bluuebunny/crossref_metadata_2025 huggingface dataset:
On causal inference in the presence of interference
Authors: Tchetgen Eric J Tchetgen , VanderWeele Tyler J
Published: November 2010

Interference is said to be present when the exposure or treatment received by one individual may affect the outcomes of other individuals. Such interference can arise in settings in which the outcomes of the various individuals come about through social interactions. When interference is present, causal inference is rendered considerably more complex, and the literature on causal inference in the presence of interference has just recently begun to develop. In this article we summarise some of the concepts and results from the existing literature and extend that literature in considering new results for finite sample inference, new inverse probability weighting estimators in the presence of interference and new causal estimands of interest.
Current Trends in Remediating Adolescent Self-Injury
Authors: Wilkinson Beverly
Published: November 2010

The increasing prevalence of self-injurious behavior (SIB) among mainstream adolescents has led to a growing body of research. This maladaptive behavior is used as a means of regulating negative emotions. Best practices regarding therapy are unclear, with many types of intervention being tried. Analysis of 36 qualitative and quantitative studies, reviews, and theory articles addressing adolescent SIB was conducted looking at aspects such as history, demographics, motivators, risk factors, techniques, and treatment options. An explosion of research is surfacing to determine effective care through creative approaches. Dialectical Behavior Therapy (DBT) shows great promise. The school setting is a natural environment for the identification and intervention of SIB which requires knowledge of indicators and risk factors. Education of school staff will increase awareness and enhance communication among disciplines. A circle of care can then surround the student to provide support and guidance while the proper interventions for emotional regulation and individual health promotion are developed.
Exploring Family Caregivers’ Rationales for Nonuse of Formal Home Health Services When Caring for a Dying Family Member
Authors: Funk Laura M. , Stajduhar Kelli I. , Cloutier-Fisher Denise
Published: November 2010

Drawing on interviews with 26 bereaved individuals who provided care to a dying family member at home, the purpose of this article is to identify and explore motivations behind the “nonuse” of home health services. Participants resided in a Western Canadian regional health authority. In their accounts of not asking for help from formal providers, participants highlighted personal reasons, coping needs, and a lack of knowledge. In their accounts of refused help, they placed more emphasis on a perceived lack of need for help (including constructing themselves as capable and coping), as well as their perceptions of the quality and competence of formal services. Findings are compared against existing literature. Implications for health system policy and planning, and for home health nursing practice, training and education, particularly with reference to situations in which responsibility is left with families to ask for help from formal providers, are also discussed.
Development of Spelling and Differential Relations to Text Reading in Grades 3-12
Authors: Foorman Barbara R. , Petscher Yaacov
Published: November 2010

The authors claim that assessing spelling in Grades 3—12 has utility. They base their claim on data from 875,040 students in Grades 3—12 in 52,923 classes in 840 Florida schools who took the Reading Comprehension, Maze, and Word Analysis spelling portions of the Florida Assessments for Instruction in Reading during the 2009—2010 school year. The importance of instruction to spelling ability was evident in (a) the large intraclass correlations at the class relative to the school level, (b) the greater variability in spelling at the class level rather than at the student level, (c) the greater role of demographics at the class level compared to the student level, and (d) the role of high ability spelling classrooms compared to low ability spelling classrooms in differentiating Reading Comprehension and Maze performance. Growth in spelling was evident in the elementary grades but stagnant above Grade 7. The authors conclude with the hope that secondary teachers will include spelling instruction as part of their goal to engage students in reading for understanding.
Spell It Out: The Need for Detailed Spelling Assessment to Inform Instruction
Authors: Al Otaiba Stephanie , Hosp John L.
Published: November 2010

Spelling is an important, but often overlooked, component of literacy instruction and development. Although it is related to other aspects of literacy, there are independent theories of spelling development as well as assessment and instructional strategies that align with these theories. This article summarizes the rationale for linking assessment and instruction within the domain of spelling and provides an overview of this special series on spelling assessment and instruction.
Circulating human CD4 and CD8 T cells do not have large intracellular pools of CCR5
Authors: Pilch-Cooper Heather A. , Sieg Scott F. , Hope Thomas J. , Koons Ann , Escola Jean-Michel , Offord Robin , Veazey Ronald S. , Mosier Donald E. , Clagett Brian , Medvik Kathy , Jadlowsky Julie K. , Chance Mark R. , Kiselar Janna G. , Hoxie James A. , Collman Ronald G. , Riddick Nadeene E. , Mercanti Valentina , Hartley Oliver , Lederman Michael M.
Published: November 2010

CC Chemokine Receptor 5 (CCR5) is an important mediator of chemotaxis and the primary coreceptor for HIV-1. A recent report by other researchers suggested that primary T cells harbor pools of intracellular CCR5. With the use of a series of complementary techniques to measure CCR5 expression (antibody labeling, Western blot, quantitative reverse transcription polymerase chain reaction), we established that intracellular pools of CCR5 do not exist and that the results obtained by the other researchers were false-positives that arose because of the generation of irrelevant binding sites for anti-CCR5 antibodies during fixation and permeabilization of cells.
The Caenorhabditis elegansCDT-2 ubiquitin ligase is required for attenuation of EGFR signalling in vulva precursor cells
Authors: Poulin Gino B , Ahringer Julie
Published: November 2010

Background

Attenuation of the EGFR (Epidermal Growth Factor Receptor) signalling cascade is crucial to control cell fate during development. A candidate-based RNAi approach in C. elegans identified CDT-2 as an attenuator of LET-23 (EGFR) signalling. Human CDT2 is a component of the conserved CDT2/CUL4/DDB1 ubiquitin ligase complex that plays a critical role in DNA replication and G2/M checkpoint. Within this complex, CDT2 is responsible for substrate recognition. This ubiquitin ligase complex has been shown in various organisms, including C. elegans, to target the replication-licensing factor CDT1, and the CDK inhibitor p21. However, no previous link to EGFR signalling has been identified.

Results

We have characterised CDT-2's role during vulva development and found that it is a novel attenuator of LET-23 signalling. CDT-2 acts redundantly with negative modulators of LET-23 signalling and CDT-2 or CUL-4 downregulation causes persistent expression of the egl-17::cfp transgene, a marker of LET-23 signalling during vulva development. In addition, we show that CDT-2 physically interacts with SEM-5 (GRB2), a known negative modulator of LET-23 signalling that directly binds LET-23, and provide genetic evidence consistent with CDT-2 functioning at or downstream of LET-23. Interestingly, both SEM-5 and CDT-2 were identified independently in a screen for genes involved in receptor-mediated endocytosis in oocytes, suggesting that attenuation of LET-23 by CDT-2 might be through regulation of endocytosis.

Conclusions

In this study, we have shown that CDT-2 and CUL-4, members of the CUL-4/DDB-1/CDT-2 E3 ubiquitin ligase complex attenuate LET-23 signalling in vulval precursor cells. In future, it will be interesting to investigate the potential link to endocytosis and to determine whether other signalling pathways dependent on endocytosis, e.g. LIN-12 (Notch) could be regulated by this ubiquitin ligase complex. This work has uncovered a novel function for the CUL-4/DDB-1/CDT-2 E3 ligase that may be relevant for its mammalian oncogenic activity.
Genetic variation in the odorant receptors family 13 and the mhc loci influence mate selection in a multiple sclerosis dataset
Authors: Khankhanian Pouya , Gourraud Pierre-Antoine , Caillier Stacy J , Santaniello Adam , Hauser Stephen L , Baranzini Sergio E , Oksenberg Jorge R
Published: November 2010

Background

When selecting mates, many vertebrate species seek partners with major histocompatibility complex (MHC) genes different from their own, presumably in response to selective pressure against inbreeding and towards MHC diversity. Attempts at replication of these genetic results in human studies, however, have reached conflicting conclusions.

Results

Using a multi-analytical strategy, we report validated genome-wide relationships between genetic identity and human mate choice in 930 couples of European ancestry. We found significant similarity between spouses in the MHC at class I region in chromosome 6p21, and at the odorant receptor family 13 locus in chromosome 9. Conversely, there was significant dissimilarity in the MHC class II region, near theHLA-DQA1and -DQB1genes. We also found that genomic regions with significant similarity between spouses show excessive homozygosity in the general population (assessed in the HapMap CEU dataset). Conversely, loci that were significantly dissimilar among spouses were more likely to show excessive heterozygosity in the general population.

Conclusions

This study highlights complex patterns of genomic identity among partners in unrelated couples, consistent with a multi-faceted role for genetic factors in mate choice behavior in human populations.
Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin
Authors: Pinheiro Manuela , Ahlquist Terje , Danielsen Stine A , Lind Guro E , Veiga Isabel , Pinto Carla , Costa Vera , Afonso Luís , Sousa Olga , Fragoso Maria , Santos Lúcio , Henrique Rui , Lopes Paula , Lopes Carlos , Lothe Ragnhild A , Teixeira Manuel R
Published: November 2010

Background

Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel.

Methods

Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for BAX, IGF2R, TGFBR2, MSH3, and MSH6 microsatellite sequence alterations, BRAF and KRAS mutations, and MLH1 promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate.

Results

In the test series, IGFR2 and BAX mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in TGFBR2, MSH3, and MSH6. We confirmed these findings in the validation series, with TGFBR2 and MSH3 microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (P = 0.00005 and P = 0.0000005, respectively, when considering all MSI-carcinomas of both series). No MLH1 promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (P = 0.004). KRAS and BRAF mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively.

Conclusion

The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease.
Neck dissection and post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin protocol are useful for oral mucosal melanoma
Authors: Yang Xi , Ren Guo-xin , Zhang Chen-ping , Zhou Guo-yu , Hu Yong-jie , Yang Wen-jun , Guo Wei , Li Jiang , Zhong Lai-ping
Published: November 2010

Background

Oral mucosal melanoma (OMM) is a clinically rare disease with poor prognosis. Various treatment methods have been investigated with the aim of improving the prognosis. This study aimed to analyze the data of a single institution in the management of OMM.

Methods

A total of 78 consecutive OMM patients were included in this retrospective study. The intraoral lesion was treated either by cryotherapy, surgery or both; the neck was treated by neck dissection or observation; post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin was performed in some patients. The Kaplan-Meier method was used for statistical analysis.

Results

Among the 78 patients, there were 50 males and 28 females with an average age of 53.8 years (ranging from 27 to 85 years). The most common sites of OMM were the hard palate and gingiva. The main cause of death in OMM was distant metastasis. No significant difference was found between the intraoral/cervical lesion recurrence/post-operative distant metastasis and the intraoral lesion site/biopsy method/treatment method. The metastasis rate of cervical lymph node was high in the OMM patients, even in the patients with clinically negative necks. Cervical lesion recurrence was correlated with N stage and intraoral lesion recurrence. The survival period was longer in the patients with T3 staging, clinical stage III disease, with post-operative chemotherapy and without post-operative distant metastasis when compared to those patients with T4a staging, clinical stage IV disease, without post-operative chemotherapy and with post-operative distant metastasis.

Conclusions

Radical surgery including wide intraoral resection and neck dissection is recommended for OMM patients. Post-operative chemotherapy may also be beneficial for both primary and recurrent OMM patients.
Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells
Authors: Alford Spencer , Watson-Hurthig Adam , Scott Nadia , Carette Amanda , Lorimer Heather , Bazowski Jessa , Howard Perry L
Published: November 2010

Background

Ephrin A1 (EFNA1) is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. In malignancy, the precise role of EFNA1 and its preferred receptor, EPHA2, is controversial. Several studies have found that EFNA1 may suppress EPHA2-mediated oncogenesis, or enhance it, depending on cell type and context. However, little is known about the conditions that influence whether EFNA1 promotes or suppresses tumorigenicity. EFNA1 exists in a soluble form as well as a glycophosphatidylinositol (GPI) membrane attached form. We investigated whether the contradictory roles of EFNA1 in malignancy might in part be related to the existence of both soluble and membrane attached forms of EFNA1 and potential differences in the manner in which they interact with EPHA2.

Results

Using a RNAi strategy to reduce the expression of endogenous EFNA1 and EPHA2, we found that both EFNA1 and EPHA2 are required for growth of HeLa and SK-BR3 cells. The growth defects could be rescued by conditioned media from cells overexpressing soluble EFNA1. Interestingly, we found that overexpression of the membrane attached form of EFNA1 suppresses growth of HeLa cells in 3D but not 2D. Knockdown of endogenous EFNA1, or overexpression of full-length EFNA1, resulted in relocalization of EPHA2 from the cell surface to sites of cell-cell contact. Overexpression of soluble EFNA1 however resulted in more EPHA2 distributed on the cell surface, away from cell-cell contacts, and promoted the growth of HeLa cells.

Conclusions

We conclude that soluble EFNA1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation.
Supernumerary, ectopic tooth in the maxillary antrum presenting with recurrent haemoptysis
Authors: Saleem Taimur , Khalid Umair , Hameed Anam , Ghaffar Shehzad
Published: November 2010

Background

Ectopic eruption of teeth in non-dental sites is a rare phenomenon and can present in a variety of ways such as chronic or recurrent sinusitis, sepsis, nasolacrimal duct obstruction, headaches, ostiomeatal complex disease and facial numbness. However, presentation of such patients with recurrent haemoptysis has not been described in the literature so far. We have described a case of an ectopic, supernumerary molar tooth in the maxillary antrum in a patient who initially presented with haemoptysis.

Case presentation

A 45-year-old male presented with a 2-month history of episodic haemoptysis. A pedunculated growth from the inferior nasal turbinate was seen with fibre-optic visualization. Although the patient was empirically started on antibiotic and anti-allergic therapy, there was no improvement after a few weeks and the patient had recurrent episodes of haemoptysis. Fibre-optic visualization was repeated showing bilateral osteomeatal erythema. Computed tomography scan of the paranasal sinuses demonstrated complete opacification of the left maxillary antrum along with a focal area of density comparable to bone. An ectopic, supernumerary molar tooth was found in the left maxillary antrum on endoscopic examination and subsequently removed. In addition, copious purulent discharge was seen. Post-operatively, the patient was treated with a 10-day course of oral amoxicillin-clavulanate. On follow-up, he reported resolution of symptoms.

Conclusion

Recurrent haemoptysis has not been described as a presentation for a supernumerary, ectopic tooth in literature before. We recommend that in patients with sinusitis-type of opacification of maxillary antrum and whose condition is refractory to conventional medical treatment, consideration should be given to the investigation of possible underlying anomalies as the cause of such symptoms. Presence of foreign bodies and ectopic teeth in paranasal sinuses can be reliably excluded with the use of appropriate radiological imaging and endoscopic examination.
Targeting the hotspots: investigating spatial and demographic variations in HIV infection in small communities in South Africa
Authors: Wand Handan , Ramjee Gita
Published: November 2010

Background

In South Africa, the severity of the HIV/AIDS epidemic varies according to geographical location; hence, localized monitoring of the epidemic would enable more effective prevention strategies. Our objectives were to assess the core areas of HIV infection in KwaZulu‐Natal, South Africa, using epidemiological data among sexually active women from localized communities.

Methods

A total of 5753 women from urban, peri‐rural and rural communities in KwaZulu‐Natal were screened from 2002 to 2005. Each participant was geocoded using a global information system, based on residence at time of screening. The Spatial Scan Statistics programme was used to identify areas with disproportionate excesses in HIV prevalence and incidence.

Results

This study identified three hotspots with excessively high HIV prevalence rates of 56%, 51% and 39%. A total of 458 sexually active women (19% of all cases) were included in these hotspots, and had been exclusively recruited by the Botha's Hill (west of Durban) and Umkomaas (south of Durban) clinic sites. Most of these women were Christian and Zulu‐speaking. They were also less likely to be married than women outside these areas (12% vs. 16%, p = 0.001) and more likely to have sex more than three times a week (27% vs. 20%, p < 0.001) and to have had more than three sexual partners (55% vs. 45%, p < 0.001). Diagnosis of genital herpes simplex virus type 2 was also more common in the hotspots. This study also identified areas of high HIV incidence, which were broadly consistent with those with high prevalence rates.

Conclusions

Geographic excesses of HIV infections at rates among the highest in the world were detected in certain rural communities of Durban, South Africa. The results reinforce the inference that risk of HIV infection is associated with definable geographical areas. Localized monitoring of the epidemic is therefore essential for more effective prevention strategies ‐ and particularly urgent in a region such as KwaZulu‐Natal, where the epidemic is particularly rampant.
Regulation of Placental Growth by Aldosterone and Cortisol
Authors: Gennari-Moser Carine , Khankin Eliyahu V. , Schüller Simone , Escher Geneviève , Frey Brigitte M. , Portmann C.-Bettina , Baumann Marc U. , Lehmann Andrea D. , Surbek Daniel , Karumanchi S. Ananth , Frey Felix J. , Mohaupt Markus G.
Published: November 2010

During pregnancy, trophoblasts grow to adapt the feto-maternal unit to fetal requirements. Aldosterone and cortisol levels increase, the latter being inactivated by a healthy placenta. By contrast, preeclamptic placental growth is reduced while aldosterone levels are low and placental cortisol tissue levels are high due to improper deactivation. Aldosterone acts as a growth factor in many tissues, whereas cortisol inhibits growth. We hypothesized that in preeclampsia low aldosterone and enhanced cortisol availability might mutually affect placental growth and function. Proliferation of cultured human trophoblasts was time- and dose-dependently increased with aldosterone (P < 0.04 to P < 0.0001) and inhibited by spironolactone and glucocorticoids (P < 0.01). Mineralo- and glucocorticoid receptor expression and activation upon agonist stimulation was verified by visualization of nuclear translocation of the receptors. Functional aldosterone deficiency simulated in pregnant mice by spironolactone treatment (15 μg/g body weight/day) led to a reduced fetal umbilical blood flow (P < 0.05). In rat (P < 0.05; R2 = 0.2055) and human (X2 = 3.85; P = 0.0249) pregnancy, placental size was positively related to plasma aldosterone. Autocrine production of these steroid hormones was excluded functionally and via the absence of specific enzymatic transcripts for CYP11B2 and CYP11B1. In conclusion, activation of mineralocorticoid receptors by maternal aldosterone appears to be required for trophoblast growth and a normal feto-placental function. Thus, low aldosterone levels and enhanced cortisol availability may be one explanation for the reduced placental size in preeclampsia and related disorders.
Activation of Central, But Not Peripheral, Estrogen Receptors Is Necessary for Estradiol’s Anorexigenic Effect in Ovariectomized Rats
Authors: Rivera Heidi M. , Eckel Lisa A.
Published: November 2010

Estradiol appears to exert its anorexigenic effect by activating nuclear estrogen receptors (ERs), which are expressed widely in peripheral tissues and in the brain. Here, we used ICI-182,780 (ICI), a pure antiestrogen with limited ability to cross the blood-brain barrier, to assess the relative involvement of peripheral vs. central ERs to estradiol’s anorexigenic effect. Food intake was measured after peripheral (sc) administration of ICI or vehicle in ovariectomized rats treated with acute injections of estradiol benzoate and sesame oil over a 2-wk period. Uterine weight was assessed as a biological assay of peripheral ER activation. In a second experiment, food intake was measured after central (lateral ventricular) administration of ICI or vehicle in ovariectomized rats receiving acute injections of estradiol benzoate and oil over a period of 10 d. In order to assess the possible spread of ICI from the brain to the periphery, vaginal cytology samples were examined as a biological assay of peripheral ER activation. Peripherally administered ICI failed to attenuate estradiol’s anorexigenic effect at a dose that was sufficient to block estradiol’s uterotrophic effect. This suggests that peripheral activation of ERs is not necessary for estradiol’s anorexigenic effect. Although central infusion of 4 nm ICI blocked estradiol’s anorexigenic effect, it did not attenuate estradiol’s ability to increase the presence of cornified cells in vaginal cytology samples, suggesting that ICI did not leak into the periphery. We conclude that activation of central, but not peripheral, ERs is necessary for estradiol’s anorexigenic effect.
A Treasure Trove of Hypothalamic Neurocircuitries Governing Body Weight Homeostasis
Authors: Vianna Claudia R. , Coppari Roberto
Published: November 2010

Changes in physical activities and feeding habits have transformed the historically rare disease of obesity into a modern metabolic pandemic. Obesity occurs when energy intake exceeds energy expenditure over time. This energy imbalance significantly increases the risk for cardiovascular disease and type 2 diabetes mellitus and as such represents an enormous socioeconomic burden and health threat. To combat obesity, a better understanding of the molecular mechanisms and neurocircuitries underlying normal body weight homeostasis is required. In the 1940s, pioneering lesion experiments unveiled the importance of medial and lateral hypothalamic structures. In the 1980s and 1990s, several neuropeptides and peripheral hormones critical for appropriate feeding behavior, energy expenditure, and hence body weight homeostasis were identified. In the 2000s, results from metabolic analyses of genetically engineered mice bearing mutations only in selected neuronal groups greatly advanced our knowledge of the peripheral/brain feedback-loop modalities by which central neurons control energy balance. In this review, we will summarize these recent progresses with particular emphasis on the biochemical identities of hypothalamic neurons and molecular components underlying normal appetite, energy expenditure, and body weight homeostasis. We will also parse which of those neurons and molecules are critical components of homeostatic adaptive pathways against obesity induced by hypercaloric feeding.
Exercise Induces a Marked Increase in Plasma Follistatin: Evidence That Follistatin Is a Contraction-Induced Hepatokine
Authors: Hansen Jakob , Brandt Claus , Nielsen Anders R. , Hojman Pernille , Whitham Martin , Febbraio Mark A. , Pedersen Bente K. , Plomgaard Peter
Published: November 2010

Follistatin is a member of the TGF-β super family and inhibits the action of myostatin to regulate skeletal muscle growth. The regulation of follistatin during physical exercise is unclear but may be important because physical activity is a major intervention to prevent age-related sarcopenia. First, healthy subjects performed either bicycle or one-legged knee extensor exercise. Arterial-venous differences were assessed during the one-legged knee extensor experiment. Next, mice performed 1 h of swimming, and the expression of follistatin was examined in various tissues using quantitative PCR. Western blotting assessed follistatin protein content in the liver. IL-6 and epinephrine were investigated as drivers of follistatin secretion. After 3 h of bicycle exercise, plasma follistatin increased 3 h into recovery with a peak of 7-fold. No net release of follistatin could be detected from the exercising limb. In mice performing a bout of swimming exercise, increases in plasma follistatin as well as follistatin mRNA and protein expression in the liver were observed. IL-6 infusion to healthy young men did not affect the follistatin concentration in the circulation. When mice were stimulated with epinephrine, no increase in the hepatic mRNA of follistatin was observed. This is the first study to demonstrate that plasma follistatin is increased during exercise and most likely originates from the liver. These data introduce new perspectives regarding muscle-liver cross talk during exercise and during recovery from exercise.
Plasticity of the Reproductive Axis Caused by Social Status Change in an African Cichlid Fish: I. Pituitary Gonadotropins
Authors: Maruska Karen P. , Levavi-Sivan Berta , Biran Jakob , Fernald Russell D.
Published: November 2010

Social position in a dominance hierarchy is often tightly coupled with fertility. Consequently, an animal that can recognize and rapidly take advantage of an opportunity to rise in rank will have a reproductive advantage. Reproduction in all vertebrates is controlled by the brain-pituitary-gonad axis, and in males of the African cichlid fish Astatotilapia burtoni, GnRH1 neurons at the apex of this axis are under social control. However, little is known about how quickly social information is transformed into functional reproductive change, or about how socially controlled changes in GnRH1 neurons influence downstream actions of the brain-pituitary-gonad axis. We created an opportunity for reproductively suppressed males to ascend in status and then measured how quickly the perception of this opportunity caused changes in mRNA and protein levels of the pituitary gonadotropins. mRNA levels of the β-subunits of LH and FSH rose rapidly in the pituitary 30 min after suppressed males perceived an opportunity to ascend. In contrast, mRNA levels of GnRH receptor-1 remained unchanged during social transition but were higher in stable dominant compared with subordinate males. In the circulation, levels of both LH and FSH were also quickly elevated. There was a positive correlation between mRNA in the pituitary and circulating protein levels for LH and FSH, and both gonadotropins were positively correlated with plasma 11-ketotestosterone. Our results show that the pituitary is stimulated extremely rapidly after perception of social opportunity, probably to allow suppressed males to quickly achieve reproductive success in a dynamic social environment.
Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion
Authors: Feng Xuesong , Krebs Luke T. , Gridley Thomas
Published: November 2010

The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus and is one of the most common congenital heart defects. Mice with smooth muscle cell-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from patent ductus arteriosus. These mice exhibit defects in contractile smooth muscle cell differentiation in the vascular wall of the ductus arteriosus and adjacent descending aorta. These defects arise through an inability to propagate the JAG1-Notch signal via lateral induction throughout the width of the vascular wall. Both heterotypic endothelial smooth muscle cell interactions and homotypic vascular smooth muscle cell interactions are required for normal patterning and differentiation of the ductus arteriosus and adjacent descending aorta. This new model for a common congenital heart defect provides novel insights into the genetic programs that underlie ductus arteriosus development and closure.
BMP signaling in the development of the mouse esophagus and forestomach
Authors: Rodriguez Pavel , Da Silva Susana , Oxburgh Leif , Wang Fan , Hogan Brigid L. M. , Que Jianwen
Published: November 2010

The stratification and differentiation of the epidermis are known to involve the precise control of multiple signaling pathways. By contrast, little is known about the development of the mouse esophagus and forestomach, which are composed of a stratified squamous epithelium. Based on prior work in the skin, we hypothesized that bone morphogenetic protein (BMP) signaling is a central player. To test this hypothesis, we first used a BMP reporter mouse line harboring a BRE-lacZ allele, along with in situ hybridization to localize transcripts for BMP signaling components, including various antagonists. We then exploited a Shh-Cre allele that drives recombination in the embryonic foregut epithelium to generate gain- or loss-of-function models for the Bmpr1a (Alk3) receptor. In gain-of-function (Shh-Cre;Rosa26CAG-loxpstoploxp-caBmprIa) embryos, high levels of ectopic BMP signaling stall the transition from simple columnar to multilayered undifferentiated epithelium in the esophagus and forestomach. In loss-of-function experiments, conditional deletion of the BMP receptor in Shh-Cre;Bmpr1aflox/flox embryos allows the formation of a multilayered squamous epithelium but this fails to differentiate, as shown by the absence of expression of the suprabasal markers loricrin and involucrin. Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach.
Non-cell-autonomously coordinated organ size regulation in leaf development
Authors: Kawade Kensuke , Horiguchi Gorou , Tsukaya Hirokazu
Published: November 2010

The way in which the number and size of cells in an organ are determined poses a central challenge in our understanding of organ size control. Compensation is an unresolved phenomenon, whereby a decrease in cell proliferation below some threshold level triggers enhanced postmitotic cell expansion in leaf primordia. It suggests an interaction between these cellular processes during organogenesis and provides clues relevant to an understanding of organ size regulation. Although much attention has been given to compensation, it remains unclear how the cellular processes are coordinated. Here, we used a loss-of-function mutation in the transcriptional coactivator gene ANGUSTIFOLIA3 (AN3), which causes typical compensation in Arabidopsis thaliana. We established Cre/lox systems to generate leaves chimeric for AN3 expression and investigated whether compensation occurs in a cell-autonomous or non-cell-autonomous manner. We found that an3-dependent compensation is a non-cell-autonomous process, and that an3 cells seem to generate and transmit an intercellular signal that enhances postmitotic cell expansion. The range of signalling was restricted to within one-half of a leaf partitioned by the midrib. Additionally, we also demonstrated that overexpression of the cyclin-dependent kinase inhibitor gene KIP-RELATED PROTEIN2 resulted in cell-autonomous compensation. Together, our results revealed two previously unknown pathways that coordinate cell proliferation and postmitotic cell expansion for organ size control in plants.
Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations
Authors: Bauler Timothy J. , Kamiya Nobuhiro , Lapinski Philip E. , Langewisch Eric , Mishina Yuji , Wilkinson John E. , Feng Gen-Sheng , King Philip D.
Published: November 2010

SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.
Self-generated Motion of Droplets Induced by Korteweg Force
Authors: Ban Takahiko , Aoyama Ai , Matsumoto Takuya
Published: November 2010

Phase-separating droplets exhibit self-generated motion depending on the composition of the constituent solution of a biocompatible material, aqueous two phase system. For higher concentrations than the equilibrium concentration, a droplet moved unidirectionally even in a homogeneous concentration field. For lower concentrations, the droplets hardly moved. The translational motion we observed is an effect of convection caused by Korteweg force.
Blocking Oxidation of Al Surfaces with Organic Thiol Monolayers Cured by Electron Beam
Authors: Nomura Shuhei , Yamada Taro , Kawai Maki
Published: November 2010

In order to expand the processing utility of metallic aluminum as a material for nanometer-scale fabrication, we attempted to block oxidation of Al(111) surface in O2 gas up to 1000 Torr, by predeposited organic monolayers. A full monolayer of biphenyl-4-thiol (BPT), appropriately treated by electron-beam irradiation, exhibited a significantly enhanced robustness against oxidation, compared to clean Al(111).
Thermal Properties of Alkali (Fluorosulfonyl)(trifluoromethylsulfonyl)amides
Authors: Kubota Keigo , Nohira Toshiyuki , Hagiwara Rika , Matsumoto Hajime
Published: November 2010

An asymmetric perfluorosulfonylamide anion, [(FSO2)(CF3SO2)N]− (C0C1−), has a significant ability to lower the melting temperatures of alkali salts down to around 373 K. Among alkali salts which have melting temperatures around 373 K, they have comparatively high decomposition temperature. The melting point of LiC0C1 is the lowest among the lithium salts of perfluoroalkyl- or fluorosulfonylamide anions of this kind.
Origin of the 1918 pandemic H1N1 influenza A virus as studied by codon usage patterns and phylogenetic analysis
Authors: Anhlan Darisuren , Grundmann Norbert , Makalowski Wojciech , Ludwig Stephan , Scholtissek Christoph
Published: November 2010

The pandemic of 1918 was caused by an H1N1 influenza A virus, which is a negative strand RNA virus; however, little is known about the nature of its direct ancestral strains. Here we applied a broad genetic and phylogenetic analysis of a wide range of influenza virus genes, in particular thePB1gene, to gain information about the phylogenetic relatedness of the 1918 H1N1 virus. We compared the RNA genome of the 1918 strain to many other influenza strains of different origin by several means, including relative synonymous codon usage (RSCU), effective number of codons (ENC), and phylogenetic relationship. We found that thePB1gene of the 1918 pandemic virus had ENC values similar to the H1N1 classical swine and human viruses, but different ENC values from avian as well as H2N2 and H3N2 human viruses. Also, according to the RSCU of thePB1gene, the 1918 virus grouped with all human isolates and “classical” swine H1N1 viruses. The phylogenetic studies of all eight RNA gene segments of influenza A viruses may indicate that the 1918 pandemic strain originated from a H1N1 swine virus, which itself might be derived from a H1N1 avian precursor, which was separated from the bulk of other avian viruses in toto a long time ago. The high stability of the RSCU pattern of thePB1gene indicated that the integrity of RNA structure is more important for influenza virus evolution than previously thought.
Large Deviations of Max-Weight Scheduling Policies on Convex Rate Regions
Authors: Subramanian Vijay G.
Published: November 2010

We consider a single server discrete-time system with a fixed number of users where the server picks operating points from a compact, convex, and coordinate convex set. For this system, we analyse the performance of a stabilising policy that at any given time picks operating points from the allowed rate region that maximise a weighted sum of rates, where the weights depend on the work loads of the users. Assuming a large deviations principle (LDP) for the arrival processes in the Skorohod space of functions that are right continuous with left-hand limits, we establish an LDP for the work load process using a generalised version of the contraction principle to derive the corresponding rate function. With the LDP result available, we then analyse the tail probabilities of the work loads under different buffering scenarios.
A Geometric Proof of Calibration
Authors: Mannor Shie , Stoltz Gilles
Published: November 2010

We provide yet another proof of the existence of calibrated forecasters; it has two merits. First, it is valid for an arbitrary finite number of outcomes. Second, it is short and simple and it follows from a direct application of Blackwell's approachability theorem to a carefully chosen vector-valued payoff function and convex target set. Our proof captures the essence of existing proofs based on approachability (e.g., the proof by Foster [Foster, D. 1999. A proof of calibration via Blackwell's approachability theorem. Games Econom. Behav. 29 73–78] in the case of binary outcomes) and highlights the intrinsic connection between approachability and calibration.
Strategies to Address Appropriate Fluoroquinolone Use in the Hospital
Authors: Kaye Keith S. , Auwaerter Paul , Bosso John A. , Dean Nathan C. , Doern Gary V. , Kays Michael B. , Pogue Jason M. , Ritchie David J. , Wispelwey Brian
Published: November 2010

Purpose

Strategies to optimally use fluoroquinolones in the hospital setting are reviewed.

Fluoroquinolones possess broad-spectrum antimicrobial coverage and are widely used to treat a variety of infections including some serious, life-threatening conditions. Overuse and inappropriate use of fluoroquinolones has led to rapid emergence of fluoroquinolone-resistant organisms as well as multidrug-resistant pathogens. Preserving the fluoroquinolone class is important, especially given the lack of new antibiotics currently in clinical development. Maintaining the fluoroquinolone class as a therapeutic option requires the successful implementation of guidelines to promote appropriate, optimal use of these agents. Among many recommendations to control the growing problem of antimicrobial resistance, antimicrobial stewardship programs offer the most comprehensive solution to gain appropriate antimicrobial prescribing. Effective programs include selection of the most effective agents, specific dosages, frequency of administration, routes of administration, and duration of therapy. Additionally, a dual fluoroquinolone formulary, which typically incorporates one respiratory fluoroquinolone and ciprofloxacin, has been employed to increase the diversity of fluoroquinolone treatment and thus reduce the selective antimicrobial pressure. A combination of antimicrobial stewardship programs and a dual formulary option has been demonstrated to be a good approach to optimize the use of fluoroquinolones in the hospital. Two successful experiences in applying such strategies have been reported; in both cases the empiric fluoroquinolone prescribing was reduced.

Conclusion

Implementation of aggressive optimization strategies such as the combined use of antimicrobial stewardship programs and a dual fluoroquinolone formulary may maintain the efficacy of fluoroquinolones and preserve their utility for future patients.
Recent Publications on Medications and Pharmacy
Authors: Russett Flint
Published: November 2010

Hospital Pharmacy presents this feature to keep pharmacists abreast of new publications in the medical/pharmacy literature. Articles of interest regarding a broad scope of topics are abstracted monthly.
Application of Pulsed Buffer Gas Jets for the Signal Enhancement of Laser-Induced Breakdown Spectroscopy
Authors: Son Joon Gon , Choi Sung-Chul , Oh Myoung-Kyu , Kang Hoonsoo , Suk Hyyong , Lee Yonghoon
Published: November 2010

We report a new simple method for the signal enhancement of laser-induced breakdown spectroscopy using a pulsed buffer gas jet. The signal is enhanced up to more than 10 fold by using argon gas jets, which are injected through a pulsed nozzle onto the sample area to be analyzed. By synchronizing the buffer gas pulse with the laser pulse and optimizing the spatial arrangements between the gas jet and the sample surface, we have successfully exploited the useful properties of the buffer gas in open atmosphere. The signal-enhancement mechanism in our buffer gas jet has been discussed. Also, applications to various samples (metal, glass, and paper) have been demonstrated.
Parallel Analysis of Individual Biological Cells Using Multifocal Laser Tweezers Raman Spectroscopy
Authors: Liu Rui , Taylor Douglas S. , Matthews Dennis L. , Chan James W.
Published: November 2010

We report on the development and characterization of a multifocal laser tweezers Raman spectroscopy (M-LTRS) technique for parallel Raman spectral acquisition of individual biological cells. Using a 785-nm diode laser and a time-sharing laser trapping scheme, multiple laser foci are generated to optically trap single polystyrene beads and suspension cells in a linear pattern. Raman signals from the trapped objects are simultaneously projected through the slit of a spectrometer and spatially resolved on a charge-coupled device (CCD) detector with minimal signal crosstalk between neighboring cells. By improving the rate of single-cell analysis, M-LTRS is expected to be a valuable method for studying single-cell dynamics of cell populations and for the development of high-throughput Raman based cytometers.
Far-Infrared Spectroscopy of Protein Higher-Order Structures
Authors: Falconer Robert J. , Zakaria Hidayatul A. , Fan Yuan Y. , Bradley Andrew P. , Middelberg Anton P. J.
Published: November 2010

Far-infrared (FIR) spectroscopy in the spectral region of 50–450 cm−1 was used to study a series of protein higher-order structures constructed using β-lactoglobulin and polyomavirus capsid protein VP1. There were marked differences in the spectra for β-lactoglobulin monomer and dimer and between untreated β-lactoglobulin and heat-induced gels formed at neutral pH. Untreated β-lactoglobulin and heat-induced gels formed at acidic pH exhibited little difference in their spectra. Assembly of the quaternary structure of polyomavirus virus-like particles also caused large changes in the FIR spectra. These findings suggest that FIR spectroscopy may prove useful in studying some protein quaternary and higher-order structures. There was evidence of detection of β-lactoglobulin dimerization, intermolecular disulfide bonding in heat-induced neutral gels, and polyomavirus virus-like particle assembly but no evidence that FIR could detect β-lactoglobulin fibrils with their polymeric structure and hydrogen-bonded intermolecular β-pleated sheeting.