bluuebunny/crossref_metadata_2025 huggingface dataset:
Zinc finger protein STOP1 is critical for proton tolerance in
Arabidopsis
and coregulates a key gene in aluminum tolerance
Authors: Iuchi Satoshi , Koyama Hiroyuki , Iuchi Atsuko , Kobayashi Yasufumi , Kitabayashi Sadako , Kobayashi Yuriko , Ikka Takashi , Hirayama Takashi , Shinozaki Kazuo , Kobayashi Masatomo
Published: May 2007

Acid soil syndrome causes severe yield losses in various crop plants because of the rhizotoxicities of ions, such as aluminum (Al
3+
). Although protons (H
+
) could be also major rhizotoxicants in some soil types, molecular mechanisms of their tolerance have not been identified yet. One mutant that was hypersensitive to H
+
rhizotoxicity was isolated from ethyl methanesulfonate mutagenized seeds, and a single recessive mutation was found on chromosome 1. Positional cloning followed by genomic sequence analysis revealed that a missense mutation in the zinc finger domain in a predicted Cys
2
His
2
-type zinc finger protein, namely sensitive to proton rhizotoxicity (STOP)1, is the cause of hypersensitivity to H
+
rhizotoxicity. The STOP1 protein belongs to a functionally unidentified subfamily of zinc finger proteins, which consists of two members in
Arabidopsis
based on a Blast search. The
stop1
mutation resulted in no effects on cadmium, copper, lanthanum, manganese and sodium chloride sensitivitities, whereas it caused hypersensitivity to Al
3+
rhizotoxicity. This
stop1
mutant lacked the induction of the AtALMT1 gene encoding a malate transporter, which is concomitant with Al-induced malate exudation. There was no induction of
AtALMT1
by Al
3+
treatment in the
stop1
mutant. These results indicate that
STOP1
plays a critical role in
Arabidopsis
tolerance to major stress factors in acid soils.
Mechanisms for climate-induced mortality of fish populations in whole-lake experiments
Authors: Biro Peter A. , Post John R. , Booth David J.
Published: May 2007

The effects of climate change on plant and animal populations are widespread and documented for many species in many areas of the world. However, projections of climate impacts will require a better mechanistic understanding of ecological and behavioral responses to climate change and climate variation. For vertebrate animals, there is an absence of whole-system manipulative experiments that express natural variation in predator and prey behaviors. Here we investigate the effect of elevated water temperature on the physiology, behavior, growth, and survival of fish populations in a multiple whole-lake experiment, by using 17 lake-years of data collected over 2 years with differing average temperatures. We found that elevated temperatures in excess of the optimum reduced the scope for growth through reduced maximum consumption and increased metabolism in young rainbow trout,
Oncorhynchus mykiss
. Increased metabolism at high temperatures resulted in increased feeding activity (consumption) by individuals to compensate and maintain growth rates similar to that observed at cooler (optimum) temperatures. However, greater feeding activity rates resulted in greater vulnerability to predators that reduced survival to only half that of the cooler year. Our work therefore identifies temperature-dependent physiology and compensatory feeding behavior as proximate mechanisms for substantial climate-induced mortality in fish populations at the scale of entire populations and waterbodies.
Formation of native prions from minimal components
in vitro
Authors: Deleault Nathan R. , Harris Brent T. , Rees Judy R. , Supattapone Surachai
Published: May 2007

The conformational change of a host protein, PrP
C
, into a disease-associated isoform, PrP
Sc
, appears to play a critical role in the pathogenesis of prion diseases such as Creutzfeldt–Jakob disease and scrapie. However, the fundamental mechanism by which infectious prions are produced in neurons remains unknown. To investigate the mechanism of prion formation biochemically, we conducted a series of experiments using the protein misfolding cyclic amplification (PMCA) technique with a preparation containing only native PrP
C
and copurified lipid molecules. These experiments showed that successful PMCA propagation of PrP
Sc
molecules in a purified system requires accessory polyanion molecules. In addition, we found that PrP
Sc
molecules could be formed
de novo
from these defined components in the absence of preexisting prions. Inoculation of samples containing either prion-seeded or spontaneously generated PrP
Sc
molecules into hamsters caused scrapie, which was transmissible on second passage. These results show that prions able to infect wild-type hamsters can be formed from a minimal set of components including native PrP
C
molecules, copurified lipid molecules, and a synthetic polyanion.
Internal DNA pressure modifies stability of WT phage
Authors: Ivanovska Irena , Wuite Gijs , Jönsson Bengt , Evilevitch Alex
Published: May 2007

dsDNA in bacteriophages is highly stressed and exerts internal pressures of many atmospheres (1 atm = 101.3 kPa) on the capsid walls. We investigate the correlation between packaged DNA length in λ phage (78–100% of WT DNA) and capsid strength by using an atomic force microscope indentation technique. We show that phages with WT DNA are twice as strong as shorter genome mutants, which behave like empty capsids, regardless of high internal pressure. Our analytical model of DNA-filled capsid deformation shows that, because of DNA-hydrating water molecules, an osmotic pressure exists inside capsids that increases exponentially when the packaged DNA density is close to WT phage. This osmotic pressure raises the WT capsid strength and is approximately equal to the maximum breaking force of empty shells. This result suggests that the strength of the shells limits the maximal packaged genome length. Moreover, it implies an evolutionary optimization of WT phages allowing them to survive greater external mechanical stresses in nature.
Oxygen metabolism and reactive oxygen species cause chromosomal rearrangements and cell death
Authors: Ragu Sandrine , Faye Gérard , Iraqui Ismail , Masurel-Heneman Amélie , Kolodner Richard D. , Huang Meng-Er
Published: May 2007

The absence of Tsa1, a key peroxiredoxin that functions to scavenge H
2
O
2
in
Saccharomyces cerevisiae
, causes the accumulation of a broad spectrum of mutations including gross chromosomal rearrangements (GCRs). Deletion of
TSA1
also causes synthetic lethality in combination with mutations in
RAD6
and several key genes involved in DNA double-strand break repair. In the present study we investigated the causes of GCRs and cell death in these mutants.
tsa1
-associated GCRs were independent of the activity of the translesion DNA polymerases ζ, η, and Rev1. Anaerobic growth reduced substantially GCR rates of WT and
tsa1
mutants and restored the viability of
tsa1 rad6
,
tsa1 rad51
, and
tsa1 mre11
double mutants. Anaerobic growth also reduced the GCR rate of
rad27
,
pif1
, and
rad52
mutants, indicating a role of reactive oxygen species in GCR formation in these mutants. In addition, deletion of
TSA1
or H
2
O
2
treatment of WT cells resulted in increased formation of Rad52 foci, sites of repair of multiple DNA lesions. H
2
O
2
treatment also induced the GCRs. Our results provide
in vivo
evidence that oxygen metabolism and reactive oxygen species are important sources of DNA damages that can lead to GCRs and lethal effects in
S. cerevisiae
.
[18F]MK-9470, a positron emission tomography (PET) tracer forin vivohuman PET brain imaging of the cannabinoid-1 receptor
Authors: Burns H. Donald , Van Laere Koen , Sanabria-Bohórquez Sandra , Hamill Terence G. , Bormans Guy , Eng Wai-si , Gibson Ray , Ryan Christine , Connolly Brett , Patel Shil , Krause Stephen , Vanko Amy , Van Hecken Anne , Dupont Patrick , De Lepeleire Inge , Rothenberg Paul , Stoch S. Aubrey , Cote Josee , Hagmann William K. , Jewell James P. , Lin Linus S. , Liu Ping , Goulet Mark T. , Gottesdiener Keith , Wagner John A. , de Hoon Jan , Mortelmans Luc , Fong Tung M. , Hargreaves Richard J.
Published: May 2007

[18F]MK-9470 is a selective, high-affinity, inverse agonist (human IC50, 0.7 nM) for the cannabinoid CB1 receptor (CB1R) that has been developed for use in human brain imaging. Autoradiographic studies in rhesus monkey brain showed that [18F]MK-9470 binding is aligned with the reported distribution of CB1 receptors with high specific binding in the cerebral cortex, cerebellum, caudate/putamen, globus pallidus, substantia nigra, and hippocampus. Positron emission tomography (PET) imaging studies in rhesus monkeys showed high brain uptake and a distribution pattern generally consistent with that seen in the autoradiographic studies. Uptake was blocked by pretreatment with a potent CB1 inverse agonist, MK-0364. The ratio of total to nonspecific binding in putamen was 4–5:1, indicative of a strong specific signal that was confirmed to be reversible via displacement studies with MK-0364. Baseline PET imaging studies in human research subject demonstrated behavior of [18F]MK-9470 very similar to that seen in monkeys, with very good test–retest variability (7%). Proof of concept studies in healthy young male human subjects showed that MK-0364, given orally, produced a dose-related reduction in [18F]MK-9470 binding reflecting CB1R receptor occupancy by the drug. Thus, [18F]MK-9470 has the potential to be a valuable, noninvasive research tool for thein vivostudy of CB1R biology and pharmacology in a variety of neuropsychiatric disorders in humans. In addition, it allows demonstration of target engagement and noninvasive dose-occupancy studies to aid in dose selection for clinical trials of CB1R inverse agonists.
Cooperative light-induced molecular movements of highly ordered azobenzene self-assembled monolayers
Authors: Pace Giuseppina , Ferri Violetta , Grave Christian , Elbing Mark , von Hänisch Carsten , Zharnikov Michael , Mayor Marcel , Rampi Maria Anita , Samorì Paolo
Published: May 2007

Photochromic systems can convert light energy into mechanical energy, thus they can be used as building blocks for the fabrication of prototypes of molecular devices that are based on the photomechanical effect. Hitherto a controlled photochromic switch on surfaces has been achieved either on isolated chromophores or within assemblies of randomly arranged molecules. Here we show by scanning tunneling microscopy imaging the photochemical switching of a new terminally thiolated azobiphenyl rigid rod molecule. Interestingly, the switching of entire molecular 2D crystalline domains is observed, which is ruled by the interactions between nearest neighbors. This observation of azobenzene-based systems displaying collective switching might be of interest for applications in high-density data storage.
Three-dimensional architecture of murine rod outer segments determined by cryoelectron tomography
Authors: Nickell Stephan , Park Paul S.-H. , Baumeister Wolfgang , Palczewski Krzysztof
Published: May 2007

The rod outer segment (ROS) of photoreceptor cells houses all components necessary for phototransduction, a set of biochemical reactions that amplify and propagate a light signal. Theoretical approaches to quantify this process require precise information about the physical boundaries of the ROS. Dimensions of internal structures within the ROS of mammalian species have yet to be determined with the precision required for quantitative considerations. Cryoelectron tomography was utilized to obtain reliable three-dimensional morphological information about this important structure from murine retina. Vitrification of samples permitted imaging of the ROS in a minimally perturbed manner and the preservation of substructures. Tomograms revealed the characteristic highly organized arrangement of disc membranes stacked on top of one another with a surrounding plasma membrane. Distances among the various membrane components of the ROS were measured to define the space available for phototransduction to occur. Reconstruction of segments of the ROS from single-axis tilt series images provided a glimpse into the three-dimensional architecture of this highly differentiated neuron. The reconstructions revealed spacers that likely maintain the proper distance between adjacent discs and between discs and the plasma membrane. Spacers were found distributed throughout the discs, including regions that are distant from the rim region of discs.
Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses
Authors: Precopio Melissa L. , Betts Michael R. , Parrino Janie , Price David A. , Gostick Emma , Ambrozak David R. , Asher Tedi E. , Douek Daniel C. , Harari Alexandre , Pantaleo Giuseppe , Bailer Robert , Graham Barney S. , Roederer Mario , Koup Richard A.
Published: May 2007

Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8+ T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus–specific CD8+ T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon γ, interleukin 2, macrophage inflammatory protein 1β, and tumor necrosis factor α after antigenic stimulation. Responding CD8+ T cells exhibited an unusual phenotype (CD45RO−CD27intermediate). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8+ T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated.
A normal form for elliptic curves
Authors: Edwards Harold
Published: May 2007

The normal form

x
2

+

y
2

=

a
2

+

a
2

x
2

y
2

x^2 + y^2 = a^2 + a^2x^2y^2

for elliptic curves simplifies formulas in the theory of elliptic curves and functions. Its principal advantage is that it allows the addition law, the group law on the elliptic curve, to be stated explicitly
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper X equals StartFraction 1 Over a EndFraction dot StartFraction x y Superscript prime Baseline plus x prime y Over 1 plus x y x prime y Superscript prime Baseline EndFraction comma upper Y equals StartFraction 1 Over a EndFraction dot StartFraction y y Superscript prime Baseline minus x x Superscript prime Baseline Over 1 minus x y x prime y Superscript prime Baseline EndFraction period">

X
=

1
a

⋅

x

y
′

+

x
′

y

1
+
x
y

x
′

y
′

,

Y
=

1
a

⋅

y

y
′

−
x

x
′

1
−
x
y

x
′

y
′

.

X = \frac 1a \cdot \frac {xy’ + x’y}{1 + xyx’y’}, \quad Y = \frac 1a \cdot \frac {yy’ - xx’}{1 - xyx’y’}.

\]
The

j
j

-invariant of an elliptic curve determines 24 values of

a
a

for which the curve is equivalent to

x
2

+

y
2

=

a
2

+

a
2

x
2

y
2

x^2 + y^2 = a^2 + a^2x^2y^2

, namely, the roots of

(

x
8

+
14

x
4

(x^8 + 14x^4

+
1

)
3

−

j
16

(

x
5

−
x

)
4

+ 1)^3 - \frac j{16}(x^5 - x)^4

. The symmetry in

x
x

and

y
y

implies that the two transcendental functions

x
(
t
)

x(t)

and

y
(
t
)

y(t)

that parameterize

x
2

+

y
2

=

a
2

+

a
2

x
2

y
2

x^2 + y^2 = a^2 + a^2x^2y^2

in a natural way are essentially the same function, just as the parameterizing functions

sin
⁡
t

\sin t

and

cos
⁡
t

\cos t

of the circle are essentially the same function. Such a parameterizing function is given explicitly by a quotient of two simple theta series depending on a parameter

τ
\tau

in the upper half plane.
Asymptotic analysis for shear waves in a fluid‐filled borehole
Authors: Yao Gui‐jin , Wang Ke‐xie , Ma Jun , Yang Bao‐jun , Zhang Hai‐rong
Published: May 2007

We focus on the theoretical analysis of the resonance phenomena and the geometric attenuation behaviour of critical refracted shear waves propagating along a fluid‐filled borehole. Using integration by parts, we asymptotically expand the vertical branch‐cut integral of shear waves in an infinite series related to each order of the derivative of the response function of the formation. It is proved that the vertical branch‐cut integral of shear waves at large offsets consists mainly of the contribution of the second asymptotic series, which is related to the first derivative of the response function of the formation at the shear branch point. Using the asymptotic expansion, we develop a simplified amplitude expression for shear waves, and the resonant frequency formula. The validity of the resonance frequencies obtained by the resonant frequency formula is verified numerically by comparison with the corresponding frequencies of the numerical integral results. We also give a rational explanation for the phenomenon of two peaks appearing within each resonant peak zone: i.e. that these are the contributions of the constructive interference of the shear waves and the mode poles.
The trajectory of minor stroke recovery for men and their female spousal caregivers: literature review
Authors: Green Theresa L. , King Kathryn M.
Published: May 2007

Title. The trajectory of minor stroke recovery for men and their female spousal caregivers: literature review

Aim.  This paper is a report of a narrative review to examine the current state of knowledge regarding the impact of minor stroke on male patients and their female spousal caregivers’ recovery trajectory and quality of life.

Background.  Minor stroke survivors are often discharged early in the recovery process. The perception of the healthcare community that these patients and their female spousal caregivers will experience an uneventful recovery may lead to inadequate preparation for the postdischarge period.

Methods.  A range of databases was searched to identify papers addressing ‘minor stroke’, ‘transitions’, ‘quality of life’, ‘chronic disease’, ‘caregivers’ and ‘spouse caregivers’, including AARP Ageline, AMED, CINAHL, Evidence Based Medicine Reviews, MEDLINE and PsychInfo. Papers published in English from 1990 to December 2006 were included. Thirty‐four papers were in the final data set.

Results.  Minor stroke survivors and their female spousal caregivers may experience major challenges in adaptations postdischarge. The trajectory of minor stroke recovery may necessitate a re‐evaluation of life plans, rethinking of priorities and integration of resulting disabilities into current and emerging life situations for both stroke survivors and their female spousal caregivers. In many cases these adaptations are compounded by transitions associated with the normal ageing process.

Conclusion.  While there is extensive literature on stroke recovery and the role of caregivers in general, there is little available describing the recovery of minor stroke survivors in relation to the normal ageing process. Further research is needed examining recovery from a transitional perspective, to support nurses and other health professionals discharge planning.
Driven by the West Wind Drift? A synthesis of southern temperate marine biogeography, with new directions for dispersalism
Authors: Waters Jonathan M.
Published: May 2007

Aim Twentieth century biogeographers developed intriguing hypotheses involving West Wind Drift dispersal of Southern Hemisphere biota, but such models were largely abandoned in favour of vicariance following the development of plate tectonic theory. Here I present a synthesis of southern temperate marine biogeography, and suggest some new directions for phylogeographic research.

Location The southern continents, formerly contiguous components of Gondwana, are now linked only by ocean currents driven by the West Wind Drift.

Methods While vicariance theory certainly facilitates the development of testable hypotheses, it does not necessarily follow that vicariance explains much of contemporary southern marine biogeography. To overcome the limitations of narratives that simplyassumevicariance or dispersal, it is essential for analyses to test biogeographic hypotheses by incorporating genetic, ecological and geological data.

Results Recent molecular studies have provided strong evidence for dispersal, but relatively little evidence for the biogeographic role of plate tectonics in distributing southern marine taxa. Despite confident panbiogeographic claims to the contrary, molecular and ecological studies of buoyant macroalgae, such asMacrocystis, indicate that dispersal predominates. Ironically, some of the better supported evidence for marine vicariance in southern waters has little or nothing to do with plate tectonics. Rather, it involves far more localized and recent vicariant models, such as the isolating effect of the Bassian Isthmus during Pleistocene low sea‐level stands (Nerita).

Main conclusions Recent phylogeographic studies of southern marine taxa (e.g.DilomaandParvulastra) imply that passive rafting cannot be ignored as an important mechanism of long‐distance dispersal. I outline a new direction for southern hemisphere phylogeography, involving genetic analyses of bull‐kelp (Durvillaea) and its associated holdfast invertebrate communities.
Testing biogeographical hypotheses in space and time: faunal relationships of the putative ancient Lake Egˇirdir in Asia Minor
Authors: Wilke Thomas , Albrecht Christian , Anistratenko Vitaliy V. , Sahin Serap Kosal , Yildirim Mehmet Zeki
Published: May 2007

Aim The aims of this study are to establish a multi‐locus phylogeny‐based hypothesis for the biogeographical relationship of gastropods from the putative ancient Lake Egˇirdir, to test the respective null hypothesis, to estimate the timing of biogeographical events based on independent molecular clock approaches, and to interpret the data with respect to the putative ancient character of Lake Egˇirdir.

Location Lake Egˇirdir, western Taurus Lake District, Turkey.

Methods DNA sequences from the putatively only extant endemic taxon of Lake Egˇirdir,Falsipyrgula pfeiferi, as well as representatives of other pyrgulinid genera from Europe and western Asia are used for phylogenetic analyses based on Bayesian inference. The respective null hypothesis is tested utilizing parametric bootstrapping. The timing of evolutionary events is estimated based on two independent molecular clock approaches, which involve the modelling of judicious errors associated with branch‐length calculations and calibration points.

Results Bayesian inference indicates a very close relationship between the Lake Egˇirdir and Ponto‐Caspian taxa. Parametric bootstrapping rejects the null hypothesis that these taxa are not monophyletic (P ≤ 0.01). The alternative hypothesis, namely monophyly of the Ponto‐Caspian and Egˇirdir taxa, can therefore be accepted. The two independent molecular clock approaches show diversion times for the Ponto‐Caspian/Egˇirdir taxa of 0.42 ± 0.18 and 0.43 ± 0.63 Ma.

Main conclusions The present study shows that there is no close biogeographical affiliation between the probably only remaining endemic taxon of Lake Egˇirdir and taxa from central Europe or the Balkan region. Instead, there is a very close and relatively young (i.e. late Pleistocene) biogeographical relationship with the Ponto‐Caspian pyrgulinids. However, fossil and comparative data from other invertebrates indicate that biogeographical connections between Lake Egˇirdir and the Ponto‐Caspian region existed during various time periods, i.e. the Miocene/Pliocene, early Pleistocene, and late Pleistocene. Acknowledging the still‐restricted knowledge of the evolutionary history of the lake, the data presented here do not reject the putative ancient status of Lake Egˇirdir. Future studies utilizing endemic taxa of other lakes in the region need to show whether the western Taurus Lake District represents a melting pot of Pleistocene refuge biodiversity from different regions, and whether the admixture of divergent lineages has created a genetically distinct set of taxa that would warrant the designation of the area as a unique biogeographical subregion.
Factors influencing change in health‐related quality of life after liver transplantation
Authors: Estraviz Begoña , Quintana José M. , Valdivieso Andrés , Bilbao Amaia , Padierna Angel , De Urbina Jorge Ortiz , Sarabia Sebastian
Published: May 2007

Abstract: Objective: To assess health‐related quality of life (HRQoL) in patients following liver transplantation and the factors associated with HRQoL variation.

Methods and Materials: Sociodemographic and clinical data were collected for 60 consecutive patients activated for liver transplantation in a single hospital. Patients were classified according to the severity of the cirrhosis (Child–Pugh class) and disease etiology (alcoholic cirrhosis, viral cirrhosis, cholestatic diseases, and hepatocarcinoma). HRQoL was assessed by three different questionnaires: the Health Survey Short Form 36 (SF‐36), the Hospital Anxiety and Depression Scale (HAD), and a specific‐symptom questionnaire. Questionnaires were completed during the pre‐operative period and six months after transplantation.

Results: In the pre‐operative period, patients with Child A had higher mean levels of HRQoL than did those in other groups. At six months following transplantation, there were no significant differences among the groups, largely because gains obtained by patients with Child B and C were much greater than those attained by patients with Child A. Across the four etiological groups, there were significant differences in all domains of the three questionnaires, except SF‐36‐bodily pain and HAD‐anxiety, prior to transplantation, because patients with hepatocarcinoma had much better HRQoL. After transplantation, there were no differences because patients with viral and alcohol‐induced cirrhosis achieved greater gains with respect to the neoplastic group. During the pre‐operative period, the scores for all areas of the SF‐36 and for all groups were below the general population normalized score of 50 (except for patients with Child class A and those affected with hepatocarcinoma). Six‐months post‐transplantation, the scores on most of the domains remained below 50, except for certain mental areas in which higher scores were attained.

Conclusions: Health‐related quality of life is influenced by the severity and etiology of cirrhosis—patients with Child class C and those with alcoholic or viral cirrhosis have the poorest quality of life. There were no differences observed among the groups after the transplantation, as the patients with the lowest HRQoLs prior to surgery demonstrated greater gains in HRQoL associated with liver transplantation.
Can a rural community‐based work‐related activity program make a difference for chronic pain‐disabled injured workers?
Authors: Dunstan Debra A. , Covic Tanya
Published: May 2007

Objective:  To assess the effectiveness of a clinical guidelines‐informed multidisciplinary work‐related activity program, and to improve the physical, psychological and occupational functioning of chronic pain‐disabled injured workers.

Design:  An uncontrolled, repeated‐measures, pilot study was conducted.

Setting:  The intervention was delivered in a community setting in regional New South Wales.

Participants:  Participants (n = 30), mean age of 41 years, had a compensable musculoskeletal injury: 60% were male, 63% had back injuries; the mean time off work was 13 months.

Intervention:  A cognitive‐behavioural, interdisciplinary intervention was delivered using a multi‐contributor provider model (a clinical psychologist and physiotherapist from separate practices, working in liaison with the participant's occupational rehabilitation provider and treating doctor). Groups of six participants attended for one half day per week for six weeks.

Main outcome measures:  The outcome measures included: physical functioning, pain intensity and psychological variables, which were assessed pre‐ and post‐program; and medical certification and work participation, which was recorded pre‐program and at six‐month follow up.

Results:  Significant gains were made in pain intensity, physical and psychological functioning, and medical certification. The mean effect size of the intervention was medium to large (
d = 0.70). There was no significant change in employment status at six‐month follow up.

Conclusions:  The results of this pilot study suggest that independent, rural or community‐based practitioners, working collaboratively using an integrated treatment program, can produce positive outcomes for pain‐disabled injured workers, and achieve results similar to those reported by metropolitan‐based pain clinics.
Australian rural adolescents' experiences of accessing psychological help for a mental health problem
Authors: Boyd Candice , Francis Kristy , Aisbett Damon , Newnham Krystal , Sewell Jessica , Dawes Graham , Nurse Sarah
Published: May 2007

Objective:  This study aims to explore Australian rural adolescents' experiences of accessing help for a mental health problem in the context of their rural communities.

Design and setting:  A qualitative research design was used whereby university students who had sought help for a mental health problem during their adolescence were interviewed about their experiences. Interviews were conducted face‐to‐face at the university.

Main outcome measures:  A semi‐structured interview schedule was designed around the study's main research questions. Audio‐taped interviews were transcribed and thematically coded using a constant comparative method.

Participants:  Participants were first‐year undergraduate psychology students between the ages of 17 and 21 years who sought help for a mental health issue during their adolescence and who at that time resided in a rural area.

Results:  Participants highlighted various barriers to seeking help for mental health problems in the context of a rural community, including: social visibility, lack of anonymity, a culture of self‐reliance, and social stigma of mental illness. Participants' access to help was primarily school‐based, and participants expressed a preference for supportive counselling over structured interventions. Characteristics of school‐based helpers that made them approachable included: ‘caring’, ‘nonjudgemental’, ‘genuine’, ‘young’, and able to maintain confidentiality.

Conclusions:  The findings support previous research that reveals barriers to help seeking for mental health problems that are unique to the culture of rural communities. The study raises questions about the merit of delivery of primary mental health care to young people via GPs alone and suggests that school‐based counsellors be considered as the first step in a young person's access to mental health care.
Depression and remoteness from health services in South Australia
Authors: Goldney Robert D. , Taylor Anne W. , Bain Marcus A.
Published: May 2007

Objective:  To determine whether the prevalence of depression, its associated quality of life, treatment and mental health literacy about depression varied according to accessibility to health services.

Design:  Face‐to‐face interviews with a random and representative sample of the South Australian population (aged ≥ 15 years) were conducted between March and June 2004, with the respondents stratified using the Accessibility and Remoteness Index of Australia into categories of ‘highly accessible’, ‘accessible’, and ‘moderately accessible and remote’.

Results:  From 4700 households selected, 3015 participants were interviewed (65.9% response rate). The prevalence of major depression and other depressions was not significantly different between each of the categories, although there was a trend for those from moderately accessible and remote areas to be less depressed overall. A significantly lower proportion of respondents from moderately accessible and remote locations reported that they had family or close friends who had suffered from symptoms consistent with depression, or that they had ever had treatment for those symptoms. However, there was no significant difference between the groups in those who had ever had or who were currently taking antidepressant medication. For those who were depressed, a significantly higher proportion from the accessible, and moderately accessible and remote regions had seen a community or district health service, social worker or other counsellor as compared with those from the highly accessible area.

Conclusions:  These findings indicate that depression is no more prevalent in less accessible regions of South Australia, and that when it is present, its treatment, in terms of antidepressants, which can be considered as a proxy marker for the overall management of depression, is similar to treatment in more accessible areas.
Has natural selection in human populations produced two types of metabolic syndrome (with and without fatty liver)?
Authors: Caldwell Stephen H , Ikura Yoshihiro , Iezzoni Julia C , Liu Zhenqi
Published: May 2007

Fatty liver is closely related to the development of the insulin resistance syndrome that largely results from abnormal insulin signaling in three major organs: (i) skeletal muscle in which insulin sensitivity depends on fat content and metabolic activity (exercise); (ii) adipose tissue, which serves as a reservoir of energy in the form of triglycerides; and (iii) the liver, which variably serves as a source or storage site of carbohydrates and lipids. In many respects, the fatty liver resembles a mixture of brown adipose tissue (microvesicular steatosis) and white adipose tissue (macrovesicular steatosis) including the stages of fatty droplet accumulation, and the expression of uncoupling proteins and perilipin‐like substances. Furthermore, the development of an inflammatory infiltrate and the increased production of cytokines as occurs in adipose tissue, suggest that the liver in some individuals serves as an extension of adipose tissue. Moreover, current evidence indicates that these morphological changes represent altered gene expression similar to that of adipocytes. However, fatty liver does not appear to be a uniform feature of the metabolic syndrome and there is substantial variation in humans in the development of fatty liver independent of insulin resistance. In this regard, the variable development of fatty liver in Palmipedes (migratory fowl) and its close relationship to skeletal muscle utilization of fatty acids, lipoprotein metabolism and thermoregulation are instructive. The predilection to non‐alcoholic fatty liver disease among some varieties of Palmipedes suggests that the development of fatty liver represents an adaptive process, closely integrated with skeletal muscle fat utilization and adipose tissue distribution, and facilitates survival in a very cold, resource‐scarce environment. Variation in human populations with metabolic syndrome likewise suggests that the trait evolved in populations exposed in ancient times to different environmental challenges and, because the liver plays a central role in lipid metabolism, the presence or absence of fatty liver is likely to be integrated with insulin sensitivity in other target organs and with lipoprotein metabolism.
Role of mitochondria in non‐alcoholic fatty liver disease
Authors: Pessayre Dominique
Published: May 2007

Mitochondrial dysfunction is involved in the three stages of the transition from lack of exercise and excessive food intake to insulin resistance, diabetes and non‐alcoholic steatohepatitis (NASH). In muscle, lack of exercise, a fat‐rich diet, a polymorphism in peroxisome proliferator‐activated receptor γ coactivator‐1 (PGC‐1), and possibly age‐related mitochondrial DNA (mtDNA) mutations may variously combine their effects to decrease PGC‐1 expression, mitochondrial biogenesis and fat oxidation. Together with excessive food intake, insufficient fat oxidation causes fat accumulation and cellular stress in myocytes. The activation of Jun N‐terminal kinase and protein kinase C‐θ triggers the serine phosphorylation and inactivation of the insulin receptor substrate, and hampers the insulin‐mediated translocation of glucose transporter‐4 to the plasma membrane. Initially, the trend for increased blood glucose increases insulin secretion by pancreatic β‐cells. High plasma insulin levels compensate for insulin resistance in muscle and maintain normal blood glucose levels. Eventually, however, increased uncoupling protein‐2 expression and possibly acquired mtDNA mutations in pancreatic β‐cells can blunt glucose‐mediated adenosine triphosphate (ATP) formation and insulin secretion, to cause diabetes in some patients. High plasma glucose and/or insulin levels induce hepatic lipogenesis and cause hepatic steatosis. In fat‐engorged hepatocytes, several vicious cycles involving tumor necrosis factor‐α, reactive oxygen species (ROS), peroxynitrite, and lipid peroxidation products alter respiratory chain polypeptides and mtDNA, thus partially blocking the flow of electrons in the respiratory chain. The overreduction of upstream respiratory chain complexes increases mitochondrial ROS and peroxynitrite formation. Oxidative stress increases the release of lipid peroxidation products and cytokines, which together trigger the liver lesions of NASH.
Role of innate immune response in liver regeneration
Authors: Iimuro Yuji , Seki Ekihiro , Son Gakuhei , Tsutsui Hiroko , Nakanishi Kenji , Fujimoto Jiro
Published: May 2007

Liver regeneration following partial hepatectomy (PH) requires several steps including innate immune responses, particularly interleukin‐6 (IL‐6) and tumor necrosis factor‐(TNF‐)α production by Kupffer cells, although the activation processes are still unknown. Toll‐like receptors (TLR) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLR. When the receptors are activated, cells bearing TLR produce various pro‐nflammatory cytokines in a MyD88‐dependent manner. The authors investigated whether TLR/MyD88 signaling is critical for induction of innate immune responses after PH. In Myd88‐/‐ mice after PH, induction of expression of immediate early genes involved in hepatocyte replication and phosphorylation of signal transducer and activators of transcription 3 (STAT3) in the liver, and production of TNF‐α/IL‐6 by and activation of NF‐κB in the Kupffer cells were grossly subnormal and were associated with impaired liver regeneration, while TLR2, 4 and 9, which recognize Gram‐negative and ‐positive bacterial products, are not essential for NF‐κB activation and IL‐6 production after PH. In conclusion, the TLR/MyD88 pathway is essential for liver restoration after PH, particularly its early phase.
Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis
Authors: Kisseleva Tatiana , Brenner David A
Published: May 2007

Liver fibrosis is caused by many chronic diseases. Liver injury results in activation of collagen‐producing cells and excessive deposition of extracellular matrix proteins. This process is orchestrated by many cell types. Hepatocytes apoptosis and inflammatory cells trigger secretion of profibrogenic and proinflammatory cytokines, such as transforming growth factor‐β1, angiotensin II, leptin, which in turn activates hepatic stellate cells, the major source of collagen type I. This review is focused on recent progress in the study of the pathogenesis of liver fibrosis.
Molecular mechanisms of hepatic fibrogenesis
Authors: Parsons Christopher J , Takashima Motoki , Rippe Richard A
Published: May 2007

Liver fibrosis, a wound‐healing response to a variety of chronic stimuli, is characterized by excessive deposition of extracellular matrix (ECM) proteins, of which type I collagen predominates. This alters the structure of the liver leading to organ dysfunction. The activated hepatic stellate cell (HSC) is primarily responsible for excess collagen deposition during liver fibrosis. Two important aspects are involved in mediating the fibrogenic response: first the HSC becomes directly fibrogenic by synthesizing ECM proteins; second, the activated HSC proliferates, effectively amplifying the fibrogenic response. Although the precise mechanisms responsible for HSC activation remain elusive, substantial insight is being gained into the molecular mechanisms responsible for ECM production and cell proliferation in the HSC. The activated HSC becomes responsive to both proliferative (platelet‐derived growth factor) and fibrogenic (transforming growth factor‐β[TGF‐β]) cytokines. It is becoming clear that these cytokines activate both mitogen‐activated protein kinase (MAPK) signaling, involving p38, and focal adhesion kinase–phosphatidylinositol 3‐kinase–Akt–p70 S6 kinase (FAK‐PI3K‐Akt‐p70S6K) signaling cascades. Together, these regulate the proliferative response, activating cell cycle progression as well as collagen gene expression. In addition, signaling by both TGF‐β, mediated by Smad proteins, and p38 MAPK influence collagen gene expression. Smad and p38 MAPK signaling have been found to independently and additively regulate α1(I) collagen gene expression by transcriptional activation while p38 MAPK, but not Smad signaling, increases α1(I) collagen mRNA stability, leading to increased synthesis and deposition of type I collagen. It is anticipated that by understanding the molecular mechanisms responsible for HSC proliferation and excess ECM production new therapeutic targets will be identified for the treatment of liver fibrosis.
Non‐alcoholic steatohepatitis and hepatocellular carcinoma: Lessons from hepatocyte‐specific phosphatase and tensin homolog (PTEN)‐deficient mice
Authors: Watanabe Sumio , Horie Yasuo , Kataoka Ei , Sato Wataru , Dohmen Takahiro , Ohshima Shigetoshi , Goto Takashi , Suzuki Akira
Published: May 2007

Non‐alcoholic steatohepatitis (NASH) is a term used to describe a spectrum of conditions characterized by histological findings of hepatic macrovesicular steatosis with inflammation in individuals who consume little or no alcohol. The NASH patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Hepatocyte‐specific phosphatase and tensin homolog (PTEN)‐deficient mice (PTEN‐deficient mice), which the authors had generated previously, showed massive hepatomegaly and steatohepatitis with triglyceride accumulation followed by liver fibrosis and HCC, a phenotype similar to human NASH. Therefore, it was shown that PTEN deficiency in hepatocytes could induce hepatic steatosis, inflammation, fibrosis and tumors and that PTEN‐deficient mice were a useful animal model for not only the understanding of the pathogenesis of NASH but also the development of treatment for NASH.
Role of apoptosis in acetaminophen hepatotoxicity
Authors: Kon Kazuyoshi , Ikejima Kenichi , Okumura Kyoko , Aoyama Tomonori , Arai Kumiko , Takei Yoshiyuki , Lemasters John J , Sato Nobuhiro
Published: May 2007

Acetaminophen overdose causes liver injury by mechanisms involving glutathione depletion, oxidative stress and mitochondrial dysfunction. The role of apoptosis in acetaminophen‐induced cell killing is still controversial. Here, our aim was to evaluate the mitochondrial permeability transition (MPT) as a key factor in acetaminophen‐induced necrotic and apoptotic killing of primary cultured mouse hepatocytes. Acetaminophen (10 μmol/L) induced necrotic killing in approximately 50% of hepatocytes after 6 h and cyclosporin A (CsA), MPT inhibitor, temporarily decreased necrotic killing after 6 h, but cytoprotection was lost after 16 h. Confocal microscopy revealed mitochondrial depolarization and inner membrane permeabilization at approximately 4.5 h after acetaminophen. CsA delayed these changes indicative of the MPT to about 11 h after acetaminophen. TUNEL labeling and caspase 3 activation also increased after acetaminophen. Fructose (20 mmol/L, an ATP‐generating glycolytic substrate) plus glycine (5 mmol/L, a membrane stabilizing amino acid) prevented nearly all necrotic cell killing but paradoxically increased apoptosis. In conclusion, acetaminophen induces the MPT and ATP‐depletion‐dependent necrosis or caspase‐dependent apoptosis as determined, in part, by ATP availability from glycolysis.
Allelic Association and Recombination Hotspots in the Mucin Gene (MUC) Complex on Chromosome 11p15.5
Authors: Rousseau K. , Byrne C. , Griesinger G. , Leung A. , Chung A. , Hill A. S. , Swallow D. M.
Published: May 2007

A family of four highly polymorphic genes encoding secreted gel forming mucins is located in the middle of a recombination rich region of the short arm of chromosome 11 (11p15.5; tel MUC6‐MUC2‐MUC5AC‐MUC5B cen; approx. 400 kb). These genes are of interest as risk factors for inflammatory diseases of the epithelia, and we have for example reported association of a VNTR polymorphism of the major mucin domain of MUC2 with asthma, despite the fact that MUC2 is not a major respiratory mucin. To understand the significance of this and other mucin gene associations it is important to describe the patterns of linkage disequilibrium (LD) across this chromosomal region, which is still incomplete on HapMap and the UCSC Golden Path sequence. Our previous studies on the 40 core CEPH families provided direct evidence for several recombination events within the immediate region of the gene complex. This study examines these recombination events in more detail, and also the patterns of LD across the gene complex. We refine the location of the breakpoints, and the combined data suggest two probable recombination hotspots. Three breakpoints are located between MUC6 and MUC2: there is no association between MUC6 and MUC2, and the data collected here, combined with that publicly available, maps a hotspot to a region of 4 kb. The other recombinants map between MUC2 and intron 8 of MUC5B. Relatively strong LD is detected between MUC2 and MUC5AC, and although 10/70 of the chromosomes tested shared a common haplotype, which extends from MUC2 to MUC5B, statistically significant association was not detected between MUC2 and the markers tested in MUC5B. We discuss the possibility that the previously reported association between MUC2 and asthma is most likely attributable to association with functional variation in MUC5AC, which encodes one of the two major mucins expressed in both healthy and diseased airways.
BUILDING A BRIDGE TO THE PAST: ARCHAEOMETRY AT THE IPEN REACTOR
Authors: DELGADO M. , OLIVERA P. , MONTOYA E. , BUSTAMANTE A.
Published: May 2007

Neutron activation analysis has contributed to research in Peru in different scientific fields, particularly in archaeometry. In archaeometry, applications include the characterization of copper alloy artefacts from the tomb of El Señor de Sican to determine production methods, ceramics from the Wari Culture to study production, and distribution of Middle Horizon pottery in Cuzco, ceramics from Villa El Salvador to determine production groups, and obsidian source analysis.