bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Protein Phosphatase 4 in Regulating Microtubule Severing in theCaenorhabditis elegansEmbryo
Authors: Han Xue , Gomes José-Eduardo , Birmingham Cheryl L , Pintard Lionel , Sugimoto Asako , Mains Paul E 
Published: December 2008

AbstractMEI-1, the catalytic subunit of the Caenorhabditis elegans “katanin” microtubule-severing complex, is required for meiotic spindle formation. However, MEI-1 must be inactivated after the completion of meiosis to allow formation of the first mitotic spindle. Recent work demonstrated that post-meiotic MEI-1 undergoes ubiquitin-dependent degradation mediated by two independent pathways. Here we describe another level of MEI-1 regulation involving the protein phosphatase 4 (PP4) complex. The PP4 R1 regulatory subunit protein phosphatase four regulatory subunit 1 (ppfr-1) was identified in an RNA interference (RNAi) screen for suppressors of a mei-1(gf) allele that is refractory to post-meiotic degradation. RNAi to the PP4 catalytic subunit PPH-4.1 or to the α4 regulatory PPFR-4 also suppressed lethality of ectopic MEI-1. These results suggest that PP4(+) activates MEI-1, and therefore loss of PP4 decreases ectopic MEI-1(gf) activity. PPH-4.1 and MEI-1 co-immunoprecipitate with one another, indicating that the PP4 complex likely regulates MEI-1 activity directly rather than through an intermediate. The ppfr-1 mutant has subtle meiotic defects indicating that PPFR-1 also regulates MEI-1 during meiosis. MBK-2 is the only kinase known to phosphorylate MEI-1 and triggers post-meiotic MEI-1 degradation. However, genetic interactions between PP4 and mbk-2 were not consistent with an antagonistic relationship between the phosphatase and kinase. Additionally, reducing PP4 in mei-1(gf) did not change the level or localization of post-meiotic MEI-1. Thus, by making use of a genetic background where MEI-1 is ectopically expressed, we have uncovered a third mechanism of MEI-1 regulation, one based on phosphorylation but independent of degradation. The redundant regulatory pathways likely contribute in different ways to the rapid and precise post-meiotic inactivation of MEI-1 microtubule-severing activity.
The Ras/cAMP Pathway and the CDK-Like Kinase Ime2 Regulate the MAPK Smk1 and Spore Morphogenesis in Saccharomyces cerevisiae
Authors: McDonald Christine M , Wagner Marisa , Dunham Maitreya J , Shin Marcus E , Ahmed Noreen T , Winter Edward 
Published: December 2008

Abstract
Meiotic development (sporulation) in the yeast Saccharomyces cerevisiae is induced by nutritional deprivation. Smk1 is a meiosis-specific MAP kinase homolog that controls spore morphogenesis after the meiotic divisions have taken place. In this study, recessive mutants that suppress the sporulation defect of a smk1-2 temperature-sensitive hypomorph were isolated. The suppressors are partial function alleles of CDC25 and CYR1, which encode the Ras GDP/GTP exchange factor and adenyl cyclase, respectively, and MDS3, which encodes a kelch-domain protein previously implicated in Ras/cAMP signaling. Deletion of PMD1, which encodes a Mds3 paralog, also suppressed the smk1-2 phenotype, and a mds3-Δ pmd1-Δ double mutant was a more potent suppressor than either single mutant. The mds3-Δ, pmd1-Δ, and mds3-Δ pmd1-Δ mutants also exhibited mitotic Ras/cAMP phenotypes in the same rank order. The effect of Ras/cAMP pathway mutations on the smk1-2 phenotype required the presence of low levels of glucose. Ime2 is a meiosis-specific CDK-like kinase that is inhibited by low levels of glucose via its carboxy-terminal regulatory domain. IME2-ΔC241, which removes the carboxy-terminal domain of Ime2, exacerbated the smk1-2 spore formation phenotype and prevented cyr1 mutations from suppressing smk1-2. Inhibition of Ime2 in meiotic cells shortly after Smk1 is expressed revealed that Ime2 promotes phosphorylation of Smk1's activation loop. These findings demonstrate that nutrients can negatively regulate Smk1 through the Ras/cAMP pathway and that Ime2 is a key activator of Smk1 signaling.
Genetic and Genomewide Analysis of Simultaneous Mutations in Acetylated and Methylated Lysine Residues in Histone H3 inSaccharomyces cerevisiae
Authors: Jin Yi , Rodriguez Amy M , Wyrick John J 
Published: December 2008

AbstractAcetylated and methylated lysine residues in histone H3 play important roles in regulating yeast gene expression and other cellular processes. Previous studies have suggested that histone H3 acetylated and methylated lysine residues may functionally interact through interdependent pathways to regulate gene transcription. A common genetic test for functional interdependence is to characterize the phenotype of a double mutant. Using this strategy, we tested the genetic interaction between histone H3 mutant alleles that simultaneously eliminate acetylated or methylated lysine residues. Our results indicate that mutation of histone H3 acetylated lysine residues alleviates growth phenotypes exhibited by the H3 methylated lysine mutant. In contrast, histone H3 acetylated and methylated lysine mutants display largely independent effects on yeast gene expression. Intriguingly, these expression changes are preferentially associated with chromosomal regions in which histone H3 lysine residues are hypoacetylated and hypomethylated. Finally, we show that the acetylated and methylated lysine mutants have strikingly different effects on the binding of Sir4 to yeast telomeres, suggesting that histone H3 acetylated lysine residues regulate yeast silencing through a mechanism independent of SIR binding.
Association Mapping in Outbred Populations: Power and Efficiency When Genotyping Parents and Phenotyping Progeny
Authors: Chenoweth Stephen F , Visscher Peter M 
Published: December 2008

AbstractWe develop expressions for the power to detect associations between parental genotypes and offspring phenotypes for quantitative traits. Three different “indirect” experimental designs are considered: full-sib, half-sib, and full-sib–half-sib families. We compare the power of these designs to detect genotype–phenotype associations relative to the common, “direct,” approach of genotyping and phenotyping the same individuals. When heritability is low, the indirect designs can outperform the direct method. However, the extra power comes at a cost due to an increased phenotyping effort. By developing expressions for optimal experimental designs given the cost of phenotyping relative to genotyping, we show how the extra costs associated with phenotyping a large number of individuals will influence experimental design decisions. Our results suggest that indirect association studies can be a powerful means of detecting allelic associations in outbred populations of species for which genotyping and phenotyping the same individuals is impractical and for life history and behavioral traits that are heavily influenced by environmental variance and therefore best measured on groups of individuals. Indirect association studies are likely to be favored only on purely economical grounds, however, when phenotyping is substantially less expensive than genotyping. A web-based application implementing our expressions has been developed to aid in the design of indirect association studies.
Genetic Interactions Between Regulators of Chlamydomonas Phosphorus and Sulfur Deprivation Responses
Authors: Moseley Jeffrey L , Gonzalez-Ballester David , Pootakham Wirulda , Bailey Shaun , Grossman Arthur R 
Published: December 2008

Abstract
The Chlamydomonas reinhardtii PSR1 gene is required for proper acclimation of the cells to phosphorus (P) deficiency. P-starved psr1 mutants show signs of secondary sulfur (S) starvation, exemplified by the synthesis of extracellular arylsulfatase and the accumulation of transcripts encoding proteins involved in S scavenging and assimilation. Epistasis analysis reveals that induction of the S-starvation responses in P-limited psr1 cells requires the regulatory protein kinase SNRK2.1, but bypasses the membrane-targeted activator, SAC1. The inhibitory kinase SNRK2.2 is necessary for repression of S-starvation responses during both nutrient-replete growth and P limitation; arylsulfatase activity and S deficiency-responsive genes are partially induced in the P-deficient snrk2.2 mutants and become fully activated in the P-deficient psr1snrk2.2 double mutant. During P starvation, the sac1snrk2.2 double mutants or the psr1sac1snrk2.2 triple mutants exhibit reduced arylsulfatase activity compared to snrk2.2 or psr1snrk2.2, respectively, but the sac1 mutation has little effect on the abundance of S deficiency-responsive transcripts in these strains, suggesting a post-transcriptional role for SAC1 in elicitation of S-starvation responses. Interestingly, P-starved psr1snrk2.2 cells bleach and die more rapidly than wild-type or psr1 strains, suggesting that activation of S-starvation responses during P deprivation is deleterious to the cell. From these results we infer that (i) P-deficient growth causes some internal S limitation, but the S-deficiency responses are normally inhibited during acclimation to P deprivation; (ii) the S-deficiency responses are not completely suppressed in P-deficient psr1 cells and consequently these cells synthesize some arylsulfatase and exhibit elevated levels of transcripts for S-deprivation genes; and (iii) this increased expression is controlled by regulators that modulate transcription of S-responsive genes during S-deprivation conditions. Overall, the work strongly suggests integration of the different circuits that control nutrient-deprivation responses in Chlamydomonas.
General Pediatrics Resident Perspectives on Training Decisions and Career Choice
Authors: Freed Gary L. , Dunham Kelly M. , Jones M. Douglas , McGuinness Gail A. , Althouse Linda ,   and the Research Advisory Committee of the American Board of Pediatrics
Published: December 2008

OBJECTIVE. Little is known regarding at what point during the training period residents in pediatrics make decisions on their future career choices. As part of a dedicated process of reexamining the structure of residency training in pediatrics, the American Board of Pediatrics sought information to better understand the influences, process, and sequencing of both residency program selection and career decision-making among residents.METHODS. All pediatrics resident physicians in all training programs in the United States and Canada (N = 8290) received the survey as part of the general pediatrics in-training examination. The survey focused on exploring how and when pediatrics residents make career choices and assessed perceived flexibility of their individual pediatrics residency program.RESULTS. The response rate was 95%. Location was the most important factor in selecting a residency program for 42% of all residents. Almost half of the pediatrics residents planned to pursue fellowship training after residency, a proportion that changed little across the 3 training years (level 1: 47%; level 2: 49%; level 3: 47%). Those who planned to pursue a general pediatrics career (either with or without inpatient care) were more likely than those who intended to pursue fellowship training to report that lifestyle was the most important factor in their career choice (63% vs 21%).CONCLUSIONS. Not surprisingly, different priorities motivate pediatricians to pursue specific programs for training and specific career options. The finding that those with the highest priority regarding lifestyle are more likely to pursue generalist training has implications for the generalist workforce, because those persons may also be more likely to seek part-time employment. Lifestyle concerns may need to be addressed in subspecialty training and subsequent subspecialty careers to ensure a continued flow of residents into fellowship training.
Recently Trained Pediatric Subspecialists: Perspectives on Training and Scope of Practice
Authors: Freed Gary L. , Dunham Kelly M. , Switalski Kara E. , Jones M. Douglas , McGuinness Gail A. ,   and the Research Advisory Committee of the American Board of Pediatrics
Published: December 2008

OBJECTIVES. Little is known regarding the factors influencing the decision to pursue pediatric subspecialty fellowship training and the timing of when such a decision is made. In addition, there is no information regarding whether the general pediatrics training received in residency is perceived as valuable by subspecialists. This study was conducted to characterize the strengths and weaknesses of residency and fellowship training from the perspective of recently trained pediatric subspecialists and to assess their current and future career goals and intended scope of practice.METHODS. A random sample of 550 subspecialists whose initial application for pediatric subspecialty certification occurred between 2002 and 2003 (4–5 years out of training) and 550 subspecialists who applied for board certification between 2005 and 2006 (1–2 years out of training) received a structured questionnaire by mail. The survey focused on decision-making in selection of residency and fellowship programs, strength of residency training in preparation for clinical care provision, and scope of current practice.RESULTS. The overall response rate was 77%. More than half (54%) of the recently trained subspecialists would have shortened either their pediatric residency or fellowship training if given the opportunity, and 7% were unsure. More than one third of the respondents made the decision to pursue subspecialty training before the start of residency (36% [n = 198]), whereas approximately half of them made this decision during the first (19% [n = 106]) or second (27% [n = 150]) year of residency.CONCLUSIONS. Many subspecialists would have been interested in modifications to their pediatric residency and fellowship training programs, which may reflect changing patterns of professional activities or the preferences of a younger generation of subspecialists. Given that a substantial proportion of subspecialists decide to pursue subspecialty training before or early in residency, greater flexibility in configuring some residency experiences to meet their career goals would be feasible.
Electronic Results Management in Pediatric Ambulatory Care: Qualitative Assessment
Authors: Ferris Timothy G. , Johnson Sarah A. , Co John Patrick T. , Backus Meghan , Perrin James , Bates David W. , Poon Eric G. 
Published: December 2008

BACKGROUND. Electronic results management may improve the reliability and efficiency of test results management, but few studies have investigated this topic in pediatrics.
METHODS. We conducted semi-structured, key informant interviews before and after implementation of electronic results management at 8 pediatric ambulatory care practices. We also surveyed all pediatricians at 18 practices (10 additional practices). All practices were members of Partners Healthcare and had been using an electronic health record when they were offered electronic results management. We assessed baseline processes for results management, barriers to electronic results management adoption, and the perceived impact of electronic results management on quality, efficiency, and provider satisfaction.
RESULTS. From interviews, we found a range of processes in place to manage test results, but all practices reported losing some results and no practice tracked all test results from the time of ordering to parent/patient notification. Practices that fully adopted electronic results management reported gains in efficiency, reliability, timeliness, and provider satisfaction, whereas some partial adopters reported decreased efficiency and increased risk of lost test results. Barriers to electronic results management adoption included lack of inclusion of all ordered tests in the electronic results management system, user interface design issues, and lack of sufficient pediatric customization. Survey results (response rate: 62%) indicated that pediatricians thought electronic results management improved the quality and efficiency of care, with 72% of pediatricians reporting safer care and 63% reporting more-effective care.
CONCLUSIONS. We found that pediatric practices have room for improvement in the management of test results, and electronic results management may be an effective method for improving the efficiency and safety of test results management. However, partial adoption of electronic results management may decrease efficiency and pose a threat to patient safety.
Oral and Perioral Piercing Complications
Authors: Escudero-Castaño N , Perea-García M.A , Campo-Trapero J , Sánchez Cano , Bascones-Martínez A 
Published: December 2008

Background.The oral an perioral piercing has a long history as part of religious, tribal,cultural or sexual symbolism and nowdays there is a high incidence of oral and perioral piercing in the adolescent population. This practice has a long history as part of religious, tribal, cultural or sexual symbolism. This article reviews current knowledge on injuries or diseases that might be produced by piercing in the oral cavity. We propose a classification to diagnosed the pathologies related to oral an perioral piercingMethods.A search was conducted of articles in PubMed, Scielo published between 1997 and 2007, using the key words ``oral and perioral, piercing ´´, ``oral, piercing and disease”, ``recessions and oral piercing´´. It has reviewed about twentythree articles 17 were narrative reviews and 6 case seriesResults.A review was carried out on the origins of oral and perioral body piercing and its local implications, classifying the different alterations like recessions, systemic implications that it can produce in the oral and perioral cavity.Conclusion.Patients with oral and perioral piercing should be regularly followed up because of the possible development of different types of adverse effects.Clinical implications.Adverse effects of oral and perioral piercing can be systemic, with transmission of infectious diseases such as hepatitis B or C, or can be local, with alteration of oral mucosae or even of dental structures.
Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data
Authors: Laumen Helmut , Saningong Akuma D. , Heid Iris M. , Hess Jochen , Herder Christian , Claussnitzer Melina , Baumert Jens , Lamina Claudia , Rathmann Wolfgang , Sedlmeier Eva-Maria , Klopp Norman , Thorand Barbara , Wichmann H.-Erich , Illig Thomas , Hauner Hans 
Published: December 2008

OBJECTIVE
Adiponectin (APM1, ACDC) is an adipocyte-derived protein with downregulated expression in obesity and insulin-resistant states. Several potentially regulatory single nucleotide polymorphisms (SNPs) within the APM1 gene promoter region have been associated with circulating adiponectin levels. None of them have been functionally characterized in adiponectin-expressing cells. Hence, we investigated three SNPs (rs16861194, rs17300539, and rs266729) for their influence on adiponectin promoter activity and their association with circulating adiponectin levels.

RESEARCH DESIGN AND METHODS
Basal and rosiglitazone-induced promoter activity of different SNP combinations (haplotypes) was analyzed in 3T3-L1 adipocytes using luciferase reporter gene assays and DNA binding studies comparing all possible APM1 haplotypes. This functional approach was complemented with analysis of epidemiological population-based data of 1,692 participants of the MONICA/KORA S123 cohort and 696 participants from the KORA S4 cohort for SNP and haplotype association with circulating adiponectin levels.

RESULTS
Major to minor allele replacements of the three SNPs revealed significant effects on promoter activity in luciferase assays. Particularly, a minor variant in rs16861194 resulted in reduced basal and rosiglitazone-induced promoter activity and hypoadiponectinemia in the epidemiological datasets. The haplotype with the minor allele in all three SNPs showed a complete loss of promoter activity, and no subject carried this haplotype in either of the epidemiological samples (combined P value for statistically significant difference from a random sample was 0.006).

CONCLUSIONS
Our results clearly demonstrate that promoter variants associated with hypoadiponectinemia in humans substantially affect adiponectin promoter activity in adipocytes. Our combination of functional experiments with epidemiological data overcomes the drawback of each approach alone.
Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced Endoplasmic Reticulum Stress
Authors: Delibegovic Mirela , Zimmer Derek , Kauffman Caitlin , Rak Kimberly , Hong Eun-Gyoung , Cho You-Ree , Kim Jason K. , Kahn Barbara B. , Neel Benjamin G. , Bence Kendra K. 
Published: December 2008

OBJECTIVE—The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling; consequently, mice deficient in PTP1B are hypersensitive to insulin. Because PTP1B−/− mice have diminished fat stores, the extent to which PTP1B directly regulates glucose homeostasis is unclear. Previously, we showed that brain-specific PTP1B−/− mice are protected against high-fat diet–induced obesity and glucose intolerance, whereas muscle-specific PTP1B−/− mice have increased insulin sensitivity independent of changes in adiposity. Here we studied the role of liver PTP1B in glucose homeostasis and lipid metabolism.
RESEARCH DESIGN AND METHODS—We analyzed body mass/adiposity, insulin sensitivity, glucose tolerance, and lipid metabolism in liver-specific PTP1B−/− and PTP1Bfl/fl control mice, fed a chow or high-fat diet.
RESULTS—Compared with normal littermates, liver-specific PTP1B−/− mice exhibit improved glucose homeostasis and lipid profiles, independent of changes in adiposity. Liver-specific PTP1B−/− mice have increased hepatic insulin signaling, decreased expression of gluconeogenic genes PEPCK and G-6-Pase, enhanced insulin-induced suppression of hepatic glucose production, and improved glucose tolerance. Liver-specific PTP1B−/− mice exhibit decreased triglyceride and cholesterol levels and diminished expression of lipogenic genes SREBPs, FAS, and ACC. Liver-specific PTP1B deletion also protects against high-fat diet–induced endoplasmic reticulum stress response in vivo, as evidenced by decreased phosphorylation of p38MAPK, JNK, PERK, and eIF2α and lower expression of the transcription factors C/EBP homologous protein and spliced X box-binding protein 1.
CONCLUSIONS—Liver PTP1B plays an important role in glucose and lipid metabolism, independent of alterations in adiposity. Inhibition of PTP1B in peripheral tissues may be useful for the treatment of metabolic syndrome and reduction of cardiovascular risk in addition to diabetes.