bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Epstein–Barr virus DNAemia after lung transplantation and its potential relationship with the development of post‐transplant complications
Authors: Silva J.T. , López‐Medrano F. , Alonso‐Moralejo R. , Fernández‐Ruiz M. , de Pablo‐Gafas A. , Pérez‐González V. , San‐Juan R. , Pérez‐Jacoiste Asín M.A. , Ruiz‐Merlo T. , Folgueira M.D. , Aguado J.M.
Published: April 2016

Background

Recent studies suggest that Epstein–Barr virus DNAemia (EBVd) may act as a surrogate marker of post‐transplant immunosuppression. This hypothesis has not been tested so far in lung transplant (LT) recipients.

Methods

We included 63 patients undergoing lung transplantation at our center between October 2008 and May 2013. Whole blood EBVd was systematically assessed by real‐time polymerase chain reaction assay on a quarterly basis. The occurrence of late complications (overall and opportunistic infection [OI] and chronic lung allograft dysfunction [CLAD]) was analyzed according to the detection of EBVd within the first 6 months post transplantation.

Results

Any EBVd was detected in 30 (47.6%) patients. Peak EBVd was higher in patients with late overall infection (2.23 vs. 1.73 log10 copies/mL; P = 0.026) and late OI (2.39 vs. 1.74 log10 copies/mL; P = 0.004). The areas under receiver operating characteristic curves for predicting both events were 0.806 and 0.871 respectively. The presence of an EBVd ≥2 log10 copies/mL during the first 6 months post transplantation was associated with a higher risk of late OI (adjusted hazard ratio [aHR] 7.92; 95% confidence interval [CI] 2.10–29.85; P = 0.002). Patients with detectable EBVd during the first 6 months also had lower CLAD‐free survival (P = 0.035), although this association did not remain statistically significant in the multivariate analysis (aHR 1.26; 95% CI 0.87–5.29; P = 0.099).

Conclusions

Although preliminary in nature, our results suggest that the detection of EBVd within the first 6 months after transplantation is associated with the subsequent occurrence of late OI in LT recipients.
A naïve Bayesian classifier for identifying plant microRNAs
Authors: Douglass Stephen , Hsu Ssu‐Wei , Cokus Shawn , Goldberg Robert B. , Harada John J. , Pellegrini Matteo
Published: April 2016

MicroRNAs (miRNAs) are important regulatory molecules in eukaryotic organisms. Existing methods for the identification of mature miRNA sequences in plants rely extensively on the search for stem–loop structures, leading to high false negative rates. Here, we describe a probabilistic method for ranking putative plant miRNAs using a naïve Bayes classifier and its publicly available implementation. We use a number of properties to construct the classifier, including sequence length, number of observations, existence of detectable predicted miRNA* sequences, the distribution of nearby reads and mapping multiplicity. We apply the method to small RNA sequence data from soybean, peach, Arabidopsis and rice and provide experimental validation of several predictions in soybean. The approach performs well overall and strongly enriches for known miRNAs over other types of sequences. By utilizing a Bayesian approach to rank putative miRNAs, our method is able to score miRNAs that would be eliminated by other methods, such as those that have low counts or lack detectable miRNA* sequences. As a result, we are able to detect several soybean miRNA candidates, including some that are 24 nucleotides long, a class that is almost universally eliminated by other methods.
Tropomyosin‐Mediated Regulation of Cytoplasmic Myosins
Authors: Manstein Dietmar J. , Mulvihill Daniel P.
Published: April 2016

The ability of the actin‐based cytoskeleton to rapidly reorganize is critical for maintaining cell organization and viability. The plethora of activities in which actin polymers participate require different biophysical properties, which can vary significantly between the different events that often occur simultaneously at separate cellular locations. In order to modify the biophysical properties of an actin polymer for a particular function, the cell contains diverse actin‐binding proteins that modulate the growth, regulation and molecular interactions of actin‐based structures according to functional requirements. In metazoan and yeast cells, tropomyosin is a key regulator of actin‐based structures. Cells have the capacity to produce multiple tropomyosin isoforms, each capable of specifically associating as copolymers with actin at distinct cellular locations to fine‐tune the functional properties of discrete actin structures. Here, we present a unifying theory in which tropomyosin isoforms critically define the surface landscape of copolymers with cytoplasmic β‐ or γ‐actin. Decoration of filamentous actin with different tropomyosin isoforms determines the identity and modulates the activity of the interacting myosin motor proteins. Conversely, changes in the nucleotide state of actin and posttranslational modifications affect the composition, morphology, subcellular localization and allosteric coupling of the associated actin‐based superstructures.
Red blood cells stored 35 days or more are associated with adverse outcomes in high‐risk patients
Authors: Goel Ruchika , Johnson Daniel J. , Scott Andrew V. , Tobian Aaron A.R. , Ness Paul M. , Nagababu Enika , Frank Steven M.
Published: April 2016

BACKGROUND

Clinical trials have shown that longer red blood cell (RBC) storage duration does not worsen outcomes; however, these studies included few RBCs near the end of the 42‐day storage limit. We tested the hypothesis that these “oldest” RBCs are associated with adverse outcomes.

STUDY DESIGN AND METHODS

In a retrospective study, 28,247 transfused patients given 129,483 RBC units were assessed. Morbidity, mortality, and length of stay (LOS) were compared in patients transfused exclusively with RBCs stored not more than 21 days versus patients transfused exclusively with RBCs stored 28 days or more and patients transfused exclusively with RBCs stored 35 days or more.

RESULTS

After risk adjustment, ≥35‐day RBCs were associated with increased morbidity (adjusted odds ratio [adjOR], 1.19; 95% confidence interval [CI], 1.07‐1.32; p = 0.002), but ≥28‐day RBCs were not (adjOR, 1.06; 95% CI, 0.97‐1.15; p = 0.2). Neither ≥35‐day nor ≥28‐day RBCs were associated with increased mortality. In critically ill patients, ≥35‐day RBCs were associated with increased morbidity (adjOR, 1.25; 95% CI, 1.08‐1.44; p = 0.002) and mortality (adjOR, 1.38; 95% CI, 1.08‐1.74; p = 0.009), but ≥28‐day RBCs were associated with neither. In older patients, ≥35‐day RBCs were associated with increased morbidity (adjOR, 1.22; 95% CI, 1.04‐1.42; p = 0.01), but not mortality (adjOR, 1.28; 95% CI, 0.96‐1.71; p = 0.1), and ≥28‐day RBCs were associated with neither. LOS was increased for both ≥28‐ and ≥35‐day RBCs for all patients and the critically ill and older subgroups.

CONCLUSIONS

RBCs transfused in the last 7 days of their 42‐day storage limit may be associated with adverse clinical outcomes in high‐risk patients.
High‐throughput strategy for molecular identification of Vel– blood donors employing nucleic acids extracted from plasma pools used for viral nucleic acid test screening
Authors: Dezan Marcia R. , Dinardo Carla L. , Bosi Silvia R.A. , Vega Sileni , Salles Nanci A. , Mendrone‐Júnior Alfredo , Levi José E.
Published: April 2016

BACKGROUND

Serologic methods to determine the Vel– phenotype require the use of rare human antisera and do not allow for many samples to be tested simultaneously, which limits their application as a tool to search for rare donors. This study developed a low‐cost molecular screening strategy using real‐time polymerase chain reaction (PCR) and DNA, extracted from plasma pools for viral nucleic acid test (NAT) screening, to identify Vel– and Vel+W donors.

STUDY DESIGN AND METHODS

A total of 4680 blood donors from the Brazilian southeast region were genotyped through real‐time PCR targeting the 17‐nucleotide (c.64_80del) deletion in the SMIM1 gene, which determines the Vel– phenotype, by using remaining nucleic acid from plasma pools of six donors, routinely discarded after the release of viral NAT results.

RESULTS

Twenty pools tested reactive and individual testing of samples from reactive pools identified 19 heterozygous donors with the SMIM1*64_80del deletion (0.40%) and one homozygous donor (0.02%). Fourteen of the 19 donors were confirmed as Vel– or Vel+W using anti‐Vel human antiserum.

CONCLUSION

The DNA pool genotyping strategy using real‐time PCR designed to detect the deletion in the SMIM1 gene proved effective and accurate in identifying donors with the Vel– and Vel+W phenotypes. The fact that remaining nucleic acid from routine viral NAT screening was used makes this technique economically attractive and definitely superior to the serologic techniques available to search for this rare phenotype.
Comparison of 4 point‐of‐care blood gas analyzers for arterial blood gas analysis in healthy dogs and dogs with cardiopulmonary disease
Authors: Roels Elodie , Gommeren Kris , Farnir Frédéric , Delvaux François , Billen Frédéric , Clercx Cécile
Published: April 2016

Objective

To compare blood gas results obtained from 4 point‐of‐care (POC) blood gas analyzers under routine working conditions in order to determine their interchangeability.

Design

Prospective study.

Setting

University teaching hospital.

Animals

Arterial blood samples from 34 dogs, 22 presented for cardiorespiratory disease and 12 healthy experimental Beagles.

Measurements

Each sample was analyzed by 4 POC blood gas analyzers in a random order: Cobas b‐123 POC system, IRMA TruPoint, Idexx VetStat, and ABL80 FLEX. Values obtained for pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) were compared between analyzers using a statistical mixed linear model and the Bland–Altman method; P < 0.05 was set as the level of significance. One sample was also repeatedly measured 5 times on each machine to calculate and compare intra‐analyzer variance for each measured variable using Fisher‐statistics.

Results

PO2 and PCO2 values were significantly higher when measured with the Idexx and IRMA machine than with Cobas and ABL80 (PO2: P < 0.001; PCO2: P < 0.05). pH values were significantly higher when measured with the Idexx instrument than with others' devices (P < 0.01). An interaction between health status and results delivered by devices was found only for PO2 values. There was no significant difference in intra‐analyzer variance between the 4 machines, for any of the measured variables.

Conclusions

PO2, PCO2, and pH differed significantly between the 4 analyzers. Differences in PO2 results were substantial and clinically relevant. All 4 analyzers displayed good intra‐analyzer variance. Consequently, serial blood gas analysis should be performed on a single device and interpreted in accordance of the device's specific reference intervals.
Suspected drug‐induced infiltrative lung disease culminating in acute respiratory failure in a dog treated with cytarabine and prednisone
Authors: Hart Samantha K. , Waddell, Lori
Published: April 2016

Objective

To describe a case of suspected drug‐induced infiltrative lung disease (ILD) and acute respiratory failure associated with the administration of cytarabine and prednisone in a dog requiring mechanical ventilation.

Case Summary

A 4.5‐year‐old, female spayed Yorkshire Terrier presented to the ICU with acute onset of respiratory distress following a 24‐hour cytarabine infusion. The patient was previously diagnosed with meningoencephalitis of unknown etiology (MUO), caudal occipital malformation, and syringohydromyelia, and was being treated with oral prednisone and levetiracetam, and cytarabine infusions. The patient developed tachypnea and dyspnea, and had diffuse crackles on auscultation of all lung fields, and hypoxemia 6 hours following completion of the fourth cytarabine infusion (300 mg/m2). Thoracic radiographs revealed diffuse, bilateral infiltrates consistent with noncardiogenic pulmonary edema or acute respiratory distress syndrome. Respiratory distress and hypoxemia persisted despite oxygen supplementation and furosemide therapy and led to initiation of mechanical ventilation. Approximately 12 hours later, the dog became progressively hypoxemic with worsening pulmonary edema. The owners elected euthanasia. Postmortem examination revealed pulmonary edema and diffuse interstitial pneumonia. Histopathologic evaluation revealed pulmonary edema, severe acute neutrophilic and histiocytic pneumonia, and multifocal interstitial fibrosis. Bacterial culture yielded no growth.

New or Unique Information Provided

Drug‐induced ILD is rarely reported in the veterinary literature, and has not previously been reported in dogs receiving cytarabine. As with administration of any medication, adverse events may occur. While ILD is unlikely to be commonly recognized, it may be considered in veterinary patients receiving chemotherapy that acutely become dyspneic.
Impact of fungal species cultured on outcome in horses with fungal keratitis
Authors: Sherman Amanda B. , Clode Alison B. , Gilger Brian C.
Published: April 2016

Purpose

To determine the significance ofAspergillusandFusariumspp., as identified by culture, on clinical outcome in equine keratomycosis.

Methods

Retrospective analysis of 66 horses (66 eyes) evaluated at the NCSU‐VH diagnosed with keratomycosis from whichAspergillusorFusariumspp. were cultured. Horses were classified into those who improved with medical management alone or those who required surgical intervention to improve. Horses who underwent surgery were divided into globe‐sparing procedures or enucleation. Effects of bacterial co‐infection, previous topical steroid or antifungal use, and time of year on fungal genus and outcome were evaluated.

Results

Aspergillusspp. was cultured from 41 eyes (63%), while 24 eyes (37%) culturedFusariumspp. One horse cultured both species and was not included in further evaluation. From the horses that culturedAspergillusspp., 28 eyes (68%) required surgical intervention to control the infection: 21 (75%) of these eyes maintained globe integrity, while 7 eyes (25%) were enucleated. Of those horses withFusariumspp., 14 eyes (58%) required surgical intervention: 11 (79%) of these eyes maintained globe integrity, while 3 eyes (21%) were enucleated. Genus of fungus cultured was not significantly associated with the need for surgical intervention nor was it significantly associated with the necessity of globe‐sparing surgery versus enucleation. Additionally, bacterial co‐infection, previous steroidal or antifungal use, and time of year did not affect outcome or type of fungal species cultured.

Conclusion

Equine keratomycosis fromFusariumspp. compared to keratomycosis fromAspergillusspp. is not associated with a different clinical outcome.
EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID‐TO‐SALIVARY RATIO AND THYROID‐TO‐BACKGROUND RATIOS
Authors: Peterson Mark E. , Guterl Jade N. , Rishniw Mark , Broome Michael R.
Published: April 2016

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid‐to‐salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid‐to‐background ratios (T/B) or percent thyroidal uptake of 99mTcO−4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross‐sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4), triiodothyronine (T3), free T4 (fT4), and thyroid‐stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland.
Combined Campylobacter jejuni and Campylobacter coli Rapid Testing and Molecular Epidemiology in Conventional Broiler Flocks
Authors: Schallegger G. , Muri‐Klinger S. , Brugger K. , Lindhardt C. , John L. , Glatzl M. , Wagner M. , Stessl B.
Published: April 2016

Campylobacter spp. are important causes of bacterial zoonosis, most often transmitted by contaminated poultry meat. From an epidemiological and risk assessment perspective, further knowledge should be obtained on Campylobacter prevalence and genotype distribution in primary production. Consequently, 15 Austrian broiler flocks were surveyed in summer for their thermophilic Campylobacter spp. contamination status. Chicken droppings, dust and drinking water samples were collected from each flock at three separate sampling periods. Isolates were confirmed by PCR and subtyped. We also compared three alternative methods (culture‐based enrichment in Bolton broth, culture‐independent real‐time PCR and a lateral‐flow test) for their applicability in chicken droppings. Twelve flocks were found to be positive for thermophilic Campylobacter spp. during the entire sampling period. Seven flocks (46.6%) were contaminated with both, C. jejuni and C. coli, five flocks harboured solely one species. We observed to a majority flock‐specific C. jejuni and C. coli genotypes, which dominated the respective flock. Flocks within a distance <2 km shared the same C. jejuni genotypes indicating a cross‐contamination event via the environment or personnel vectors. Multilocus sequence typing (MLST) of C. jejuni revealed that the majority of isolates were assigned to globally distributed clonal complexes or had a strong link to the human interface (CC ST‐446 and ST4373). The combination of techniques poses an advantage over risk assessment studies based on cultures alone, as, in the case of Campylobacter, occurrence of a high variety of genotypes might be present among a broiler flock. We suggest applying the lateral‐flow test under field conditions to identify ‘high‐shedding’ broiler flocks at the farm level. Consequently, poultry farmers and veterinarians could improve hygiene measurements and direct sanitation activities, especially during the thinning period. Ultimately, real‐time PCR could be applied to quantify Campylobacter spp. directly from chicken droppings and avoid non‐interpretable results achieved by culture‐dependent methods.
Cryptic diversity in the lizard genus Plica (Squamata): phylogenetic diversity and Amazonian biogeography
Authors: de Oliveira Deyla Paula , de Carvalho Vinícius Tadeu , Hrbek Tomas
Published: April 2016

Intra‐ and interspecific genetic diversity of the lizard species Plica plica (9 localities) and Plica umbra (19 localities) from the Brazilian Amazon was analysed using two mitochondrial (16S rDNA and CO1) and one nuclear (prolactin receptor – PRLR) genes. We generated a maximum‐likelihood and Bayesian hypotheses of phylogenetic relationships, and using the bPTP and ABGD lineage delimiting methods inferred the most likely number of lineages within each species. Both methods delimited five distinct lineages in Plica plica and six lineages within Plica umbra. The nominal subspecies of Plica umbra was comprised of one lineage, while Plica umbra ochrocollaris was comprised of five lineages. In majority of the cases, lineages were restricted to the interfluves of major Amazonian rivers, and different lineages occupied distinct areas of endemism. Phylogenetic relationships of the lineages are largely concordant with the hypothesized formation of the areas of endemism. The geographic structuring of the clades and the delimitation of these clades as distinct lineages suggest the possibility that these lineages represent species. If the observed diversity of lineages within the genus Plica is characteristic of squamate reptiles of the Amazon region, the diversity of squamates is grossly underestimated.
Lessons from the laboratory; integrated regulation of cerebral blood flow during hypoxia
Authors: Ainslie Philip N. , Hoiland Ryan L. , Bailey Damian M.
Published: April 2016

New Findings

What is the topic of this review?

What is the mechanism underlying the control of human cerebral blood flow in hypoxia and what are the consequences?

What advances does it highlight?

Although appropriate elevations in cerebral blood flow occur in acute and chronic hypoxia, neuronal processes are more sensitive to even small hypoxic insults; hence, they can result in maladaptive consequences despite maintenance of global oxygen delivery.

Exposure to acute or chronic hypoxaemia in otherwise healthy humans results in compensatory increases in cerebral blood flow (CBF) at rest and during exercise, referred to as hypoxic cerebral vasodilatation. These elevations in CBF offset the reduction in arterial oxygen content and maintain cerebral O2 delivery, conforming to the conservation of mass principle. In this review, we discuss the fundamental principles that contribute to the defence of cerebral O2 delivery and the corresponding implications for metabolism. We critically address to what extent the increase in CBF reflects an adaptive or indeed maladaptive physiological response. The molecular mechanisms of CBF regulation in hypoxia are also briefly discussed and future directions proposed.
Mitochondria in the middle: exercise preconditioning protection of striated muscle
Authors: Lawler John M. , Rodriguez Dinah A. , Hord Jeffrey M.
Published: April 2016

Cellular and physiological adaptations to an atmosphere which became enriched in molecular oxygen spurred the development of a layered system of stress protection, including antioxidant and stress response proteins. At physiological levels reactive oxygen and nitrogen species regulate cell signalling as well as intracellular and intercellular communication. Exercise and physical activity confer a variety of stressors on skeletal muscle and the cardiovascular system: mechanical, metabolic, oxidative. Transient increases of stressors during acute bouts of exercise or exercise training stimulate enhancement of cellular stress protection against future insults of oxidative, metabolic and mechanical stressors that could induce injury or disease. This phenomenon has been termed both hormesis and exercise preconditioning (EPC). EPC stimulates transcription factors such as Nrf‐1 and heat shock factor‐1 and up‐regulates gene expression of a cadre of cytosolic (e.g. glutathione peroxidase and heat shock proteins) and mitochondrial adaptive or stress proteins (e.g. manganese superoxide dismutase, mitochondrial KATP channels and peroxisome proliferator activated receptor γ coactivator‐1 (PGC‐1)). Stress response and antioxidant enzyme inducibility with exercise lead to protection against striated muscle damage, oxidative stress and injury. EPC may indeed provide significant clinical protection against ischaemia–reperfusion injury, Type II diabetes and ageing. New molecular mechanisms of protection, such as δ‐opioid receptor regulation and mitophagy, reinforce the notion that mitochondrial adaptations (e.g. heat shock proteins, antioxidant enzymes and sirtuin‐1/PGC‐1 signalling) are central to the protective effects of exercise preconditioning.

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Anti‐inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation
Authors: Bonaz Bruno , Sinniger Valérie , Pellissier Sonia
Published: April 2016

Brain and viscera interplay within the autonomic nervous system where the vagus nerve (VN), containing approximately 80% afferent and 20% efferent fibres, plays multiple key roles in the homeostatic regulations of visceral functions. Recent data have suggested the anti‐inflammatory role of the VN. This vagal function is mediated through several pathways, some of them still debated. The first one is the anti‐inflammatory hypothalamic–pituitary–adrenal axis which is stimulated by vagal afferent fibres and leads to the release of cortisol by the adrenal glands. The second one, called the cholinergic anti‐inflammatory pathway, is mediated through vagal efferent fibres that synapse onto enteric neurons which release acetylcholine (ACh) at the synaptic junction with macrophages. ACh binds to α‐7‐nicotinic ACh receptors of those macrophages to inhibit the release of tumour necrosis (TNF)α, a pro‐inflammatory cytokine. The last pathway is the splenic sympathetic anti‐inflammatory pathway, where the VN stimulates the splenic sympathetic nerve. Norepinephrine (noradrenaline) released at the distal end of the splenic nerve links to the β2 adrenergic receptor of splenic lymphocytes that release ACh. Finally, ACh inhibits the release of TNFα by spleen macrophages through α‐7‐nicotinic ACh receptors. Understanding of these pathways is interesting from a therapeutic point of view, since they could be targeted in various ways to stimulate anti‐inflammatory regulation in TNFα‐related diseases such as inflammatory bowel disease and rheumatoid arthritis. Among others, VN stimulation, either as an invasive or non‐invasive procedure, is becoming increasingly frequent and several clinical trials are ongoing to evaluate the potential effectiveness of this therapy to alleviate chronic inflammation.

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Emerging roles of the myocardin family of proteins in lipid and glucose metabolism
Authors: Swärd Karl , Stenkula Karin G , Rippe Catarina , Alajbegovic Azra , Gomez Maria F. , Albinsson Sebastian
Published: April 2016

Members of the myocardin family bind to the transcription factor serum response factor (SRF) and act as coactivators controlling genes of relevance for myogenic differentiation and motile function. Binding of SRF to DNA is mediated by genetic elements called CArG boxes, found often but not exclusively in muscle and growth controlling genes. Studies aimed at defining the full spectrum of these CArG elements in the genome (i.e. the CArGome) have in recent years, unveiled unexpected roles of the myocardin family proteins in lipid and glucose homeostasis. This coactivator family includes the protein myocardin (MYOCD), the myocardin‐related transcription factors A and B (MRTF‐A/MKL1 and MRTF‐B/MKL2) and MASTR (MAMSTR). Here we discuss growing evidence that SRF‐driven transcription is controlled by extracellular glucose through activation of the Rho‐kinase pathway and actin polymerization. We also describe data showing that adipogenesis is influenced by MLK activity through actions upstream of peroxisome proliferator‐activated receptor γ with consequences for whole body fat mass and insulin sensitivity. The recently demonstrated involvement of myocardin coactivators in the biogenesis of caveolae, Ω‐shaped membrane invaginations of importance for lipid and glucose metabolism, is finally discussed. These novel roles of myocardin proteins may open the way for new unexplored strategies to combat metabolic diseases such as diabetes, which, at the current incidence, is expected to reach 333 million people worldwide by 2025.

This review highlights newly discovered roles of myocardin‐related transcription factors in lipid and glucose metabolism as well as novel insights into their well‐established role as mediators of stretch‐dependent effects in smooth muscle. As co‐factors for serum response factor (SRF), MKLs regulates transcription of genes involved in the contractile function of smooth muscle cells. In addition to mechanical stimuli, this regulation has now been found to be promoted by extracellular glucose levels in smooth muscle. Recent reports also suggest that MKLs can regulate a subset of genes involved in the formation of lipid‐rich invaginations in the cell membrane called caveolae. Finally, a potential role of MKLs in non‐muscle cells has been discovered as they negatively influence adipocyte differentiation.

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Hepatic mitochondrial oxidative phosphorylation is normal in obese patients with and without type 2 diabetes
Authors: Lund Michael Taulo , Kristensen Marianne , Hansen Merethe , Tveskov Louise , Floyd Andrea Karen , Støckel Mikael , Vainer Ben , Poulsen Steen Seier , Helge Jørn Wulff , Prats Clara , Dela Flemming
Published: April 2016

Key points

Hepatic insulin resistance in patients with obesity or type 2 diabetes has been suggested to result from hepatic mitochondrial dysfunction.

High‐resolution respirometry (HRR) can be used to assess oxidative phosphorylation by measuring the mitochondrial oxygen consumption rate in the individual complexes of the mitochondria.

By using HRR, the present study demonstrates no difference in hepatic mitochondrial oxidative phosphorylation among subjects with obesity with or without type 2 diabetes and non‐obese controls.

Furthermore, the amount of mitochondria, assessed by the citrate synthase activity, is not different between the three groups.

Together the present findings indicate that hepatic mitochondrial oxidative phosphorylation capacity is not impaired in patients with obesity or type 2 diabetes.

Obese patients with type 2 diabetes (T2DM) and without type 2 diabetes (OB) are characterized by high hepatic lipid content and hepatic insulin resistance. This may be linked to impaired hepatic mitochondrial oxidative phosphorylation (OXPHOS) capacity. The aim of the present study was to investigate and compare hepatic mitochondrial OXPHOS capacity in T2DM, OB and non‐obese controls (CON). Seventeen obese patients (nine OB and eight T2DM) and six CON patients had perioperative liver biopsies taken. Samples were divided into three parts to measure (1) complex I, II and IV linked respiration, (2) citrate synthase (CS) activity and (3) lipid droplet (LD) size and area (% of total tissue area filled by LDs). State 3 respiration of complex I, II and IV and the CS activity did not differ in OB, T2DM and CON. LD size was significantly higher in T2DM compared with CON, and LD area tended (P = 0.10) to be higher in T2DM and OB compared with CON. The present findings indicate that hepatic OXPHOS capacity is not different in patients with markedly different weight and glycaemic control. Furthermore, the results do not support impaired hepatic mitochondrial respiratory capacity playing a major role in the development of obesity‐induced type 2 diabetes.
Immature endothelial cells initiate endothelin‐mediated constriction of newborn arteries
Authors: Chang Fumin , Flavahan Sheila , Flavahan Nicholas A.
Published: April 2016

Key points

Endothelial expression and the release of endothelin‐1 (ET‐1) in levels sufficient to initiate vasoconstriction is considered to be a hallmark feature of pathological endothelial dysfunction.

During the immediate postnatal period, arterial endothelial cells undergo remarkable structural and functional changes as they transition to a mature protective cell layer, which includes a marked increase in NO dilator activity.

The present study demonstrates that endothelial cells lining newborn central arteries express high levels of ET‐1 peptides and, in response to endothelial stimulation, rapidly release ET‐1 and initiate powerful ET‐1‐mediated constriction. This activity is lost as the endothelium matures in the postnatal period.

Heightened activity of ET‐1 in the neonatal endothelium might contribute to inappropriate responses of immature arteries to stress or injury. Indeed, the immature endothelium resembles dysfunctional endothelial cells, and retention or re‐emergence of this phenotype may contribute to the development of vascular disease.

Endothelial cells lining fetal and newborn arteries have an unusual phenotype, including reduced NO activity, prominent actin stress fibres and poorly developed cellular junctions. Experiments were performed to determine whether the immature endothelium of newborn arteries also expresses and releases endothelin‐1 (ET‐1) and initiates endothelium‐dependent constriction. Carotid arteries were isolated from newborn (postnatal day 1; P1), postnatal day 7 (P7) and postnatal day 21 (P21) mice and assessed in a pressure myograph system. Endothelial stimulation with A23187 or thrombin caused constriction in P1 arteries, no significant change in diameter of P7 arteries, and dilatation in P21 arteries. In P1 arteries, constriction to thrombin or A23187 was inhibited by endothelial‐denudation, by ET‐1 receptor antagonists (BQ123 plus BQ788) or by inhibition of endothelin‐converting enzyme (phosphoramidon or SM19712). ET‐1 receptor antagonism did not affect responses to thrombin or A23187 in more mature arteries. Exogenous ET‐1 caused similar concentration‐dependent constrictions of P1, P7 and P21 arteries. Endothelial stimulation with thrombin rapidly increased the endothelial release of ET‐1 from P1 but not P21 aortas. Endothelial expression of ET‐1 peptides, as assessed by immunofluorescence analysis, was increased in P1 compared to P21 arteries. Therefore, newborn endothelial cells express high levels of ET‐1 peptides, rapidly release ET‐1 in response to endothelial stimulation, and initiate ET‐1‐mediated endothelium‐dependent constriction. This activity is diminished as the endothelium matures in the immediate postnatal period. Heightened activity of ET‐1 in neonatal endothelium probably reflects an early developmental role of the peptide, although this might contribute to inappropriate responses of immature arteries to stress or injury.
An augmented CO2 chemoreflex and overactive orexin system are linked with hypertension in young and adult spontaneously hypertensive rats
Authors: Li Aihua , Roy Sarah H. , Nattie Eugene E.
Published: April 2016

Key points

Activation of central chemoreceptors by CO2 increases sympathetic nerve activity (SNA), arterial blood pressure (ABP) and breathing. These effects are exaggerated in spontaneously hypertensive rats (SHRs), resulting in an augmented CO2 chemoreflex that affects both breathing and ABP.

The augmented CO2 chemoreflex and the high ABP are measureable in young SHRs (postnatal day 30–58) and become greater in adult SHRs.

Blockade of orexin receptors can normalize the augmented CO2 chemoreflex and the high ABP in young SHRs and normalize the augmented CO2 chemoreflex and significantly lower the high ABP in adult SHRs.

In the hypothalamus, SHRs have more orexin neurons, and a greater proportion of them increase their activity with CO2.

The orexin system is overactive in SHRs and contributes to the augmented CO2 chemoreflex and hypertension. Modulation of the orexin system may be beneficial in the treatment of neurogenic hypertension.

Activation of central chemoreceptors by CO2 increases arterial blood pressure (ABP), sympathetic nerve activity and breathing. In spontaneously hypertensive rats (SHRs), high ABP is associated with enhanced sympathetic nerve activity and peripheral chemoreflexes. We hypothesized that an augmented CO2 chemoreflex and overactive orexin system are linked with high ABP in both young (postnatal day 30–58) and adult SHRs (4–6 months). Our main findings are as follows. (i) An augmented CO2 chemoreflex and higher ABP in SHRs are measureable at a young age and increase in adulthood. In wakefulness, the ventilatory response to normoxic hypercapnia is higher in young SHRs (mean ± SEM: 179 ± 11% increase) than in age‐matched normotensive Wistar–Kyoto rats (114 ± 9% increase), but lower than in adult SHRs (226 ± 10% increase; P < 0.05). The resting ABP is higher in young SHRs (122 ± 5 mmHg) than in age‐matched Wistar–Kyoto rats (99 ± 5 mmHg), but lower than in adult SHRs (152 ± 4 mmHg; P < 0.05). (ii) Spontaneously hypertensive rats have more orexin neurons and more CO2‐activated orexin neurons in the hypothalamus. (iii) Antagonism of orexin receptors with a dual orexin receptor antagonist, almorexant, normalizes the augmented CO2 chemoreflex in young and adult SHRs and the high ABP in young SHRs and significantly lowers ABP in adult SHRs. (iv) Attenuation of peripheral chemoreflexes by hyperoxia does not abolish the augmented CO2 chemoreflex (breathing and ABP) in SHRs, which indicates an important role for the central chemoreflex. We suggest that an overactive orexin system may play an important role in the augmented central CO2 chemoreflex and in the development of hypertension in SHRs.
Effects of tensor couplings of ω and ρ mesons on 1S0 nucleon superfluidity in neutron star matter
Authors: Huang Xiu-Lin , Xu Yan , Liu Cheng-Zhi , Liu Guang-Zhou
Published: April 2016

The [Formula: see text] nucleon superfluidity in neutron star matter was investigated in the framework of relativistic [Formula: see text] model with the tensor couplings of [Formula: see text] and [Formula: see text] mesons using the relativistic Hartree–Fock (RHF) approximation. It was found that the tensor couplings of [Formula: see text] and [Formula: see text] mesons lead to a clear growth of the [Formula: see text] neutron pairing gap in the density range where there exists [Formula: see text] neutron superfluidity. The [Formula: see text] pairing gap of proton with the tensor couplings of [Formula: see text] and [Formula: see text] mesons in the density range of [Formula: see text]–[Formula: see text][Formula: see text]fm[Formula: see text] is lower and then in the density range of [Formula: see text]–[Formula: see text][Formula: see text]fm[Formula: see text] higher than the corresponding value without the tensor couplings of [Formula: see text] and [Formula: see text] mesons. Our results provide a basic to understand the influence of the tensor couplings of [Formula: see text] and [Formula: see text] mesons on the cooling properties of neutron star.
A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis
Authors: Leiter Odette , Kempermann Gerd , Walker Tara L.
Published: April 2016

Immune regulation of the brain is generally studied in the context of injury or disease. Less is known about how the immune system regulates the brain during normal brain function. Recent work has redefined the field of neuroimmunology and, as long as their recruitment and activation are well regulated, immune cells are now known to have protective properties within the central nervous system in maintaining brain health. Adult neurogenesis, the process of new neuron generation in the adult brain, is highly plastic and regulated by diverse extrinsic and intrinsic cues. Emerging research has shown that immune cells and their secreted factors can influence adult neurogenesis, both under baseline conditions and during conditions known to change neurogenesis levels, such as aging and learning in an enriched environment. This review will discuss how, under nonpathological conditions, the immune system can interact with the neural stem cells to regulate adult neurogenesis with particular focus on the hippocampus—a region crucial for learning and memory.
Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells
Authors: Singh Krishna K. , Matkar Pratiek N. , Quan Adrian , Mantella Laura-Eve , Teoh Hwee , Al-Omran Mohammed , Verma Subodh
Published: April 2016

Objective. To evaluate the relationship between TGFβsignaling and endothelial lncRNA expression.Methods.Human umbilical vein endothelial cell (HUVECs) lncRNAs and mRNAs were profiled with the Arraystar Human lncRNA Expression Microarray V3.0 after 24 hours of exposure to TGFβ1 (10 ng/mL).Results. Of the 30,584 lncRNAs screened, 2,051 were significantly upregulated and 2,393 were appreciably downregulated (P<0.05) in response to TGFβ. In the same HUVEC samples, 2,148 of the 26,106 mRNAs screened were upregulated and 1,290 were downregulated. Of these 2,051 differentially expressed upregulated lncRNAs, MALAT1, which is known to be induced by TGFβin endothelial cells, was the most (~220-fold) upregulated lncRNA. Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in hippo signaling, Wnt signaling, focal adhesion, neuroactive ligand-receptor interaction, and pathways in cancer. The most downregulated are notably involved in olfactory transduction, PI3-Akt signaling, Ras signaling, neuroactive ligand-receptor interaction, and apoptosis.Conclusions.This is the first lncRNA and mRNA transcriptome profile of TGFβ-mediated changes in human endothelial cells. These observations may reveal potential new targets of TGFβin endothelial cells and novel therapeutic avenues for cardiovascular disease-associated endothelial dysfunction.
Osteoporosis Recovery by Antrodia camphorata Alcohol Extracts through Bone Regeneration in SAMP8 Mice
Authors: Liu Hen-Yu , Huang Chiung-Fang , Li Chun-Hao , Tsai Ching-Yu , Chen Wei-Hong , Wei Hong-Jian , Wang Ming-Fu , Kuo Yueh-Hsiung , Cheong Mei-Leng , Deng Win-Ping
Published: April 2016

Antrodia camphorata has previously demonstrated the efficacy in treating cancer and anti‐inflammation. In this study, we are the first to evaluate Antrodia camphorata alcohol extract (ACAE) for osteoporosis recovery in vitro with preosteoblast cells (MC3T3‐E1) and in vivo with an osteoporosis mouse model established in our previous studies, ovariectomized senescence accelerated mice (OVX‐SAMP8). Our results demonstrated that ACAE treatment was slightly cytotoxic to preosteoblast at 25 μg/mL, by which the osteogenic gene expression (RUNX2, OPN, and OCN) was significantly upregulated with an increased ratio of OPG to RANKL, indicating maintenance of the bone matrix through inhibition of osteoclastic pathway. Additionally, evaluation by Alizarin Red S staining showed increased mineralization in ACAE‐treated preosteoblasts. For in vivo study, our results indicated that ACAE inhibits bone loss and significantly increases percentage bone volume, trabecular bone number, and bone mineral density in OVX‐SAMP8 mice treated with ACAE. Collectively, in vitro and in vivo results showed that ACAE could promote osteogenesis and prevent bone loss and should be considered an evidence‐based complementary and alternative medicine for osteoporosis therapy through the maintenance of bone health.
Macular Pigment Optical Density in Chinese Primary Open Angle Glaucoma Using the One-Wavelength Reflectometry Method
Authors: Ji Yuying , Zuo Chengguo , Lin Mingkai , Zhang Xiongze , Li Miaoling , Mi Lan , Liu Bing , Wen Feng
Published: April 2016

Purpose. To investigate macular pigment optical density (MPOD) and its relationship with retinal thickness in primary open angle glaucoma (POAG) patients using the one-wavelength reflectometry method.Methods. A total of 30 eyes from 30 POAG patients (18 males and 12 females, mean age47.27±16.93) and 52 eyes from 52 controls (27 males and 25 females, mean age49.54±19.15) were included in this prospective, observational, case-control study. MPOD was measured in a 7-degree area using one-wavelength reflectometry method. Two parameters, max and mean optical density (OD), were used for analyses. Spectral-domain-optical coherence tomography was used to measure retinal thickness, including central retinal thickness (CRT), the macular ganglion cell complex (GCC), and the circumpapillary retinal nerve fiber layer (RNFL).Results. Both maxOD and meanOD were significantly reduced in POAG patients compared with normal subjects (P<0.001). GCC, CRT, and RNFL thicknesses were also significantly reduced in POAG patients (P<0.001). GCC thickness had a positive relationship with MPOD.Conclusions. MPOD within the 7-degree area was significantly lower in Chinese POAG patients than in control subjects, and GCC thickness was significantly and positively associated with MPOD. Whether the observed lower MPOD in POAG contributes to the disease process or is secondary to pathological changes caused by the disease (such as loss of ganglion cells) warrants further and longitudinal study.
Stab Incision Glaucoma Surgery: A Modified Guarded Filtration Procedure for Primary Open Angle Glaucoma
Authors: Jacob Soosan , Figus Michele , Ashok Kumar Dhivya , Agarwal Ashvin , Agarwal Amar , Areeckal Incy Saijimol
Published: April 2016

Purpose. To describe a modified guarded filtration surgery, stab incision glaucoma surgery (SIGS), for primary open angle glaucoma (POAG).Methods. This prospective, interventional case series included patients with POAG (IOP ≥21 mmHg with glaucomatous visual field defects). After sliding superior conjunctiva down over limbus, 2.8 mm bevel-up keratome was used to create conjunctival entry and superficial corneoscleral tunnel in a single step starting 1.5 mm behind limbus. Lamellar corneoscleral tunnel was carefully dissected 0.5–1 mm into cornea and anterior chamber (AC) was entered. Kelly Descemet’s punch (1 mm) was slid along the tunnel into AC to punch internal lip of the tunnel, thereby compromising it. Patency of ostium was assessed by injecting fluid in AC and visualizing leakage from tunnel. Conjunctival incision alone was sutured.Results. Mean preoperative IOP was27.41±5.54 mmHg and mean postoperative IOP was16.47±4.81 mmHg (n=17). Mean reduction in IOP was38.81±16.55%. There was significant reduction of IOP (p<0.000). 64.7% had IOP at final follow-up of <18 mmHg without medication and 82.35% had IOP <18 mmHg with ≤2 medications. No sight threatening complications were encountered.Conclusion. Satisfactory IOP control was noted after SIGS in interim follow-up (14.18±1.88months).
Fiber in Diet Is Associated with Improvement of Glycated Hemoglobin and Lipid Profile in Mexican Patients with Type 2 Diabetes
Authors: Velázquez-López Lubia , Muñoz-Torres Abril Violeta , García-Peña Carmen , López-Alarcón Mardia , Islas-Andrade Sergio , Escobedo-de la Peña Jorge
Published: April 2016

Objective.To assess the association of dietary fiber on current everyday diet and other dietary components with glycated hemoglobin levels (HbA1c), glucose, lipids profile, and body weight body weight, in patients with type 2 diabetes.Methods.A cross-sectional survey of 395 patients with type 2 diabetes was performed. HbA1c, fasting glucose, triglycerides, and lipids profile were measured. Weight, waist circumference, blood pressure, and body composition were measured. Everyday diet with a semiquantitative food frequency questionnaire was evaluated. ANOVA, Kruskal-Wallis, chi-square tests and multivariate logistic regression were used in statistical analysis.Results.Higher fiber intake was associated with a low HbA1c, high HDL-c levels, low weight, and waist circumference. The highest tertile of calories consumption was associated with a higher fasting glucose level and weight. The highest tertile of carbohydrate consumption was associated with a lower weight. The lowest tertile of total fat and saturated fat was associated with the highest tertile of HDL-c levels, and lower saturated fat intake was associated with lower weight(p<0.05).Conclusions.A higher content of fiber in the diet reduces HbA1c and triglycerides, while improving HDL-c levels. Increasing fiber consumption while lowering calorie consumption seems to be an appropriate strategy to reduce body weight and promote blood glucose control.