bluuebunny/crossref_metadata_2025 huggingface dataset:
Tinbergen's fourth question, ontogeny: sexual and individual differentiation
Authors: Crews David , Groothuis Ton
Published: November 2005

Based on Tinbergen's view of the study of behavioural development we describe some recent advances and their importance in this field. We argue that the study of behavioural development should combine both proximate and ultimate approaches, and can help to understand how early subtle environmental factors shape consistent individual variation both between and within sexes. This is illustrated by reviewing the profound effects of incubation temperature on the development of brain and social behaviour in the leopard gecko, a species with temperature-dependent sex determination, and the effects of early exposure to steroid hormones on social behaviour in rodents and especially birds. Both are maternal effects: incubation temperature can be partly determined by the nest site where the mother deposited her eggs, while in both oviparous and viviparous vertebrates maternal hormones reach and influence the embryo. In the gecko, incubation temperature affects sexual and aggressive behaviour, growth, the hypothalamus-pituitary-gonadal axis, as well as the size, connectivity and metabolic capacity of certain brain areas. In this way not only is the gonad type determined, but so too is the morphological, physiological, neural, and behavioural phenotype established that explains much of within-sex variation. In rodents, maternal hormones affect similar aspects. In avian species, maternal hormones, deposited in the eggs, vary systematically between and within clutches and have both short- and long-lasting effects on competitive behaviour. Evidence suggests that mothers adaptively adjust hormone allocation to the environmental context. In addition, we discuss some effects of postnatal experience on behavioural development in geckos, mice and bird species. Our results also illustrate how the study of animal models other than rodents can help in understanding important developmental processes.
The Momentum Imbalance Paradox Revisited
Authors: Nof Doron
Published: November 2005

The classical problem of a point source situated along a southern boundary emptying buoyant water into a (β plane) ocean is revisited. Pichevin and Nof (PN) have shown that, in contrast to the view prevailing at the time, such an inviscid outflow does not simply turn to the right. Rather, it bifurcates into two branches: a steady branch that does turn to the right (eastward) and an unsteady branch that periodically sheds eddies to the left (westward). This partition is because a simple turn to the right of the entire outflow leaves the outflow’s long-shore momentum flux unbalanced, creating a paradox. In contrast, the branching allows the westward-drifting eddies (westward branch) to balance the momentum flux of the steady current (eastward branch). Although the analytical PN solution is useful and informative, it is cumbersome and difficult to apply to actual outflows. Here, a considerably simpler nonlinear analytical solution is presented. Using the idea that the eddies grow slowly relative to their rotation rate, it is shown that an intense (i.e., large Rossby number) and large relative vorticity outflow dumps most of its mass flux (Q) into the eddies (66%). (The remaining 33% goes into the eastward long-shore current.) By contrast, a weak outflow (i.e., an outflow with weak anticyclonic vorticity −αf, where α is analogous to the Rossby number and is much smaller than unity and f is the Coriolis parameter) dumps most of its water into the downstream current [(1–2α)Q]. Unexpectedly, this partition of mass turns out to be the same as the one taking place on an f plane. (Note that this is not at all the case for southward outflow nor is it the case for either eastward or westward outflow, where β alters the balance drastically.) Although the above partition of mass is independent of β, the size of the eddies generated by the above process is a function of β. It is given by [768g′Q/βπf 2α(2 − α)(1 + 2α)]1/5, where g′ is the reduced gravity. This gives a reasonable estimate for the Loop Current eddies’ size and generation frequency. Numerical simulations are in agreement with the above nonlinear solution, though the agreement is not necessarily any better than that of PN.
On the Separation of a Barotropic Western Boundary Current from a Cape
Authors: Munday David R. , Marshall David P.
Published: November 2005

The problem of western boundary current separation is investigated using a barotropic vorticity model. Specifically, a boundary current flowing poleward along a boundary containing a cape is considered. The meridional gradient of the Coriolis parameter (the β effect), the strength of dissipation, and the geometry of the cape are varied. It is found that 1) all instances of flow separation are coincident with the presence of a flow deceleration, 2) an increase in the strength of the β effect is able to suppress flow separation, and 3) increasing coastline curvature can overcome the suppressive β effect and induce separation. These results are supported by integrated vorticity budgets, which attribute the acceleration of the boundary current to the β effect and changes in flow curvature. The transition to unsteady final model states is found to have no effect upon the qualitative nature of these conclusions.
Diagnosing Mesoscale Vertical Motion from Horizontal Velocity and Density Data
Authors: Sanz Enric Pallàs , Viúdez Álvaro
Published: November 2005

The mesoscale vertical velocity is obtained by solving a generalized omega equation (ω equation) using density and horizontal velocity data from three consecutive quasi-synoptic high-resolution surveys in the Alboran Sea. The Atlantic Jet (AJ) and the northern part of the Western Alboran Gyre (WAG) were observed as a large density anticyclonic front extending down to 200–230 m. The horizontal velocity uh in the AJ reached maxima of 1.2 m s−1 for the three surveys, with extreme Rossby numbers of ζ/f ≈ −0.9 in the WAG and +0.9 in the AJ (where ζ is the vertical vorticity and f is the Coriolis parameter). The generalized ω equation includes the ageostrophic horizontal flow. It is found that the most important “forcing” term in this equation is ( fζph + ∇hϱ) · ∇2huh, where ζph is the horizontal (pseudo) vorticity and ϱ is the buoyancy. This term is related to the horizontal advection of vertical vorticity by the vertical shear velocity, uhz · ∇hζ. Extreme values of the diagnosed vertical velocity w were located at 80–100 m with max{w} ⊂ [34, 45] and min{w} ⊂ [−64, −34] m day−1. Comparison with the quasigeostrophic (QG) ω equation shows that, because of the large Rossby numbers, non-QG terms are important. The differences between w and the QG vertical velocity are mainly related to the divergence of the ageostrophic part of the total Q vector (Qh ≡ ∇huh · ∇hϱ) in the ω equation.
The Ventilation of the Deep Gulf of Mexico
Authors: Rivas David , Badan Antoine , Ochoa José
Published: November 2005

Recent measurements over the sill in the Yucatan Channel indicate that the deepest flows between the Caribbean Sea and the Gulf of Mexico, those that take place below the sill level at the Florida Straits, have zero mean net mass transport but carry significant amounts of heat and oxygen. The heat flux associated with the mean exchange exports approximately 150 GW from the deep Gulf toward the Caribbean and may be related to the formation of the Yucatan Undercurrent. The eddy heat transfer is also significantly different from zero and exports on average an additional 60 GW. This eddy transfer is attributable mostly to events that last from a few days to about 1.5 months, during which colder water from deeper levels in the Caribbean (beneath 2000 m) flows over the sill within a bottom boundary layer close to 200 m thick. The colder water is also very rich in oxygen, and the deep exchange sustains the near-bottom oxygen maximum in the Gulf of Mexico, whence that cold water must slide down the northern slope of the Yucatan Sill. Estimates of oxygen transport by diffusion from the deep water into the overlying intermediate water (∼50 m3 s−1) and the oxygen consumption reported in the literature (∼100 m3 s−1) are balanced by the rates of mean and eddy transfers over the sill (∼150 m3 s−1). The near-bottom mass transport [∼0.32 Sv (1 Sv ≡ 106 m3 s−1)] measured across the deepest portion of the central Yucatan Channel suggests a residence time for the deep waters of the Gulf of about 250 yr.
Generalized Conditions for Hydraulic Criticality of Oceanic Overflows
Authors: Pratt Larry , Helfrich Karl
Published: November 2005

Two methods for assessing the hydraulic criticality of an observed or modeled overflow are discussed. The methods are valid for single-layer deep flows with arbitrary potential vorticity and cross section. The first method is based on a purely steady view in which the flow at a given section is divided up into a group of “streamtubes.” A hydraulic analysis requires an extension of Gill’s functional formulation to systems with many degrees of freedom. The general form of the critical condition and associated compatibility condition for such a system are derived and applied to the streamtube model. As an aside, it is shown by example that Gill’s original critical condition can fail to capture all possible critical states, but that this problem is fixed when the multivariable approach is used. It is also shown how Gill’s method can be applied to certain dispersive or dissipative systems. The second method of assessing criticality involves direct calculation of linear, long-wave speeds using a time-dependent version of the streamtube model. This approach turns out to be better suited to the analysis of geophysical datasets. The significance of the local Froude number F is discussed. It is argued that F must take on the value unity at some point across a critical section.
Decadal Variability of Pycnocline Flows from the Subtropical to the Equatorial Pacific*
Authors: Wang Qi , Huang Rui Xin
Published: November 2005

A method based on isopycnal trajectory analysis is proposed to quantify the pathways from the subtropics to the Tropics. For a continuous stratified ocean a virtual streamfunction is defined, which can be used to characterize these pathways. This method is applied to the climatological dataset produced from a data-assimilated model. Analysis indicates that in each layer contours of the virtual streamfunction are a good approximation for streamlines, even if there is a cross-isopycnal mass flux. The zonal-integrated meridional transport per unit layer thickness through each pathway varies in proportion to 1/sinθ, where θ is latitude. The vertical-integrated total transport through pathways behaves similarly. Transport through pathways has a prominent decadal variability. Results suggest that in decadal time scales the interior pathway transport (IPT) anomaly may be mainly caused by the wind stress anomaly at low latitude. The western boundary pathway transport (WBPT) anomaly often has a sign opposite to the IPT anomaly, reflecting compensation between the IPT and the WBPT. However, more often than not the wind stress anomaly within tropical latitudes can also be used to explain the WBPT anomaly.
The Effect of Channel Length on the Residual Circulation in Tidally Dominated Channels
Authors: Li Chunyan , O’Donnell James
Published: November 2005

With an analytic model, this paper describes the subtidal circulation in tidally dominated channels of different lengths, with arbitrary lateral depth variations. The focus is on an important parameter associated with the reversal of the exchange flows. This parameter (δ) is defined as the ratio between the channel length and one-quarter of the tidal wavelength, which is determined by water depth and tidal frequency. In this study, a standard bottom drag coefficient, CD = 0.0025, is used. For a channel with δ smaller than 0.6–0.7 (short channels), the exchange flow at the open end has an inward transport in deep water and an outward transport in shallow water. This situation is just the opposite of channels with a δ value larger than 0.6–0.7 (long channels). For a channel with a δ value of about 0.35–0.5, the exchange flow at the open end reaches the maximum of a short channel. For a channel with a δ value of about 0.85–1.0, the exchange flow at the open end reaches the maximum of a long channel, with the inward flux of water occurring over the shoal area and the outward flow in the deep-water area. However, near the closed end of a long channel, the exchange flow appears as that in a short channel—that is, the exchange flow changes direction along the channel from the head to the open end of the channel. For a channel with a δ value of about 0.6–0.7, the tidally induced subtidal exchange flow at the open end reaches its minimum when there is little flow across the open end and the water residence time reaches its maximum. The mean sea level increases toward the closed end for all δ values. However, the spatial gradient of the mean sea level in a short channel is much smaller than that of a long channel. The differences between short and long channels are caused by a shift in dynamical balance of momentum or, equivalently, a change in tidal wave characteristics from a progressive wave to a standing wave.
Music service teachers’ life histories in the United Kingdom with implications for practice
Authors: Baker David
Published: November 2005

Music service teachers’ biographies and occupational stages are discussed in this article. The life histories of 28 instrumental and vocal teachers, aged between 22 and 60 years, are explored. These individuals work for a Local Education Authority music service in the United Kingdom. Their occupation entails travelling between various state primary and secondary schools to provide specialist instrumental and vocal tuition. Respondents participated in the inquiry between October 2002 and March 2004. In the context of this study, life histories are purposefully co-constructed narratives without the commitment to an objective past. Instead, the foci are storytellers’ perspectives. The analytic induction of these multiple histories reveals a five-tier qualitative model of shared biographical phases; that is, stark transformations in the teachers’ perspectives across time. Storytellers’ notions of career, and their critical phases, signal the need for greater collaboration between music services and schools, and between music services and higher education providers. Pre-service and in-service training are also questioned, as is the career structure of music service teachers. Suggestions are made for future policy and practice.
Social Relations, Firms and Societies
Authors: Brookes Michael , Brewster Chris , Wood Geoffrey
Published: November 2005

Business systems theory holds that specific nations are locked onto a particular developmental trajectory reflecting differences in both institutional configuration and corresponding social agency; these variations are reflected in the role and structuring of firms and employment practices. This article uses an international survey of firms to test the extent to which specific national business systems are distinguished by the nature and extent of employer-employee interdependence and the degree of delegation to employees. The evidence provides empirical support for the theory, though with some need for subtle modification, showing continuing difference between the employment practices of nations and business systems.
Sources of Capital and Structures of Influence
Authors: Okhmatovskiy Ilya
Published: November 2005

A number of theories have been employed to explain positions of banks in the corporate networks of developed economies. This article investigates whether these theories are consistent with the empirical findings about banks in the Russian corporate network. Russian banks are subject to many ties created by the executives of industrial corporations on boards of banks. A similar network position is interpreted as an indicator of the power of banks in the US, but this interpretation is not applicable in Russia. This article argues that the network position of Russian banks reflects a subordinate role of banks in today’s Russian economy. This subordinate role is explained by the fact that Russian banks are dependent on large industrial corporations (first of all, exporters of raw materials) as major sources of financial capital. An empirical test of hypotheses about the association between banks’ reliance on different sources of financial capital and their network positions provides support for this context-specific application of the resource dependence argument.
‘Twenty years mean nothing’
Authors: Mastrini Guillermo , de Charras Diego
Published: November 2005

What happened after the New World Information and Communication Order (NWICO) and the report prepared by the MacBride Commission: is it the case, in the words of the popular tango Volverby Carlos Gardel, that 20 years mean nothing? This article analyses the global discussions around the flow of information and communication from the NWICO to the WSIS. The aim of this article is to look at the movements, breaks and continuities which relate not only to the relationship between governments, but also to the main economic, technological, political and social trends in both historical moments. Additionally, the article notes the changes in the agents involved and conceptual shifts in the various stages of the discussion. The article reconstructs the evolution of the proposals aimed at democratizing the communication structures, to enable an analysis of their relevance to the current debate about the ‘Information Society’, a term which, though repeatedly used in recent years, gained momentum in the first phase of the World Summit on the Information Society (WSIS) held in December 2003 in Geneva. Our hypothesis is that the frustration resulting from the NWICO debates at UNESCO in the 1970s is a key motivation for the new players at the WSIS summits in Geneva and Tunis – they do not want to repeat past mistakes. However, we consider that the struggle is still political; it is based on a dispute over economic and symbolic resources. It has become increasingly important to re-state the need to democratize the communicational resources of society.
Evaluation of the efficacy and safety of etoricoxib in the treatment of hemophilic arthropathy
Authors: Tsoukas Christos , Eyster M. Elaine , Shingo Sumiko , Mukhopadhyay Saurabh , Giallella Karen M. , Curtis Sean P. , Reicin Alise S. , Melian Agustin
Published: November 2005

This 2-part, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of etoricoxib, a COX-2 selective inhibitor, for the treatment of hemophilic arthropathy. In part 1 (6 weeks), 102 patients (≥ 12 years old) with hemophilic arthropathy were randomized to receive 90 mg etoricoxib once daily or placebo (1:1 ratio). In part 2 (6 months), 51 patients taking placebo in part 1 were randomized to receive 90 mg etoricoxib or 25 mg rofecoxib once daily; patients taking etoricoxib in part 1 continued the same treatment. Efficacy end points included Patient Assessment of Arthropathy Pain, Patient Global Assessment of Arthropathy Disease Status, and Investigator Global Assessment of Arthropathy Disease Status. Safety was evaluated at each study visit. Etoricoxib provided significant improvement in all end points versus placebo (P < .001). Fewer patients taking etoricoxib discontinued due to a lack of efficacy versus placebo (P = .048). During part 2, efficacy was maintained; etoricoxib and rofecoxib demonstrated similar results. The most common adverse experiences were upper respiratory infection and headache. The incidence of joint bleeding during part 1 was similar between etoricoxib (66.7%) and placebo (72.6%) and during part 2 between etoricoxib (77.0%) and rofecoxib (78.9%). We conclude that etoricoxib provided superior efficacy versus placebo for the treatment of hemophilic arthropathy and was generally safe and well tolerated.
Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma
Authors: Wang Siqing , Yang Jing , Qian Jianfei , Wezeman Michele , Kwak Larry W. , Yi Qing
Published: November 2005

Dendritic cells (DCs) from patients with cancer are functionally defective, but the molecular mechanisms underlying these defects are poorly understood. In this study, we used the murine 5TGM1 myeloma model to examine the effects and mechanisms of tumor-derived factors on the differentiation and function of DCs. Myeloma cells or tumor culture conditioning medium (TCCM) were shown to inhibit the differentiation and function of BM-derived DCs (BMDCs), as evidenced by the down-regulated expression of DC-related surface molecules, decreased IL-12, and compromised capacity of the cells to activate allospecific T cells. Moreover, TCCM-treated BMDCs were inferior to normal BMDCs at priming tumor-specific immune responses in vivo. Neutralizing antibodies against IL-6, IL-10, and TGF-β partially abrogated the effects. TCCM treatment activated p38 mitogen-activated protein kinase (MAPK) and Janus kinase (JNK) but inhibited extracellular regulated kinase (ERK). Inhibiting p38 MAPK restored the phenotype, cytokine secretion, and function of TCCM-treated BMDCs. BMDCs from cultures with TCCM and p38 inhibitor was as efficacious as normal BMDCs at inducing tumor-specific antibody, type 1 T cell, and cytotoxic T lymphocyte (CTL) responses and at prolonging mouse survival. Thus, our results suggested that tumor-induced p38 MAPK activation and ERK inhibition in DCs may be a new mechanism for tumor evasion and that regulating these pathways during DC differentiation provides new strategies for generating potent DC vaccines for immunotherapy in patients with cancer. (Blood. 2006;107:2432-2439)
Recent insights into the role of Notch signaling in tumorigenesis
Authors: Leong Kevin G. , Karsan Aly
Published: November 2005

Members of the Notch family of transmembrane receptors play an important role in cell fate determination. Over the past decade, a role for Notch in the pathogenesis of hematologic and solid malignancies has become apparent. Numerous cellular functions and microenvironmental cues associated with tumorigenesis are modulated by Notch signaling, including proliferation, apoptosis, adhesion, epithelial-to-mesenchymal transition, and angiogenesis. It is becoming increasingly evident that Notch signaling can be both oncogenic and tumor suppressive. This review highlights recent findings regarding the molecular and functional aspects of Notch-mediated neoplastic transformation. In addition, cellular mechanisms that potentially explain the complex role of Notch in tumorigenesis are discussed.
Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine
Authors: Waldman Elisha , Lu Sydney X. , Hubbard Vanessa M. , Kochman Adam A. , Eng Jeffrey M. , Terwey Theis H. , Muriglan Stephanie J. , Kim Theo D. , Heller Glenn , Murphy George F. , Liu Chen , Alpdogan Onder , van den Brink Marcel R. M.
Published: November 2005

The α4β7 integrin plays a central role in the homing of T cells to the gut. We hypothesized that absence of the β7 subunit would result in a reduction of intestinal graft-versus-host disease (GVHD) and an improvement in overall GVHD morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT). Analysis of alloreactive β7-/- T cells showed intact activation, proliferation, cytokine production, and cytotoxicity. However, recipients of β7-/- donor T cells in murine HSCT models experienced less GVHD morbidity and mortality than recipients of wild-type (WT) T cells, associated with a decrease in donor T-cell infiltration of the liver and intestine and with an overall significant decrease in hepatic and intestinal GVHD. In graft-versus-tumor (GVT) experiments, we demonstrated intact or even enhanced GVT activity of β7-/- donor T cells. In conclusion, β7-/- donor T cells caused less GVHD morbidity and mortality than WT donor T cells because of selectively decreased T-cell infiltration of the liver and intestines. Our data suggest that strategies to target the β7 integrin have the clinical potential to alleviate or prevent GVHD while sparing or potentiating GVT activity.
Ancestral sequence alignment under optimal conditions
Authors: Hudek Alexander K , Brown Daniel G
Published: November 2005

Background

Multiple genome alignment is an important problem in bioinformatics. An important subproblem used by many multiple alignment approaches is that of aligning two multiple alignments. Many popular alignment algorithms for DNA use the sum-of-pairs heuristic, where the score of a multiple alignment is the sum of its induced pairwise alignment scores. However, the biological meaning of the sum-of-pairs of pairs heuristic is not obvious. Additionally, many algorithms based on the sum-of-pairs heuristic are complicated and slow, compared to pairwise alignment algorithms.

An alternative approach to aligning alignments is to first infer ancestral sequences for each alignment, and then align the two ancestral sequences. In addition to being fast, this method has a clear biological basis that takes into account the evolution implied by an underlying phylogenetic tree.

In this study we explore the accuracy of aligning alignments by ancestral sequence alignment. We examine the use of both maximum likelihood and parsimony to infer ancestral sequences. Additionally, we investigate the effect on accuracy of allowing ambiguity in our ancestral sequences.

Results

We use synthetic sequence data that we generate by simulating evolution on a phylogenetic tree. We use two different types of phylogenetic trees: trees with a period of rapid growth followed by a period of slow growth, and trees with a period of slow growth followed by a period of rapid growth.

We examine the alignment accuracy of four ancestral sequence reconstruction and alignment methods: parsimony, maximum likelihood, ambiguous parsimony, and ambiguous maximum likelihood. Additionally, we compare against the alignment accuracy of two sum-of-pairs algorithms: ClustalW and the heuristic of Ma, Zhang, and Wang.

Conclusion

We find that allowing ambiguity in ancestral sequences does not lead to better multiple alignments. Regardless of whether we use parsimony or maximum likelihood, the success of aligning ancestral sequences containing ambiguity is very sensitive to the choice of gap open cost. Surprisingly, we find that using maximum likelihood to infer ancestral sequences results in less accurate alignments than when using parsimony to infer ancestral sequences. Finally, we find that the sum-of-pairs methods produce better alignments than all of the ancestral alignment methods.
Acquired homotypic and heterotypic immunity against oculogenital Chlamydia trachomatis serovars following female genital tract infection in mice
Authors: Lyons Joseph M , Morré Servaas A , Airo-Brown Lucy P , Peña A Salvador , Ito James I
Published: November 2005

Background

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen causing female genital tract infection throughout the world. Reinfection with the same serovar, as well as multiple infections with different serovars, occurs in humans. Using a murine model of female C. trachomatis genital tract infection, we determined if homotypic and/or heterotypic protection against reinfection was induced following infection with human oculogenital strains of C. trachomatis belonging to two serovars (D and H) that have been shown to vary significantly in the course of infection in the murine model.

Methods

Groups of outbred CF-1 mice were reinfected intravaginally with a strain of either serovar D or H, two months after initial infection with these strains. Cellular immune and serologic status, both quantitative and qualitative, was assessed following initial infection, and the course of infection was monitored by culturing vaginal samples collected every 2–7 days following reinfection.

Results

Serovar D was both more virulent (longer duration of infection) and immunogenic (higher level of circulating and vaginal IgG and higher incidence of IgA in vaginal secretions) in the mouse genital tract. Although both serovars induced cross-reacting antibodies during the course of primary infection, prior infection with serovar H resulted in only a slight reduction in the median duration of infection against homotypic reinfection (p ~ 0.10), while prior infection with serovar D resulted in significant reduction in the median duration of infection against both homotypic (p < 0.01) and heterotypic reinfection (p < 0.01) when compared to primary infection in age and conditions matched controls.

Conclusion

Serovar D infection resulted in significant homotypic and heterotypic protection against reinfection, while primary infection with serovar H resulted in only slight homotypic protection. In addition to being the first demonstration of acquired heterotypic immunity between human oculogenital serovars, the differences in the level and extent of this immunity could in part explain the stable difference in serovar prevalence among human isolates.
Quality of life in bipolar disorder: A review of the literature
Authors: Michalak Erin E , Yatham Lakshmi N , Lam Raymond W
Published: November 2005

A sizable body of research has now examined the complex relationship between quality of life (QoL) and depressive disorder. Uptake of QoL research in relation to bipolar disorder (BD) has been comparatively slow, although increasing numbers of QoL studies are now being conducted in bipolar populations. We aimed to perform a review of studies addressing the assessment of generic and health-related QoL in patients with bipolar disorder.

A literature search was conducted in a comprehensive selection of databases including MEDLINE up to November 2004. Key words included: bipolar disorder or manic-depression, mania, bipolar depression, bipolar spectrum and variants AND quality of life, health-related QoL, functional status, well-being and variants. Articles were included if they were published in English and reported on an assessment of generic or health-related QoL in patients with BD. Articles were not included if they had assessed fewer than 10 patients with BD, were only published in abstract form or only assessed single dimensions of functioning.

The literature search initially yielded 790 articles or abstracts. Of these, 762 did not meet our inclusion criteria, leaving a final total of 28 articles. These were sub-divided into four categories (assessment of QoL in patients with BD at different stages of the disorder, comparisons of QoL in Patients with BD with that of other patient populations, QoL instrument evaluation in patients with BD and treatment studies using QoL instruments to assess outcome in Patients with BD) and described in detail.

The review indicated that there is growing interest in QoL research in bipolar populations. Although the scientific quality of the research identified was variable, increasing numbers of studies of good design are being conducted. The majority of the studies we identified indicated that QoL is markedly impaired in patients with BD, even when they are considered to be clinically euthymic. We identified several important avenues for future research, including a need for more assessment of QoL in hypo/manic patients, more longitudinal research and the development of a disease-specific measure of QoL for patients with BD.
Local treatment in unresectable hepatic metastases of carcinoid tumors: Experiences with hepatic artery embolization and radiofrequency ablation
Authors: Meij Vincent , Zuetenhorst Johanna M , van Hillegersberg Richard , Kröger Robert , Prevoo Warner , van Coevorden Frits , Taal Babs G
Published: November 2005

Background

Hepatic metastases of carcinoid tumors cause incapacitating symptoms, but are usually diffuse and therefore unresectable. In this article we evaluate our experiences with local treatment techniques in the management of carcinoid patients with hepatic metastases and failing systemic treatment.

Methods

Fifteen consecutive carcinoid patients (11 men and 4 women; median age 60 years; range 45–71 years) were treated with either hepatic artery embolization (HAE) with Ivalon particles or radiofrequency ablation (RFA) (percutaneously or intra-operatively). Follow-up evaluation was performed by CT scan and 24-hours urinary 5-HIAA excretions.

Results

A total of 18 HAE's was performed in 13 patients, while 10 lesions in 3 patients were treated with RFA. Median follow-up was 12.5 months (2 – 25 months). Median duration of symptoms was 22 months (8 – 193 months). Median overall decrease of 5-HIAA excretion 2 months after HAE was 32% with tumor regression on CT-scan in 4 patients (30%) and improvement of symptoms with a median duration of 15 months in 3 of them (23%). Embolization led to fatal hepatic failure in one patient. The 3 patients treated with RFA showed a decrease of urinary 5-HIAA values of 34, 81 and 93% respectively, with tumor regression in all of them. Improvement of symptoms was reported in 2 patients up to 25 months.

Conclusion

Liver embolization performed late in the clinical course had limited effect on symptoms and biochemical and radiological parameters. First experiences with RFA are favorable and might encourage to apply RFA more widely in metastatic carcinoid.
Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa
Authors: Gao Xiaobo , Chen Xing , Taglienti Mary , Rumballe Bree , Little Melissa H. , Kreidberg Jordan A.
Published: November 2005

Most studies on kidney development have considered the interaction of the metanephric mesenchyme and the ureteric bud to be the major inductive event that maintains tubular differentiation and branching morphogenesis. The mesenchyme produces Gdnf, which stimulates branching, and the ureteric bud stimulates continued growth of the mesenchyme and differentiation of nephrons from the induced mesenchyme. Null mutation of the Wt1 gene eliminates outgrowth of the ureteric bud, but Gdnf has been identified as a target of Pax2, but not of Wt1. Using a novel system for microinjecting and electroporating plasmid expression constructs into murine organ cultures, it has been demonstrated that Vegfa expression in the mesenchyme is regulated by Wt1. Previous studies had identified a population of Flk1-expressing cells in the periphery of the induced mesenchyme, and adjacent to the stalk of the ureteric bud, and that Vegfa was able to stimulate growth of kidneys in organ culture. Here it is demonstrated that signaling through Flk1 is required to maintain expression of Pax2 in the mesenchyme of the early kidney, and for Pax2 to stimulate expression of Gdnf. However, once Gdnf stimulates branching of the ureteric bud, the Flk1-dependent angioblast signal is no longer required to maintain branching morphogenesis and induction of nephrons. Thus,this work demonstrates the presence of a second set of inductive events,involving the mesenchymal and angioblast populations, whereby Wt1-stimulated expression of Vegfa elicits an as-yet-unidentified signal from the angioblasts, which is required to stimulate the expression of Pax2 and Gdnf,which in turn elicits an inductive signal from the ureteric bud.
Sim1andSim2are required for the correct targeting of mammillary body axons
Authors: Marion Jean-François , Yang Chun , Caqueret Aurore , Boucher Francine , Michaud Jacques L.
Published: November 2005

The mammillary body (MB), and its axonal projections to the thalamus(mammillothalamic tract, MTT) and the tegmentum (mammillotegmental tract,MTEG), are components of a circuit involved in spatial learning. The bHLH-PAS transcription factors SIM1 and SIM2 are co-expressed in the developing MB. We have found that MB neurons are generated and that they survive at least until E18.5 in embryos lacking both Sim1 and Sim2(Sim1-/-;Sim2-/-). However, the MTT and MTEG are histologically absent in Sim1-/-;Sim2-/- embryos, and are reduced in embryos lacking Sim1 but bearing one or two copies of Sim2, indicating a contribution of the latter to the development of MB axons. We have generated, by homologous recombination, a null allele of Sim1 (Sim1tlz) in which the tau-lacZfusion gene was introduced, allowing the staining of MB axons. Consistent with the histological studies, lacZ staining showed that the MTT/MTEG is barely detectable in Sim1tlz/tlz;Sim2+/- and Sim1tlz/tlz;Sim2-/- brains. Instead, MB axons are splayed and grow towards the midline. Slit1 and Slit2,which code for secreted molecules that induce the repulsion of ROBO1-producing axons, are expressed in the midline at the level of the MB, whereas Robo1 is expressed in the developing MB. The expression of Rig-1/Robo3, a negative regulator of Slit signalling, is upregulated in the prospective MB of Sim1/Sim2 double mutants,raising the possibility that the growth of mutant MB axons towards the midline is caused by a decreased sensitivity to SLIT. Finally, we found that Sim1 and Sim2 act along compensatory, but not hierarchical,pathways, suggesting that they play similar roles in vivo.
Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless inDrosophilaimaginal discs
Authors: Piddini Eugenia , Marshall Francis , Dubois Laurence , Hirst Elizabeth , Vincent Jean-Paul
Published: November 2005

Lysosome-mediated ligand degradation is known to shape morphogen gradients and modulate the activity of various signalling pathways. We have investigated the degradation of Wingless, a Drosophila member of the Wnt family of secreted growth factors. We find that one of its signalling receptors,Frizzled2, stimulates Wingless internalization both in wing imaginal discs and cultured cells. However, this is not sufficient for degradation. Indeed, as shown previously, overexpression of Frizzled2 leads to Wingless stabilization in wing imaginal discs. We show that Arrow (the Drosophila homologue of LRP5/6), another receptor involved in signal transduction, abrogates such stabilization. We provide evidence that Arrow stimulates the targeting of Frizzled2-Wingless (but not Dally-like-Wingless) complexes to a degradative compartment. Thus, Frizzled2 alone cannot lead Wingless all the way from the plasma membrane to a degradative compartment. Overall, Frizzled2 achieves ligand capture and internalization, whereas Arrow, and perhaps downstream signalling, are essential for lysosomal targeting.
Wnt3alinks left-right determination with segmentation and anteroposterior axis elongation
Authors: Nakaya Masa-aki , Biris Kristin , Tsukiyama Tadasuke , Jaime Shaulan , Rawls J. Alan , Yamaguchi Terry P.
Published: November 2005

The alignment of the left-right (LR) body axis relative to the anteroposterior (AP) and dorsoventral (DV) axes is central to the organization of the vertebrate body plan and is controlled by the node/organizer. Somitogenesis plays a key role in embryo morphogenesis as a principal component of AP elongation. How morphogenesis is coupled to axis specification is not well understood. We demonstrate that Wnt3a is required for LR asymmetry. Wnt3a activates the Delta/Notch pathway to regulate perinodal expression of the left determinant Nodal, while simultaneously controlling the segmentation clock and the molecular oscillations of the Wnt/β-catenin and Notch pathways. We provide evidence that Wnt3a, expressed in the primitive streak and dorsal posterior node, acts as a long-range signaling molecule, directly regulating target gene expression throughout the node and presomitic mesoderm. Wnt3a may also modulate the symmetry-breaking activity of mechanosensory cilia in the node. Thus, Wnt3a links the segmentation clock and AP axis elongation with key left-determining events, suggesting that Wnt3a is an integral component of the trunk organizer.
Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn
Authors: Glasgow Stacey M. , Henke R. Michael , MacDonald Raymond J. , Wright Christopher V. E. , Johnson Jane E.
Published: November 2005

Mutations in the human and mouse PTF1A/Ptf1a genes result in permanent diabetes mellitus and cerebellar agenesis. We show that Ptf1a is present in precursors to GABAergic neurons in spinal cord dorsal horn as well as the cerebellum. A null mutation in Ptf1a reveals its requirement for the dorsal horn GABAergic neurons. Specifically, Ptf1a is required for the generation of early-born (dI4, E10.5) and late-born (dILA, E12.5)dorsal interneuron populations identified by homeodomain factors Lhx1/5 and Pax2. Furthermore, in the absence of Ptf1a, the dI4 dorsal interneurons trans-fate to dI5 (Lmx1b+), and the dILA to dILB (Lmx1b+;Tlx3+). This mis-specification of neurons results in a complete loss of inhibitory GABAergic neurons and an increase in the excitatory glutamatergic neurons in the dorsal horn of the spinal cord by E16.5. Thus, Ptf1a function is essential for GABAergic over glutamatergic neuronal cell fates in the developing spinal cord, and provides an important genetic link between inhibitory and excitatory interneuron development.
FRIGIDA-ESSENTIAL 1 interacts genetically with FRIGIDAand FRIGIDA-LIKE 1 to promote the winter-annual habit of Arabidopsis thaliana
Authors: Schmitz Robert J. , Hong Lewis , Michaels Scott , Amasino Richard M.
Published: November 2005

Studies of natural variation have revealed that the winter-annual habit of many accessions of Arabidopsis is conferred by two genes, FRIGIDA (FRI) and FLOWERING LOCUS C (FLC),whose activities impose a vernalization requirement. To better understand the mechanism underlying the winter-annual habit, a genetic screen was performed to identify mutants that suppress the late-flowering behavior of a non-vernalized winter-annual strain. We have identified a locus, FRIGIDA-ESSENTIAL 1 (FES1), which, like FRI, is specifically required for the upregulation of FLC expression. FES1 is predicted to encode a protein with a CCCH zinc finger, but the predicted sequence does not otherwise share significant similarity with other known proteins. fes1 is a complete suppressor of FRI-mediated delayed flowering, but has little effect on the late-flowering phenotype of autonomous-pathway mutants. Thus, FES1activity is required for the FRI-mediated winter-annual habit, but not for the similar phenotype resulting from autonomous-pathway mutations. Epistasis analysis between FES1, FRI and another specific suppressor of FRI-containing lines, FRIGIDA-LIKE 1(FRL1), indicates that these genes do not function in a linear pathway, but instead act cooperatively to promote the expression of FLC.
NO-dependent osteoclast motility: reliance on cGMP-dependent protein kinase I and VASP
Authors: Yaroslavskiy Beatrice B. , Zhang Yongjun , Kalla Sara E. , Palacios Verónica García , Sharrow Allison C. , Li Yanan , Zaidi Mone , Wu Chuanyue , Blair Harry C.
Published: November 2005

The osteoclast degrades bone in cycles; between cycles, the cell is motile. Resorption occurs by acid transport into an extracellular compartment defined by an αvβ3 integrin ring. NO has been implicated in the regulation of bone turnover due to stretch or via estrogen signals, but a specific mechanism linking NO to osteoclastic activity has not been described. NO stimulates osteoclast motility, and at high concentrations NO causes detachment and terminates resorption. Here we demonstrate that NO regulates attachment through the cGMP-dependent protein kinase I (PKG I) via phosphorylation of the intermediate protein VASP. VASP colocalized with the αvβ3 ring in stationary cells, but alternating bands of VASP and αvβ3 occurred when motility was induced by NO donors or cGMP. Redistribution of VASP correlated with its phosphorylation. Dependency of NO-induced motility on PKG I and on VASP was shown by siRNA knockdown of each protein. VASP knockdown also altered distribution of αvβ3 at the attachment site. We conclude that PKG I and VASP are essential for reorganization of attachment and cytoplasmic proteins in motility induced by NO or by cGMP.
CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration
Authors: Klaile Esther , Müller Mario M. , Kannicht Christoph , Singer Bernhard B. , Lucka Lothar
Published: November 2005

The carcinoembryonic antigen-related cell adhesion molecule CEACAM1 (CD66a) and the scaffolding protein filamin A have both been implicated in tumor cell migration. In the present study we identified filamin A as a novel binding partner for the CEACAM1-L cytoplasmic domain in a yeast two-hybrid screen. Direct binding was shown by surface plasmon resonance analysis and by affinity precipitation assays. The association was shown for human and rodent CEACAM1-L in endogenous CEACAM1-L expressing cells. To address functional aspects of the interaction, we used a well-established melanoma cell system. We found in different migration studies that the interaction of CEACAM1-L and filamin A drastically reduced migration and cell scattering, whereas each of these proteins when expressed alone, acted promigratory. CEACAM1-L binding to filamin A reduced the interaction of the latter with RalA, a member of the Ras-family of GTPases. Furthermore, co-expression of CEACAM1-L and filamin A led to a reduced focal adhesion turnover. Independent of the presence of filamin A, the expression of CEACAM1-L led to an increased phosphorylation of focal adhesions and to altered cytoskeletal rearrangements during monolayer wound healing assays. Together, our data demonstrate a novel mechanism for how CEACAM1-L regulates cell migration via its interaction with filamin A.
Cell wall remodeling at the fission yeast cell division site requires the Rho-GEF Rgf3p
Authors: Morrell-Falvey Jennifer L. , Ren Liping , Feoktistova Anna , Haese Greg Den , Gould Kathleen L.
Published: November 2005

Cytokinesis in Schizosaccharomyces pombe is accompanied by several stages of cell wall remodeling at the division site. Coincident with actomyosin ring constriction, primary and secondary septa are deposited and then the primary septum is degraded to release daughter cells from one another. These steps require the activities of glucan synthases and glucanases, respectively, which must be coordinated with one another to prevent cell lysis. The lad1-1 mutation undergoes cell lysis specifically at cell division owing to the absence of the Rgf3p Rho1-guanine nucleotide exchange factor (GEF) at the division site. Electron microscopic analysis indicates that lysis occurs only as the primary septum begins to be degraded. Overproduction of either Rho1p or the previously uncharacterized Rab-GTPase-activating protein (GAP) involved in secretion, Gyp10p, suppresses lad1-1 lethality. Rgf3p is periodically produced in an Ace2p-dependent manner and localizes to the medial region of the cell early in mitosis, a pattern of expression distinct from the highly related Rho-GEF, Rgf1p. Although rgf1+ is not an essential gene, it is synthetically lethal with rgf2-deleted cells whereas no negative genetic interactions were detected between rgf2-deleted cells and lad1-1. Our data suggest that the three closely related fission yeast Rho-GEF molecules perform two distinct essential functions. Rgf3p appears necessary to stimulate Rho1p-mediated activation of a glucan synthase crucial after septation for proper new cell-end formation.