The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex

The E2F transcription factors play a key role in the regulation of cellular proliferation and terminal differentiation. E2F6 is the most recently identified and the least well understood member of the E2F family. It is only distantly related to the other E2Fs and lacks the sequences responsible for both transactivation and binding to the retinoblastoma protein. Consistent with this finding, E2F6 can behave as a dominant negative inhibitor of the other E2F family members. In this study, we continue to investigate the possible role(s) of E2F6 in vivo. We report the isolation of RYBP, a recently identified member of the mammalian polycomb complex, as an E2F6-interacting protein. Mapping studies indicate that RYBP binds within the known “repression domain” of E2F6. Moreover, we demonstrate that endogenous E2F6 and polycomb group proteins, including RYBP, Ring1, MEL-18, mph1, and the oncoprotein Bmi1, associate with one another. These findings suggest that the biological properties of E2F6 are mediated through its ability to recruit the polycomb transcriptional repressor complex.

The genomic and physical organization of Ty1-copia-like sequences as a component of large genomes in Pinus elliottii var. elliottii and other gymnosperms.

A DNA sequence, TPE1, representing the internal domain of a Ty1-copia retroelement, was isolated from genomic DNA of Pinus elliottii Engelm. var. elliottii (slash pine). Genomic Southern analysis showed that this sequence, carrying partial reverse transcriptase and integrase gene sequences, is highly amplified within the genome of slash pine and part of a dispersed element >4.8 kbp. Fluorescent in situ hybridization to metaphase chromosomes shows that the element is relatively uniformly dispersed over all 12 chromosome pairs and is highly abundant in the genome. It is largely excluded from centromeric regions and intercalary chromosomal sites representing the 18S-5.8S-25S rRNA genes. Southern hybridization with specific DNA probes for the reverse transcriptase gene shows that TPE1 represents a large subgroup of heterogeneous Ty1-copia retrotransposons in Pinus species. Because no TPE1 transcription could be detected, it is most likely an inactive element--at least in needle tissue. Further evidence for inactivity was found in recombinant reverse transcriptase and integrase sequences. The distribution of TPE1 within different gymnosperms that contain Ty1-copia group retrotransposons, as shown by a PCR assay, was investigated by Southern hybridization. The TPE1 family is highly amplified and conserved in all Pinus species analyzed, showing a similar genomic organization in the three- and five-needle pine species investigated. It is also present in spruce, bald cypress (swamp cypress), and in gingko but in fewer copies and a different genomic organization.

Operator's, organizational, field and depot maintenance manual for body, stake, component of truck bridging, FSN 2320-200-1682 (all makes and models) for mounting on ORD M-139 chassis, (FSN 2510-510-5191).

Includes index.

Organizational maintenance manual : crusher, jaw, diesel and electric driven, wheel mounted, pneumatic tires, 75 ton per hour (Eagle crusher model 5157), FSN 3820-783-7311, component of crushing and screening plant, diesel and electric driven, wheel mounted, 75 ton per hour.

"February 1964."

Operator's manual : crusher, jaw, diesel and electric driven; wheel mounted pneumatic tires; 75 ton per hour (Eagle crusher model 5157) FSN 3820-783-7311, component of crushing and screening plant; diesel and electric driven; wheel mounted; 75 ton per hour.

Includes index.

Improved physical performance in older adults undertaking a short-term programme of high-velocity resistance training

Background: The age-related loss of muscle power in older adults is greater than that of muscle strength and is associated with a decline in physical performance. Objective: To investigate the effects of a short-term high-velocity varied resistance training programme on physical performance in healthy community-dwelling adults aged 60-80 years. Methods: Subjects undertook exercise (EX; n = 15) or maintained customary activity (controls, CON; n = 10) for 8 weeks. The EX group trained 2 days/week using machine weights for three sets of eight repetitions at 35, 55, and 75% of their one-repetition maximum (the maximal weight that an individual can lift once with acceptable form) for seven upper- and lower-body exercises using explosive concentric movements. Results: Fourteen EX and 10 CON subjects completed the study. Dynamic muscle strength significantly increased (p = 0.001) in the EX group for all exercises (from 21.4 +/- 9.6 to 82.0 +/- 59.2%, mean +/- SD) following training, as did knee extension power (p < 0.01). Significant improvement occurred for the EX group in the floor rise to standing (10.4 &PLUSMN; 11.5%, p = 0.004), usual 6-metre walk (6.6 &PLUSMN; 8.2%, p = 0.010), repeated chair rise (10.4 &PLUSMN; 15.6%, p = 0.013), and lift and reach (25.6 &PLUSMN; 12.1%, p = 0.002) performance tasks but not in the CON group. Conclusions: Progressive resistance training that incorporates rapid rate-of-force development movements may be safely undertaken in healthy older adults and results in significant gains in muscle strength, muscle power, and physical performance. Such improvements could prolong functional independence and improve the quality of life. Copyright (C) 2005 S. Karger AG, Basel.

Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A(2) in young spontaneously hypertensive rats

The development of fibrosis in the chronically hypertensive heart is associated with infiltration of inflammatory cells and cardiac hypertrophy. In this study, an inhibitor of the proinflammatory enzyme, group IIA human secretory phospholipase A(2) (sPLA(2)-IIA), has been found to prevent collagen deposition as an important component of cardiovascular remodeling in a rat model of developing chronic hypertension. Daily treatment of young male spontaneously hypertensive rats (SHR) with an sPLA2-IIA inhibitor (KH064, 5-(4-benzyloxyphenyl)-4S-(phenyl-heptanoylamino)-pentanoic acid, 5 mg/kg/day p.o.) prevented increases in the content of perivascular,(SHR 20.6 +/- 0.9%, n = 5; SHR+KH064 14.0 +/- 1.2%, n = 5) and interstitial (SHR 7.9 +/- 0.3%, n = 6; SHR+KH064 5.4 +/- 0.7%, n = 6) collagen in the left ventricle of rat hearts, but did not affect numbers of infiltrating monocytes/macrophages, left ventricular hypertrophy (SHR 2.88 +/- 0.08, n = 12; SHR+KH064 3.09 +/- 0.08 mg/g body weight, n = 9), increased systolic blood pressure, or thoracic aortic responses. This selective antifibrotic activity suggests that sPLA2-IIA may have an important but specific role in cardiac fibrosis, and that its inhibitors could be useful in dissecting molecular pathways leading to fibrotic conditions.

Nucleoside diphosphate kinase--a component of the [Na+1]- and [Cl-]-sensitive phosphorylation cascade in human and murine airway epithelium

We have shown that proteins within apically enriched fractions of human nasal respiratory epithelium vary their phosphohistidine content with ambient [Cl-] and other anion concentrations. This membrane-delimited phosphorylation cascade includes a multifunctional protein histidine kinase - nucleoside diphosphate kinase (NDPK). NDPK is itself a cascade component in both human and ovine airway, the self-phosphorylation of which is inhibited selectively by [Na+] in the presence of ATP (but not GTP). These findings led us to propose the existence of a dual anion-/cation-controlled phosphorylation-based "sensor" bound to the apical membrane. The present study showed that this cascade uses ATP to phosphorylate a group of proteins above 45 kDa (p45-group, identities unknown). Additionally, the Cl- dependence of ATP (but not GTP) phosphorylation is conditional on phosphatase activity and that interactions exist between the ATP- and GTP-phosphorylated components of the cascade under Cl--free conditions. As a prelude to studies in cystic fibrosis (CF) mice, we showed in the present study that NDPK is present and functionally active in normal murine airway. Since NDPK is essential for UTP synthesis and regulates fetal gut development, G proteins, K+channels, neutrophil-mediated inflammation and pancreatic secretion, the presence of ion-regulated NDPK protein in mouse airway epithelium might aid understanding of the pathogenesis of CF.

Estudo da estrutura subsuperficial da província Borborema com correlação de ruído sísmico

Ambient seismic noise has traditionally been considered as an unwanted perturbation in seismic data acquisition that "contaminates" the clean recording of earthquakes. Over the last decade, however, it has been demonstrated that consistent information about the subsurface structure can be extracted from cross-correlation of ambient seismic noise. In this context, the rules are reversed: the ambient seismic noise becomes the desired seismic signal, while earthquakes become the unwanted perturbation that needs to be removed. At periods lower than 30 s, the spectrum of ambient seismic noise is dominated by microseism, which originates from distant atmospheric perturbations over the oceans. The microsseism is the most continuous seismic signal and can be classified as primary – when observed in the range 10-20 s – and secondary – when observed in the range 5-10 s. The Green‘s function of the propagating medium between two receivers (seismic stations) can be reconstructed by cross-correlating seismic noise simultaneously recorded at the receivers. The reconstruction of the Green‘s function is generally proportional to the surface-wave portion of the seismic wavefield, as microsseismic energy travels mostly as surface-waves. In this work, 194 Green‘s functions obtained from stacking of one month of daily cross-correlations of ambient seismic noise recorded in the vertical component of several pairs of broadband seismic stations in Northeast Brazil are presented. The daily cross-correlations were stacked using a timefrequency, phase-weighted scheme that enhances weak coherent signals by reducing incoherent noise. The cross-correlations show that, as expected, the emerged signal is dominated by Rayleigh waves, with dispersion velocities being reliably measured for periods ranging between 5 and 20 s. Both permanent stations from a monitoring seismic network and temporary stations from past passive experiments in the region are considered, resulting in a combined network of 33 stations separated by distances between 60 and 1311 km, approximately. The Rayleigh-wave, dispersion velocity measurements are then used to develop tomographic images of group velocity variation for the Borborema Province of Northeast Brazil. The tomographic maps allow to satisfactorily map buried structural features in the region. At short periods (~5 s) the images reflect shallow crustal structure, clearly delineating intra-continental and marginal sedimentary basins, as well as portions of important shear zones traversing the Borborema Province. At longer periods (10 – 20 s) the images are sensitive to deeper structure in the upper crust, and most of the shallower anomalies fade away. Interestingly, some of them do persist. The deep anomalies do not correlate with either the location of Cenozoic volcanism and uplift - which marked the evolution of the Borborema Province in the Cenozoic - or available maps of surface heat-flow, and the origin of the deep anomalies remains enigmatic.

Multi-physics modelling - A vital component of virtual manufacturing

One of the core tasks of the virtual-manufacturing environment is to characterise the transformation of the state of material during each of the unit processes. This transformation in shape, material properties, etc. can only be reliably achieved through the use of models in a simulation context. Unfortunately, many manufacturing processes involve the material being treated in both the liquid and solid state, the trans-formation of which may be achieved by heat transfer and/or electro-magnetic fields. The computational modelling of such processes, involving the interactions amongst various interacting phenomena, is a consider-able challenge. However, it must be addressed effectively if Virtual Manufacturing Environments are to become a reality! This contribution focuses upon one attempt to develop such a multi-physics computational toolkit. The approach uses a single discretisation procedure and provides for direct interaction amongst the component phenomena. The need to exploit parallel high performance hardware is addressed so that simulation elapsed times can be brought within the realms of practicality. Examples of Multiphysics modelling in relation to shape casting, and solder joint formation reinforce the motivation for this work.

When is bigger better? The effects of group size on the evolution of helping behaviours.

Understanding the evolution of sociality in humans and other species requires understanding how selection on social behaviour varies with group size. However, the effects of group size are frequently obscured in the theoretical literature, which often makes assumptions that are at odds with empirical findings. In particular, mechanisms are suggested as supporting large-scale cooperation when they would in fact rapidly become ineffective with increasing group size. Here we review the literature on the evolution of helping behaviours (cooperation and altruism), and frame it using a simple synthetic model that allows us to delineate how the three main components of the selection pressure on helping must vary with increasing group size. The first component is the marginal benefit of helping to group members, which determines both direct fitness benefits to the actor and indirect fitness benefits to recipients. While this is often assumed to be independent of group size, marginal benefits are in practice likely to be maximal at intermediate group sizes for many types of collective action problems, and will eventually become very small in large groups due to the law of decreasing returns. The second component is the response of social partners on the past play of an actor, which underlies conditional behaviour under repeated social interactions. We argue that under realistic conditions on the transmission of information in a population, this response on past play decreases rapidly with increasing group size so that reciprocity alone (whether direct, indirect, or generalised) cannot sustain cooperation in very large groups. The final component is the relatedness between actor and recipient, which, according to the rules of inheritance, again decreases rapidly with increasing group size. These results explain why helping behaviours in very large social groups are limited to cases where the number of reproducing individuals is small, as in social insects, or where there are social institutions that can promote (possibly through sanctioning) large-scale cooperation, as in human societies. Finally, we discuss how individually devised institutions can foster the transition from small-scale to large-scale cooperative groups in human evolution.

Citrus as a component of the Mediterranean Diet

Citrus are native to southeastern Asia, but are present in the Mediterranean basin for centuries. This group of species has reached great importance in some of the Mediterranean countries and, in the case of orange, mandarin and lemon trees, they found here soil and climatic conditions which allows them to achieve a high level of fruit quality, even better than in the regions where they came from. Citrus fruits are present in the diet of the peoples living on the Mediterranean basin, at least since the time of the Roman Empire. In the 20th century they became the main crop in various agricultural areas of the Mediterranean, playing an important role in the landscape, in the diet of the overall population, and also in international trade. They are present in the gardens of palaces and monasteries, but also in the courtyards and orchards of the poorest families. Their fruits are not only a refreshing dessert, but also a condiment, or even a major component of many dishes. Citrus fruits have well-documented nutritional and health benefits. They can actually help prevent and cure some diseases and, above all, they are essential in a balanced and tasty diet.