bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLUMSY VEIN, the Arabidopsis DEAH‐box Prp16 ortholog, is required for auxin‐mediated development
Authors: Tsugeki Ryuji , Tanaka‐Sato Nana , Maruyama Nozomi , Terada Shiho , Kojima Mikiko , Sakakibara Hitoshi , Okada Kiyotaka 
Published: November 2014

SummaryPre‐messenger RNA (pre‐mRNA) splicing is essential in eukaryotic cells. In animals and yeasts, the DEAH‐box RNA‐dependent ATPase Prp16 mediates conformational change of the spliceosome, thereby facilitating pre‐mRNA splicing. In yeasts, Prp16 also plays an important role in splicing fidelity. Conversely, PRP16 orthologs in Chlamydomonas reinhardtii and nematode do not have an important role in general pre‐mRNA splicing, but are required for gene silencing and sex determination, respectively. Functions of PRP16 orthologs in higher plants have not been described until now. Here we show that the CLUMSY VEIN (CUV) gene encoding the unique Prp16 ortholog in Arabidopsis thaliana facilitates auxin‐mediated development including male‐gametophyte transmission, apical–basal patterning of embryonic and gynoecium development, stamen development, phyllotactic flower positioning, and vascular development. cuv‐1 mutation differentially affects splicing and expression of genes involved in auxin biosynthesis, polar auxin transport, auxin perception and auxin signaling. The cuv‐1 mutation does not have an equal influence on pre‐mRNA substrates. We propose that Arabidopsis PRP16/CUV differentially facilitates expression of genes, which include genes involved in auxin biosynthesis, transport, perception and signaling, thereby collectively influencing auxin‐mediated development.
Impact of priming on the response of neutrophils to human neutrophil alloantigen‐3a antibodies
Authors: Berthold Tom , Muschter Stefan , Schubert Nicole , Wesche Jan , Ameling Sabine , Teumer Alexander , Reil Angelika , Bux Jürgen , Bakchoul Tamam , Greinacher Andreas 
Published: November 2014

BackgroundHuman neutrophil alloantigen‐3a (HNA‐3a) antibodies can induce transfusion‐related acute lung injury (TRALI). The severity of TRALI varies largely among the affected patients. Severe comorbidity seems to increase the susceptibility for TRALI, potentially by priming of neutrophils. Thus, the impact of neutrophil priming on HNA‐3a antibody–mediated neutrophil aggregation and CD11b surface expression was investigated.Study Design and MethodsNeutrophils were primed using formyl‐methionyl‐leucyl‐phenylalanine (fMLP) or bacterial lipopolysaccharide (LPS). Granulocyte aggregation and CD11b surface expression were evaluated by the granulocyte agglutination test and by flow cytometry (FC), respectively. Priming‐induced changes in the surface expression of choline transporter‐like protein 2 (CTL2) and the CTL2 mRNA expression were assessed by FC and quantitative real‐time polymerase chain reaction, respectively.ResultsPriming of neutrophils lowered the amount of HNA‐3a antibodies required for inducing granulocyte aggregation in a dose‐dependent manner by 50% to 75%. The priming agent concentration necessary for this response differed between donors. Priming slightly enhanced binding of HNA‐3a antibodies to neutrophils. However, CTL2 de novo synthesis was not induced after priming with LPS, indicating that increased HNA‐3a antibody binding was likely caused by translocation of intracellular CTL2 to the surface or by increased affinity of HNA‐3a antibodies to CTL2. HNA‐3a antibodies influenced CD11b surface expression on neutrophils only marginally, which was also not potentiated by priming with fMLP or LPS.ConclusionThis study provides experimental evidence supporting the “threshold model” of TRALI. Priming of neutrophils with fMLP or LPS increases their aggregation response to HNA‐3a antibodies by lowering the required antibody amount.
Efficacy of plasmapheresis on donor‐specific antibody reduction by HLA specificity in post–kidney transplant recipients
Authors: Yamada Chisa , Ramon Daniel S. , Cascalho Marilia , Sung Randall S. , Leichtman Alan B. , Samaniego Milagros , Davenport Robertson D. 
Published: November 2014

BackgroundDonor‐specific antibodies (DSAs) to HLA antigens can cause acute antibody‐mediated rejection (AMR) after kidney transplantation (Txp). Therapeutic plasma exchange (TPE) has been used for AMR treatment; however, DSA reduction rates are inconsistent. We investigated DSA reduction rates by HLA specificity and clinical outcome.Study Design and MethodsSixty‐four courses of TPE for 56 kidney Txp recipients with high DSA were investigated. Dates of TPE procedures and Txp, patients' age, sex, race, creatinine (Cr), and mean fluorescent intensity (MFI) of DSA were retrieved. MFI reduction rate after one to three TPE and four to six TPE procedures were calculated by HLA DSA specificity in each patient, and the mean reduction rates were compared. The relationship of TPE treatment, MFI or Cr improvement rate, and graft age was also investigated.ResultsPatients received a mean 6.0 TPE procedures. Most received intravenous immunoglobulin after TPE and immunosuppressives. Forty‐two cases (65.6%) had DSA to HLA Class I and 54 cases (84.4%) to Class II, including 32 cases (50.0%) to both. Mean MFI reduction rates after one to three TPE and four to six TPE procedures were 25.7 and 37.1% in HLA Class I, 25.1 and 34.2% in Class II, and 14.3 and 19.9% in DR51‐53. The mean Cr improvements at the end of TPE and 3 and 6 months after TPE were 3.41, −0.37, and −0.72%, respectively.ConclusionSix TPE procedures decreased DSA more than three TPE procedures, but reduction rate was lower by the second three TPE procedures than the first three TPE procedures. Although the mean Cr improvement was minimal, the treatment has good potential to stop further deterioration of kidney function. Better Cr improvement rate is correlated with the graft age.
Heterotopic gastric mucosa associated with abdominal abscess formation, hypotension, and acute abdominal pain in a puppy
Authors: Tobleman Bridget N. , Sinnott Virginia B. 
Published: November 2014

AbstractObjectiveTo describe the presence of heterotopic gastric mucosa forming an abscess associated with acute abdominal pain and shock in a puppy.Case SummaryA 7‐month‐old male intact Shih‐Tzu was presented to the emergency service for evaluation of a 12‐hour history of vomiting and lethargy progressing to weakness. On presentation, the puppy was obtunded and hypotensive. Radiographs revealed an ill‐defined mid‐ventral abdominal mass. Ultrasound revealed an echogenic, fluid‐filled mass associated with the jejunum. The puppy had an exploratory celiotomy and a 2 × 4 cm oval fluid‐filled soft tissue mass was found to be intimately associated, but not communicating with, a section of the mid‐jejunum. The mass and associated jejunum were removed via enterectomy. Histopathology of the resected mass revealed heterotopic gastric mucosa; bacterial culture of the fluid contained in the mass revealed heavy growth of Escherichia coli. The puppy recovered from surgery, was discharged from the hospital, and has had no further complications from this episode.Unique Information ProvidedHeterotopic gastric mucosa is commonly found incidentally on necropsy. When it has been associated with acute gastrointestinal signs, mechanical intestinal obstruction with or without perforation was noted. To the authors' knowledge, this is the first reported case of heterotopic gastric mucosa leading to abscess formation and acute abdominal pain in the dog.
Facing the challenge of mammalian neural microcircuits: taking a few breaths may help
Authors: Feldman Jack L. , Kam Kaiwen 
Published: November 2014

AbstractBreathing in mammals is a seemingly straightforward behaviour controlled by the brain. A brainstem nucleus called the preBötzinger Complex sits at the core of the neural circuit generating respiratory rhythm. Despite the discovery of this microcircuit almost 25 years ago, the mechanisms controlling breathing remain elusive. Given the apparent simplicity and well‐defined nature of regulatory breathing behaviour, the identification of much of the circuitry, and the ability to study breathing in vitro as well as in vivo, many neuroscientists and physiologists are surprised that respiratory rhythm generation is still not well understood. Our view is that conventional rhythmogenic mechanisms involving pacemakers, inhibition or bursting are problematic and that simplifying assumptions commonly made for many vertebrate neural circuits ignore consequential detail. We propose that novel emergent mechanisms govern the generation of respiratory rhythm. That a mammalian function as basic as rhythm generation arises from complex and dynamic molecular, synaptic and neuronal interactions within a diverse neural microcircuit highlights the challenges in understanding neural control of mammalian behaviours, many (considerably) more elaborate than breathing. We suggest that the neural circuit controlling breathing is inimitably tractable and may inspire general strategies for elucidating other neural microcircuits.
Ageing and neurotrophic signalling effects on diaphragm neuromuscular function
Authors: Greising Sarah M. , Ermilov Leonid G. , Sieck Gary C. , Mantilla Carlos B. 
Published: November 2014

Key points
Sarcopenia of the diaphragm muscle, i.e. loss of muscle force and size with increasing age, may contribute to respiratory impairment in old age but the exact mechanisms underlying this are currently unknown.
Across the lifespan in mice there is worsening neuromuscular function of the diaphragm muscle, specifically reduced force and impaired neuromuscular transmission.
We tested the hypothesis that age‐related changes to the diaphragm muscle depend on brain‐derived neurotrophic factor (BDNF), acting through its high affinity receptor.
BDNF improves neuromuscular transmission in the diaphragm muscle into early old age, but not older ages. Inhibition of BDNF signalling impairs neuromuscular transmission only in young adult mice.
Our results suggest that the loss of endogenous BDNF precedes reduced activity of the high affinity receptor tropomyosin‐related kinase receptor B in the ageing mouse diaphragm muscle.
AbstractThe age‐related mechanisms underlying sarcopenia are largely unknown. We hypothesize that age‐related neuromuscular changes depend on brain‐derived neurotrophic factor (BDNF) acting through the tropomyosin‐related kinase receptor B (TrkB). Maximal specific force and neuromuscular transmission failure were assessed at 6, 18 and 24 months following control, BDNF or phosphoprotein phosphatase 1 derivative (1NMPP1) treatment in male TrkBF616A mice. Phosphoprotein phosphatase‐1 derivatives such as 1NMPP1 inhibit TrkB kinase activity as a result of this single amino acid mutation in the ATP binding domain. Maximal twitch and isometric tetanic force were reduced at 24 months compared to 6 and 18 months (P < 0.001). Neuromuscular transmission failure significantly increased at 18 and 24 months compared to 6 months (age × treatment interaction: P < 0.001). Neuromuscular transmission was improved following BDNF at 6 and 18 months and was impaired only at 6 months following 1NMPP1 treatment. Age and inhibition of TrkB kinase activity had similar effects on neuromuscular transmission failure, supporting a critical role for BDNF/TrkB signalling on neuromuscular changes in ageing. These results suggest that an age‐related loss of endogenous BDNF precedes reductions in TrkB kinase activity in the diaphragm muscle.
Contributions of white and brown adipose tissues and skeletal muscles to acute cold‐induced metabolic responses in healthy men
Authors: Blondin Denis P. , Labbé Sébastien M. , Phoenix Serge , Guérin Brigitte , Turcotte Éric E. , Richard Denis , Carpentier André C. , Haman François 
Published: November 2014

Key points
Both brown adipose tissue (BAT) and skeletal muscle activation contribute to the metabolic response of acute cold exposure in healthy men even under minimal shivering.
Activation of adipose tissue intracellular lipolysis is associated with BAT metabolic response upon acute cold exposure in healthy men.
Although BAT glucose uptake per volume of tissue is important, the bulk of glucose turnover during cold exposure is mediated by skeletal muscle metabolic activation even when shivering is minimized.
AbstractCold exposure stimulates the sympathetic nervous system (SNS), triggering the activation of cold‐defence responses and mobilizing substrates to fuel the thermogenic processes. Although these processes have been investigated independently, the physiological interaction and coordinated contribution of the tissues involved in producing heat or mobilizing substrates has never been investigated in humans. Using [U‐13C]‐palmitate and [3‐3H]‐glucose tracer methodologies coupled with positron emission tomography using 11C‐acetate and 18F‐fluorodeoxyglucose, we examined the relationship between whole body sympathetically induced white adipose tissue (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal muscle shivering and metabolic activation pattern during a mild, acute cold exposure designed to minimize shivering response in 12 lean healthy men. Cold‐induced increase in whole‐body oxygen consumption was not independently associated with BAT volume of activity, BAT oxidative metabolism, or muscle metabolism or shivering intensity, but depended on the sum of responses of these two metabolic tissues. Cold‐induced increase in non‐esterified fatty acid (NEFA) appearance rate was strongly associated with the volume of metabolically active BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004) and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism. The total glucose uptake was more than one order of magnitude greater in skeletal muscles compared to BAT during cold exposure (674 ± 124 vs. 12 ± 8 μmol min−1, respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally located muscles of the neck, back and inner thigh were the greatest contributors of muscle glucose uptake during cold exposure due to their more important shivering response. In summary, these results demonstrate for the first time that the increase in plasma NEFA appearance from WAT lipolysis is closely associated with BAT metabolic activation upon acute cold exposure in healthy men. In humans, muscle glucose utilization during shivering contributes to a much greater extent than BAT to systemic glucose utilization during acute cold exposure.
Control of vascular smooth muscle function by Src‐family kinases and reactive oxygen species in health and disease
Authors: MacKay Charles E. , Knock Greg A. 
Published: November 2014

AbstractReactive oxygen species (ROS) are now recognised as second messenger molecules that regulate cellular function by reversibly oxidising specific amino acid residues of key target proteins. Amongst these are the Src‐family kinases (SrcFKs), a multi‐functional group of non‐receptor tyrosine kinases highly expressed in vascular smooth muscle (VSM). In this review we examine the evidence supporting a role for ROS‐induced SrcFK activity in normal VSM contractile function and in vascular remodelling in cardiovascular disease. VSM contractile responses to G‐protein‐coupled receptor stimulation, as well as hypoxia in pulmonary artery, are shown to be dependent on both ROS and SrcFK activity. Specific phosphorylation targets are identified amongst those that alter intracellular Ca2+ concentration, including transient receptor potential channels, voltage‐gated Ca2+ channels and various types of K+ channels, as well as amongst those that regulate actin cytoskeleton dynamics and myosin phosphatase activity, including focal adhesion kinase, protein tyrosine kinase‐2, Janus kinase, other focal adhesion‐associated proteins, and Rho guanine nucleotide exchange factors. We also examine a growing weight of evidence in favour of a key role for SrcFKs in multiple pro‐proliferative and anti‐apoptotic signalling pathways relating to oxidative stress and vascular remodelling, with a particular focus on pulmonary hypertension, including growth‐factor receptor transactivation and downstream signalling, hypoxia‐inducible factors, positive feedback between SrcFK and STAT3 signalling and positive feedback between SrcFK and NADPH oxidase dependent ROS production. We also discuss evidence for and against the potential therapeutic targeting of SrcFKs in the treatment of pulmonary hypertension.
Accuracy of surface registration compared to conventional volumetric registration in patient positioning for head‐and‐neck radiotherapy: A simulation study using patient data
Authors: Kim Youngjun , Li Ruijiang , Na Yong Hum , Lee Rena , Xing Lei 
Published: November 2014

Purpose:3D optical surface imaging has been applied to patient positioning in radiation therapy (RT). The optical patient positioning system is advantageous over conventional method using cone‐beam computed tomography (CBCT) in that it is radiation free, frameless, and is capable of real‐time monitoring. While the conventional radiographic method uses volumetric registration, the optical system uses surface matching for patient alignment. The relative accuracy of these two methods has not yet been sufficiently investigated. This study aims to investigate the theoretical accuracy of the surface registration based on a simulation study using patient data.Methods:This study compares the relative accuracy of surface and volumetric registration in head‐and‐neck RT. The authors examined 26 patient data sets, each consisting of planning CT data acquired before treatment and patient setup CBCT data acquired at the time of treatment. As input data of surface registration, patient's skin surfaces were created by contouring patient skin from planning CT and treatment CBCT. Surface registration was performed using the iterative closest points algorithm by point–plane closest, which minimizes the normal distance between source points and target surfaces. Six degrees of freedom (three translations and three rotations) were used in both surface and volumetric registrations and the results were compared. The accuracy of each method was estimated by digital phantom tests.Results:Based on the results of 26 patients, the authors found that the average and maximum root‐mean‐square translation deviation between the surface and volumetric registrations were 2.7 and 5.2 mm, respectively. The residual error of the surface registration was calculated to have an average of 0.9 mm and a maximum of 1.7 mm.Conclusions:Surface registration may lead to results different from those of the conventional volumetric registration. Only limited accuracy can be achieved for patient positioning with an approach based solely on surface information.
How Sedentary Are Older People? A Systematic Review of the Amount of Sedentary Behavior
Authors: Harvey Juliet A. , Chastin Sebastien F.M. , Skelton Dawn A. 
Published: November 2014

Background/objectives:Sedentary behavior (SB), defined as sitting (nonexercising), reclining, and lying down (posture), or by low energy expenditure, is a public health risk independent to physical activity. The objective of this systematic literature review was to synthesize the available evidence on amount of SB reported by and measured in older adults.Data source:Studies published between 1981 and 2014 were identified from electronic databases and manual searching. Large-scale population studies/surveys reporting the amount of SB (objective/subjective) in older adults aged ≥ 60 years of age were included. Appraisal and synthesis was completed using MOOSE guidelines.Results:349,698 adults aged ≥ 60 within 22 studies (10 countries and 1 EU-wide) were included. Objective measurement of SB shows that older adults spend an average of 9.4 hr a day sedentary, equating to 65–80% of their waking day. Self-report of SB is lower, with average weighted self-reports being 5.3 hr daily. Within specific domains of SB, older adults report 3.3 hr in leisure sitting time and 3.3 hr watching TV. There is an association with more time spent in SB as age advances and a trend for older men to spend more time in SB than women.Conclusion/implications:Time spent sedentary ranges from 5.3–9.4 hr per waking day in older adults. With recent studies suggesting a link between SB, health, and well-being, independent of physical activity, this is an area important for successful aging.Limitations:Different methodologies of measurement and different reporting methods of SB made synthesis difficult. Estimated SB time from self-report is half of that measured objectively; suggesting that most self-report surveys of SB will vastly underestimate the actual time spent in SB.
Contribution of Clinically Derived Mutations in
ERG11
to Azole Resistance in Candida albicans
Authors: Flowers Stephanie A. , Colón Brendan , Whaley Sarah G. , Schuler Mary A. , Rogers P. David 
Published: November 2014

ABSTRACT

In
Candida albicans
, the
ERG11
gene encodes lanosterol demethylase, the target of the azole antifungals. Mutations in
ERG11
that result in an amino acid substitution alter the abilities of the azoles to bind to and inhibit Erg11, resulting in resistance. Although
ERG11
mutations have been observed in clinical isolates, the specific contributions of individual
ERG11
mutations to azole resistance in
C. albicans
have not been widely explored. We sequenced
ERG11
in 63 fluconazole (FLC)-resistant clinical isolates. Fifty-five isolates carried at least one mutation in
ERG11
, and we observed 26 distinct positions in which amino acid substitutions occurred. We mapped the 26 distinct variant positions in these alleles to four regions in the predicted structure for Erg11, including its predicted catalytic site, extended fungus-specific external loop, proximal surface, and proximal surface-to-heme region. In total, 31 distinct
ERG11
alleles were recovered, with 10
ERG11
alleles containing a single amino acid substitution. We then characterized 19 distinct
ERG11
alleles by introducing them into the wild-type azole-susceptible
C. albicans
SC5314 strain and testing them for susceptibilities to FLC, itraconazole (ITC), and voriconazole (VRC). The strains that were homozygous for the single amino acid substitutions Y132F, K143R, F145L, S405F, D446E, G448E, F449V, G450E, and G464S had a ≥4-fold increase in FLC MIC. The strains that were homozygous for several double amino acid substitutions had decreased azole susceptibilities beyond those conferred by any single amino acid substitution. These findings indicate that mutations in
ERG11
are prevalent among azole-resistant clinical isolates and that most mutations result in appreciable changes in FLC and VRC susceptibilities.