On the structure and dynamics of the complex of the nucleosome and the linker histone

Several different models of the linker histone (LH)–nucleosome complex have been proposed, but none of them has unambiguously revealed the position and binding sites of the LH on the nucleosome. Using Brownian dynamics-based docking together with normal mode analysis of the nucleosome to account for the flexibility of two flanking 10 bp long linker DNAs (L-DNA), we identified binding modes of the H5-LH globular domain (GH5) to the nucleosome. For a wide range of nucleosomal conformations with the L-DNA ends less than 65 Å apart, one dominant binding mode was identified for GH5 and found to be consistent with fluorescence recovery after photobleaching (FRAP) experiments. GH5 binds asymmetrically with respect to the nucleosomal dyad axis, fitting between the nucleosomal DNA and one of the L-DNAs. For greater distances between L-DNA ends, docking of GH5 to the L-DNA that is more restrained and less open becomes favored. These results suggest a selection mechanism by which GH5 preferentially binds one of the L-DNAs and thereby affects DNA dynamics and accessibility and contributes to formation of a particular chromatin fiber structure. The two binding modes identified would, respectively, favor a tight zigzag chromatin structure or a loose solenoid chromatin fiber.     

Behaviour and Ecology of the Chough and the Alpine Chough

Analysis of Nest Record Cards reveals altitudinal and habitat differencesbetween these two species. The resident or partially migratory Stonechat has a longer breeding season (with a potential for rearing three broods) than the Whinchat which is a trans-Saharan migrant and arrives later. It is suggested that the greater productivity of the Stonechat might counterbalance a higher winter mortality.     

Epigenetics and aging: the targets and the marks

'Aging epigenetics' is an emerging field that promises exciting revelations in the near future. Here we focus on the functional and biological significance of the epigenetic alterations that accumulate during aging and are important in tumorigenesis. Paradigmatic examples are provided by the global loss of DNA methylation in aging and cancer and by the promoter hypermethylation of genes with a dual role in tumor suppression and progeria, such as the Werner syndrome (WRN) and lamin A/C genes. Another twist is provided by sirtuins, a family of NAD-dependent deacetylases that act on Lys16 of histone H4, which are emerging as a link between cellular transformation and lifespan.     

Co-operation and defection: playing the field and the ESS

If food is patchily dispersed, food clumps being very rich, but rare and hard to find, each individual in a foraging flock then faces an evident dilemma: whether to co-operate and participate in the search, thus enhancing the rate by which rich patches are discovered, or to defect and let others do the searching, thus avoiding any possible expenditures and risks involved in the search (but enjoying the abundant resources once a rich patch is discovered). This conflict (and its possible solution) is treated as an example in the analysis of the synergistic n-player game presented in this paper. After deriving conditions for the existence of a mixed ESS in such games, the evolutionary stability of the mixed strategy against invasions by pure strategists, in particular against invasions by recognizable defectors, is analyzed. Whereas in any "degenerating" mixed-strategy model a recognizable defector can invade and spread, a "non-degenerating" model can sometimes yield a mixed ESS which is immune to such invasions.     

Metamorphosis in the Cirripedia Rhizocephala and the homology of the kentrogon and trichogon

The Rhizocephala are considered to be monophyletic due to several synapomorphies in the ontogeny of the cndoparasitic phase. The various types of metamorphosis described in the Rhizocephala are discussed and compared to metamorphosis in the Cirripedia Thoracica and Acrothoracica. In males and females of the suborder Kentrogonida. the cyprid settles and metamorphoses into a new instar, in males the trichogen and in females the infective kentrogon. The kentrogon goes through yet another. incomplete moult associated with the development of the stylet. Within the three kentrogonidan families. the Iernaeodiscid-peltogastrid type of kentrogon differs from the sacculinid type in the mode of attachment to the host. in the complexity of internal anatomy. in the position and penetration of the stylet, and in whether or not the cyprid carapace must be shed prior to penetration of the stylet. In the Akentrogonida metamorphosis never results in a new instar. Where observed (Clistosaccidae and Thompsoniidae). both male and female cyprids settle and penetrate into their substrate (female parasite or new host) with one of the antennules. Using the antennule as a syringe. male cyprids inject spermatogonia while female cyprids injects embryonic cells developing into an endoparasite. By comparison with metamorphosis in the Cirripedia Thoracica and Acrothoracica it is concluded that the presence of a metamorphic moult leading to a post-cyprid instar is plesiomorphic and that the trichogon and kentrogon are homologous with the first metamorphosed juvenile in these outgroups. The abbreviated ontogeny in the Akentrogonida without metamorphic moult and post-cyprid larval instars is considered apomorphic. This contradicts the long-held supposition that the Akentrogonida are the most‘primitive’Rhizocephala and dovetails with new information that this suborder contains many advanced traits. Within the Kentrogonida. the lernacodiseid-peltogastrid type of kentrogon is considered more plesiomorphic than the sacculinid type, which resembles the clistosaccidthompsoniid type in having the antennules involved in the penetration process. The homologization of the kentrogon with a juvenile barnacle indicates that presence of a kentrogon is plesiomorphic within the Rhizocephala and that the Kentrogonida is paraphyletic.     

Biophysics and Structure of the Patch and the Gigaseal

Interpreting channel behavior in patches requires an understanding of patch structure and dynamics, especially in studies of mechanosensitive channels. High resolution optical studies show that patch formation occurs via blebbing that disrupts normal membrane structure and redistributes in situ components including ion channels. There is a 1-2 μm region of the seal below the patch where proteins are excluded and this may consist of extracted lipids that form the gigaseal. Patch domes often have complex geometries with inhomogeneous stresses due to the membrane-glass adhesion energy (E_a), cytoskeletal forces, and possible lipid subdomains. The resting tension in the patch dome ranges from 1-4 mN/m, a significant fraction of the lytic tension of a bilayer (∼10 mN/m). Thus, all patch experiments are conducted under substantial, and uneven, resting tension that may alter the kinetics of many channels. E_a seems dominated by van der Waals attraction overlaid with a normally repulsive Coulombic force. High ionic strength pipette saline increased E_a and, surprisingly, increased cytoskeletal rigidity in cell-attached patches. Low pH pipette saline also increased E_a and reduced the seal selectivity for cations, presumably by neutralizing the membrane surface charge. The seal is a negatively charged, cation selective, space with a resistance of ∼7 gigohm/μm in 100 mM KCl, and the high resistivity of the space may result from the presence of high viscosity glycoproteins. Patches creep up the pipette over time with voltage independent and voltage dependent components. Voltage-independent creep is expected from the capillary attraction of E_a and the flow of fresh lipids from the cell. Voltage-dependent creep seems to arise from electroosmosis in the seal. Neutralization of negative charges on the seal membrane with low pH decreased the creep rate and reversed the direction of creep at positive pipette potentials.     

When time and numerosity interfere: the longer the more, and the more the longer

There is strong evidence that magnitudes in different dimensions can interfere. A majority of previous studies on the interaction of temporal magnitudes on numerosity showed no interfering effect, while many studies have reported the interference of numerosity on judgement of temporal magnitudes. We speculated that this one-way interference is confounded by the magnitudes used in the studies. We used a methodology that allowed us to study this interaction reciprocally. Moreover, we selected magnitudes for two dimensions that enabled us to detect their interfering effects. Participants had to either judge which of two successive sets of items was more numerous (numerosity judgement task), or which set of items was presented longer (duration judgement task). We hypothesised that a longer presentation of a set will be judged as being more numerous, and vice versa, a more numerous set will be judged as being presented longer. Results confirmed our hypothesis. A positive correlation between duration of presentation and judged numerosity as well as a positive correlation between the number of items and judged duration of presentation was found. This observation supports the idea that duration and numerosity judgements are not completely independent and implies the existence of (partly) generalised and abstract components in the magnitude representations.     

pRb and the cdks in apoptosis and the cell cycle

Apoptosis is a fundamental biological process present in metazoan cells. Linking apoptosis to the cell cycle machinery provides a mechanism to maintain proper control of cell proliferation in a multicellular organism. pRb and the cyclin-dependent kinases may have dual roles as integral components of the cell cycle and regulators of apoptosis. In many instances manipulation of the cell cycle through these molecules can induce or inhibit apoptosis. Recent studies also identify pRb as a substrate for an apoptotic protease; however, other cell cycle components are not known substrates. While it is clear that many common molecules can affect cell proliferation and cell death, the universality of any one cell cycle molecule in apoptosis has yet to be determined.     

Serology and systematics of the Ebenales and the Theales

The systematic position ofthe Ebenaceae, Sapotaceae, Styracaceae, Ochnaceae, Stachyuraceae, Dipterocarpaceae, Clusiaceae and Hypericaceae has been investigated using serological comparisons of sets of antigenic determinants. The results show that the Sytracaceae and Sapotaceae are undoubtedly more closely associated with the Actinidiaeceae and Theaceae, respectively, than with each other. We found no corresponding determinants betnween antigen systems from the Ebenaceae and systems from any other family whose relations to this family have been proposed. As discovered previously, investigations of antigen systems from the Ochnaceae, Dipterocarpaceae, Stachyuraceae, Clusiaceae and Hypericaceae are against the idea of a natural order “Theales” in which these families, or at least some of them, are combined with the Theaceae and Actinidiaceae. This paper completes our previous investigations which largely support a superorder Ericanae sensu Ehrendorfer and Takhtajan. We propose to include the Actinidiaceae and Theaceae in this superorder, assigning them a central position laong with the Sapotaceae and Sytracaeae on one side and the Primulales and Ericales on the other. Another most interesting finding is that there are corresponding determinants between antigen systems from the members of the Ericanae and representatives of the Polemoniaceae and Loasaceae.     

Modelling and the fall and rise of the handicap principle

The story of the fall and rise of Zahavi??s handicap principle is one of a battle between models. Early attempts at formal modeling produced negative results and, unsurprisingly, scepticism about the principle. A major change came in 1990 with Grafen??s production of coherent models of a handicap mechanism of honest signalling. This paper??s first claim is that acceptance of the principle, and its dissemination into other disciplines, has been driven principally by that, and subsequent modeling, rather than by empirical results. Secondly, there is a vast literature on biological signalling but few studies that make all of the observations necessary to diagnose the handicap mechanism. My final claim is that many of the applications of ??costly signalling theory?? in other disciplines are conceptually confused. Misinterpretations of what is meant by ??costly signalling?? are common. Demonstrating that a signal is costly is insufficient and is not always necessary in order to prove that, and explain why, a signal is honest. In addition to the biological modelling of signals, there is an economic literature on the same subject. The two run in parallel in the sense that they have had little mutual interaction. Additionally, it is the biological modelling that has been picked up, and often misapplied, by other disciplines.     

The Choroid Plexuses and the Barriers Between the Blood and the Cerebrospinal Fluid

1. The fluid homeostasis of the brain depends both on the endothelial blood–brain barrier and on the epithelial blood–cerebrospinal fluid (CSF) barrier located at the choroid plexuses and the outer arachnoid membrane.2. The brain has two fluid environments: the brain interstitial fluid, which surrounds the neurons and glia, and the CSF, which fills the ventricles and external surfaces of the central nervous system.3. CSF acts as a fluid cushion for the brain and as a drainage route for the waste products of cerebral metabolism.4. Recent findings suggest that CSF may also act as a third circulation conveying substances secreted into the CSF rapidly to many brain regions.     

Senescence: the good the bad and the dysfunctional

Nearly 50 years have elapsed since Hayflick challenged the dogma that individual human cells were immortal by demonstrating that after a predictable number of cellular divisions, normal human fibroblasts eventually entered a state of permanent growth arrest [Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965, 37:614-636.; Hayflick L, Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res 1961, 25:585-621]. This growth arrest, referred to as senescence, was hypothesized to function as a tumor suppressive mechanism, capable of limiting the replicative capacity of an incipient tumor cell. While originally met with skepticism, the existence of senescence and its importance as a tumor suppressive mechanism is now accepted. Here, we highlight this work and introduce studies that indicate that while senescent cells themselves cannot produce a neoplasia, they possess the ability to promote the growth of nearby preneoplastic cells and in this way may contribute to age-related increases in tumor incidences. This added level of complexity suggests that senescence functions as a biological 'double edged sword.'     

Beyond the cross and the crescent: plural identities and the Copts in contemporary Egypt

This paper examines the slow but steady transformation in how Coptic identity has been articulated and expressed since the mid-1990s. In the past, Copts were careful not to challenge a particular narrative of national unity, which formally included Copts in the Egyptian nation (‘religion is for God, and the nation is for all’), but which in practice imposed a kind of public invisibility on them. Today, a growing number of activists are seeking a public identity for Copts, a form of the ‘politics of recognition’ and the ‘right to difference’. This is a controversial approach within the Coptic community, as well as between the Copts and the Muslim majority and the Egyptian state, and to some extent has required new vehicles for Coptic self-organization and expression, outside the older ‘neo-millet’ institutions that had governed Coptic life for decades.     

Schistosoma haematobium: the effect of Astiban on the cell composition and ultrastructure of the vitelline gland and the ultrastructure of the tegument and gastrodermis

Treatment of Schistosoma haematobium (Nigerian strain) in hamsters with a single dose of 40 mg/kg of Astiban caused a reduction in the number of S1, S2, and S3 vitelline cells and an increase in S4 cells. Following seven daily doses of the drug, a marked reduction in S1 cells and a complete loss of S2 and S3 cells occurred such that 95% of the cells were S4 cells, all of which were structurally abnormal. Coagulation and disintegration of the protein granules of the vitelline droplets occurred with increase in lipid droplets, swelling of the nuclear membrane and an increase in cytosegresomes. Blebbing of the tegument in both sexes occurred following a single treatment and vacuolation of the basal infolds and alterations to the mitochondria also resulted, but severe erosion of the tegument was rare even following repeated drug treatment. Damage to the gastrodermis was severe with the development of autophagic vacuoles containing whorls of myelin and sequestered portions of damaged tissue. The degree of damage increased with the number of drug treatments.     

Diacylglycerol and phosphatidate production and the exocytosis of the sperm acrosome

We have investigated the production of diacylglycerol (DAG) and phosphatidate (PtdOH) during the exocytosis of the sperm acrosome. Ram spermatozoa treated with Ca2+ and the ionophore A23187 experienced a rapid breakdown of the polyphosphoinositides (PPIs), and a rise in [32P]Pi-labelled PtdOH and DAG mass; PtdOH mass, however, was unaffected. Treatment with Ca2+/A23187 and the DAG kinase inhibitor R59022 resulted in a dose-dependent increase in DAG mass and a concomitant decrease in [32P]PtdOH; such treatment showed a dose-dependent stimulation of acrosomal exocytosis. Pre-incubation with exogenous PtdOHs before stimulation with Ca2+/A23187 did not affect the time-course of exocytosis, whereas treatment with Ca2+/A23187 and exogenous DAGs (dioctanoylglycerol, oleoyl-acetyl-glycerol, or dioleoylglycerol) resulted in a dose-dependent stimulation of acrosomal exocytosis. Our results suggest that DAG, rather than PtdOH, is the important metabolite generated upon PPI hydrolysis; however, since spermatozoa lack protein kinase C, the target of DAG in most cells, a role for DAG in acrosomal exocytosis is as yet unclear.     

Inductive signal and tissue responsiveness defining the tectum and the cerebellum

The mes/metencephalic boundary (isthmus) has an organizing activity for mesencephalon and metencephalon. The candidate signaling molecule is Fgf8 whose mRNA is localized in the region where the cerebellum differentiates. Responding to this signal, the cerebellum differentiates in the metencephalon and the tectum differentiates in the mesencephalon. Based on the assumption that strong Fgf8 signal induces the cerebellum and that the Fgf8b signal is stronger than that of Fgf8a, we carried out experiments to misexpress Fgf8b and Fgf8a in chick embryos. Fgf8a did not affect the expression pattern of Otx2, Gbx2 or Irx2. En2 expression was upregulated in the mesencephalon and in the diencephalon by Fgf8a. Consequently, Fgf8a misexpression resulted in the transformation of the presumptive diencephalon to the fate of the mesencephalon. In contrast, Fgf8b repressed Otx2 expression, but upregulated Gbx2 and Irx2 expression in the mesencephalon. As a result, Fgf8b completely changed the fate of the mesencephalic alar plate to cerebellum. Quantitative analysis showed that Fgf8b signal is 100 times stronger than Fgf8a signal. Co-transfection of Fgf8b with Otx2 indicates that Otx2 is a key molecule in mesencephalic generation. We have shown by RT-PCR that both Fgf8a and Fgf8b are expressed, Fgf8b expression prevailing in the isthmic region. The results all support our working hypothesis that the strong Fgf8 signal induces the neural tissue around the isthmus to differentiate into the cerebellum.     

Effect of stress and the antioxidant ionol on the biosynthesis of catecholamines and the content of dopamine in the heart and adrenal glands

The effects of a synthetic antioxidant ionol (dibunol) on the biosynthesis and content of catecholamines in the heart and adrenal glands were studied. It was shown that in stress a mobilization of catecholamine reserve is combined with a considerable increase in dopamine concentration. In conditions of physiological rest, ionol did not affect the studied indices of adrenal catecholamine biosynthesis, while in the heart it enhanced the dopamine synthesis and content. With ionol administration, stress did not suppress but, on the contrary, increased the neuronal uptake and noradrenaline biosynthesis, catecholamine concentration remaining practically unchanged. Simultaneously, a manyfold increase in the biosynthesis along with a considerable increase in the concentration of dopamine developed in both organs. The data obtained suggest that ionol realizes its stress-defensive effect to a great extent due to the activation of catecholamine biosynthesis and to a concomitant increase in dopamine accumulation.     

On the origin of the Hirudinea and the demise of the Oligochaeta

The phylogenetic relationships of the Clitellata were investigated with a data set of published and new complete 18S rRNA gene sequences of 51 species representing 41 families. Sequences were aligned on the basis of a secondary structure model and analysed with maximum parsimony and maximum likelihood. In contrast to the latter method, parsimony did not recover the monophyly of Clitellata. However, a close scrutiny of the data suggested a spurious attraction between some polychaetes and clitellates. As a rule, molecular trees are closely aligned with morphology-based phylogenies. Acanthobdellida and Euhirudinea were reconciled in their traditional Hirudinea clade and were included in the Oligochaeta with the Branchiobdellida via the Lumbriculidae as a possible link between the two assemblages. While the 18S gene yielded a meaningful historical signal for determining relationships within clitellates, the exact position of Hirudinea and Branchiobdellida within oligochaetes remained unresolved. The lack of phylogenetic signal is interpreted as evidence for a rapid radiation of these taxa. The placement of Clitellata within the Polychaeta remained unresolved. The biological reality of polytomies within annelids is suggested and supports the hypothesis of an extremely ancient radiation of polychaetes and emergence of clitellates.     

A contribution to knowledge of the compartments and the fascial and septal formations of the popliteal fossa in the human fetus and the adult.

A contribution to knowledge of the compartments and the fascial and septal formations of the popliteal fossa in the human fetus and the adult. A study was made in human fetuses from the 3rd month onwards, newborn and the adult of the fascial and septal formations and the compartments of the popliteal fossa. Observations of serial sections of the knee of human fetuses, of macroscopic preparations of the knee of newborns and of ultrasound images of the popliteal fossa in adults showed that: the fascial formation covering the popliteal fossa consists of the popliteal fascia and the superficial fascia. The bud of the popliteal fascia is observable in the 3-month fetus as a layer of thin fibrillar connective tissue which is thicker in the tracts between the muscle buds. At birth the popliteal fascia is clearly a separate anatomical entity of continuous laminar structure which is thicker in the tracts between the muscles and thinner where it covers them. The superficial fascia becomes evident in fetuses at a later stage (6th month) in the form of a thin lamina in the frontal plane which at birth is well defined and observable as a thin continuous line deep below the subcutaneous layer. The septal formation consists of four septa: two in the sagittal plane (lateral and medial) and two in the frontal plane (lateral and medial). The bud of these septa appears in 4-month fetuses after the appearance of the popliteal fascia. They branch off from the thicker connective areas between the muscles buds as connective prolongations which later assume a laminar aspect and eventually become compact and form septa. In at-term fetuses and newborns these septal formations are clearly recognizable as antomical entities, which branch off from the deep surface of the thicker tracts of the popliteal fascia and are inserted into the femur. The relationships and connections with the muscular groups are also clearly visible. The organization and demarcation of the compartments, which is already delineated in the 6-month fetus, seems to be completed at birth, considering the presence of the superficial fascia, the popliteal fascia and the septa. It is possible to distinguish a superficial compartment between the popliteal and the superficial fascia an a deep compartment between the frontal septa, the skeletal plane and the popliteal fascia. This deep compartment is clearly subdivided by the two sagittal septa into three sectors (medial, intermediate and lateral). The medial and lateral sectors contain muscles, while the intermediate compartment contains the vasculonervous bundle and the popliteal adipose body.