bluuebunny/crossref_metadata_2025 huggingface dataset:
The Metabolic Syndrome Adds Incremental Value to the Framingham Risk Score in Identifying Asymptomatic Individuals With Higher Degrees of Inflammation
Authors: Campbell Catherine Y. , Nasir Khurram , Carvalho Jose A. M. , Blumenthal Roger S. , Santos Raul D.
Published: March 2008

Recent studies have shown that elevated white blood cell (WBC) counts independently predict adverse cardiovascular disease (CVD) outcomes. The metabolic syndrome (MS) is known to be associated with a higher degree of inflammation and increased CVD risk. It is unclear, however, whether MS provides incremental information to the Framingham risk score (FRS). The authors studied 458 asymptomatic men, of whom 112 had MS. WBC count was used as a marker of inflammation. The odds ratio (OR) for presence of WBCs in the highest quartile vs the lower 3 quartiles was 2.2; 95% confidence interval (CI), 1.39–3.40 for MS. After further adjustment for the FRS, the relationship remained significant (OR, 1.97; 95% CI, 1.25–3.13). The ability to identify higher levels of WBCs with MS was especially important in the low‐risk men (OR, 2.66; 95% CI, 1.39–5.07). The study findings suggest that MS adds value to the FRS in identifying those with higher degrees of inflammation, especially among those classified as low‐risk by the FRS.
Ethnic Gap in Coronary Artery Disease: Comparison of the Extent, Severity, and Risk Factors in Arab and Jewish Middle‐Aged Women
Authors: Salameh Shaden , Hochner‐Celnikier Drorit , Chajek‐Shaul Tova , Manor Orly , Bursztyn Michael
Published: March 2008

The authors examined risk factors and extent of coronary artery disease (CAD) among Jewish and Arab women in Jerusalem, where Arab women were found to have worse outcome. All angiographically confirmed cases of CAD among women aged 45 to 65 years who were hospitalized during 1990 to 1995 consisted of 40 Arab and 179 Jewish patients. Arab women had more atypical clinical presentations (P<.0001) and more extensive CAD (P=.0016) despite younger age (53±3 vs 55±5 years; P<.0003) and lesser smoking (P<.0006). The Arab women, however, were more likely to be obese (80% vs 46%; P=.0002), be physically inactive (100% vs 89%; P=.0285), and have diabetes mellitus (73% vs 40%; P=.0004). Moreover, they were more likely to have 3 or more risk factors (45% vs 23%; P=.036). Thus, a combination of an atypical presentation and higher risk (ie, diabetes mellitus combined with hypertension and other risk factors) and much more extensive disease readily explains their worse outcome.
Tumor‐induced tolerance and immune suppression by myeloid derived suppressor cells
Authors: Marigo Ilaria , Dolcetti Luigi , Serafini Paolo , Zanovello Paola , Bronte Vincenzo
Published: March 2008

Summary: Emerging evidence indicates that the Achilles' heel of cancer immunotherapies is often the complex interplay of tumor‐derived factors and deviant host properties, which involve a wide range of immune elements in the lymphoid and myeloid compartments. Regulatory lymphocytes, tumor‐conditioned myeloid‐derived suppressor cells (MDSCs), tumor‐associated macrophages, and dysfunctional and immature dendritic cells take part in a complex immunoregulatory network. Despite the fact that some mechanisms governing tumor‐induced immune tolerance and suppression are starting to be better understood and their complexity dissected, little is known about the diachronic picture of immune tolerance. Based on observations of MDSCs, we present a time‐structured and topologically consistent idea of tumor‐dependent tolerance progression in tumor‐bearing hosts.
A paradigm shift in therapeutic vaccination of cancer patients: the need to apply therapeutic vaccination strategies in the preventive setting
Authors: Gray Andrew , Raff Adam B. , Chiriva‐Internati Maurizio , Chen Si‐Yi , Kast W. Martin
Published: March 2008

Summary: An extraordinary variety of potential therapeutic vaccine strategies directed against a wide variety of tumor antigens has been explored in clinical trials. To date, none of these cancer immunotherapies have been approved by the Food and Drug Administration for use in humans. A significant problem is that the vast majority of such clinical trials are carried out in patients with advanced or metastatic cancer. The immune systems of these patients are considerably compromised as a result of tumor‐ and treatment‐mediated immunosuppression. Even in cases where patients are immunized in the adjuvant setting, where there is minimal residual disease, vaccines directed against tumor‐associated antigens have failed to mediate eradication of tumors in the overwhelming majority of cases. Recently, we and others have experimented with administering therapeutic cancer vaccines in the preventive setting. This is achieved by vaccinating at the earliest possible stage of carcinogenesis. These studies have demonstrated that early vaccination is extremely effective in eliciting an anti‐tumor immune response that leads to unprecedented improvements in the survival of mice that spontaneously develop cancer. Certain human cancers, notably prostate adenocarcinoma and cervical cancer, can currently be detected at very early stages of carcinogenesis. Therapeutic vaccines are available for these diseases, opening up the possibility of administering vaccinations early to patients diagnosed with pre‐malignant lesions to halt disease progression. In addition, new technologies have become available in the past decade that will soon yield very sensitive and specific diagnostic tests for a plethora of other cancers. Earlier detection of these cancers, combined with existing vaccines directed against them, will soon make them targets for therapeutic vaccination in the preventive setting. The ability to immunize patients at the very earliest stages of carcinogenesis, when they have fully competent immune systems, has the potential to cause a paradigm shift in how therapeutic cancer vaccines are tested and used clinically.
The flip side of immune surveillance: immune dependency
Authors: Prehn Richmond T. , Prehn Liisa M.
Published: March 2008

Summary: The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti‐tumor immunity exhibits the phenomenon of hormesis, i.e. the dose–response curve is non‐linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.
Cancer vaccines for established cancer: how to make them better?
Authors: Andrews Daniel M. , Maraskovsky Eugene , Smyth Mark J.
Published: March 2008

Summary: If one envisions dendritic cells (DCs) as nature's adjuvant, then it is easy to predict that they would be advantageous for cancer immunotherapy. Advances in culture processes that generate large numbers of purified and functionally mature DCs raised the possibility that DCs might be promising clinical agents to generate effective immune responses against cancer. The use of mature DCs as cellular vaccines was proposed to be superior to conventional strategies aimed at treating cancer, yet a phase III clinical trial in patients with melanoma demonstrated no increased benefit of DCs over standard therapy. Despite this and other apparent failures, we propose that DC‐based therapy should not be discarded but rather reassessed. The heterogeneity of DCs and their interaction with other innate cells and regulatory and effector pathways must be clearly understood before the full therapeutic benefit of DCs are recognized. Several aspects of DC vaccination require optimization including the following: effective delivery of vaccines to DCs in lymphoid tissues; incorporation of components that induce appropriate DC activation; and facilitation of innate and adaptive interactions and reduction of regulatory T‐cell networks or suppressive microenvironments that hinder the function of immune effectors. Application of this knowledge is resulting in encouraging new data in pre‐clinical settings, where multiple arms of the immune system are targeted for cancer therapy.
Tumor necrosis factor‐mediated interactions between inflammatory response and tumor vascular bed
Authors: Ten Hagen Timo L. M. , Seynhaeve Ann L. B. , Eggermont Alexander M. M.
Published: March 2008

Summary: Solid tumor therapy with chemotherapeutics greatly depends on the efficiency with which drugs are delivered to tumor cells. The typical characteristics of the tumor physiology promote but also appose accumulation of blood‐borne agents. The leaky tumor vasculature allows easy passage of drugs. However, the disorganized vasculature causes heterogeneous blood flow, and together with the often‐elevated interstitial fluid pressure, this state results in poor intratumoral drug levels and failure of treatment. Manipulation of the tumor vasculature could overcome these barriers and promote drug delivery. Targeting the vasculature has several advantages. The endothelial lining is readily accessible and the first to be encountered after systemic injection. Second, endothelial cells tend to be more stable than tumor cells and thus less likely to develop resistance to therapy. Third, targeting the tumor vasculature can have dual effects: (i) manipulation of the vasculature can enhance concomitant chemotherapy, and (ii) subsequent destruction of the vasculature can help to kill the tumor. In particular, tumor necrosis factor α is studied. Its action on solid tumors, both directly through tumor cell killing and destruction of the tumor vasculature and indirectly through manipulation of the tumor physiology, is complex. Understanding the mechanism of TNF and agents with comparable action on solid tumors is an important focus to further develop combination immunotherapy strategies.
Influence of age and regional differences on skin elasticity as measured by the Cutometer®
Authors: Ryu Hyo Sub , Joo Young Hyun , Kim Sun Ok , Park Kyoung Chan , Youn Sang Woong
Published: March 2008

Background/aim: Aging of skin is accompanied by decrease of skin elasticity. Using the noninvasive suction device Cutometer®, we evaluated the age and regional body differences of the viscoelastic properties of human skin. The objectives of this study were to evaluate the correlation between age and the biomechanical parameters and the regional skin variations.

Methods: A total of 96 healthy women aged 20–75 years were included in this study. The biomechanical properties of the skin were measured by using the Cutometer®. Measurements were made on the face, upper arm and back.

Results: The age of subjects showed significant positive correlation with R4 and R6, and negative correlation with R2, R5 and R7. The face showed bigger changes of elastic properties than the arm and the back. Especially, the R7 of face was most significantly decreased with aging. We could estimate the so‐called ‘skin age’ by using a correlation equation for this parameter.

Conclusion: The viscoelastic properties were significantly influenced by aging. Also, significant regional variations in the viscoelastic properties were observed. Skin elasticity measurement is useful for the quantitative evaluation of age‐related changes.
Insulin-Like Growth Factor-1 Restores Erectile Function in Aged Rats: Modulation the Integrity of Smooth Muscle and Nitric Oxide-Cyclic Guanosine Monophosphate Signaling Activity
Authors: Pu Xiao-Yong , Wang Xing-Huan , Gao Wai-Chen , Yang Zhong-Hua , Li Shi-Lin , Wang Huai-Peng , Wu Yi-Long
Published: March 2008

Introduction

Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks.

Aim

To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat.

Main Outcome Measures

Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined.

Methods

Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N=10), IGF-1 1 µg/kg (N=10) and IGF-1 10 µg/kg treatment group (N=10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3′,5′-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed.

Results

After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 µg/kg and the IGF-1 10 µg/kg group compared with the vehicle-only group at 4 and 8 weeks (P <0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats.

Conclusions

IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways.
PHYSICAL, SENSORY AND FLOW PROPERTIES OF WHEAT STARCH–DAIRY BY‐PRODUCT SPRAY‐DRIED PEKMEZ MIXTURES
Authors: SERT DURMUŞ , YILMAZ MUSTAFA T. , KARAKAYA MUSTAFA
Published: March 2008

Pekmez, also known as a concentrated grape juice, was spray dried in a laboratory‐type pilot drying unit to obtain pekmez powder (PP). The flow characteristics of PP, wheat starch (WS) and some dairy by‐products (whey powder, skim milk powder, calcium caseinate and sodium caseinate) systems as binary and ternary mixtures were studied. The empirical power law model fitted the apparent viscosity–rotational speed data. PP–dairy by‐product and WS–dairy by‐product mixed solutions exhibited a shear‐thinning behavior at 21C with flow behavior index (n) values of 0.86 ≤ n ≤ 0.92 and 0.06 ≤ n ≤ 0.27, respectively. WS–dairy by‐product mixed solutions showed high shear‐thinning behavior with the highest consistency index (k = 25,425–180,599 mPa·sn). However, PP–WS and PP–WS–dairy by‐product mixed solutions at the same temperature exhibited the shear‐thickening behavior with flow behavior index (n) values of 1.05 ≤ n ≤ 1.18.

PRACTICAL APPLICATIONS

Pekmez has become popular as a healthy food product; therefore, its rheologic properties were extensively studied by some researchers. However, pekmez powder (PP) is a new product and has not been produced yet in the food industry. Spray drying of foods has been spread recently in almost all food industry branches because it provides some advantages such as extending the shelf life, storage stability, decreasing the storage costs of the food products, etc. For this reason, production technology is first developed; PP is produced and studied in this study. There is no published data informing the rheologic, physical and sensory properties of pekmez or PP as binary and ternary mixtures with other components such as wheat starch (WS) and any dairy by‐product. The purpose of this study was mainly to characterize the rheologic behavior of the PP–WS–dairy by‐product mixed solutions and determine their physical and sensory properties.
STRESS RELAXATION BEHAVIOR OF MICROWAVE‐VACUUM‐DRIED ALGINATE GELS
Authors: JAYA S. , DURANCE T.D.
Published: March 2008

Swelling of alginate polymer matrix in water involves a build up of network pressure due to an elastic extension of the polymeric matrix. When this network pressure undergoes relaxation by means of dehydration, shrinkage may take place. Three different types of wet alginate gels were prepared and dried using microwave‐vacuum‐drying technique. Dried alginate gel solids had a porous structure. To understand the stress relaxation behavior of alginate gel‐based porous solid structures, uniaxial compressive relaxation studies were performed at selected strain rates, preloads and relaxation times Experimental relaxation curves were normalized and fitted to an empirical relationship, and relaxation behavior was explained. Stress relaxation data were also fitted to another empirical model. All three types of gels had similar elastic components. At lower strain rate, all samples had more resistance to elastic deformation. Stress relaxation information of the dried gel was related to its microstructure. Type 2 gel had more stiffness than type 1 and type 3 gels. The mechanism involved in stress relaxation was entanglement coupling of larger polymer chains in covalently cross‐linked alginate gels.
The Ailing Healthcare Supply Chain: A Prescription for Change
Authors: McKone‐Sweet Kathleen E. , Hamilton Paul , Willis Susan B.
Published: March 2008

Despite well‐documented evidence of significant competitive advantage and cost reduction resulting from supply chain management (SCM) practices, the healthcare industry has been extremely slow to embrace these practices. This article, through literature review and case studies within the healthcare industry supply chain, explores the barriers to implementation of SCM practices. These barriers include: lack of executive support; misaligned or conflicting incentives; need for data collection and performance measurement; limited education on supply chain; and inconsistent relationships with group purchasing organizations and other supply chain partners. Practical recommendations are made for hospitals and supply chain partners struggling to implement workable SCM solutions.
SCM Involving Small Versus Large Suppliers: Relational Exchange and Electronic Communication Media
Authors: Larson Paul D. , Carr Peter , Dhariwal Kewal S.
Published: March 2008

This article develops and tests hypotheses on relational exchange and electronic communication media in supply chains involving small versus large suppliers. Through a combination of focus groups, e‐mail surveys and case studies, the article addresses the differences in relational exchange due to supplier size. Findings indicate significantly greater use of relational exchange and electronic communication media with large suppliers compared to small suppliers. The article offers solutions to reducing the relational and technological gaps between large and small suppliers.
An extended outbreak of congenital chondrodysplasia in calves in South East Australia
Authors: Cave JG , Mclaren PJ , Whittaker SJ , Rast L , Stephens A , Parker EM
Published: March 2008

Objective  To report an outbreak of congenital chondrodystrophy in calves in South East Australia.

Methods  District veterinarians investigated reported cases of calf deformities. Owners of affected herds were interviewed using a standard questionnaire to identify potential risk factors. Dams of several affected calves were serologically tested for Akabane virus, Aino virus, pestivirus and bluetongue, and affected calves were tested for pestivirus antigen and serum immunoglobulin concentrations. Gross and histopathological examinations of numerous calves were performed, concentrating on the musculoskeletal system.

Results  A case definition of distinctive skeletal deformities was established, and 89 property owners reported calves with chondrodystrophy in Spring 2003, 2004 or 2005. Some 14 property owners reported affected calves in more than one year. Prevalence and severity of deformity varied greatly between and within properties. None of breed, sex, age of dam, lineage, pasture type, supplementary feeding, fertiliser use or toxic plants was consistently associated with the disease. All dams experienced hot, dry conditions during the first trimester of pregnancy and were exposed to adverse conditions thereafter. Consistently dams were reported to have been grazing undulating to hilly terrain during early pregnancy. All serological tests were negative for Akabane virus, Aino virus, pestivirus and bluetongue. Histopathology of affected skeletal samples showed chondrodysplasia.

Conclusion  The outbreak had similarities with previous outbreaks reported in the region. No specific aetiology could be determined. There is some evidence that the cause of the deformities could be a manganese deficiency during foetal development. Ongoing work to test this hypothesis is therefore warranted.
Cross species transmission of ovine Johne's disease from sheep to cattle: an estimate of prevalence in exposed susceptible cattle
Authors: Moloney BJ , Whittington RJ
Published: March 2008

Objective  To determine the prevalence of infection of cattle with the sheep strain of Mycobacterium avium subsp paratuberculosis at least two years after exposure at < 6 months old.

Design  Prospective survey One thousand seven hundred and seventy‐four cattle from 12 properties (Farms A to L) were sampled by ELISA and faecal culture to detect evidence of infection with M a paratuberculosis. All properties had a known history of Johne's disease (JD) in sheep, and sampled cattle were likely to be susceptible to JD at the time they were first exposed, being at an age of 6 months or less. In addition, opportunistic investigations were undertaken of ELISA reactor cattle discovered during testing for the Australian Johne's Disease Market Assurance Program for Cattle (Farms M and N).

Results  All animals in the survey gave negative results on serology while one animal from a herd of 349 gave a positive faecal culture result. Follow‐up faecal culture, post‐mortem and histopathology on the latter animal were negative, suggesting that it was a passive faecal shedder or carrier.

Two occurrences of OJD transmission to cattle were detected during the opportunistic investigations.

Conclusion  These observations confirm existing beliefs about the risk of transmission of OJD to cattle, that the risk of transmission is low. However transmission occurs sporadically. An estimated upper limit of prevalence of S strain M a paratuberculosis infection in susceptible exposed cattle in the OJD high prevalence area of New South Wales is 0.8%, assuming a common prevalence within herds.
Hypokalaemic paresis, hypertension, alkalosis and adrenal‐dependent hyperadrenocorticism in a dog
Authors: Davies DR , Foster SF , Hopper BJ , Staudte KL , O’hara AJ , Irwin PJ
Published: March 2008

Generalised paresis, severe hypokalaemia and kaliuresis, metabolic alkalosis and hypertension, characteristic of mineralocorticoid excess, were identified in a dog with hyperadrenocorticism due to a functional adrenocortical carcinoma. Aldosterone concentration was decreased and deoxycorticosterone concentration increased in the presence of hypokalaemia. These metabolic abnormalities resolved with resection of the carcinoma. Mineralocorticoid excess in dogs with hyperadrenocorticism is generally considered to be of little clinical significance but resulted in the acute presentation of this patient. The possible pathogenesis of mineralocorticoid excess in this case of canine hyperadrenocorticism is discussed.
An Algorithm for Analytically Calculating the Positions of the Secondary Instant Centers of Indeterminate Linkages
Authors: Di Gregorio Raffaele
Published: March 2008

In a planar mechanism, the position of the instant centers reveals important pieces of information about its static and kinematic behaviors. Such pieces of information are useful for designing the mechanism. Unfortunately, when the mechanism architecture becomes complex, common methods to locate the instant centers, which are based on the direct application of the Aronold–Kennedy theorem, fail. Indeterminate linkages are single-degree-of-freedom (single-dof) planar linkages where the secondary instant centers cannot be found by direct application of the Aronold–Kennedy theorem. This paper presents an analytical method to locate all the instant centers of any single-dof planar mechanism, which, in particular, succeeds in determining the instant centers of indeterminate linkages. In order to illustrate the proposed method, it will be applied to locate the secondary instant centers of the double butterfly linkage and of the single flier eight-bar linkage.
Homing Strategy for a Redundantly Actuated Parallel Kinematic Machine
Authors: Wang Jinsong , Wu Jun , Wang Liping , Li Tiemin
Published: March 2008

In the homing process of a regular parallel kinematic machine (PKM), all servoaxes are independently driven to return to their homing positions. However, in a redundantly actuated PKM, the redundant limb will interfere with other servoaxes. This paper concerns the homing of a redundant four degree of freedom PKM, and an assistant homing strategy is proposed for the machine to pass the singular configuration in the homing process. After the assistant homing is finished, the other four nonredundant axes are driven to return to their home positions independently. Based on the kinematic model and the length of the redundant limb, the condition that the redundant limb performs assistant homing is determined. The homing strategy is incorporated into the numerical control system of the studied PKM. The test shows that the homing strategy is effective, and it can also be useful for other kinds of redundantly actuated PKMs.
Comparison of Molecular Simulation and Pseudo-Rigid-Body Model Predictions for a Carbon Nanotube–Based Compliant Parallel-Guiding Mechanism
Authors: DiBiasio Christopher M. , Culpepper Martin L. , Panas Robert , Howell Larry L. , Magleby Spencer P.
Published: March 2008

We report on the accuracy of the pseudo-rigid-body model (PRBM) in predicting the behavior of a nanoscale parallel-guiding mechanism (nPGM) that uses two single-walled (5,5) carbon nanotubes (CNTs) as the flexural guiding elements. The nPGM has two regions of behavior: region 1 is governed by the bulk deformation of the nanotubes, and region 2 is characterized by hingelike flexing of four “kinks” that occur due to buckling of the nanotube walls. PRBM parameters for (5,5) CNTs are proposed. Molecular simulation results of region 1 behavior match PRBM predictions of (1) kinematic behavior with less than 7.3% error and (2) elastomechanic behavior with less than 5.7% error. Although region 1 is of more interest because of its well-defined and stable nature, region 2 motion is also investigated. We show that the PRBM parameters are dependent on the selection of the effective tube thickness and moment of inertia, the lesson being that designers must take care to consider the thickness and moment of inertia values when deriving PRBM constants.
Size-Driven Structural and Thermodynamic Complexity in Iron Oxides
Authors: Navrotsky Alexandra , Mazeina Lena , Majzlan Juraj
Published: March 2008

Iron oxides occur ubiquitously in environmental, geological, planetary, and technological settings. They exist in a rich variety of structures and hydration states. They are commonly fine-grained (nanophase) and poorly crystalline. This review summarizes recently measured thermodynamic data on their formation and surface energies. These data are essential for calculating the thermodynamic stability fields of the various iron oxide and oxyhydroxide phases and understanding their occurrence in natural and anthropogenic environments. The competition between surface enthalpy and the energetics of phase transformation leads to the general conclusion that polymorphs metastable as micrometer-sized or larger crystals can often be thermodynamically stabilized at the nanoscale. Such size-driven crossovers in stability help to explain patterns of occurrence of different iron oxides in nature.
Titan's Rotation Reveals an Internal Ocean and Changing Zonal Winds
Authors: Lorenz Ralph D. , Stiles Bryan W. , Kirk Randolph L. , Allison Michael D. , del Marmo Paolo Persi , Iess Luciano , Lunine Jonathan I. , Ostro Steven J. , Hensley Scott
Published: March 2008

Cassini radar observations of Saturn's moon Titan over several years show that its rotational period is changing and is different from its orbital period. The present-day rotation period difference from synchronous spin leads to a shift of ∼0.36° per year in apparent longitude and is consistent with seasonal exchange of angular momentum between the surface and Titan's dense superrotating atmosphere, but only if Titan's crust is decoupled from the core by an internal water ocean like that on Europa.
Synchronous Aggregate Growth in an Abundant New Ediacaran Tubular Organism
Authors: Droser Mary L. , Gehling James G.
Published: March 2008

The most abundant taxon of the Neoproterozoic soft-bodied biota near Ediacara, South Australia, occurs as clusters of similarly sized individuals, which suggests synchronous aggregate growth by spatfall. Tubes of
Funisia dorothea
gen. et sp. nov. were anchored within the shallow, sandy sea bed and lived in dense, typically monospecific concentrations. Tubes were composed of modular, serially repeating elements. Individuals grew by adding serial elements to the tubular body and by branching of tubes. Their construction and close-packed association imply likely affinity within the Porifera or Cnidaria. These data suggest that several of the most successful marine invertebrate ecological strategies known today were in place in Earth's oldest known metazoan ecosystems before the advent of skeletonization and widespread predation.
Low-Magnetic-Field Control of Electric Polarization Vector in a Helimagnet
Authors: Ishiwata Shintaro , Taguchi Yasujiro , Murakawa Hiroshi , Onose Yoshinori , Tokura Yoshinori
Published: March 2008

The mutual control of the electric and magnetic properties of a solid is currently of great interest because of the possible application for novel electronic devices. We report on the low-magnetic-field (for example,
B
values of ±30 milliteslas) control of the polarization (

P

) vector in a hexaferrite, Ba
2
Mg
2
Fe
12
O
22
, which shows the helimagnetic spin structure with the propagation vector

k

0
parallel to [001]. The
B
-induced transverse conical spin structure carries the

P

vector directing perpendicular to both

B

and

k

0
, in accord with the recently proposed spin-current model. Then, the oscillating or multidirectionally rotating

B

produces the cyclic displacement current via the flexible handling of the magnetic cone axis.
Sex-Dependent Differences in Plasma Cytokine Responses to Hantavirus Infection
Authors: Klingström Jonas , Lindgren Therese , Ahlm Clas
Published: March 2008

There are often sex differences in susceptibility to infectious diseases and in level of mortality after infection. These differences probably stem from sex-related abilities to mount proper or unwanted immune responses against an infectious agent. We report that hantavirus-infected female patients show significantly higher plasma levels of interleukin-9 (IL-9), fibroblast growth factor 2, and granulocyte-macrophage colony-stimulating factor and lower levels of IL-8 and gamma interferon-induced protein 10 than male patients. The results demonstrate that a virus infection can induce sex-dependent differences in acute immune responses in humans. This finding may, at least partly, explain the observed sex differences in susceptibility to infectious diseases and in mortality following infection.
Vaccine-Induced Opsonophagocytic Immunity to
Neisseria meningitidis
Group B
Authors: Plested J. S. , Granoff D. M.
Published: March 2008

The role of opsonophagocytosis (OP) in protection against meningococcal disease is controversial because patients with deficiencies in terminal complement proteins whose sera support OP but not bactericidal activity (BA) are at greatly increased risk of disease. We assayed complement-mediated BA and OP bactericidal activity in sera from 32 adults immunized with an outer membrane vesicle vaccine given alone or combined with an investigational recombinant protein, genome-derived neisserial antigen (GNA2132). The sera were heat inactivated to remove internal complement activity, and BA was measured with exogenous nonimmune human serum as a complement source. OP was measured with human polymorphonuclear cells (PMNs) and C6-depleted complement, which without PMNs did not support BA. Before immunization, 9 to 19% of sera from subjects in both vaccine groups combined had BA titers of ≥1:4, which increased to 41 to 72% after immunization (
P
< 0.01 against each of three test strains). The percentages of sera with OP titers of ≥1:5 were 3 to 16%, which increased to 55 to 72% (
P
< 0.001 for each strain). Most postimmunization BA-positive sera were OP positive, but 10 to 37% of BA-negative sera also were OP positive. Comparing the two vaccine groups, there were no significant differences in the percentages of sera with BA or OP activity except for a higher percentage of OP against one strain in postimmunization sera from subjects in the combination vaccine group (
P
≤ 0.02). The data support independent roles for serum BA and OP bactericidal activity in protection against group B disease.
Direct Comparison of the GenoType MTBC and Genomic Deletion Assays in Terms of Ability To Distinguish between Members of the
Mycobacterium tuberculosis
Complex in Clinical Isolates and in Clinical Specimens
Authors: Somoskovi Akos , Dormandy Jillian , Rivenburg Jeremy , Pedrosa Maria , McBride Melinda , Salfinger Max
Published: March 2008

The automated GenoType MTBC assay was evaluated for the ability to detect and identify members of the
Mycobacterium tuberculosis
complex. In addition to 35 reference strains and 157 clinical isolates, performance of this assay was tested directly on 79 smear-positive clinical specimens. The assay proved as accurate as the reference deletion analysis for all 192 isolates and detected and identified
M. tuberculosis
complex members in 93.2% of the specimens containing the
M. tuberculosis
complex.
Differences in Virulence Markers betweenHelicobacter pyloriStrains from Iraq and Those from Iran: Potential Importance of Regional Differences inH. pylori-Associated Disease
Authors: Hussein Nawfal R. , Mohammadi Marjan , Talebkhan Yeganeh , Doraghi Masoumeh , Letley Darren P. , Muhammad Merdan K. , Argent Richard H. , Atherton John C.
Published: March 2008

Helicobacter pyloricauses peptic ulceration and gastric adenocarcinoma; the latter is common in Iran but not in Iraq. We hypothesized that more virulentH. pyloristrains may be found in Iran than in Iraq and so compared established and newly described virulence factors in strains from these countries. We studied 59 unselected dyspeptic patients from Iran and 49 from Iraq.cagAwas found in similar proportions of strains from both countries (76% in Iran versus 71% in Iraq) and was significantly associated with peptic ulcer disease in Iraq (P≤ 0.01) but not in Iran.cagAalleles encoding four or more tyrosine phosphorylation motifs were found in 12% of the Iranian strains but none of the Iraqi strains (P= 0.02). There were no significant differences in thevacAsignal-, middle-, or intermediate-region types between Iranian and Iraqi strains. Among the strains from Iran,vacAgenotypes showed no specific peptic ulcer associations, but among the strains from Iraq,vacAi1 strains were associated with gastric ulcer (P≤ 0.02), mimicking their previously demonstrated association with gastric cancer in Iran.dupAwas found in similar proportions of Iranian and Iraqi strains (38% and 32%, respectively) and was associated with peptic ulceration in Iraqi patients (P≤ 0.01) but not Iranian patients.H. pyloristrains from Iraq and Iran possess virulence factors similar to those in Western countries. The presence ofcagAwith more phosphorylation motifs in Iranian strains may contribute to the higher incidence of gastric cancer. However, the association between strain virulence markers and disease in Iraq but not Iran suggests that other host and environmental factors may be more important in the disease-prone Iranian population.
Optimum Diagnostic Assay and Clinical Specimen for Routine Rotavirus Surveillance
Authors: Stockman Lauren J. , Staat Mary A. , Holloway Michol , Bernstein David I. , Kerin Tara , Hull Jennifer , Yee Eileen , Gentsch Jon , Parashar Umesh D.
Published: March 2008

Rates of detection of rotavirus were compared by diagnostic assay and specimen type. For bulk stools, rates of detection by reverse transcriptase PCR (RT-PCR) and enzyme immunoassay (EIA) were similar, but 18% of healthy controls tested positive by RT-PCR. Testing of bulk stools by EIA appears to be optimum for rotavirus surveillance.
Whole-Genome Expression Profiling Reveals That Inhibition of Host Innate Immune Response Pathways by Ebola Virus Can Be Reversed by a Single Amino Acid Change in the VP35 Protein
Authors: Hartman Amy L. , Ling Ling , Nichol Stuart T. , Hibberd Martin L.
Published: March 2008

Ebola hemorrhagic fever is a rapidly progressing acute febrile illness characterized by high virus replication, severe immunosuppression, and case fatalities of ca. 80%. Inhibition of phosphorylation of interferon regulatory factor 3 (IRF-3) by the Ebola VP35 protein may block the host innate immune response and play an important role in the severity of disease. We used two precisely defined reverse genetics-generated Ebola viruses to investigate global host cell responses resulting from the inhibition of IRF-3 phosphorylation. The two viruses encoded either wild-type (WT) VP35 protein (recEbo-VP35/WT) or VP35 with an arginine (R)-to-alanine (A) amino acid substitution at position 312 (recEbo-VP35/R312A) within a previously defined IRF-3 inhibitory domain. When sucrose-gradient purified virus was used for infection, host cell whole-genome expression profiling revealed striking differences in human liver cell responses to these viruses differing by a single amino acid. The inhibition of host innate immune responses by WT Ebola virus was so potent that little difference in interferon and antiviral gene expression could be discerned between cells infected with purified WT, inactivated virus, or mock-infected cells. However, infection with recEbo-VP35/R312A virus resulted in a strong innate immune response including increased expression of MDA-5, RIG-I, RANTES, MCP-1, ISG-15, ISG-54, ISG-56, ISG-60, STAT1, IRF-9, OAS, and Mx1. The clear gene expression differences were obscured if unpurified virus stocks were used to initiate infection, presumably due to soluble factors present in virus-infected cell supernatant preparations. Ebola virus VP35 protein clearly plays a pivotal role in the potent inhibition of the host innate immune responses, and the present study indicates that VP35 has a wider effect on host cell responses than previously shown. The ability to eliminate this inhibitory effect with a single amino acid change in VP35 demonstrates the critical role this protein must play in the severe aspects this highly fatal disease.
Structural and Genetic Requirements for the Biogenesis of
Tobacco Rattle Virus
-Derived Small Interfering RNAs
Authors: Donaire Livia , Barajas Daniel , Martínez-García Belén , Martínez-Priego Llucia , Pagán Israel , Llave César
Published: March 2008

In plants, small RNA-guided processes referred to as RNA silencing control gene expression and serve as an efficient antiviral mechanism. Plant viruses are inducers and targets of RNA silencing as infection involves the production of functional virus-derived small interfering RNAs (siRNAs). Here we investigate the structural and genetic components influencing the formation of
Tobacco rattle virus
(TRV)-derived siRNAs. TRV siRNAs are mostly 21 nucleotides in length and derive from positive and negative viral RNA strands, although TRV siRNAs of positive polarity are significantly more abundant. This asymmetry appears not to correlate with the presence of highly structured regions of single-stranded viral RNA. The Dicer-like enzyme DCL4, DCL3, or DCL2 targets, alone or in combination, viral templates to promote synthesis of siRNAs of both polarities from all regions of the viral genome. The heterogeneous distribution profile of TRV siRNAs reveals differential contributions throughout the TRV genome to siRNA formation. Indirect evidence suggests that DCL2 is responsible for production of a subset of siRNAs derived from the 3′ end region of TRV. TRV siRNA biogenesis and antiviral silencing are strongly dependent on the combined activity of the host-encoded RNA-dependent RNA polymerases RDR1, RDR2, and RDR6, thus providing evidence that perfectly complementary double-stranded RNA serves as a substrate for siRNA production. We conclude that the overall composition of viral siRNAs in TRV-infected plants reflects the combined action of several interconnected pathways involving different DCL and RDR activities.
An Alteration of Human Immunodeficiency Virus gp41 Leads to Reduced CCR5 Dependence and CD4 Independence
Authors: Taylor Brian M. , Foulke J. Scott , Flinko Robin , Heredia Alonso , DeVico Anthony , Reitz Marvin
Published: March 2008

Human immunodeficiency virus (HIV) type 1 infection requires functional interactions of the viral surface (gp120) glycoprotein with cell surface CD4 and a chemokine coreceptor (usually CCR5 or CXCR4) and of the viral transmembrane (gp41) glycoprotein with the target cell membrane. Extensive genetic variability, generally in gp120 and the gp41 ectodomain, can result in altered coreceptor use, fusion kinetics, and neutralization sensitivity. Here we describe an R5 HIV variant that, in contrast to its parental virus, infects T-cell lines expressing low levels of cell surface CCR5. This correlated with an ability to infect cells in the absence of CD4, increased sensitivity to a neutralizing antibody recognizing the coreceptor binding site of gp120, and increased resistance to the fusion inhibitor T-20. Surprisingly, these properties were determined by alterations in gp41, including the cytoplasmic tail, a region not previously shown to influence coreceptor use. These data indicate that HIV infection of cells with limiting levels of cell surface CCR5 can be facilitated by gp41 sequences that are not exposed on the envelope ectodomain yet induce allosteric changes in gp120 that facilitate exposure of the CCR5 binding site.
Robust NK Cell-Mediated Human Immunodeficiency Virus (HIV)-Specific Antibody-Dependent Responses in HIV-Infected Subjects
Authors: Stratov Ivan , Chung Amy , Kent Stephen J.
Published: March 2008

Antibody-dependent cellular cytotoxicity (ADCC) is a potentially effective adaptive immune response to human immunodeficiency virus (HIV) infection. The study of ADCC responses has been hampered by the lack of simple methods to quantify these responses and map effective epitopes. We serendipitously observed that standard intracellular cytokine assays on fresh whole blood from a cohort of 26 HIV-infected subjects identified non-T lymphocytes expressing gamma interferon (IFN-γ) in response to overlapping linear peptides spanning HIV-1 proteins. The effector cells were CD3−CD4−CD8−CD14−CD2+CD56+/−NK lymphocytes and degranulated granzyme B and perforin in response to antigen stimulation. Serum transfer assays demonstrated that the specific response was mediated by immunoglobulin G. Fresh blood samples from half of the HIV-infected cohort demonstrated robust HIV peptide-specific IFN-γ expression by NK cells, predominately to Env, Pol, and Vpu HIV-1 proteins. Responses were readily mapped to define minimal epitopes utilizing this assay. Antibody-dependent, HIV-specific NK cell recognition, involving components of both innate and adaptive immune systems, represents a potentially effective immune response to induce by vaccination.
HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control
Authors: Emu Brinda , Sinclair Elizabeth , Hatano Hiroyu , Ferre April , Shacklett Barbara , Martin Jeffrey N. , McCune J. M. , Deeks Steven G.
Published: March 2008

A rare subset of human immunodeficiency virus (HIV)-infected individuals maintains undetectable HIV RNA levels without therapy (“elite controllers”). To clarify the role of T-cell responses in mediating virus control, we compared HLA class I polymorphisms and HIV-specific T-cell responses among a large cohort of elite controllers (HIV-RNA < 75 copies/ml), “viremic” controllers (low-level viremia without therapy), “noncontrollers” (high-level viremia), and“antiretroviral therapy suppressed” individuals (undetectable HIV-RNA levels on antiretroviral therapy). The proportion of CD4+and CD8+T cells that produce gamma interferon (IFN-γ) and interleukin-2 (IL-2) in response to Gag and Pol peptides was highest in the elite and viremic controllers (P< 0.0001). Forty percent of the elite controllers were HLA-B*57 compared to twenty-three percent of viremic controllers and nine percent of noncontrollers (P< 0.001). Other HLA class I alleles more common in elite controllers included HLA-B*13, HLA-B*58, and HLA-B*81 (P< 0.05 for each). Within elite and viremic controller groups, those with protective class I alleles had higher frequencies of Gag-specific CD8+T cells than those without these alleles (P= 0.01). Noncontrollers, with or without protective alleles, had low-level CD8+responses. Thus, certain HLA class I alleles are enriched in HIV controllers and are associated with strong Gag-specific CD8+IFN-γ+IL-2+T cells. However, the absence of evidence of T cell-mediated control in many controllers suggests the presence of alternative mechanisms for viral control in these individuals. Defining mechanisms for virus control in “non-T-cell controllers” might lead to insights into preventing HIV transmission or preventing virus replication.
Persistence of Transmitted Drug Resistance among Subjects with Primary Human Immunodeficiency Virus Infection
Authors: Little Susan J. , Frost Simon D. W. , Wong Joseph K. , Smith Davey M. , Pond Sergei L. Kosakovsky , Ignacio Caroline C. , Parkin Neil T. , Petropoulos Christos J. , Richman Douglas D.
Published: March 2008

Following interruption of antiretroviral therapy among individuals with acquired drug resistance, preexisting drug-sensitive virus emerges relatively rapidly. In contrast, wild-type virus is not archived in individuals infected with drug-resistant human immunodeficiency virus (HIV) and thus cannot emerge rapidly in the absence of selective drug pressure. Fourteen recently HIV-infected patients with transmitted drug-resistant virus were followed for a median of 2.1 years after the estimated date of infection (EDI) without receiving antiretroviral therapy. HIV drug resistance andpolreplication capacity (RC) in longitudinal plasma samples were assayed. Resistance mutations were characterized as pure populations or mixtures. The mean time to first detection of a mixture of wild-type and drug-resistant viruses was 96 weeks (1.8 years) (95% confidence interval, 48 to 192 weeks) after the EDI. The median time to loss of detectable drug resistance using population-based assays ranged from 4.1 years (conservative estimate) to longer than the lifetime of the individual (less conservative estimate). The transmission of drug-resistant virus was not associated with virus with reduced RC. Sexual transmission of HIV selects for highly fit drug-resistant variants that persist for years. The prolonged persistence of transmitted drug resistance strongly supports the routine use of HIV resistance genotyping for all newly diagnosed individuals.