bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular biology of mammalian amino acid receptors
Authors: Dingledine Raymond , Myers Scott J. , Nicholas Robert A.
Published: January 2018

The amino acid receptor proteins are ubiquitous transducers of most excitatory and inhibitory synaptic transmission in the brain. In July 1987 two reports appeared describing the molecular cloning of a pair of subunits of the GABAA receptor (7) and one subunit of the glycine receptor (13). These papers sparked wide interest and led quickly to the concept of a ligand‐gated receptor‐ion channel superfamily that includes nicotinic acetylcholine receptors as well as certain amino acid receptors. The identification of additional subunits of each receptor followed; with the recent cloning of a kainate receptor subunit (14), only the NMDA receptor remains elusive. Several disciplines have been brought to bear on these receptor clones, including in situ hybridization and functional expression in Xenopus laevis oocytes and mammalian cell lines. In this review we compare cloning strategies that have been used for amino acid receptors and discuss structural similarities among the receptor subunits. Two findings that have arisen from molecular cloning and expression of these receptors receive special attention. First, the molecular heterogeneity of GABAA receptors is larger than expected from pharmacological studies of native receptors. Second, although the native receptors are thought to be heterooligomers, much like the model proposed for the nicotinic receptors, some individual amino acid receptor subunits can form functional receptor channels, presumably in a homomeric configuration. This review focuses, therefore, on what we have learned from cloning efforts about amino acid receptors and what might lie ahead in this field.—Dingledine, R.; Myers, S. J.; Nicholas, R. A. Molecular biology of mammalian amino acid receptors. FASEB J. 4: 2636‐2645, 1990.
Hypoperfusion and Wound Healing: Another Dimension of Wound Assessment
Authors: Smollock Wendy , Montenegro Paul , Czenis Amy , He Yuan
Published: January 2018

OBJECTIVE:

To examine the correlation between mean arterial pressure (MAP) and wound healing indices and describe an analytical process that can be used accurately and prospectively when evaluating all types of skin ulcerations.

METHODS:

A correlational study in a long-term-care facility.

Participants (N = 230) were adults residing in a long-term-care facility with an average age of 77.8 years (range, 35–105).

MAIN OUTCOME MEASURES:

Assessment through both an index of wound healing and wound surface area. Signs of wound healing included a reduction of surface area and surface necrosis and increased granulation or epithelialization.

RESULTS:

Aggregate analyses for all wound locations revealed a positive correlation between the MAP and index of wound healing (r = 0.86, n = 501, P < .0001). A well-defined positive correlation between the MAP and stalled or poor wound healing was noted for all wound locations in this data set when MAP values were 80 mm Hg or less (r = 0.95, n = 141, P < .0001). Further, the data set of truncal wounds and MAP of less than 80 mm Hg yielded a very strong positive correlation. The data indicated that as perfusion decreased, wounds within the sample population declined (r = 0.93, n = 102, P < .0001).

CONCLUSION:

The data suggest that MAP values less than 80 mm Hg can independently result in stalled wound healing or worsened wounds. A predictability of wounds stalling or declining related to the MAP was observed, regardless of topical treatment or standard-of-care interventions. Therefore, the data also suggest that remediating states of low perfusion should take precedence in making treatment decisions.
Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats
Authors: Breuer Thomas , Bleilevens Christian , Rossaint Rolf , Marx Gernot , Gehrenkemper Julian , Dierksen Henning , Delpierre Antoine , Weis Joachim , Gayan-Ramirez Ghislaine , Bruells Christian S.
Published: January 2018

Background

Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients’ mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction.

Methods

Twenty-four rats were separated into three groups (n = 8/group). Two groups were mechanically ventilated during either dexmedetomidine or pentobarbital exposure for 24 h, referred to as interventional groups. A third group of directly euthanized rats served as control. Force generation, fiber dimensions, proteolysis markers, protein oxidation and lipid peroxidation, calcium homeostasis markers, and glucose transporter–4 (Glut-4) translocation were measured in the diaphragm.

Results

Diaphragm force, corrected for cross-sectional area, was significantly decreased in both interventional groups compared to controls and was significantly lower with dexmedetomidine compared to pentobarbital (e.g., 100 Hz: –18%, P < 0.0001). In contrast to pentobarbital, dexmedetomidine did not lead to diaphragmatic atrophy, but it induced more protein oxidation (200% vs. 73% in pentobarbital, P = 0.0015), induced less upregulation of muscle atrophy F-box (149% vs. 374% in pentobarbital, P < 0.001) and impaired Glut-4 translocation (–73%, P < 0.0005). It activated autophagy, the calcium-dependent proteases, and caused lipid peroxidation similarly to pentobarbital.

Conclusions

Twenty-four hours of mechanical ventilation during dexmedetomidine sedation led to a worsening of ventilation-induced diaphragm dysfunction, possibly through impaired Glut-4 translocation. Although dexmedetomidine prevented diaphragmatic fiber atrophy, it did not inhibit oxidative stress and activation of the proteolytic pathways.
Effect of Maternal Body Mass Index on Postpartum Hemorrhage
Authors: Butwick Alexander J. , Abreo Anisha , Bateman Brian T. , Lee Henry C. , El-Sayed Yasser Y. , Stephansson Olof , Flood Pamela
Published: January 2018

Background

It is unclear whether obesity is a risk factor for postpartum hemorrhage. The authors hypothesized that obese women are at greater risk of hemorrhage than women with a normal body mass index.

Methods

The authors conducted a cohort study of women who underwent delivery hospitalization in California between 2008 and 2012. Using multilevel regression, the authors examined the relationships between body mass index with hemorrhage (primary outcome), atonic hemorrhage, and severe hemorrhage (secondary outcomes). Stratified analyses were performed according to delivery mode.

Results

The absolute event rate for hemorrhage was 60,604/2,176,673 (2.8%). In this cohort, 4% of women were underweight, 49.1% of women were normal body mass index, 25.9% of women were overweight, and 12.7%, 5.2%, and 3.1% of women were in obesity class I, II, and III, respectively. Compared to normal body mass index women, the odds of hemorrhage and atonic hemorrhage were modestly increased for overweight women (hemorrhage: adjusted odds ratio [aOR], 1.06; 99% CI, 1.04 to 1.08; atonic hemorrhage: aOR, 1.07; 99% CI, 1.05 to 1.09) and obesity class I (hemorrhage: aOR, 1.08; 99% CI, 1.05 to 1.11; atonic hemorrhage; aOR, 1.11; 99% CI, 1.08 to 1.15). After vaginal delivery, overweight and obese women had up to 19% increased odds of hemorrhage or atonic hemorrhage; whereas, after cesarean delivery, women in any obesity class had up to 14% decreased odds of severe hemorrhage.

Conclusions

The authors’ findings suggest that, at most, maternal obesity has a modest effect on hemorrhage risk. The direction of the association between hemorrhage and body mass index may differ by delivery mode.
Behavioral Health Training in Pediatric Residency Programs: A National Survey of Training Directors
Authors: Shahidullah Jeffrey D. , Kettlewell Paul W. , Palejwala Mohammed H. , Forman Susan G. , Billups Andrew , Anismatta Stephanie L. , Madsen Benjamin
Published: January 2018

Objective:

To identify perceptions of behavioral health (BH) training in pediatric residency programs, the degree of involvement from behavioral health providers (BHPs), and opportunities for and barriers to innovation in training.

Method:

A tailored design methodology was used to target all pediatric residency program directors in the United States (N = 214). Participants were identified from the Electronic Residency Application Service website of the Association of American Medical Colleges and were asked to complete a 22-item item survey on BH training.

Results:

A 69.2% usable response rate (N = 148) was obtained. A total of 62.8% of directors described training in the developmental-behavioral pediatrics (DBP) rotation as optimal; 36% described BH training in the residency program as a whole (i.e., outside the DBP rotation) as optimal. Only 20.3% described “common factors” training as optimal, and the quality of training in this area was positively and significantly related to the quality of BH training in the residency program as a whole (χ2 = 35.05, p < 0.001). The quality of common factors training was significantly higher in programs that had embedded BHPs (i.e., psychologists and social workers) in the continuity clinic than programs that did not (χ2 = 7.65, p = 0.04). Barriers to quality training included instructional content, instructional methods, stakeholder support, and resources.

Conclusion:

Despite substantial improvement in residency training in BH over the last decade, additional improvement is needed. Barriers to continued improvement include training content, training methods, support from faculty and administrator stakeholders, and resource issues. Strategies derived from implementation science have the potential to address these barriers.
High Inflammatory Infiltrate Correlates With Poor Symptomatic Improvement After Surgical Treatment for Superior Limbic Keratoconjunctivitis
Authors: Zoroquiain Pablo , Sanft Debra-Meghan , Esposito Evangelina , Cheema Devinder , Dias Ana Beatriz , Burnier Miguel N.
Published: January 2018

Purpose:

Superior limbic keratoconjunctivitis (SLK) is a chronic and recurrent condition of unknown etiology. It is often managed conservatively, but there is a high rate of success with surgical management for severe or recalcitrant cases. The purpose of this article is to describe and analyze clinicopathological features of patients with SLK who underwent surgical treatment and their association with the clinical outcome.

Methods:

A total of 22 eyes from 18 patients who underwent surgical SLK management were retrospectively analyzed. Clinicopathological data were collected including details of follow-up and patient satisfaction (n = 15). Moreover, 12 cases had specimens available for review of histopathologic findings and COX-2 expression analysis by immunohistochemistry.

Results:

From a clinical perspective, 66.7% of the SLK eyes had nonmechanical factors contributing to SLK, and 66.7% of eyes demonstrated significant symptomatic improvement after surgery. Histopathological analysis of all the lesions showed acanthosis and goblet cell loss. Unexpectedly, in 93% of the eyes, dilated lymphatic vessels were found. Furthermore, a high inflammatory infiltrate correlated with minimal symptomatic improvements (P = 0.013). Moreover, COX-2 expression was higher in patients with SLK than in a normal conjunctiva (P = 0.001).

Conclusions:

In this study, the most common systemic association with SLK was the patient's autoimmune status. Histopathological evaluation revealed that high inflammatory infiltration in the biopsy might be predictive of minimal symptomatic improvement with surgical management. Finally, the higher COX-2 expression in patients with SLK compared with that in individuals with a normal conjunctiva supports the use of anti-COX-2 drugs as a possible therapeutic target.
Effectiveness of CenteringPregnancy on Breastfeeding Initiation Among African Americans
Authors: Robinson Karen , Garnier-Villarreal Mauricio , Hanson Lisa
Published: January 2018

While breastfeeding initiation rates for African American mothers are low, an innovative model of group prenatal care, CenteringPregnancy, holds promise to increase breastfeeding rates. The aim of this systematic review and meta-analysis was to examine the effects of CenteringPregnancy versus individual prenatal care on breastfeeding initiation among African American mothers. Using a systematic approach and PRISMA guidelines, 4 electronic databases were used to search the literature. English-language studies, comparing CenteringPregnancy and individual prenatal care, including African American participants, and specifying breastfeeding initiation as an outcome were screened for inclusion. Study strength and quality were assessed and 7 studies were systematically reviewed and meta-analyzed. Participation in CenteringPregnancy increased the probability of breastfeeding initiation by 53% (95% confidence interval = 29%-81%) (n = 8047). A subgroup analysis of breastfeeding initiation among only African American participants was performed on 4 studies where data were available. Participation in CenteringPregnancy increased the probability of breastfeeding initiation by 71% (95% confidence interval = 27%-131%) (n = 1458) for African American participants. CenteringPregnancy is an effective intervention to increase breastfeeding initiation for participants, especially for African Americans. To close the racial gap in breastfeeding initiation, high-quality research providing specific outcomes for African American participants in CenteringPregnancy are needed.
Association Between Cotinine-verified Smoking Status and Risk of Colorectal Neoplasia
Authors: Kim Nam Hee , Jung Yoon Suk , Yang Hyo-Joon , Park Soo-Kyung , Park Jung Ho , Park Dong Il , Sohn Chong Il
Published: January 2018

Goals:

We evaluated the association of urinary cotinine-verified smoking status with the risk of colorectal neoplasia (CRN).

Background:

Many studies have reported the association between the risk of CRN and smoking status, based on self-reported questionnaires. Although self-reported smoking status may be inaccurate, to our knowledge, no study has yet assessed the association between objective biomarkers of tobacco exposure and the risk of CRN.

Study:

A cross-sectional study was conducted on 96,806 asymptomatic examinees who underwent colonoscopy and urinary cotinine measurements as part of a health check-up. Cotinine-verified current smokers were participants having a urinary cotinine level ≥50 ng/mL.

Results:

The mean participant age was 38.4 years, and the proportion of cotinine-verified current smokers was 23.0%. Cotinine-verified current smoking was an independent risk factor for CRN [adjusted odds ratio (AOR), 1.49; 95% confidence interval (CI), 1.42-1.56] and advanced CRN (ACRN) (AOR, 1.79; 95% CI, 1.57-2.05). Moreover, the risk of CRN and ACRN increased with increasing cotinine levels. Among self-reported never smokers, cotinine-verified current smokers had a higher risk of CRN (AOR, 1.77; 95% CI, 1.57-2.00) and ACRN (AOR, 1.94; 95% CI, 1.37-2.74) than cotinine-verified never smokers did, whereas among self-reported current smokers, cotinine-verified never smokers had a lower risk of CRN (AOR, 0.78; 95% CI, 0.70-0.87) and ACRN (AOR, 0.71; 95% CI, 0.52-0.98) than cotinine-verified current smokers did.

Conclusions:

Cotinine-captured smoking status and metabolic variation exhibit associations with CRN more accurately and objectively than self-reporting does, providing clearer evidence for the role of tobacco in the development of CRN.
Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid
Authors: Nath Meryl C. , Erickson Lori A.
Published: January 2018

Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.
A Teenager With Acute Anterograde Amnesia
Authors: Hoffmann Jennifer A. , Goldman Michael P. , Bachur Richard G.
Published: January 2018

Isolated amnesia is an uncommon presenting complaint in the pediatric age group. We report the case of an 18-year-old woman who presented with the acute onset of memory difficulty and an otherwise normal neurologic examination. Brain magnetic resonance imaging demonstrated inflammation in the bilateral temporal lobes. Serum and cerebrospinal fluid testing ultimately revealed a diagnosis of autoimmune encephalitis. Although rare, the acute onset of isolated amnesia deserves a prompt, comprehensive evaluation.
The Four Corners Sign
Authors: Walkoff Lara , White Darin B. , Chung Jonathan H. , Asante Dennis , Cox Christian W.
Published: January 2018

Purpose:

Differentiating between systemic sclerosis-related interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is important because of the differences in workup, prognosis, and treatment. However, there is much overlap in the appearance of these 2 entities on high-resolution computed tomography. We propose that inflammation and/or fibrosis focally or disproportionately involving the bilateral anterolateral upper lobes and posterosuperior lower lobes [“Four Corners” Sign (FCS)] is specific for SSc-ILD.

Materials and Methods:

Randomized high-resolution computed tomography studies from 74 IPF and 73 SSc-ILD cases were evaluated by 2 thoracic radiologists blinded to all patient data. For each case the reviewers noted whether the FCS was present and assigned a confidence level on the basis of a 7-point Likert scale. The same process was then performed on a randomized external validation group of 42 SSc-ILD and 42 IPF cases.

Results:

For Likert scores of 6 or 7 (“mostly agree” or “entirely agree” that the FCS is present, respectively) the sensitivity in SSc was 16.4% (95% confidence interval, 9.7%, 26.6%), specificity 100.0% (95% confidence interval, 95.1%, 100.0%). There was a significant association between a confidently present FCS and SSc compared with a confidently present FCS and IPF (P=0.0003). Analysis on an external validation group of 42 SSc and 42 IPF cases conferred similarly high specificity for SSc in cases characterized as FCS with high confidence.

Conclusion:

The FCS, a pattern of focal or disproportionate inflammation and/or fibrosis involving the bilateral anterolateral upper lobes and posterosuperior lower lobes, is specific for SSc-ILD when readers are confident of its presence.
Sonography of the Cecum
Authors: Jeffrey R. Brooke , Wentland Andrew L. , Olcott Eric W.
Published: January 2018

Sonography of the cecum has come of age largely as a consequence of the successful evolution of appendiceal sonography as a useful tool in the evaluation of patients with right lower-quadrant pain. At some medical centers, graded-compression sonography (GCS) has become the initial imaging study of choice in the assessment of these individuals. The cecum serves as a helpful anatomic landmark for localization of the appendix in these examinations—providing a sonographic starting point in the search for the appendix. During GCS, primary pathology within the cecum itself can become evident, including a variety of processes, such as infectious, inflammatory, or neoplastic disorders, whose presentations commonly mimic that of appendicitis. The accurate diagnosis of cecal abnormalities and their differentiation from acute appendicitis play valuable roles in the management of affected patients because the options for further workup and subsequent treatment vary greatly according to the diagnosis at hand. Additionally, the compressed cecum often becomes an acoustic window into the right lower quadrant, revealing pathology apart from the appendix within the right iliac fossa. The purpose of this pictorial essay is to highlight the importance and value of performing a careful evaluation of the cecum during GCS of patients with suspected appendicitis and to review the differential diagnosis and imaging findings of primary cecal abnormalities whose clinical presentations can mimic that of acute appendicitis.
Circadian Rhythms Disturbances in Alzheimer Disease
Authors: Milán-Tomás Ángela , Shapiro Colin M.
Published: January 2018

The purpose of this review is to provide an overview of the research regarding circadian rhythms in Alzheimer disease (AD). Furthermore, this paper explores the role of melatonin in the pathogenesis of AD and the limitation of trials addressing circadian rhythms disturbances in the AD population. A literature search using Medline with PubMed and Embase was carried out identifying papers focusing on circadian rhythms in AD. Sleep disorders and especially circadian rhythm disturbances are very common in the elderly population but definitely more pronounced in patients with AD. The lack of trials evaluating the management of circadian rhythms disorders in the elderly population and especially in AD should be considered of the utmost importance. Although there is a better understanding about the pathophysiology of AD and its relationship with circadian disorders, further studies in human models need to be conducted.
Comparative transcriptomics of Aspergillus fumigatus strains upon exposure to human airway epithelial cells
Authors: Watkins Tonya N. , Liu Hong , Chung Matthew , Hazen Tracy H. , Dunning Hotopp Julie C. , Filler Scott G. , Bruno Vincent M.
Published: January 2018

Aspergillus fumigatus is an opportunistic, ubiquitous, saprophytic mould that can cause severe allergic responses in atopic individuals as well as life-threatening infections in immunocompromised patients. A critical step in the establishment of infection is the invasion of airway epithelial cells by the inhaled fungi. Understanding how A. fumigatus senses and responds to airway cells is important to understand the pathogenesis of invasive pulmonary aspergillosis. Here, we analysed the transcriptomes of two commonly used clinical isolates, Af293 and CEA10, during infection of the A549 type II pneumocyte cell line in vitro. We focused our RNA-seq analysis on the core set of genes that are present in the genomes of the two strains. Our results suggest that: (a) A. fumigatus does not mount a conserved transcriptional response to airway epithelial cells in our in vitro model and (b) strain background and time spent in the tissue culture media have a greater impact on the transcriptome than the presence of host cells. Our analyses reveal both common and strain-specific transcriptional programmes that allow for the generation of hypotheses about gene function as it pertains to pathogenesis and the significant phenotypic heterogeneity that is observed among A. fumigatus isolates.
Spike sorting with Gaussian mixture models
Authors: Souza Bryan C. , Lopes-dos-Santos Vítor , Bacelo João , Tort Adriano B. L.
Published: January 2018

The shape of extracellularly recorded action potentials is a product of several variables, such as the biophysical and anatomical properties of the neuron and the relative position of the electrode. This allows for isolating spikes of different neurons recorded in the same channel into clusters based on waveform features. However, correctly classifying spike waveforms into their underlying neuronal sources remains a main challenge. This process, called spike sorting, typically consists of two steps: (1) extracting relevant waveform features (e.g., height, width), and (2) clustering them into non-overlapping groups believed to correspond to different neurons. In this study, we explored the performance of Gaussian mixture models (GMMs) in these two steps. We extracted relevant waveform features using a combination of common techniques (e.g., principal components and wavelets) and GMM fitting parameters (e.g., standard deviations and peak distances). Then, we developed an approach to perform unsupervised clustering using GMMs, which estimates cluster properties in a data-driven way. Our results show that the proposed GMM-based framework outperforms previously established methods when using realistic simulations of extracellular spikes and actual extracellular recordings to evaluate sorting performance. We also discuss potentially better techniques for feature extraction than the widely used principal components. Finally, we provide a friendly graphical user interface in MATLAB to run our algorithm, which allows for manual adjustment of the automatic results.
Conserved collateral susceptibility networks in diverse clinical strains of Escherichia coli
Authors: Podnecky Nicole L. , Fredheim Elizabeth G. A. , Kloos Julia , Sørum Vidar , Primicerio Raul , Roberts Adam P. , Rozen Daniel E. , Samuelsen Ørjan , Johnsen Pål J.
Published: January 2018

There is urgent need to develop novel treatment strategies to reduce antimicrobial resistance. Collateral sensitivity (CS), where resistance to one antimicrobial increases susceptibility to other drugs, is a uniquely promising strategy that enables selection against resistance during treatment. However, using CS-informed therapy depends on conserved CS networks across genetically diverse bacterial strains. We examined CS conservation in 10 clinical strains of E. coli resistant to four clinically relevant antibiotics. Collateral susceptibilities of these 40 resistant mutants were then determined against a panel of 16 antibiotics. Multivariate statistical analyses demonstrate that resistance mechanisms, in particular efflux-related mutations, as well as relative fitness were principal contributors to collateral changes. Moreover, collateral responses shifted the mutant selection window suggesting that CS-informed therapies could affect evolutionary trajectories of antimicrobial resistance. Our data allow optimism for CS-informed therapy and further suggest that early detection of resistance mechanisms is important to accurately predict collateral antimicrobial responses.
Trait and state patterns of basolateral amygdala connectivity at rest are related to endogenous testosterone and aggression in healthy young women
Authors: Buades-Rotger Macià , Engelke Christin , Krämer Ulrike M.
Published: January 2018

The steroid hormone testosterone (T) has been suggested to influence reactive aggression upon its action on the basolateral amygdala (BLA), a key brain region for threat detection. However, it is unclear whether T modulates resting-state functional connectivity (rsFC) of the BLA, and whether this predicts subsequent aggressive behavior. Aggressive interactions themselves, which often induce changes in T concentrations, could further alter BLA rsFC, but this too remains untested. Here we investigated the effect of endogenous T on rsFC of the BLA at baseline as well as after an aggressive encounter, and whether this related to behavioral aggression in healthy young women (n=39). Pre-scan T was negatively correlated with basal rsFC between BLA and left superior temporal gyrus (STG), which in turn predicted increased aggression. BLA-STG coupling at rest might thus underlie hostile readiness in low-T women. In addition, coupling between the BLA and the right superior parietal lobule (SPL), a brain region involved in higher-order perceptual processes, was reduced in aggressive participants. On the other hand, post-task increases in rsFC between BLA and medial orbitofrontal cortex (mOFC) were linked to reduced aggression, consistent with the established notion that the mOFC regulates amygdala activity in order to curb aggressive impulses. Finally, competition-induced changes in T were associated with increased coupling between the BLA and the right lateral OFC, but this effect was unrelated to aggression. We thus identified connectivity patterns that prospectively predict aggression in women, and showed how aggressive interactions in turn impact these neural systems.
Engineering Translational Resource Allocation Controllers: Mechanistic Models, Design Guidelines, and Potential Biological Implementations
Authors: Darlington Alexander P.S. , Kim Juhyun , Jiménez José I. , Bates Declan G.
Published: January 2018

The use of orthogonal ribosomes in combination with dynamic resource allocation controllers is a promising approach for relieving the negative effects of cellular resource limitations on the modularity of synthetic gene circuits. Here, we develop a detailed mechanistic model of gene expression and resource allocation, which when simplified to a tractable level of complexity, allows the rational design of translational resource allocation controllers. Analysis of this model reveals a fundamental design trade-off; that reducing coupling acts to decrease gene expression. Through a sensitivity analysis of the experimentally tuneable controller parameters, we identify how each controller design parameter affects the overall closed-loop behaviour of the system, leading to a detailed set of design guidelines for optimally managing this trade-off. Based on our designs, we evaluated a number of alternative potential experimental implementations of the proposed system using commonly available biological components. Finally, we show that the controller is capable of dynamically allocating ribosomes as needed to restore modularity in a number of more complex synthetic circuits, such as the repressilator, and activation cascades composed of multiple interacting modules.
A low-threshold potassium current enhances sparseness and reliability in a model of avian auditory cortex
Authors: Bjoring Margot C. , Meliza C. Daniel
Published: January 2018

Birdsong is a complex vocal communication signal, and like humans, birds need to discriminate between similar sequences of sound with different meanings. The caudal mesopallium (CM) is a cortical-level auditory area implicated in song discrimination. CM neurons respond sparsely to conspecific song and are tolerant of production variability. Intracellular recordings in CM have identified a diversity of intrinsic membrane dynamics, which could contribute to the emergence of these higher-order functional properties. We investigated this hypothesis using a novel linear-dynamical cascade model that incorporated detailed biophysical dynamics to simulate auditory responses to birdsong. Neuron models that included a low-threshold potassium current present in a subset of CM neurons showed increased selectivity and coding efficiency relative to models without this current. These results demonstrate the impact of intrinsic dynamics on sensory coding and the importance of including the biophysical characteristics of neural populations in simulation studies.
Identification of novel mutations in LprG (rv1411c), rv0521, rv3630, rv0010c, ppsC, cyp128 associated with pyrazinoic acid/pyrazinamide resistance in Mycobacterium tuberculosis
Authors: Shi Wanliang , Chen Jiazhen , Zhang Shuo , Zhang Wenhong , Zhang Ying
Published: January 2018

There is currently considerable interest in understanding the mechanisms of action of pyrazinamide (PZA), a critical frontline tuberculosis (TB) drug that plays a unique role in shortening TB therapy due to its unique activity against Mycobacterium tuberculosis persisters that are not killed by other TB drugs.1,2 Despite the importance of PZA in the treatment of both drug susceptible and drug-resistant TB and its simple structure, its mechanisms of action are complex and are not well understood.1,2 PZA is a prodrug that is converted to the active form pyrazinoic acid (POA) by nicotinamidase/pyrazinamidase (PZase) encoded by the pncA gene,3 whose mutation is the most common mechanism of PZA resistance in M. tuberculosis.3-5 However, some low level PZA-resistant strains (MIC=200-300 μg/ml, pH6.0) do not have mutations in the pncA gene.5,6 Recent studies have identified rpsA, which encodes the ribosomal protein S1 involved in both translation and trans-translation process, as a target of PZA,7 where its mutations are associated with PZA resistance from clinical isolates. In addition, mutations in panD encoding aspartate decarboxylase were identified as a new mechanism of PZA resistance from in vitro mutants resistant to PZA and the PanD protein was found to be another target of PZA.8,9panD mutations were initially found in mutants resistant to PZA 8 and then in mutants resistant to POA. 9,10 It is worth noting that previously POA-resistant mutants could not be isolated at acid pH which is required for higher activity of PZA against M. tuberculosis. However, we were able to successfully isolate POA-resistant mutants with high POA concentrations at close to neutral pH (pH 6.8),9 which led to discovery of new genes involved in POA and PZA resistance. For example, clpC1, which was also isolated from mutants resistant to PZA,11 was identified in mutants resistant to POA.12
Multi-scale mapping along the auditory hierarchy using high-resolution functional UltraSound in the awake ferret
Authors: Bimbard Célian , Demené Charlie , Girard Constantin , Radtke-Schuller Susanne , Shamma Shihab , Tanter Mickael , Boubenec Yves
Published: January 2018

A major challenge in neuroscience is to longitudinally monitor whole brain activity across multiple spatial scales in the same animal. Functional UltraSound (fUS) is an emerging technology that offers images of cerebral blood volume over large brain portions. Here we show for the first time its capability to resolve the functional organization of sensory systems at multiple scales in awake animals, both within structures by precisely mapping sensory responses, and between structures by elucidating the connectivity scheme of top-down projections. We demonstrate that fUS provides stable (over days), yet rapid, highly-resolved 3D tonotopic maps in the auditory pathway of awake ferrets, with unprecedented sharp functional resolution (100μm). This was performed in four different brain regions, including small (1-2mm3 size), subcortical (8mm deep) and previously undescribed structures in the ferret. Furthermore, we used fUS to map longdistance projections from frontal cortex, a key source of sensory response modulation, to auditory cortex.
Homologous recombination and transposon propagation shapes the population structure of an organism from the deep subsurface with minimal metabolism
Authors: Probst Alexander J , Banfield Jillian F.
Published: January 2018

DPANN archaea are primarily known based on genomes from metagenomes and single cells. We reconstructed a complete population genome for Candidatus “Forterrea”, a Diapherotrite with a predicted symbiotic lifestyle probably centered around nucleotide metabolism and RuBisCO. Genome-wide analysis of sequence variation provided insights into the processes that shape its population structure in the deep subsurface. The genome contains many transposons, yet reconstruction of a complete genome from a short-read insert dataset was possible because most occurred only in some individuals. Accuracy of the final reconstruction could be verified because the genome displays the pattern of cumulative GC skew known for some archaea but more typically associated with bacteria. Sequence variation is highly localized, and most pronounced around transposons and relatively close to the origin of replication. Patterns of variation are best explained by homologous recombination, a process previously not described for DPANN archaea.
Nuclear and mitochondrial genomes of the hybrid fungal plant pathogen Verticillium longisporum display a mosaic structure
Authors: Depotter Jasper R.L. , Beveren Fabian van , C.M. van den Berg Grardy , Wood Thomas A. , Thomma Bart P.H.J. , Seidl Michael F.
Published: January 2018

Allopolyploidization, genome duplication through interspecific hybridization, is an important evolutionary mechanism that can enable organisms to adapt to environmental changes or stresses. This increased adaptive potential of allopolyploids can be particularly relevant for plant pathogens in their quest for host immune response evasion. Allodiploidization likely caused the shift in host range of the fungal pathogen plant Verticillium longisporum, as V. longisporum mainly infects Brassicaceae plants in contrast to haploid Verticillium spp. In this study, we investigated the allodiploid genome structure of V. longisporum and its evolution in the hybridization aftermath. The nuclear genome of V. longisporum displays a mosaic structure, as numerous contigs consists of sections of both parental origins. V. longisporum encountered extensive genome rearrangements, whereas the contribution of gene conversion is negligible. Thus, the mosaic genome structure mainly resulted from genomic rearrangements between parental chromosome sets. Furthermore, a mosaic structure was also found in the mitochondrial genome, demonstrating its bi-parental inheritance. In conclusion, the nuclear and mitochondrial genomes of V. longisporum parents interacted dynamically in the hybridization aftermath. Conceivably, novel combinations of DNA sequence of different parental origin facilitated genome stability after hybridization and consecutive niche adaptation of V. longisporum.
The Innate Immune Response to Ischemic Injury: a Multiscale Modeling Perspective
Authors: Dimitrova Elena , Caromile Leslie A. , Laubenbacher Reinhard , Shapiro Linda H.
Published: January 2018

Background

Cell death as a result of ischemic injury triggers powerful mechanisms regulated by germline-encoded Pattern Recognition Receptors (PRRs) with shared specificity that recognize invading pathogens and endogenous ligands released from dying cells, and as such are essential to human health. Alternatively, dysregulation of these mechanisms contributes to extreme inflammation, deleterious tissue damage and impaired healing in various diseases. The Toll-like receptors (TLRs) are a prototypical family of PRRs that may be powerful anti-inflammatory targets if agents can be designed that antagonize their harmful effects while preserving host defense functions. This requires an understanding of the complex interactions and consequences of targeting the TLR-mediated pathways as well as technologies to analyze and interpret these, which will then allow the simulation of perturbations targeting specific pathway components, predict potential outcomes and identify safe and effective therapeutic targets.

Results

We constructed a multiscale mathematical model that spans the tissue and intracellular scales, and captures the consequences of targeting various regulatory components of injury-induced TLR4 signal transduction on potential pro-inflammatory or pro-healing outcomes. We applied known interactions to simulate how inactivation of specific regulatory nodes affects dynamics in the context of injury and to predict phenotypes of potential therapeutic interventions. We propose rules to link model behavior to qualitative estimates of pro-inflammatory signal activation, macrophage infiltration, production of reactive oxygen species and resolution. We tested the validity of the model by assessing its ability to reproduce published data not used in its construction.

Conclusions

These studies will enable us to form a conceptual framework focusing on TLR4-mediated ischemic repair to assess potential molecular targets that can be utilized therapeutically to improve efficacy and safety in treating ischemic/inflammatory injury.
Identification of human vaccinees that possess antibodies targeting the egg-adapted hemagglutinin receptor binding site of an H1N1 influenza vaccine strain
Authors: Garretson Tyler A. , Petrie Joshua G. , Martin Emily T. , Monto Arnold S. , Hensley Scott E.
Published: January 2018

Human influenza viruses passaged in eggs often acquire mutations in the hemagglutinin (HA) receptor binding site (RBS). To determine if egg-adapted H1N1 vaccines commonly elicit antibodies targeting the egg-adapted RBS of HA, we completed hemagglutinin-inhibition assays with A/California/7/2009 HA and egg-adapted A/California/7/2009-X-179A HA using sera collected from 159 humans vaccinated with seasonal influenza vaccines during the 2015-16 season. We found that ~5% of participants had ≥4-fold higher antibody titers to the egg-adapted viral strain compared to wild type viral strain. We used reverse-genetics to demonstrate that a single egg-adapted HA RBS mutation (Q226R) was responsible for this phenotype.
Environmental activity management: its use and impact on environmental performance
Authors: Phan Thanh Nguyet , Baird Kevin , Su Sophia
Published: January 2018

Purpose

The study provides an insight into the application and usefulness of activity management (AM) principles in an environmental context. Specifically, the purpose of this paper is to examine the extent of use of environmental activity management (EAM) utilising Gosselin’s (1997) three levels of AM (namely, environmental activity analysis (EAA), environmental activity cost analysis (EACA), and environmental activity-based costing (EABC)). The study also examines the association between EAM and environmental performance, and the role of decision quality as a mediator in this relationship.

Design/methodology/approach

Data were collected from 208 Australian organisations across different industries using a mail survey questionnaire.

Findings

The results indicate a relatively high extent of EAA use but a low extent of use of EACA and EABC. In addition, organisations using each level of EAM to a greater extent were found to experience higher levels of environmental performance. Furthermore, the relationship between EAA and EABC with environmental performance was found to be mediated by decision quality.

Practical implications

The findings suggest that organisations should endeavour to increase their use of EAM, and modify their existing costing systems to consider the drivers and costs of environmental activities.

Originality/value

This is the first study to empirically examine the extent of use of EAM and its association with environmental performance.
The role of accounting in transforming public tertiary institutions in New Zealand
Authors: Narayan Anil , Stittle John
Published: January 2018

Purpose

The purpose of this paper is to identify and evaluate the role and influence played by the discipline of accounting through its association with the multiple logics of government reforms to transform the public tertiary education sector in New Zealand.

Design/methodology/approach

The study adopts a case study approach utilising multiple data collection methods. Neo-institutional theory provides an insightful complement to neo-liberalism and enhances the understanding of institutional logics driving government reforms and the transformation of public tertiary institutions.

Findings

The findings reveal that accounting has become a powerful conduit for the exercise of the neo-liberalism reforms by government and implemented by managerial control over public tertiary education institutions.

Research limitations/implications

By addressing a gap in the literature, the paper shows how political and economic neo-liberal policies have been implemented in tertiary education with the discipline of accounting being adopted as a prime driver of these reforms. The paper has significant implications for educational management, academics and learners in understanding how and why the inherent nature, objectives and processes of the overall educational experience have undergone a radical reformation.

Originality/value

New Zealand is one of the first countries to implement these educational reforms and adopted “accounting technologies” to reduce costs and improve performance. But the reality has often been very different. Most of the government’s original objectives have not been fulfilled and the reforms have been costly for the academic profession. This paper provides a valuable source of learning for academics, managers and politicians.
Preliminary framework to manage tenant satisfaction in facilities management service encounters
Authors: Karunasena Gayani , Vijerathne Dimuthu , Muthmala Harsha
Published: January 2018

Purpose

Homogeneity in the main business of renting office spaces among commercial facilities has led to fierce competition. To retain tenant attractiveness, many are now concerned about the quality of facilities management (FM) services in addition to the rent, office space and location. The quality of FM service can be attained with successful service encounters. Thus, this paper aims to establish an initial platform on which tenant satisfaction in FM service encounters can be achieved.

Design/methodology/approach

The preliminary survey focused on gaining insights into FM encounters in commercial sector and applicability of service attributes under SERVQUAL model. The detailed survey concentrated on determining tenant perceptions on satisfactory levels of service attributes developed in the preliminary study and relationships between FM encounters and different service attributes. The collection of descriptive and inferential statistics was used to analyze the results.

Findings

This study’s findings reveal assurance and empathy to be highly correlated to tenant satisfaction, while other attributes are less correlated. However, perceptions of satisfaction levels of tenants on tangibility and reliability provides contradictory results to its correlation values. Satisfaction level in remote service encounters is lower compared to phone and face-to-face encounters. Complexity and management concerns toward physical facilities are imperative to uplift satisfaction in remote encounters.

Research limitations/implications

The scope of study was limited to FM encounters in Sri Lankan Grade “A” commercial office properties with high quality standard finishes, state-of-the-art systems, exceptional accessibility and a definite market presence in Colombo.

Originality/value

The study developed a preliminary framework that guides users to identify the best combinations of service attributes with respective FM encounters, where tenant satisfaction needs to be achieved.