bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioral characterization of the 6-hydroxidopamine model of Parkinson’s disease and pharmacological rescuing of non-motor deficits
Authors: Carvalho Miguel M , Campos Filipa L , Coimbra Bárbara , Pêgo José M , Rodrigues Carla , Lima Rui , Rodrigues Ana J , Sousa Nuno , Salgado António J 
Published: April 2013

Abstract

Background
Parkinson’s disease (PD) is a chronic neurodegenerative condition that is characterized by motor symptoms as a result of dopaminergic degeneration, particularly in the mesostriatal pathway. However, in recent years, a greater number of clinical studies have focused on the emergence of non-motor symptoms in PD patients, as a consequence of damage on the mesolimbic and mesocortical dopaminergic networks, and on their significant impact on the quality of life of PD patients. Herein, we performed a thorough behavioral analysis including motor, emotional and cognitive dimensions, of the unilateral medial forebrain bundle (MFB) 6-hydroxidopamine (6-OHDA)-lesioned model of PD, and further addressed the impact of pharmacological interventions with levodopa and antidepressants on mood dimensions.

Results
Based on apomorphine-induced turning behaviour and degree of dopaminergic degeneration, animals submitted to MFB lesions were subdivided in complete and incomplete lesion groups. Importantly, this division also translated into a different severity of motor and exploratory impairments and depressive-like symptoms; in contrast, no deficits in anxiety-like and cognitive behaviors were found in MFB-lesioned animals. Subsequently, we found that the exploratory and the anhedonic behavioural alterations of MFB-lesioned rats can be partially improved with the administration of both levodopa or the antidepressant bupropion, but not paroxetine.

Conclusions
Our results suggest that this model is a relevant tool to study the pathophysiology of motor and non-motor symptoms of PD. In addition, the present data shows that pharmacological interventions modulating dopaminergic transmission are also relevant to revert the non-motor behavioral deficits found in the disease.
Dynamic cross-regulation of antigen-specific effector and regulatory T cell subpopulations and microglia in brain autoimmunity
Authors: Martinez-Pasamar Sara , Abad Elena , Moreno Beatriz , Velez de Mendizabal Nieves , Martinez-Forero Ivan , Garcia-Ojalvo Jordi , Villoslada Pablo 
Published: April 2013

Abstract

Background
Multiple Sclerosis (MS) is considered a T-cell-mediated autoimmune disease with a prototypical oscillatory behavior, as evidenced by the presence of clinical relapses. Understanding the dynamics of immune cells governing the course of MS, therefore, has many implications for immunotherapy. Here, we used flow cytometry to analyze the time-dependent behavior of antigen-specific effector (Teff) and regulatory (Treg) T cells and microglia in mice model of MS, Experimental Autoimmune Encephalomyelitis (EAE), and compared the observations with a mathematical cross-regulation model of T-cell dynamics in autoimmune disease.

Results
We found that Teff and Treg cells specific to myelin olygodendrocyte glycoprotein (MOG) developed coupled oscillatory dynamics with a 4- to 5-day period and decreasing amplitude that was always higher for the Teff populations, in agreement with the mathematical model. Microglia activation followed the oscillations of MOG-specific Teff cells in the secondary lymphoid organs, but they were activated before MOG-specific T-cell peaks in the CNS. Finally, we assessed the role of B-cell depletion induced by anti-CD20 therapy in the dynamics of T cells in an EAE model with more severe disease after therapy. We observed that B-cell depletion decreases Teff expansion, although its oscillatory behavior persists. However, the effect of B cell depletion was more significant in the Treg population within the CNS, which matched with activation of microglia and worsening of the disease. Mathematical modeling of T-cell cross-regulation after anti-CD20 therapy suggests that B-cell depletion may influence the dynamics of T cells by fine-tuning their activation.

Conclusions
The oscillatory dynamics of T-cells have an intrinsic origin in the physiological regulation of the adaptive immune response, which influences both disease phenotype and response to immunotherapy.
Synthesis, insecticidal, and antibacterial activities of novel neonicotinoid analogs with dihydropyridine
Authors: He Yinju , Hu Deyu , Lv Mingming , Jin Linhong , Wu Jian , Zeng Song , Yang Song , Song Baoan 
Published: April 2013

AbstractBackgroundNilaparvata lugens, a major pest in rice-growing areas, is extremely difficult to manage. Neonicotinoids have increasingly been used in crop protection and animal health care againstN. lugens. To discover new bioactive molecules and pesticides, we combined the active structure of cyanoacrylates, aromatic aldehydes, and substituted pyridyl (thiazolyl) methyl-2-substituted-methylidene-imidazolidine derivatives for the design and synthesis of a series of novel neonicotinoid analogs with dihydropyridine.ResultsA series of neonicotinoid analogs with dihydropyridine were synthesized. Their structures were characterized by IR,1H NMR,13C NMR, and elemental analysis and their insecticidal and antibacterial activities were assessed. Preliminary biological activity tests showed that all of the title compounds feature insecticidal activities againstN. lugensat 500 mg/L. Moreover, some compounds showed promising antibacterial activities againstPseudomonas solanacearum(e.g., Tobacco bacterial wilt and Tomato bacterial wilt) at a dose of 200 mg/L.ConclusionA synthetic route to obtain neonicotinoid analogs with dihydropyridine by the reaction of intermediates2(pyridyl (thiazolyl) methyl-2-substituted-methyl-ideneimidazolidine) and intermediates1(cyanoacrylates) and different aromatic aldehydes in acetonitrile under reflux conditions is presented. The effects of different solvents, bases, and reaction time on the reaction of3awere investigated. The results of this study suggest that neonicotinoid analogs with dihydropyridine could causeN. lugensdeath and restrainP. solanacearumgrowth.
Extreme intra-familial variability of congenital central hypoventilation syndrome: a case series
Authors: Bygarski Elizabeth , Paterson Melanie , Lemire Edmond G 
Published: April 2013

Abstract

Introduction
Congenital central hypoventilation syndrome is an autosomal dominant disorder that classically presents as sudden death in infancy secondary to central hypoventilation. Most cases are caused by polyalanine repeat mutations in the paired-like homeobox 2B gene, PHOX2B. More severe disease is typically associated with nonpolyalanine repeat mutations. We report the case of a family with nonpolyalanine repeat mutations that uncharacteristically has many individuals who were mildly symptomatic and only diagnosed after genetic testing. We highlight the highly variable clinical presentation of this condition and the need for clinicians to remain vigilant.

Case presentation
We identified 10 individuals in a large extended Caucasian family of German and Austrian background with congenital central hypoventilation syndrome.
Case 1: A 16-year old male proband presented for reproductive counseling. He had a previous history of apneic spells and Hirschsprung disease in the neonatal period. A PHOX2B nonpolyalanine repeat mutation was identified in the proband and used to screen his extended family.
Cases 2 to 10: Several mildly symptomatic family members (males aged 5, 13, 42 and 80 years; females aged 28, 44, 46 and 48 years) spanning four generations were identified after genetic screening. A newborn boy from this family was also recently diagnosed with Hirschsprung disease and went on to have an abnormal sleep study.

Conclusions
In this report, we highlight the significant phenotypic variability of congenital central hypoventilation syndrome, previously thought to be a rare genetic condition. Given the extreme clinical variability, it is possible that the prevalence of congenital central hypoventilation syndrome in the general population is much higher than previous estimates. This is of major importance to all clinicians who will need to maintain a high index of suspicion for this not so rare and highly clinically variable genetic condition that spans all ages. As the familial mutation has been identified, presymptomatic and prenatal diagnostic testing are available options for family members.
Lignin biosynthesis perturbations affect secondary cell wall composition and saccharification yield in Arabidopsis thaliana
Authors: Van Acker Rebecca , Vanholme Ruben , Storme Véronique , Mortimer Jennifer C , Dupree Paul , Boerjan Wout 
Published: April 2013

Abstract

Background
Second-generation biofuels are generally produced from the polysaccharides in the lignocellulosic plant biomass, mainly cellulose. However, because cellulose is embedded in a matrix of other polysaccharides and lignin, its hydrolysis into the fermentable glucose is hampered. The senesced inflorescence stems of a set of 20 Arabidopsis thaliana mutants in 10 different genes of the lignin biosynthetic pathway were analyzed for cell wall composition and saccharification yield. Saccharification models were built to elucidate which cell wall parameters played a role in cell wall recalcitrance.

Results
Although lignin is a key polymer providing the strength necessary for the plant’s ability to grow upward, a reduction in lignin content down to 64% of the wild-type level in Arabidopsis was tolerated without any obvious growth penalty. In contrast to common perception, we found that a reduction in lignin was not compensated for by an increase in cellulose, but rather by an increase in matrix polysaccharides. In most lignin mutants, the saccharification yield was improved by up to 88% cellulose conversion for the cinnamoyl-coenzyme A reductase1 mutants under pretreatment conditions, whereas the wild-type cellulose conversion only reached 18%. The saccharification models and Pearson correlation matrix revealed that the lignin content was the main factor determining the saccharification yield. However, also lignin composition, matrix polysaccharide content and composition, and, especially, the xylose, galactose, and arabinose contents influenced the saccharification yield. Strikingly, cellulose content did not significantly affect saccharification yield.

Conclusions
Although the lignin content had the main effect on saccharification, also other cell wall factors could be engineered to potentially increase the cell wall processability, such as the galactose content. Our results contribute to a better understanding of the effect of lignin perturbations on plant cell wall composition and its influence on saccharification yield, and provide new potential targets for genetic improvement.
DNA methylation and transcriptional noise
Authors: Huh Iksoo , Zeng Jia , Park Taesung , Yi Soojin V 
Published: April 2013

Abstract

Background
DNA methylation is one of the most phylogenetically widespread epigenetic modifications of genomic DNA. In particular, DNA methylation of transcription units (‘gene bodies’) is highly conserved across diverse taxa. However, the functional role of gene body methylation is not yet fully understood. A long-standing hypothesis posits that gene body methylation reduces transcriptional noise associated with spurious transcription of genes. Despite the plausibility of this hypothesis, an explicit test of this hypothesis has not been performed until now.

Results
Using nucleotide-resolution data on genomic DNA methylation and abundant microarray data, here we investigate the relationship between DNA methylation and transcriptional noise. Transcriptional noise measured from microarrays scales down with expression abundance, confirming findings from single-cell studies. We show that gene body methylation is significantly negatively associated with transcriptional noise when examined in the context of other biological factors.

Conclusions
This finding supports the hypothesis that gene body methylation suppresses transcriptional noise. Heavy methylation of vertebrate genomes may have evolved as a global regulatory mechanism to control for transcriptional noise. In contrast, promoter methylation exhibits positive correlations with the level of transcriptional noise. We hypothesize that methylated promoters tend to undergo more frequent transcriptional bursts than those that avoid DNA methylation.
Microwave imaging for neoadjuvant chemotherapy monitoring: initial clinical experience
Authors: Meaney Paul M , Kaufman Peter A , Muffly Lori S , Click Michael , Poplack Stephen P , Wells Wendy A , Schwartz Gary N , di Florio-Alexander Roberta M , Tosteson Tor D , Li Zhongze , Geimer Shireen D , Fanning Margaret W , Zhou Tian , Epstein Neil R , Paulsen Keith D 
Published: April 2013

Abstract
Introduction
Microwave tomography recovers images of tissue dielectric properties, which appear to be specific for breast cancer, with low-cost technology that does not present an exposure risk, suggesting the modality may be a good candidate for monitoring neoadjuvant chemotherapy.

Methods
Eight patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer were imaged longitudinally five to eight times during the course of treatment. At the start of therapy, regions of interest (ROIs) were identified from contrast-enhanced magnetic resonance imaging studies. During subsequent microwave examinations, subjects were positioned with their breasts pendant in a coupling fluid and surrounded by an immersed antenna array. Microwave property values were extracted from the ROIs through an automated procedure and statistical analyses were performed to assess short term (30 days) and longer term (four to six months) dielectric property changes.

Results
Two patient cases (one complete and one partial response) are presented in detail and demonstrate changes in microwave properties commensurate with the degree of treatment response observed pathologically. Normalized mean conductivity in ROIs from patients with complete pathological responses was significantly different from that of partial responders (P value = 0.004). In addition, the normalized conductivity measure also correlated well with complete pathological response at 30 days (P value = 0.002).

Conclusions
These preliminary findings suggest that both early and late conductivity property changes correlate well with overall treatment response to neoadjuvant therapy in locally advanced breast cancer. This result is consistent with earlier clinical outcomes that lesion conductivity is specific to differentiating breast cancer from benign lesions and normal tissue.
Cross-talk between intraepithelial γδ T cells and epithelial cells
Authors: Witherden Deborah A , Havran Wendy L 
Published: April 2013

ABSTRACT
Intraepithelial γδ T cells play pivotal roles in homeostasis, tissue repair, inflammation, and protection from malignancy. In some tissues, γδ T cells are the only resident T cell population, whereas in others, they coexist with αβ T cells and other lymphocyte populations. γδ T cell function in the epithelium requires constant communication between cells in the form of cell-to-cell contacts and cell-to-matrix interactions. These interactions coordinate with the timely production of specific cytokines, chemokines, growth factors, and glycosaminoglycans, which have specialized effects on neighboring epithelial cells. Antigens that activate these T cells are not well-defined, and they do not express classic costimulatory or coreceptor molecules. As such, an understanding of the mechanisms used by epithelial γδ T cells to maintain homeostasis and facilitate wound repair has necessitated the identification of novel molecular interactions between γδ T cells and their neighboring epithelial cells.
How psychiatrists should introduce themselves in the first consultation: an experimental study
Authors: Priebe Stefan , Palumbo Claudia , Ahmed Sajjad , Strappelli Nadia , Gavrilovic Jelena Jankovic , Bremner Stephen 
Published: April 2013

BackgroundHow psychiatrists introduce themselves in the first consultation may influence the therapeuticrelationship. There is no evidence about what type of introduction patients prefer.AimsTo assess experimentally patients' preferences for how psychiatrists introduce themselves.MethodTwelve psychiatrists were filmed, each with three different introductions: stating name, profession and reason for consultation; the same, plus information on what will happen during the consultation; and the same, plus disclosure of a personal difficulty. Six randomly selected videos, of different psychiatrists, two of each type of introduction, were rated by each of 120 psychiatric in- and out-patients on Likert-type scales.ResultsPatients gave the most positive ratings to psychiatrists who introduced themselves with information about what will happen in the consultation rather than ones with briefer introductions or with additional personal disclosure (P = 0.002). Preferences were similar in different subgroups.ConclusionsPsychiatrists should introduce themselves with information about what they intend to do in theconsultation, but without personal disclosure.
Nitrogen metabolism of the intestine during digestion in a teleost fish, the plainfin midshipman (Porichthys notatus)
Authors: Bucking Carol , LeMoine Christophe M.R. , Craig Paul M. , Walsh Patrick J. 
Published: April 2013

SummaryDigestion affects nitrogen metabolism in fish, as both exogenous and endogenous proteins and amino acids are catabolized, liberating ammonia in the process. Here we present a model of local detoxification of ammonia by the intestinal tissue of the plainfin midshipman (Porichthys notatus) during digestion, resulting in an increase in urea excretion of gastrointestinal origin. Corroborating evidence indicated whole animal ammonia and urea excretion increased following feeding and ammonia levels within the lumen of the midshipman intestine increased to high levels (1.8 ± 0.4 μmol N g-1). We propose that this ammonia entered the enterocytes and was detoxified to urea via the ornithine urea cycle (OU-C) enzymes, as evidenced by a 1.5 – 2.9 fold post-prandial increase in glutamine synthetase activity (0.14 ± 0.05 μmol min-1g-1 and 0.28 ± 0.02 μmol min-1 g-1 vs. 0.41 ± 0.03 μmol min-1g-1) and an 8.7 fold increase in carbamoyl phosphate synthetase III activity (0.3 ± 1.2 nmol min-1g-1 vs. 2.6 ± 0.4 nmol min-1g-1). Furthermore, digestion increased urea production by isolated gastrointestinal tissue 1.7 fold supporting our hypothesis that intestinal tissue synthesizes urea in response to feeding. We further propose that the intestinal urea may have been excreted into the intestinal lumen via an apical urea transporter (UT) as visualized using immunohistochemistry. A portion of the urea was then excreted to the environment along with the feces, resulting in the observed increase in urea excretion, while another portion may have been used by intestinal ureolytic bacteria. Overall, we propose that P. notatus produces urea within the enterocytes via a functional OU-C which is then excreted into the intestinal lumen. Our model of intestinal nitrogen metabolism does not appear to be universal as we were unable to activate the OU-C in the intestine of fed rainbow trout. However, literature values suggest that multiple fish species could follow this model.
Prolonged fasting activates Nrf2 in postweaned elephant seals
Authors: Vázquez-Medina José Pablo , Soñanez-Organis José G. , Rodriguez Ruben , Viscarra Jose A. , Nishiyama Akira , Crocker Daniel E. , Ortiz Rudy M. 
Published: April 2013

Summary
Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the up-regulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated if prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 2.5 fold at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 50-fold and 3-fold higher at week 7 than at week 1. Smad2 phosphorylation, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 5-fold at week 7, while Nox4 protein expression, which can activate Nrf2, was 2.5-fold higher at wk 7 than at wk 1. Results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. Results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals.
Flies developed small bodies and small cells in warm and in thermally fluctuating environments.
Authors: Czarnoleski Marcin , Cooper Brandon S. , Kierat Justyna , Angilletta Michael J. 
Published: April 2013

Summary
Although plasma membranes benefit cells by regulating the flux of materials to and from the environment, these membranes cost energy to maintain. Since smaller cells provide relatively more membrane area for transport, ectotherms that develop in warm environments should consist of small cells despite the energetic cost. Effects of constant temperatures on cell size qualitatively match this prediction, but effects of thermal fluctuations on cell size are unknown. Thermal fluctuations could favour either small or large cells: small cells facilitate transport during peaks in metabolic demand whereas large cells minimize the resources needed for homeoviscous adaptation. To explore this problem, we examined effects of thermal fluctuations during development on the size of epidermal cells in the wings of Drosophila melanogaster. Flies derived from a temperate population were raised at two mean temperatures (18° and 25°C), with either no variation or a daily variation of ± 4°C. Flies developed faster at a mean temperature of 25°C. Thermal fluctuations sped development, but only at 18°C. An increase in the mean and variance of temperature caused flies to develop smaller cells and wings. Thermal fluctuations reduced the size of males at 18°C and the size of females at 25°C. The thorax, the wings, and the cells decreased with an increase in the mean and in the variance of temperature, but the response of cells was the strongest. Based on this pattern, we hypothesize that development of the greater area of membranes under thermal fluctuations provides a metabolic advantage that outweighs the greater energetic cost of remodelling membranes.