bluuebunny/crossref_metadata_2025 huggingface dataset:
Massive expansions of Dscam splicing diversity via staggered homologous recombination during arthropod evolution
Authors: Lee Christopher , Kim Namshin , Roy Meenakshi , Graveley Brenton R.
Published: November 2009

The arthropod Down syndrome cell adhesion molecule (Dscam) gene can generate tens of thousands of protein isoforms via combinatorial splicing of numerous alternative exons encoding immunoglobulin variable domains organized into three clusters referred to as the exon 4, 6, and 9 clusters. Dscam protein diversity is important for nervous system development and immune functions. We have performed extensive phylogenetic analyses of Dscam from 20 arthropods (each containing between 46 and 96 alternative exons) to reconstruct the detailed history of exon duplication and loss events that built this remarkable system over 450 million years of evolution. Whereas the structure of the exon 4 cluster is ancient, the exon 6 and 9 clusters have undergone massive, independent expansions in each insect lineage. An analysis of nearly 2000 duplicated exons enabled detailed reconstruction of the timing, location, and boundaries of these duplication events. These data clearly show that new Dscam exons have arisen continuously throughout arthropod evolution and that this process is still occurring in the exon 6 and 9 clusters. Recently duplicated regions display boundaries corresponding to a single exon and the adjacent intron. The boundaries, homology, location, clustering, and relative frequencies of these duplication events strongly suggest that staggered homologous recombination is the major mechanism by which new Dscam exons evolve. These data provide a remarkably detailed picture of how complex gene structure evolves and reveal the molecular mechanism behind this process.
Daptomycin Versus Other Antimicrobial Agents for the Treatment of Skin and Soft Tissue Infections: A Meta-Analysis
Authors: Bliziotis loannis A , Plessa Eleni , Peppas George , Falagas Matthew E
Published: November 2009

BACKGROUND

Skin and soft tissue infections (SSTIs) are common in everyday clinical practice. Daptomycin has been shown to achieve very good concentrations in skin and soft tissues.

OBJECTIVE

To compare the effectiveness and toxicity of daptomycin with that of other antimicrobials for the treatment of SSTIs.

METHODS

PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up to March 2009. Comparative studies in which daptomycin was used in the intervention group were included in this meta-analysis. The primary outcome of interest was clinical success; secondary outcomes were microbiologic success, clinical success in subsets with complicated SSTIs (cSSTIs) or infections due to methicillin-resistant Staphylococcus aureus; (MRSA), clinical success of daptomycin-versus vancomycin-treated patients, time to clinical cure, treatment-related adverse events, withdrawal from treatment due to toxicity, all-cause mortality, and development of resistance.

RESULTS

Four studies were included in the analysis (3 were randomized controlled trials [RCTs]). Vancomycin and semisynthetic penicillins were used in the comparator arm. Three studies reported on patients with cSSTIs. The intention-to-treat (ITT) population was 1557 patients. No statistically significant difference between daptomycin and comparators was found regarding clinical success in clinically evaluable (OR 0.89; 95% CI 0.63 to 1.25 in the 3 RCTs and OR 1.34; 95% CI 0.38 to 4.66 with all 4 studies included), ITT, MRSA-infected patients, and those with cSSTIs. Two studies reported that significantly fewer patients with cSSTIs required prolonged treatment in the daptomycin arm and that clinical cure was faster than with comparators. No difference between the compared regimens was found in other outcomes.

CONCLUSIONS

Daptomycin is effective and safe for the treatment of SSTIs. Studies evaluating the optimal duration of daptomycin therapy for cSSTIs, comparing daptomycin with new agents, and focusing on proven MRSA SSTIs will be helpful for the further evaluation of the drug.
Psychotropic Medication Changes, Polypharmacy, and the Risk of Early Readmission in Suicidal Adolescent Inpatients
Authors: Fontanella Cynthia A , Bridge Jeffrey A , Campo John V
Published: November 2009

Background:

Adolescents with acute suicidal ideation and attempts are frequently treated with psychotropic medications in psychiatric hospitals. However, little is known about whether pharmacologic interventions used to stabilize suicidal adolescents within inpatient settings are effective in reducing early readmission.

Objective:

To examine whether psychotropic medication changes and polypharmacy are associated with 30-day readmission rates for suicidal adolescents.

Methods:

We conducted a retrospective cohort study of 318 Medicaid-enrolled adolescents admitted for suicidal behaviors to 3 major inpatient psychiatric hospitals in Maryland. Comprehensive data on patient demographics, clinical factors, service history, and inpatient treatment practices were collected from hospital medical records. Medications prescribed prior to admission and during the hospital stay were matched and compared with regard to drug, dosage, and frequency of administration to identify the different types of medication changes. Multivariate Cox proportional hazard analysis was used to examine the association of medication changes and polypharmacy with readmission.

Results:

At least one medication change was made in 78% of suicidal adolescent inpatients, typically the addition of an antidepressant, mood stabilizer, or antipsychotic. At discharge, nearly one quarter (23%) of youths were prescribed 3 or more medications from different drug classes. Controlling for demographic and clinical factors, the addition of an antidepressant was associated with an 85% lower risk of readmission (HR 0.15; 95% CI 0.03 to 0.68). However, the use of 3 or more medications from different drug classes was associated with a 2.6 times higher risk of readmission (95% CI 1.03 to 6.52).

Conclusions:

In this sample of suicidal adolescents, antidepressant treatment was associated with a lower risk of readmission and polypharmacy was associated with a higher risk of readmission. Study findings highlight the need for quality improvement efforts that optimize pharmacologic treatment and physician decision making.
Myxedema Coma Associated with Combination Aripiprazole and Sertraline Therapy
Authors: Church Chelsea O , Callen Erin C
Published: November 2009

Objective:

To describe a case of myxedema coma (MC) associated with combination aripiprazole and sertraline therapy.

Case Summary:

A 41-year-old male presented to the emergency department with confusion, right-sided numbness and tingling, slurred speech, dizziness, and facial edema. His blood pressure was 160/113 mm Hg, with a pulse of 56 beats/min and temperature of 35.4 °C, Initial abnormal laboratory values included creatine kinase (CK) 439 U/L; serum creatinine 1.6 mg/dL; aspartate aminotransferase 85 U/L; and alanine aminotransferase 35 U/L. Repeat cardiac markers revealed an elevated CK level of 3573 U/L with a CK-MB of 24 ng/mL. Thyroid function tests showed thyroid-stimulating hormone 126.4 μIU/mL and free thyroxine 0.29 ng/dL. Home medications of unknown duration were sertraline 200 mg and aripiprazole 20 mg daily. He was admitted to the intensive care unit and initially treated with intravenous levothyroxine and dexamethasone. By hospital day 4, the patient was clinically stable and discharged to home.

Discussion:

Myxedema coma, the most significant form of hypothyroidism (HT), is a rare but potentially fatal condition. The known precipitating causes of MC were ruled out in this patient, which left his home medications as the likely cause. Cases of HT caused by certain atypical antipsychotics and antidepressants are found in the literature, but none was reported with aripiprazole therapy. There are also no reported cases of sertraline or aripiprazole inducing MC. Use of the Naranjo probability scale indicates that the combination of aripiprazole and sertraline was a probable inducer of MC in this patient.

Conclusions:

Due to the widespread use of psychotropic medications, clinicians should be reminded of the rare, yet life-threatening, occurrence of MC when treating patients, especially with combination therapies such as sertraline and aripiprazole.
Drug-Drug Interaction Between Itraconazole and the Protease Inhibitor Lopinavir/Ritonavir
Authors: Hills-Nieminen Cara , Hughes Christine A , Houston Stan , Shafran Stephen D
Published: November 2009

Objective:

To report the results of therapeutic drug monitoring of lopinavir/ritonavir and itraconazole concentrations in an HIV-infected male who was treated for histoplasmosis.

Case Summary:

A 34-year-old HIV-infected man who had recently initiated efavirenz-based antiretroviral therapy was diagnosed with disseminated Histoplasma capsulatum infection. In the hospital, lopinavir/ritonavir 400 mg/100 mg twice daily replaced efavirenz to avoid etavirenz-itraconazole interactions. After 14 days of liposomal amphotericin B therapy, itraconazole solution was initiated at 150 mg twice daily for 3 days, followed by 200 mg daily. Prior to itraconazole initiation, lopinavir trough concentration was 7.4 mg/L. The lopinavir trough concentration 15 days later, after 14 days of itraconazole, was 6.8 mg/L. An itraconazole concentration measured 2 hours post-dose on day 15 of oral therapy was 1.9 pg/mL. After 2 weeks of liposomal amphotericin, urine Histoplasma antigen was 27.23 ng/mL; after 5 months of oral itraconazole therapy, it decreased to 5.24 ng/mL. Plasma HIV RNA decreased 4.26 log10 in 5 months to less than 40 copies/mL The patient has demonstrated marked clinical improvement.

Discussion:

In this case, dosing recommendations of itraconazole 200 mg daily with lopinavir/ritonavir were appropriate. Lopinavir trough concentrations were not significantly different following the addition of itraconazole and were above the minimum target of 1 mg/L in treatment-naive patients. The itraconazole concentration was above the recommended concentration of at least 1 μg/mL.

Conclusions:

The dose of itraconazole was reduced to 200 mg daily as recommended by current guidelines, and therapeutic drug monitoring of both itraconazole and lopinavir concentrations confirmed that no further dosage adjustments were necessary.
Lopinavir Cerebrospinal Fluid Steady-State Trough Concentrations in HIV-Infected Adults
Authors: DiCenzo Robert , DiFrancesco Robin , Cruttenden Kim , Donnelly Julie , Schifitto Giovanni
Published: November 2009

Background:

The central nervous system may act as a sanctuary site for viral replication in the setting of low antiretroviral penetration. Data on lopinavir cerebrospinal fluid (CSF) trough concentration (Ctrough) values have yet to be reported.

Objective:

To describe lopinavir CSF Ctrough values and compare them with a measure of HIV susceptibility.

Methods:

In a prospective, open-label design, HIV-infected adults whose regimen included lopinavir/ritonavir 400/100-mg soft-gel capsules twice daily for at least 4 weeks were enrolled. Each subject had 8 plasma lopinavir concentrations determined over a 12-hour dosing interval and 1 CSF lopinavir Ctrough value determined at the end of the study. Linear regression methods tested for associations between CSF or CSF to plasma concentration ratio and covariates including pharmacokinetic parameters and CSF protein.

Results:

Ten patients (7 male; median [range] ± SD age 45.3 ± 2.8 y) completed the study. Median (intraquartile range [IQR]) lopinavir plasma 0- to 12-hour area under the curve (AUC0-12) and minimum concentrations were 71.3 h•μg/mL (48.4-87.6) and 3.82 /jg/mL (2.76-5.34). Median (IQR) CSF Ctrough, paired plasma concentration, and time since last dose were 11,200 pg/mL (6760–16.400), 5.42 μg/mL (3.88–5.85), and 9.9 hours (9.7-10.2), respectively. Median (IQR) CSF to plasma concentration ratio was 0.225% (0.194-0,324). Lopinavir CSF Ctrough was above the median 50% inhibitory concentration (IC50) for wild-type HIV-1 (wfHIV-1) (1900 pg/mL) in all subjects. Lopinavir plasma AUC0-12 (r2= 0.65; p = 0.009) and CSF protein (r2 = 0.26; p = 0.006) were associated with lopinavir CSF concentration, while CSF protein (r2 = 0.66; p = 0.008) was associated with CSF to plasma concentration ratio.

Conclusions:

Lopinavir CSF Ctrough was above the median IC50 for wfHIV-1 replication in all patients receiving lopinavir/ritonavir 400/100-mg soft-gel capsules twice daily.
Gemfibrozil-Induced Myositis in a Patient with Normal Renal Function
Authors: Hahn Martin , Sriharan Kalavally , McFarland M Shawn
Published: November 2009

OBJECTIVE

To describe a case of gemfibrozil monotherapy-induced myositis in a patient with normal renal function

CASE SUMMARY

A 68-year-old white man presented to his primary care clinic complaining of a 6-month history of total body pain. His past medical history was significant for hypertension, diabetes mellitus, hyperlipidemia, gastroesophageal reflux disease, benign prostatic hypertrophy, arthritis, impotence, and pancreatic cancer that required excision of part of his pancreas. His home drug regimen included bupropion 75 mg twice daily, gemfibrozil 600 mg twice daily for the past 8 months, glimiperide 1 mg daily, insulin glargine 5 units at bedtime, insulin aspart 5 units in the evening, lisinopril 10 mg daily, omeprazole 40 mg daily, pregabalin 100 mg daily, and sildenafil 100 mg as needed. Laboratory test results were significant for elevated aspartate aminotransferase (AST) 78 U/L (reference range 15–46 U/L), alanine aminotransferase (ALT) 83 U/L (13–69 U/L), and creatine kinase (CK) 3495 U/L (55–170 U/L). Serum creatinine was normal at 1.19 mg/dL. The physician determined that the elevated CK indicated myositis secondary to gemfibrozil use, and gemfibrozil was subsequently discontinued. The patient returned 1 week later to repeat the laboratory tests. Results were CK 220 U/L, AST 26 U/L, ALT 43 U/L, and serum creatinine 1.28 mg/dL. The patient was asked to return in 3 weeks to repeat the laboratory tests. At that time, CK had continued to decrease to 142 U/L, and the AST and ALT had returned to normal, at 22 and 29 U/L, respectively. The patient reported complete resolution of total body pain 3 weeks after discontinuation of gemfibrozil. Follow-up 5 weeks after discontinuation revealed no change compared to the 3-week follow-up.

DISCUSSION

Myositis most often produces weakness and elevated CK levels more than 10 times the upper limit of normal. The risk of developing myositis, myopathy, or rhabdomyolysis is low (1%) when fibrates such as gemfibrozil are used as monotherapy. Evaluation of the literature revealed one case of gemfibrozilrelated myositis in a patient with chronic renal failure. There is also one report of myopathy associated with gemfibrozil monotherapy in a patient with normal renal function. The present case is the first documented case of gemfibrozil monotherapy-induced myositis in a patient with normal renal function. The Naranjo probability scale indicated a probable relationship between gemfibrozil treatment and the onset of myositis in our patient. Other potential causes of myositis were ruled out by patient interview and chart review.

CONCLUSIONS

Although the risk of myositis appears to be low with gemfibrozil monotherapy, clinicians should be aware of the potential for this adverse event. For patients taking gemfibrozil monotherapy who present with myalgia, discontinuation of the medication may be necessary for the alleviation of pain.
A Retrospective Poison Center Review of Varenicline-Exposed Patients
Authors: Kreshak Allyson A , Clark Alycia K , Clark Richard F , Ly Binh T , Cantrell F Lee
Published: November 2009

Background:

Varenicline was approved by the Food and Drug Administration (FDA) as a prescription smoking cessation aid in May 2006. Varenicline is both a partial nicotine agonist and an antagonist. Recent reports by the Institute of Safe Medication Practices identified safety problems associated with varenicline use, and the FDA recently issued a boxed warning. These safety concerns regarding varenicline use prompted this study.

Objective:

To characterize varenicline-exposed patients as reported to a poison control system.

Methods:

We performed a retrospective search of the California Poison Control System electronic database from August 2006 through August 2008, using the term varenicline or Chantix. Cases matching these results were reviewed. All ages were included. Excluded were patients with coingestants and unknown outcomes. Clinical parameters and medical outcomes were extracted from the database.

Results:

Thirty-six cases met inclusion criteria and 17 cases were excluded, Ten cases involved nonpediatric patients; 9 cases involved patients less than 6 years old, which were defined as pediatric patients. The median duration of poison center follow-up for pediatric patients was 253 minutes; median duration of follow-up for nonpediatric patients with unintentional exposures was 28.5 minutes. The majority of exposures were unintentional and included all the pediatric patients and 6 nonpediatric patients who had unintentional medication errors, Gastrointestinal and neuropsychiatric adverse events were most frequently reported. The majority of these patients were managed at home. Among those evaluated at a healthcare facility, only 1 pediatric patient was admitted. Of the remaining patients, 1 nonpediatric patient reported a deliberate exposure and 3 nonpediatric patients experienced adverse effects at therapeutic doses. Median duration of follow-up for these patients was 308 minutes.

Conclusions:

Patients exposed to varenicline in our study had favorable outcomes. Gastrointestinal and neuropsychiatric effects were the most commonly reported adverse events. A dose-response relationship could not be determined and triage criteria to a healthcare facility remain undetermined.
Suicidal Behavior and Psychotropic Medications for Adolescents: An Uneasy Association, as Yet Not Clarified
Authors: Alderman Christopher P
Published: November 2009

Despite considerable recent attention and wide-scale interventions by regulatory authorities that have changed drug usage patterns, the possible relationship between psychotropic pharmacotherapy and suicidal behavior among children and adolescents remains unclear. Confounding by diagnosis adds to confusion in the interpretation of the relationship between antidepressant use and suicidal behavior among young people. Recent research suggests that antidepressants may be protective against early readmission after hospitalization for suicide attempts or ideation, but that psychotropic polypharmacy (although common) may be associated with increased risk of rehospitalization. There remains an urgent need for high-quality, ongoing research into these clinical dilemmas.
Localization of ATP-sensitive K+ Channel Subunits in Rat Submandibular Gland
Authors: Zhou Ming , He Hui-Jing , Hirano Maki , Sekiguchi Masaki , Tanaka Osamu , Kawahara Katsumasa , Abe Hiroshi
Published: November 2009

ATP-sensitive K+ (Katp) channel subunits were investigated in rat submandibular gland (SMG). RT-PCR detected the presence of mRNA transcripts of the Kir6.1, Kir6.2, SUR2A, and SUR2B in the SMG, whereas SUR1 mRNA was barely detected. Western blot analysis provided the evidence that these four Katp channel subunits are expressed in rat SMG. Immunostaining detected that these four Katp channel subunits are widely distributed, with different intensities, in myoepithelial cells, epithelial cells of intercalated ducts, granular convoluted tubules, striated ducts, and excretory ducts. Immunofluorescence double staining showed that Kir6.1 and Kir6.2 colocalized with SUR2A in the myoepithelial cells, granular convoluted tubules, striated ducts, and excretory ducts. Kir6.1 and Kir6.2 also colocalized with SUR2B, mainly in the duct system, e.g., the granular convoluted tubules, striated ducts, and excretory ducts. Taken together, these results indicate that the Katp channels in SMG may consist of Kir6.1, Kir6.2, SUR2A, and SUR2B, with various combinations of colocalization with each other, and may play important roles in rat SMG during salivary secretion.
Radio, modern communication media and the technological sublime
Authors: Craig Douglas B
Published: November 2009

Leo Marx and others have argued that the reception of technology in the United States during the nineteenth century was conditioned by the technological sublime. John F. Kasson defined this as a powerful emotion, utility, and moral purpose, suffused with the conviction that the health of the republic was indicated and improved by technological progress. This article provides different perspectives on the American technological sublime, as well as an exploration of its transference to radio and then television. Although there was no shortage of enthusiasm for radio, and for its potential to reconfigure the republic, its reception was not as uncomplicated as the idea of the technological sublime suggests. Interwar hopes for broadcasting and its potential social effects spoke as much to American insecurities as to their dreams; deep fears about social cohesion, cosmopolitanism and pluralism underpinned promises of a new age of radio culture and citizenship. Most Americans did not need to be persuaded of the benefits of radio and later media technologies, but those who identified with the cultural and political establishments needed to be reassured that their position and values would not be threatened by it.
Radioscreens. Radio and cinema in Italy, radio on Italian cinema
Authors: Perrotta Marta
Published: November 2009

This article examines the relationship between radio and cinema, both from historic and aesthetic points of view. The aim of its first section is to consider the mutual impact of the two media and of their output on the specific terrain of Italian popular culture and media history.
The second section outlines a range of approaches to the representation of the radio medium in Italian cinema. In particular, looking at Italian movies from the early stages of sound cinema in Italy to the present-day developments of national film production, the article aims to sketch a framework
of possible uses of radio sounds, radio tales, radio programmes and stars within the cinema discourses and narrations.
From hero to zero: how commercialism ruined community radio in Flanders
Authors: Evens Tom , Hauttekeete Laurence
Published: November 2009

In this article, we analyze to what degree a situation of ruinous competition or commercialism affects the economic viability of local radio in Flanders and its duty to supply societal diversity. By examining evidence from both quantitative and qualitative survey approaches, we found
that many idealistic, non-commercial stations were pushed out of the market by the rise of large-scale networks and that the overall financial performance of these stations has dramatically deteriorated. Furthermore, the ongoing competition for listeners has driven stations to a market conformity
approach leading to similar programming strategies and to shrink local content. With structural handicaps challenging local radio's viability, we aim to formulate some major recommendations for the reorganization of local broadcasting to strengthen both its economical and societal value.
Defenses of polar macroalgae against herbivores and biofoulers
Authors: Amsler Charles D. , Iken Katrin , McClintock James B. , Baker Bill J.
Published: November 2009

Chemical defenses against herbivores are common in macroalgae from Antarctica, particularly in those species that typically dominate benthic communities. Conversely, although little studied, chemical defenses do not appear to be as important in the ecological relationships of Arctic macroalgae. Mesoherbivory may be particularly heavy in Antarctic macroalgal communities, but Antarctic macroalgae produce chemical defenses against both mesoherbivores and macroherbivores. Antarctic macroalgae have been useful in testing and extending chemical defense theories. While physical defenses may also be important in some Antarctic macroalgal-herbivore relationships, particularly with respect to mesoherbivores, physical defenses do not appear to have wide-spread importance against macroherbivores. In Arctic macroalgae, physical defenses may be of more overall importance in reducing mesoherbivory. Antarctic macroalgae also produce compounds with the potential to control biofouling by sympatric microalgae.
Biodiversity, biogeography and zonation of marine benthic micro- and macroalgae in the Arctic and Antarctic
Authors: Wulff Angela , Iken Katrin , Quartino María Liliana , Al-Handal Adil , Wiencke Christian , Clayton Margaret N.
Published: November 2009

This paper reviews the composition, biogeography and zonation of benthic algae in Arctic and Antarctic polar regions. There is a marked contrast in the literature between the amount of information on microalgae vs. macroalgae. Perhaps not surprising in view of their size and conspicuous nature, the macroalgae are better known than the microalgae and they have been studied more intensively. Macroalgal biodiversity is greater in Antarctica than in the Arctic, as is the number of endemic species. Both these characteristics of the Antarctic marine macroalgal flora can be explained by the biogeographical histories of the regions. In contrast, endemism amongst Arctic and Antarctic benthic microalgae is generally considered to be low; however, there is very little evidence to support this and further molecular research is needed to document and clarify the biodiversity of marine benthic microalgae of both polar regions. The zonation or local distribution of polar macroalgae and microalgae is influenced by physiological, morphological, chemical and ecological characteristics that determine responses to a range of environmental factors, including the ability to resist and survive algal grazing. Typically, the lower depth distribution limit elevates with increasing latitude.
Light and temperature demands of marine benthic microalgae and seaweeds in polar regions
Authors: Gómez Iván , Wulff Angela , Roleda Michael Y. , Huovinen Pirjo , Karsten Ulf , Quartino María Liliana , Dunton Ken , Wiencke Christian
Published: November 2009

Polar algae have a striking ability to photosynthesize and grow under very low light and temperatures. In seaweeds, minimum light demands for photosynthetic saturation and compensation can be as low as 10 and 2 μmol photons m-2 s-1, respectively. For benthic microalgae, these values can be even lower because of the limited irradiance reaching deep sea floors. The extreme shade adaptation of these organisms sets their distributional limits at depths close to 40 m and enables them to tolerate long periods of extended darkness. In addition to their capability for efficient photosynthesis at extremely low light levels, polar algae possess metabolic adaptations to persist at low temperatures, which permit them to complete their life cycles at year-round temperatures close to 0°C. Seaweeds with the lowest temperature demands are the species endemic to the Antarctic while Arctic algae are comparatively less cold-adapted. These adaptive characteristics allow benthic marine algae to make high contributions to high latitude coastal primary productivity and energy fluxes, exceeding or equaling the production of primary producers in more temperate systems. The studies summarized here give important insights into the major physiological adaptations allowing marine benthic microalgae and seaweeds to colonize these extreme habitats.
Impact of oceanic warming on the distribution of seaweeds in polar and cold-temperate waters
Authors: Müller Ruth , Laepple Thomas , Bartsch Inka , Wiencke Christian
Published: November 2009

Temperature is one of the most important factors controlling the biogeographic distribution of seaweeds and is expected to increase due to the rise in anthropogenic greenhouse gas concentrations, especially in polar and cold-temperate regions. To estimate prospective distributional shifts in cold-water key structural seaweeds from both hemispheres, we related temperature requirements and recent distributions of seaweeds to observed mean sea surface temperature (SST) isotherms for the periods 1980–1999 (Meteorological Office Hadley Centre's SST data set; HadISST) and to modelled temperatures for 2080–2099 [Coupled Model Intercomparison Project 3 (CMIP3) database prepared for the Intergovernmental Panel on Climate Change Fourth Assessment Report (IPCC AR4) report] based on moderate greenhouse gas emissions Special Report on Emission Scenarios – Scenario B1 (SRESA1B). Under this scenario, North Atlantic polar to cold-temperate seaweeds investigated will extend their distribution into the High Arctic until the end of the 21st century, but retreat along the northeastern Atlantic coastline. In contrast, selected Antarctic seaweeds will probably not significantly alter their latitudinal distributions, as deduced from our presently incomplete knowledge of their temperature requirements. We identified several cold-temperate regions where seaweed composition and abundance will certainly change with elevated temperatures. The results are discussed in the context of local temperature conditions, effects of multifactorial abiotic and biotic interactions and expected ecological consequences for seaweed-dominated ecosystems.
Biology of polar benthic algae
Authors: Wiencke Christian , Clayton Margaret N.
Published: November 2009

No abstract available
Biological variation of free plasma amino acids in healthy individuals
Authors: Corte Zoraida , Venta Rafael
Published: November 2009

Background: Biological variation data for free plasma amino acids are lacking from the more comprehensive databases. Therefore, we determined the intra- and inter-individual components of variation in healthy subjects. These data were used to define desirable goals for imprecision, bias and total error, indices of individuality and reference change values.

Methods: Plasma samples were collected from 11 volunteers at weekly intervals over 5 weeks. Free plasma amino acids were analyzed by reversed-phase HPLC and analytical and biological variation data were derived using ANOVA.

Results: Intra-individual coefficients of variation ranged from 9.5% to 46.4%, with lower values among the essential amino acids. The mean inter-individual coefficient of variation was 46.6% and was higher than intra-individual values for all amino acids. Thus, indices of individuality were below 0.8. Reference change values ranged from 30.9% to 128.4% and total error values ranged from 15.2% to 61.0%.

Conclusions: Plasma amino acids exhibit relatively low intra-individual coefficients of variation, with essential amino acids showing tighter homeostatic control. Analytical quality goals can be reasonably achieved with current methods. Reference intervals are of limited value in the detection of unusual results in an individual. Therefore, comparison of serial results by means of the reference change values is recommended.

Clin Chem Lab Med 2010;48:99–104.
An Analogue of the Erdős–Ginzburg–Ziv Theorem for Quadratic Symmetric Polynomials
Authors: Bialostocki Arie , Luong Tran Dinh
Published: November 2009

Let
Generalization of an Identity Involving the Generalized Fibonacci Numbers and Its Applications
Authors: Mohammad Farrokhi D. G.
Published: November 2009

We first generalize an identity involving the generalized Fibonacci numbers and then apply it to establish some general identities concerning special sums. We also give a sufficient condition on a generalized Fibonacci sequence {
Inductive Methods and Zero-Sum Free Sequences
Authors: Bhowmik Gautami , Halupczok Immanuel , Schlage-Puchta Jan-Christoph
Published: November 2009

A fairly long-standing conjecture is that the Davenport constant of a group

We also prove the conjecture for groups of the form ℤ
On the Number of Zero-Sum Subsequences of Restricted Size
Authors: Gao Weidong , Peng Jiangtao
Published: November 2009

Let
On the Average Asymptotic Behavior of a Certain Type of Sequence of Integers
Authors: Farhi Bakir
Published: November 2009

In this paper, we prove the following result: Let

In the two particular cases when
On the Kernel of the Coprime Graph of Integers
Authors: Sander J. W. , Sander T.
Published: November 2009

Let (
Synaptic Activity Induces Dramatic Changes in the Geometry of the Cell Nucleus: Interplay between Nuclear Structure, Histone H3 Phosphorylation, and Nuclear Calcium Signaling
Authors: Wittmann Malte , Queisser Gillian , Eder Anja , Wiegert J. Simon , Bengtson C. Peter , Hellwig Andrea , Wittum Gabriel , Bading Hilmar
Published: November 2009

Synaptic activity initiates many adaptive responses in neurons. Here we report a novel form of structural plasticity in dissociated hippocampal cultures and slice preparations. Using a recently developed algorithm for three-dimensional image reconstruction and quantitative measurements of cell organelles, we found that many nuclei from hippocampal neurons are highly infolded and form unequally sized nuclear compartments. Nuclear infoldings are dynamic structures, which can radically transform the geometry of the nucleus in response to neuronal activity. Action potential bursting causing synaptic NMDA receptor activation dramatically increases the number of infolded nuclei via a process that requires the ERK-MAP kinase pathway and new protein synthesis. In contrast, death-signaling pathways triggered by extrasynaptic NMDA receptors cause a rapid loss of nuclear infoldings. Compared with near-spherical nuclei, infolded nuclei have a larger surface and increased nuclear pore complex immunoreactivity. Nuclear calcium signals evoked by cytosolic calcium transients are larger in small nuclear compartments than in the large compartments of the same nucleus; moreover, small compartments are more efficient in temporally resolving calcium signals induced by trains of action potentials in the theta frequency range (5 Hz). Synaptic activity-induced phosphorylation of histone H3 on serine 10 was more robust in neurons with infolded nuclei compared with neurons with near-spherical nuclei, suggesting a functional link between nuclear geometry and transcriptional regulation. The translation of synaptic activity-induced signaling events into changes in nuclear geometry facilitates the relay of calcium signals to the nucleus, may lead to the formation of nuclear signaling microdomains, and could enhance signal-regulated transcription.
PACAP Neurons in the Hypothalamic Ventromedial Nucleus Are Targets of Central Leptin Signaling
Authors: Hawke Zoe , Ivanov Tina R. , Bechtold David A. , Dhillon Harveen , Lowell Brad B. , Luckman Simon M.
Published: November 2009

The adipose-derived hormone, leptin, was discovered over 10 years ago, but only now are we unmasking its downstream pathways which lead to reduced energy intake (feeding) and increased energy expenditure (thermogenesis). Recent transgenic models have challenged the long-standing supposition that the hypothalamic arcuate nucleus (Arc) is omnipotent in the central response to leptin, and research focus is beginning to shift to examine roles of extra-arcuate sites. Dhillon et al. (2006) demonstrated that targeted knock out of the signaling form of the leptin receptor (lepr-B) in steroidogenic factor 1 (SF-1) cells of the hypothalamic ventromedial nucleus (VMN) produces obesity of a similar magnitude to the pro-opiomelanocortin (POMC)-driven lepr-B deleted mouse, via a functionally distinct mechanism. These findings reveal that SF-1 cells of the VMN could be equally as important as POMC cells in mediating leptin's anti-obesity effects. However, the identification of molecular and cellular correlates of this relationship remains tantalizingly unknown. Here, we have shown that mRNA expression of the VMN-expressed neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is regulated according to energy status and that it exerts catabolic effects when administered centrally to mice. Furthermore, we have shown that SF-1 and PACAP mRNAs are colocalized in the VMN, and that leptin signaling via lepr-B is required for normal PACAP expression in these cells. Finally, blocking endogenous central PACAP signaling with the antagonist PACAP6-38markedly attenuates leptin-induced hypophagia and hyperthermiain vivo. Thus, it appears that PACAP is an important mediator of central leptin effects on energy balance.
Proneurotrophin-3 Is a Neuronal Apoptotic Ligand: Evidence for Retrograde-Directed Cell Killing
Authors: Yano Hiroko , Torkin Risa , Martin Laura Andrés , Chao Moses V. , Teng Kenneth K.
Published: November 2009

Although mature neurotrophins are well described trophic factors that elicit retrograde survival signaling, the precursor forms of neurotrophins (i.e., proneurotrophins) can function as high-affinity apoptotic ligands for selected neural populations. An outstanding question is whether target-derived proneurotrophins might affect neuronal survival/death decisions through a retrograde transport mechanism. Since neurotrophin-3 (NT-3) is highly expressed in non-neural tissues that receive peripheral innervation, we investigated the localized actions of its precursor (proNT-3) on sympathetic neurons in the present study. Pharmacological inhibition of intracellular furin proteinase activity in 293T cells resulted in proNT-3 release instead of mature NT-3, whereas membrane depolarization in cerebellar granule neurons stimulated endogenous proNT-3 secretion, suggesting that proNT-3 is an inducible bona fide ligand in the nervous system. Our data also indicate that recombinant proNT-3 induced sympathetic neuron death that is p75NTR- and sortilin-dependent, with hallmark features of apoptosis including JNK (c-Jun N-terminal kinase) activation and nuclear fragmentation. Using compartmentalized culture systems that segregate neuronal cell bodies from axons, proNT-3, acting within the distal axon compartment, elicited sympathetic neuron death and overrode the survival-promoting actions of NGF. Together, these results raise the intriguing possibility that dysregulation of proneurotrophin processing/release by innervated targets can be deleterious to the neurons projecting to these sites.
Prostate Stem Cell Antigen Is an Endogenous lynx1-Like Prototoxin That Antagonizes α7-Containing Nicotinic Receptors and Prevents Programmed Cell Death of Parasympathetic Neurons
Authors: Hruska Martin , Keefe Julie , Wert David , Tekinay Ayse Begum , Hulce Jonathan J. , Ibañez-Tallon Ines , Nishi Rae
Published: November 2009

Vertebrate α-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouselynx1andlynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases >100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of α7-containing nicotinic acetylcholine receptors (α7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks α7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of α7 signaling-induced cell death during development.
Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses
Authors: Wright Megan C. , Potluri Srilatha , Wang Xueyong , Dentcheva Eva , Gautam Dinesh , Tessler Alan , Wess Jürgen , Rich Mark M. , Son Young-Jin
Published: November 2009

Muscarinic acetylcholine receptors (mAChRs) modulate synaptic function, but whether they influence synaptic structure remains unknown. At neuromuscular junctions (NMJs), mAChRs have been implicated in compensatory sprouting of axon terminals in paralyzed or denervated muscles. Here we used pharmacological and genetic inhibition and localization studies of mAChR subtypes at mouse NMJs to demonstrate their roles in synaptic stability and growth but not in compensatory sprouting. M2mAChRs were present solely in motor neurons, whereas M1, M3, and M5mAChRs were associated with Schwann cells and/or muscle fibers. Blockade of all five mAChR subtypes with atropine evoked pronounced effects, including terminal sprouting, terminal withdrawal, and muscle fiber atrophy. In contrast, methoctramine, an M2/4-preferring antagonist, induced terminal sprouting and terminal withdrawal, but no muscle fiber atrophy. Consistent with this observation, M2−/−but no other mAChR mutant mice exhibited spontaneous sprouting accompanied by extensive loss of parental terminal arbors. Terminal sprouting, however, seemed not to be the causative defect because partial loss of terminal branches was common even in the M2−/−NMJs without sprouting. Moreover, compensatory sprouting after paralysis or partial denervation was normal in mice deficient in M2or other mAChR subtypes. We also found that many NMJs of M5−/−mice were exceptionally small and reduced in proportion to the size of parental muscle fibers. These findings show that axon terminals are unstable without M2and that muscle fiber growth is defective without M5. Subtype-specific muscarinic signaling provides a novel means for coordinating activity-dependent development and maintenance of the tripartite synapse.
Role of Striatum in Updating Values of Chosen Actions
Authors: Kim Hoseok , Sul Jung Hoon , Huh Namjung , Lee Daeyeol , Jung Min Whan
Published: November 2009

The striatum is thought to play a crucial role in value-based decision making. Although a large body of evidence suggests its involvement in action selection as well as action evaluation, underlying neural processes for these functions of the striatum are largely unknown. To obtain insights on this matter, we simultaneously recorded neuronal activity in the dorsal and ventral striatum of rats performing a dynamic two-armed bandit task, and examined temporal profiles of neural signals related to animal's choice, its outcome, and action value. Whereas significant neural signals for action value were found in both structures before animal's choice of action, signals related to the upcoming choice were relatively weak and began to emerge only in the dorsal striatum ∼200 ms before the behavioral manifestation of the animal's choice. In contrast, once the animal revealed its choice, signals related to choice and its value increased steeply and persisted until the outcome of animal's choice was revealed, so that some neurons in both structures concurrently conveyed signals related to animal's choice, its outcome, and the value of chosen action. Thus, all the components necessary for updating values of chosen actions were available in the striatum. These results suggest that the striatum not only represents values associated with potential choices before animal's choice of action, but might also update the value of chosen action once its outcome is revealed. In contrast, action selection might take place elsewhere or in the dorsal striatum only immediately before its behavioral manifestation.
BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury
Authors: Sasaki Masanori , Radtke Christine , Tan Andrew M. , Zhao Peng , Hamada Hirofumi , Houkin Kiyohiro , Honmou Osamu , Kocsis Jeffery D.
Published: November 2009

Transplantation of mesenchymal stem cells (MSCs) derived from bone marrow has been shown to improve functional outcome in spinal cord injury (SCI). We transplanted MSCs derived from human bone marrow (hMSCs) to study their potential therapeutic effect in SCI in the rat. In addition to hMSCs, we used gene-modified hMSCs to secrete brain-derived neurotrophic factor (BDNF-hMSCs). After a dorsal transection lesion was induced at T9, cells were microinjected on each side of the transection site. Fluorogold (FG) was injected into the epicenter of the lesion cavity to identify transected corticospinal tract (CST) neurons. At 5 weeks after transplantation, the animals were perfused. Locomotor recovery improvement was observed for the BDNF-hMSC group, but not in the hMSC group. Structurally there was increased sprouting of injured corticospinal tract and serotonergic projections after hMSC and BDNF-hMSC transplantation. Moreover, an increased number of serotonergic fibers was observed in spinal gray matter including the ventral horn at and below the level of the lesion, indicating increased innervation in the terminal regions of a descending projection important for locomotion. Stereological quantification was performed on the brains to determine neuronal density in primary motor (M1) cortex. The number of FG backfilled cells demonstrated an increased cell survival of CST neurons in M1 cortex in both the hMSC and BDNF-hMSC groups at 5 weeks, but the increase for the BDNF-hMSC group was greater. These results indicate that transplantation of hMSCs hypersecreting BDNF results in structural changes in brain and spinal cord, which are associated with improved functional outcome in acute SCI.
Three Stages and Four Neural Systems in Time Estimation
Authors: Morillon Benjamin , Kell Christian A. , Giraud Anne-Lise
Published: November 2009

Gibbon's scalar expectancy theory assumes three processing stages in time estimation: a collating level in which event durations are automatically tracked, a counting level that reads out the time-tracking system, and a comparing level in which event durations are matched to abstract temporal references. Pöppel's theory, however, postulates a dual system for perception of durations below and above 2 s. By testing the neurophysiological plausibility of Gibbon's proposal using functional magnetic resonance imaging, we validate a three-staged model of time estimation and further show that the collating process is duplicated. Although the motor system automatically tracks durations below 2 s, mesial brain regions of the so-called “default mode network” keep track of longer events. Our results further support unique counting and comparing systems, involving prefrontal and parietal cortices in collators' readout, and the temporal cortex in contextual time estimation. These findings provide a coherent neuroanatomical framework for two theories of time perception.
Dopamine-Stimulated Dephosphorylation of Connexin 36 Mediates AII Amacrine Cell Uncoupling
Authors: Kothmann W. Wade , Massey Stephen C. , O'Brien John
Published: November 2009

Gap junction proteins form the substrate for electrical coupling between neurons. These electrical synapses are widespread in the CNS and serve a variety of important functions. In the retina, connexin 36 (Cx36) gap junctions couple AII amacrine cells and are a requisite component of the high-sensitivity rod photoreceptor pathway. AII amacrine cell coupling strength is dynamically regulated by background light intensity, and uncoupling is thought to be mediated by dopamine signaling via D1-like receptors. One proposed mechanism for this uncoupling involves dopamine-stimulated phosphorylation of Cx36 at regulatory sites, mediated by protein kinase A. Here we provide evidence against this hypothesis and demonstrate a direct relationship between Cx36 phosphorylation and AII amacrine cell coupling strength. Dopamine receptor-driven uncoupling of the AII network results from protein kinase A activation of protein phosphatase 2A and subsequent dephosphorylation of Cx36. Protein phosphatase 1 activity negatively regulates this pathway. We also find that Cx36 gap junctions can exist in widely different phosphorylation states within a single neuron, implying that coupling is controlled at the level of individual gap junctions by locally assembled signaling complexes. This kind of synapse-by-synapse plasticity allows for precise control of neuronal coupling, as well as cell-type-specific responses dependent on the identity of the signaling complexes assembled.