bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital in the Home in Victoria: Factors Influencing Allocation Decisions
Authors: Cooper Genevieve
Published: August 2009

There is a question surrounding the funding of Hospital in the Home (HITH) as to whether the allocation policy was driven by customer service preference or was largely a financial imperative. HITH has the capacity to increase the throughput and therefore the efficiency of acute care facilities which is attractive to Government and Health Service Managers. There is insufficient evidence to indicate that this is true in all circumstances. Hospital in the Home is a desirable and safe option for some clients. Hospital in the Home has the potential to provide a more cost effective mode of delivery of acute care than hospital facilities. However, there is a need for identification of which clients, with which conditions and care needs, will benefit from being part of a HITH program in emotional, health and financial terms. Health professionals are still grappling with the impact that HITH has on their roles and relationships with other health care providers. More qualitative and quantitative research needs to be undertaken to identify the best models of HITH in both organisational and financial tems, and its impact on the wellbeing of clients and carers.
Infant Weaning Practices among Hmong Women in Melbourne
Authors: Liamputtong Rice Pranee
Published: August 2009

This paper examines infant weaning practices and describes the role of cultural beliefs and practices on infant feeding patterns among Hmong immigrants in Melbourne. The paper is based on in-depth interviews and participant observation conducted with 27 Hmong mothers and some traditional healers during 1993 and 1998. Traditionally, Hmong women breastfeed their newborn infants. Exclusive breastfeeding continues until the infant is at least five months old when supplementary food is commenced. Hmong women practise prolonged breastfeeding, usually until a subsequent birth. However, solid foods are gradually given to the child and common household foods are offered when the child is ready for them. Weaning, therefore, does not usually present an abrupt interruption in the infant's habits and hence does not cause much upset. Cultural beliefs and practices relating to infant feeding and weaning among the Hmong constitute a favourable trend, as currently recommended by the World Health Organization. It is proposed that knowledge about cultural beliefs and practices among the Hmong will help to promote better understanding among health care professionals who work with immigrants, so that culturally appropriate care can be provided.
Chronic Fatigue Syndrome: A Problem of Legitimation
Authors: Peterson Chris , Millen Neville , Woodward Roslyn
Published: August 2009

Chronic fatigue syndrome (ME-CFS) is a condition which has not been readily accepted by the medical or broader community as 'real', despite a growing reported incidence. In order to understand its current status, two models of illness are drawn upon. These have been used to explain social and political processes important to Repetitive Strain Injury (RSI), more recently known as Occupational Overuse Syndrome (OOS), and Alzheimer's disease gaining acceptance medically and in the wider community. They are used to provide a framework for understanding the socio-political context of ME-CFS and to provide an understanding of the transitions ME-CFS may need to go through before being a widely acknowledged condition. This framework is developed further to explore the illness in relation to broader social and political issues.
Life as a Male 'Anorexic'
Authors: Drummond Murray
Published: August 2009

Information surrounding male anorexia and bulimia nervosa is limited. Currently, health promoters and practitioners in this field have little to guide them apart from the data that informs female anorexia and bulimia nervosa. This paper is based on in-depth interviews with past and present eating disordered men. Using life historical accounts, the men provide rich descriptive information to document their plight with body image concerns and eating disorders. The paper provides insight into the lives of male anorexia and bulimia nervosa sufferers. Further it attempts to draw on their perceptions of what it is like being a male with a disorder that is often perceived as being a female phenomenon. The paper also explores the issues surrounding men and body image in contemporary Western culture. It highlights some of the significant issues confronting men and boys in relation to the social construction of masculinity and the links with body image concerns and eating disorders. Although the paper is not grounded in practitioner based information, it does seek to arouse awareness in those working in this emerging field of study.
An Integrated Model of Practice: Organisational Change to Achieve Population Health Outcomes
Authors: White Ian , Ashton Lesley
Published: August 2009

The move towards health outcomes internationally and in Australia has produced an agenda for meeting population health goals and targets which in the primary health care sector falls mainly on community health services. The workforce within these services is trained to deliver mainly secondary and tertiary care with a smattering of primary prevention. However, achieving population health outcomes will require health workers to become not only familiar with the language of Alma Ata and the Ottawa Charter, but also proficient in practice. The challenge for Wagga Wagga Community Health Services was to bring about this change by turning theory into practice in such a way as to make the change meaningful to the various disciplines working in it. An Integrated Model of Practice (IMP) was developed after examination of current practice revealed that deficits in skills and knowledge at health worker level and deficits in understanding about population health and health promotion at health service executive level specifically, would prevent the organisation achieving population health outcomes. The answer was the establishment of a task force response to identified health issues which addressed health problems systematically at the population level while retaining relevance to individual disciplines within the community health centre. The paper describes briefly the authors' experience with the process involved in organisational change towards achieving population health outcomes within a community health centre. It is the first of two papers, the second of which describes the gains made in the introduction of the Task Force Program within the Centre.
Being 'Real' in Suicide Prevention Evaluation: The Role of the Ethnographer's Emotions Under Traumatic Conditions
Authors: Ridge Damien , Hee Amos , Aroni Rosalie
Published: August 2009

While there is a tradition of recognising and contending with the emotional content of ethnography (e.g. informant emotions, researcher empathy), there are few accounts of research which illustrate clearly the emotional work done by researchers, and the value of such work as an analytical tool. Yet, in the human services, and especially where trauma is involved, ignoring emotional dynamics actually runs the risk of 'dumbing down' our analyses. The current paper draws on ethnographer experiences during an evaluation of a youth suicide prevention project at the Connexions agency in inner-city Melbourne. The organisation, which is a part of Jesuit Social Services, provides outreach, therapy and other services (e.g. drop-in, labour market program) to marginalised young people. The paper argues that researcher emotions are actually important to isolate and examine in order to adequately capture the meanings participants attribute to their realities and actions. Nevertheless, through the exploration of specific dilemmas, it is shown that recognising and processing difficult emotions can be a confronting yet rewarding exercise for researchers, both personally and in terms of research outcomes. The paper also discusses how the ethnographer managed to conduct research in a setting involving trauma.
Evaluating Coordinated Care: Complex Problems do not Have Simple Solutions
Authors: Kalucy Libby
Published: August 2009

The current trials of coordinated health care are aimed at changing health service delivery to be more patient-focussed, through care planning and funds pooling. The strategies being implemented with patients with a variety of chronic conditions include creating more supportive environments, developing personal skills and re-orientation of health services.
Maternal Alienation: the Use of Motherblaming in Abuse
Authors: Morris Anne
Published: August 2009

This paper reports on the early stages of a qualitative research project jointly supervised by Northern Women's Community Health Centre and the Univerity of Adelaide. The study uses a feminist framework to focus on the extent of motherblaming in various types of abuse, identifying motherblaming as a strategy rather than a by-product of abuse, and examining how systems and professionals have perpetuated this phenomenon. The project stemmed from the experiences of women attending the Centre, and the lack of acknowledgement of their experiences in mainstream practice. The research method includes semi-structured interviews with a small number of mothers and survivors of abuse, and this report uses material derived from these interviews to identify the tactics and effects of motherblaming. Suggestions are made for the development of programs and practice models that will address women's and children's needs in these situations.
A Community Partnership with Parents: Investing in the Future
Authors: Miller Marian , Hughes Barbara
Published: August 2009

This article presents the findings of a home based parents support program that focuses on the human environment surrounding children. In collaboration between a health service, a public health unit and a university school of nursing in Perth, Western Australia, a three year (1995-1998) health promotion pilot project has been implemented. The program model is based on the Child Development Program developed in the United Kingdom and Republic of Ireland in the early eighties. This empowerment program is comprehensive, rather than targeting particular issues and focuses on the family's child-rearing environment in holistic terms. Raising the self-esteem of parents is a priority on the grounds that people lacking self-esteem and confidence often struggle to cope with life events and the demands of child rearing. The program, a partnership between community child health nurses and the community, recognises and builds on the skills of experienced mothers. Through semi-structured home visits, these women provide peer support and encouragement for new parents in their fundamental role of parenting. Evaluated through the collection of both qualitative and quantitative data, the outcomes of the pilot project have demonstrated an increase in the self-esteem of mothers, and gains in child development, immunisation, breast-feeding and family nutrition. In addition there is evidence of parents 'looking out for each other' and indications of a strengthening of social cohesion in the local community.
Health Promotion Evaluation and Research in Schools: Issues for Consideration
Authors: McBride Nyanda
Published: August 2009

Schools offer an attractive means for health promotion practitioners interested in improving the health of young people and therefore schools play a critical role as a setting for health promotion and public health program implementation. As a consequence schools are also settings in which evaluation and research is undertaken. This paper will discuss some broad issues that the literature suggests are important considerations for evaluation and research undertaken in school settings and discusses some of the practical implications of these considerations. Evaluation of school health promotion requires a balance between systematic, regulated research design and the variable, uncontrolled environment inherent in naturalistic settings. A clear understanding about the nature of the school setting, coupled with an evaluation targeted at the appropriate research phase and incorporating lessons learnt from previous interventions are various issues that need to be considered in well planned evaluations. A planning approach that takes into consideration the evaluation issues raised in this paper will help to ensure that appropriate and useful interventions and evaluations are developed, which also play an important role in contributing to the development of the field as a whole.
The Ottawa Charter for Health Promotion as a Framework to Design an Interview Schedule
Authors: Verrinder Glenda
Published: August 2009

The municipalities of Mildura in Victoria and Wentworth in NSW undertook a review of public health issues within their communities in preparation for the development of a Municipal Public Health Plan. The Ottawa Charter for Health Promotion provided an appropriate framework to develop an interview schedule used in focus groups to investigate the community perceptions of public health issues. The interview schedule provided a rich source of data and subsequently, provided a framework for the development of a Municipal Public Health Plan. This is a new use for the Ottawa Charter. It provided a vehicle that enabled the community to reflect upon, and discuss, public health issues within their municipality. Moreover, the schedule was easily administered, applied in a number of settings, and provided an approach that was acceptable to diverse community groups.
Evidence for the effectiveness of sponsorship as a health promotion tool
Authors: J. Donovan Robert , Jalleh Geoffrey , Clarkson Johanna , Giles-Corti Billie
Published: August 2009

Health sponsorships are undertaken to achieve both structural and individual objectives. Structural objectives refer to the sponsored organisation being required to undertake activities such as the imposition of smoke free areas, or the provision of low alcohol beverages and healthy food choices at the sponsored event. Individual objectives refer to creating or reinforcing people's awareness of a health issue or message, and their beliefs, attitudes and behaviours with respect to the issue or message. This paper focuses on sponsorship's capacity to achieve individual level objectives, describing several studies undertaken by the Health Promotion Evaluation Unit (HPEU) at the University of Western Australia to evaluate the health promotion sponsorship activities of Healthway, the Western Australian Health Promotion Foundation. Given the results of evaluations of Healthway's (and other organisations') sponsorship activities, using a variety of methodologies and across a broad range of events and health issues, it is concluded that health sponsorships can be effective at increasing people's salience of a health issue, and can result in attitudinal and behavioural change.
Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice
Authors: Baraban Scott C. , Southwell Derek G. , Estrada Rosanne C. , Jones Daniel L. , Sebe Joy Y. , Alfaro-Cervello Clara , García-Verdugo Jose M. , Rubenstein John L. R. , Alvarez-Buylla Arturo
Published: August 2009

Epilepsy, a disease characterized by abnormal brain activity, is a disabling and potentially life-threatening condition for nearly 1% of the world population. Unfortunately, modulation of brain excitability using available antiepileptic drugs can have serious side effects, especially in the developing brain, and some patients can only be improved by surgical removal of brain regions containing the seizure focus. Here, we show that bilateral transplantation of precursor cells from the embryonic medial ganglionic eminence (MGE) into early postnatal neocortex generates mature GABAergic interneurons in the host brain. In mice receiving MGE cell grafts, GABA-mediated synaptic and extrasynaptic inhibition onto host brain pyramidal neurons is significantly increased. Bilateral MGE cell grafts in epileptic mice lacking a Shaker-like potassium channel (a gene mutated in one form of human epilepsy) resulted in significant reductions in the duration and frequency of spontaneous electrographic seizures. Our findings suggest that MGE-derived interneurons could be used to ameliorate abnormal excitability and possibly act as an effective strategy in the treatment of epilepsy.
High-sensitivity microfluidic calorimeters for biological and chemical applications
Authors: Lee Wonhee , Fon Warren , Axelrod Blake W. , Roukes Michael L.
Published: August 2009

High-sensitivity microfluidic calorimeters raise the prospect of achieving high-throughput biochemical measurements with minimal sample consumption. However, it has been challenging to realize microchip-based calorimeters possessing both high sensitivity and precise sample-manipulation capabilities. Here, we report chip-based microfluidic calorimeters capable of characterizing the heat of reaction of 3.5-nL samples with 4.2-nW resolution. Our approach, based on a combination of hard- and soft-polymer microfluidics, provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that can be scaled to automated, highly multiplexed array architectures. Polydimethylsiloxane microfluidic valves and pumps are interfaced to parylene channels and reaction chambers to automate the injection of analyte at 1 nL and below. We attained excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers. We demonstrate performance of these calorimeters by resolving measurements of the heat of reaction of urea hydrolysis and the enthalpy of mixing of water with methanol. The device structure can be adapted easily to enable a wide variety of other standard calorimeter operations; one example, a flow calorimeter, is described.
The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake
Authors: Bailey Steven W. , Ayling June E.
Published: August 2009

Numerous clinical trials using folic acid for prevention of cardiovascular disease, stroke, cognitive decline, and neural tube defects have been completed or are underway. Yet, all functions of folate are performed by tetrahydrofolate and its one-carbon derivatives. Folic acid is a synthetic oxidized form not significantly found in fresh natural foods; to be used it must be converted to tetrahydrofolate by dihydrofolate reductase (DHFR). Increasing evidence suggests that this process may be slow in humans. Here we show, using a sensitive assay we developed, that the reduction of folic acid by DHFR per gram of human liver (n= 6) obtained from organ donors or directly from surgery is, on average, less than 2% of that in rat liver at physiological pH. Moreover, in contrast to rats, there was almost a 5-fold variation of DHFR activity among the human samples. This limited ability to activate the synthetic vitamer raises issues about clinical trials using high levels of folic acid. The extremely low rate of conversion of folic acid suggests that the benefit of its use in high doses will be limited by saturation of DHFR, especially in individuals possessing lower than average activity. These results are also consistent with the reports of unmetabolized folic acid in plasma and urine.
Colloidal glasses and gels: The interplay of bonding and caging
Authors: Zaccarelli Emanuela , Poon Wilson C. K.
Published: August 2009

We report simulations of glassy arrest in hard-core particles with short-range interparticle attraction. Previous experiments, theory, and simulations suggest that in this kind of system, two qualitatively distinct kinds of glasses exist, dominated respectively by repulsion and attraction. It is thought that in the former, particles are trapped “topologically,” by nearest-neighbor cages, whereas in the latter, nonergodicity is due to interparticle “bonds.” Subsequent experiments and simulations have suggested that bond breaking destabilizes attractive glasses, but the long-term fate of these arrested states remains unknown. By running simulations to times a few orders of magnitude longer than those reached by previous experiments or simulations, we show that arrest in an attractive glass is, in the long run, also topological. Nevertheless, it is still possible to distinguish between “nonbonded” and “bonded” repulsive glassy states. We study the melting of bonded repulsive glasses into a hitherto unknown “dense gel” state, which is distinct from dense, ergodic fluids. We propose a “modified state diagram” for concentrated attractive particles, and discuss the relevance of our results in the light of recent rheological measurements in colloid–polymer mixtures.
Collapse of proteostasis represents an early molecular event in
Caenorhabditis elegans
aging
Authors: Ben-Zvi Anat , Miller Elizabeth A. , Morimoto Richard I.
Published: August 2009

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of
C. elegans
. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.
Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations
Authors: Nakamura Tomoki , Gulick James , Pratt Ronald , Robbins Jeffrey
Published: August 2009

A gain of function mutation in SHP2, a protein phosphatase encoded by
PTPN11
, causes Noonan syndrome (NS), which is characterized in part by developmental deficits in both the cardiac and skull fields. Previously, we found that expression of the mutated protein SHP2 Q79R in the heart led to a phenotypic presentation that mimicked some aspects of NS and that this was dependent upon activation of the ERK1/2 pathway. To understand the role that ERK1/2 signaling plays in skull development through signaling in the neural crest, we explored the consequences of Q79R expression in neural crest cells, which contribute to a subset of the bony and cartilaginous structures of the skull. Hyperactivation of ERK1/2 led to craniofacial defects that included smaller skull lengths, greater inner canthal distances, and taller frontal bone heights. In proportion to the smaller skull length, mandibular bone length was also reduced. Inhibition of ERK1/2 hyperactivity as a result of Q79R expression was achieved by injection of the MAPK/ERK kinase inhibitor U0126 during pregnancy. The drug effectively decreased the severity of the craniofacial defects and restored normal skull shape and fontanelle closure. X-ray computer-assisted microtomography analysis of the head confirmed that decreasing ERK1/2 activity led to an abrogation of the craniofacial deficits and brain shape changes that presented in the mice. These data show that normal ERK1/2 signaling in the neural crest is imperative for normal craniofacial development and offer insight into how the heart and craniofacial developmental fields might be affected in some congenital syndromic presentations.
Slow oscillation electrical brain stimulation during waking promotes EEG theta activity and memory encoding
Authors: Kirov Roumen , Weiss Carsten , Siebner Hartwig R. , Born Jan , Marshall Lisa
Published: August 2009

The application of transcranial slow oscillation stimulation (tSOS; 0.75 Hz) was previously shown to enhance widespread endogenous EEG slow oscillatory activity when applied during a sleep period characterized by emerging endogenous slow oscillatory activity. Processes of memory consolidation typically occurring during this state of sleep were also enhanced. Here, we show that the same tSOS applied in the waking brain also induced an increase in endogenous EEG slow oscillations (0.4–1.2 Hz), although in a topographically restricted fashion. Applied during wakefulness tSOS, additionally, resulted in a marked and widespread increase in EEG theta (4–8 Hz) activity. During wake, tSOS did not enhance consolidation of memories when applied after learning, but improved encoding of hippocampus-dependent memories when applied during learning. We conclude that the EEG frequency and related memory processes induced by tSOS critically depend on brain state. In response to tSOS during wakefulness the brain transposes stimulation by responding preferentially with theta oscillations and facilitated encoding.
Adsorption of thiocyanate ions to the dodecanol/water interface characterized by UV second harmonic generation
Authors: Onorato Robert M. , Otten Dale E. , Saykally Richard J.
Published: August 2009

Recent experimental and theoretical results have firmly established the existence of enhanced concentrations of selected ions at the air/water interface. Ion adsorption to aqueous interfaces involving complex organic molecules is relevant to biology in connection with the familiar but incompletely understood Hofmeister effects. Here, we describe resonant UV second harmonic generation (SHG) studies of the strongly chaotropic thiocyanate ion adsorbed to the interface formed by water and a monolayer of dodecanol, wherein the Gibbs free energy of adsorption was determined to be −6.7 ± 1.1 and −6.3 ± 1.8 kJ/mol for sodium and potassium thiocyanate, respectively, coincident with the value determined for thiocyanate at the air/water interface. Interestingly, near 4 M and higher concentrations, the resonant SHG signal increases discontinuously, indicating a structural change in the interfacial region.
Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Authors: Fabbrini Elisa , Magkos Faidon , Mohammed B. Selma , Pietka Terri , Abumrad Nada A. , Patterson Bruce W. , Okunade Adewole , Klein Samuel
Published: August 2009

Visceral adipose tissue (VAT) is an important risk factor for obesity-related metabolic disorders. Therefore, a reduction in VAT has become a key goal in obesity management. However, VAT is correlated with intrahepatic triglyceride (IHTG) content, so it is possible that IHTG, not VAT, is a better marker of metabolic disease. We determined the independent association of IHTG and VAT to metabolic function, by evaluating groups of obese subjects, who differed in IHTG content (high or normal) but matched on VAT volume or differed in VAT volume (high or low) but matched on IHTG content. Stable isotope tracer techniques and the euglycemic–hyperinsulinemic clamp procedure were used to assess insulin sensitivity and very-low-density lipoprotein–triglyceride (VLDL-TG) secretion rate. Tissue biopsies were obtained to evaluate cellular factors involved in ectopic triglyceride accumulation. Hepatic, adipose tissue and muscle insulin sensitivity were 41, 13, and 36% lower (
P
< 0.01), whereas VLDL-triglyceride secretion rate was almost double (
P
< 0.001), in subjects with higher than normal IHTG content, matched on VAT. No differences in insulin sensitivity or VLDL-TG secretion were observed between subjects with different VAT volumes, matched on IHTG content. Adipose tissue CD36 expression was lower (
P
< 0.05), whereas skeletal muscle CD36 expression was higher (
P
< 0.05), in subjects with higher than normal IHTG. These data demonstrate that IHTG, not VAT, is a better marker of the metabolic derangements associated with obesity. Furthermore, alterations in tissue fatty acid transport could be involved in the pathogenesis of ectopic triglyceride accumulation by redirecting plasma fatty acid uptake from adipose tissue toward other tissues.
Symmetry breaking in smectics and surface models of their singularities
Authors: Chen Bryan Gin-ge , Alexander Gareth P. , Kamien Randall D.
Published: August 2009

The homotopy theory of topological defects in ordered media fails to completely characterize systems with broken translational symmetry. We argue that the problem can be understood in terms of the lack of rotational Goldstone modes in such systems and provide an alternate approach that correctly accounts for the interaction between translations and rotations. Dislocations are associated, as usual, with branch points in a phase field, whereas disclinations arise as critical points and singularities in the phase field. We introduce a three-dimensional model for two-dimensional smectics that clarifies the topology of disclinations and geometrically captures known results without the need to add compatibility conditions. Our work suggests natural generalizations of the two-dimensional smectic theory to higher dimensions and to crystals.
Cyclic tensile strain triggers a sequence of autocrine and paracrine signaling to regulate angiogenic sprouting in human vascular cells
Authors: Yung Yu Ching , Chae Jeiwook , Buehler Markus J. , Hunter Craig P. , Mooney David J.
Published: August 2009

Mechanical signals regulate blood vessel development in vivo, and have been demonstrated to regulate signal transduction of endothelial cell (EC) and smooth muscle cell (SMC) phenotype in vitro. However, it is unclear how the complex process of angiogenesis, which involves multiple cell types and growth factors that act in a spatiotemporally regulated manner, is triggered by a mechanical input. Here, we describe a mechanism for modulating vascular cells during sequential stages of an in vitro model of early angiogenesis by applying cyclic tensile strain. Cyclic strain of human umbilical vein (HUV)ECs up-regulated the secretion of angiopoietin (Ang)-2 and PDGF-ββ, and enhanced endothelial migration and sprout formation, whereas effects were eliminated with shRNA knockdown of endogenous Ang-2. Applying strain to colonies of HUVEC, cocultured on the same micropatterned substrate with nonstrained human aortic (HA)SMCs, led to a directed migration of the HASMC toward migrating HUVECs, with diminished recruitment when PDGF receptors were neutralized. These results demonstrate that a singular mechanical cue (cyclic tensile strain) can trigger a cascade of autocrine and paracrine signaling events between ECs and SMCs critical to the angiogenic process.
Convergent evolution of metabolic roles in bacterial co-symbionts of insects
Authors: McCutcheon John P. , McDonald Bradon R. , Moran Nancy A.
Published: August 2009

A strictly host-dependent lifestyle has profound evolutionary consequences for bacterial genomes. Most prominent is a sometimes-dramatic amount of gene loss and genome reduction. Recently, highly reduced genomes from the co-resident intracellular symbionts of sharpshooters were shown to exhibit a striking level of metabolic interdependence. One symbiont, called
Sulcia muelleri
(Bacteroidetes), can produce eight of the 10 essential amino acids, despite having a genome of only 245 kb. The other,
Baumannia cicadellinicola
(γ-Proteobacteria), can produce the remaining two essential amino acids as well as many vitamins. Cicadas also contain the symbiont
Sulcia
, but lack
Baumannia
and instead contain the co-resident symbiont
Hodgkinia cicadicola
(α-Proteobacteria). Here we report that, despite at least 200 million years of divergence, the two
Sulcia
genomes have nearly identical gene content and gene order. Additionally, we show that despite being phylogenetically distant and drastically different in genome size and architecture,
Hodgkinia
and
Baumannia
have converged on gene sets conferring similar capabilities for essential amino acid biosynthesis, in both cases precisely complementary to the pathways conserved in
Sulcia
. In contrast, they have completely divergent capabilities for vitamin biosynthesis. Despite having the smallest gene set known in bacteria,
Hodgkinia
devotes at least 7% of its proteome to cobalamin (vitamin B
12
) biosynthesis, a significant metabolic burden. The presence of these genes can be explained by
Hodgkinia
's retention of the cobalamin-dependent version of methionine synthase instead of the cobalamin-independent version found in
Baumannia
, a situation that necessitates retention of cobalamin biosynthetic capabilities to make the essential amino acid methionine.
Diameter-dependent dopant location in silicon and germanium nanowires
Authors: Xie Ping , Hu Yongjie , Fang Ying , Huang Jinlin , Lieber Charles M.
Published: August 2009

We report studies defining the diameter-dependent location of electrically active dopants in silicon (Si) and germanium (Ge) nanowires (NWs) prepared by nanocluster catalyzed vapor-liquid-solid (VLS) growth without measurable competing homogeneous decomposition and surface overcoating. The location of active dopants was assessed from electrical transport measurements before and after removal of controlled thicknesses of material from NW surfaces by low-temperature chemical oxidation and etching. These measurements show a well-defined transition from bulk-like to surface doping as the diameter is decreased <22–25 nm for
n
- and
p
-type Si NWs, although the surface dopant concentration is also enriched in the larger diameter Si NWs. Similar diameter-dependent results were also observed for
n
-type Ge NWs, suggesting that surface dopant segregation may be general for small diameter NWs synthesized by the VLS approach. Natural surface doping of small diameter semiconductor NWs is distinct from many top-down fabricated NWs, explains enhanced transport properties of these NWs and could yield robust properties in ultrasmall devices often dominated by random dopant fluctuations.
Restriction versus guidance in protein structure prediction
Authors: Hegler Joseph A. , Lätzer Joachim , Shehu Amarda , Clementi Cecilia , Wolynes Peter G.
Published: August 2009

Conformational restriction by fragment assembly and guidance in molecular dynamics are alternate conformational search strategies in protein structure prediction. We examine both approaches using a version of the associative memory Hamiltonian that incorporates the influence of water-mediated interactions (AMW). For short proteins (<70 residues), fragment assembly, while searching a restricted space, compares well to molecular dynamics and is often sufficient to fold such proteins to near-native conformations (4Å) via simulated annealing. Longer proteins encounter kinetic sampling limitations in fragment assembly not seen in molecular dynamics which generally samples more native-like conformations. We also present a fragment enriched version of the standard AMW energy function, AMW-FME, which incorporates the local sequence alignment derived fragment libraries from fragment assembly directly into the energy function. This energy function, in which fragment information acts as a guide not a restriction, is found by molecular dynamics to improve on both previous approaches.
OLA1, an Obg-like ATPase, suppresses antioxidant response via nontranscriptional mechanisms
Authors: Zhang Jiawei , Rubio Valentina , Lieberman Michael W. , Shi Zheng-Zheng
Published: August 2009

Oxidative stress has been implicated in diverse disease states and aging. To date, induction of cellular responses to combat oxidative stress has been characterized largely at the transcriptional level, with emphasis on Nrf2-mediated activation of antioxidant response elements. In this study, we demonstrate that OLA1, a novel Obg-like ATPase, functions as a negative regulator of the cellular antioxidant response independent of transcriptional processes. Knockdown of OLA1 in human cells elicited an increased resistance to oxidizing agents includingtert-butyl hydroperoxide (tBH) and diamide without affecting cell proliferation, baseline apoptosis, or sensitivity to other cytotoxic agents that target the mitochondria, cytoskeleton, or DNA. Conversely, overexpression of OLA1 increased cellular sensitivity to tBH and diamide. When challenged with oxidants, OLA1-knockdown cells had decreased production of intracellular reactive oxygen species and exhibited less depletion of reduced glutathione. Surprisingly, knockdown of OLA1 caused only minimal genomic response; no changes were found in the mRNA levels of genes encoding antioxidant enzymes, enzymes that produce antioxidants (including glutathione), or other genes known to respond to Nrf2. Moreover, when de novo protein synthesis was blocked by cycloheximide in OLA1-knockdown cells, they continued to demonstrate increased resistance to both tBH and diamide. These data demonstrate that OLA1 suppresses the antioxidant response through nontranscriptional mechanisms. The beneficial effects observed upon OLA1-knockdown suggest that this regulatory ATPase is a potential novel target for antioxidative therapy.
Establishment of trophoblast stem cell lines from somatic cell nuclear-transferred embryos
Authors: Oda Mayumi , Tanaka Satoshi , Yamazaki Yukiko , Ohta Hiroshi , Iwatani Misa , Suzuki Masako , Ohgane Jun , Hattori Naka , Yanagimachi Ryuzo , Wakayama Teruhiko , Shiota Kunio
Published: August 2009

Placental abnormalities occur frequently in cloned animals. Here, we attempted to isolate trophoblast stem (TS) cells from mouse blastocysts produced by somatic cell nuclear transfer (NT) at the blastocyst stage (NT blastocysts). Despite the predicted deficiency of the trophoblast cell lineage, we succeeded in isolating cell colonies with typical morphology of TS cells and cell lines from the NT blastocysts (ntTS cell lines) with efficiency as high as that from native blastocysts. The established 10 ntTS cell lines could be maintained in the undifferentiated state and induced to differentiate into several trophoblast subtypes in vitro. A comprehensive analysis of the transcriptional and epigenetic traits demonstrated that ntTS cells were indistinguishable from control TS cells. In addition, ntTS cells contributed exclusively to the placenta and survived until term in chimeras, indicating that ntTS cells have developmental potential as stem cells. Taken together, our data show that NT blastocysts contain cells that can produce TS cells in culture, suggesting that proper commitment to the trophoblast cell lineage in NT embryos occurs by the blastocyst stage.
Aortic dissection in pregnancy: A life‐threatening disease and a diagnosis of worth considering
Authors: NASIELL JOSEFINE , NORMAN MIKAEL , LINDQVIST PELLE G , MALMSTEDT JONAS , BOTTINGA ROGER , BLENNOW MATS
Published: August 2009

Acute aortic dissection is a life‐threatening disease. To increase the awareness of this diagnosis as a cause of feto‐maternal mortality during pregnancy, we have analyzed risk factors using information from five pregnant women admitted for acute aortic dissection to the Karolinska University Hospital over an eight‐year period (1999–2007). Four of the women died and only one survived. One fetus was stillborn and all newborn infants showed signs of asphyxia at birth. Of the women, who were on average five years above the mean age for delivery in Sweden, three had hypertension, two had first‐degree relatives with aortic dissection which had occurred during the second half of pregnancy (gestational age at diagnosis 26–41 weeks). The most common presenting symptoms were severe back, abdominal and leg pain, and confusion. If a rapid diagnosis is not made, the risk of mortality for both mother and fetus is high. The incidence of aortic rupture during pregnancy in Sweden appears to be 14.5/1,000,000 and the case maternal fatality ratio 4.4/1,000,000.
Quantitative assessment of 99mtc-depreotide uptake in patients with non-small-cell lung cancer: immunohistochemical correlations
Authors: Herlin G. , Kölbeck K.-G. , Menzel P. L. , Svensson L. , Aspelin P. , Capitanio A. , Axelsson R.
Published: August 2009

Background: Somatostatin receptor (SSTR) scintigraphy with 99mTc-depreotide is used for differential diagnosis of solitary pulmonary nodules. The method is based on SSTR expression in cancer tissue.

Purpose: To estimate the expression of SSTRs in non-small-cell lung cancer (NSCLC) in vitro, and to determine the correlation between 99mTc-depreotide uptake in vivo and different tumor characteristics determined in vitro, such as tumor grade, and presence of SSTR2, MIB-1, and p53.

Material and Methods: A total of 127 patients with lung lesions detected on computed tomography (CT) were investigated with SSTR scintigraphy after injection of 740 MBq 99mTc-depreotide. This study includes 19 patients with NSCLC with histologically proven diagnosis. The quantitative evaluation of 99mTc-depreotide was performed using region-of-interest analysis and includes tumor counts/cm3, background counts/cm3, and the ratio between tumor and background counts.

Results: 99mTc-depreotide uptake was found in all NSCLC tumors, which expressed SSTR2 defined in vitro by immunochemical methods. SSTR2 expression was negatively correlated to the degree of the tumor's differentiation ( P<0.05). 99mTc-depreotide uptake in tumor cells did not correlate with tumor grade, or SSTR2, MIB-1, or p53 expression.

Conclusion: There is an expression of SSTRs in NSCLC. The degree of tumor differentiation correlates negatively with SSTR2 measured in vitro and positively with MIB-1 expression in tumor tissue. No correlation was found between 99mTc-depreotide uptake and possible prognostic factors such as MIB-1 and p53 expression in tumor cells in NSCLC. Lastly, no correlation was found between 99mTc-depreotide uptake and tumor grade or SSTR2 expression.
A role for CD47 in the development of experimental colitis mediated by SIRPα+CD103− dendritic cells
Authors: Fortin Genevieve , Raymond Marianne , Van Vu Quang , Rubio Manuel , Gautier Patrick , Sarfati Marika , Franchimont Denis
Published: August 2009

Mesenteric lymph node (mLN) CD103 (αE integrin)+ dendritic cells (DCs) induce regulatory T cells and gut tolerance. However, the function of intestinal CD103− DCs remains to be clarified. CD47 is the ligand of signal regulatory protein α (SIRPα) and promotes SIRPα+ myeloid cell migration. We first show that mucosal CD103− DCs selectively express SIRPα and that their frequency was augmented in the lamina propria and mLNs of mice that developed Th17-biased colitis in response to trinitrobenzene sulfonic acid. In contrast, the percentage of SIRPα+CD103− DCs and Th17 responses were decreased in CD47-deficient (CD47 knockout [KO]) mice, which remained protected from colitis. We next demonstrate that transferring wild-type (WT), but not CD47 KO, SIRPα+CD103− DCs in CD47 KO mice elicited severe Th17-associated wasting disease. CD47 expression was required on the SIRPα+CD103− DCs for efficient trafficking to mLNs in vivo, whereas it was dispensable on both DCs and T cells for Th17 polarization in vitro. Finally, administration of a CD47-Fc molecule resulted in reduced SIRPα+CD103− DC–mediated Th17 responses and the protection of WT mice from colitis. We thus propose SIRPα+CD103− DCs as a pathogenic DC subset that drives Th17-biased responses and colitis, and the CD47–SIRPα axis as a potential therapeutic target for inflammatory bowel disease.
Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection
Authors: Robinson Matthew J. , Osorio Fabiola , Rosas Marcela , Freitas Rui P. , Schweighoffer Edina , Groß Olaf , Verbeek J. Sjef , Ruland Jürgen , Tybulewicz Victor , Brown Gordon D. , Moita Luis Ferreira , Taylor Philip R. , Reis e Sousa Caetano
Published: August 2009

Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of immune responses to infection. Studies with Dectin-1, a PRR for fungi, have defined a novel innate signaling pathway involving Syk kinase and the adaptor CARD9, which is critical for inducing Th17 responses to fungal infection. We show that another C-type lectin, Dectin-2, also signals via Syk and CARD9, and contributes to dendritic cell (DC) activation by fungal particles. Unlike Dectin-1, Dectin-2 couples to Syk indirectly, through association with the FcRγ chain. In a model of Candida albicans infection, blockade of Dectin-2 did not affect innate immune resistance but abrogated Candida-specific T cell production of IL-17 and, in combination with the absence of Dectin-1, decreased Th1 responses to the organism. Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk–CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection.
Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses
Authors: Kimura Akihiro , Naka Tetsuji , Nakahama Taisuke , Chinen Ichino , Masuda Kazuya , Nohara Keiko , Fujii-Kuriyama Yoshiaki , Kishimoto Tadamitsu
Published: August 2009

Toll-like receptor (TLR) signals perform a crucial role in innate immune responses to pathogens. In this study, we found that the aryl hydrocarbon receptor (Ahr) negatively regulates inflammatory responses mediated by lipopolysaccharide (LPS) in macrophages. Ahr was induced in macrophages stimulated by LPS, but not by transforming growth factor (TGF)-β plus interleukin (IL)-6, which can induce Ahr in naive T cells. The production of IL-6 and tumor necrosis factor (TNF)-α by LPS was significantly elevated in Ahr-deficient macrophages compared with that in wild-type (WT) cells. Ahr-deficient mice were more highly sensitive to LPS-induced lethal shock than WT mice. Signal transducer and activator of transcription 1 (Stat1) deficiency, as well as Ahr deficiency, augmented LPS-induced IL-6 production. We found that Ahr forms a complex with Stat1 and nuclear factor-kappa B (NF-κB) in macrophages stimulated by LPS, which leads to inhibition of the promoter activity of IL-6. Ahr thus plays an essential role in the negative regulation of the LPS signaling pathway through interaction with Stat1.
Distinction of the memory B cell response to cognate antigen versus bystander inflammatory signals
Authors: Benson Micah J. , Elgueta Raul , Schpero William , Molloy Michael , Zhang Weijun , Usherwood Edward , Noelle Randolph J.
Published: August 2009

The hypothesis that bystander inflammatory signals promote memory B cell (BMEM) self-renewal and differentiation in an antigen-independent manner is critically evaluated herein. To comprehensively address this hypothesis, a detailed analysis is presented examining the response profiles of B-2 lineage B220+IgG+ BMEM toward cognate protein antigen in comparison to bystander inflammatory signals. After in vivo antigen encounter, quiescent BMEM clonally expand. Surprisingly, proliferating BMEM do not acquire germinal center (GC) B cell markers before generating daughter BMEM and differentiating into plasma cells or form structurally identifiable GCs. In striking contrast to cognate antigen, inflammatory stimuli, including Toll-like receptor agonists or bystander T cell activation, fail to induce even low levels of BMEM proliferation or differentiation in vivo. Under the extreme conditions of adjuvanted protein vaccination or acute viral infection, no detectable bystander proliferation or differentiation of BMEM occurred. The absence of a BMEM response to nonspecific inflammatory signals clearly shows that BMEM proliferation and differentiation is a process tightly controlled by the availability of cognate antigen.