bluuebunny/crossref_metadata_2025 huggingface dataset:
A Murine Model of Obesity With Accelerated Atherosclerosis
Authors: King Victoria L. , Hatch Nicholas W. , Chan Huei‐Wei , de Beer Marcielle C. , de Beer Frederick C. , Tannock Lisa R.
Published: June 2009

The epidemic of obesity sweeping developed nations is accompanied by an increase in atherosclerotic cardiovascular diseases. Dyslipidemia, diabetes, hypertension, and obesity are risk factors for cardiovascular disease. However, delineating the mechanism of obesity‐accelerated atherosclerosis has been hampered by a paucity of animal models. Similar to humans, apolipoprotein E–deficient (apoE−/−) mice spontaneously develop atherosclerosis over their lifetime. To determine whether apoE−/− mice would develop obesity with accelerated atherosclerosis, we fed mice diets containing 10 (low fat (LF)) or 60 (high fat (HF)) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total cholesterol, triglycerides, or leptin concentrations. Plasma concentrations of the acute‐phase reactant serum amyloid A (SAA) are elevated in both obesity and cardiovascular disease. Accordingly, plasma SAA concentrations were increased fourfold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro‐ and antiatherogenic lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the antiatherogenic lipoprotein high‐density lipoprotein (HDL). Moreover, SAA was localized with apoB‐containing lipoproteins and biglycan in the vascular wall. Taken together, these data suggest male apoE‐deficient mice are a model of metabolic syndrome and that chronic low level inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.
Health Outcomes of Gastric Bypass Patients Compared to Nonsurgical, Nonintervened Severely Obese
Authors: Adams Ted D. , Pendleton Robert C. , Strong Michael B. , Kolotkin Ronette L. , Walker James M. , Litwin E. Sheldon , Berjaoui Wael K. , LaMonte Michael J. , Cloward Tom V. , Avelar Erick , Owan Theophilus E. , Nuttall Robert T. , Gress Richard E. , Crosby Ross D. , Hopkins Paul N. , Brinton Eliot A. , Rosamond Wayne D. , Wiebke Gail A. , Yanowitz Frank G. , Farney Robert J. , Halverson R. Chad , Simper Steven C. , Smith Sherman C. , Hunt Steven C.
Published: June 2009

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight‐loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m2) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population‐based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes‐related variables, resting metabolic rate (RMR), sleep apnea, and health‐related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF‐36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux‐en‐Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight‐loss intervention was highly effective for weight loss, improved health‐related quality of life, and resolution of major obesity‐associated complications measured at 2 years.
Impacts of Visceral Adipose Tissue and Subcutaneous Adipose Tissue on Metabolic Risk Factors in Middle‐aged Japanese
Authors: Oka Rie , Miura Katsuyuki , Sakurai Masaru , Nakamura Koshi , Yagi Kunimasa , Miyamoto Susumu , Moriuchi Tadashi , Mabuchi Hiroshi , Koizumi Junji , Nomura Hideki , Takeda Yoshiyu , Inazu Akihiro , Nohara Atsushi , Kawashiri Masa‐Aki , Nagasawa Shinya , Kobayashi Junji , Yamagishi Masakazu
Published: June 2009

Regional fat distribution rather than overall fat volume has been considered to be important to understanding the link between obesity and metabolic disorders. We aimed to evaluate the independent associations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with metabolic risk factors in apparently healthy middle‐aged Japanese. Participants were 1,119 men and 854 women aged 38–60 years who were not taking medications for diabetes, hypertension, or dyslipidemia. VAT and SAT were measured by use of computed tomography (CT) scanning. VAT and SAT were significantly and positively correlated with each other in men (r = 0.531, P < 0.001) and women (r = 0.589, P < 0.001). In multiple regression analyses, either measure of abdominal adiposity (VAT or SAT) was positively associated with blood pressure, fasting plasma glucose, and log triglyceride (P < 0.001) and inversely with high‐density lipoprotein (HDL)‐cholesterol (P < 0.001). When VAT and SAT were simultaneously included in the model, the association of VAT with triglycerides was maintained (P < 0.001) but that of SAT was lost. The same was true for HDL‐cholesterol in women. For fasting plasma glucose, the association with VAT was strong (P < 0.001) and the borderline association with SAT was maintained (P = 0.060 in men and P = 0.020 in women). Both VAT and SAT were independently associated with blood pressure (P < 0.001). Further adjustment for anthropometric indices resulted in the independent association only with VAT for all risk factors. In conclusion, impacts of VAT and SAT differed among risk factors. VAT showed dominant impacts on triglyceride concentrations in both genders and on HDL‐cholesterol in women, while SAT also had an independent association with blood pressure.
Silica-Based Materials for Advanced Chemical Applications
Authors: Pagliaro Mario
Published: June 2009

This is the first book to address the hot topic of functional silica gels and their applications. Originally used mainly in chromatography, specialized silica gels have evolved into crucially important functional nanomaterials suitable for use in, amongst other things, chemical synthesis, analysis, purification, surface protection and drug release. It is estimated that the world's current 1 billion dollar market for sol-gels (mostly silica-based) will grow by more than 5% per year from 2006 to 2011. Actually, as many revolutionary products are now reaching the market, it will increase much faster. Commercial applications include glasses, paints, catalysts and fragrances. Medical uses include the delivery of vitamins, hormones and acne treatments and the synthesis of the powerful anticancer drug, taxol. Sol-gel technology also forms the basis of the MetaChip, thanks to which potential new drugs can be identified rapidly and simultaneously. With content relevant to both scientific and commercial viewpoints, the book will interest researchers and undergraduates as well as managers and consultants in the chemical industry. Those from an industrial background will gain a clear picture of what this technology is all about and how it can be used to solve their specific problems. All readers will benefit from the clear, concise style and consistent treatment of topics. The book demonstrates how chemists synthesize, from the bottom-up, tailor-made (nano)materials of immense practical importance spanning the fields of chemistry, physics, materials science, engineering, biology and medicine. It also shows how the versatility of silica gels results from their physical and chemical properties. An updated outlook on new commercial products, and the companies which make them, greatly adds relevance and practical value to the text.
Leadership: Finding Your Inner Throgmartin
Authors: Golper Lee Ann C.
Published: June 2009

This article suggests we all have leadership potential within us (our inner Throgmartin). Unlocking and cultivating that potential requires acquiring leadership knowledge, perfecting leadership skills, and developing a leadership style that fits best with one's personality and role (director, manager, volunteer). This article looks at sources of empowerment available to leaders and the sources of stress in leadership. The keys to achieving and sustaining resilient, healthy leaders, particularly in difficult times, are discussed. The article suggests resilient leadership lies with work and home life integration, and networking with other leaders.
Facilitating Supervisee Cultural Fluency for a Multicultural Society
Authors: Staub Kenneth J.
Published: June 2009

Multiculturalism has been, and will only continue to become more of a fact in our society and professional practice. Because of this, supervisors have both a practical reason and ethical responsibility for facilitating their supervisees' cultural fluency. This article explores multiculturalism, offering a working definition, emphasizing the dynamic nature of the concept, and reasserting its need for inclusion in the supervisory process. The development of cultural fluency is presented, primarily as a process predicated upon the supervisee's attainment of self-awareness as a means of establishing responsive, reciprocal, and respectful relationships. Supervisor facilitation of cultural fluency is addressed in the context of modeling relevant skills for the supervisee in the clinical setting. Indicators for assessing supervisor performance as multicultural clinic educators are presented, as are criteria for evaluating the supervisee's progression toward becoming a culturally fluent practitioner and individual.
Responses to Intervention Program Outcomes for Pre-K
Authors: Webb Lisa , Griggs Leigh Anne , Green Charlette
Published: June 2009

This article addresses outcomes as they relate to a responsiveness-to-intervention (RTI/RtI) model used in a pre-kindergarten (pre-k) setting. The RTI model requires frequent progress monitoring of at-risk students' responses to evidence-based interventions. Treatment outcomes studies judge whether interventions are effective for their intended purpose. This article defines outcomes, describes the importance of outcomes in an RTI model, and tells how to obtain outcome data. Outcomes from a pre-k language intervention will be presented.
Counseling Adolescents With Hearing Loss Using a Narrative Therapy Approach
Authors: Crowell Rebecca L. Nelson , Hanenburg Julie , Gilbertson Amy
Published: June 2009

Audiologists have a responsibility to counsel patients with auditory concerns on methods to manage the inherent challenges associated with hearing loss at every point in the process: evaluation, hearing aid fitting, and follow-up visits. Adolescents with hearing loss struggle with the typical developmental challenges along with communicative challenges that can erode one's self-esteem and self-worth. The feeling of “not being connected” to peers can result in feelings of isolation and depression. This article advocates the use of a Narrative Therapy approach to counseling adolescents with hearing loss. Adolescents with hearing loss often have problem-saturated narratives regarding various components of their daily life, friendships, amplification, academics, etc. Audiologists can work with adolescents with hearing loss to deconstruct the problem-saturated narratives and rebuild the narratives into a more empowering message. As the adolescent retells their positive narrative, they are likely to experience increased self-esteem and self-worth.
The Speech-Language Pathologist and Reading: Opportunities to Extend Services for the Children We Serve
Authors: Ritter Michaela J.
Published: June 2009

In recent years, major changes have occurred in the field of speech-language pathology and education. In the past 2 decades researchers, educators, and speech-language pathologists (SLPs) have increased their focus on the identification, assessment, and treatment of reading disabilities in children (Catts, 1991; Catts, Fey, Zhang, & Tomblin, 2001; Justice & Ezell, 2004; Kaderavek & Justice, 2004). The primary goal of this article is to discuss a variety of ways that the speech-language pathologist can be both directly and indirectly involved in working with children who present with language and reading impairments. For example, Baylor University's Department of Communication Sciences and Disorders has had the opportunity to be involved in the prevention, identification, and treatment of reading disabilities in children both in a direct and indirect way.
How Do I Work With the Reading Teacher Without Becoming One?
Authors: Angel Susan E. , Butler Yolonda G. , Cichra Deborah L. , Moore Cheriee C. , Simonet Judith
Published: June 2009

The Speech-Language Program of Orange County Public Schools (OCPS), Orlando, FL has provided ongoing intensive professional development and support to their speech-language pathologists to facilitate inclusive services for students who are identified as speech-language impaired. However, providing inclusive services in the general and special education classrooms often raises the question, “How should speech-language pathologists provide services in the classroom, focusing on classroom curriculum without becoming the reading teacher?” This article discusses how a speech-language pathologist differentiates his/her services from the responsibilities of the reading teacher.
Science Through Language: Language Through Science; Working With Teachers to Make Every Moment a Language Moment
Authors: Gottfred Catherine H. , Lybolt John
Published: June 2009

Preschool teachers have been tasked with developing emergent literacy skills, frequently co-teaching with a speech-language pathologist. Science activities offer opportunities to provide both content and language experiences in preschool and kindergarten. A “Language Through Science” (LTS) approach integrates language and science in preschool and kindergarten classrooms, emphasizing techniques that can be the language underpinnings of emergent literacy. We review the theory, background, outcomes data, and sample activities of a language-focused science program that can help the speech-language pathologist support content with emergent literacy activities in a classroom curriculum.
SLPs Then and Now: Keeping the Vision While Infusing Accountability and Function
Authors: Kerins Marie R. , Sheridan Karen , Feinberg Karen
Published: June 2009

Incorporating literacy into the caseload of the school-based speech-language pathologist is often met with mixed feelings. This article explores the role of the speech-language pathologist (SLP) in the literacy arena from the mid 1970s to the present. It becomes apparent that SLPs have long recognized the relationship between the areas of language we are trained to address and an individual's ability to read and write. Changes have occurred over the last 25 years with an increase in research supporting the reciprocal relationship between language and literacy, a movement toward evidenced-based practice, and greater accountability regarding education and related service goals. While SLPs were exploring the language-literacy relationships several decades ago, current practice patterns demonstrate exemplary examples of collaboration with classroom teachers and SLPs. Two speech-language pathologists from a public school system in Maryland share how they have effectively worked on areas of prevention and intervention in a collaborative manner. Examples are also provided of “other roles” we often provide to general educators and families.
Research on Reading: What SLPs Want (or Need) to Know
Authors: Montgomery Judy
Published: June 2009

As increasing numbers of speech language pathologists (SLPs) have embraced their burgeoning roles in written as well as spoken language intervention, they have recognized that there is much to be gained from the research in reading. While some SLPs reportedly fear they will “morph” into reading teachers, many more are confidently aware that SLPs who work with adult clients routinely use reading as one of their rehabilitation modalities. Reading functions as both a tool to reach language in adults, and as a measure of successful therapy. This advanced cognitive skill can serve the same purpose for children. Language is the foundational support to reading. Consequently spoken language problems are often predictors of reading and writing challenges that may be ahead for the student (Juel & Deffes, 2004; Moats, 2001; Wallach, 2004). A targeted review of reading research may assist the SLP to appreciate the language/reading interface.
What Does the User Want to See? What do the Data Want to Be?
Authors: Pretorius A. Johannes , Van Wijk Jarke J.
Published: June 2009

Information visualization is a user-centered design discipline. In this article we argue, however, that designing information visualization techniques often requires more than designing for user requirements. Additionally, the data that are to be visualized must also be carefully considered. An approach based on both the user and their data is encapsulated by two questions, which we argue information visualization designers should continually ask themselves: ‘What does the user want to see?’ and ‘What do the data want to be?’ As we show by presenting cases, these two points of departure are mutually reinforcing. By focusing on the data, new insight is gained into the requirements of the user, and vice versa, resulting in more effective visualization techniques.
An Imaginable Community: The Material Culture of Nation-Building in Early Republican Turkey
Authors: Kezer Zeynep
Published: June 2009

This paper examines the spatial strategies used to achieve national integration in the formative years (1923–45) of the Turkish Republic. During this critical period, despite a severe shortage of human and material resources, Turkey's leaders undertook ambitious infrastructural projects, including the construction of roads, railroads, bridges, institutional buildings, and the implementation of uniform urban plans, which were meant to transform the face of the country. These projects generated webs of uniform and centralized services, which enabled the state to assume a more active role in shaping the daily life of its citizens. Crucially, they also forged a standard recognizable material culture throughout Turkey. I argue that this extensive tangible scaffolding of public works, which introduced new types of spaces and practices, reworked the rhythms and routines of daily life, and created new networks of accessibility across the country, was instrumental for cultivating people's ability to relate the local with a larger national geography, thus rendering the nation an imaginable community.
Becoming Tourist: Renegotiating the Visual in the Tourist Experience
Authors: Scarles Caroline
Published: June 2009

This paper seeks to renegotiate the role of visuals and visual practice within the tourist experience. Embracing recent developments in tourist studies, I seek to move from understanding tourism as a series of predetermined, linear, and static stages through which we pass to be a tourist. In doing so, I explore the ways in which visuals, in particular photography and subsequent visualities, enliven tourists' becoming through a multiplicity of fluid and dynamic performances, practices, and processes. I suggest photography is not merely an empty practice, but, rather, lights up the tourist experience. The emerging dynamics of visual practice renegotiate new understandings between tourists and place to establish a series of conceptual moments that outline photography as: political artefacts, reflexive performances, the imagination of space, embodied visualities, and ethical prompts. Such conceptualisations and practices of tourist photography are by no means arbitrary, but are situated in a framework of visuality that highlights key moments of anticipation, rewriting, and remembrance and reliving. Thus, I move beyond notions of the hermeneutic cycle of travel, and present photographs and photography as complex performative spaces that extend beyond divisible boundaries of the before, during, and after travel experiences and infiltrate the entire tourist experience.
Biopolitics, Biopower, and the Return of Sovereignty
Authors: Coleman Mathew , Grove Kevin
Published: June 2009

In this paper we want to open up for discussion what counts as ‘biopolitics’—a term frequently used by critics and devotees alike to describe the organization of political power and authority in a world after Bretton Woods, the Cold War, and 9/11. We do so on two fronts. On the one hand, we contrast Foucault on war and the normalizing society, Agamben on thanatopolitics, and Hardt and Negri on biopotenza. Our goal here is to draw attention to multiple competing definitions of biopolitics, and in so doing problematize the term as a catchall category to describe either the ‘nonsovereign’ or the ‘postsovereign’ operation of power. On the other hand, while refusing some baseline definition of what counts as biopolitics, we develop our own specifically geographical criticisms of Agamben and Hardt and Negri on the topic of biopolitics. Following Sparke's recent interrogation of postfoundational thought on account of its oftentimes buried metaphysics of geopresence, we submit that Agamben as well as Hardt and Negri deploy biopolitics in both metaphysical and metageographical ways. We contrast this with Foucault's inductive, genealogical, and time-specific and place-specific use of the concept.
Revision of the oribatid mite genus Austronothrus Hammer (Acari:Oribatida):sexual dimorphism and a re-evaluation of the phylogenetic relationships of the family Crotoniidae
Authors: Colloff Matthew J. , Cameron Stephen L.
Published: June 2009

The Gondwanan relict oribatid mite family Crotoniidae contains the genera Austronothrus Hammer, 1966, Crotonia Thorell, 1876 and Holonothrus Wallwork, 1963. This family is of considerable interest biogeographically and also because the members of the family may have re-evolved sexuality from thelytokous parthenogenetic ancestors. Crotonia and Holonothrus are speciose and widely distributed whereas Austronothrus is obscure, hitherto monospecific and known only from New Zealand. We revise Austronothrus and compare it with its better-known congeners. Two new species of Austronothrus are described from New Zealand, namely A. clarki, sp. nov., and A. flagellatus, sp. nov. The only previously known species, Austronothrus curviseta Hammer, 1966, is redescribed and the genus is redefined. The presence of male specimens of all species confirmed Austronothrus as a sexual genus, like its congeners. Secondary sexual characteristics within Austronothrus and Crotonia include significant differences in body size and proportion, as well as the lengths and shapes of various setae, predominantly those of the notogastral region. Because these characters are frequently used by taxonomists to separate and define species within the Crotoniidae, it is important that the sex of adult specimens be determined to avoid describing conspecific males and females as separate species. A phylogenetic analysis based on morphological characters shows the crotoniid genera nested within the Camisiidae, with Camisia von Heyden, 1826 basal to the crotoniid clade of Austronothrus, Holonothrus and Crotonia, and with a clade of Platynothrus Berlese, 1913, Heminothrus Berlese, 1913 and Paracamisia Olszanowski & Norton, 2002 (Camisiidae) forming the sister clade of Camisia + Crotoniidae. Thus, Camisiidae is paraphyletic with respect to Crotoniidae. The family Crotoniidae is revised in light of the cladistic analysis, and relegated to subfamily rank. Three subfamilies are defined within the Camisiidae : Crotoniinae (containing Crotonia, Austronothrus and Holonothrus), Camisiinae (containing Camisia) and Heminothridae, subfam. nov. (containing Heminothrus, Platynothrus and Neonothrus Forsslund, 1955). Nothrus maximus Trägårdh, 1901 belongs to the genus Platynothrus and is recombined.
Methodological issues in the design and conduct of public health computer assisted telephone interview surveys: the case of informal carers in Australia
Authors: Van Dyke Nina
Published: June 2009

The academic literature contains surprisingly little information regarding the design and conduct of surveys dealing with sensitive social issues. The present paper is an attempt to help fill that gap so that other researchers conducting similar projects can learn from our experience. In particular, I focus on the various challenges we encountered in carrying out a computer assisted telephone interview (CATI) survey of informal carers in Australia, our responses to these challenges and our learnings from this endeavour. In the present article, I discuss the following issues: cost-efficient sampling for small numbers; opt-out versus opt-in approaches to respondent participation; status errors in administrative data; reducing respondent refusals; interviewing non-English speakers; questionnaire topic order; carers who care for more than one person; and interviewer training, including interviewer and/or respondent distress. The conclusions were: (1) carers are generally willing and able to answer quite sensitive questions around caring, despite the fact that they may become distressed in doing so; (2) carers are willing to answer a rather long (25 min) telephone survey; (3) thorough interviewer training is critically important, with an emphasis on achieving a balance between sensitivity and efficiency; and (4) respondents should be given the opportunity at the end of the interview to make additional comments and to provide their contact details should they desire follow up from an appropriate authority.
Environmental transmission of low pathogenicity avian influenza viruses and its implications for pathogen invasion
Authors: Rohani Pejman , Breban Romulus , Stallknecht David E. , Drake John M.
Published: June 2009

Understanding the transmission dynamics and persistence of avian influenza viruses (AIVs) in the wild is an important scientific and public health challenge because this system represents both a reservoir for recombination and a source of novel, potentially human-pathogenic strains. The current paradigm locates all important transmission events on the nearly direct fecal/oral bird-to-bird pathway. In this article, on the basis of overlooked evidence, we propose that an environmental virus reservoir gives rise to indirect transmission. This transmission mode could play an important epidemiological role. Using a stochastic model, we demonstrate how neglecting environmentally generated transmission chains could underestimate the explosiveness and duration of AIV epidemics. We show the important pathogen invasion implications of this phenomenon: the nonnegligible probability of outbreak even when direct transmission is absent, the long-term infectivity of locations of prior outbreaks, and the role of environmental heterogeneity in risk.
mTOR complex 2 in adipose tissue negatively controls whole-body growth
Authors: Cybulski Nadine , Polak Pazit , Auwerx Johan , Rüegg Markus A. , Hall Michael N.
Published: June 2009

Mammalian target of rapamycin (mTOR), a highly conserved protein kinase that controls cell growth and metabolism in response to nutrients and growth factors, is found in 2 structurally and functionally distinct multiprotein complexes termed mTOR complex 1 (mTORC1) and mTORC2. mTORC2, which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB. Though the role of mTOR in single cells is relatively well characterized, the role of mTOR signaling in specific tissues and how this may contribute to overall body growth is poorly understood. To examine the role of mTORC2 in an individual tissue, we generated adipose-specific
rictor
knockout mice (
rictor
ad−/−
).
Rictor
ad−/−
mice are increased in body size due to an increase in size of nonadipose organs, including heart, kidney, spleen, and bone. Furthermore,
rictor
ad−/−
mice have a disproportionately enlarged pancreas and are hyperinsulinemic, but glucose tolerant, and display elevated levels of insulin-like growth factor 1 (IGF1) and IGF1 binding protein 3 (IGFBP3). These effects are observed in mice on either a high-fat or a normal diet, but are generally more pronounced in mice on a high-fat diet. Our findings suggest that adipose tissue, in particular mTORC2 in adipose tissue, plays an unexpectedly central role in controlling whole-body growth.
Two roles for theDrosophilaIKK complex in the activation of Relish and the induction of antimicrobial peptide genes
Authors: Ertürk-Hasdemir Deniz , Broemer Meike , Leulier François , Lane William S. , Paquette Nicholas , Hwang Daye , Kim Chan-Hee , Stöven Svenja , Meier Pascal , Silverman Neal
Published: June 2009

TheDrosophilaNF-κB transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after Gram-negative bacterial infection. Relish is a bipartite NF-κB precursor protein, with an N-terminal Rel homology domain and a C-terminal IκB-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-κB module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both theDrosophilaIκB kinase (IKK) and death-related ced-3/Nedd2-like protein (DREDD), theDrosophilacaspase-8 like protease. In this report, we show that the IKK complex controls Relish by direct phosphorylation on serines 528 and 529. Surprisingly, these phosphorylation sites are not required for Relish cleavage, nuclear translocation, or DNA binding. Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish.
Functional features cause misfolding of the ALS-provoking enzyme SOD1
Authors: Nordlund Anna , Leinartaitė Lina , Saraboji Kadhirvel , Aisenbrey Christopher , Gröbner Gerhard , Zetterström Per , Danielsson Jens , Logan Derek T. , Oliveberg Mikael
Published: June 2009

The structural integrity of the ubiquitous enzyme superoxide dismutase (SOD1) relies critically on the correct coordination of Cu and Zn. Loss of these cofactors not only promotes SOD1 aggregation in vitro but also seems to be a key prerequisite for pathogenic misfolding in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We examine here the consequences of Zn
2+
loss by selectively removing the Zn site, which has been implicated as the main modulator of SOD1 stability and disease competence. After Zn-site removal, the remaining Cu ligands can coordinate a nonnative Zn
2+
ion with μM affinity in the denatured state, and then retain this ion throughout the folding reaction. Without the restriction of a metallated Zn site, however, the Cu ligands fail to correctly coordinate the nonnative Zn
2+
ion: Trapping of a water molecule causes H48 to change rotamer and swing outwards. The misligation is sterically incompatible with the native structure. As a consequence, SOD1 unfolds locally and interacts with neighboring molecules in the crystal lattice. The findings point to a critical role for the native Zn site in controlling SOD1 misfolding, and show that even subtle changes of the metal-loading sequence can render the wild-type protein the same structural properties as ALS-provoking mutations. This frustrated character of the SOD1 molecule seems to arise from a compromise between optimization of functional and structural features.
The water footprint of bioenergy
Authors: Gerbens-Leenes Winnie , Hoekstra Arjen Y. , van der Meer Theo H.
Published: June 2009

All energy scenarios show a shift toward an increased percentage of renewable energy sources, including biomass. This study gives an overview of water footprints (WFs) of bioenergy from 12 crops that currently contribute the most to global agricultural production: barley, cassava, maize, potato, rapeseed, rice, rye, sorghum, soybean, sugar beet, sugar cane, and wheat. In addition, this study includes jatropha, a suitable energy crop. Since climate and production circumstances differ among regions, calculations have been performed by country. The WF of bioelectricity is smaller than that of biofuels because it is more efficient to use total biomass (e.g., for electricity or heat) than a fraction of the crop (its sugar, starch, or oil content) for biofuel. The WF of bioethanol appears to be smaller than that of biodiesel. For electricity, sugar beet, maize, and sugar cane are the most favorable crops [50 m
3
/gigajoule (GJ)]. Rapeseed and jatropha, typical energy crops, are disadvantageous (400 m
3
/GJ). For ethanol, sugar beet, and potato (60 and 100 m
3
/GJ) are the most advantageous, followed by sugar cane (110 m
3
/GJ); sorghum (400 m
3
/GJ) is the most unfavorable. For biodiesel, soybean and rapeseed show to be the most favorable WF (400 m
3
/GJ); jatropha has an adverse WF (600 m
3
/GJ). When expressed per L, the WF ranges from 1,400 to 20,000 L of water per L of biofuel. If a shift toward a greater contribution of bioenergy to energy supply takes place, the results of this study can be used to select the crops and countries that produce bioenergy in the most water-efficient way.
LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis
Authors: Hu Xin , Li Xingguo , Valverde Kristell , Fu Xueqi , Noguchi Constance , Qiu Yi , Huang Suming
Published: June 2009

TAL1 is a critical transcription factor required for hematopoiesis. However, perturbation of its activity often leads to T cell leukemia. Whether and how its transcriptional activities are regulated during hematopoiesis remains to be addressed. Here, we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells. The enzymatic domain of LSD1 plays an important role in repressing the TAL1-directed transcription of GAL4 reporter linked to a thymidine kniase minimal promoter. Furthermore, we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation. Consistent with the rapid changes of TAL1–corepressor complex during differentiation, TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells. Finally, shRNA-mediated knockdown of LSD1 in MEL cells resulted in derepression of the TAL1 target gene accompanied by increasing dimeH3K4 at the promoter region. Thus, our data revealed that histone lysine demethylase LSD1 may negatively regulate TAL1-mediated transcription and suggest that the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs.
Engineering size-scaling of plastic deformation in nanoscale asperities
Authors: Ward D. K. , Farkas D. , Lian J. , Curtin W. A. , Wang J. , Kim K.-S. , Qi Y.
Published: June 2009

Size-dependent plastic flow behavior is manifested in nanoindentation, microbending, and pillar-compression experiments and plays a key role in the contact mechanics and friction of rough surfaces. Recent experiments using a hard flat plate to compress single-crystal Au nano-pyramids and others using a Berkovich indenter to indent flat thin films show size scaling into the 100-nm range where existing mechanistic models are not expected to apply. To bridge the gap between single-dislocation nucleation at the 1-nm scale and dislocation-ensemble plasticity at the 1-μm scale, we use large-scale molecular dynamics (MD) simulations to predict the magnitude and scaling of hardness
H
versus contact size ℓ

c

in nano-pyramids. Two major results emerge: a regime of near-power-law size scaling
H
≈ ℓ

c

−η
exists, with η
MD
≈ 0.32 compared with η
expt
≈ 0.75, and unprecedented quantitative and qualitative agreement between MD and experiments is achieved, with
H
MD
≈ 4 GPa at ℓ

c

= 36 nm and
H
expt
≈ 2.5 GPa at ℓ

c

= 100 nm. An analytic model, incorporating the energy costs of forming the geometrically necessary dislocation structures that accommodate the deformation, is developed and captures the unique magnitude and size scaling of the hardness at larger MD sizes and up to experimental scales while rationalizing the transition in scaling between MD and experimental scales. The model suggests that dislocation–dislocation interactions dominate at larger scales, whereas the behavior at the smallest MD scales is controlled by nucleation over energy barriers. These results provide a basic framework for understanding and predicting size-dependent plasticity in nanoscale asperities under contact conditions in realistic engineered surfaces.
Structure of a mitochondrial ribosome with minimal RNA
Authors: Sharma Manjuli R. , Booth Timothy M. , Simpson Larry , Maslov Dmitri A. , Agrawal Rajendra K.
Published: June 2009

The
Leishmania tarentolae
mitochondrial ribosome (Lmr) is a minimal ribosomal RNA (rRNA)-containing ribosome. We have obtained a cryo-EM map of the Lmr. The map reveals several features that have not been seen in previously-determined structures of eubacterial or eukaryotic (cytoplasmic or organellar) ribosomes to our knowledge. Comparisons of the Lmr map with X-ray crystallographic and cryo-EM maps of the eubacterial ribosomes and a cryo-EM map of the mammalian mitochondrial ribosome show that (
i
) the overall structure of the Lmr is considerably more porous, (
ii
) the topology of the intersubunit space is significantly different, with fewer intersubunit bridges, but more tunnels, and (
iii
) several of the functionally-important rRNA regions, including the α-sarcin-ricin loop, have different relative positions within the structure. Furthermore, the major portions of the mRNA channel, the tRNA passage, and the nascent polypeptide exit tunnel contain Lmr-specific proteins, suggesting that the mechanisms for mRNA recruitment, tRNA interaction, and exiting of the nascent polypeptide in Lmr must differ markedly from the mechanisms deduced for ribosomes in other organisms. Our study identifies certain structural features that are characteristic solely of mitochondrial ribosomes and other features that are characteristic of both mitochondrial and chloroplast ribosomes (i.e., organellar ribosomes).
Key role of coupling, delay, and noise in resting brain fluctuations
Authors: Deco Gustavo , Jirsa Viktor , McIntosh A. R. , Sporns Olaf , Kötter Rolf
Published: June 2009

A growing body of neuroimaging research has documented that, in the absence of an explicit task, the brain shows temporally coherent activity. This so-called “resting state” activity or, more explicitly, the default-mode network, has been associated with daydreaming, free association, stream of consciousness, or inner rehearsal in humans, but similar patterns have also been found under anesthesia and in monkeys. Spatiotemporal activity patterns in the default-mode network are both complex and consistent, which raises the question whether they are the expression of an interesting cognitive architecture or the consequence of intrinsic network constraints. In numerical simulation, we studied the dynamics of a simplified cortical network using 38 noise-driven (Wilson–Cowan) oscillators, which in isolation remain just below their oscillatory threshold. Time delay coupling based on lengths and strengths of primate corticocortical pathways leads to the emergence of 2 sets of 40-Hz oscillators. The sets showed synchronization that was anticorrelated at <0.1 Hz across the sets in line with a wide range of recent experimental observations. Systematic variation of conduction velocity, coupling strength, and noise level indicate a high sensitivity of emerging synchrony as well as simulated blood flow blood oxygen level-dependent (BOLD) on the underlying parameter values. Optimal sensitivity was observed around conduction velocities of 1–2 m/s, with very weak coupling between oscillators. An additional finding was that the optimal noise level had a characteristic scale, indicating the presence of stochastic resonance, which allows the network dynamics to respond with high sensitivity to changes in diffuse feedback activity.
Asymmetric fMRI adaptation reveals no evidence for mirror neurons in humans
Authors: Lingnau Angelika , Gesierich Benno , Caramazza Alfonso
Published: June 2009

Neurons in macaque ventral premotor cortex and inferior parietal lobe discharge during both the observation and the execution of motor acts. It has been claimed that these so-called mirror neurons form the basis of action understanding by matching the visual input with the corresponding motor program (
direct matching
). Functional magnetic resonance imaging (fMRI) adaptation can be used to test the direct matching account of action recognition by determining whether putative mirror neurons show adaptation for repeated motor acts independently of whether they are observed or executed. An unambiguous test of the hypothesis requires that the motor acts be meaningless to ensure that any adaptation effect is directly because of movement recognition/motor execution and not contextually determined inferences. We found adaptation for motor acts that were repeatedly observed or repeatedly executed. We also found adaptation for motor acts that were first observed and then executed, as would be expected if a previously seen act primed the subsequent execution of that act. Crucially, we found no signs of adaptation for motor acts that were first executed and then observed. Failure to find cross-modal adaptation for executed and observed motor acts is not compatible with the core assumption of mirror neuron theory, which holds that action recognition and understanding are based on motor simulation.
A primate subfamily of galectins expressed at the maternal–fetal interface that promote immune cell death
Authors: Than Nandor Gabor , Romero Roberto , Goodman Morris , Weckle Amy , Xing Jun , Dong Zhong , Xu Yi , Tarquini Federica , Szilagyi Andras , Gal Peter , Hou Zhuocheng , Tarca Adi L. , Kim Chong Jai , Kim Jung-Sun , Haidarian Saied , Uddin Monica , Bohn Hans , Benirschke Kurt , Santolaya-Forgas Joaquin , Grossman Lawrence I. , Erez Offer , Hassan Sonia S. , Zavodszky Peter , Papp Zoltan , Wildman Derek E.
Published: June 2009

Galectins are proteins that regulate immune responses through the recognition of cell-surface glycans. We present evidence that 16 human galectin genes are expressed at the maternal–fetal interface and demonstrate that a cluster of 5 galectin genes on human chromosome 19 emerged during primate evolution as a result of duplication and rearrangement of genes and pseudogenes via a birth and death process primarily mediated by transposable long interspersed nuclear elements (LINEs). Genes in the cluster are found only in anthropoids, a group of primate species that differ from their strepsirrhine counterparts by having relatively large brains and long gestations. Three of the human cluster genes (LGALS13, -14, and-16) were found to be placenta-specific. Homology modeling revealed conserved three-dimensional structures of galectins in the human cluster; however, analyses of 24 newly derived and 69 publicly available sequences in 10 anthropoid species indicate functional diversification by evidence of positive selection and amino acid replacements in carbohydrate-recognition domains. Moreover, we demonstrate altered sugar-binding capacities of 6 recombinant galectins in the cluster. We show that human placenta-specific galectins are predominantly expressed by the syncytiotrophoblast, a primary site of metabolic exchange where, early during pregnancy, the fetus comes in contact with immune cells circulating in maternal blood. Because ex vivo functional assays demonstrate that placenta-specific galectins induce the apoptosis of T lymphocytes, we propose that these galectins reduce the danger of maternal immune attacks on the fetal semiallograft, presumably conferring additional immune tolerance mechanisms and in turn sustaining hemochorial placentation during the long gestation of anthropoid primates.
Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes
Authors: Wang Zhu , Zhou X. Edward , Motola Daniel L. , Gao Xin , Suino-Powell Kelly , Conneely Aoife , Ogata Craig , Sharma Kamalesh K. , Auchus Richard J. , Lok James B. , Hawdon John M. , Kliewer Steven A. , Xu H. Eric , Mangelsdorf David J.
Published: June 2009

Nematode parasitism is a worldwide health problem resulting in malnutrition and morbidity in over 1 billion people. The molecular mechanisms governing infection are poorly understood. Here, we report that an evolutionarily conserved nuclear hormone receptor signaling pathway governs development of the stage 3 infective larvae (iL3) in several nematode parasites, including
Strongyloides stercoralis, Ancylostoma spp.
, and
Necator americanus
. As in the free-living
Caenorhabditis elegans
, steroid hormone-like dafachronic acids induced recovery of the dauer-like iL3 in parasitic nematodes by activating orthologs of the nuclear receptor DAF-12. Moreover, administration of dafachronic acid markedly reduced the pathogenic iL3 population in
S. stercoralis
, indicating the potential use of DAF-12 ligands to treat disseminated strongyloidiasis. To understand the pharmacology of targeting DAF-12, we solved the 3-dimensional structure of the
S. stercoralis
DAF-12 ligand-binding domain cocrystallized with dafachronic acids. These results reveal the molecular basis for DAF-12 ligand binding and identify nuclear receptors as unique therapeutic targets in parasitic nematodes.
Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands
Authors: Zidar David A. , Violin Jonathan D. , Whalen Erin J. , Lefkowitz Robert J.
Published: June 2009

CCL19 and CCL21 are endogenous agonists for the seven-transmembrane receptor CCR7. They are equally active in promoting G protein stimulation and chemotaxis. Yet, we find that they result in striking differences in activation of the G protein-coupled receptor kinase (GRK)/ß-arrestin system. CCL19 leads to robust CCR7 phosphorylation and β-arrestin2 recruitment catalyzed by both GRK3 and GRK6 whereas CCL21 activates GRK6 alone. This differential GRK activation leads to distinct functional consequences. Although each ligand leads to β-arrestin2 recruitment, only CCL19 leads to redistribution of β-arrestin2-GFP into endocytic vesicles and classical receptor desensitization. In contrast, these agonists are both capable of signaling through GRK6 and β-arrestin2 to ERK kinases. Thus, this mechanism for “ligand bias” whereby endogenous agonists activate different GRK isoforms leads to functionally distinct pools of β-arrestin.