Experimental hand pain delays recognition of the contralateral hand: Evidence that acute and chronic pain have opposite effects on information processing?

Recognising the laterality of a pictured hand involves making an initial decision and confirming that choice by mentally moving one's own hand to match the picture. This depends on an intact body schema. Because patients with complex regional pain syndrome type 1 (CRPS1) take longer to recognise a hand's laterality when it corresponds to their affected hand, it has been proposed that nociceptive input disrupts the body schema. However, chronic pain is associated with physiological and psychosocial complexities that may also explain the results. In three studies, we investigated whether the effect is simply due to nociceptive input. Study one evaluated the temporal and perceptual characteristics of acute hand pain elicited by intramuscular injection of hypertonic saline into the thenar eminence. In studies two and three, subjects performed a hand laterality recognition task before, during, and after acute experimental hand pain, and experimental elbow pain, respectively. During hand pain and during elbow pain, when the laterality of the pictured hand corresponded to the painful side, there was no effect on response time (RT). That suggests that nociceptive input alone is not sufficient to disrupt the working body schema. Conversely to patients with CRPS1, when the laterality of the pictured hand corresponded to the non-painful hand, RT increased similar to 380 ms (95% confidence interval 190 ms-590 ms). The results highlight the differences between acute and chronic pain and may reflect a bias in information processing in acute pain toward the affected part.

Autopathogenic T helper cell type 1 (Th1) and protective Th2 clones differ in their recognition of the autoantigenic peptide of myelin proteolipid protein

We previously generated a panel of T helper cell 1 (Th1) clones specific for an encephalitogenic peptide of myelin proteolipid protein (PLP) peptide 139-151 (HSLGKWLGHPDKF) that induces experimental autoimmune encephalomyelitis (EAE) upon adoptive transfer. In spite of the differences in their T cell receptor (TCR) gene usage, all these Th1 clones required W144 as the primary and most critical TCR contact residue for the activation. In this study, we determined the TCR contact residues of a panel of Th2/Th0 clones specific for the PLP peptide 139-151 generated either by immunization with the PLP 139-151 peptide with anti-B7-1 antibody or by immunization with an altered peptide Q144. Using alanine-substituted peptide analogues of the native PLP peptide, we show that the Th2 clones have shifted their primary contact residue to the NH2-terminal end of the peptide. These Th2 cells do not show any dependence on the W144, but show a critical requirement for L141/G142 as their major TCR contact residue. Thus, in contrast with the Th1 clones that did not proliferate to A144-substituted peptide, the Th2 clones tolerated a substitution at position 144 and proliferated to A144 peptide. This alternative A144 reactive repertoire appears to have a critical role in the regulation of autoimmune response to PLP 139-151 because preimmunization with A144 to expand the L141/G142-reactive repertoire protects mice from developing EAE induced with the native PLP 139-151 peptide. These data suggest that a balance between two different T cell repertoires specific for same autoantigenic epitope can determine disease phenotype, i.e., resistance or susceptibility to an autoimmune disease.

Role of flanking sequences and phosphorylation in the recognition of the simian-virus-40 large T-antigen nuclear localization sequences by importin-a

The nuclear import of simian-virus-40 large T-antigen (tumour antigen) is enhanced via phosphorylation by the protein kinase CK2 at Ser(112) in the vicinity of the NLS (nuclear localization sequence). To determine the structural basis of the effect of the sequences flanking the basic cluster KKKRK, and the effect of phosphorylation on the recognition of the NLS by the nuclear import factor importin-alpha (Impalpha), we co-crystallized non-autoinhibited Impalpha with peptides corresponding to the phosphorylated and non-phosphorylated forms of the NLS, and determined the crystal structures of the complexes. The structures show that the amino acids N-terminally flanking the basic cluster make specific contacts with the receptor that are distinct from the interactions between bipartite NLSs and Impalpha. We confirm the important role of flanking sequences using binding assays. Unexpectedly, the regions of the peptides containing the phosphorylation site do not make specific contacts with the receptor. Binding assays confirm that phosphorylation does not increase the affinity of the T-antigen NLS to Impalpha. We conclude that the sequences flanking the basic clusters in NLSs play a crucial role in nuclear import by modulating the recognition of the NLS by Impalpha, whereas phosphorylation of the T-antigen enhances nuclear import by a mechanism that does not involve a direct interaction of the phosphorylated residue with Impalpha.

Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha

Importin-alpha is the nuclear import receptor that recognizes cargo proteins which contain classical monopartite and bipartite nuclear localization sequences (NLSs), and facilitates their transport into the nucleus. To determine the structural basis of the recognition of the two classes of NLSs by mammalian importin-alpha, we co-crystallized an N-terminally truncated mouse receptor protein with peptides corresponding to the monopartite NLS from the simian virus 40 (SV40) large T-antigen, and the bipartite NLS from nucleoplasmin. We show that the monopartite SV40 large T-antigen NLS binds to two binding sites on the receptor, similar to what was observed in yeast importin-alpha. The nucleoplasmin NLS-importin-alpha complex shows, for the first time, the mode of binding of bipartite NLSs to the receptor. The two basic clusters in the NLS occupy the two binding sites used by the monopartite NLS, while the sequence linking the two basic clusters is poorly ordered, consistent with its tolerance to mutations. The structures explain the structural basis for binding of diverse NLSs to the sole receptor protein. (C) 2000 Academic Press.

A review of the Apocreadiidae Skrjabin, 1942 (Trematoda : Digenea) and description of Australian species

The Apocreadiidae is reviewed and is considered to include genera recognised previously within the families Apocreadiidae, Homalometridae, Schistorchiidae, Sphincterostomatidae and Trematobrienidae. Key features of the family are extensive vitelline follicles, eye-spot pigment dispersed in forebody, I-shaped excretory vesicle, no cirrus-sac and genital pore opening immediately anterior to the ventral sucker (usually) or immediately posterior to it (Postporus Manter, 1949). Three subfamilies and 18 genera are recognised within the Apocreadiidae. The Apocreadiinae comprises Homalometron Stafford, 1904 (new syn. Barbulostomum Ramsey, 1965), Callohelmis n. g., Choanodera Manter, 1940, Crassicutis Manter, 1936, Dactylotrema Bravo-Hollis & Manter, 1957, Marsupioacetabulum Yamaguti, 1952, Microcreadium Simer, 1929, Myzotus Manter, 1940, Neoapocreadium Siddiqi & Cable, 1960, Neomegasolena Siddiqi & Cable, 1960, Pancreadium Manter, 1954, Procaudotestis Szidat, 1954 and Trematobrien Dollfus, 1950. The Schistorchiinae comprises Schistorchis Luhe, 1906, Sphincterostoma Yamaguti, 1937, Sphincteristomum Oshmarin, Mamaev & Parukhin, 1961 and Megacreadium Nagaty, 1956. The Postporinae comprises only Postporus. A key to subfamilies and genera of the Apocreadiidae is provided. It is argued that there is no convincing basis for the recognition of the genus Apocreadium Manter, 1937 and all its constituent species are combined with Homalometron. The following new combinations are proposed for species previously recognised within Apocreadium: Homalometron balistis (Manter, 1947), H. caballeroi (Bravo-Hollis, 1953), H. cryptum (Overstreet, 1969), H. longisinosum (Manter, 1937), H. manteri (Overstreet, 1970), H. mexicanum (Manter, 1937) and H. vinodae (Ahmad, 1985). Apocreadium uroproctoferum Sogandares-Bernal, 1959 is found to lack a uroproct and is made a synonym of H. mexicanum. Homalometron verrunculi nom. nov. is proposed to replace the secondarily pre-occupied H. caballeroi Lamothe-Argumedo, 1965. Barbulostomum is made a synonym of Homalometron and H. cupuloris (Ramsey, 1965) n. comb. is proposed. Neochoanodera is made a synonym of Choanodera and Choanodera ghanensis (Fischthal & Thomas, 1970) n. comb. is proposed. Species within the Apocreadiinae and Postporinae are reviewed and the following are recorded or described from Australian fishes: Homalometron wrightae n. sp. from Achlyopa nigra (Macleay), H. synagris (Yamaguti, 1953) n. comb. from Scolopsis monogramma (Cuvier), H. stradbrokensis n. sp. from Gerres subfasciatus Cuvier, Marsupioacetabulum opallioderma n. sp. from G. subfasciatus, Neoapocreadium karwarensis (Hafeezullah, 1970) n. comb. from G. subfasciatus, N. splendens n. sp. from S. monogramma and Callohelmis pichelinae n. g., n. sp. from Hemigymnus melapterus (Bloch), H. fasciatus (Bloch), Stethojulis bandanensis (Bleeker) andChoerodon venustus (De Vis). Callohelmis is recognised by the combination of absence of tegumental spines, caeca terminating midway between the testes and posterior end of body, ventral sucker enclosed in a tegumental pouch, prominent muscles radiating through the body from the ventral sucker, vitelline follicles not extending into the forebody, and a very short excretory vesicle that opens ventrally. New combinations for species previously recognised within Crassicutis are proposed as follows: Neoapocreadium caranxi (Bilqees, 1976) n. comb., N. gerridis (Nahhas & Cable, 1964) n. comb., N. imtiazi (Ahmad, 1984) n. comb. and N. marina (Manter, 1947) n. comb. The host-specificity and zoogeography of the Apocreadiinae are considered.

An evaluation of the evidence for linkages between mangroves and fisheries: A synthesis of the literature and identification of research directions

There is a widely held paradigm that mangroves are critical for sustaining production in coastal fisheries through their role as important nursery areas for fisheries species. This paradigm frequently forms the basis for important management decisions on habitat conservation and restoration of mangroves and other coastal wetlands. This paper reviews the current status of the paradigm and synthesises the information on the processes underlying these potential links. In the past, the paradigm has been supported by studies identifying correlations between the areal and linear extent of mangroves and fisheries catch. This paper goes beyond the correlative approach to develop a new framework on which future evaluations can be based. First, the review identifies what type of marine animals are using mangroves and at what life stages. These species can be categorised as estuarine residents, marine-estuarine species and marine stragglers. The marine-estuarine category includes many commercial species that use mangrove habitats as nurseries. The second stage is to determine why these species are using mangroves as nurseries. The three main proposals are that mangroves provide a refuge from predators, high levels of nutrients and shelter from physical disturbances. The recognition of the important attributes of mangrove nurseries then allows an evaluation of how changes in mangroves will affect the associated fauna. Surprisingly few studies have addressed this question. Consequently, it is difficult to predict how changes in any of these mangrove attributes would affect the faunal communities within them and, ultimately, influence the fisheries associated with them. From the information available, it seems likely that reductions in mangrove habitat complexity would reduce the biodiversity and abundance of the associated fauna, and these changes have the potential to cause cascading effects at higher trophic levels with possible consequences for fisheries. Finally, there is a discussion of the data that are currently available on mangrove distribution and fisheries catch, the limitations of these data and how best to use the data to understand mangrove-fisheries links and, ultimately, to optimise habitat and fisheries management. Examples are drawn from two relatively data-rich regions, Moreton Bay (Australia) and Western Peninsular Malaysia, to illustrate the data needs and research requirements for investigating the mangrove-fisheries paradigm. Having reliable and accurate data at appropriate spatial and temporal scales is crucial for mangrove-fisheries investigations. Recommendations are made for improvements to data collection methods that would meet these important criteria. This review provides a framework on which to base future investigations of mangrove-fisheries links, based on an understanding of the underlying processes and the need for rigorous data collection. Without this information, the understanding of the relationship between mangroves and fisheries will remain limited. Future investigations of mangrove-fisheries links must take this into account in order to have a good ecological basis and to provide better information and understanding to both fisheries and conservation managers.

Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone?

The effect of adding thickening agents on the penetration of a sunscreen benzophenone-3 through epidermal and a high-density polyethylene membrane was studied using both very thick (infinite dose) and thin tin use) applications. Contradictory results were obtained. Thickening agents retard skin penetration, in a manner consistent with a diffusional resistance in the formulation, when applied as an infinite dose. In contrast, when applied as in thin (in use) doses, thickening agents promote penetration, most likely through greater stratum corneum diffusivity arising from an enhanced hydration by the thicker formulations. The two key implications from this work are (i) a recognition of the danger in the potential extrapolation of infinite dosing to in use situations, and (ii) to recognize that thicker formulations may sometimes enhance the penetration of other topical agents when applied in use.

A molecular phylogeny of the Australian skink genera Eulamprus, Gnypetoscincus and Nangura

Skinks from the genera Eulamprus, Gnypetoscincus and Nangura are a prominent component of the reptile fauna of the mesic forests of the east coast of Australia and have been the subject of numerous ecological studies. Highly conserved morphology and the retention of ancestral traits have limited our understanding of the relationships within and among these genera beyond an initial identification of species groups within Eulamprus. To address this deficit and to explore the relationships between Eulamprus and the monotypic genera Nangura and Gnypetoscincus, sections of two mitochondrial genes (ND4 and 16S rRNA) were sequenced and subjected to Bayesian phylogenetic analysis. This phylogenetic analysis supports recognition of the three species groups proposed for Eulamprus (murrayi, quoyii and tenuis) and indicates that this genus is paraphyletic, with Gnypetoscincus and Nangura being proximal to basal lineages of the tenuis group. To resolve these and broader problems of paraphyly, we suggest that each of the species groups from 'Eulamprus' should be recognised as a distinct genus. The phylogenetically and ecologically distinct water skinks of the quoyii group would be retained within Eulamprus and the diverse species of the tenuis group allocated to Concinnia. We suggest placing the monophyletic murrayi group, endemic to the rainforests of central eastern Australia, in a new genus ( yet to be formally described). The sequencing data also revealed the existence of a genetically divergent but morphologically cryptic lineage within E. murrayi and substantial diversity within E. quoyii. There is evidence for two major habitat shifts from rainforest towards drier habitats, one leading to the quoyii group and the second defining a clade of three species within the tenuis complex. These ecological transitions may represent adaptations to general drying across eastern Australia during the late Miocene - Pliocene. Each of the major areas of east coast tropical or subtropical rainforest contains multiple phylogenetically diverse endemic species, reflecting the long-term persistence and high conservation value of wet forest habitats in each area.

Magnetic resonance microscopy of the equine hoof wall: a study of resolution and potential

Reasons for performing study: Obtaining magnetic resonance images of the inner hoof wall tissue at the microscopic level would enable early accurate diagnosis of laminitis and therefore more effective therapy. Objectives: To optimise magnetic resonance imaging (MRI) parameters in order to obtain the highest possible resolution of the structures beneath the equine hoof wall. Methods: Magnetic resonance microscopy (MRM) was performed in front feet from 6 cadaver horses using T-2-weighted fast spin echo (FSE-T-2), and T-1-weighted gradient echo (GRE-T-1) sequences. Results: In T-2 weighted FSE images most of the stratum medium showed no signal, however the coronary, terminal and sole papillae were visible. The stratum lamellatum was clearly visible and primary epidermal lamellae could be differentiated from dermal lamellae. Conclusion: Most structures beneath the hoof wall were differentiated. Conventional scanners for diagnostic MRI in horses are low or high field. However this study used ultra-high field scanners currently not available for clinical use. Signal-to-noise ratio (SIN) increases as a function of field strength. An increase of spatial resolution of the image results in a decreased SIN. SIN can also be improved with better coils and the resolution of high field MRI scanners will increase as technology develops and surface array coils become more readily available. Potential relevance: Although MR images with microscopic resolution were obtained ex vivo, this study demonstrates the potential for detection of lamellar pathology as it occurs. Early recognition of the development of laminitis to instigate effective therapy at an earlier stage and may improve the outcome for laminitic horses. Clinical MR is now readily available at 3 T, while 4 T, 7 T and 9 T systems are being used for human whole body applications.

Reproducibility of the cycling time to exhaustion at VO(2)peak in highly trained cyclists

The purpose of the present study was to examine, in highly trained cyclists, the reproducibility of cycling time to exhaustion (T-max) at the power output equal to that attained at peak oxygen uptake ((V) over dot O(2)peak) during a progressive exercise test. Forty-three highly trained male cyclists (M +/- SD; age = 25 +/- 6yrs; weight = 75 +/- 7 kg; (V) over dot(2)peak = 64.8 +/- 5.2 ml.kg(-1) . min(-1)) performed two T-max tests one week apart. While the two measures of T-max were strongly related (r = 0.884; p < 0.001), T-max from the second test (245 +/- 57 s) was significantly higher than that of the first (237 +/- 57 s; p = 0.047; two-tailed). Within-subject variability in the present study was calculated to be 6 +/- 6%, which was lower than that previously reported for Tmax in sub-elite runners (25%). The mean T-max was significantly (p < 0.05) related to both the second ventilatory turnpoint (VT2; r = 0.38) and to (V) over dot O(2)peak (r = 0.34). Despite a relatively low within-subject coefficient of variation, these data demonstrate that the second score in a series of two T-max tests may be significantly greater than the first. Moreover the present data show that T-max in highly trained cyclists is moderately related to VT2 and (V) over dot O(2)peak.

Timing and duration of the last interglacial inferred from high resolution U-series chronology of stalagmite growth in Southern Hemisphere

High-precision Th-230-U-238 ages for a stalagmite from Newdegate Cave in southern Tasmania, Australia define a rare record of precipitation between 100 and 155 ka before the present. The fastest stalagmite growth occurred between 129.2 +/- 1.6 and 122.1 +/- 2.0 ka (similar to 61.5 mm/ka), coinciding with a time of prolific coral growth from Western Australia (128-122 ka). This is the first high-resolution continental record in the Southern Hemisphere that can be compared and correlated with the marine record. Such correlation shows that in southern Australia the onset of full interglacial sea level and the initiation of highest precipitation on land were synchronous. The stalagmite growth rate between 129.2 and 142.2 ka (similar to 5.9 mm/ka) was lower than that between 142.2 and 154.5 ka (similar to 18.7 mm/ka), implying drier conditions during the Penultimate Deglaciation, despite rising temperature and sea level. This asymmetrical precipitation pattern is caused by latitudinal movement of subtropical highs and an associated Westerly circulation, in response to a changing Equator-to-Pole temperature gradient. Both marine and continental records in Australia strongly suggest that the insolation maximum between 126 and 128 ka at 65 degreesN was directly responsible for the maintenance of full Last Interglacial conditions, although the triggers that initiated Penultimate Deglaciation (at similar to 142 ka) remain unsolved. (C) 2001 Elsevier Science B.V. All rights reserved.

Search for time variation of the fine structure constant

An order of magnitude sensitivity gain is described for using quasar spectra to investigate possible time or space variation in the fine structure constant alpha. Applied to a sample of 30 absorption systems, spanning redshifts 0.5 < z < 1.6, we derive limits on variations in alpha over a wide range of epochs. For the whole sample, Delta alpha/alpha = (-1.1 +/- 0.4) x 10(-5). This deviation is dominated by measurements at z > 1, where Delta alpha/alpha = (-1.9 +/- 0.5) x 10(-5). For z < 1, Delta alpha/alpha = (-0.2 +/- 0.4) x 10(-5). While this is consistent with a time-varying alpha, further work is required to explore possible systematic errors in the data, although careful searches have so far revealed none.

An evaluation of the time dependence of the anisotropy of the water diffusion tensor in acute human ischemia

We have performed MRI examinations to determine the water diffusion tensor in the brain of six patients who were admitted to the hospital within 12 h after the onset of cerebral ischemic symptoms. The examinations have been carried out immediately after admission, and thereafter at varying intervals up to 90 days post admission. Maps of the trace of the diffusion tensor, the fractional anisotropy and the lattice index, as well as maps of cerebral blood perfusion parameters, were generated to quantitatively assess the character of the water diffusion tensor in the infarcted area. In patients with significant perfusion deficits and substantial lesion volume changes, four of six cases, our measurements show a monotonic and significant decrease in the diffusion anisotropy within the ischemic lesion as a function of time. We propose that retrospective analysis of this quantity, in combination with brain tissue segmentation and cerebral perfusion maps, may be used in future studies to assess the severity of the ischemic event. (C) 1999 Elsevier Science Inc.