bluuebunny/crossref_metadata_2025 huggingface dataset:
White matter changes and late-life depressive symptoms
Authors: Teodorczuk Andrew , O'Brien John T. , Firbank Michael J. , Pantoni Leonardo , Poggesi Anna , Erkinjuntti Timo , Wallin Anders , Wahlund Lars-Olof , Gouw Alida , Waldemar Gunhild , Schmidt Reinhold , Ferro José M. , Chabriat Hugues , Bäzner Hansjörg , Inzitari Domenico
Published: August 2007

Background

Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear.

Aims

To investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders.

Method

In a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year.

Results

Using logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01).

Conclusions

White matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.
Affective neuroscience and psychiatry
Authors: Harrison Neil A. , Critchley Hugo D.
Published: August 2007

Affective neuroscience addresses the brain mechanisms underlying emotional behaviour. In psychiatry, affective neuroscience finds application not only in understanding the neurobiology of mood disorders, but also by providing a framework for understanding the neural control of interpersonal and social behaviour and processes that underlie psychopathology. By providing a coherent conceptual framework, affective neuroscience is increasingly able to provide a mechanistic explanatory understanding of current therapies and is driving the development of novel therapeutic approaches.
Advance statements: survey of patients' views and understanding
Authors: Foy Jane , Macrae Alison , Thom Alex , Macharouthu Ajay
Published: August 2007

Aims and Method

A survey of patients was undertaken to determine their knowledge and understanding of advance statements (a new addition to Scottish mental health legislation introduced with the Mental Health (Care and Treatment) (Scotland) Act 2003). Few patients have taken up this facility and this study attempts to identify potential explanations.

Results

A minority of the initial 58 participants had heard of advance statements prior to the survey (5 of 58, 8.6%). After issuing information about advance statements, awareness and understanding increased significantly among those who completed the study, with 59% (16 of 27) now understanding the concept. The types of information that patients wished to be documented in an advance statement fell into two broad groups: treatment preferences and statements regarding loss of control and autonomy. Out of 27 participants 19 (70%) stated they would now consider drawing up an advance statement.

Clinical Implications

A lack of knowledge among patients about the existence of advance statements is highlighted. After a brief intervention, awareness, understanding and interest increased significantly, suggesting that poor uptake could be because of lack of awareness. Most participants would consult mental health professionals when drawing up an advance statement, therefore we have a responsibility to be fully informed about the process.
Higher training in liaison psychiatry for older adults: experiences of two specialist training posts
Authors: Young Maura , Morris Siobhan
Published: August 2007

Over the past decade, old age liaison psychiatry services have been developing across the UK. The driving force behind this has been the recognition of the inequity in service provision for people over the age of 65 with mental health problems in a general hospital setting. A postal survey of consultants in old age psychiatry in April 2002 showed that most respondents (71%) considered that the service they provided to older people in general hospitals was poor and needed to be improved (Holmes et al, 2002). Much work has been done to highlight this issue, and liaison psychiatry for older adults is gaining prominence. The national conference on liaison psychiatry for older people, which has been held in Leeds for the past 4 years, attracts large numbers of enthusiastic participants. The Department of Health (2006) document A New Ambition for Old Age specifically mentions the current poor standard of care that older people with mental health problems receive in a general hospital setting. The Royal College of Psychiatrists (2005) has produced guidelines for the development of liaison mental health services for older people.
Benchmarking a liaison psychiatry service: a prospective 6-month study of quality indicators
Authors: O'Keeffe Nikki , Ramaiah Umesh Sira , Nomani Erum , Fitzpatrick Michelle , Ranjith Gopinath
Published: August 2007

Aims and Method

There are no national standards to evaluate the quality of delivery of in-patient liaison psychiatry services in general hospitals in the UK. In order to benchmark our service against best international practice, we adapted quality indicators from two peer-reviewed studies from Australia and Switzerland and monitored our performance standards over a period of 6 months.

Results

There were 145 patients assessed over the study period. We set a priori target of 90% achievement on indicators in the areas of timeliness of response to all referrals, timeliness of response to referrals following self-harm and quality of supervision of junior medical staff attaining 93.8, 87.5 and 89.6% respectively.

Clinical Implications

We demonstrated that we provided a reasonably responsive consultation–liaison service with high levels of supervision of junior staff. National bodies should develop benchmarks in this area so that services can demonstrate the quality of their service and learn from others' good practice.
Nonassembled Human Chorionic Gonadotropin Subunits and αα-Homodimers Use Fast-Track Processing in the Secretory Pathway in Contrast to αβ-Heterodimers
Authors: Merz Wolfgang E. , Krause Jean-Michel , Roig Jordi , Singh Vinod , Berger Peter
Published: August 2007

In multimeric glycoproteins, like glycoprotein hormones, mutual subunit interactions are required for correct folding, assembly, and transport in the secretory pathway. However, character and time course of these interactions need further elucidation. The influence of the glycoprotein hormone α-subunit (GPHα) on the folding of the human chorionic gonadotropin (hCG) β-subunit (hCGβ) in hCG αβ-heterodimers was investigated in [35S]Met/Cys-labeled JEG-3 cells. Completeness of disulfide bridge formation during the time course of folding was estimated by labeling with [3H]N-ethylmaleinimide of free thiol groups not yet consumed. Subunit association took place between immature hCGβ (high 3H/35S ratio) and almost completely folded GPHα. Analysis revealed a highly dynamic maturation process comprising of at least eight main hCGβ folding intermediates (molecular masses from 107 to 28 kDa) that could be micro-preparatively isolated and characterized. These hCGβ variants developed while being associated with GPHα. The 107-kDa variant was identified as a complex with calnexin. In contrast to hCG αβ-heterodimers, free nonassociated hCGβ, free large GPHα, and GPHαα homodimers showed a fast-track-like processing in the secretory pathway. At 10 min before hCG secretion, sialylation of these variants had already been completed in the late Golgi, whereas hCG αβ-heterodimers had still not arrived medial Golgi. This shows that the GPHα in the hCG αβ-heterodimers decelerates the maturation of the hCGβ portion in the heterodimer complex. This results in a postponed approval of hCG αβ-heterodimers by the endoplasmic reticulum quality control unlike GPHαα homodimers, free hCGβ, and GPHα subunits.
Combination Therapy with Amylin and Peptide YY[3–36] in Obese Rodents: Anorexigenic Synergy and Weight Loss Additivity
Authors: Roth Jonathan D. , Coffey Todd , Jodka Carolyn M. , Maier Holly , Athanacio Jennifer R. , Mack Christine M. , Weyer Christian , Parkes David G.
Published: August 2007

Circulating levels of the pancreatic β-cell peptide hormone amylin and the gut peptide PYY[3–36] increase after nutrient ingestion. Both have been implicated as short-term signals of meal termination with anorexigenic and weight-reducing effects. However, their combined effects are unknown. We report that the combination of amylin and PYY[3–36] elicited greater anorexigenic and weight-reducing effects than either peptide alone. In high-fat-fed rats, a single ip injection of amylin (10 μg/kg) plus PYY[3–36] (1000 μg/kg) reduced food intake for 24 h (P < 0.05 vs. vehicle), whereas the anorexigenic effects of either PYY[3–36] or amylin alone began to diminish 6 h after injection. These anorexigenic effects were dissociable from changes in locomotor activity. Subcutaneous infusion of amylin plus PYY[3–36] for 14 d suppressed food intake and body weight to a greater extent than either agent alone in both rat and mouse diet-induced obesity (DIO) models (P < 0.05). In DIO-prone rats, 24-h metabolic rate was maintained despite weight loss, and amylin plus PYY[3–36] (but not monotherapy) increased 24-h fat oxidation (P < 0.05 vs. vehicle). Finally, a 4 × 3 factorial design was used to formally describe the interaction between amylin and PYY[3–36]. DIO-prone rats were treated with amylin (0, 4, 20, and 100 μg/kg·d) and PYY[3–36] (0, 200, 400 μg/kg·d) alone and in combination for 14 d. Statistical analyses revealed that food intake suppression with amylin plus PYY[3–36] treatment was synergistic, whereas body weight reduction was additive. Collectively, these observations highlight the importance of studying peptide hormones in combination and suggest that integrated neurohormonal approaches may hold promise as treatments for obesity.
Human Chorionic Gonadotropin Induces Neuronal Differentiation of PC12 Cells through Activation of Stably Expressed Lutropin/Choriogonadotropin Receptor
Authors: Meng Xing-Li , Rennert Owen M. , Chan Wai-Yee
Published: August 2007

Human chorionic gonadotropin (hCG) and LH play an important role in reproductive physiology. Both hCG and LH bind to the same LH/choriogonadotropin receptor (LH/CG-R). Recent reports documented the temporal and spatial expression of LH/CG-R in the developing and mature mammalian brain. Administration of hCG promoted nerve regeneration in vivo and neurite outgrowth and survival of primary neurons in vitro. The function of hCG/LH and LH/CG-R in the nervous system remains unclear. In this study, we report that hCG/LH induced distinct morphological and biochemical changes, characteristic of neuronal differentiation, in PC12 cells stably expressing LH/CG-R and that the differentiation effect is ligand dose and time dependent. Western blot analysis revealed that both the ERKs and p38 MAPK are activated after hCG treatment. Inhibitor studies showed both the ERK and p38 MAPK signal transduction pathways are required for this differentiation process, which is cAMP dependent and protein kinase A independent. These findings imply a potential role for hCG/LH and LH/CG-R in the development, maintenance, and regeneration of the mammalian nervous system, and in the neuropathogenesis of genetic diseases caused by a mutated LH/CG-R.
Gender-Dependent Role of Endogenous Somatostatin in Regulating Growth Hormone-Axis Function in Mice
Authors: Luque Raul M. , Kineman Rhonda D.
Published: August 2007

It has been previously reported that male and female somatostatin (SST) knockout mice (Sst−/−) release more GH, compared with Sst+/+ mice, due to enhanced GH-secretory vesicle release. Endogenous SST may also regulate GH secretion by directly inhibiting GHRH-stimulated GH gene expression and/or by modulating hypothalamic GHRH input. To begin to explore these possibilities and to learn more about the gender-dependent role of SST in modulating GH-axis function, hypothalamic, pituitary, and liver components of the GH-axis were compared in male and female Sst+/+ and Sst−/− mice. Pituitary mRNA levels for GH and receptors for GHRH and ghrelin were increased in female Sst−/− mice, compared with Sst+/+ controls, and these changes were reflected by an increase in circulating GH and IGF-I. Elevated levels of IGF-I in female Sst−/− mice were associated with elevated hepatic mRNA levels for IGF-I, as well as for GH and prolactin receptors. Consistent with the role of GH/IGF-I in negative feedback regulation of hypothalamic function, GHRH mRNA levels were reduced in female Sst−/− mice, whereas cortistatin (CST) mRNA levels were unaltered. In contrast to the widespread impact of SST loss on GH-axis function in females, only circulating GH, hypothalamic CST, and hepatic prolactin receptor expression were up-regulated in Sst−/− male mice, compared with Sst+/+ controls. These results confirm and extend the sexually dimorphic role of SST on GH-axis regulation, and suggest that CST, a neuropeptide that acts through SST receptors to inhibit GH secretion, may serve a compensatory role in maintaining GH-axis function in Sst−/− male mice.
Orphan Receptor TR3 Attenuates the p300-Induced Acetylation of Retinoid X Receptor-α
Authors: Zhao Wen-xiu , Tian Min , Zhao Bi-xing , Li Gui-deng , Liu Bo , Zhan Yan-yan , Chen Hang-zi , Wu Qiao
Published: August 2007

Acetylation modification regulates the functions of histone and nonhistone proteins, including transcriptional activity, protein interaction, and subcellular localization. Although many nuclear receptors have been shown to be modified by acetylation, whether retinoid X receptors (RXRs) are acetylated and how the acetylation is regulated remains unknown. Here, we provide the first evidence of RXRα acetylation by p300 on lysine 145. Acetylation of RXRα by p300 facilitated its DNA binding and subsequently increased its transcriptional activity. Furthermore, we discovered that TR3, an orphan receptor, exerted a negative regulation on p300-induced RXRα acetylation. TR3 significantly reduced the p300-induced RXRα acetylation and transcriptional activity, and such inhibition required the interaction of TR3 with RXRα. Binding of TR3 to RXRα resulted in the sequestration of RXRα from p300. 9-cis retinoic acid, a ligand for RXRα, enhanced the association of RXRα with TR3, rather than acetylation of RXRα by p300. Biological function analysis revealed that the mitogenic activity of RXRα stimulated by p300 was acetylation dependent and could be repressed by TR3. Upon the treatment of 9-cis retinoic acid, RXRα was translocated with TR3 from the nucleus to the mitochondria, and apoptosis was induced. Taken together, our data demonstrate the distinct regulatory mechanisms of p300 and TR3 on RXRα acetylation and reveal a previously unrecognized role for orphan receptor in the transcriptional control of retinoid receptors.
The Transcription Factor Snail Mediates Epithelial to Mesenchymal Transitions by Repression of Estrogen Receptor-α
Authors: Dhasarathy Archana , Kajita Masahiro , Wade Paul A.
Published: August 2007

The estrogen receptor (ER)-α (ESR1) is a key regulatory molecule in mammary epithelial cell development. Loss of ER-α in breast cancer is correlated with poor prognosis, increased recurrence after treatment, and an elevated incidence of metastasis. A proposed molecular pathway by which ER-α acts to constrain invasive growth in breast cancer cells involves direct, ER-α-dependent expression of metastasis-associated protein 3, a cell-type-specific component of the Mi-2/NuRD chromatin remodeling complex. MTA3 in turn represses expression of Snail, a transcription factor linked to epithelial to mesenchymal transition and cancer metastasis. To elucidate its role(s) in epithelial to mesenchymal transition (EMT), we expressed Snail in the noninvasive, ER-α-positive MCF-7 cell line. Snail expression led to decreased cell-cell adhesion and increased cell invasiveness. Furthermore, we observed loss of ER-α expression at both the RNA and protein level that was accompanied by direct interaction of Snail with regulatory DNA sequences at the ESR1 locus. A consequence of loss of ER-α function in this system was the increased abundance of key components of the TGF-β signaling pathway. Thus, cross-talk among ER-α, Snail, and the TGF-β pathway appears to control critical phenotypic properties of breast cancer cells.
Biomechanics of bird flight
Authors: Tobalske Bret W.
Published: August 2007

Power output is a unifying theme for bird flight and considerable progress has been accomplished recently in measuring muscular, metabolic and aerodynamic power in birds. The primary flight muscles of birds, the pectoralis and supracoracoideus, are designed for work and power output, with large stress (force per unit cross-sectional area) and strain (relative length change) per contraction. U-shaped curves describe how mechanical power output varies with flight speed, but the specific shapes and characteristic speeds of these curves differ according to morphology and flight style. New measures of induced, profile and parasite power should help to update existing mathematical models of flight. In turn, these improved models may serve to test behavioral and ecological processes. Unlike terrestrial locomotion that is generally characterized by discrete gaits, changes in wing kinematics and aerodynamics across flight speeds are gradual. Take-off flight performance scales with body size, but fully revealing the mechanisms responsible for this pattern awaits new study. Intermittent flight appears to reduce the power cost for flight, as some species flap–glide at slow speeds and flap–bound at fast speeds. It is vital to test the metabolic costs of intermittent flight to understand why some birds use intermittent bounds during slow flight. Maneuvering and stability are critical for flying birds,and design for maneuvering may impinge upon other aspects of flight performance. The tail contributes to lift and drag; it is also integral to maneuvering and stability. Recent studies have revealed that maneuvers are typically initiated during downstroke and involve bilateral asymmetry of force production in the pectoralis. Future study of maneuvering and stability should measure inertial and aerodynamic forces. It is critical for continued progress into the biomechanics of bird flight that experimental designs are developed in an ecological and evolutionary context.
Mechanical power and efficiency of level walking with different stride rates
Authors: Umberger Brian R. , Martin Philip E.
Published: August 2007

Walking humans prefer to use the stride rate that results in the lowest rate of metabolic energy expenditure. Mechanical power requirements have been suggested to underlie the metabolic response, but mechanical power is consistently reported to be minimal at stride rates 20–30% lower than preferred. This may be due to limitations in how total mechanical power has been computed, as well as a failure to account for the efficiency with which muscular work is done. We investigated how mechanical power and efficiency depend on stride rate in walking, with both quantities computed from the work done by the hip, knee and ankle joint moments. Our hypotheses were that mechanical power and efficiency are both optimized at the preferred stride rate, which would explain why metabolic energy expenditure is minimized at this rate. Contrary to our hypotheses, mechanical power curves exhibited plateaus that spanned stride rates lower than preferred (predicted optima:11–12% below preferred), while net mechanical efficiency exhibited a plateau that spanned stride rates higher than preferred (predicted optimum: 8%above preferred). As expected, preferred stride rate (54.3 strides min–1) was not different from the stride rate that minimized net metabolic energy expenditure (predicted optimum: 0.2% above preferred). Given that mechanical power and mechanical efficiency exhibited plateaus on opposite sides of the preferred stride rate, the preferred rate in walking likely represents a compromise between these two factors. This may also explain the relative flatness of the curve for metabolic rate in the vicinity of the preferred stride rate.
Modulation ofin vivomuscle power output during swimming in the African clawed frog (Xenopus laevis)
Authors: Richards Christopher T. , Biewener Andrew A.
Published: August 2007

The goal of this study is to explore how swimming animals produce the wide range of performance that is seen across their natural behaviors. In vivo recordings of plantaris longus muscle length change were obtained by sonomicrometry. Simultaneous with muscle length data, force measurements were obtained using a novel tendon buckle force transducer placed on the Achilles tendon of Xenopus laevis frogs during brief accelerating bursts of swimming. In vivo work loops revealed that the plantaris generates a variable amount of positive muscle work over a range of swimming cycle durations (from 0.23 to 0.76 s), resulting in a large range of cycle power output (from 2.32 to 74.17 W kg–1 muscle). Cycle duration correlated negatively with cycle power, and cycle work correlated positively(varying as a function of peak cycle stress and, to a much lesser extent,fascicle strain amplitude). However, variation in cycle duration only contributed to 12% of variation in power, with cycle work accounting for the remaining 88%. Peak cycle stress and strain amplitude were also highly variable, yet peak stress was a much stronger predictor of cycle work than strain amplitude. Additionally, EMG intensity correlated positively with peak muscle stress (r2=0.53). Although the timing of muscle recruitment (EMG phase and EMG duty cycle) varied considerably within and among frogs, neither parameter correlated strongly with cycle power, cycle work, peak cycle stress or strain amplitude. These results suggest that relatively few parameters (cycle duration, peak cycle stress and strain amplitude) vary to permit a wide range of muscle power output, which allows anurans to swim over a large range of velocities and accelerations.
Ventilatory and cardiovascular actions of centrally administered trout tachykinins in the unanesthetized trout
Authors: Le Mével Jean-Claude , Lancien Frédéric , Mimassi Nagi , Conlon J. Michael
Published: August 2007

The brains of teleost fish contain members of the tachykinin family that are the products of orthologous genes expressed in mammalian nervous tissues,but little is known regarding the physiological effects of these peptides in their species of origin. The present study compares the central actions of trout neuropeptide gamma (NPγ), substance P (SP) and neurokinin A (NKA)(5–250 pmol) on ventilatory and cardiovascular parameters in the unanesthetized rainbow trout Oncorhynchus mykiss. Intracerebroventricular (ICV) injection of NPγ evoked a dose-dependent elevation of the ventilation rate (fV) but a reduction of the ventilation amplitude (VAMP) that was caused by a reduction of the magnitude of the adduction phase of the ventilatory signal. The net effect of NPγ was to produce an hypoventilatory response since the total ventilation (VTOT) was significantly reduced. The minimum effective dose for a significant effect of NPγ on fV and VAMP was 50 pmol. SP evoked a significant elevation of fV, a concomitant depression of VAMP, and a resultant decrease in VTOTbut only at the highest dose (250 pmol). NKA was without action on fV but significantly decreased VAMP at only the highest dose tested. In this case also, the net effect of NKA was to reduce VTOT. When injected centrally, none of the three peptides, at any dose tested, produced changes in heart rate or mean dorsal aortic blood pressure (PDA). Intra-arterial injection of the three tachykinins (250 pmol) produced a significant (P<0.05)increase in PDA, but only SP and NKA induced concomitant bradycardia. None of the three peptides produced any change in fV or VAMP. In conclusion, our results demonstrate that centrally injected tachykinins, particularly NPγ,produce a strong hypoventilatory response in a teleost fish and so suggest that endogenous tachykinins may be differentially implicated in neuroregulatory control of ventilation.
Molecular and expression analysis of a family of theAmblyomma americanumtick Lospins
Authors: Mulenga Albert , Khumthong Rabuesak , Blandon Maria A.
Published: August 2007

Serine proteinase inhibitors (serpins) are a family of structurally similar but functionally diverse proteins that regulate several important proteolytic cascades in most branches of life. We have characterized 17 Amblyomma americanum serpin cDNAs here named as `Lospins' (L; an acronym for Lone Star tick serpin) that possess three β-sheets, eight α-helices and a reactive center loop consistent with the consensus serpin superfamily secondary structures. Visual inspection of deduced amino acid sequences revealed two patterns of basic residues: (i) 86DKSRVLKAYKRL97 in L5 and L13–16 and (ii) 158VRDKTRGKI166 in all Lospins, which are similar to consensus glycosaminoglycan (GAG) binding sites (XBnXmBX, where X and B are non-basic and basic residues, n=1 or 2 and m=1, 2 or 3). On three-dimensional models, the two putative GAG binding sites mapped onto α-helices D and F, respectively, with calculation of electrostatic surface potentials revealing basic patches on L5 and L13–16 models that are comparable to the heparin-binding site on antithrombin. RT-PCR expression analysis of 15 selected genes showed that the majority (11/15) of the Lospins were ubiquitously expressed in the midgut, ovary and salivary glands. On a neighbor-joining phylogeny guide tree, 15 serpins from other ticks and 17 Lospins from this study, a total of 32 tick serpin sequences, segregated into five groups with Lospins in groups A and D being conserved across tick species. The discovery of Lospins in this study sets the framework for future studies to understand the role of serpins in tick physiology.
How fast does a seal swim? Variations in swimming behaviour under differing foraging conditions
Authors: Gallon Susan L. , Sparling Carol E. , Georges Jean-Yves , Fedak Michael A. , Biuw Martin , Thompson Dave
Published: August 2007

The duration of breath-hold dives and the available time for foraging in submerged prey patches is ultimately constrained by oxygen balance. There is a close relationship between swim speed and oxygen utilisation, so it is likely that breath-holding divers optimise their speeds to and from the feeding patch to maximise time spent feeding at depth. Optimal foraging models suggest that transit swim speed should decrease to minimum cost of transport (MCT) speed in deeper and longer duration dives. Observations also suggest that descent and ascent swimming mode and speed may vary in response to changes in buoyancy. We measured the swimming behaviour during simulated foraging of seven captive female grey seals (two adults and five pups). Seals had to swim horizontally underwater from a breathing box to a submerged automatic feeder. The distance to the feeder and the rate of prey food delivery could be varied to simulate different feeding conditions.

Diving durations and distances travelled in dives recorded during these experiments were similar to those recorded in the wild. Mean swim speed decreased significantly with increasing distance to the patch, indicating that seals adjusted their speed in response to travel distance, consistent with optimality model predictions. There was, however, no significant relationship between the transit swim speeds and prey density at the patch. Interestingly,all seals swam 10–20% faster on their way to the prey patch compared to the return to the breathing box, despite the fact that any effect of buoyancy on swimming speed should be the same in both directions. These results suggest that the swimming behaviour exhibited by foraging grey seals might be a combination of having to overcome the forces of buoyancy during vertical swimming and also of behavioural choices made by the seals.
Light-dependent magnetoreception: quantum catches and opponency mechanisms of possible photosensitive molecules
Authors: Johnsen Sönke , Mattern Erin , Ritz Thorsten
Published: August 2007

Dozens of experiments on magnetosensitive, migratory birds have shown that their magnetic orientation behavior depends on the spectrum of light under which they are tested. However, it is not certain whether this is due to a direct effect on the magnetoreceptive system and which photosensitive molecules may be involved. We examined 62 experiments of light-dependent magnetoreception in three crepuscular and nocturnal migrants (48 for the European robin Erithacus rubecula, ten for the silvereye Zosterops lateralis, and four on the garden warbler Sylvia borin). For each experiment, we calculated the relative quantum catches of seven of the eight known photosensitive molecules found in the eyes of passerine birds: a short- (SW), medium- (MW) and long-wavelength (LW) cone pigment, rhodopsin, melanopsin, and cryptochrome in its fully-oxidized and semiquinone state. The following five opponency processes were also calculated: LW–SW, LW–MW, MW–SW, LW–(MW+SW), and cryptochrome–semiquinone. While the results do not clearly show which receptor system may be responsible for magnetoreception, it suggests several candidates that may inhibit the process. The two significant inhibitors of magnetoreceptive behavior were overall irradiances (from 400 to 700 nm) higher than those found at sunset and high quantum catch by the LW receptor. The results were also consistent with the hypothesis that high quantum catch by the semiquinone form of cryptochrome inhibits magnetoreception. The opponency mechanism that best separated oriented from non-oriented behavior was LW–MW, where a difference above a certain level inhibited orientation. Certain regions of experimental spectral space have been over-sampled, while large regions have not been sampled at all, including: (1) from 440 to 500 nm at all irradiance levels, (2) for wavelengths longer than 570 nm from 1012 to 3×1012 photons s–1cm–2 and (3) for wavelengths less than 560 nm from 1012 to 3×1012 photons s–1cm–2 and below 5×1011 photons s–1 cm–2. Experiments under these conditions are needed to draw further conclusions.
Effects of elevated ecdysteroid on tissue expression of three guanylyl cyclases in the tropical land crabGecarcinus lateralis: possible roles of neuropeptide signaling in the molting gland
Authors: Lee Sung Gu , Bader Brandon D. , Chang Ernest S. , Mykles Donald L.
Published: August 2007

Two eyestalk (ES) neuropeptides, molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH), increase intracellular cGMP levels in target tissues. Both MIH and CHH inhibit ecdysteroid secretion by the molting gland or Y-organ (YO), but apparently through different guanylyl cyclase(GC)-dependent pathways. MIH signaling may be mediated by nitric oxide synthase (NOS) and NO-sensitive GC. CHH binds to a membrane receptor GC. As molting affects neuropeptide signaling, the effects of ecdysteroid on the expression of the land crab Gecarcinus lateralis β subunit of a NO-sensitive GC (Gl-GC-Iβ), a membrane receptor GC (Gl-GC-II) and a NO-insensitive soluble GC (Gl-GC-III) were determined. Gl-GC-Iβ isoforms differing in the absence or presence of an N-terminal 32-amino acid sequence and Gl-GC-III were expressed at higher mRNA levels in ES ganglia, gill,hepatopancreas, ovary and testis, and at lower levels in YO, heart and skeletal muscle. Three Gl-GC-II isoforms, which vary in the length of insertions (+18, +9 and +0 amino acids) within the N-terminal ligand-binding domain, differed in tissue distribution. Gl-GC-II(+18) was expressed highly in striated muscle (skeletal and cardiac muscles); Gl-GC-II(+9) was expressed in all tissues examined (ES ganglia, YO, gill, hepatopancreas, striated muscles and gonads); and Gl-GC-II(+0) was expressed in most tissues and was the dominant isoform in ES and thoracic ganglia. ES ablation, which increased hemolymph ecdysteroid, increased Gl-GC-II(+18) mRNA level in claw muscle. Using real-time RT-PCR, ES ablation increased Gl-GC-Iβ, Gl-GC-III and ecdysone receptor mRNA levels in the YOs ∼ten-, ∼four- and∼twofold, respectively, whereas Gl-GC-II mRNA level was unchanged. A single injection of 20-hydroxyecdysone into intact animals transiently lowered Gl-GC-Iβ in hepatopancreas, testis and skeletal muscle, and certain Gl-GC-II isoforms in some of the tissues. These data suggest that YO and other tissues can modulate responses to neuropeptides by altering GC expression.
The spatial, temporal and contrast properties of expansion and rotation flight optomotor responses inDrosophila
Authors: Duistermars Brian J. , Chow Dawnis M. , Condro Michael , Frye Mark A.
Published: August 2007

Fruit flies respond to panoramic retinal patterns of visual expansion with robust steering maneuvers directed away from the focus of expansion to avoid collisions and maintain an upwind flight posture. Panoramic rotation elicits comparatively weak syndirectional steering maneuvers, which also maintain visual stability. Full-field optic flow patterns like expansion and rotation are elicited by distinct flight maneuvers such as body translation during straight flight or body rotation during hovering, respectively. Recent analyses suggest that under some experimental conditions the rotation optomotor response reflects the linear sum of different expansion response components. Are expansion and rotation-mediated visual stabilization responses part of a single optomotor response subserved by a neural circuit that is differentially stimulated by the two flow fields, or rather do the two behavioral responses reflect two distinct control systems? Guided by the principle that the properties of neural circuits are revealed in the behaviors they mediate, we systematically varied the spatial, temporal and contrast properties of expansion and rotation stimuli, and quantified the time course and amplitude of optomotor responses during tethered flight. Our results support the conclusion that expansion and rotation optomotor responses are indeed two separate reflexes, which draw from the same system of elementary motion detectors, but are likely mediated by separate pre-motor circuits having different spatial integration properties, low-pass characteristics and contrast sensitivity.
Haze, clouds and limited sky visibility: polarotactic orientation of crickets under difficult stimulus conditions
Authors: Henze Miriam J. , Labhart Thomas
Published: August 2007

Field crickets (Gryllus campestris L.) are able to detect the orientation of the electric vector (e-vector) of linearly polarized light. They presumably use this sense to exploit the celestial polarization pattern for course control or navigation. Polarization vision in crickets can be tested by eliciting a spontaneous polarotactic response. Previously, wide and 100% polarized stimuli were employed to induce this behavior. However, field crickets live on meadows where the observation of the sky is strongly limited by surrounding vegetation. Moreover, degrees of polarization (d) in the natural sky are much lower than 100%. We have therefore investigated thresholds for the behavioral response to polarized light under conditions mimicking those experienced by the insects in the field. We show that crickets are able to rely on polarized stimuli of just 1° diameter. We also provide evidence that they exploit polarization down to an (average) polarization level of less than 7%, irrespective of whether the stimulus is homogeneous,such as under haze, or patched, such as a sky spotted by clouds. Our data demonstrate that crickets can rely on skylight polarization even under unfavorable celestial conditions, emphasizing the significance of polarized skylight orientation for insects.
An isolated insect leg's passive recovery from dorso-ventral perturbations
Authors: Dudek Daniel M. , Full Robert J.
Published: August 2007

Cockroaches recover rapidly from perturbations during high-speed running that allows them to cross unstructured terrains with no change in gait. Characterization of the exoskeletal material properties of the legs suggests that passive mechanical feedback could contribute to the self-stabilizing behavior. We imposed large, dorsal-ventrally directed impulsive perturbations to isolated hind legs having both a fixed and free body–coxa joint and measured their recovery. We tested a frequency-independent hysteretic damping model that effectively predicted the behavior of sinusoidal oscillations of isolated legs. Leg position reached its peak amplitude within 4–6 ms following an impulse. Position was 99% recovered within 16±3.3 ms for the stiffest possible leg configuration and within 46±6.6 ms for the most compliant leg configuration. The rapid recovery supports the hypothesis that passive musculo-skeletal properties play an important role in simplifying the control of high-speed locomotion.
Neural mechanisms underlying target detection in a dragonfly centrifugal neuron
Authors: Geurten Bart R. H. , Nordström Karin , Sprayberry Jordanna D. H. , Bolzon Douglas M. , O'Carroll David C.
Published: August 2007

Visual identification of targets is an important task for many animals searching for prey or conspecifics. Dragonflies utilize specialized optics in the dorsal acute zone, accompanied by higher-order visual neurons in the lobula complex, and descending neural pathways tuned to the motion of small targets. While recent studies describe the physiology of insect small target motion detector (STMD) neurons, little is known about the mechanisms that underlie their exquisite sensitivity to target motion. Lobula plate tangential cells (LPTCs), a group of neurons in dipteran flies selective for wide-field motion, have been shown to take input from local motion detectors consistent with the classic correlation model developed by Hassenstein and Reichardt in the 1950s. We have tested the hypothesis that similar mechanisms underlie the response of dragonfly STMDs. We show that an anatomically characterized centrifugal STMD neuron (CSTMD1) gives responses that depend strongly on target contrast, a clear prediction of the correlation model. Target stimuli are more complex in spatiotemporal terms than the sinusoidal grating patterns used to study LPTCs, so we used a correlation-based computer model to predict response tuning to velocity and width of moving targets. We show that increasing target width in the direction of travel causes a shift in response tuning to higher velocities, consistent with our model. Finally, we show how the morphology of CSTMD1 allows for impressive spatial interactions when more than one target is present in the visual field.
Visuospatial and Technical Ability in the Selection and Assessment of Higher Surgical Trainees in the London Deanery
Authors: Tansley P , Kakar S , Withey S , Butler P
Published: August 2007

INTRODUCTION

Despite awareness of the limitations of current selection and competency assessments, there is little consensus and alternatives have not been readily accepted. Essential surgical skills include visuospatial and technical ability. The aim of this study was to survey current methods of higher surgical trainee selection and assessment. We suggest ways to improve the process.

MATERIALS AND METHODS

Nine surgical training programmes in the London deanery were surveyed through questionnaires to programme directors, existing trainees and examination of deanery publications.

RESULTS

Testing of visuospatial and technical ability was piloted at selection only in a single general surgical department. Practical skills were assessed in 3/9 (33%) specialties (ENT, plastic and general surgery). Once selected, no specialty tested visuospatial and technical ability. Practical skills were tested in only 1/9 (11%) specialties (plastic surgery). The remaining 8/9 (89%) were ‘assessed’ by interview.

CONCLUSIONS

Lack of visuospatial and technical ability assessment was identified at selection and during higher surgical training. Airlines have long recognised early identification of these qualities as critical for efficient training. There is a need for more objective methods in this area prior to selection as time to assess surgical trainees during long apprenticeships is no longer available. We advocate a suitably validated competency-based model during and at completion of training.
Detecting Patient Allergy: Beware the LIE
Authors: Bismil Quamar , Bowles Christopher , Edwards Mark , Arastu Mateen , Ricketts David M , Solan Matthew C
Published: August 2007

INTRODUCTION

Allergy detection is important in surgical patients. Historically, the focus has been on drug allergies. There is increasing focus on non-drug allergy, specifically latex, iodine and elastoplast.

PATIENTS AND METHODS

The practice and knowledge of 24 pre-registration house officers was evaluated, with regard to patient allergy. For the second phase of the study, the cohort of 367 consecutive patients presenting to the orthopaedic pre-assessment clinic was prospectively assessed.

RESULTS

This prospective study demonstrates that standard history-taking misses a large number (38%) of such allergies.

CONCLUSIONS

With regard to allergy detection, we are living a LIE (by ignoring latex, iodine, elastoplast allergy). We suggest junior doctors should employ the mnemonic LIED (latex, iodine, elastoplast and drugs) when taking a medical history.
Relationship Between Occupation, Social Class and Time taken off Work Following a Whiplash Injury
Authors: Hagan KS , Naqui SZH , Lovell ME
Published: August 2007

INTRODUCTION

Little has been published about occupational and social factors in relation to time off work following a whiplash injury.

PATIENTS AND METHODS

We analysed 800 medicolegal case sheets from a consultant orthopaedic surgeon's practice.

RESULTS

Of those injured, 596 were working and 204 were unemployed or retired. The working group was further analysed. Severity of injury was estimated by analysing velocity of injury combined with vehicular damage. Mean time off work for a minor injury was 10.6 days, moderate 12.1 days, severe 13.8, and very severe 24.9 (P < 0.05). Looking at work categories as previously described in the literature, 20.5 days were taken off by heavy manual workers, light manual 15.7, driving 13.9, secretarial 9.2 and sedentary 12.8 (P < 0.05). Analysing as per social class showed that professionals required 7.0 days, intermediate 14.7 days, skilled non-manual 16.1 days, skilled manual 34.2 days, semi-skilled manual 33.2 days, and unskilled manual 11.5 days (P < 0.05). Nearly a third (31.2%) required no time off work, after 4 days off, 52.1% had returned to work and 90.1% were back at work after 30 days. Time off lasting more than 12 weeks occurred in 29 cases (4.9%).

CONCLUSIONS

Job style, severity of injury and social class have a bearing on time taken off work after road traffic accidents causing whiplash injury.
Transforming Growth Factor-β Gene Expression Studies in Nasal Mucosal Biopsies in Naturally Occurring Allergic Rhinitis
Authors: Salib Rami J
Published: August 2007

Introduction

Evidence has been provided of enhanced epithelial transforming growth factor-beta (TGF-β) immunoreactivity in allergic rhinitis, including correlation with intra-epithelial mast cell numbers, and the co-localisation of TGF-β receptors to mast cells, suggesting that the epithelial expression of TGF-β may represent an important biological process involved in either the recruitment or retention of mast cells within the epithelium in naturally occurring allergic rhinitis.

Patients and Methods

In order to extend the above findings, evaluation was undertaken in whole nasal biopsies from subjects with naturally occurring allergic rhinitis, of levels of TGF-β isotypes and receptors gene expression using real-time quantitative polymerase chain reaction (TaqMan RT-PCR), and the results compared to those for tumour necrosis factor-alpha (TNF-α), as a positive control. The study was also extended to evaluate gene expression for connective tissue growth factor (CTGF) and Smad proteins, as downstream markers of TGF-β bioactivity, in the same populations.

Results

There were no significant differences between the rhinitic and non-rhinitic groups in the expression of TGF-β isoforms or Smad-3, Smad-6 and Smad-7 proteins; however, there was increased gene expression for TGF-βRI and TGF-βRII along with CTGF in seasonal allergic rhinitis. TNF-α gene expression was also increased in seasonal allergic rhinitis, consistent with a more acute inflammatory response in this form of rhinitis.

Conclusions

This study advances our understanding of the role of TGF-β in the pathogenesis of the inflammatory response in allergic rhinitis.
Consent: Luck or Law?
Authors: Elmalik K , Wheeler RA
Published: August 2007

INTRODUCTION

The aim of this study was to identify whether clinicians are obtaining a valid consent for surgery, and ascertain the parents' perception of parental responsibility when giving consent for their children.

PATIENTS AND METHODS

Adults consenting for 100 children were questioned about the possession of parental responsibility, and their understanding of the concept.

RESULTS

Only 4 children had surgery without valid consent, these forms being signed by fathers without parental responsibility. However, only 5% of the sample stated that parental responsibility was required. More than 80% believed that cohabitation was a sufficient qualification to provide consent; fewer than 15% recognising any influence of marital status. It seems that, although 96% of consenters had parental responsibility, the validity of their consent was a product more of luck than of lawful behaviour.

CONCLUSIONS

The results demonstrate a wide gulf between the standards set by the Children Act 1989 and common practice, as perceived by parents. Furthermore, this reveals a significant disparity between the principles behind the statute, and the role that parents believe that they play in the 21st century.
The UK Government Two-Week Rule and its Impact on Melanoma Prognosis: An Evidence-Based Study
Authors: Pacifico MD , Pearl RA , Grover R
Published: August 2007

INTRODUCTION

In order to tackle increasing waiting lists the UK Government's ‘two-week rule’ was introduced for a number of cancers, including melanoma, in 2000. Whilst there is evidence that secondary prevention (i.e. early diagnosis) improves patient outcome, particularly in melanoma where early surgical excision is the only intervention to improve survival, there is as yet no evidence base for a 2-week limit. Any survival benefit from this Government target will not be demonstrable until long-term follow-up is available, realistically 10-year mortality figures in 2010.

PATIENTS AND METHODS

To investigate an evidence base for the two-week rule in melanoma, we performed a retrospective study on patients with suspected skin cancers referred to a rapid access Pigmented Lesion Clinic (PLC) over a 4-year period with long-term survival data, and compared them to a historical control group.

RESULTS

A total of 4399 patients attended the PLC from January 1993 to December 1996 and all were seen within 2 weeks. Ninety-six melanomas were diagnosed during this period with 96% treated within 2 weeks of GP referral, the majority (74%) excised on the day of PLC attendance. Melanoma patients (n = 78) diagnosed in the 2 years prior to the inception of the PLC waited 3–34 days for consultation and 4–74 days for treatment. Melanoma patients diagnosed in the PLC had significantly thinner tumours (Mann Whitney test, P < 0.001) and improved overall survival (χ2 18.1924; P < 0.001) compared with melanoma patients diagnosed before the inception of the clinic.

CONCLUSIONS

This is, to our knowledge, the first example that consultation within a 2-week time-frame of GP referral impacts patient survival and the first evidence base behind Government guidelines for this particular cancer.