bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rat model for determining the postprandial response to foods
Authors: Belobrajdic Damien P , Wei Jiangqin , Bird Anthony R 
Published: July 2016

AbstractBACKGROUNDThe use of small animal models for studying postprandial changes in circulating nutrients, hormones and metabolic biomarkers is hampered by the limited quantity of blood that can be withdrawn for analysis. Here, we describe the development of an unrestrained, meal‐fed rat model, having a permanent or temporary vascular cannula that permits repeated blood sampling. The applicability and performance of the model were evaluated in a series of experiments on acute glycaemic and insulinaemic responses to carbohydrate‐based test meals.RESULTSA test food containing 0.4 g carbohydrate raised blood glucose by 1.5 mmol L−1. Postprandial blood glucose levels peaked at 15 min and returned to baseline at 180 min, whereas they remained elevated for longer when the test meal contained 1.25 g carbohydrate. The glycaemic response tended (P = 0.063) to be higher when the meal tolerance test was conducted at the start rather than the end of the dark period, but the insulinaemic response was unaffected. The magnitude of the glycaemic response was less for blood collected from the caudal vein compared to that from the jugular vein. Both cannulation strategies were equally effective in enabling return of red blood cells, thus preserving blood volume.CONCLUSIONThis improved small animal model affords new opportunities to screen foods for nutrient bioavailability and explore metabolic mechanisms mediating responses to food consumption. © 2016 Society of Chemical Industry
Intrusive Cognitive Content and Postdeployment Distress
Authors: Shipherd Jillian C. , Salters‐Pedneault Kristalyn , Matza Alexis 
Published: July 2016

AbstractAlthough intrusive cognitions (ICs) are common posttrauma, little is known about trauma‐related IC content, or associations between IC content and posttraumatic adjustment. A mixed‐method cross‐sectional approach was used in a secondary analysis of IC content and postdeployment distress. Participants were 1,521 U.S. Army soldiers 3–12 months postdeployment reporting their most distressing postdeployment ICs (mean number of ICs reported was 1.20). ICs were transcribed and content was categorized by 13 emergent themes. The most commonly reported ICs were of injury or death (48.2%) and combat (43.5%), and soldiers with probable posttraumatic stress disorder (PTSD;n= 187) were more likely to report the presence of these ICs, χ2s(1) = 35.27,ps < .001, φs < .16 than those without probable PTSD (n= 1,331). Other domains also emerged frequently, including ICs about friends (31.0%), family (15.8%), and leadership concerns (13.8%). IC content was a small, but significant correlate of distress after adjusting for combat exposure (ΔR2≥ .02,ps ≤ .001). The presence of ICs of injury or death, combat, military sexual trauma, health, leadership, and family (βs> .06,ps < .02) were unique correlates of distress. Results suggested that ICs about a wide range of topics should be addressed in postdeployment interventions.
Hunter access affects elk resource selection in the Missouri breaks, Montana
Authors: Proffitt Kelly M. , Thompson Scott , Henry Drew , Jimenez Benjamin , Gude Justin A. 
Published: July 2016

ABSTRACTElk (Cervus canadensis) populations that exceed socially tolerable population levels create problems with private landowners over property damage and competition with livestock. Increasing harvest of adult female elk is the primary management tool for curtailing elk population growth and reducing elk populations. However, this tool is not effective when elk are not accessible to hunters during hunting seasons. The purpose of this project was to evaluate the effects of hunter access and other landscape factors on second‐order and third‐order elk resource selection during the archery and rifle hunting seasons in 2 populations: the Missouri River Breaks (MRB) and Larb Hills, Montana, USA. In our resource selection models, we first treated the individual elk‐year as the sampling unit to estimate individual‐level selection coefficients and second, we pooled data from all individuals to estimate population‐level selection coefficients. Second‐order population‐level selection coefficients indicated that elk in MRB and Larb Hills selected home ranges in areas with no hunter access, and hunter access was the strongest predictor of second‐order selection. Similarly, third‐order population‐level selection coefficients indicated elk in both populations selected locations within their seasonal home range with no hunter access, and the strength of selection for locations with no hunter access was stronger in the archery season than the rifle season. However, individual models revealed that although third‐order population‐level selection for locations with no hunter access was strong, only 46% of elk in the MRB selected for no hunter access during the archery season and 24% of elk selected for no hunter access during the rifle season. Additionally, the majority of all elk locations in the MRB (i.e., 68% of archery locations, 91% of rifle locations) occurred in areas accessible to hunters. These results highlight that population‐level selection coefficients may not always represent individual selection patterns, and we recommend employing a combination of population‐level and individual animal models as the basis of developing biological inferences. Even if hunter access is restricted in a relatively small geographic area within an elk population range, those areas may have a disproportionate effect on elk distributions and prevent effective harvest of female elk to maintain populations at objective levels (i.e., 1,700–2,000 elk). Working cooperatively with stakeholders to minimize elk harboring is necessary for curtailing further elk population increases and maintaining a distribution of elk across public and private lands. © 2016 The Wildlife Society.
Stereotactic Thalamotomy for Task‐Specific Dystonia
Authors: Doshi Paresh K. , Shaikh Shabana , Karkera Bharati , Ramdasi Raghvendra 
Published: July 2016

AbstractView Supplementary Video 1View Supplementary Video 2BackgroundTask‐specific dystonia (TSD) is a focal dystonia producing abnormal posture of the fingers or the hand, occurring during selective motor activities that involve repeated use. Conventional medical management and botulinum toxin fail to provide relief in all patients. Thalamotomy or DBS have been used as surgical treatment in patients not responding to medical treatment.MethodsFive patients (all male; age, 18–47 years) with refractory focal hand dystonia underwent ventrooralis (Vo) thalamotomy using stereotactic techniques. Preoperative video recordings, Writer's Cramp Rating Scale (WCRS), and Symptom Severity Scores (SSS) were evaluated at the baseline and at a follow‐up date, which ranged between 8 and 44 months (average, 26 months).ResultsAll the patients had difficulty in performing their most common tasks. Duration of symptoms ranged from 6 months to 12 years. All patients obtained immediate postoperative relief from dystonic symptoms, and the effect was sustained during the follow up period. The WCRS improved from a mean of 20.4 before surgery to a mean of 2.4 at the last follow‐up, whereas the SSS improved from a mean of 29.8 before surgery to a mean of 12 at the last follow‐up. All patients were able to carry out their specific task with little or no difficulty. There were no surgical complications, morbidity, or mortality.ConclusionsVo thalamotomy is a safe and effective procedure providing successful symptom relief in patients of TSD.
Innovations in deep brain stimulation methodology
Authors: Kühn Andrea A. , Volkmann Jens 
Published: July 2016

AbstractDeep brain stimulation is a powerful clinical method for movement disorders that no longer respond satisfactorily to pharmacological management, but its progress has been hampered by stagnation in technological procedure solutions and device development. Recently, the combined research efforts of bioengineers, neuroscientists, and clinicians have helped to better understand the mechanisms of deep brain stimulation, and solutions for the translational roadblock are emerging. Here, we define the needs for methodological advances in deep brain stimulation from a neurophysiological perspective and describe technological solutions that are currently evaluated for near‐term clinical application. © 2016 International Parkinson and Movement Disorder Society
A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene
Authors: Schottmann Gudrun , Sarpong Akosua , Lorenz Carmen , Weinhold Natalie , Gill Esther , Teschner Lisa , Ferdinandusse Sacha , Wanders Ronald J. A. , Prigione Alessandro , Schuelke Markus 
Published: July 2016

AbstractBackgroundRecessive mutations in the 3‐hydroxyisobutyryl‐CoA hydrolase gene (HIBCH) are associated with a rare neurodegenerative disease that affects the basal ganglia. Most patients die during infancy or early childhood. Here we describe 5 adolescent and adult patients from 2 unrelated families, who presented with a movement disorder and MRI features suggestive of Leigh syndrome.MethodsClinical and metabolic assessment was followed by autozygosity mapping and whole exome and Sanger sequencing. HIBCH enzyme activity and the bioenergetic profile were determined in patient fibroblasts.ResultsThe movement disorder was dominated by ataxia in one family and by dystonia in the other. All affected family members carried the identical homozygous c.913A>G (p.T305A) HIBCH mutation. Enzyme activity was reduced, and a valine challenge reduced the oxygen consumption rate.ConclusionsWe report the first adult patients with HIBCH deficiency and a disease course much milder than previously reported, thereby expanding the HIBCH‐associated phenotypic spectrum. © 2016 International Parkinson and Movement Disorder Society
Distortion correction in diffusion‐weighted imaging of the breast: Performance assessment of prospective, retrospective, and combined (prospective + retrospective) approaches
Authors: Hancu Ileana , Lee Seung‐Kyun , Hulsey Keith , Lenkinski Robert , Holland Dominic , Sperl Jonathan I. , Tan Ek T. 
Published: July 2016

PurposeTo compare the effectiveness of prospective, retrospective, and combined (prospective + retrospective) EPI distortion correction methods in bilateral breast diffusion‐weighted imaging (DWI) scans.MethodsFive healthy female subjects underwent an axial bilateral breast DWI exam with and without prospective B0 inhomogeneity correction using slice‐by‐slice linear shimming. In each case, an additional b=0 DWI scan was performed with the polarity of the phase‐encoding gradient reversed, to generate an estimated B0 map; this map or a separately acquired B0 map was used for retrospective correction, either alone or in combination with the prospective correction. The alignment between an undistorted, anatomical reference scan with similar contrast and the corrected b=0 DWI images with different correction schemes was assessed.ResultsThe average cross‐correlation coefficient between the DWI images and the anatomical reference scan was increased from 0.82 to 0.92 over the five volunteers when combined prospective and retrospective distortion correction was applied. Furthermore, such correction substantially reduced patient‐to‐patient variation of the image alignment and the variability of the average apparent diffusion coefficient in normal glandular tissue.ConclusionCombined prospective and retrospective distortion correction can provide an efficient way to reduce susceptibility‐induced image distortions and enhance the reliability of breast DWI exams. Magn Reson Med 78:247–253, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Structural features of Cas2 from Thermococcus onnurineus in CRISPR‐cas system type IV
Authors: Jung Tae‐Yang , Park Kwang‐Hyun , An Yan , Schulga Alexy , Deyev Sergey , Jung Jong‐Hyun , Woo Eui‐Jeon 
Published: July 2016

AbstractCRISPR‐Cas is RNA‐based prokaryotic immune systems that defend against exogenous genetic elements such as plasmids and viruses. Cas1 and Cas2 are highly conserved components that play an essential part in the adaptation stage of all CRISPR‐Cas systems. Characterization of CRISPR‐Cas genes in Thermococcus onnurineus reveals the association of the Cas2 gene with the putative type IV system that lacks Cas1 or its homologous genes. Here, we present a crystal structure of T. onnurineus Cas2 (Ton_Cas2) that exhibits a deep and wide cleft at an interface lined with positive residues (Arg16, Lys18, Lys19, Arg22, and Arg23). The obvious DNA recognizing loops in Cas2 from E. coli (Eco_Cas2) are absent in Ton_Cas2 and have significantly different shapes and electrostatic potential distributions around the putative nucleotide binding region. Furthermore, Ton_Cas2 lacks the hairpin motif at the C‐terminus that is responsible for Cas1 binding in Eco_Cas2. These structural features could be a unique signature and indicate an altered functional mechanism in the adaptation stage of Cas2 in type IV CRISPR‐Cas systems.
Crystal structure and analysis of HdaB: The enteroaggregative Escherichia coli AAF/IV pilus tip protein
Authors: Lee Wei‐Chao , Matthews Steve , Garnett James. A. 
Published: July 2016

AbstractEnteroaggregative Escherichia coli is the primary cause of pediatric diarrhea in developing countries. They utilize aggregative adherence fimbriae (AAFs) to promote initial adherence to the host intestinal mucosa, promote the formation of biofilms, and mediate host invasion. Five AAFs have been identified to date and AAF/IV is amongst the most prevalent found in clinical isolates. Here we present the X‐ray crystal structure of the AAF/IV tip protein HdaB at 2.0 Å resolution. It shares high structural homology with members of the Afa/Dr superfamily of fimbriae, which are involved in host invasion. We highlight surface exposed residues that share sequence homology and propose that these may function in invasion and also non‐conserved regions that could mediate HdaB specific adhesive functions.
Neuronal Trans‐Differentiation in Prostate Cancer Cells
Authors: Farach Andrew , Ding Yi , Lee MinJae , Creighton Chad , Delk Nikki A. , Ittmann Michael , Miles Brian , Rowley David , Farach‐Carson Mary C. , Ayala Gustavo E. 
Published: July 2016

BACKGROUNDNeuroendocrine (NE) differentiation in prostate cancer (PCa) is an aggressive phenotype associated with therapy resistance. The complete phenotype of these cells is poorly understood. Clinical classification is based predominantly on the expression of standard NE markers.METHODSWe analyzed the phenotype of NE carcinoma of the prostate utilizing in vitro methods, in silico, and immunohistochemical analyses of human disease.RESULTSLNCaP cells, subjected to a variety of stressors (0.1% [v/v] fetal bovine serum, cyclic AMP) induced a reproducible phenotype consistent with neuronal trans‐differentiation. Cells developed long cytoplasmic processes resembling neurons. As expected, serum deprived cells had decreased expression in androgen receptor and prostate specific antigen. A significant increase in neuronal markers also was observed. Gene array analysis demonstrated that LNCaP cells subjected to low serum or cAMP showed statistically significant manifestation of a human brain gene expression signature. In an in silico experiment using human data, we identified that only hormone resistant metastatic prostate cancer showed enrichment of the “brain profile.” Gene ontology analysis demonstrated categories involved in neuronal differentiation. Three neuronal markers were validated in a large human tissue cohort.CONCLUSIONThis study proposes that the later stages of PCa evolution involves neuronal trans‐differentiation, which would enable PCa cells to acquire independence from the neural axis, critical in primary tumors. Prostate 76:1312–1325, 2016. © 2016 Wiley Periodicals, Inc.
Accumulation of Palmitoylcarnitine and Its Effect on Pro‐Inflammatory Pathways and Calcium Influx in Prostate Cancer
Authors: Al‐Bakheit Ala'a , Traka Maria , Saha Shikha , Mithen Richard , Melchini Antonietta 
Published: July 2016

BACKGROUNDAcylcarnitines are intermediates of fatty acid oxidation and accumulate as a consequence of the metabolic dysfunction resulting from the insufficient integration between β‐oxidation and the tricarboxylic acid (TCA) cycle. The aim of this study was to investigate whether acylcarnitines accumulate in prostate cancer tissue, and whether their biological actions could be similar to those of dihydrotestosterone (DHT), a structurally related compound associated with cancer development.METHODSLevels of palmitoylcarnitine (palcar), a C16:00 acylcarnitine, were measured in prostate tissue using LC‐MS/MS. The effect of palcar on inflammatory cytokines and calcium (Ca2+) influx was investigated in in vitro models of prostate cancer.RESULTSWe observed a significantly higher level of palcar in prostate cancerous tissue compared to benign tissue. High levels of palcar have been associated with increased gene expression and secretion of the pro‐inflammatory cytokine IL‐6 in cancerous PC3 cells, compared to normal PNT1A cells. Furthermore, we found that high levels of palcar induced a rapid Ca2+ influx in PC3 cells, but not in DU145, BPH‐1, or PNT1A cells. This pattern of Ca2+ influx was also observed in response to DHT. Through the use of whole genome arrays we demonstrated that PNT1A cells exposed to palcar or DHT have a similar biological response.CONCLUSIONSThis study suggests that palcar might act as a potential mediator for prostate cancer progression through its effect on (i) pro‐inflammatory pathways, (ii) Ca2+ influx, and (iii) DHT‐like effects. Further studies need to be undertaken to explore whether this class of compounds has different biological functions at physiological and pathological levels. Prostate 76:1326–1337, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.
Development of a population pharmacokinetic model of prucalopride in children with functional constipation
Authors: van Schaick Erno , Benninga Marc A. , Levine Amy , Magnusson Mats , Troy Steven 
Published: July 2016

AbstractA recent phase 3 trial of prucalopride in children with functional constipation (SPD555‐303 ClinicalTrials.gov Identifier: NCT01330381) reported negative efficacy results. Here, we developed a population pharmacokinetic (PK) model of prucalopride in children to assess prucalopride exposure in SPD555‐303. An initial population PK model in children was developed based on sampled single‐dose data from a phase 1 study (PRU‐USA‐12). This model was subsequently updated with sampled data from SPD555‐303 and used to simulate plasma concentration–time profiles for children aged 6 months to 18 years who were treated once daily with prucalopride 0.02, 0.04, or 0.06 mg kg−1 (maximum dose, 2 mg). Simulated PK profiles were compared with those of adults at the recommended dose of 2 mg once daily. Data were available from 38 patients (median age, 8.5 years) in PRU‐USA‐12 and 137 patients (median age, 7.9 years) in SPD555‐303. Mean (range) area under the plasma concentration–time curve (AUC) at steady state was 62.3 (40.5–82.7) ng mL−1 h (dose, 0.03 mg kg−1) in PRU‐USA‐12 and 100.3 (22.7–286.0) ng mL−1 h (dose, 0.04 mg kg−1; maximum, 2 mg) in SPD555‐303. Prucalopride 0.04 mg kg−1 once daily in children produced similar maximum plasma concentrations and approximately 10% lower AUC compared with adults receiving 2 mg once daily. This population PK analysis indicates that the PK profile of prucalopride in children in SPD555‐303 was similar to that observed in adults. The negative efficacy results of SPD555‐303 cannot be explained by differences in prucalopride exposure between children and adults.
Characterization of death receptor 3‐dependent aortic changes during inflammatory arthritis
Authors: Williams Jessica O. , Wang Eddie C. Y. , Lang Derek , Williams Anwen S. 
Published: July 2016

AbstractMurine collagen‐induced arthritis (mCIA) is characterized by decreased vascular constriction responses and increased MMP‐9. Here, we describe additional histological alterations within the aorta and surrounding perivascular adipose tissue (PVAT), study the role of PVAT in constriction response, and investigate the potential involvement of death receptor 3 (DR3). mCIA was induced in wild‐type (WT) and DR3−/− mice with nonimmunized, age‐matched controls. Vascular function was determined in isolated aortic rings ±PVAT, using isometric tension myography, in response to cumulative serotonin concentrations. Cellular expression of F4/80 (macrophages), Ly6G (neutrophils), DR3, and MMP‐9 was determined using immunohistochemistry. In WTs, arthritis‐induced vascular dysfunction was associated with increased F4/80+ macrophages and increased DR3 expression in the aorta and PVAT. MMP‐9 was also up‐regulated in PVAT, but did not correlate with alterations of PVAT intact constriction. DR3−/− mice inherently showed increased leukocyte numbers and MMP‐9 expression in the PVAT, but retained the same nonarthritic constriction response as DR3WT mice ±PVAT. Arthritic DR3−/− mice had a worsened constriction response than DR3WT and showed an influx of neutrophils to the aorta and PVAT. Macrophage numbers were also up‐regulated in DR3−/− PVAT. Despite this influx, PVAT intact DR3−/− constriction responses were restored to the same level as DR3WT. Impaired vascular constriction in inflammatory arthritis occurs independently of total MMP‐9 levels, but correlates with macrophage and neutrophil ingress. Ablating DR3 worsens the associated vasculature dysfunction, however, DR3−/− PVAT is able to protect the aorta against aberrant vasoconstriction caused in this model.
Pharmacological characterization of a novel potent, selective, and orally active phosphodiesterase 10A inhibitor, PDM‐042 [(E)‐4‐(2‐(2‐(5,8‐dimethyl‐[1,2,4]triazolo[1,5‐a]pyrazin‐2‐yl)vinyl)‐6‐(pyrrolidin‐1‐yl)pyrimidin‐4‐yl)morpholine] in rats: potential for the treatment of schizophrenia
Authors: Arakawa Keita , Maehara Shunsuke , Yuge Natsuko , Ishikawa Makoto , Miyazaki Yutaka , Naba Hiroyasu , Kato Yutaka , Nakao Kazunari 
Published: July 2016

AbstractRecently, we identified a novel phosphodiesterase 10A (PDE10A) inhibitor, PDM‐042 ((E)‐4‐(2‐(2‐(5,8‐dimethyl‐[1,2,4]triazolo[1,5‐a]pyrazin‐2‐yl)vinyl)‐6‐(pyrrolidin‐1‐yl)pyrimidin‐4‐yl)morpholine). PDM‐042 showed potent inhibitory activities for human and rat PDE10A with IC50 values of less than 1 nmol/L and more than 1000‐fold selectivity against other phosphodiesterases. Tritiated PDM‐042, [3H]PDM‐042, had high affinity for membranes prepared from rat striatum with a Kd value of 8.5 nmol/L. The specific binding of [3H]PDM‐042 was displaced in a concentration‐dependent manner by PDM‐042 and another structurally unrelated PDE10A inhibitor, MP‐10. In rat studies, PDM‐042 showed excellent brain penetration (striatum/plasma ratio = 6.3), occupancy rate (86.6% at a dose of 3 mg/kg), and good oral bioavailability (33%). These data indicate that PDM‐042 is a potent, selective, orally active, and brain‐penetrable PDE10A inhibitor. In behavioral studies using rat models relevant to schizophrenia, PDM‐042 significantly antagonized MK‐801‐induced hyperlocomotion (0.1–0.3 mg/kg) without affecting spontaneous locomotor activity and attenuated the conditioned avoidance response (CAR) (0.3–1 mg/kg). In tests for adverse effects, PDM‐042 had a minimal effect on catalepsy, even at a much higher dose (10 mg/kg) than the minimal effective dose (0.3 mg/kg) in the CAR. Furthermore, PDM‐042 had no effect on prolactin release or glucose elevation up to 3 mg/kg, while risperidone increased prolactin release and olanzapine enhanced glucose levels at doses near their efficacious ones in the CAR. Our results suggest that PDM‐042 is a good pharmacological tool that can be used to investigate the role of PDE10A and may have therapeutic potential for the treatment of schizophrenia.