bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible role of eclosion rhythm in mediating the effects of light-dark environments on pre-adult development in Drosophila melanogaster
Authors: Paranjpe Dhanashree A , Anitha D , Chandrashekaran MK , Joshi Amitabh , Sharma Vijay Kumar
Published: February 2005

Background

In insects, circadian clocks have been implicated in affecting life history traits such as pre-adult development time and adult lifespan. Studies on the period (per) mutants of Drosophila melanogaster, and laboratory-selected lines of Bactrocera cucurbitae suggested a close link between circadian clocks and development time. There is a possibility of clock genes having pleiotropic effects on clock period and pre-adult development time. In order to avoid such pleiotropic effects we have used wild type flies of same genotype under environments of different periodicities, which phenotypically either speeded up or slowed down the eclosion clock of D. melanogaster.

Results

We assayed pre-adult development time and pre-adult survivorship of four laboratory populations of D. melanogaster, under five different light regimes, continuous light (LL), continuous darkness (DD), and light-dark (LD) cycles of 10:10 h (T20), 12:12 h (T24), and 14:14 h (T28). Although the development time was significantly different in most light regimes, except for females under T24 &T28, pre-adult survivorship remained largely unaffected. The development time was shortest under LL, followed by T20, DD, T24 and T28 regimes, in that order. Interestingly the development time showed a positive correlation with the period of eclosion rhythm, i.e., faster oscillations were associated with faster development, and slower oscillations with slower development.

Conclusion

Based on these results we conclude that periodicity of imposed LD cycles, and/or of eclosion rhythm plays a key role in regulating the duration of pre-adult development in D. melanogaster in a manner that does not involve direct pleiotropic effects of clock genes on both clock period and development time.
Consequences of the historical demography on the global population structure of two highly migratory cosmopolitan marine fishes: the yellowfin tuna (Thunnus albacares) and the skipjack tuna (Katsuwonus pelamis)
Authors: Ely Bert , Viñas Jordi , Alvarado Bremer Jaime R , Black Donna , Lucas Luciano , Covello Kelly , Labrie Alexis V , Thelen Eric
Published: February 2005

Background

Yellowfin and skipjack tuna are globally distributed in the world's tropical and sub-tropical oceans. Since little, if any, migration of these fishes occurs between the Atlantic and Indo-Pacific Oceans, one might expect to see genetic differences between sub-populations in these ocean basins. However, yellowfin and skipjack tuna have extremely large population sizes. Thus, the rate of genetic drift should be slower than that observed for other tunas.

Results

Low levels of genetic differentiation were observed between Atlantic and Pacific samples of yellowfin tuna. In contrast, no genetic differentiation was observed between Atlantic and Pacific samples of skipjack tuna.

Conclusion

Much lower levels of genetic differentiation were found among sub-populations of yellowfin tuna compared to those observed for other large tunas, probably due to the large population size of yellowfin tuna. Since skipjack tuna appear to have even larger population sizes, it is not surprising that no genetic differentiation was detected between Atlantic and Pacific samples of these fish.
parkinmutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism
Authors: Poorkaj Parvoneh , Moses Lina , Montimurro Jennifer S , Nutt John G , Schellenberg Gerard D , Payami Haydeh
Published: February 2005

Background

parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage.

Methods

We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and ≥ 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons.

Results

Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations.

Conclusion

Anticipation is not linked to parkin, and may signify a distinct disease entity.
Recombinant Tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture
Authors: Plyusnina Angelina , Plyusnin Alexander
Published: February 2005

Tula hantavirus carrying recombinant S RNA segment (recTULV) grew in a cell culture to the same titers as the original cell adapted variant but presented no real match to the parental virus. Our data showed that the lower competitiveness of recTULV could not be increased by pre-passaging in the cell culture. Nevertheless, the recombinant virus was able to survive in the presence of the parental virus during five consecutive passages. The observed survival time seems to be sufficient for transmission of newly formed recombinant hantaviruses in nature.
Herpesvirus saimiri-transformed CD8+ T cells as a tool to study Chediak-Higashi syndrome cytolytic lymphocytes
Authors: Martín-Fernández José M , Cabanillas Juan A , Rivero-Carmena Miguel , Lacasa Esther , Pardo Julián , Anel Alberto , Ramírez-Duque Pedro R , Merino Fernando , Rodríguez-Gallego Carlos , Regueiro José R
Published: February 2005

Cytolytic CD8+ T lymphocytes are the main cell type involved in the fatal lymphoproliferative-accelerated phase of the Chediak-Higashi syndrome (CHS). To generate a cellular tool to study the defects of this T cell subset in vitro, we have used Herpesvirus saimiri, a lymphotropic virus that transforms human T lymphocytes into extended growth and in addition, endows them with natural killer (NK) features. Transformed CHS CD8+ T cells were generated and characterized in comparison with healthy controls. The results showed that transformed CHS T cells maintained the defects described in primary CHS lymphocytes, such as giant secretory lysosomes and impaired NK and T cell receptor/CD3-induced, perforin-mediated cytolytic activity [which, however, could be restored after extended culture in the presence of interleukin-2 (IL-2)]. Upon activation with phorbol ester plus calcium ionophore or upon extended culture with IL-2, transformed CHS T cells showed normal, perforin-independent plasma membrane CD178/CD95L/FasL-mediated cytolytic activity but negligible secretion of microvesicle-bound CD95L. Transformed (and primary) CHS T cells were otherwise normal for cytolysis-independent activation functions, such as proliferation, surface expression of several activation markers including major histocompatibility complex class II, and cytokine or surface activation-marker induction. Therefore, the CHS protein [CHS1/LYST (for lysosomal traffic regulator)] can be dispensable for certain NK and T cell cytolytic activities of activated CHS CD8+ T lymphocytes, but it seems to be required for microvesicle secretion of CD95L. We conclude that transformed CHS T cells may be useful as a tool to study in vitro the relative role of CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation.
Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts
Authors: Barshes Neal R , Wyllie Samuel , Goss John A
Published: February 2005

Recent advances in clinical protocols have improved the outcomes of pancreatic islet transplantation (PIT), yet PIT recipients typically require pancreatic islet grafts derived from multiple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involvement of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1β appears to be among the most important inflammatory mediators, causing pancreatic islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) synthase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the pancreatic islets, and depletion or inhibition of Kupffer cells improves outcomes following experimental PIT. Imediately after transplantation, the pancreatic islets are perfused only by portal vein blood until the process of angiogenesis restores arterial blood flow some 7–10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion molecules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the immediate post-transplant period, hepatocytes may contribute to pancreatic islet injury through the production of NO. This paper reviews literature regarding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the pathophysiology of hepatic ischemia-reperfusion and their relation to the survival and function of intrahepatic pancreatic islet grafts.
Modelling and control of overhead cranes with flexible variable-length cable by finite element method
Authors: Moustafa Kamal A.F. , Gad Emil H. , El-Moneer Ahmed M.A. , Ismail Mohamed I.S.
Published: February 2005

This work considers the modelling problem of the dynamics of overhead cranes with flexible cable and load hoisting or lowering during crane travel. The analysis includes the transverse vibrations of the flexible cable and trolley motion. A set of nonlinear ordinary differential equations governing the motion of the crane system with time-varying spatial domain is derived via the calculus of variation and Hamilton’s principle. A variable-domain finite element method is used to discretize the nonlinear system. A proportional -derivative controller is suggested to drive the crane to a desired destination. Numerical simulations are provided to show the effectiveness of the developed model and to illustrate the results.
Renal medullary hypoxia during experimental cardiopulmonary bypass: a pilot study
Authors: Stafford-Smith Mark , Grocott Hilary P.
Published: February 2005

Objectives: To determine the effect of cardiopulmonary bypass (CPB) on renal medullary oxygenation.

Design: Observational.

Setting: Laboratory.

Participants: Pigs ( n=3).

Interventions: Following induction of general anesthesia, a Paratrend™ blood gas probe was placed directly into the left renal medulla. Two animals were subjected to 90 min of CPB, while a third served as a non-CPB control. A probe was also placed in the left renal pelvis of one (CPB) animal to allow direct urine PO2measurements.

Measurements and main results: Medullary hypoxia (PO2B < 65 mmHg) was evident prior to CPB. With the onset of CPB, medullary PO2 further declined to nearly unmeasurable levels; PCO2 and pH were unchanged. Brief circulatory arrest during CPB in one animal resulted in rapid additional PCO2 rise and pH decline that corrected with reperfusion. Following the cessation of CPB, medullary PO2 gradually increased, but remained lower than pre-CPB levels. No changes in medullary PO2 were observed in the sham animal. Renal pelvis urine PO2, but not pH or PCO2, appeared to correlate with medullary values at all times.

Conclusions: Our findings indicate that renal medullary hypoxia is extreme during CPB and may persist following CPB. These data suggest a basis for the vulnerability of the kidney to injury during cardiac surgery. Renal pelvis urine PO2 appears to correlate closely with medullary PO2 and may be a useful tool for studying medullary oxygenation during CPB in humans.
What Should HIV/AIDS be Called in Malawi?
Authors: Muula Adamson S
Published: February 2005

HIV/AIDS is the leading cause of morbidity and mortality in the southern African country of Malawi. At the largest referral health facility in Blantyre, the Queen Elizabeth Central Hospital, the majority of patients hospitalized in medical wards and up to a third of those in the maternity unit are infected with HIV. Many patients in the surgical wards also have HIV/AIDS. Health professionals in Blantyre, however, often choose not to write down the diagnosis of HIV or AIDS; rather, they prefer to use ‘SGOT’, ‘ELISA’ and ‘spot test’ to represent the HIV test, while ‘immunosuppression’, ‘↓ CD4 disease’ and ‘ARC’ are preferred instead of ‘AIDS’. It is possible that health professionals’ belief that mentioning HIV and/or AIDS will harm patients is encouraging them to use these euphemisms. The use of less than exact terms to label HIV and AIDS may not be without cost. For instance, future attempts to conduct retrospective case study research may be hampered by this practice, which is not in accordance with the international classification of diseases. It is suggested that, although stigmatization and discrimination could be important driving factors in the use of cryptic language, it may be more worthy to fight discrimination and stigmatization head-on, rather than create avenues where these reactions may be perpetuated.
Treatment of Nonmetastatic Rhabdomyosarcoma in Childhood and Adolescence: Third Study of the International Society of Paediatric Oncology—SIOP Malignant Mesenchymal Tumor 89
Authors: Stevens Michael C.G. , Rey Annie , Bouvet Nathalie , Ellershaw Caroline , Flamant Françoise , Habrand Jean Louis , Marsden H. Basil , Martelli Helene , de Toledo Jose Sanchez , Spicer Richard D , Spooner David , Terrier-Lacombe Marie Jose , van Unnik Adrian , Oberlin Odile
Published: February 2005

Purpose

To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy.

Patients and Methods

Five hundred three previously untreated patients aged from birth to 18 years, recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage.

Results

Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy.

Conclusion

Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).
Phase I Study of BMS-214662, a Farnesyl Transferase Inhibitor in Patients With Acute Leukemias and High-Risk Myelodysplastic Syndromes
Authors: Cortes Jorge , Faderl Stefan , Estey Elihu , Kurzrock Razelle , Thomas Deborah , Beran Miloslav , Garcia-Manero Guillermo , Ferrajoli Alessandra , Giles Francis , Koller Charles , O'Brien Susan , Wright John , Bai Stephen A. , Kantarjian Hagop
Published: February 2005

Purpose

To investigate the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of BMS-214662, a farnesyl transferase (FTase) inhibitor, in patients with acute leukemias and high-risk myelodysplastic syndromes (MDS).

Patients and Methods

Patients with relapsed or refractory acute leukemias or MDS, or previously untreated but poor candidates for chemotherapy, were included in this phase I study with a 3 + 3 dose escalation design. BMS-214662 was administered as a 1-hour bolus once weekly at doses of 42 to 157 mg/m2. Once the MTD was identified, the schedule was changed to a 24-hour continuous infusion once weekly (starting dose, 300 mg/m2).

Results

Thirty patients were treated at a dose of 42 (n = 1), 56 (n = 3), 84 (n = 3), 118 (n = 13), 157 (n = 6) or 300 mg/m2 (n = 4). DLT occurred in 3 patients at 157 mg/m2, including nausea, vomiting, diarrhea, hypokalemia and cardiovascular problems. No DLT occurred with 24-hour continuous infusion. MTD with a 1-hour infusion was 118 mg/m2, with no MTD identified with the 24-hour infusion. Plasma concentrations of BMS-214662 correlated with the dose. Inhibition of FTase activity of approximately 60% occurred after the infusion with recovery to near baseline after 24 hours. Five patients had evidence of antileukemia activity, including two with complete remission with incomplete platelet recovery, one with hematologic improvement, and two with morphologic leukemia-free state.

Conclusion

BMS-214662 is well tolerated at doses of up to 118 mg/m2 as a 1-hour infusion. The toxicity profile and efficacy may be improved with prolonged exposure. Further investigation of this agent in leukemia is warranted.
Late Referrals to Specialized Palliative Care Service in Japan
Authors: Morita Tatsuya , Akechi Tatsuo , Ikenaga Masayuki , Kizawa Yoshiyuki , Kohara Hiroyuki , Mukaiyama Taketo , Nakaho Toshimichi , Nakashima Nobuaki , Shima Yasuo , Matsubara Tatsuhiro , Uchitomi Yosuke
Published: February 2005

Purpose

To clarify the bereaved family's perceptions about the appropriateness of timing when physicians first referred patients to palliative care units, and to identify the factors contributing to family-perceived late referrals.

Subjects and Methods

A multicenter questionnaire survey was conducted on 630 bereaved family members of cancer patents who were admitted to palliative care units in Japan. A total of 318 responses were analyzed (effective response rate, 62%).

Results

Half of the bereaved family members regarded the timing of referrals to palliative care units as late or very late, while less than 5% of families reported early referrals (very late [19%, n = 59], late [30%, n = 96], appropriate [48%, n = 151], early [1.6%, n = 5], and very early [2.2%, n = 7]). Multiple regression analyses revealed that the independent determinants of family-perceived late referrals were: family belief before admission that palliative care shortens the patient's life, insufficient in-advance discussion about preferred end-of-life care between patients/families and physicians, families' insufficient preparation for changes of patient conditions, and hospital admission before referrals.

Conclusion

In Japan, the timing of referrals to palliative care units was late or very late from the families' perspectives. The independent determinants of family-perceived late referrals were: family misconception about palliative care, inadequate communication with physicians, and families' insufficient preparation for deterioration of patients' conditions. Systematic strategies to overcome these barriers would contribute to providing appropriate palliative care at all stages of cancer.
PITX2, β-catenin and LEF-1 interact to synergistically regulate theLEF-1promoter
Authors: Vadlamudi Usha , Espinoza Herbert M. , Ganga Mrudula , Martin Donna M. , Liu Xiaoming , Engelhardt John F. , Amendt Brad A.
Published: February 2005

PITX2, β-catenin and lymphoid enhancer factor (LEF-1) are required for the inductive formation of several epithelial-derived organs, including teeth. Lef-1 is expressed in the dental epithelium after Pitx2, and both factors have overlapping expression patterns in the tooth bud and cap stages. Our analysis of Pitx2–/– mutant mice showed reduced Lef-1 expression in facial tissues by RT-PCR and quantitative RT-PCR. Consistent with these results we show that the human 2.5 kb LEF-1 promoter is activated by PITX2. Furthermore, the LEF-1 promoter is differentially activated by PITX2 isoforms, which are co-expressed in dental epithelium. The 2.5 kb LEF-1 promoter contains two regions that act to inhibit its transcription in concert with PITX2. The proximal region contains a Wnt-responsive element (WRE) that attenuates PITX2 activation. LEF-1 cannot autoregulate LEF-1 expression; however co-transfection of PITX2 and LEF-1 result in a synergistic activation of the 2.5 kb LEF-1 promoter. LEF-1 specifically interacts with the PITX2 C-terminal tail. Deletion of a distal 800 bp segment of the LEF-1 promoter resulted in enhanced PITX2 activation, and increased synergistic activation in the presence of LEF-1. Furthermore, β-catenin in combination with PITX2 synergistically activates the LEF-1 promoter and this activation is independent of the Wnt-responsive element. β-catenin directly interacts with PITX2 to synergistically regulate LEF-1 expression. We show a new mechanism where LEF-1 expression is regulated through PITX2, LEF-1 and β-catenin direct physical interactions. LEF-1 and β-catenin interactions with PITX2 provide new mechanisms for the regulation of PITX2 transcriptional activity.
α3β1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: a novel mechanism of integrin-mediated MMP gene expression
Authors: Iyer Vandana , Pumiglia Kevin , DiPersio C. Michael
Published: February 2005

Matrix metalloproteinases facilitate cell migration and tumor invasion through their ability to proteolyse the extracellular matrix. The laminin-binding integrin α3β1 is expressed at high levels in squamous cell carcinomas and in normal keratinocytes during cutaneous wound healing. We showed previously that α3β1 is required for MMP-9/gelatinase B secretion in immortalized mouse keratinocytes (MK cells) and that this regulation was acquired as part of the immortalized phenotype, suggesting a possible role for α3β1 during malignant conversion. In the current study, we identify a novel mechanism whereby α3β1 regulates the induction of MMP-9 expression that occurs in response to activation of a MAPK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Inhibition of MEK/ERK signaling in wild-type MK cells with a pharmacological inhibitor, U0126, showed that ERK activation was necessary for high levels of endogenous MMP-9 gene expression and activity of a transfected MMP-9 promoter. Furthermore, activation of MEK/ERK signaling in these cells with an oncogenic mutant of Ras, RasV12, increased both endogenous MMP-9 gene expression and MMP-9 promoter activity. Experiments with α3β1-deficient MK cells revealed that α3β1 was required for both baseline levels and RasV12-induced levels of MMP-9 mRNA expression. However, α3β1 was not required for RasV12-mediated activation of ERK or for ERK-dependent MMP-9 promoter activity. Direct comparison of mRNA turnover in the wild type and α3-null MK cells identified a requirement for α3β1 in stabilization of MMP-9 mRNA transcripts. These results identify a novel function for integrins in promoting mRNA stability as a mechanism to potentiate MAPK-mediated gene expression. They also suggest a role for α3β1 in maintaining high levels of MMP-9 mRNA expression in response to oncogenic activation of MEK/ERK signaling pathways.
Stress alters the subcellular distribution of hSlu7 and thus modulates alternative splicing
Authors: Shomron Noam , Alberstein Moti , Reznik Mika , Ast Gil
Published: February 2005

During pre-mRNA splicing, introns are removed and exons are ligated to form an mRNA. Exon choice is determined by different nuclear protein concentrations varying among tissues and cell types or by developmental stage. These can be altered by different cellular circumstances such as physiological stimuli, environmental effects and phosphorylation state. The splicing factor hSlu7 plays an important role in 3′ splice site selection during the second step of splicing in vitro and has been suggested to affect alternative splicing in vivo. Our results indicate that an ultraviolet-C (UV-C) stress stimulus triggers changes in the alternative splicing patterns of cellular genes by decreasing the nuclear concentration of hSlu7 through the modulation of its nucleus-to-cytoplasm transport. This shift is mostly dependent on the Jun N-terminal kinase (JNK) cascade. Although we found by RNAi knockdown that hSlu7 is not essential for cell viability, its nuclear concentration effects exon choice and inclusion:skipping ratio of alternative splicing. A possible spatial and temporal regulatory mechanism by which hSlu7 protein levels are regulated within the nucleus is suggested, thus implying a broad effect of hSlu7 on alternative splicing.
A Library Synthesis of Pyrazoles by Azomethine Imine Cycloaddition to the Polymer-supported Vinylsulfone
Authors: Fuchi Nobuhiro , Doi Takayuki , Takahashi Takashi
Published: February 2005

1,3-Dipolar cycloaddition of azomethine imines to the polymer-supported vinylsulfone was achieved. Pyrazole derivatives bearing various aryl groups were synthesized regioselectively.
Controlling Chemoselectivity in Reactions of Unprotected Naphthalene-1-carboxylic Acid with Strong Bases
Authors: Tilly David , Castanet Anne-Sophie , Mortier Jacques
Published: February 2005

Whereas treatment of unprotected naphthalene-1-carboxylic acid with alkyllithiums (RLi) affords 1,4-addition products, the reaction with LTMP/Me3SiCl under in situ quench conditions provides the arylsilane arising out from the substitution of lithium 2-lithionaphthalene carboxylate with Me3SiCl. With the Lochmann–Schlosser superbase (n-BuLi/t-BuOK), metalation occurs preferentially in the position adjacent to CO2Li although the peri and ortho, peri-dilithiated species are also formed.
Russian Retrospectives on Reforms from Yeltsin to Putin
Authors: Desai Padma
Published: February 2005

The kamikaze crew of liberal reformers, picked by former President Boris Yeltsin in the early 1990s, succeeded in overturning the planned economy and the authoritarian political arrangements of seven decades of Soviet Communism. However, the resulting breakdown of political cohesion and the urgency of restoring stability prompted Yeltsin to select Vladimir Putin as his successor. The consolidating impetus under Putin, who was elected president in early 2000, has raised concerns about the continuation of economic and political reforms under his leadership. In this essay, nine Russian interviewees look back on the reform issues under Yeltsin and look ahead on the unfolding political economy scenario under Putin. They include three principle economic reformers under Yeltsin, three economic policy analysts, and three banking professionals.
A Normal Country: Russia After Communism
Authors: Shleifer Andrei , Treisman Daniel
Published: February 2005

During the 1990s, Russia underwent an extraordinary transformation from a communist dictatorship to a multi-party democracy, from a centrally planned economy to a market economy, and from a belligerent adversary of the West to a cooperative partner. Yet a consensus in the US circa 2000 viewed Russia as a disastrous and threatening failure, and the 1990s as a decade of catastrophe for its citizens. Analyzing a variety of economic and political data, we demonstrate a large gap between this perception and the facts. In contrast to the common image, by the late 1990s Russia had become a typical middle-income capitalist democracy.
The Making of an Economist Redux
Authors: Colander David
Published: February 2005

This paper reports the findings of a survey and interviews with graduate students at seven top-ranking graduate economics programs. It finds that over the last 15 years graduate economics programs have become more empirical, less mathematical and less theoretically oriented, and that the students are generally positive about the profession. It also finds fewer differences among school. Despite the improvements, and greater student satisfaction, the paper suggests that there are serious pedagogical questions about the focus of the core on mathematical techniques rather than on creativity and economic reasoning, which students see as the true core of economics.
The Role of Oligarchs in Russian Capitalism
Authors: Guriev Sergei , Rachinsky Andrei
Published: February 2005

Using a unique dataset, we describe the degree of ownership concentration in Russian economy and its role in shaping economic and political institutions in Russia. In particular, we find that Russian ‘oligarchs’ do control a substantial part of the economy. While the relative weight of their firms in Russian economy is huge, they do not seem to be excessively large by the standards of the global economy where most of them are operating. The oligarchs seem to run their firms more efficiently than other Russian owners controlling for industry, region and size.
D2Dopamine Receptors Colocalize Regulator of G-Protein Signaling 9-2 (RGS9-2) via the RGS9 DEP Domain, and RGS9 Knock-Out Mice Develop Dyskinesias Associated with Dopamine Pathways
Authors: Kovoor Abraham , Seyffarth Petra , Ebert Jana , Barghshoon Sami , Chen Ching-Kang , Schwarz Sigrid , Axelrod Jeffrey D. , Cheyette Benjamin N. R. , Simon Melvin I. , Lester Henry A. , Schwarz Johannes
Published: February 2005

Regulator of G-protein signaling 9-2 (RGS9-2), a member of the RGS family of Gα GTPase accelerating proteins, is expressed specifically in the striatum, which participates in antipsychotic-induced tardive dyskinesia and in levodopa-induced dyskinesia. We report that RGS9 knock-out mice develop abnormal involuntary movements when inhibition of dopaminergic transmission is followed by activation of D2-like dopamine receptors (DRs). These abnormal movements resemble drug-induced dyskinesia more closely than other rodent models. Recordings from striatal neurons of these mice establish that activation of D2-like DRs abnormally inhibits glutamate-elicited currents. We show that RGS9-2, via its DEP domain (for Disheveled, EGL-10, Pleckstrin homology), colocalizes with D2DRs when coexpressed in mammalian cells. Recordings from oocytes coexpressing D2DR or the m2 muscarinic receptor and G-protein-gated inward rectifier potassium channels show that RGS9-2, via its DEP domain, preferentially accelerates the termination of D2DR signals. Thus, alterations in RGS9-2 may be a key factor in the pathway leading from D2DRs to the side effects associated with the treatment both of psychoses and Parkinson's disease.
Impaired Synaptic Plasticity and Learning in Mice Lacking β-Adducin, an Actin-Regulating Protein
Authors: Rabenstein Rebecca L. , Addy Nii A. , Caldarone Barbara J. , Asaka Yukiko , Gruenbaum Lore M. , Peters Luanne L. , Gilligan Diana M. , Fitzsimonds Reiko M. , Picciotto Marina R.
Published: February 2005

The adducin family of proteins interacts with the actin cytoskeleton and the plasma membrane in a calcium- and cAMP-dependent manner. Thus, adducins may be involved in changes in cytoskeletal organization resulting from synaptic stimulation. β-Adducin knock-out mice were examined in physiological and behavioral paradigms related to synaptic plasticity to elucidate the role the adducin family plays in processes underlying learning and memory.In situhybridization for α- and β-adducin demonstrates that these mRNAs are found throughout the brain, with high levels of expression in the hippocampus. Schaffer collateral-CA1 tetanic long-term potentiation decayed rapidly in acute hippocampal slices from β-adducin knock-out mice, although baseline spine morphology and postsynaptic density were normal. Interestingly, the input-output relationship was significantly increased in hippocampal slices from β-adducin knock-out mice. Furthermore, β-adducin knock-out mice were impaired in performance of fear conditioning and the water maze paradigm. The current results indicate that β-adducin may play an important role in the cellular mechanisms underlying activity-dependent synaptic plasticity associated with learning and memory.
Respiratory Rhythm Entrainment by Somatic Afferent Stimulation
Authors: Potts Jeffrey T. , Rybak Ilya A. , Paton Julian F. R.
Published: February 2005

Respiratory and locomotor patterns are coupled during locomotion. The objectives of this study were to (1) demonstrate that respiratory rhythms are entrained by sensory input from somatic afferents, (2) establish whether the parabrachial nucleus mediates entrainment, (3) examine responses of single respiratory neurons in the ventral respiratory group (VRG) to somatic afferent stimulation, and (4) use a computational model of the pontomedullary respiratory network (Rybak et al., 2004a,b) to suggest neuronal mechanisms for entrainment.

We used anin situpreparation in young rats that retained pontomedullary respiratory circuits and spinal pathways transmitting somatosensory input. We demonstrate that rhythmic stimulation of somatic afferents entrains respiratory rhythm on a 1:1 basis (1:1), increasing breathing frequency up to ∼1.4-2.2 times greater than spontaneous frequency. Stable entrainment occurred only when stimuli were delivered during expiration. Reversible blockade of the lateral parabrachial nucleus eliminated entrainment. Somatic afferent stimulation produced significant increases in the firing rate of augmenting expiratory (E2) neurons but shortened the firing duration of postinspiratory (post-I) neurons. A computational model reproduced 1:1 entrainment and other experimental findings based on the assumption that the somatic afferents initiate early onset of inspiration via activation of medullary E2 neurons. The model also predicted that afferent stimulation evoked transient hyperpolarization of ramp-inspiratory (ramp-I) neurons. This was confirmed experimentally by intracellular recording from ramp-I neurons. Our experimental and modeling results demonstrate that an entrainment pathway from somatic afferents to the VRG via the lateral parabrachial nucleus causes resetting of respiratory rhythm through excitation of E2 and consequent inhibition of post-I neurons.
Retinotopic Axis Specificity and Selective Clustering of Feedback Projections from V2 to V1 in the Owl Monkey
Authors: Shmuel Amir , Korman Maria , Sterkin Anna , Harel Michal , Ullman Shimon , Malach Rafael , Grinvald Amiram
Published: February 2005

Cortical maps and feedback connections are ubiquitous features of the visual cerebral cortex. The role of the feedback connections, however, is unclear. This study was aimed at revealing possible organizational relationships between the feedback projections from area V2 and the functional maps of orientation and retinotopy in area V1. Optical imaging of intrinsic signals was combined with cytochrome oxidase histochemistry and connectional anatomy in owl monkeys. Tracer injections were administered at orientation-selective domains in regions of pale and thick cytochrome oxidase stripes adjacent to the border between these stripes. The feedback projections from V2 were found to be more diffuse than the intrinsic horizontal connections within V1, but they nevertheless demonstrated clustering. The clusters of feedback axons projected preferentially to interblob cytochrome oxidase regions. The distribution of preferred orientations of the recipient domains in V1 was broad but appeared biased toward values similar to the preferred orientation of the projecting cells in V2. The global spatial distribution of the feedback projections in V1 was anisotropic. The major axis of anisotropy was systematically parallel to a retinotopic axis in V1 corresponding to the preferred orientation of the cells of origin in V2. We conclude that the feedback connections from V2 to V1 might play a role in enhancing the response in V1 to collinear contour elements.
Theta Stimulation Polymerizes Actin in Dendritic Spines of Hippocampus
Authors: Lin Bin , Kramár Enikö A. , Bi Xiaoning , Brucher Fernando A. , Gall Christine M. , Lynch Gary
Published: February 2005

It has been proposed that the endurance of long-term potentiation (LTP) depends on structural changes entailing reorganization of the spine actin cytoskeleton. The present study used a new technique involving intracellular and extracellular application of rhodamine-phalloidin to conventional hippocampal slices to test whether induction of LTP by naturalistic patterns of afferent activity selectively increases actin polymerization in juvenile to young adult spines. Rhodamine-phalloidin, which selectively binds to polymerized actin, was detected in perikarya and proximal dendrites of CA1 pyramidal cells that received low-frequency afferent activity but was essentially absent in spines and fine dendritic processes. Theta pattern stimulation induced LTP and caused a large (threefold), reliable increase in labeled spines and spine-like puncta in the proximal dendritic zone containing potentiated synapses. The spines frequently occurred in the absence of labeling to other structures but were also found in association with fluorescent dendritic processes. These effects were replicated (>10-fold increase in labeled spines) using extracellular applications of rhodamine-phalloidin. Increases in labeling appeared within 2 min, were completely blocked by treatments that prevent LTP induction, and occurred in slices prepared from young adult rats. These results indicate that near-threshold conditions for inducing stable potentiation cause the rapid polymerization of actin in mature spines and suggest that the effect is both sufficiently discrete to satisfy the synapse-specificity rule of LTP as well as rapid enough to participate in the initial stages of LTP consolidation.
Locus Ceruleus Activation Suppresses Feedforward Interneurons and Reduces β-γ Electroencephalogram Frequencies While It Enhances θ Frequencies in Rat Dentate Gyrus
Authors: Brown Robert A. M. , Walling Susan G. , Milway J. Steve , Harley Carolyn W.
Published: February 2005

The locus ceruleus is activated by novel stimuli, and its activation promotes learning and memory. Phasic activation of locus ceruleus neurons by glutamate enhances the dentate gyrus population spike amplitude and results in long-term potentiation of synaptic responses recorded after 24 h. Cholinergic activation of locus ceruleus neurons increases hippocampal θ. At the level of the cellular network, it is not clear how the potentiating effects of norepinephrine are mediated. Previous studies show that exogenous norepinephrine enhances inhibitory interneuron firing in the dentate gyrus. This finding appears at odds with evidence for potentiation. In this study, natural release of norepinephrine was induced by glutamate activation of locus ceruleus while we recorded EEGs and physiologically identified interneurons in the dentate gyrus of urethane-anesthetized rats. Feedforward neurons were inhibited (∼1-2 min) by locus ceruleus activation. Feedback interneurons showed both increased and decreased activity, whereas granule cells increased firing as predicted by evoked potential studies. EEG results replicated an increase in θ power (4-8 Hz) with locus ceruleus activation, but the effect with glutamatergic locus ceruleus activation was transient (∼1-2 min).β-γ Frequencies were also transiently suppressed. Together, the data suggest that locus ceruleus activation enhances the throughput of concomitant sensory input by reducing feedforward inhibitory interneuron activity, which may reduce “binding” in existing cell assemblies, and enhances the conditions for synaptic plasticity through disinhibition, promotion of 4-8 Hz θ, and noradrenergic potentiation to facilitate the building of new representations.
Medial Septal GABAergic Neurons Express the Somatostatin sst2AReceptor: Functional Consequences on Unit Firing and Hippocampal Theta
Authors: Bassant Marie-Hélène , Simon Axelle , Poindessous-Jazat Frédérique , Csaba Zsolt , Epelbaum Jacques , Dournaud Pascal
Published: February 2005

GABAergic septohippocampal neurons play a major role in the generation of hippocampal theta rhythm, but modulatory factors intervening in this function are poorly documented. The neuropeptide somatostatin (SST) may be one of these factors, because nearly all hippocampal GABAergic neurons projecting to the medial septum/diagonal band of Broca (MS-DB) express SST. In this study, we took advantage of the high and selective expression of the SST receptor sst2Ain MS-DB to examine its possible role on theta-related activity. Immunohistochemical experiments demonstrated that sst2Areceptors were selectively targeted to the somatodendritic domain of neurons expressing the GABAergic marker GAD67 but were not expressed by cholinergic neurons. In addition, a subpopulation of GABAergic septohippocampal projecting neurons expressing parvalbumin (PV) also displayed sst2Areceptors. Usingin vivojuxtacellular recording and labeling with neurobiotin, we showed that a number of bursting and nonbursting neurons exhibiting high discharge rates and brief spikes were immunoreactive for PV or GAD67 and expressed the sst2Areceptor. Microiontophoresis applications of SST and the sst2Aagonist octreotide (OCT) showed that sst2Areceptor activation decreased the discharge rate of both nonbursting and bursting MS-DB neurons and lessened the rhythmic activity of the latter. Finally, intraseptal injections of OCT and SST in freely moving rats reduced the power of hippocampal EEG in the theta band. Together, thesein vivoexperiments suggest that SST action on MS-DB GABAergic neurons, through sst2Areceptors, represents an important modulatory mechanism in the control of theta activity.
Rhythmic Bursting in the Cortico-Subthalamo-Pallidal Network during Spontaneous Genetically Determined Spike and Wave Discharges
Authors: Paz Jeanne Tamar , Deniau Jean-Michel , Charpier Stéphane
Published: February 2005

Absence seizures are characterized by impairment of consciousness associated with bilaterally synchronous spike-and-wave discharges (SWDs) in the electroencephalogram (EEG), which reflect paroxysmal oscillations in thalamocortical networks. Although recent studies suggest that the subthalamic nucleus (STN) provides an endogenous control system that influences the occurrence of absence seizures, the mechanisms of propagation of cortical epileptic discharges in the STN have never been explored. The present study provides the first description of the electrophysiological activity in the cortico-subthalamo-pallidal network during absence seizures in the genetic absence epilepsy rats from Strasbourg, a well established model of absence epilepsy. In corticosubthalamic neurons, the SWDs were associated with repetitive suprathreshold depolarizations correlated with EEG spikes. These cortical paroxysms were reflected in the STN by synchronized, rhythmic, high-frequency bursts of action potentials. Intracellular recordings revealed that the intraburst pattern in STN neurons was sculpted by an early depolarizing synaptic potential, followed by a short hyperpolarization and a rebound of excitation. The rhythmic hyperpolarizations in STN neurons during SWDs likely originate from a subpopulation of pallidal neurons exhibiting rhythmic bursting temporally correlated with the EEG spikes. The repetitive discharges in STN neurons accompanying absence seizures might convey powerful excitation to basal ganglia output nuclei and, consequently, may participate in the control of thalamocortical SWDs.
A Protein Phosphatase 2cα-Ca2+Channel Complex for Dephosphorylation of Neuronal Ca2+Channels Phosphorylated by Protein Kinase C
Authors: Li Dongjun , Wang Fushun , Lai Meizan , Chen Yuan , Zhang Ji-fang
Published: February 2005

Phosphorylation and dephosphorylation are primary means for rapid regulation of a variety of neuronal functions, such as membrane excitability, neurotransmitter release, and gene expression. Voltage-gated Ca2+channels are targets for phosphorylation by a variety of second messengers through activation of different types of protein kinases (PKs). Protein phosphatases (PPs), like PKs, are equally important in regulating Ca2+channels in neurons. However, much less is understood about whether and how a particular type of PP contributes to regulating neuronal Ca2+channel activities. This is primarily because of the lack of specific inhibitors/activators for different types of PPs, particularly the PP2c family. The functional roles of PP2c and its substrates in the brain remain virtually unknown. During our yeast two-hybrid screening, PP2cα was pulled out by both N- and P/Q-type Ca2+channel C termini. This raised the possibility that PP2cα might be associated with voltage-gated Ca2+channels for regulation of the Ca2+channel activity. Biochemical studies show that PP2cα binds directly to neuronal Ca2+channels forming a functional protein complexin vivo. PP2cα, unlike PP1, PP2a and PP2b, is more effective in dephosphorylation of neuronal Ca2+channels after their phosphorylation by PKC. In hippocampal neurons, disruption of the PP2cα-Ca2+channel interaction significantly enhances the response of Ca2+channels to modulation by PKC. Thus, the PP2cα-Ca2+channel complex is responsible for rapid dephosphorylation of Ca2+channels and may contribute to regulation of synaptic transmission in neurons.
Polysialylated Neural Cell Adhesion Molecule Is Necessary for Selective Targeting of Regenerating Motor Neurons
Authors: Franz Colin K. , Rutishauser Urs , Rafuse Victor F.
Published: February 2005

It is well established that peripheral nerves regenerate after injury. Therefore, incomplete functional recovery usually results from misguided axons rather than a lack of regeneration per se. Despite this knowledge very little is known about the molecular mechanisms regulating axon guidance during regeneration. In the developing neuromuscular system the neural cell adhesion molecule (NCAM) and its polysialic acid (PSA) moiety are essential for proper motor axon guidance. In this study we used a well established model of nerve transection and repair to examine whether NCAM and/or PSA promotes selective regeneration of femoral motor nerves in wild-type and NCAM (-/-) mice. We found that regenerating axons innervating the muscle pathway and, to a lesser extent, cutaneous axons in the sensory pathway reexpress high levels of PSA during the time when the cut axons are crossing the lesion site. Second, we found that motor neurons in wild-type mice preferentially reinnervated muscle pathways, whereas motor neurons in NCAM (-/-) mice reinnervated muscle and cutaneous pathways with equal preference. Preferential regeneration was not observed in wild-type mice when PSA was removed enzymatically from the regenerating nerve, indicating that this form of selective motor axon targeting requires PSA. Finally, transgenic mice were used to show that the number of collateral sprouts, their field of arborization, and the withdrawal of misprojected axons were all attenuated significantly in mice lacking PSA. These results indicate that regenerating motor axons must express polysialylated NCAM, which reduces axon-axon adhesion and enables motor neurons to reinnervate their appropriate muscle targets selectively.