bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic coregulation of age of female sexual maturation and lifespan through circulating IGF1 among inbred mouse strains
Authors: Yuan Rong , Meng Qingying , Nautiyal Jaya , Flurkey Kevin , Tsaih Shirng-Wern , Krier Rebecca , Parker Malcolm G. , Harrison David E. , Paigen Beverly
Published: May 2012

We previously reported that mouse strains with lower circulating insulin-like growth factor 1 (IGF1) level at 6 mo have significantly extended longevity. Here we report that strains with lower IGF1 have significantly delayed age of female sexual maturation, measured by vaginal patency (VP). Among strains with normal lifespans (mean lifespan >600 d), delayed age of VP associated with greater longevity (
P =
0.015), suggesting a genetically regulated tradeoff at least partly mediated by IGF1. Supporting this hypothesis, C57BL/6J females had 9% lower IGF1, 6% delayed age of VP, and 24% extended lifespan compared with C57BL/6J.C3H/HeJ-Igf1, which carries a C3H/HeJ allele on chromosome (Chr) 10 that increases IGF1. To identify genetic loci/genes that regulate female sexual maturation, including loci that mediate lifespan tradeoffs, we performed haplotype association mapping for age of VP and identified significant loci on Chrs 4 (
Vpq1
) and 16 (
Vpq2
and
3
). At each locus, wild-derived strains share a unique haplotype that associates with delayed VP. Substitution of Chr 16 of C57BL/6J with Chr 16 from a wild-derived strain significantly reduced IGF1 and delayed VP. Strains with a wild-derived allele at
Vpq3
have significantly extended longevity compared with strains with other alleles. Bioinformatic analysis identified
Nrip1
at
Vpq3
as a candidate gene.
Nrip1
−/−
females have significantly reduced IGF1 and delayed age of VP compared with
Nrip1
+/+
females. We conclude that IGF1 may coregulate female sexual maturation and longevity; wild-derived strains carry specific alleles that delay sexual maturation; and
Nrip1
is involved in regulating sexual maturation and may affect longevity by regulating IGF1 level.
Direct observation of turbulent magnetic fields in hot, dense laser produced plasmas
Authors: Mondal Sudipta , Narayanan V. , Ding Wen Jun , Lad Amit D. , Hao Biao , Ahmad Saima , Wang Wei Min , Sheng Zheng Ming , Sengupta Sudip , Kaw Predhiman , Das Amita , Kumar G. Ravindra
Published: May 2012

Turbulence in fluids is a ubiquitous, fascinating, and complex natural phenomenon that is not yet fully understood. Unraveling turbulence in high density, high temperature plasmas is an even bigger challenge because of the importance of electromagnetic forces and the typically violent environments. Fascinating and novel behavior of hot dense matter has so far been only indirectly inferred because of the enormous difficulties of making observations on such matter. Here, we present direct evidence of turbulence in giant magnetic fields created in an overdense, hot plasma by relativistic intensity (10
18
W/cm
2
) femtosecond laser pulses. We have obtained magneto-optic polarigrams at femtosecond time intervals, simultaneously with micrometer spatial resolution. The spatial profiles of the magnetic field show randomness and their
k
spectra exhibit a power law along with certain well defined peaks at scales shorter than skin depth. Detailed two-dimensional particle-in-cell simulations delineate the underlying interaction between forward currents of relativistic energy “hot” electrons created by the laser pulse and “cold” return currents of thermal electrons induced in the target. Our results are not only fundamentally interesting but should also arouse interest on the role of magnetic turbulence induced resistivity in the context of fast ignition of laser fusion, and the possibility of experimentally simulating such structures with respect to the sun and other stellar environments.
Shifting hydrogen bonds may produce flexible transmembrane helices
Authors: Cao Zheng , Bowie James U.
Published: May 2012

The intricate functions of membrane proteins would not be possible without bends or breaks that are remarkably common in transmembrane helices. The frequent helix distortions are nevertheless surprising because backbone hydrogen bonds should be strong in an apolar membrane, potentially rigidifying helices. It is therefore mysterious how distortions can be generated by the evolutionary currency of random point mutations. Here we show that we can engineer a transition between distinct distorted helix conformations in bacteriorhodopsin with a single-point mutation. Moreover, we estimate the energetic cost of the conformational transitions to be smaller than 1 kcal/mol. We propose that the low energy of distortion is explained in part by the shifting of backbone hydrogen bonding partners. Consistent with this view, extensive backbone hydrogen bond shifts occur during helix conformational changes that accompany functional cycles. Our results explain how evolution has been able to liberally exploit transmembrane helix bending for the optimization of membrane protein structure, function, and dynamics.
Distinct phytochrome actions in nonvascular plants revealed by targeted inactivation of phytobilin biosynthesis
Authors: Chen Yu-Rong , Su Yi-shin , Tu Shih-Long
Published: May 2012

The red/far-red light photoreceptor phytochrome mediates photomorphological responses in plants. For light sensing and signaling, phytochromes need to associate with open-chain tetrapyrrole molecules as the chromophore. Biosynthesis of tetrapyrrole chromophores requires members of ferredoxin-dependent bilin reductases (FDBRs). It was shown that LONG HYPOCOTYL 2 (HY2) is the only FDBR in flowering plants producing the phytochromobilin (PΦB) for phytochromes. However, in the mossPhyscomitrella patens, we found a second FDBR that catalyzes the formation of phycourobilin (PUB), a tetrapyrrole pigment usually found as the protein-bound form in cyanobacteria and red algae. Thus, we named the enzyme PUB synthase (PUBS). Severe photomorphogenic phenotypes, including the defect of phytochrome-mediated phototropism, were observed inPhyscomitrella patenswhen bothHY2andPUBSwere disrupted by gene targeting. This indicates HY2 and PUBS function redundantly in phytochrome-mediated responses of nonvascular plants. Our studies also show that functional PUBS orthologs are found in selected lycopod and chlorophyte genomes. Using mRNA sequencing for transcriptome profiling, we demonstrate that expression of the majority of red-light-responsive genes are misregulated in thepubs hy2double mutant. These studies showed that moss phytochromes rapidly repress expression of genes involved in cell wall organization, transcription, hormone responses, and protein phosphorylation but activate genes involved in photosynthesis and stress signaling during deetiolation. We propose that, in nonvascular plants, HY2 and PUBS produce structurally different but functionally similar chromophore precursors for phytochromes. Holophytochromes regulate biological processes through light signaling to efficiently reprogram gene expression for vegetative growth in the light.
Contrastive linguistics and language comparison
Authors: König Ekkehard
Published: May 2012

After receiving enthusiastic support during the 1960s and 1970s, the program of ‘Contrastive linguistics’ led a somewhat modest, if not marginal, existence during the two subsequent decades. The main reason for the apparent failure of this program was, of course, that the high hopes seen in its potential for making foreign language teaching more efficient were disappointed. Empirical work on the process of L2-acquisition from different native languages as starting points showed that contrastive linguistics cannot simply be equated with a theory of foreign language acquisition. A second problem was that a central aspect of the contrastive program, i.e. the writing of comprehensive contrastive grammars for language pairs, was hardly ever properly implemented. Finally, there was the problem of finding a place for contrastive linguistics within the spectrum of language comparison, relative to other comparative approaches to linguistic analysis. It is the third of these issues that is addressed by the present article. It will be shown that only by relating contrastive linguistics to other subfields of comparative linguistics and by delimiting it from them will we obtain a clear picture of its agenda, its potential and its limits.
An alternative mechanism of clathrin-coated pit closure revealed by ion conductance microscopy
Authors: Shevchuk Andrew I. , Novak Pavel , Taylor Marcus , Diakonov Ivan A. , Ziyadeh-Isleem Azza , Bitoun Marc , Guicheney Pascale , Lab Max J. , Gorelik Julia , Merrifield Christien J. , Klenerman David , Korchev Yuri E.
Published: May 2012

Current knowledge of the structural changes taking place during clathrin-mediated endocytosis is largely based on electron microscopy images of fixed preparations and x-ray crystallography data of purified proteins. In this paper, we describe a study of clathrin-coated pit dynamics in living cells using ion conductance microscopy to directly image the changes in pit shape, combined with simultaneous confocal microscopy to follow molecule-specific fluorescence. We find that 70% of pits closed with the formation of a protrusion that grew on one side of the pit, covered the entire pit, and then disappeared together with pit-associated clathrin–enhanced green fluorescent protein (EGFP) and actin-binding protein–EGFP (Abp1-EGFP) fluorescence. This was in contrast to conventionally closing pits that closed and cleaved from flat membrane sheets and lacked accompanying Abp1-EGFP fluorescence. Scission of both types of pits was found to be dynamin-2 dependent. This technique now enables direct spatial and temporal correlation between functional molecule-specific fluorescence and structural information to follow key biological processes at cell surfaces.
Fascin promotes filopodia formation independent of its role in actin bundling
Authors: Zanet Jennifer , Jayo Asier , Plaza Serge , Millard Tom , Parsons Maddy , Stramer Brian
Published: May 2012

Fascin is an evolutionarily conserved actin-binding protein that plays a key role in forming filopodia. It is widely thought that this function involves fascin directly bundling actin filaments, which is controlled by an N-terminal regulatory serine residue. In this paper, by studying cellular processes in Drosophila melanogaster that require fascin activity, we identify a regulatory residue within the C-terminal region of the protein (S289). Unexpectedly, although mutation (S289A) of this residue disrupted the actin-bundling capacity of fascin, fascin S289A fully rescued filopodia formation in fascin mutant flies. Live imaging of migrating macrophages in vivo revealed that this mutation restricted the localization of fascin to the distal ends of filopodia. The corresponding mutation of human fascin (S274) similarly affected its interaction with actin and altered filopodia dynamics within carcinoma cells. These data reveal an evolutionarily conserved role for this regulatory region and unveil a function for fascin, uncoupled from actin bundling, at the distal end of filopodia.
Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation
Authors: Franzke Claus-Werner , Cobzaru Cristina , Triantafyllopoulou Antigoni , Löffek Stefanie , Horiuchi Keisuke , Threadgill David W. , Kurz Thomas , van Rooijen Nico , Bruckner-Tuderman Leena , Blobel Carl P.
Published: May 2012

ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17ΔKC) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17ΔKC skin, and topical treatment of A17ΔKC mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (EgfrΔKC) closely resembled A17ΔKC mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17–EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects.
Elliptic Weyl group elements and unipotent isometries with 𝑝=2
Authors: Lusztig George , Xue Ting
Published: May 2012

Let

G
G

be a classical group over an algebraically closed field of characteristic

2
2

and let

C
C

be an elliptic conjugacy class in the Weyl group. In a previous paper the first named author associated to

C
C

a unipotent conjugacy class

Φ
(
C
)

\Phi (C)

of

G
G

. In this paper we show that

Φ
(
C
)

\Phi (C)

can be characterized in terms of the closure relations between unipotent classes. Previously, the analogous result was known in odd characteristic and for exceptional groups in any characteristic.
Aggregate and Farm‐Level Productivity Growth in Tobacco: Before and After the Quota Buyout
Authors: Kirwan Barrett E. , Uchida Shinsuke , White T. Kirk
Published: May 2012

We examine the distortionary effects of agricultural policy on farm productivity by examining the response of U.S. tobacco farmers’ productivity to the quota buyout of 2004. We focus on the impact of distortionary policy, i.e., the tobacco quota, by decomposing aggregate productivity growth into the contribution of farm‐level productivity growth and the contribution of reallocation of resources among tobacco growers. We find that the aggregate productivity of Kentucky tobacco farms grew 44% between 2002 and 2007. The elimination of quota rental costs and reallocation of resources, including entry and exit, accounted for most of the post‐buyout productivity growth.
Nonparametric Estimates of the Components of Productivity and Profitability Change in U.S. Agriculture
Authors: O'Donnell Christopher J.
Published: May 2012

Recent theoretical advances in total factor productivity (TFP) measurement mean that TFP indexes can now be exhaustively decomposed into unambiguous measures of technical change and efficiency change. To date, all applications of this new methodology have involved decomposing indexes that have poor theoretical properties. This article shows how the methodology can be used to decompose a new TFP index that satisfies all economically‐relevant axioms from index theory. The application is to state‐level data from 1960 to 2004. In most states, the main drivers of agricultural TFP change are found to have been technical change and scale and mix efficiency change.
Pitfalls of Prescribing and Risk Disclosure
Authors: Aung Damian
Published: May 2012

The prescribing of medication is a significant element of the overall workload of a GP and it is estimated that an average of 300 prescription items are prescribed each week by every GP. The workload in primary care continues to increase and consequently, GPs are expected to prescribe ever more complex and expensive drugs. Data from the NHS Information centre show that in 2008, drug expenditure by GPs in UK stood at £4.5 billion, representing 50% of primary care costs, and this is expected to rise annually by 9%. The prescribing of large numbers of drugs inevitably leads to medication errors, with the Medical Protection Society (MPS) suggesting in 2010 that medication errors account for 20% of all errors in general practice with the cost of adverse events estimated at £750million a year. The data suggest that many of the errors are preventable; so it is advisable for doctors to consider potential risks when prescribing and for practices to have safety systems in place to avoid adverse events.
Marker-Assisted Selection for Disease Resistance in Wheat and Barley Breeding
Authors: Miedaner Thomas , Korzun Viktor
Published: May 2012

Marker-assisted selection (MAS) provides opportunities for enhancing the response from selection because molecular markers can be applied at the seedling stage, with high precision and reductions in cost. About each of 50 genes conferring monogenic resistances and hundreds of quantitative trait loci (QTL) for quantitative disease resistances have been reported in wheat and barley. For detecting single-major gene resistance, MAS could be easily applied, but is often not necessary because the resistances are selected phenotypically. In quantitative disease resistances, MAS would be very useful, but the individual QTL often have small effects. Additionally, only a few monogenic resistances are durable and only a few QTL with high effects have been successfully transferred into elite breeding material. Further economic and biological constraints, e.g., a low return of investment in small-grain cereal breeding, lack of diagnostic markers, and the prevalence of QTL–background effects, hinder the broad implementation of MAS. Examples in which MAS has been successfully applied to practical breeding are the wheat rust resistance genes Lr34 and Yr36, the eyespot resistance gene Pch1, the recessive resistance genes rym4/rym5 to barley yellow mosaic viruses, mlo to barley powdery mildew, and two QTL for resistance to Fusarium head blight in wheat (Fhb1 and Qfhs.ifa-5A). Newly identified broad-spectrum resistance genes/QTL conferring resistance to multiple taxa of pathogens offer additional perspectives for MAS. In the future, chip-based, high-throughput genotyping platforms and the introduction of genomic selection will reduce the current problems of integrating MAS in practical breeding programs and open new avenues for a molecular-based resistance breeding.
Effect of OverexpressingrsmAfromPseudomonas aeruginosaon Virulence of Select Phytotoxin-Producing Strains ofP. syringae
Authors: Kong Hye Suk , Roberts Daniel P. , Patterson Cheryl D. , Kuehne Sarah A. , Heeb Stephan , Lakshman Dilip K. , Lydon John
Published: May 2012

The GacS/GacA two-component system functions mechanistically in conjunction with global post-transcriptional regulators of the RsmA family to allow pseudomonads and other bacteria to adapt to changing environmental stimuli. Analysis of this Gac/Rsm signal transduction pathway in phytotoxin-producing pathovars of Pseudmonas syringae is incomplete, particularly with regard to rsmA. Our approach in studying it was to overexpress rsmA in P. syringae strains through introduction of pSK61, a plasmid constitutively expressing this gene. Disease and colonization of plant leaf tissue were consistently diminished in all P. syringae strains tested (pv. phaseolicola NPS3121, pv. syringae B728a, and BR2R) when harboring pSK61 relative to these isolates harboring the empty vector pME6031. Phaseolotoxin, syringomycin, and tabtoxin were not produced in any of these strains when transformed with pSK61. Production of protease and pyoverdin as well as swarming were also diminished in all of these strains when harboring pSK61. In contrast, alginate production, biofilm formation, and the hypersensitive response were diminished in some but not all of these isolates under the same growth conditions. These results indicate that rsmA is consistently important in the overarching phenotypes disease and endophtyic colonization but that its role varies with pathovar in certain underpinning phenotypes in the phytotoxin-producing strains of P. syringae.
Defining the limits of physiological plasticity: how gene expression can assess and predict the consequences of ocean change
Authors: Evans Tyler G. , Hofmann Gretchen E.
Published: May 2012

Anthropogenic stressors, such as climate change, are driving fundamental shifts in the abiotic characteristics of marine ecosystems. As the environmental aspects of our world's oceans deviate from evolved norms, of major concern is whether extant marine species possess the capacity to cope with such rapid change. In what many scientists consider the post-genomic era, tools that exploit the availability of DNA sequence information are being increasingly recognized as relevant to questions surrounding ocean change and marine conservation. In this review, we highlight the application of high-throughput gene-expression profiling, primarily transcriptomics, to the field of marine conservation physiology. Through the use of case studies, we illustrate how gene expression can be used to standardize metrics of sub-lethal stress, track organism condition in natural environments and bypass phylogenetic barriers that hinder the application of other physiological techniques to conservation. When coupled with fine-scale monitoring of environmental variables, gene-expression profiling provides a powerful approach to conservation capable of informing diverse issues related to ocean change, from coral bleaching to the spread of invasive species. Integrating novel approaches capable of improving existing conservation strategies, including gene-expression profiling, will be critical to ensuring the ecological and economic health of the global ocean.
Conservation physiology in practice: how physiological knowledge has improved our ability to sustainably manage Pacific salmon during up-river migration
Authors: Cooke Steven J. , Hinch Scott G. , Donaldson Michael R. , Clark Timothy D. , Eliason Erika J. , Crossin Glenn T. , Raby Graham D. , Jeffries Ken M. , Lapointe Mike , Miller Kristi , Patterson David A. , Farrell Anthony P.
Published: May 2012

Despite growing interest in conservation physiology, practical examples of how physiology has helped to understand or to solve conservation problems remain scarce. Over the past decade, an interdisciplinary research team has used a conservation physiology approach to address topical conservation concerns for Pacific salmon. Here, we review how novel applications of tools such as physiological telemetry, functional genomics and laboratory experiments on cardiorespiratory physiology have shed light on the effect of fisheries capture and release, disease and individual condition, and stock-specific consequences of warming river temperatures, respectively, and discuss how these findings have or have not benefited Pacific salmon management. Overall, physiological tools have provided remarkable insights into the effects of fisheries capture and have helped to enhance techniques for facilitating recovery from fisheries capture. Stock-specific cardiorespiratory thresholds for thermal tolerances have been identified for sockeye salmon and can be used by managers to better predict migration success, representing a rare example that links a physiological scope to fitness in the wild population. Functional genomics approaches have identified physiological signatures predictive of individual migration mortality. Although fisheries managers are primarily concerned with population-level processes, understanding the causes of en route mortality provides a mechanistic explanation and can be used to refine management models. We discuss the challenges that we have overcome, as well as those that we continue to face, in making conservation physiology relevant to managers of Pacific salmon.
Determining environmental causes of biological effects: the need for a mechanistic physiological dimension in conservation biology
Authors: Seebacher Frank , Franklin Craig E.
Published: May 2012

The emerging field of Conservation Physiology links environmental change and ecological success by the application of physiological theory, approaches and tools to elucidate and address conservation problems. Human activity has changed the natural environment to a point where the viability of many ecosystems is now under threat. There are already many descriptions of how changes in biological patterns are correlated with environmental changes. The next important step is to determine the causative relationship between environmental variability and biological systems. Physiology provides the mechanistic link between environmental change and ecological patterns. Physiological research, therefore, should be integrated into conservation to predict the biological consequences of human activity, and to identify those species or populations that are most vulnerable.
Oil and Protein Accumulation in Developing Seeds Is Influenced by the Expression of a Cytosolic Pyrophosphatase in Arabidopsis
Authors: Meyer Knut , Stecca Kevin L. , Ewell-Hicks Kim , Allen Stephen M. , Everard John D.
Published: May 2012

This study describes a dominant low-seed-oil mutant (lo15571) of Arabidopsis (Arabidopsis thaliana) generated by enhancer tagging. Compositional analysis of developing siliques and mature seeds indicated reduced conversion of photoassimilates to oil. Immunoblot analysis revealed increased levels of At1g01050 protein in developing siliques of lo15571. At1g01050 encodes a soluble, cytosolic pyrophosphatase and is one of five closely related genes that share predicted cytosolic localization and at least 70% amino acid sequence identity. Expression of At1g01050 using a seed-preferred promoter recreated most features of the lo15571 seed phenotype, including low seed oil content and increased levels of transient starch and soluble sugars in developing siliques. Seed-preferred RNA interference-mediated silencing of At1g01050 and At3g53620, a second cytosolic pyrophosphatase gene that shows expression during seed filling, led to a heritable oil increase of 1% to 4%, mostly at the expense of seed storage protein. These results are consistent with a scenario in which the rate of mobilization of sucrose, for precursor supply of seed storage lipid biosynthesis by cytosolic glycolysis, is strongly influenced by the expression of endogenous pyrophosphatase enzymes. This emphasizes the central role of pyrophosphate-dependent reactions supporting cytosolic glycolysis during seed maturation when ATP supply is low, presumably due to hypoxic conditions. This route is the major route providing precursors for seed oil biosynthesis. ATP-dependent reactions at the entry point of glycolysis in the cytosol or plastid cannot fully compensate for the loss of oil content observed in transgenic events with increased expression of cytosolic pyrophosphatase enzyme in the cytosol. These findings shed new light on the dynamic properties of cytosolic pyrophosphate pools in developing seed and their influence on carbon partitioning during seed filling. Finally, our work uniquely demonstrates that genes encoding cytosolic pyrophosphatase enzymes provide novel targets to improve seed composition for plant biotechnology applications.
Can needle and syringe programmes and opiate substitution therapy achieve substantial reductions in hepatitis C virus prevalence? Model projections for different epidemic settings
Authors: Vickerman Peter , Martin Natasha , Turner Katy , Hickman Matthew
Published: May 2012

Aims

To investigate the impact of scaling‐up opiate substitution therapy (OST) and high coverage needle and syringe programmes (100%NSP—obtaining more sterile syringes than you inject) on HCV prevalence among injecting drug users (IDUs).

Design

Hepatitis C virus HCV transmission modelling using UK estimates for effect of OST and 100%NSP on individual risk of HCV infection.

Setting

Range of chronic HCV prevalent (20/40/60%) settings with no OST/100%NSP, and UK setting with 50% coverage of both OST and 100%NSP.

Participants

Injecting drug users.

Measurements

Decrease in HCV prevalence after 5–20 years due to scale‐up of OST and 100%NSP to 20/40/60% coverage in no OST/100%NSP settings, or from 50% to 60/70/80% coverage in the UK setting.

Findings

For 40% chronic HCV prevalence, scaling‐up OST and 100%NSP from 0% to 20% coverage reduces HCV prevalence by 13% after 10 years. This increases to a 24/33% relative reduction at 40/60% coverage. Marginally less impact occurs in higher prevalence settings over 10 years, but this becomes more pronounced over time. In the United Kingdom, without current coverage levels of OST and 100%NSP the chronic HCV prevalence could be 65% instead of 40%. However, increasing OST and 100%NSP coverage further is unlikely to reduce chronic prevalence to less than 30% over 10 years unless coverage becomes ≥80%.

Conclusions

Scaling‐up opiate substitution therapy and high coverage needle and syringe programmes can reduce hepatitis C prevalence among injecting drug users, but reductions can be modest and require long‐term sustained intervention coverage. In high coverage settings, other interventions are needed to further decrease hepatitis C prevalence. In low coverage settings, sustained scale‐up of both interventions is needed.
Evaluating the impact of community‐based treatment options on methamphetamine use: findings from the Methamphetamine Treatment Evaluation Study (MATES)
Authors: McKetin Rebecca , Najman Jake M. , Baker Amanda L. , Lubman Dan I. , Dawe Sharon , Ali Robert , Lee Nicole K. , Mattick Richard P. , Mamun Abdullah
Published: May 2012

Aims

To evaluate the impact of community‐based drug treatment on methamphetamine use using inverse probability of treatment‐weighted (IPTW) estimators to derive treatment effects.

Design

A longitudinal prospective cohort study with follow‐ups at 3 months, 1 year and 3 years. Treatment effects were derived by comparing groups at follow‐up. IPTW estimators were used to adjust for pre‐treatment differences between groups.

Setting

Sydney and Brisbane, Australia.

Participants

Participants were methamphetamine users entering community‐based detoxification (n = 112) or residential rehabilitation (n = 248) services and a quasi‐control group of methamphetamine users (n = 101) recruited from the community.

Measurements

Frequency of methamphetamine use between interviews (no use, less than weekly, 1–2 days per week, 3+ days per week), continuous abstinence from methamphetamine use, past month methamphetamine use and methamphetamine dependence.

Findings

Detoxification did not reduce methamphetamine use at any follow‐up relative to the quasi‐control group. Relative to quasi‐control and detoxification groups combined, residential rehabilitation produced large reductions in the frequency of methamphetamine use at 3 months [odds ratio (OR) = 0.23, 95% confidence interval (CI) 0.15–0.36, P < 0.001), with a marked attenuation of this effect at 1 year (OR 0.62, 95% CI 0.40–0.97, P = 0.038) and 3 years (OR = 0.71, 95% CI 0.42–1.19, P = 0.189). The greatest impact was for abstinence: for every 100 residential rehabilitation clients there was a gain of 33 being continuously abstinent at 3 months, with this falling to 14 at 1 year and 6 at 3 years.

Conclusions

Community‐based residential rehabilitation may produce a time‐limited decrease in methamphetamine use, while detoxification alone does not appear to do so.
Checking Anaesthetic Equipment 2012
Authors:   Membership of the Working Party: A. Hartle (Chair), Anderson E. , Bythell V. , Gemmell L. , Jones H. , McIvor D. , Pattinson A. , Sim P. , Walker I.
Published: May 2012

A pre‐use check to ensure the correct functioning of anaesthetic equipment is essential to patient safety. The anaesthetist has a primary responsibility to understand the function of the anaesthetic equipment and to check it before use. Anaesthetists must not use equipment unless they have been trained to use it and are competent to do so. A self‐inflating bag must be immediately available in any location where anaesthesia may be given. A two‐bag test should be performed after the breathing system, vaporisers and ventilator have been checked individually. A record should be kept with the anaesthetic machine that these checks have been done. The ‘first user’ check after servicing is especially important and must be recorded.
Plasma brain‐derived neurotrophic factor in prepubertal obese children: results from a 2‐year lifestyle intervention programme
Authors: Corripio Raquel , Gónzalez‐Clemente José‐Miguel , Jacobo Pérez‐Sánchez , Silvia Näf , Lluis Gallart , Joan Vendrell , Assumpta Caixàs
Published: May 2012

Context

Brain‐derived neurotrophic factor (BDNF) is a neurotrophin potentially involved in the pathophysiology of obesity and metabolic syndrome in adults. In children, it has scarcely been studied.

Objective

To analyse plasma BDNF and its relationship with metabolic syndrome components before and after 2 years of a lifestyle intervention programme in a prepubertal obese cohort.

Design and setting

Case–control study with a 2‐year prospective follow‐up in a referral paediatric endocrine outpatient centre.

Patients and methods

Seventy‐three prepubertal obese children, 8·03 ± 1·08 years old, and 47 age‐ and gender‐matched lean controls were studied. Anthropometric parameters, blood pressure, platelet count (PLT), oral glucose tolerance test, homoeostatic model assessment for insulin resistance (HOMA‐IR), lipid profile, BDNF, diet and physical activity were evaluated. Weight loss was considered if z‐score body mass index (BMI) decreased at least 0·5 SD.

Results

At baseline, BDNF tended to be lower in prepubertal obese children compared with lean controls (P = 0·076). BDNF did not correlate with any metabolic syndrome component. After 2 years, obese patients showed an increase in BDNF. Regression model analysis adjusted by age, sex, puberty, BMI, PLT and HOMA‐IR showed that BDNF increased in subjects who lost weight (P = 0·036), practiced sports (P = 0·008) and had an adequate carbohydrate intake (P = 0·032).

Conclusions

Plasma BDNF tends to be lower in obese prepubertal children than in lean controls, is not related to any other metabolic syndrome component and increases after a lifestyle intervention programme.
Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self‐reporting very good health: the healthy man study
Authors: Sartorius Gideon , Spasevska Sasa , Idan Amanda , Turner Leo , Forbes Elise , Zamojska Anna , Allan Carolyn A. , Ly Lam P. , Conway Ann J. , McLachlan Robert I. , Handelsman David J.
Published: May 2012

Objective

To determine serum concentrations, intra‐individual variability and impact of age‐related co‐morbidities on serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2) and estrone (E1) in older men.

Design

Observational, repeated measures study.

Participants

Men (n = 325) with 40 years and older self‐reporting very good or excellent health.

Measurements

Standardized history, physical examination and collection of nine blood samples at fixed time intervals were measured over 3 months (three at 20 min intervals on days 1 (fasting) and 2 (non‐fasting), one at days 7, 30 and 90). Serum T, DHT, E2 and E1 (n = 2900, > 99% of scheduled samples) measured by liquid chromatography‐tandem mass spectrometry (LC‐MS) were analysed by linear mixed model analysis with fasting, age and obesity as covariables.

Results

Mean serum T did not vary with age (P = 0·76) but obesity (−0·35 nm per body mass index (BMI) unit, P < 0·0001) and ex‐smoker status (−1·6 nm, P < 0·001) had significant effects. Serum DHT was increased with age (+0·011 nm per year, P = 0·001) but decreased with obesity (−0·05 nm per BMI unit, P < 0·0001). Serum E2 did not vary with age (P = 0·31) or obesity (P = 0·12). Overnight fasting increased (by 9–16%, all P < 0·001) and reduced variability in morning serum T, DHT, E2 and E1. Non‐fasting serum T and DHT were stable over time (day, week, month or 3 months; P > 0·28).

Conclusions

Serum T, DHT and E2 displayed no decrease associated with age among men over 40 years of age who self‐report very good or excellent health although obesity and ex‐smoking status were associated with decreased serum androgens (T and DHT) but not E2. These findings support the interpretation that the age‐related decline in blood T accompanying non‐specific symptoms in older men may be due to accumulating age‐related co‐morbidities rather than a symptomatic androgen deficiency state.
Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean Sarcopenic Obesity Study
Authors: Kim Tae Nyun , Park Man Sik , Lim Kang Il , Choi Hae Yoon , Yang Sae Jeong , Yoo Hye Jin , Kang Hyun Joo , Song Wook , Choi Hyuk , Baik Sei Hyun , Choi Dong Seop , Choi Kyung Mook
Published: May 2012

Objective

It has been suggested that insulin resistance, low‐grade inflammation and vitamin D deficiency are associated with obesity and sarcopenia. However, their relationships with sarcopenic obesity (SO) are unclear. We evaluated the impact of homoeostasis model assessment of insulin resistance (HOMA‐IR), high‐sensitivity C‐reactive protein (hsCRP) and 25‐hydroxyvitamin D (25[OH]D) levels on SO in Korean adults.

Study subject/measurements

This study included 493 apparently healthy adults (180 men and 313 women) enrolled in the Korean Sarcopenic Obesity Study. Sarcopenia was defined as a skeletal muscle mass index (SMI) of 1 SD below the sex‐specific mean value for a young reference group. Obesity was defined as a visceral fat area (VFA) ≥100 cm2. We classified the participants into four sarcopenia/obesity groups based on both SMI and VFA.

Results

The prevalence of SO was 17·8% in men and 24·9% in women. In women, the SO group had higher HOMA‐IR and hsCRP levels compared with the non‐SO group. In men, the 25[OH]D levels were significantly lower in the SO group than the non‐SO group. Both hsCRP and HOMA‐IR levels were negatively correlated with SMI and positively correlated with VFA in both men and women, whereas 25[OH]D levels were positively correlated with SMI in both men and women. Multiple binary logistic regression analysis showed that HOMA‐IR and 25[OH]D levels were independently associated with SO in men, while HOMA‐IR and hsCRP were significant factors predicting SO in women.

Conclusion

Insulin resistance, inflammation and vitamin D deficiency were associated with SO in a Korean adult population.
The utility of diagnostic biopsy specimens for predictive molecular testing in colorectal cancer
Authors: Fadhil Wakkas , Ibrahem Salih , Seth Rashmi , AbuAli Ghada , Ragunath Krishna , Kaye Philip , Ilyas Mohammad
Published: May 2012

Fadhil W, Ibrahem S, Seth R, AbuAli G, Ragunath K, Kaye P & Ilyas M  (2012) Histopathology The utility of diagnostic biopsy specimens for predictive molecular testing in colorectal cancer

Aims:  If stratified medicine is to be applied in the neoadjuvant setting, predictive testing will have to be undertaken on preoperative diagnostic biopsy specimens. The aim of this study was to evaluate whether a diagnostic biopsy was adequately representative of the main tumour in colorectal cancer.

Methods and results:  Thirty cases of paired biopsy and subsequent resection specimens were randomly selected. Samples were screened for mutation in KRAS (codons 12/13, 61, and 146), BRAF (codon 600 and exon 11), PIK3CA (exons 1, 9, and 20), TP53 (exons 5–8), and microsatellite instability, using the quick multiplex consensus or standard polymerase chain reaction (PCR) protocols followed by high‐resolution melting analysis. A total of 570 paired PCR tests were performed for mutation detection, and identical results were obtained in both biopsy and resection specimens in 569 tests (>99% concordance). Four cases (13%) showed microsatellite instability, and, in all four cases, instability was seen at identical mononucleotide markers in both biopsy and matched resection specimens.

Conclusions:  This is the first study to show that diagnostic biopsy specimens, even though they are a tiny sample of the tumour, are sufficiently representative for use in predictive testing for early driver mutations in colorectal cancer.
Chemical composition, antioxidative capacity and interactive antimicrobial potency of Satureja khuzestanica Jamzad essential oil and antimicrobial agents against selected food‐related microorganisms
Authors: Siavash Saei‐Dehkordi S. , Fallah Aziz A. , Heidari‐Nasirabadi Mahbubeh , Moradi Mehran
Published: May 2012

This study aimed to determine the chemical composition, antimicrobial and antioxidative activity of Satureja khuzestanica Jamzad essential oil. The oil was analysed by GC and GC/MS. Twenty‐eight constituents were identified. The oxygenated monoterpenes (78.22%) were the principal compound group. Among them, carvacrol (53.86%) and thymol (19.84%) were the most abundant constituents. The oil exhibited an acceptable antimicrobial activity against most of the tested microorganisms. The checkerboard method was applied to determine fractional inhibitory concentration indices (FICIs) to interpret the synergetic, additive, indifference or antagonistic interactions between essential oil and each of antimicrobials (lysozyme, ciprofloxacin, fluconazole and amphotericin B) against food‐related microorganisms. The synergetic phenomenon (FICI ≤ 0.5) was observed in majority of combinations with the exception of the essential oil and lysozyme. The oil exhibited good 1,1‐diphenyl‐2‐picrylhydrazyl radical scavenging activity (IC50 = 28.71 μg mL−1). Also, the oil had strong antioxidative activity in β‐carotene‐linoleic acid assay relative antioxidant activity (RAA% = 95.45). This study demonstrated that the essential oil has beneficial biological properties and its simultaneous application with standard antimicrobials against food‐related microorganisms result in reduction in inhibitory doses of the antimicrobials in vitro.
Shelf life of ready‐to‐cook cauliflower mixtures as affected by packaging film mass transport properties
Authors: Lucera Annalisa , Conte Amalia , Del Nobile Matteo Alessandro
Published: May 2012

In this work, the influence of packaging mass transport properties on quality loss of fresh‐cut cauliflower mixtures was addressed. The study was organised in two subsequent experimental steps; first, the selection of micro‐perforated packaging films was carried out by monitoring the package headspace gas concentrations of fresh‐cut white, green cauliflower and roman cabbage. Then, the effects of the barrier properties of the selected micro‐perforated film on shelf life of two different fresh‐cut cauliflower mixtures, stored at 4 ± 1 °C, were addressed. Results suggested that, among the investigated films, the micro‐perforated polymeric matrix with the lowest oxygen transmission rate value showed the best performance as it created the optimum headspace gas composition for each cauliflower variety, as well as, for the product mixtures. The appearance of visible moulds was the factor limiting product shelf life that accounted for about 18 days for both the investigated cauliflower mixtures.
The olfactory sense: a developmental and lifespan perspective
Authors: Wittmann‐Price Ruth A
Published: May 2012

Aim and objective.  The objective of this literature review is to discuss human olfactory development, function and assessment through the lifespan. This article will highlight the importance of accurate olfactory function assessment.

Background.  Olfactory function in humans is an understudied sense and may contribute significantly to patient safety and quality of life. Studies related to olfactory function are presented for different life stages. Olfactory development is reviewed as is terminology used to describe functionality. This article highlights the need for nursing assessment of olfactory function to develop holistic nursing interventions since there are implications for patient safety, quality of life issues related to respiratory function, bonding and nutrition.

Design.  Literature review.

Method.  Articles were searched in CINAHL, PsychInfo and PubMed limited to those published in English to 2010 with the key terms ‘olfactory and nursing’. The search yielded 47 articles that were clinically based on patient care. Those articles that dealt specifically with traumatic brain syndrome were excluded. However, peer reviewed and research article were both specified.

Results.  There is evidence that olfactory assessment should be completed by nurses on high risk populations to ensure patent safety and enhance quality of life.

Conclusions.  More studies are needed to improve clinical knowledge about the role of olfactory function.

Relevance to clinical practice.  Nurses are in a prime position to assess olfactory function for patients at high risk for deficits to provide holistic nursing care.
Long‐term demographic consequences of eavesdropping for sagebrush
Authors: Karban Richard , Ishizaki Satomi , Shiojiri Kaori
Published: May 2012

1. There are now approximately 10 examples of plants that use volatile cues emitted by damaged neighbours to adjust their defences against herbivores. For two of these examples, preliminary evidence suggested that plants may experience net benefits from such eavesdropping, although eavesdropping was uncommon in one case and estimates of plant fitness were ambiguous in the other case.

2. In the current study, we examined the long‐term consequences of exposure to cues emitted by experimentally clipped sagebrush neighbours. In this sagebrush system we have repeatedly found that sagebrush plants that have experimentally clipped neighbours experience less herbivore damage over the season than plants with unclipped control neighbours under field conditions. We followed a cohort of young sagebrush plants from emergence in 1999 for 12 years. Neighbours of half of these plants were artificially clipped every spring from 2004–08 and survival and flowering was measured in each autumn from 1999–2011.

3. Survival of marked branches of young plants was not consistently affected by whether its neighbour was clipped. Plants near clipped neighbours produced more branches during this period than those near unclipped neighbours. There were no measurable treatment effects on plant survival over the 12 years. Branches near clipped neighbours produced more inflorescences than branches near unclipped neighbours.

4. Seedlings were more likely to survive to the end of their first dry season in two different years near clipped neighbours compared to unclipped neighbours.

5. Synthesis. The results suggest different effects of clipped neighbours that depend on plant age. Responding to the cues of experimental clipping may provide a slight net benefit, considering these results and other published studies, even though these cues provided little predictive value about actual risk of herbivory. Responding to reliable cues may be even more beneficial and may favour plants that eavesdrop on neighbours.
Emotional and behavioural problems in children with visual impairment, intellectual and multiple disabilities
Authors: Alimovic S.
Published: May 2012

Background  Children with multiple impairments have more complex developmental problems than children with a single impairment.

Method  We compared children, aged 4 to 11 years, with intellectual disability (ID) and visual impairment to children with single ID, single visual impairment and typical development on ‘Child Behavior Check List/4–18’ (CBCL/4–18), Parent Report.

Results  Children with ID and visual impairment had more emotional and behavioural problems than other groups of children: with single impairment and with typical development (F = 23.81; d.f.1/d.f.2 = 3/156; P < 0.001). All children with special needs had more emotional and behavioural problems than children with typical development. The highest difference was found in attention problems syndrome (F = 30.45; d.f.1/d.f.2 = 3/156; P < 0.001) where all groups of children with impairments had more problems. Children with visual impairment, with and without ID, had more somatic complaints than children with normal vision.

Conclusion  Intellectual disability had greater influence on prevalence and kind of emotional and behavioural problems in children than visual impairment.