bluuebunny/crossref_metadata_2025_split huggingface dataset:
Composition and regulation of maternal and zygotic transcriptomes reflects species-specific reproductive mode
Authors: Shen-Orr Shai S , Pilpel Yitzhak , Hunter Craig P 
Published: June 2010

Abstract
Background
Early embryos contain mRNA transcripts expressed from two distinct origins; those expressed from the mother's genome and deposited in the oocyte (maternal) and those expressed from the embryo's genome after fertilization (zygotic). The transition from maternal to zygotic control occurs at different times in different animals according to the extent and form of maternal contributions, which likely reflect evolutionary and ecological forces. Maternally deposited transcripts rely on post-transcriptional regulatory mechanisms for precise spatial and temporal expression in the embryo, whereas zygotic transcripts can use both transcriptional and post-transcriptional regulatory mechanisms. The differences in maternal contributions between animals may be associated with gene regulatory changes detectable by the size and complexity of the associated regulatory regions.

Results
We have used genomic data to identify and compare maternal and/or zygotic expressed genes from six different animals and find evidence for selection acting to shape gene regulatory architecture in thousands of genes. We find that mammalian maternal genes are enriched for complex regulatory regions, suggesting an increase in expression specificity, while egg-laying animals are enriched for maternal genes that lack transcriptional specificity.

Conclusions
We propose that this lack of specificity for maternal expression in egg-laying animals indicates that a large fraction of maternal genes are expressed non-functionally, providing only supplemental nutritional content to the developing embryo. These results provide clear predictive criteria for analysis of additional genomes.
Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates
Authors: Brahmer Julie R. , Drake Charles G. , Wollner Ira , Powderly John D. , Picus Joel , Sharfman William H. , Stankevich Elizabeth , Pons Alice , Salay Theresa M. , McMiller Tracee L. , Gilson Marta M. , Wang Changyu , Selby Mark , Taube Janis M. , Anders Robert , Chen Lieping , Korman Alan J. , Pardoll Drew M. , Lowy Israel , Topalian Suzanne L. 
Published: June 2010

Purpose Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti–PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. Patients and Methods Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non–small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti–PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. Results Anti–PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti–PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. Conclusion Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
J. B. S. Haldane's Last Years: His Life and Work in India (1957–1964)
Authors: Dronamraju Krishna 
Published: June 2010

Abstract
J. B. S. Haldane (1892–1964) was an outstanding scientist and a polymath who contributed significantly to physiology, genetics, biochemistry, statistics, biometry, cosmology, and philosophy, although he himself possessed no formal qualifications in any branch of science. His early science training was provided by his father, Oxford University physiologist J. S. Haldane, and the rest was self-taught. The author came to know him well as his student during his last years, which were spent in India (1957–1964). Haldane's unique intellectual qualities and the research undertaken by his associates in India during those years are described.
Evaluation of a Point-of-Care Blood Analyzer for Use in Determination of Select Hematological Indices in the Seminole Killifish
Authors: DiMaggio Matthew A , Ohs Cortney L , Petty B Denise 
Published: June 2010

Abstract
Conventional methodologies for hematological analysis are gradually being replaced with new technologies. Point-of-care blood analyzers are both efficient and user friendly. As the use of such technologies becomes more pervasive in current literature, investigations into the accuracy and reliability of point-of-care analyzers for evaluating fish hematological indices are warranted. The purpose of this study was to evaluate a point-of-care blood analyzer (i-STAT®) and chosen cartridge (E3+) against conventionally accepted instrumentation (CAI) for use in determination of hematocrit, sodium, potassium, and chloride values in Seminole killifish Fundulus seminolis. Whole blood, a whole-blood heparin dilution, and undiluted plasma were analyzed in the point-of-care unit to determine hematological parameters of interest. The Bland–Altman method for assessing agreement between two methods of clinical measurement was used as well as calculations of correlation coefficients and two-tailed paired Student's t-tests. Generally, mean values obtained from CAI were higher than those from the i-STAT using whole blood, heparin-diluted blood, and plasma. Significant differences (P ≤ 0.05) were observed between all means analyzed by t-tests. When compared with CAI results, none of the blood index values generated by the i-STAT in these experiments could be considered reliable.
Optimal management strategies to control local population growth or population spread may not be the same
Authors: Shea Katriona , Jongejans Eelke , Skarpaas Olav , Kelly Dave , Sheppard Andy W. 
Published: June 2010

The objective of most pest management programs is to “control” the pest species. However, optimal control of local abundance and population growth may require different management strategies than optimal control of spatial spread. We use coupled demographic–dispersal models to address the relative importance of different management approaches to these two main control objectives for the invasive thistle Carduus nutans. The models are parameterized with data from thistle populations in the native (France) and invaded ranges (Australia and New Zealand). We assess a wide range of commonly used management strategies for their absolute and relative impacts on population growth and spread in both invaded‐range scenarios.The projected population growth rate in New Zealand is more than twice that in Australia, while the spread rate is more than four times the Australian value. In general, spread and growth are both most strongly affected by the same life cycle transitions; however, in a few cases certain vital rates disproportionately affect either spread or growth. The transition that represents the contribution of large rosettes in one year to the number of large rosettes in the following year (the large rosette–large rosette transition) in Australia is dominated by reproduction (rather than survival) and hence is relatively more important to spread than to population growth. In New Zealand, the small rosette–small rosette transition is also predominantly dispersal‐related. However, establishment of small plants from the seed bank contributes more to population growth than spread, as no dispersal is involved.The fine‐resolution vital‐rate‐based modeling approach allows us to identify potentially novel optimal management strategies: approaches that reduce microsite availability show promise for reducing both population growth and spread, while strategies that affect dispersal parameters will affect spread. Additionally, the relative ranking of some biocontrol agents shifts depending on whether control of population growth or population spread is the desired outcome and therefore could alter which of the agents are preferred for release in a new area. The possibility of differences in ranked agent effectiveness has been predicted theoretically, but never before demonstrated using field data.
The Effect of Local Anesthetic on Quality of Recovery Characteristics Following Dental Rehabilitation Under General Anesthesia in Children
Authors: Townsend Janice A. , Ganzberg Steven , Thikkurissy S. 
Published: June 2010

Abstract
This study is a randomized, prospective, double-blind study to evaluate the effects of the combination of local anesthetics and an intravenous nonsteroidal anti-inflammatory drug (NSAID) vs NSAID alone on quality of recovery following dental rehabilitation under general anesthesia (GA). Twenty-seven healthy children aged 3–5.5 years underwent dental rehabilitation under GA. Fifteen children in the experimental group received oral infiltration of local anesthetic in addition to intravenous ketorolac tromethamine, while 12 children in the control group received intravenous ketorolac tromethamine alone for postoperative pain management. Pain behaviors were evaluated immediately postoperatively using a FLACC scale and 4 hours postoperatively by self-report using various scales. Parents reported perception of child pain and comfort and any occurrences of postoperative cheek biting. The use of intraoral infiltration local anesthesia for complete dental rehabilitation under general anesthesia for children aged 3–5.5 years did not result in improved pain behaviors in the postanesthesia care unit (PACU), nor did it result in improved pain behaviors 4–6 hours postoperatively as measured by the FLACC scale, FACES scale, and subjective reports of parents or a PACU nurse. Those children receiving local anesthesia had a higher incidence of negative symptoms related to local anesthetic administration, including a higher incidence of lip and cheek biting, which was of clinical importance, but not statistically significant. Infiltration of local anesthetic for dental rehabilitation under general anesthesia did not improve quality of recovery in children aged 3–5.5 years.
Local and Systemic Toxicity of Intraoral Submucosal Injections of Phentolamine Mesylate (OraVerse)
Authors: Rutherford Bruce , Zeller Jillynne R. , Thake Daryl 
Published: June 2010

Abstract
OraVerseTM, an injectable formulation of phentolamine mesylate (PM), was recently approved by the U.S. Food and Drug Administration (FDA) for reversal of anesthesia of the lip and tongue and associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor. Because PM had not been approved previously for submucosal administration, 2 Good Laboratory Practices (GLP) studies in dogs designed to investigate systemic toxicity and the local effects of single and repeated dosing of OraVerse on the inferior alveolar nerve and branches of the superior alveolar nerve and adjacent soft tissues after local administration were conducted. Systemic toxicity was measured by preinjection and postinjection clinical examinations, clinical chemistry, and gross and microscopic examinations of major organs after necropsy. No evidence of systemic toxicity was detected. Local nerve and adjacent tissue damage was assessed by conventional histopathology. Nerve degeneration was evident in 1 animal. Mild perineural inflammation adjacent to the inferior alveolar nerve and inflammatory exudates were observed in submucosal tissues in several animals. No changes were observed in the nerves at injection sites of dogs from any dose group that were considered directly related to the test articles. These data reveal that single and repeated intraoral administrations of OraVerse are well tolerated in beagle dogs.
Preoperative Medical Evaluation: Part 2: Pulmonary, Endocrine, Renal, and Miscellaneous Considerations
Authors: Becker Daniel E. 
Published: June 2010

Abstract
A thorough assessment of a patient's medical status is standard practice when dental care is provided. Although this is true for procedures performed under local anesthesia alone, the information gathered may be viewed somewhat differently if the dentist is planning to provide sedation or general anesthesia as an adjunct to dental treatment. This article, the second of a 2-part sequence on preoperative assessment, will address pulmonary and other noncardiovascular disorders.
Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs when administered as a preanesthetic via various routes or in combination with butorphanol
Authors: Zwijnenberg Raphael J. , del Rio Carlos L. , Pollet Robert A. , Muir William W. 
Published: June 2010

Abstract
Objective—To determine the anesthetic-sparing effects of perzinfotel when administered as a preanesthetic via IV, IM, or SC routes or IM in combination with butorphanol.
Animals—6 healthy sexually intact Beagles (4 males and 2 females; age, 18.5 to 31 months; body weight, 9.8 to 12.4 kg).
Procedures—After administration of a placebo, perzinfotel (10 to 30 mg/kg), or a perzinfotel-butorphanol combination, anesthesia was induced in dogs with propofol and maintained with isoflurane in oxygen. The following variables were continuously monitored: bispectral index; heart rate; systolic, diastolic, and mean arterial blood pressures; end-tidal concentration of isoflurane; end-tidal partial pressure of CO2; oxygen saturation as measured by pulse oximetry; rectal temperature; and inspiration and expiration concentrations of isoflurane. A noxious stimulation protocol was used, and the minimum alveolar concentration (MAC) was determined twice during anesthesia.
Results—IV, IM, and SC administration of perzinfotel alone decreased the mean isoflurane MAC values by 32% to 44% and significantly increased bispectral index values. A dose of 30 mg of perzinfotel/kg IM resulted in significant increases in heart rate and diastolic arterial blood pressure. The greatest MAC reduction (59%) was obtained with a combination of 20 mg of perzinfotel/kg IM and 0.2 mg of butorphanol/kg IM, whereas administration of butorphanol alone yielded a 15% reduction in the isoflurane MAC.
Conclusions and Clinical Relevance—SC, IM, or IV administration of perzinfotel prior to induction of isoflurane anesthesia improved anesthetic safety by reducing inhalant anesthetic requirements in healthy dogs.
Ease of oral administration and owner-perceived acceptability of triglyceride oil, dissolving thin film strip, and gelatin capsule formulations to healthy cats
Authors: Traas Anne M. , Fleck Timothy , Ellings Andrea , Mahabir Sean , Stuebner Kathy , Brown Dorothy C. , Durso Dana , DiGregorio Michael , Bode Lora , Kievit Kelly I. , McCall Robert 
Published: June 2010

Abstract
Objective—To compare owner-assessed ease of administration and overall acceptability of 3 chemically inactive formulations administered PO to cats.
Animals—90 healthy client-owned cats.
Procedures—Cats were randomly assigned to receive 1 of 3 formulations PO once daily for 14 days: medium chain triglyceride (MCT) oil, dissolving thin film strips (proprietary ingredients), or gelatin capsules filled with microcrystalline cellulose. Owners administered the formulations and rated ease of administration daily on a 10-cm visual analogue scale (VAS). At the end of the study, owners rated overall acceptability of formulations from their own perspective and their overall perception of acceptability to their cat.
Results—Mean VAS scores for daily ease of administration of MCT oil and film strips were significantly higher than scores for gelatin capsules at all time points, except on days 2, 4, and 7. There was no difference between MCT oil and film strip formulation scores. Mean VAS scores were 8.8 (MCT oil), 8.9 (film strips), and 7.4 (gelatin capsules) for overall acceptability to owners and 8.0 (MCT oil), 8.3 (film strips), and 6.7 (gelatin capsules) for overall owner-perceived acceptability to cats.
Conclusions and Clinical Relevance—Daily ease of administration on 11 of 14 days and overall owner-perceived acceptability to cats were scored significantly higher for film strips and MCT oil, compared with scores for gelatin capsules. Overall acceptability to owners followed a similar pattern; however, the differences were not significant. Dissolving thin film strip or MCT oil vehicles may allow for easier PO administration of medication to cats than does administration of gelatin capsules.
Histologic and immunohistochemical evaluation of intestinal innervation in dogs with and without intussusception
Authors: Oliveira-Barros Leda M. , Costa-Casagrande Thais A. , Cogliati Bruno , Sá Lílian R. M. , Matera Julia M. 
Published: June 2010

Abstract
Objective—To assess viability of innervation in bowel segments appearing macroscopically viable from dogs with intussusception.
Animals—7 dogs without gastrointestinal dysfunction that had been euthanized for reasons unrelated to the study (control dogs) and 13 dogs with intussusception that underwent enterectomy and intestinal anastomosis (affected dogs).
Procedures—A total of 31 samples of intestinal tissue were obtained from the control dogs; 28 samples were obtained from affected dogs during surgery. Samples were histologically and immunohistochemically prepared and subjectively scored for degree of vacuolization and staining, respectively. Other data collected included mean muscle cell density of circular and longitudinal muscular layers, ratio between areas of muscular layers, mean number of myenteric plexuses, mean ganglion cell density of myenteric plexuses, and degree of degeneration in neuronal plexuses as estimated through synaptophysin and neuron-specific enolase (NSE) immunoreactivity.
Results—Mean muscle cell density of longitudinal muscular layers, ratio between areas of muscular layers, and synaptophysin immunoreactivity did not differ significantly between affected and control dogs; values of all other variables did. Correlations were evident between mean ganglion cell density in myenteric plexuses and mean muscle cell density in circular muscular layers, degree of neuronal degeneration in myenteric plexuses and NSE immunoreactivity, and degree of neuronal degeneration in myenteric plexuses and mean ganglion cell density of myenteric plexuses.
Conclusions and Clinical Relevance—Innervation may be impaired in bowel segments that appear macroscopically viable. Therefore, careful evaluation of preserved surgical margins during enterectomy and enteroanastomosis and monitoring of digestive function after surgery are important.
Evaluation of activation of G proteins in response to thyroid stimulating hormone in thyroid gland cells from euthyroid and hyperthyroid cats
Authors: Ward Cynthia R. , Windham William R. , Dise Darrell 
Published: June 2010

Abstract
Objective—To evaluate alterations in ligand-stimulated activity of G proteins in thyroid gland cells of hyperthyroid cats.
Sample Population—Membranes of thyroid gland cells isolated from 5 hyperthyroid cats and 3 age-matched euthyroid (control) cats immediately after the cats were euthanatized.
Procedures—Isolated thyroid cell membranes were treated with thyroid-stimulating hormone (TSH), and activation of G protein was quantified by measurement of the binding of guanosine triphosphate γ labeled with sulfur 35 (GTPγ35S). The separate effects of G-protein inhibitory (Gi) and G-protein stimulatory (Gs) proteins were determined by the use of pertussis toxin and cholera toxin, respectively.
Results—Thyroid cell membranes from hyperthyroid cats had higher basal GTPγ35S binding than did thyroid cell membranes from euthyroid cats. Thyroid cell membranes from hyperthyroid and euthyroid cats had a concentration-dependent increase in TSH-stimulated GTPγ35S binding over the TSH range of 0 to 100 mU/mL, with maximal activity at 1 to 100 mU/mL for both. The percentage increase in GTPγ35S binding stimulated by TSH was similar in magnitude between the membranes from hyperthyroid and euthyroid cats. The TSH-stimulated activation of Gs and Gi was not different between euthyroid and hyperthyroid cats.
Conclusions and Clinical Relevance—Ligand-stimulated activation of G proteins was the same in thyroid cell membranes obtained from hyperthyroid and euthyroid cats. Therefore, alterations in inherent Gs or Gi activities did not appear to be part of the pathogenesis of hyperthyroidism in cats.
Gene expression of proteolytic systems and growth regulators of skeletal muscle in horses with myopathy associated with pituitary pars intermedia dysfunction
Authors: Aleman Monica , Nieto Jorge E. 
Published: June 2010

Abstract
Objective—To investigate gene expression of the major proteolytic systems and growth regulators in skeletal muscle of horses with myopathy associated with pituitary pars intermedia dysfunction (PPID).
Animals—14 horses with PPID-associated myopathy and 7 healthy control horses.
Procedures—Horses with PPID and controls were age matched (15 to 28 years old). Muscle biopsy specimens were collected from both groups and processed for RNA and cDNA extraction. Validation of the most stable housekeeping genes for skeletal muscle was performed and used to compare gene expression of the following proteolytic systems: cysteine aspartate protease–dependent systems (caspases), lysosomal-dependent systems (cathepsins), non–lysosomal calcium protease–dependent systems (calpains), and ubiquitin-proteasome–dependent systems (ubiquitins). Gene expression of negative regulators of muscle growth (myostatin and inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α) was also determined.
Results—No significant difference between groups was detected in expression of the major proteolytic systems except for m-calpain, which was greater in horses with PPID. No differences in gene expression of myostatin and interleukin-1β, interleukin-6, and tumor necrosis factor-α were detected between groups.
Conclusions and Clinical Relevance—Greater expression of m-calpain may suggest that calpains play an important role in development of muscle atrophy in horses with PPID. However, because posttranslational events may alter protein activation, inactivation, and functions not studied here, other mechanisms of muscle atrophy cannot be excluded.