate role in angiotensin‐induced hypertension. The difference in the time course of development of hypertension between the mice with global AT1AR knockout from catecholaminergic cells and the mice with C1 AT1AR deletion suggests that other catecholaminergic neurons are important.
Periaqueductal grey cyclooxygenase‐dependent facilitation of C‐nociceptive drive and encoding in dorsal horn neurons in the rat
Authors: Leith J. Lianne , Wilson Alex W. , You Hao‐Jun , Lumb Bridget M. , Donaldson Lucy F.
Published: September 2014

Key points

A‐ and C‐nociceptors make different contributions to pain. They signal fast and slow pain, respectively, and C‐nociceptors drive central sensitisation.

Cyclooxygenase‐1 (COX‐1)‐dependent descending facilitation from the periaqueductal grey (PAG) affects C‐nociceptor spinal reflexes, but leaves A‐nociceptor reflexes largely untouched.

We studied the responses of spinal wide dynamic‐range dorsal horn neurons to A‐ and C‐nociceptor stimulation before and after COX‐1 inhibition in the PAG.

Inhibition of COX‐1 descending facilitation disrupted the neuronal encoding of C‐nociceptor information, but left the encoding of A‐nociceptor information untouched.

Inhibition of COX‐1‐dependent descending facilitation increased the activation threshold of wide dynamic range neurons to both A‐ and C‐nociceptor input.

The COX‐dependent descending system from the PAG can therefore control the amount of C‐nociceptor information reaching the CNS (slow, burning, aching, debilitating pain) without affecting the protective A‐nociceptor information (sharp, well‐localised, protective pain).

The experience of pain is strongly affected by descending control systems originating in the brainstem ventrolateral periaqueductal grey (VL‐PAG), which control the spinal processing of nociceptive information. A‐ and C‐fibre nociceptors detect noxious stimulation, and have distinct and independent contributions to both the perception of pain quality (fast and slow pain, respectively) and the development of chronic pain. Evidence suggests a separation in the central processing of information arising from A‐ vs. C‐nociceptors; for example, inhibition of the cyclooxygenase‐1 (COX‐1)–prostaglandin system within the VL‐PAG alters spinal nociceptive reflexes evoked by C‐nociceptor input in vivo via descending pathways, leaving A‐nociceptor‐evoked reflexes largely unaffected. As the spinal neuronal mechanisms underlying these different responses remain unknown, we determined the effect of inhibition of VL‐PAG COX‐1 on dorsal horn wide dynamic‐range neurons evoked by C‐ vs. A‐nociceptor activation. Inhibition of VL‐PAG COX‐1 in anaesthetised rats increased firing thresholds of lamina IV–V wide dynamic‐range dorsal horn neurons in response to both A‐ and C‐nociceptor stimulation. Importantly, wide dynamic‐range dorsal horn neurons continued to faithfully encode A‐nociceptive information, even after VL‐PAG COX‐1 inhibition, whereas the encoding of C‐nociceptor information by wide dynamic‐range spinal neurons was significantly disrupted. Dorsal horn neurons with stronger C‐nociceptor input were affected by COX‐1 inhibition to a greater extent than those with weak C‐fibre input. These data show that the gain and contrast of C‐nociceptive information processed in individual wide dynamic‐range dorsal horn neurons is modulated by prostanergic descending control mechanisms in the VL‐PAG.
Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition
Authors: Yoon Bo‐Eun , Woo Junsung , Chun Ye‐Eun , Chun Heejung , Jo Seonmi , Bae Jin Young , An Heeyoung , Min Joo Ok , Oh Soo‐Jin , Han Kyung‐Seok , Kim Hye Yun , Kim Taekeun , Kim Young Soo , Bae Yong Chul , Lee C. Justin
Published: September 2014

Key points

Here we show that glial gamma aminobutyric acid (GABA) is produced by monoamine oxidase B (MAOB), utilizing a polyamine, putrescine.

The concentration of GABA in Bergmann glial cells is estimated to be around 5–10 mM.

General gene silencing of MAOB resulted in elimination of tonic GABA currents recorded from granule cells in the cerebellum and medium spiny neurons (MSN) in the striatum.

Glial‐specific rescue of MAOB resulted in complete restoration of tonic GABA currents.

Our results identify MAOB as a synthesizing enzyme of glial GABA, which is released to mediate tonic inhibition in the cerebellum and striatum.

GABA is the major inhibitory transmitter in the brain and is released not only from a subset of neurons but also from glia. Although neuronal GABA is well known to be synthesized by glutamic acid decarboxylase (GAD), the source of glial GABA is unknown. After estimating the concentration of GABA in Bergmann glia to be around 5–10 mm by immunogold electron microscopy, we demonstrate that GABA production in glia requires MAOB, a key enzyme in the putrescine degradation pathway. In cultured cerebellar glia, both Ca2+‐induced and tonic GABA release are significantly reduced by both gene silencing of MAOB and the MAOB inhibitor selegiline. In the cerebellum and striatum of adult mice, general gene silencing, knock out of MAOB or selegiline treatment resulted in elimination of tonic GABA currents recorded from granule neurons and medium spiny neurons. Glial‐specific rescue of MAOB resulted in complete rescue of tonic GABA currents. Our results identify MAOB as a key synthesizing enzyme of glial GABA, which is released via bestrophin 1 (Best1) channel to mediate tonic inhibition in the brain.
Development of a Fluidic Actuator for Adaptive Flow Control on a Thick Wind Turbine Airfoil
Authors: Niether Sebastian , Bobusch Bernhard , Marten David , Pechlivanoglou Georgios , Navid Nayeri Christian , Oliver Paschereit Christian
Published: September 2014

Wind turbines are exposed to unsteady incident flow conditions such as gusts or tower interference. These cause a change in the blades' local angle of attack, which often leads to flow separation at the inner rotor sections. Recirculation areas and dynamic stall may occur, which lead to an uneven load distribution along the blade. In this work, a fluidic actuator is developed that reduces flow separation. The functional principle is adapted from a fluidic amplifier. High pressure air fed by an external supply flows into the interaction region of the actuator. Two control ports, oriented perpendicular to the inlet, allow for a steering of the actuation flow. One of the control ports is connected to the suction side, the other to the pressure side of the airfoil. Depending on the pressure difference that varies with the angle of attack, the actuation air is directed into one of four outlet channels. These guide the air to different chordwise exit locations on the airfoil's suction side. The appropriate actuation location adjusts automatically according to the pressure difference between the control ports and therefore incidence. Suction side flow separation is delayed as the boundary layer is enriched with kinetic energy. Experiments were conducted on a DU97-W-300 airfoil at Re = 2.2 × 105. Compared to the baseline, lift variations due to varying angles of attack were reduced by an order of magnitude. A Fast/Aerodyn simulation of a full wind turbine rotor was performed to show the real world load reduction potential. Additionally, system integration is discussed, which includes suggestions on producibility and operational details.
From the Scale Model of the Sky to the Armillary Sphere
Authors: Gangui Alejandro , Casazza Roberto , Paez Carlos
Published: September 2014

It is customary to employ a semi-spherical scale model to describe the apparent path of the Sun across the sky, whether it be its diurnal motion or its variation throughout the year. A flat surface and three bent semi-rigid wires (representing the three solar arcs during solstices and equinoxes) will do the job. On the other hand, since very early times, there have been famous armillary spheres built and employed by the most outstanding astronomers for the description of the celestial movements. In those instruments, many of them now considered true works of art, Earth lies in the center of the cosmos and the observer looks at the whole “from the outside.” Of course, both devices, the scale model of the sky and the armillary sphere, serve to represent the movement of the Sun, and in this paper we propose to show their equivalence by a simple construction. Knowing the basics underlying the operation of the armillary sphere will give us confidence to use it as a teaching resource in school.
A Simple Derivation of Time Dilation and Length Contraction in Special Relativity
Authors: Behroozi Fred
Published: September 2014

Undergraduate physics majors typically begin their study of modern physics with special relativity. It is here that physics students first encounter the counterintuitive concepts of time dilation and length contraction. Unfortunately, the derivations of these results are often cloaked in several layers of analysis that render them rather mysterious and otherworldly for novice students. Here we show how a very simple thought experiment leads directly to a student-friendly derivation of time dilation and length contraction. The only assumption needed is the constancy of the speed of light.
Complete Cycle Experiments Using the Adiabatic Gas Law Apparatus
Authors: Kutzner Mickey D. , Plantak Mateja
Published: September 2014

The ability of our society to make informed energy-usage decisions in the future depends partly on current science and engineering students retaining a deep understanding of the thermodynamics of heat engines. Teacher imaginations and equipment budgets can both be taxed in the effort to engage students in hands-on heat engine activities. The experiments described in this paper, carried out using the Adiabatic Gas Law Apparatus1 (AGLA), quantitatively explore popular complete cycle heat engine processes.
Active Commuting to School in Mexican Adolescents: Evidence From the Mexican National Nutrition and Health Survey
Authors: Jáuregui Alejandra , Medina Catalina , Salvo Deborah , Barquera Simon , Rivera-Dommarco Juan A.
Published: September 2014

Background:

Travel to school offers a convenient way to increase physical activity (PA) levels in youth. We examined the prevalence and correlates of active commuting to school (ACS) in a nationally representative sample of Mexican adolescents. A secondary objective was to explore the association between ACS and BMI status.

Methods:

Using data of adolescents (10–14 years old) from the 2012 Mexican National Health and Nutrition Survey (n = 2952) we ran multivariate regression models to explore the correlates of ACS and to test the association between ACS and BMI z-score or overweight/obesity. Models were adjusted for potential confounders and design effect.

Results:

70.8% of adolescents engaged in ACS (walking: 68.8%, bicycling: 2.0%). ACS was negatively associated with travel time, age, mother’s education level, household motor vehicle ownership, family socioeconomic status, and living in urban areas or the North region of the country (P < .05). Time in ACS was negatively associated with overweight/obesity: Each additional minute of ACS was associated with a 1% decrease in the odds for being overweight or obese (P < .05).

Conclusions:

Potential correlates of ACS that may result in benefits for Mexican adolescents are identified. More studies on this relationship are needed to develop interventions aimed at increasing PA through ACS in Mexico.
Multiple Influenza A (H3N2) Mutations Conferring Resistance to Neuraminidase Inhibitors in a Bone Marrow Transplant Recipient
Authors: Eshaghi Alireza , Shalhoub Sarah , Rosenfeld Paul , Li Aimin , Higgins Rachel R. , Stogios Peter J. , Savchenko Alexei , Bastien Nathalie , Li Yan , Rotstein Coleman , Gubbay Jonathan B.
Published: September 2014

Immunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid deletion at residues 245 to 248 (Δ245-248) accompanied by the E119V substitution occurred, causing resistance to or reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness, and transmission.
Bacillus anthracis GrlA
V96A
Topoisomerase IV, a Quinolone Resistance Mutation That Does Not Affect the Water-Metal Ion Bridge
Authors: Aldred Katie J. , Breland Erin J. , McPherson Sylvia A. , Turnbough Charles L. , Kerns Robert J. , Osheroff Neil
Published: September 2014

The rise in quinolone resistance is threatening the clinical use of this important class of broad-spectrum antibacterials. Quinolones kill bacteria by increasing the level of DNA strand breaks generated by the type II topoisomerases gyrase and topoisomerase IV. Most commonly, resistance is caused by mutations in the serine and acidic amino acid residues that anchor a water-metal ion bridge that facilitates quinolone-enzyme interactions. Although other mutations in gyrase and topoisomerase IV have been reported in quinolone-resistant strains, little is known regarding their contributions to cellular quinolone resistance. To address this issue, we characterized the effects of the V96A mutation in the A subunit of
Bacillus anthracis
topoisomerase IV on quinolone activity. The results indicate that this mutation causes an ∼3-fold decrease in quinolone potency and reduces the stability of covalent topoisomerase IV-cleaved DNA complexes. However, based on metal ion usage, the V96A mutation does not disrupt the function of the water-metal ion bridge. A similar level of resistance to quinazolinediones (which do not use the bridge) was seen. V96A is the first topoisomerase IV mutation distal to the water-metal ion bridge demonstrated to decrease quinolone activity. It also represents the first A subunit mutation reported to cause resistance to quinazolinediones. This cross-resistance suggests that the V96A change has a global effect on the structure of the drug-binding pocket of topoisomerase IV.
Operon for Biosynthesis of Lipstatin, the Beta-Lactone Inhibitor of Human Pancreatic Lipase
Authors: Bai Tingli , Zhang Daozhong , Lin Shuangjun , Long Qingshan , Wang Yemin , Ou Hongyu , Kang Qianjin , Deng Zixin , Liu Wen , Tao Meifeng
Published: September 2014

Lipstatin, isolated from
Streptomyces toxytricini
as a potent and selective inhibitor of human pancreatic lipase, is a precursor for tetrahydrolipstatin (also known as orlistat, Xenical, and Alli), the only FDA-approved antiobesity medication for long-term use. Lipstatin features a 2-hexyl-3,5-dihydroxy-7,10-hexadecadienoic-β-lactone structure with an
N
-formyl-
l
-leucine group attached as an ester to the 5-hydroxy group. It has been suggested that the α-branched 3,5-dihydroxy fatty acid β-lactone moiety of lipstatin in
S. toxytricini
is derived from Claisen condensation between two fatty acid substrates, which are derived from incomplete oxidative degradation of linoleic acid based on feeding experiments. In this study, we identified a six-gene operon (
lst
) that was essential for the biosynthesis of lipstatin by large-deletion, complementation, and single-gene knockout experiments.
lstA
,
lstB
, and
lstC
, which encode two β-ketoacyl–acyl carrier protein synthase III homologues and an acyl coenzyme A (acyl-CoA) synthetase homologue, were indicated to be responsible for the generation of the α-branched 3,5-dihydroxy fatty acid backbone. Subsequently, the nonribosomal peptide synthetase (NRPS) gene
lstE
and the putative formyltransferase gene
lstF
were involved in decoration of the α-branched 3,5-dihydroxy fatty acid chain with an N-formylated leucine residue. Finally, the 3β-hydroxysteroid dehydrogenase-homologous gene
lstD
might be responsible for the reduction of the β-keto group of the biosynthetic intermediate, thereby facilitating the formation of the unique β-lactone ring.
Origin and Effect of Alpha 2.2 Acetobacteraceae in Honey Bee Larvae and Description of Parasaccharibacter apium gen. nov., sp. nov
Authors: Corby-Harris Vanessa , Snyder Lucy A. , Schwan Melissa R. , Maes Patrick , McFrederick Quinn S. , Anderson Kirk E.
Published: September 2014

The honey bee hive environment contains a rich microbial community that differs according to niche.
Acetobacteraceae
Alpha 2.2 (Alpha 2.2) bacteria are present in the food stores, the forager crop, and larvae but at negligible levels in the nurse and forager midgut and hindgut. We first sought to determine the source of Alpha 2.2 in young larvae by assaying the diversity of microbes in nurse crops, hypopharyngeal glands (HGs), and royal jelly (RJ). Amplicon-based pyrosequencing showed that Alpha 2.2 bacteria occupy each of these environments along with a variety of other bacteria, including
Lactobacillus kunkeei
. RJ and the crop contained fewer bacteria than the HGs, suggesting that these tissues are rather selective environments. Phylogenetic analyses showed that honey bee-derived Alpha 2.2 bacteria are specific to bees that “nurse” the hive's developing brood with HG secretions and are distinct from the
Saccharibacter
-type bacteria found in bees that provision their young differently, such as with a pollen ball coated in crop-derived contents.
Acetobacteraceae
can form symbiotic relationships with insects, so we next tested whether Alpha 2.2 increased larval fitness. We cultured 44 Alpha 2.2 strains from young larvae that grouped into nine distinct clades. Three isolates from these nine clades flourished in royal jelly, and one isolate increased larval survival
in vitro
. We conclude that Alpha 2.2 bacteria are not gut bacteria but are prolific in the crop-HG-RJ-larva niche, passed to the developing brood through nurse worker feeding behavior. We propose the name
Parasaccharibacter apium
for this bacterial symbiont of bees in the genus
Apis
.