bluuebunny/crossref_metadata_2025 huggingface dataset:
Populations who die without specialist palliative care: does lower uptake equate with unmet need?
Authors: Currow David C. , Agar Meera , Sanderson Christine , Abernethy Amy P.
Published: January 2008

Background: In palliative care, the target population (all people with life-limiting illnesses and their family/caregivers) and the complexity of their needs from diagnosis to bereavement should define the subpopulation who access specialist palliative care services (SPCS). Have caregivers of patients who have not accessed SPCS had their needs met?Methods: As part of a broader state-wide randomized face-to-face population health survey over six years (18 224 interviews, 71% response), questions were asked of people bereaved in the previous five years when someone close to them died an `expected' death (39% of respondents). Questions included respondent demographics, the diagnosis of the deceased and, for one year, whether SPCS was of benefit (if used) or needed (if not used). Differential uptake rates were calculated for diagnosis, income, country of birth and age and 2 × 2 tables reflecting the accuracy of match of service with caregiver needs were generated for each group (accuracy = true positives + true negatives/total) *100.Results: Uptake of SPCS was significantly lower in people with a non-cancer diagnosis (40% versus 62%; P = 0.0001), lower income (56% versus 61%; P = 0.0006) and people born where English was not the first language (52% versus 58%; P = 0.0096). The only subgroup where the accuracy of matching between palliative care service uptake and identified needs was lower than the overall average (83%) was where cancer was not the life-limiting illness (69%; cancer 86%).Discussion: SPCS under utilization has previously been described in the population subgroups explored in this study and assumed to equal unmet needs and poorer outcomes. Caregiver responses suggest that, except for people with a non-cancer diagnosis, lack of service uptake may not represent unmet needs. These results are limited to people with caregivers. Palliative Medicine 2008;22: 43—50
Curriculum Currency: Integrating Direct and Interactive Marketing Content in Introductory Marketing Courses
Authors: Spiller Lisa D. , Scovotti Carol
Published: January 2008

This study investigates the extent to which educators address direct and interactive marketing concepts in undergraduate introductory marketing courses. As practitioners seek more accountability from their marketing efforts, so too must academia respond with more relevant content. Results from textbook content analysis suggest that direct and interactive marketing content coverage has grown significantly over the past decade, but survey results from marketing faculty indicate coverage in the classroom lags. This study establishes a baseline of the related topic coverage in introductory marketing courses and suggests a variety of teaching resources to integrate direct and interactive marketing content to improve curricular currency without trying to add more to an already “saturated sponge.”
Abused South Korean Women
Authors: Kim Bitna , Titterington Victoria B.
Published: January 2008

This study compares two groups of women in South Korea: one group incarcerated for the deaths of their male partners and the other staying in a shelter for battered women. The analysis serves to answer two questions: First, are the findings regarding women who kill their intimate partners in Western societies generally applicable to their counterparts in South Korea? Second, how are abused South Korean women who resort to lethal violence against their abusers different from those who do not? Regarding both abused and nonabused women incarcerated for criminal homicide against their partners, results indicate that they have less experience of psychological and physical abuse by their partners and that they are less educated, underemployed, and more supportive of traditional patriarchal norms than are the women who utilize domestic violence shelters. This research explores implications for intervention strategies to encourage abused women to seek help from legal and extralegal sources.
Postoperative Range of Motion following Anterior Cruciate Ligament Reconstruction Using Autograft Hamstrings
Authors: Bottoni Craig R. , Liddell Travis R. , Trainor Timothy J. , Freccero David M. , Lindell Kenneth K.
Published: January 2008

Background

There is a common belief that surgical reconstruction of an acutely torn anterior cruciate ligament (ACL) should be delayed for at least 3 weeks because of the increased incidence of postoperative motion loss (arthrofibrosis) and suboptimal clinical results.

Hypothesis

There is no difference in postoperative range of motion or stability after ACL reconstructions performed either acutely or delayed.

Study Design

Randomized controlled trial; Level of evidence, 1.

Methods

Patients with an acute ACL tear were prospectively randomized to either early (within 21 days) or delayed (beyond 6 weeks) reconstruction using autograft hamstring tendon. Previous knee surgery on the index extremity and a multiligamentous injury were exclusionary criteria. Surgical technique and postoperative rehabilitation were identical for all patients. Postoperative assessments included range of motion and KT-1000 arthrometer measurements compared with the contralateral knee. Standardized outcome measures were used including single assessment numeric evaluation (SANE), Lysholm, and Tegner Activity Score.

Results

Seventy consecutive patients were enrolled, and 1 patient was dropped after a postoperative infection. Sixty-nine patients (34 acute, 35 delayed) with an average age of 27 years composed the study cohort. The mean time from injury to surgery was 9 days (range, 2–17 days) for patients in the early group and 85 days (range, 42–192) for those in the delayed group. The average follow-up from surgery was 366 days (range, 185–869). Articular cartilage and meniscal injuries were comparable between the 2 groups. There were no significant differences between the 2 treatment groups in degrees of extension or flexion lost relative to the nonoperative side, operative time, KT-1000 arthrometer differences, or subjective knee evaluations.

Conclusion

Excellent clinical results can be achieved after ACL reconstructions performed soon after injury using autograft hamstrings. Although the authors do not advocate that all reconstructions should be performed acutely, they found that early ACL reconstructions do not result in loss of motion or suboptimal clinical results as long as a rehabilitation protocol emphasizing extension and early range of motion is employed.
Nonstandard, Not Substandard
Authors: Broschak Joseph P. , Davis-Blake Alison , Block Emily S.
Published: January 2008

The authors investigate how nonstandard work arrangements shape work attitudes and behaviors. They find that attitudes and behaviors vary across different types of nonstandard work arrangements. As expected, retention part-time workers have more positive and agency temporary workers more negative attitudes toward their work arrangements than do standard workers. But contrary to conventional wisdom about temporary work arrangements, agency temporary workers who have opportunities to transition to standard employment arrangements have more positive attitudes toward supervisors and coworkers and are better performers than their peers in standard work arrangements. Part-time arrangements designed to retain valued workers do not produce increased commitment or other attitudinal benefits consistent with retention. The authors discuss the implications of the findings for the study of nonstandard work and the management of nonstandard workers.
A Discursive Approach to Disinhibition Theory: The Normalization of Unsafe Sex Among Gay Men
Authors: Aguinaldo Jeffrey P. , Myers Ted
Published: January 2008

HIV research and prevention commonly cite disinhibition theory as an explanation for HIV infection among gay men. Analyzing qualitative interview data in which men talk about recreational substance use and their safer sex practices, we interrogate the concept of disinhibition theory from a discursive perspective. From this perspective, we treat talk not as a route or resource to something presumed to lie beyond the talk, but as a form of action designed for its interactional context. We demonstrate how the men normalize unsafe sex through constructions of disinhibition as common and widespread. In doing so, the men manage accountability for their own experiences with foregoing condom use while using substances. Our analysis demonstrates the men's displayed concerns to avoid individualized explanations for having engaged in unprotected sex. This may explain why some gay men may resist HIV prevention campaigns, based on these very individualized explanations.
Life Trajectories of Female Child Abuse Survivors Thriving in Adulthood
Authors: Thomas Sandra P. , Hall Joanne M.
Published: January 2008

A narrative study of thriving adult female survivors of childhood maltreatment was undertaken to discover how they had achieved success. Life trajectory patterns, turning points, and setbacks were identified. Data consisted of 81 interview transcripts derived from a series of three interviews, spaced over 6 to 12 months, with 27 survivors. The childhood abuse was intrafamilial, beginning as early as infancy and continuing, in most cases, until participants left home. The onset and pace of the healing trajectory were quite variable, including a roller-coaster pattern as well as patterns of slow, steady progress and continued struggle. Four types of redemption narratives were delineated. Survivors had not been spared depression but had made achievements in work and education and displayed remarkable generativity, parenting their own children well, and mentoring other young girls, especially victims of abuse.
Homebirth as Systems-Challenging Praxis: Knowledge, Power, and Intimacy in the Birthplace
Authors: Cheyney Melissa J.
Published: January 2008

In this article, I examine the processes and motivations involved when women in the United States choose to circumvent the dominant obstetric care paradigm by delivering at home with a group of care providers called direct-entry midwives. Using grounded theory, participant observation, and open-ended, semistructured interviewing, I collected and analyzed homebirth narratives from a theoretical sample of women ( n = 50) in two research locales. Findings interpreted from the perspective of critical medical anthropology suggest that women who choose to birth at home negotiate fears associated with the “just in case something bad happens” argument that forms the foundation for hospital birth rationales through complex individual and social processes. These involve challenging established forms of authoritative knowledge, valuing alternative and more embodied or intuitive ways of knowing, and knowledge sharing through the informed consent process. Adherence to subjugated discourses combined with lived experiences of personal power and the cultivation of intimacy in the birthplace fuel homebirth not only as a minority social movement, but also as a form of systems-challenging praxis.
Municipal Waste Generation and Socioeconomic Drivers
Authors: Mazzanti Massimiliano , Montini Anna , Zoboli Roberto
Published: January 2008

Using data sets from Italian provinces that include rich northern and poorer southern regions, this article examines to what extent income and municipal waste generation are linked and at what level of income they become delinked. The analysis shows that the turning point occurs at very high levels of value added per capita (in the range of 22,586 to 31,611), exemplified by a very limited number of wealthy (northern) Italian provinces. The authors also find that some recently adopted waste policy and waste management instruments have influenced waste generation at source, independent of socioeconomic characteristics. This supports the argument that more effective waste management instruments that target waste prevention at the source need to be implemented in line with the stated priorities of the EU and member countries. The findings also imply that developing countries in particular should not wait to implement waste reduction policies until household incomes and consumption levels increase.
Physiologic Properties and Regulation of the Actin Cytoskeleton in Vascular Smooth Muscle
Authors: Tang Dale D. , Anfinogenova Yana
Published: January 2008

Vascular smooth muscle tone plays a fundamental role in regulating blood pressure, blood flow, microcirculation, and other cardiovascular functions. The cellular and molecular mechanisms by which vascular smooth muscle contractility is regulated are not completely elucidated. Recent studies show that the actin cytoskeleton in smooth muscle is dynamic, which regulates force development. In this review, evidence for actin polymerization in smooth muscle upon external stimulation is summarized. Protein kinases such as Abelson tyrosine kinase, focal adhesion kinase, Src, and mitogen-activated protein kinase have been documented to coordinate actin polymerization in smooth muscle. Transmembrane integrins have also been reported to link to signaling pathways modulating actin dynamics. The roles of Rho family of the small proteins that bind to guanosine triphosphate (GTP), also known as GTPases, and the actin-regulatory proteins, including Crk-associated substrate, neuronal Wiskott-Aldrich Syndrome protein, the Arp2/3 complex, and profilin, and heat shock proteins in regulating actin assembly are discussed. These new findings promote our understanding on how smooth muscle contraction is regulated at cellular and molecular levels.
Steady-State Pharmacokinetics of Nevirapine in HIV-1 Infected Adults in India
Authors: Ramachandran Geetha , Hemanthkumar A.K. , Rajasekaran S. , Padmapriyadarsini C. , Narendran G. , Anitha S. , Subramanyam Sudha , Kumaraswami V. , Swaminathan Soumya
Published: January 2008

Background and Objectives: A variety of demographic factors, sex, and degree of immunosuppression can influence antiretroviral drug concentrations. The authors studied the influence of immune status, sex, and body mass index (BMI) on the steady-state pharmacokinetics of nevirapine delivered as a fixed-dose combination in HIV-1-infected patients in India. Methods: Twenty-six HIV-1-infected adult patients undergoing treatment with nevirapine-based highly active antiretroviral therapy regimens participated in the study. Pharmacokinetic variables were compared between patients divided based on CD4 cell counts, sex, and BMI. Results: Patients with higher BMI had lower peak and trough concentration and exposure of nevirapine than those with lower BMI; none of the differences in the pharmacokinetic variables of nevirapine between the various patient groups was statistically significant. Conclusions: Patients' immune status, sex, or BMI had no impact on the pharmacokinetics of nevirapine. Plasma nevirapine concentrations were maintained within the therapeutic range of the drug in the majority of the patients.
Development of bioluminescent Salmonella strains for use in food safety
Authors: Karsi Attila , Howe Kevin , Kirkpatrick Tasha B , Wills Robert , Bailey R Hartford , Lawrence Mark L
Published: January 2008

Background

Salmonella can reside in healthy animals without the manifestation of any adverse effects on the carrier. If raw products of animal origin are not handled properly during processing or cooked to a proper temperature during preparation, salmonellosis can occur. In this research, we developed bioluminescent Salmonella strains that can be used for real-time monitoring of the pathogen's growth on food products. To accomplish this, twelve Salmonella strains from the broiler production continuum were transformed with the broad host range plasmid pAKlux 1, and a chicken skin attachment model was developed.

Results

Salmonella strains carrying pAKlux 1 constitutively expressed the luxCDABE operon and were therefore detectable using bioluminescence. Strains were characterized in terms of bioluminescence properties and plasmid stability. To assess the usefulness of bioluminescent Salmonella strains in food safety studies, we developed an attachment model using chicken skin. The effect of washing on attachment of Salmonella strains to chicken skin was tested using bioluminescent strains, which revealed the attachment properties of each strain.

Conclusion

This study demonstrated that bioluminescence is a sensitive and effective tool to detect Salmonella on food products in real-time. Bioluminescence imaging is a promising technology that can be utilized to evaluate new food safety measures for reducing Salmonella contamination on food products.
Hepatitis B virus genotypes and resistance mutations in patients under long term lamivudine therapy: characterization of genotype G in Brazil
Authors: Bottecchia Marcelle , Souto Francisco JD , Ó Kycia MR , Amendola Marcia , Brandão Carlos E , Niel Christian , Gomes Selma A
Published: January 2008

Background

Lamivudine is an oral nucleoside analogue widely used for the treatment of chronic hepatitis B. The main limitation of lamivudine use is the selection of resistant mutations that increases with time of utilization. Hepatitis B virus (HBV) isolates have been classified into eight genotypes (A to H) with distinct geographical distributions. HBV genotypes may also influence pathogenic properties and therapeutic features. Here, we analyzed the HBV genotype distribution and the nature and frequency of lamivudine resistant mutations among 36 patients submitted to lamivudine treatment for 12 to 84 months.

Results

Half of the patients were homosexual men. Only 4/36 (11%) patients were HBV DNA negative. As expected for a Brazilian group, genotypes A (24/32 positive individuals, 75%), D (3/32, 9.3%) and F (1/32, 3%) were present. One sample was from genotype C, which is a genotype rarely found in Brazil. Three samples were from genotype G, which had not been previously detected in Brazil. Lamivudine resistance mutations were identified in 20/32 (62%) HBV DNA positive samples. Mean HBV loads of patients with and without lamivudine resistance mutations were not very different (2.7 × 107and 6.9 × 107copies/mL, respectively). Fifteen patients showed the L180M/M204V lamivudine resistant double mutation. The triple mutant rt173V/180M/204V, which acts as a vaccine escape mutant, was found in two individuals. The three isolates of genotype G were entirely sequenced. All three showed the double mutation L180M/M204V and displayed a large genetic divergence when compared with other full-length genotype G isolates.

Conclusion

A high (55%) proportion of patients submitted to long term lamivudine therapy displayed resistant mutations, with elevated viral load. The potential of transmission of such HBV mutants should be monitored. The identification of genotypes C and G, rarely detected in South America, seems to indicate a genotype distribution different to that observed in non treated patients. Disparities in routes of transmission (genotype G seems to be linked to homosexual behavior) and in pathogenic properties (genotype C is very aggressive) among HBV genotypes may explain the presence of rare genotypes in the present work.
Towards defining the nuclear proteome
Authors: Fink J Lynn , Karunaratne Seetha , Mittal Amit , Gardiner Donald M , Hamilton Nicholas , Mahony Donna , Kai Chikatoshi , Suzuki Harukazu , Hayashizaki Yosihide , Teasdale Rohan D
Published: January 2008

Background

The nucleus is a complex cellular organelle and accurately defining its protein content is essential before any systematic characterization can be considered.

Results

We report direct evidence for 2,568 mammalian proteins within the nuclear proteome: the nuclear subcellular localization of 1,529 proteins based on a high-throughput subcellular localization protocol of full-length proteins and an additional 1,039 proteins for which clear experimental evidence is documented in published literature. This is direct evidence that the nuclear proteome consists of at least 14% of the entire proteome. This dataset was used to evaluate computational approaches designed to identify additional nuclear proteins.

Conclusion

This represents direct experimental evidence that the nuclear proteome consists of at least 14% of the entire proteome. This high-quality nuclear proteome dataset was used to evaluate computational approaches designed to identify additional nuclear proteins. Based on this analysis, researchers can determine the stringency and types of lines of evidence they consider to infer the size and complement of the nuclear proteome.
Urinary Cortisol and Catecholamine Excretion after Burn Injury in Children
Authors: Norbury William B. , Herndon David N. , Branski Ludwik K. , Chinkes David L. , Jeschke Marc G.
Published: January 2008

Introduction: A severe burn causes increased levels of urine cortisol and catecholamines. However, little is known about the magnitude of this increase or how and when the levels return to normal. The purpose of this study was to determine in a large clinical prospective trial the acute and long-term pattern of urine cortisol and catecholamine expression in severely burned children.

Methods: Pediatric patients with burns greater than 40% total body surface area (TBSA), admitted to our unit over a 6-yr period, were included into the study. Clinical data including length of stay, number of operations, and duration and number of infections were determined. Patients had regular 24-h urine collections during their acute admission and reconstructive periods. Urine collections were analyzed for cortisol, epinephrine, and norepinephrine. Each urine cortisol was compared with age-adjusted reference ranges. Ninety-five percent confidence intervals and ANOVA analysis were used where appropriate.

Results: Two hundred twelve patients were included in the study (75 females and 137 males), with a mean ± sem TBSA of 58 ± 1% (third-degree 45 ± 2%) and mean age of 9 ± 0.4 yr. Urinary cortisol levels were significantly increased (3- to 5-fold) up to 100 d after the burn and then approached normal levels (P < 0.05). The rise in urine cortisol was significantly higher in male than female patients (P < 0.05). Early hypercortisolemia was associated with increased duration of severe infection (P < 0.05). Persistent hypercortisolemia was associated with increases in both infection rates and duration of severe infection (P < 0.05). Urinary catecholamines showed a significant increase at 11–20 d after the burn (P < 0.05). Urinary norepinephrine levels were significantly increased up to 20 d and then returned to normal (P < 0.05).

Conclusions: Urinary levels of cortisol, epinephrine, and norepinephrine are significantly increased after a major burn. Early hypercortisolemia is associated with increased duration of severe infection. Persistent hypercortisolemia is associated with increases in both infection rates and duration of severe infection.
Associations of Insulin-Like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein (IGFBP)-2 and IGFBP-3 with Ultrasound Measures of Atherosclerosis and Plaque Stability in an Older Adult Population
Authors: Martin Richard M. , Gunnell David , Whitley Elise , Nicolaides Andrew , Griffin Maura , Georgiou Niki , Davey Smith George , Ebrahim Shah , Holly Jeff M. P.
Published: January 2008

Context: Circulating IGF-I is inversely associated with ischemic heart disease incidence. Whether this association relates to alterations in plaque growth or stability, and the role of IGF-II and the major binding proteins [IGF binding protein (IGFBP)-2 and -3], is unclear.

Objective: Our objective was to test the hypothesis that circulating IGF-I is inversely, and IGF-II is positively, associated with subclinical atherosclerosis and plaque stability.

Design, Setting, and Participants: This was a cross-sectional analysis based on 310 participants in the United Kingdom-based Boyd Orr cohort who were aged 63–82 yr. Cohort members from Aberdeen, Bristol, Dundee, Wisbech, and London were invited to clinics for fasted venepuncture and arterial ultrasound examination.

Main Outcomes: Arterial intima-media thickness, arterial plaque prevalence, and computerized assessment of plaque echogenicity (a measure of stability), undertaken using the gray scale median, were calculated.

Results: In total, 269 of 310 (86.8%) participants had at least one carotid or femoral plaque. In models controlling for IGFBP-3, there was a 44% (95% confidence interval 12–64%) reduction in the odds of any plaque and a 28% lower (0–48%) odds of echolucent (unstable) plaques per sd increase in IGF-I. IGFBP-3 was positively associated with plaque instability (odds ratio: 1.38; 0.99–1.93). IGF-II was positively associated (0.05-mm increase per sd; 95% confidence interval 0.01–0.09), and IGFBP-2 was inversely associated, with carotid bifurcation intima-media thickness. Neither IGF-II nor IGFBP-2 was associated with plaque prevalence or echogenicity.

Conclusion: High-circulating IGF-I levels may promote arterial plaque stability. IGF-II and IGFBP-2 do not appear to play a role in plaque development or stability.
Processing of recombinant AAV genomes occurs in specific nuclear structures that overlap with foci of DNA-damage-response proteins
Authors: Cervelli Tiziana , Palacios Jose Alejandro , Zentilin Lorena , Mano Miguel , Schwartz Rachel A. , Weitzman Matthew D. , Giacca Mauro
Published: January 2008

Despite increasing utilization of rAAV vectors in gene transfer applications, several aspects of the biology of these vectors remain poorly understood. We have visualized the conversion of rAAV vector genomes from single-stranded to double-stranded DNA in real time. We report that rAAV DNA accumulates into discrete foci inside the nucleus. These rAAV foci are defined in number, increase in size over time after transduction, are relatively immobile, and their presence correlates with the efficiency of cell transduction. These structures overlap with, or lie in close proximity to, the foci in which proteins of the MRN (MRE11-RAD50-NBS1) complex as well as the MDC1 protein accumulate after DNA damage. The downregulation of MRN or MDC1 by RNA interference markedly increases both the formation of rAAV foci and the extent of rAAV transduction. Chromatin immunoprecipitation experiments indicate that the MRE11 protein associates with the incoming rAAV genomes and that this association decreases upon cell treatment with DNA damaging agents. These findings are consistent with a model whereby cellular DNA-damage-response proteins restrict rAAV transduction by negatively regulating rAAV genome processing.
Dynein-dependent nuclear dynamics affect morphogenesis inCandida albicansby means of the Bub2p spindle checkpoint
Authors: Finley Kenneth R. , Bouchonville Kelly J. , Quick Aaron , Berman Judith
Published: January 2008

Candida albicans, the most prevalent fungal pathogen of humans, grows with multiple morphologies. The dynamics of nuclear movement are similar in wild-type yeast and pseudohyphae: nuclei divide across the bud neck. By contrast, in hyphae, nuclei migrate 10-20 μm into the growing germ tube before dividing. We analyzed the role of the dynein-dynactin complex in hyphal and yeast cells using time-lapse fluorescence microscopy. Cells lacking the heavy chain of cytoplasmic dynein or the p150Glued subunit of dynactin were defective in the position and orientation of the spindle. Hyphal cells often failed to deliver a nucleus to the daughter cell, resulting in defects in morphogenesis. Under yeast growth conditions, cultures included a mixture of yeast and pseudohyphal-like cells that exhibited distinctive defects in nuclear dynamics: in yeast, nuclei divided within the mother cell, and the spindle position checkpoint protein Bub2p ensured the delivery of the daughter nucleus to the daughter cell before cytokinesis; in pseudohyphal-like cells, pre-mitotic nuclei migrated into the daughter and no checkpoint ensured return of a nucleus to the mother cell before cytokinesis. Analysis of double mutants indicated that Bub2p also mediated the pre-anaphase arrest and polarization of pseudohyphal-like cells. Thus, Bub2p has two distinct roles in C. albicans cells lacking dynein: it mediates pre-anaphase arrest and it coordinates spindle disassembly with mitotic exit.
Tetrahymena IFT122Ais not essential for cilia assembly but plays a role in returning IFT proteins from the ciliary tip to the cell body
Authors: Tsao Che-Chia , Gorovsky Martin A.
Published: January 2008

Intraflagellar transport (IFT) moves multiple protein particles composed of two biochemically distinct complexes, IFT-A and IFT-B, bi-directionally within cilia and is essential for cilia assembly and maintenance. We identified an ORF from the Tetrahymena macronuclear genome sequence, encoding IFT122A, an ortholog of an IFT-A complex protein. Tetrahymena IFT122A is induced during cilia regeneration, and epitope-tagged Ift122Ap could be detected in isolated cilia. IFT122A knockout cells still assembled cilia, albeit with lower efficiency, and could regenerate amputated cilia. Ift172p and Ift88p, two IFT-B complex proteins that localized mainly to basal bodies and along the cilia in wild-type cells, became preferentially enriched at the ciliary tips in IFT122A knockout cells. Our results indicate that Tetrahymena IFT122A is not required for anterograde transport-dependent ciliary assembly but plays a role in returning IFT proteins from the ciliary tip to the cell body.
ER stress is associated with dedifferentiation and an epithelial-to-mesenchymal transition-like phenotype in PC Cl3 thyroid cells
Authors: Ulianich Luca , Garbi Corrado , Treglia Antonella Sonia , Punzi Dario , Miele Claudia , Raciti Gregory Alexander , Beguinot Francesco , Consiglio Eduardo , Di Jeso Bruno
Published: January 2008

Conditions perturbing the homeostasis of the endoplasmic reticulum (ER) cause accumulation of unfolded proteins and trigger ER stress. In PC Cl3 thyroid cells, thapsigargin and tunicamycin interfered with the folding of thyroglobulin, causing accumulation of this very large secretory glycoprotein in the ER. Consequently, mRNAs encoding BiP and XBP-1 were induced and spliced, respectively. In the absence of apoptosis, differentiation of PC Cl3 cells was inhibited. mRNA and protein levels of the thyroid-specific genes encoding thyroglobulin, thyroperoxidase and the sodium/iodide symporter and of the genes encoding the thyroid transcription factors TTF-1, TTF-2 and Pax-8 were dramatically downregulated. These effects were, at least in part, transcriptional. Moreover, they were selective and temporally distinct from the general and transient PERK-dependent translational inhibition. Thyroid dedifferentiation was accompanied by changes in the organization of the polarized epithelial monolayer. Downregulation of the mRNA encoding E-cadherin, and upregulation of the mRNAs encoding vimentin, α-smooth muscle actin, α(1)(I) collagen and SNAI1/SIP1, together with formation of actin stress fibers and loss of trans-epithelial resistance were found, confirming an epithelial-mesenchymal transition (EMT). The thyroid-specific and epithelial dedifferentiation by thapsigargin or tunicamycin were completely prevented by the PP2 inhibitor of Src-family kinases and by stable expression of a dominant-negative Src. Together, these data indicate that ER stress induces dedifferentiation and an EMT-like phenotype in thyroid cells through a Src-mediated signaling pathway.
Palmitoylation and localisation of RAS isoforms are modulated by the hypervariable linker domain
Authors: Laude Alex J. , Prior Ian A.
Published: January 2008

RAS isoforms have been proposed to exhibit differing biological outputs due to differences in their relative occupancy of cellular organelles and signalling microdomains. The membrane binding and targeting motifs of RAS are encoded by the C-terminal hypervariable region (HVR), and the precise localisation depends upon interactions between the HVR and the host membrane. Classic studies revealed that all RAS proteins rely on farnesylation and either palmitoylation or a polybasic stretch for stable binding to membranes. We now show that, for N-RAS and Ki-RAS4A, mono-palmitoylation and farnesylation are not sufficient for specifying stable cell-surface localisation. A third motif that is present within the linker domain of all palmitoylated RAS HVRs is necessary for stabilising localisation to the plasma membrane. This motif comprises acidic residues that stabilise palmitoylation and basic amino acids that are likely to interact electrostatically with acidic phospholipids enriched at the cell surface. Importantly, altered localisation is achieved without changes in palmitoylation status. Our data provide a mechanism for distinct HVR membrane interactions controlling subcellular distribution. In the context of the full-length RAS proteins, this is likely to be of crucial importance for controlling signalling output and engagement with different pools of effectors.
A S-bridged CoIIIAuICoIII Trinuclear Complex with l-Cysteinate Acting as a Flexible Dicarboxylate-type Metalloligand toward Manganese(II)
Authors: Aridomi Takashi , Takamura Keiichi , Igashira-Kamiyama Asako , Konno Takumi
Published: January 2008

Treatment of a S-bridged CoIIIAuICoIII trinuclear complex [1]3+, newly prepared from ΔL-[Co(l-cys-N,S)(en)2]+ and AuI, with MnCl2 gave a 1D (CoIII2MnIIAuI)n polymeric complex, in which two carboxylate groups of [1]3+ bind to two MnCl2 moieties. On the other hand, a discrete CoIII2MnIIAuI tetranuclear complex, in which two carboxylate groups of [1]3+ chelate to a Mn(NO3)2 moiety, was produced by similar treatment of [1]3+ with Mn(NO3)2.
Design and Synthesis of Near-infrared-active Heptamethine–Cyanine Dyes to Suppress Aggregation in a Dye-sensitized Porous Zinc Oxide Solar Cell
Authors: Otsuka Atsuhiro , Funabiki Kazumasa , Sugiyama Naoyuki , Mase Hiroyoshi , Yoshida Tsukasa , Minoura Hideki , Matsui Masaki
Published: January 2008

New heptamethine–cyanine dyes were synthesized and used for dye-sensitization of porous zinc oxide cells in the near-infrared region (800 nm). The introduction of alkyl groups into the cyclohexene and indolenium moieties remarkably prevented H-aggregation of the dyes. Consequently, the photovoltaic performance of the dye-sensitized zinc oxide cells with DCA was improved; a solar-to-electricity conversion efficiency (η) of 0.67%, a short-circuit current density of 2.22 mA cm−2, an open-circuit photovoltage of 0.46 V, and a fill factor of 0.66 under standard AM 1.5 irradiation (100 mW cm−2).
Synthesis and Characterization of Novel Monodisperse Starburst Oligo(fluoreneethynylene) Based on Truxene Moiety
Authors: Chen Qing-Quan , Liu Feng , Ma Zhun , Peng Bo , Wei Wei , Huang Wei
Published: January 2008

A series of novel monodisperse star-shaped oligo(fluoreneethynylene)s, which contain hexahexyltruxene as the central core linked with oligo(fluoreneethynylene) as the arms, are presented.
Selective Oxidation of Alcohols by Orthorhombic Mo–V–O Phase with Molecular Oxygen
Authors: Wang Feng , Ueda Wataru
Published: January 2008

We have investigated heterogeneous oxidation of alcohols using crystalline molybdenum vanadium oxide (Mo–V–O) as catalyst with molecular oxygen as oxidant. The major product from primary alcohol was aldehyde, the secondary alcohol was mainly dehydrated to olefin, and the oxidation of cyclic alcohols chiefly afforded ketones. A Hammett plot suggested that hydride abstraction might be involved in the reaction step. We have discussed possible reaction mechanism based on substrate adsorption and activation on catalytically active sites.
Reexamining Syphilis: An Update on Epidemiology, Clinical Manifestations, and Management
Authors: Kent Molly E , Romanelli Frank
Published: January 2008

Objective:

To review the epidemiology, clinical features, diagnosis, and treatment of syphilis.

Data Sources:

Studies and reviews were abstracted from MEDLINE (1950–April 2007) using the search term syphilis. AN papers were cross-referenced to identify additional studies and reviews for inclusion.

Study Selection and Data Extraction:

Pertinent original research articles, review articles, and book chapters were evaluated.

Data Synthesis:

Syphilis is a spirochetal disease that has plagued mankind for centuries. Following a low incidence of syphilis in the US for the last 2 decades, rates are now increasing both in the US and other parts of (he world. Once acquired, syphilis can pass through 4 distinct stages of disease: primary syphilis. secondary syphilis, latent syphilis, and tertiary syphilis, with each stage being characterized by different symptoms and levels of infectivity. Diagnosis is made primarily by serologic assays with nontreponemal tests such as the Venereal Disease Research Laboratory and the Rapid Plasma Reagin assay used for screening. Treponemal tests including the Treponema pallidum particle agglutination and the fluorescent treponemal antibody absorption test are then used for confirmation. Recommended treatment regimens are based largely on uncontrolled trials and clinical experience. Penicillin is the treatment of choice, with the preparation and treatment duration varying for different stages. Benzathine penicillin is the treatment of choice lor all stages of syphilis except neurosyphilis, for which aqueous crystalline penicillin or procaine penicillin is used due to the central nervous system penetration of these formulations. Coinfection with both syphilis and HIV occurs frequently due to common risk factors. These 2 diseases interact with each other, making both diagnosis and treatment more complicated.

Conclusions:

Clinicians should be aware of the signs and symptoms of syphitis as well as current guidelines for the management and treatment of this disease.
Mustard Gas: Imminent Danger or Eminent Threat?
Authors: Geraci Matthew J
Published: January 2008

Objective:

To increase awareness of the widespread environmental prevalence of the chemical warfare agent mustard gas, examine the acute and chronic toxic effects to exposed humans, and discuss medical treatment guidelines for mustard gas exposures.

Data Sources:

Literature retrieval of medical case reports and clinical studies was accomplished using PubMed and the Cochrane Database (1919–March 2007). Search terms included mustard, mustard gas, sulfur mustard, chemical warfare, blister agents, vesicants, and war gas. Historical information and current events were accessed through military field manuals and Internet searches.

Study Selection and Data Extraction:

All articles in English identified from the data sources were evaluated. Adult and pediatric populations were included in the review.

Data Synthesis:

Mustard gas and other chemical weapons are feared for their use as weapons of terror; however, the major threat of mustard gas lies elsewhere. Tons of this chemical agent were produced for war, then subsequently buried in landfills, disposed of at sea, or teft to decay in storage lacrlities. There are documented and anecdotal reports of chemical weapon buriat sites and ocean dumps across the globe spanning from the Arctic Circle to Australia. Numerous accidental exposures have occurred over the past decade. Mustard gas is corrosive to the skin, eyes, and respiratory tract. Extensive exposures can also affect other organ systems. Its ability to cause harm to multiple organ systems at extremely low doses in virtually any environmental condition makes it an extremely dangerous agent. Immediate decontamination of people exposed to mustard gas liquids and vapors is paramount. Supportive care and long-term followup is necessary for exposed persons. Research is under way to find antidotes or treatment methods for mustard gas exposure, but currently there are no definitive treatment guidelines.

Conclusions:

Mustard gas is a weapon, but also a prevalent environmental threat. Recognizing the immense environmental presence of mustard gas disposal sites and the signs and symptoms of exposure will help speed treatment to those accidentally or purposefully exposed.
Tips for Writing and Publishing an Article
Authors: Nahata Milap C
Published: January 2008

Peer reviewed publications are the primary source of important new information. This editorial provides tips for writing various sections of research papers, review articles, and case reports. Additional topics discussed include making decisions about authorship, selecting a journal for submission of an article, understanding the peer review process and expectations of editors and reviewers, and revising the article. Successful authors combine appropriate knowledge and experience, personal attributes, and effective collaborations to produce insightful and important contributions to the literature.
In-Pile Criteria for the Initiation of Massive Hydriding of Zr in Steam-Hydrogen Environment
Authors: Evdokimov I. A. , Likhanskii V. V.
Published: January 2008

It is shown that irradiation of oxide film on the surface of zirconium alloy by fission fragments may promote the breakdown of oxide protective properties and lead to massive hydriding of zirconium in a steam-hydrogen environment far beyond the condition of “oxygen starvation.” Massive hydriding of zirconium claddings may cause severe secondary degradation of failed fuel rods in commercial nuclear reactors. The effect of irradiation is concerned with two factors. The first one is radiolysis of steam-hydrogen mixture and chemical interaction of highly reactive radicals with the oxide surface. The second factor is intense generation of radiation-induced defects in crystal lattice of ZrO2 which enhance the rate of oxide reduction. A model is proposed for assessment of the threshold conditions for the onset of massive hydriding depending on composition of steam-hydrogen mixture and irradiation dose rate.
Neuropeptide Y in the Amygdala Induces Long-Term Resilience to Stress-Induced Reductions in Social Responses But Not Hypothalamic–Adrenal–Pituitary Axis Activity or Hyperthermia
Authors: Sajdyk Tammy J. , Johnson Philip L. , Leitermann Randy J. , Fitz Stephanie D. , Dietrich Amy , Morin Michelle , Gehlert Donald R. , Urban Janice H. , Shekhar Anantha
Published: January 2008

Resilience to mental and physical stress is a key determinant for the survival and functioning of mammals. Although the importance of stress resilience has been recognized, the underlying neural mediators have not yet been identified. Neuropeptide Y (NPY) is a peptide known for its anti-anxiety-like effects mediated via the amygdala. The results of our current study demonstrate, for the first time that repeated administration of NPY directly into the basolateral nucleus of the amygdala (BLA) produces selective stress-resilient behavioral responses to an acute restraint challenge as measured in the social interaction test, but has no effect on hypothalamic–adrenal–pituitary axis activity or stress-induced hyperthermia. More importantly, the resilient behaviors observed in the NPY-treated animals were present for up to 8 weeks. Antagonizing the activity of calcineurin, a protein phosphatase involved in neuronal remodeling and present in NPY receptor containing neurons within the BLA, blocked the development of long-term, but not the acute increases in social interaction responses induced by NPY administration. This suggests that the NPY-induced long-term behavioral resilience to restraint stress may occur via mechanisms involving neuronal plasticity. These studies suggest one putative physiologic mechanism underlying stress resilience and could identify novel targets for development of therapies that can augment the ability to cope with stress.
Currents in Response to Rapid Concentration Jumps of Amphetamine Uncover Novel Aspects of Human Dopamine Transporter Function
Authors: Erreger Kevin , Grewer Christof , Javitch Jonathan A. , Galli Aurelio
Published: January 2008

Amphetamine (AMPH) is a widely abused psychostimulant that acts as a substrate for the human dopamine transporter (hDAT). Using a piezoelectric rapid application system, we measured AMPH-induced currents mediated by hDAT. Whole-cell patch-clamp recordings in a heterologous expression system reveal that AMPH induces a rapidly activating and subsequently decaying inward current mediated by hDAT. We hypothesize that this transient inward current reflects a conformational change associated with substrate translocation. The AMPH-induced current strictly depends on extracellular Na+. Elevated intracellular Na+has no effect on the peak AMPH-induced current amplitude but inhibits the steady-state current. In addition, elevated intracellular Na+causes an overshoot outward current upon washout of AMPH that reflects hDAT locked in a Na+-exchange mode. Furthermore, elevated intracellular Na+dramatically accelerates the recovery time from desensitization of the AMPH-induced current, revealing a new role for intracellular Na+in promoting the transition to the hDAT “outward-facing” conformation. Ion substitution suggests that both extracellular and intracellular Cl−facilitate transporter turnover in contrast to the classical model of Cl−as a cotransported ion. We present an alternating-access model of hDAT function that accurately fits the main features of the experimental data. The model predicts that translocation of substrate occurs within milliseconds of substrate binding but that slow reorientation of the empty transporter is the rate-limiting factor for turnover. The model provides a framework for interpreting perturbations of hDAT activity.
Modulation of Muscle Synergy Recruitment in Primate Grasping
Authors: Overduin Simon A. , d'Avella Andrea , Roh Jinsook , Bizzi Emilio
Published: January 2008

In grasping, the CNS controls a particularly large number of degrees of freedom. We tested the idea that this control is facilitated by the presence of muscle synergies. According to the strong version of this concept, these synergies are invariant, hard-wired patterns of activation across muscles. Synergies may serve as modules that linearly sum, each with specific amplitude and timing coefficients, to generate a large array of muscle patterns. We tested two predictions of the synergy model. A small number of synergies should (1) account for a large fraction of variation in muscle activity, and (2) be modulated in their recruitment by task variables, even in novel behavioral contexts. We also examined whether the synergies would (3) have broadly similar structures across animals. We recorded from 15 to 19 electrodes implanted in forelimb muscles of two rhesus macaques as they grasped and transported 25 objects of variable shape and size. We show that three synergies accounted for 81% of the electromyographic data variation in each monkey. Each synergy was modulated in its recruitment strength and/or timing by object shape and/or size. Even when synergies were extracted from a small subset of object shape and size conditions and then used to reconstruct the entire dataset, we observed highly similar synergies and patterns of modulation. The synergies were well conserved between monkeys, with two of the synergies exceeding chance structural similarity, and the third being recruited, in both animals, in proportion to the size of the object handled.