bluuebunny/crossref_metadata_2025 huggingface dataset:
Breed and Sex Risk Factors for Canine Babesiosis in South Africa
Authors: Mellanby R.J. , Handel I.G. , Clements D.N. , de C. Bronsvoort B.M. , Lengeling A. , Schoeman J.P.
Published: September 2011

Background:

In South Africa, canine babesiosis typically is an acute disease in susceptible individuals and is a major cause of morbidity and mortality. Despite the importance of the disease, there have been no large studies that have examined the influence of breed and sex on disease susceptibility.

Hypothesis:

Toy breeds have a lower risk of babesiosis than working dogs.

Animals:

A total of 1,222 dogs diagnosed with canine babesiosis and 11,484 noninfected dogs presented to the Onderstepoort Veterinary Academic Hospital's small animal outpatient clinic between 2004 and 2010.

Methods:

Retrospective study.

Results:

Intact male, neutered male, and neutered female dogs had a significantly higher odds of being diagnosed with canine babesiosis compared to intact female dogs. Five of the 6 Toy breeds had significantly lower odds of being diagnosed with canine babesiosis than did the reference breed, Labrador Retrievers. In contrast, none of the 8 working dog breeds had significantly lower odds compared to the reference breed.

Conclusions and Clinical Importance:

Intact male, neutered male, and neutered female dogs were at increased risk of canine babesiosis compared to intact female dogs. Several dog breeds, notably Toy breeds, had a lower risk of babesiosis in a hospital population of dogs in South Africa. The mechanism or mechanisms by which Toy breeds are protected from developing canine babesiosis may be related to genetic background or environmental exposure and deserves further study.
Evaluation of Predictors for the Diagnosis of Hyperthyroidism in Cats
Authors: Wakeling Jennifer , Elliott Jonathan , Syme Harriet
Published: September 2011

Background:

In humans, subclinical hyperthyroidism is diagnosed when serum thyroid hormone concentrations are within the reference range but thyroid stimulating hormone (TSH) concentration is subnormal. In a previous study, a higher prevalence of thyroid nodular disease was found in euthyroid geriatric cats with undetectable TSH (<0.03 ng/mL) compared to those with detectable TSH concentrations, suggesting subclinical hyperthyroidism might also exist in cats.

Hypothesis:

Euthyroid cats with undetectable TSH concentrations have subclinical hyperthyroidism and may subsequently develop overt signs of hyperthyroidism.

Animals:

One‐hundred four client‐owned cats.

Methods:

In this prospective cohort study, euthyroid geriatric (≥9 years) cats were recruited during routine health checks. Plasma biochemistry was performed at baseline and every 6 months thereafter. Total thyroxine and TSH concentrations were determined annually. Short‐term follow‐up data (within 14 months of recruitment) were used to detect variables at entry that were predictive of the diagnosis of hyperthyroidism, using univariable analysis followed by multivariable logistic regression analysis. Log rank analysis was used to test the association of initial TSH concentration with diagnosis of hyperthyroidism during the total available follow‐up.

Results and Conclusions:

Median (range) follow‐up was 26 (0–54) months and annual incidence of hyperthyroidism during the study was 7.4%. Cats that became hyperthyroid within 14 months had higher ALKP activity (P = 0.02) and higher prevalence of goiter (P = .03) at baseline than controls. Cats with undetectable TSH at baseline (29/104; 28%) were significantly (P < .001) more likely to be diagnosed with hyperthyroidism. However, not all cats with undetectable TSH became hyperthyroid during the study.
Alcohol‐Related Problems and Risk of Suicide among College Students: The Mediating Roles of Belongingness and Burdensomeness
Authors: Lamis Dorian A. , Malone Patrick S.
Published: September 2011

The relationship among alcohol‐related problems, perceived burdensomeness, thwarted belongingness, and suicide proneness in undergraduate college students (N = 996) was examined. As hypothesized, alcohol‐related problems, perceived burdensomeness, and thwarted belongingness were all significantly and positively correlated with suicide proneness. The relation between experiencing alcohol‐related problems and suicide proneness was, in part, accounted for by perceived burdensomeness and thwarted belongingness. Additionally, the mediation via perceived burdensomeness was significantly stronger than the mediation via thwarted belongingness. Results suggest that it would be advisable for clinicians to be aware of students’ experiences with alcohol‐related problems in conjunction with their levels of burdensomeness and belongingness when assessing for suicide risk.
Megavesica in a neonatal foal
Authors: Tóth T. , Liman J. , Larsdotter S. , Ley C. , Karlstam E. , Kendall A.
Published: September 2011

A newborn male foal was diagnosed with a greatly enlarged urinary bladder (megavesica), a urinary bladder diverticulum, and a herniated and abnormal umbilical remnant. Approximately 50% of the cranial bladder including the abnormal structures was surgically resected; the foal recovered and was still asymptomatic 15 months after surgery. The aetiology of megavesica in foals is unknown but successful outcome may be achieved with surgical intervention and adequate medical support.
Ultrasonographic examination of the dorsal aspect of the distal interphalangeal joint of the horse
Authors: Dupays A.‐G. , Coudry V. , Denoix J.‐M.
Published: September 2011

Ultrasonographic examination of the dorsal aspect of the distal interphalangeal joint is part of the routine examination of the foot structures. The purpose of this paper is to describe the ultrasonographic anatomy of the area, and normal transverse and longitudinal images. Clinical cases are presented to illustrate abnormal findings and lesions of the dorsal aspect of the joint. Ultrasonography can complement radiography for the diagnosis and documentation of many soft tissue and joint abnormalities such as synovitis, fluid distension, cartilaginous defects, periarticular osteophytes and bone fragments.
Close, impinging and overriding spinous processes in the thoracolumbar spine: The relationship between radiological and scintigraphic findings and clinical signs
Authors: ZIMMERMAN M. , DYSON S. , MURRAY R.
Published: September 2011

Reasons for performing study:There has been no objective study comparing radiological features of spinous processes (SPs) in the thoracolumbar region and/or scintigraphic findings with clinical signs.

Objectives:To investigate the relationship between the presence or absence of clinical signs of back pain and: 1) radiological findings of close, impinging or overriding SPs; 2) increased radiopharmaceutical uptake (IRU) in the SPs; and 3) the combination of radiological findings and IRU. Also to determine the prevalence of concurrent osseous pathology.

Methods:Five‐hundred and eighty‐two horses, presented for perceived back pain and poor performance, underwent comprehensive clinical investigation including diagnostic analgesia of the forelimbs, hindlimbs, back and sacroiliac joints, and radiographic and scintigraphic evaluation of the thoracolumbar spine. Radiological and scintigraphic grades were determined subjectively. Statistical analysis was performed to determine the relationships between clinical signs of back pain, radiological and scintigraphic features, age, breed, gender, discipline, height and weight.

Results:Thoroughbreds (TBs) were over‐represented with thoracolumbar pain compared with Warmbloods and TB cross breeds. There was a significant association between maximum and total radiological grades of the SPs and thoracolumbar pain, between maximum and total grades of IRU and thoracolumbar pain, and between a combination of radiological and scintigraphic abnormalities and thoracolumbar pain. Horses with osteoarthritis (OA) of the synovial intervertebral articulations (SIAs) were more likely to have thoracolumbar pain than horses with lesions of the SPs alone, but the presence of OA of the SIAs and lesions of the SPs was associated with the highest likelihood of thoracolumbar pain.

Conclusions and potential relevance:Fore‐ or hindlimb lameness and/or pain associated with the sacroiliac joints could mimic primary thoracolumbar pain. A combination of radiology and scintigraphy gives the most accurate prediction of thoracolumbar pain, but diagnostic analgesia is crucial for accurate diagnosis.
A randomised, double‐blinded, placebo‐controlled study on the efficacy of a unique extract of green‐lipped mussel (Perna canaliculus) in horses with chronic fetlock lameness attributed to osteoarthritis
Authors: CAYZER J. , HEDDERLEY D. , GRAY S.
Published: September 2011

Reasons for performing study: Lyophilised products from green‐lipped mussel (Perna canaliculus[LPPC]) are used to orally treat horses with osteoarthritis (OA). However, no randomised, controlled or double‐blinded studies on the efficacy of this treatment in horses have been reported to date.

Objective: To investigate the effects of a unique LPPC (Biolane)1 in improving clinical signs of OA in the fetlock.

Methods: Data were analysed from 26 horses with primary fetlock lameness in a controlled, randomised and double‐blinded, multi‐centre clinical trial. The study design was a partial crossover with a washout period and consisted of 19 horses treated with LPPC and 20 with a placebo. Horses were dosed orally with 25 mg/kg bwt/day LPPC or placebo for 56 days. Efficacy was evaluated by clinical assessment of lameness, passive flexion, pain, swelling and heat in the affected joint. Relationships between variables were analysed using an ordinal logistic model with random effects for horse and horse x treatment according to a modified intention‐to‐treat analysis.

Results: Clinical evaluation of horses with a fetlock lameness treated with LPPC showed a significant reduction in severity of lameness (P<0.001), improved response to the joint flexion test (P<0.001) and reduced joint pain (P = 0.014) when compared with horses treated with placebo.

Conclusions: The LPPC significantly alleviated the severity of lameness and joint pain and improved response to joint flexion in horses with lameness attributable to OA in the fetlock.
The application and limitations of mathematical modelling in the prediction of permeability across mammalian skin and polydimethylsiloxane membranes
Authors: Moss Gary P , Sun Yi , Wilkinson Simon C , Davey Neil , Adams Rod , Martin Gary P , Prapopopolou M , Brown Marc B
Published: September 2011

Objectives

Predicting the rate of percutaneous absorption of a drug is an important issue with the increasing use of the skin as a means of moderating and controlling drug delivery. One key feature of this problem domain is that human skin permeability (as Kp) has been shown to be inherently non-linear when mathematically related to the physicochemical parameters of penetrants. As such, the aims of this study were to apply and evaluate Gaussian process (GP) regression methods to datasets for membranes other than human skin, and to explore how the nature of the dataset may influence its analysis.

Methods

Permeability data for absorption across rodent and pig skin, and artificial membranes (polydimethylsiloxane, PDMS, i.e. Silastic) membranes was collected from the literature. Two quantitative structure–permeability relationship (QSPR) models were used to compare with the GP models. Further performance metrics were computed in terms of all predictions, and a range of covariance functions were examined: the squared exponential (SE), neural network (NNone) and rational quadratic (QR) covariance functions, along with two simple cases of Matern covariance function (Matern3 and Matern5) where the polynomial order is set to 1 and 2, respectively. As measures of performance, the correlation coefficient (CORR), negative log estimated predictive density (NLL, or negative log loss) and mean squared error (MSE) were employed.

Key findings

The results demonstrated that GP models with different covariance functions outperform QSPR models for human, pig and rodent datasets. For the artificial membranes, GPs perform better in one instance, and give similar results in other experiments (where different covariance parameters produce similar results). In some cases, the GP predictions for some of the artificial membrane dataset are poorly correlated, suggesting that the physicochemical parameters employed in this study might not be appropriate for developing models that represent this membrane.

Conclusions

While the results of this study indicate that permeation across rodent (mouse and rat) and pig skin is, in a statistical sense, similar, and that the artificial membranes are poor replacements of human or animal skin, the overriding issue raised in this study is the nature of the dataset and how it can influence the results, and subsequent interpretation, of any model produced for particular membranes. The size of the datasets, in both absolute and comparative senses, appears to influence model quality. Ideally, to generate viable cross-comparisons the datasets for different mammalian membranes should, wherever possible, exhibit as much commonality as possible.
Constrained Sparse Estimation for Improved Fault Isolation
Authors: Borguet S. , Léonard O.
Published: September 2011

Least-squares-based methods are very popular in the jet engine community for health monitoring purpose. Their isolation capability can be improved by using a prior knowledge on the health parameters that better matches the expected pattern of the solution i.e., a sparse one as accidental faults impact at most one or two component(s) simultaneously. On the other hand, complimentary information about the feasible values of the health parameters can be derived in the form of constraints. The present contribution investigates the effect of the addition of such constraints on the performance of the sparse estimation tool. Due to its quadratic programming formulation, the constraints are integrated in a straightforward manner. Results obtained on a variety of fault conditions simulated with a commercial turbofan model show that the inclusion of constraints further enhance the isolation capability of the sparse estimator. In particular, the constraints help resolve a confusion issue between high pressure compressor and variable stator vanes faults.
Spring Stiffness Selection Criteria for Nozzle Check Valves Employed in Compressor Stations
Authors: Botros K. K.
Published: September 2011

Nozzle type check valves are often employed in compressor stations in three locations: compressor outlet, station discharge, and station bypass. The fundamental design concept of these valves is based on creating a converging diverging flow through the valve internal geometry such that a minimum area is achieved at a location corresponding to the back of the check valve disk at the fully open position. This will ensure maximum hydrodynamic force coefficient which allows the valve to be fully open with minimum flow. Spring forces and stiffness determine the performance of this type of check valves and impact the overall operation and integrity of the compressor station. This paper examines the effects of various spring characteristics and stiffness in relation to the compressor and station flow characteristics. The results show that when the spring forces are higher than the maximum hydrodynamic force at minimum flow, the disk will not be at the fully open position, which will give rise to disk fluttering and potential for cyclic high velocity impact between components of the internal valve assembly. This could lead to self destruction of the check valve and subsequent risk of damage to the compressor unit itself. The paper also points to the fact that the spring selection criteria for a unit check valve are different than that for station and bypass check valves. An example of a case study with actual field data from a high pressure ratio compressor station employing this type of check valves is presented to illustrate the associated dynamic phenomena and fluid-structure interaction within the internal assembly of the check valve.
Potential for Chemolithoautotrophy Among Ubiquitous Bacteria Lineages in the Dark Ocean
Authors: Swan Brandon K. , Martinez-Garcia Manuel , Preston Christina M. , Sczyrba Alexander , Woyke Tanja , Lamy Dominique , Reinthaler Thomas , Poulton Nicole J. , Masland E. Dashiell P. , Gomez Monica Lluesma , Sieracki Michael E. , DeLong Edward F. , Herndl Gerhard J. , Stepanauskas Ramunas
Published: September 2011

Bacteria isolated from a deep seawater mass seem to fix carbon using energy from the oxidation of inorganic sulfur.
Synthetic Biology: Integrated Gene Circuits
Authors: Nandagopal Nagarajan , Elowitz Michael B.
Published: September 2011

A major goal of synthetic biology is to develop a deeper understanding of biological design principles from the bottom up, by building circuits and studying their behavior in cells. Investigators initially sought to design circuits “from scratch” that functioned as independently as possible from the underlying cellular system. More recently, researchers have begun to develop a new generation of synthetic circuits that integrate more closely with endogenous cellular processes. These approaches are providing fundamental insights into the regulatory architecture, dynamics, and evolution of genetic circuits and enabling new levels of control across diverse biological systems.
Switching Light by Vacuum
Authors: Fleischhauer Michael
Published: September 2011

An opaque cloud of cold atoms becomes transparent when a few photons occupy an empty cavity, creating an optical switch for processing quantum information.
Through Thick and Thin
Authors: Brown Eric , Jaeger Heinrich M.
Published: September 2011

New experimental results probe the relationship between rheology and particle-scale structure of suspensions.
Panel Blasts Ethics, Science of 1940s Guatemala Studies
Authors: Kaiser Jocelyn
Published: September 2011

An exhaustive high-level review of unethical syphilis experiments conducted in Guatemala by U.S. researchers in the 1940s has found little to redeem the work or its lead researcher.
Sweet Here, Salty There: Evidence for a Taste Map in the Mammalian Brain
Authors: Miller Greg
Published: September 2011

A paper published this week in
Science
presents a new picture of how taste is encoded in the mouse gustatory cortex, the region of the brain devoted to processing taste stimuli.
A Lab of Their Own
Authors: Kean Sam
Published: September 2011

Do-it-yourself biologists in New York are following their dreams, setting up a community lab that combines synthetic biology with art, fun, and perhaps profit.
Cancer's Food Network
Authors: Emadi Ashkan
Published: September 2011

A variation in glutamine dependence and metabolism among tumor subtypes may point to a target for selective induction of cancer death.
A Gut Check for Asthma
Authors: Shum Anthony K.
Published: September 2011

Mice infected with
Helicobacter pylori
are protected against developing asthma.
Beta-
d
-Glucan Detection as a Diagnostic Test for Invasive Aspergillosis in Immunocompromised Critically Ill Patients with Symptoms of Respiratory Infection: an Autopsy-Based Study
Authors: De Vlieger Greet , Lagrou Katrien , Maertens Johan , Verbeken Eric , Meersseman Wouter , Van Wijngaerden Eric
Published: September 2011

Beta-(1,3)-
d
-glucan (BG) detection is an emerging tool to diagnose invasive fungal infections (IFIs). Invasive aspergillosis (IA) is the second most common IFI in immunocompromised intensive care unit (ICU) patients. We retrospectively analyzed the serum BG concentration (Fungitell; Associates of Cape Cod) in immunocompromised ICU patients with proven IA and in immunocompromised ICU patients in whom autopsy failed to show IFI. The study was performed in a 17-bed medical ICU in a 1,900-bed referral hospital. Patients at risk for IA were eligible for inclusion when at least two additional clinical signs were present. Patients with other IFIs were excluded. Fourteen patients with IA and 33 patients who had no IFI were eligible for inclusion. Serum BG levels were significantly higher in patients with IA than patients without an IFI (
P
< 0.01). Using a cutoff of 140 pg/ml, the sensitivity and specificity were 85.7 and 69.7%, respectively; the positive and negative predictive values were 54.5 and 92.0%, respectively. The positive and negative likelihood ratios were 2.83 and 0.21, respectively. Although serum BG concentrations were higher in immunocompromised ICU patients with IA than in patients with the same risk factors who did not have IFI on autopsy, the moderate performance characteristics of this test limit its use as a diagnostic test for IA in this population.
First Report of Disseminated Mycobacterium Skin Infections in Two Liver Transplant Recipients and Rapid Diagnosis by
hsp65
Gene Sequencing
Authors: Lau Susanna K. P. , Curreem Shirly O. T. , Ngan Antonio H. Y. , Yeung Chi-Keung , Yuen Kwok-Yung , Woo Patrick C. Y.
Published: September 2011

We present here the first report of disseminated skin
Mycobacterium
infections in two liver transplant recipients, in which
hsp65
gene sequencing was used for rapid species identification. Both patients had hepatitis B virus-related cirrhosis and diabetes mellitus and presented with progressive generalized, nodular skin lesions. In one patient, a 50-year-old woman who had frequent contact with marine fish, an acid-fast bacillus was isolated from skin biopsy tissue after 2 months of culture. While awaiting phenotypic identification results,
hsp65
gene sequencing showed that it was most closely related to that of
Mycobacterium marinum
with 100% nucleotide identity. The patient was treated with oral rifampin, ethambutol, and moxifloxacin. In the other patient, a 59-year-old woman, direct PCR for
Mycobacterium
using
hsp65
gene from skin biopsy tissue was positive, with the sequence most closely related to that of
M. haemophilum
with 100% nucleotide identity. Based on PCR results, the patient was treated with clarithromycin, ethambutol, moxifloxacin, and amikacin. A strain of
M. haemophilum
was only isolated after 3 months. Skin lesions of both patients resolved after 1 year of antimycobacterial therapy. Nontuberculous
Mycobacterium
infections should be considered in liver transplant recipients presenting with chronic, nodular skin lesions. This report highlights the crucial role of
hsp65
gene PCR and sequencing on both cultured isolates and direct clinical specimens for rapid diagnosis of slow-growing
Mycobacterium
infection.
Infection of Calves with Bovine Norovirus GIII.1 Strain Jena Virus: an Experimental Model To Study the Pathogenesis of Norovirus Infection
Authors: Otto Peter H. , Clarke Ian N. , Lambden Paul R. , Salim Omar , Reetz Jochen , Liebler-Tenorio Elisabeth M.
Published: September 2011

The experimental infection of newborn calves with bovine norovirus was used as a homologous large animal model to study the pathogenesis of norovirus infection and to determine target cells for viral replication. Six newborn calves were inoculated orally with Jena virus (JV), a bovine norovirus GIII.1 strain, and six calves served as mock-inoculated controls. Following infection, calves were euthanized before the onset of diarrhea (12 h postinoculation [hpi]), shortly after the onset of diarrhea (18 to 21 hpi), and postconvalescence (4 days pi [dpi]). Calves inoculated with JV developed severe watery diarrhea at 14 to 16 hpi, and this symptom lasted for 53.5 to 67.0 h. Intestinal lesions were characterized by severe villus atrophy together with loss and attenuation of villus epithelium. Viral capsid antigen (JV antigen) was detected by immunohistochemistry in the cytoplasm of epithelial cells on villi. In addition, granular material positive for JV antigen was detected in the lamina propria of villi. Lesions first appeared at 12 hpi and were most extensive at 18 to 19 hpi, extending from midjejunum to ileum. The intestinal mucosa had completely recovered at 4 dpi. There was no indication of systemic infection as described for norovirus infection in mice. JV was found in intestinal contents by reverse transcription-PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) as early as 12 hpi. Fecal shedding of the virus started at 13 hpi and stopped at 23 hpi or at necropsy (4 dpi), respectively. Throughout the trial, none of the control calves tested positive for JV by ELISA or RT-PCR.
Increased Frequency of Regulatory T Cells Accompanies Increased Immune Activation in Rectal Mucosae of HIV-Positive Noncontrollers
Authors: Shaw Julia M. , Hunt Peter W. , Critchfield J. William , McConnell Delandy H. , Garcia Juan Carlos , Pollard Richard B. , Somsouk Ma , Deeks Steven G. , Shacklett Barbara L.
Published: September 2011

Gut-associated lymphoid tissue (GALT) is a major site of HIV replication and CD4+T cell depletion. Furthermore, microbial translocation facilitated by mucosal damage likely contributes to the generalized immune activation observed in HIV infection. Regulatory T cells (Treg) help maintain homeostasis and suppress harmful immune activation during infection; however, in the case of persistent viral infections such as HIV, their role is less clear. Although a number of studies have examined Treg in blood during chronic infection, few have explored Treg in the gastrointestinal mucosa. For this study, paired blood and rectal biopsy samples were obtained from 12 HIV noncontrollers (viral load of >10,000 copies/ml plasma), 10 HIV controllers (viral load of <500 copies/ml plasma for more than 5 years), and 12 HIV seronegative control subjects. Noncontrollers had significantly higher percentages of Treg in rectal mononuclear cells (RMNC), but not in blood, compared to seronegative subjects (P= 0.001) or HIV controllers (P= 0.002). Mucosal Treg positively correlated with viral load (P= 0.01) and expression of immune activation markers by CD4+(P= 0.01) and CD8+(P= 0.07) T cells. Suppression assays indicated that mucosal and peripheral Treg of noncontrollers and controllers maintained their capacity to suppress non-Treg proliferation to a similar extent as Treg from seronegative subjects. Together, these findings reveal that rather than experiencing depletion, mucosal Treg frequency is enhanced during chronic HIV infection and is positively correlated with viral load and immune activation. Moreover, mucosal Treg maintain their suppressive ability during chronic HIV infection, potentially contributing to diminished HIV-specific T cell responses and viral persistence.
The Universally Conserved Prokaryotic GTPases
Authors: Verstraeten Natalie , Fauvart Maarten , Versées Wim , Michiels Jan
Published: September 2011

Members of the large superclass of P-loop GTPases share a core domain with a conserved three-dimensional structure. In eukaryotes, these proteins are implicated in various crucial cellular processes, including translation, membrane trafficking, cell cycle progression, and membrane signaling. As targets of mutation and toxins, GTPases are involved in the pathogenesis of cancer and infectious diseases. In prokaryotes also, it is hard to overestimate the importance of GTPases in cell physiology. Numerous papers have shed new light on the role of bacterial GTPases in cell cycle regulation, ribosome assembly, the stress response, and other cellular processes. Moreover, bacterial GTPases have been identified as high-potential drug targets. A key paper published over 2 decades ago stated that, “It may never again be possible to capture [GTPases] in a family portrait” (H. R. Bourne, D. A. Sanders, and F. McCormick, Nature348:125-132, 1990) and indeed, the last 20 years have seen a tremendous increase in publications on the subject. Sequence analysis identified 13 bacterial GTPases that are conserved in at least 75% of all bacterial species. We here provide an overview of these 13 protein subfamilies, covering their cellular functions as well as cellular localization and expression levels, three-dimensional structures, biochemical properties, and gene organization. Conserved roles in eukaryotic homologs will be discussed as well. A comprehensive overview summarizing current knowledge on prokaryotic GTPases will aid in further elucidating the function of these important proteins.
From Water and Ions to Crowded Biomacromolecules:In VivoStructuring of a Prokaryotic Cell
Authors: Spitzer Jan
Published: September 2011

The interactions and processes which structure prokaryotic cytoplasm (water, ions, metabolites, and biomacromolecules) and ensure the fidelity of the cell cycle are reviewed from a physicochemical perspective. Recent spectroscopic and biological evidence shows that water has no active structuring role in the cytoplasm, an unnecessary notion still entertained in the literature; water acts only as a normal solvent and biochemical reactant. Subcellular structuring arises from localizations and interactions of biomacromolecules and from the growth and modifications of their surfaces by catalytic reactions. Biomacromolecular crowding is a fundamental physicochemical characteristic of cellsin vivo. Though some biochemical and physiological effects of crowding (excluded volume effect) have been documented, crowding assays with polyglycols, dextrans, etc., do not properly mimic the compositional variety of biomacromoleculesin vivo.In vitrocrowding assays are now being designed with proteins, which better reflect biomacromolecular environmentsin vivo, allowing for hydrophobic bonding and screened electrostatic interactions. I elaborate further the concept of complex vectorial biochemistry, where crowded biomacromolecules structure the cytosol into electrolyte pathways and nanopools that electrochemically “wire” the cell. Noncovalent attractions between biomacromolecules transiently supercrowd biomacromolecules into vectorial, semiconducting multiplexes with a high (35 to 95%)-volume fraction of biomacromolecules; consequently, reservoirs of less crowded cytosol appear in order to maintain the experimental average crowding of ∼25% volume fraction. This nonuniform crowding model allows for fast diffusion of biomacromolecules in the uncrowded cytosolic reservoirs, while the supercrowded vectorial multiplexes conserve the remarkable repeatability of the cell cycle by preventing confusing cross talk of concurrent biochemical reactions.
Highways for internal virus spread: patterns of virus movement in the stoloniferous herb Trifolium repens
Authors: van Mölken Tamara , Sundelin Thomas , Snetselaar Reinier , Stuefer Josef F.
Published: September 2011

Resource sharing between connected ramets can be advantageous for clonal plants. However, widespread vascular integration bears the risks of enhanced internal pathogen spread, which may be one of the most prominent disadvantages of clonal growth. In this paper we analyzed patterns of internal virus spread in ramet groups of the stoloniferous herb Trifolium repens L. (white clover) and investigated the effect of leaf ontogeny on intraclonal disease development. We inoculated single leaves of T. repens with White clover mosaic virus and analyzed the infection status of ramets at different distances from the point of infection and in leaves from different developmental stages. White clover mosaic virus infected all young developing plant parts positioned on basal branches or on the main stolon. Leaf ontogeny strongly affected disease development, and fully mature leaves on the main stolon remained virus free. The pattern of plant-internal virus spread was not affected by heterogeneous light conditions. Despite the well-described advantages of physiological integration, our data suggest that clonal integration may lead to negative selection pressures on clonal growth in pathogen-prone environments.
Assessing hydraulic conductivities of a compacted dam core using geostatistical analysis of construction control data
Authors: Smith M. , Konrad J.-M.
Published: September 2011

The surveillance of a 94.5 m high embankment dam in northern Quebec, Canada, revealed the possibility of the existence of a zone of higher hydraulic conductivity in its till core. The spatial continuity of the measured fines content in the dam during construction was computed by geostatistical means to predict values at unsampled locations for the entire core volume. The hydraulic conductivities were inferred using the predicted fines content and in situ compaction conditions. The inferred hydraulic conductivities and their spatial representations were supported by thermal and seepage field monitoring data. This provided the necessary background information to interpret the surveillance data and determine the cause of the presence of a more pervious zone in the core, which was related to spatial variability of the fines content of the till, placement water content, and compaction procedures. The geostatistical approach complemented with laboratory and construction control data is an efficient tool to characterize dam heterogeneities permitting location of zones of more intensive seepage.
A meta-analysis of the effects of clearcut and variable-retention harvesting on soil nitrogen fluxes in boreal and temperate forests
Authors: Jerabkova Lucie , Prescott Cindy E. , Titus Brian D. , Hope Graeme D. , Walters Michael B.
Published: September 2011

One of the assumed advantages of variable-retention (VR) harvesting over clearcut harvesting is reduced postharvest leaching losses of nitrogen. We test this assumption by synthesizing results from long-term field trials in a meta-analysis. Overall, clearcutting significantly increased soil NO3-N concentration, NO3-N as a proportion of soluble inorganic nitrogen (SIN), N concentration in leachates, N flux, nitrification rates, and pH, but not total N, NH4-N, SIN concentration, ammonification, or N mineralization rate. The proportion of soil NO3-N in deciduous forests increased immediately and returned to preharvest levels within five years; the effect was delayed in coniferous forests, but levels remained elevated for several years. Deciduous leaf litter decomposed faster and needle litter decomposed more slowly on clearcut sites than in uncut forests. Single-tree selection caused smaller changes in NO3-N than removal of groups of trees (i.e., gap creation) and led to smaller increases in NO3-N as a proportion of SIN than clearcut harvesting. High levels of retention (>70%) were required to maintain uncut stand N-cycling characteristics. Postharvest NO3-N levels could be predicted from NO3-N availability in the uncut forests.
Understanding residents’ desired approaches to manage forest access roads: a case from northeastern Ontario, Canada
Authors: Mihell Kim , Hunt Len M.
Published: September 2011

Managing roads and access on publicly owned forested lands should include assessments of the public’s views of desirability for different approaches. To assess the public’s views, we explored northeastern Ontario residents’ desirability ratings towards approaches that remove, deactivate, or close forest access roads. From a social survey, respondents, on average, rated every restrictive approach as undesirable. From a principal components and cluster analysis, we identified four groups of respondents (open roads, road deactivation, road closure, and sign-based road closure supporters) that differed in their desirability ratings for the approaches. Comparisons of group members by the types and intensity of outdoor recreation use, attitudes towards roads and management, environmental value orientations, and sociodemographic characteristics revealed expected and important differences. On the one hand, almost one half of respondents had high levels of undesirability ratings towards any restrictive approach, suggesting that attempts to restrict road access might be met with stiff opposition. On the other hand, the presence of groups that support road deactivation, sign-based road closures, and general road closures suggests that many other residents might be willing to accept some access restrictions on roads. Consequently, managers must be aware of the heterogeneity in views about access when planning roads and access.
Precipitation frequency controls interannual variation of soil respiration by affecting soil moisture in a subtropical forest plantation
Authors: Wang Yidong , Li Qingkang , Wang Huimin , Wen Xuefa , Yang Fengting , Ma Zeqing , Liu Yunfen , Sun Xiaomin , Yu Guirui
Published: September 2011

Despite the significance of interannual variation of soil respiration (RS) for understanding long-term soil carbon dynamics, factors that control the interannual variation of RS have not been sufficiently investigated. Interannual variation of RS was studied using a 6-year data set collected in a subtropical plantation dominated by an exotic species, slash pine (Pinus elliottii Engelm.), in China. The results showed that seasonal variation of RS was significantly affected by soil temperature and soil water content (SWC). RS in the dry season (July–October) was constrained by seasonal drought. Mean annual RS was estimated to be 736 ± 30 g C·m–2·year–1, with a range of 706–790 g C·m–2·year–1. Although this forest was characterized by a humid climate with high precipitation (1469 mm·year–1), the interannual variation of RS was attributed to the changes of annual mean SWC (R2 = 0.66, P = 0.03), which was affected by annual rainfall frequency (R2 = 0.80, P < 0.01) and not rainfall amount (P = 0.84). Consequently, precipitation pattern indirectly controlled the interannual variation of RS by affecting soil moisture in this subtropical forest. In the context of climate change, interannual variation of RS in subtropical ecosystems is expected to increase because of the predicted changes of precipitation regime.
Phase Space and Dynamical Fluctuations of Kaon-to-Pion Ratios
Authors: Tawfik Abdel
Published: September 2011

The dynamical fluctuations of kaon-to-pion ratios have been studied over a wide range of center-of-mass energies √s. On the basis of changing phase space volume which apparently is the consequence of phase transition from hadrons to quark-gluon plasma at large √s, the single-particle distribution function f is assumed to be rather modified. Varying f and phase space volume are implemented in the grand-canonical partition function, especially at large √s, so that the hadron resonance gas model, when taking into account the experimental acceptance and quark phase space occupation factor, turns to be able to reproduce the dynamical fluctuations of kaon-to-pion ratios over the entire range of √s.
COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice
Authors: Nørregaard Rikke , Madsen Kirsten , Hansen Pernille B. L. , Bie Peter , Thavalingam Sugarna , Frøkiær Jørgen , Jensen Boye L.
Published: September 2011

It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2−/−, C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP mRNA and peptide level, AVP plasma concentration, and AVP-regulated renal transport protein abundances were measured. In male COX-2−/−, basal urine output and water intake were elevated while urine osmolality was decreased compared with WT. Water deprivation resulted in lower urine osmolality, higher plasma osmolality in COX-2−/− mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2−/− and WT after WD. AVP peptide content was higher in COX-2−/− compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2−/− mice, but after WD plasma AVP was unchanged between COX-2−/− and WT mice (43 ± 11 vs. 70 ± 16 pg/ml). Renal V2 receptor abundance was downregulated in COX-2−/− mice. Medullary interstitial osmolality increased and did not differ between COX-2−/− and WT after WD. Aquaporin-2 (AQP2; cortex-outer medulla), AQP3 (all regions), and UT-A1 (inner medulla) protein abundances were elevated in COX-2−/− at baseline and further increased after WD. COX-2−/− mice had elevated plasma urea and creatinine and accumulation of small subcapsular glomeruli. In conclusion, hypothalamic COX-2 activity is not necessary for enhanced AVP expression and secretion in response to water deprivation. Renal medullary COX-2 activity negatively regulates AQP2 and -3. The urine concentrating defect in COX-2−/− is likely caused by developmental glomerular injury and not dysregulation of AVP or collecting duct aquaporins.
The ionic mechanism of gamma resonance in rat striatal fast-spiking neurons
Authors: Sciamanna Giuseppe , Wilson Charles J.
Published: September 2011

Striatal fast-spiking (FS) cells in slices fire in the gamma frequency range and in vivo are often phase-locked to gamma oscillations in the field potential. We studied the firing patterns of these cells in slices from rats ages 16–23 days to determine the mechanism of their gamma resonance. The resonance of striatal FS cells was manifested as a minimum frequency for repetitive firing. At rheobase, cells fired a doublet of action potentials or doublets separated by pauses, with an instantaneous firing rate averaging 44 spikes/s. The minimum rate for sustained firing was also responsible for the stuttering firing pattern. Firing rate adapted during each episode of firing, and bursts were terminated when firing was reduced to the minimum sustainable rate. Resonance and stuttering continued after blockade of Kv3 current using tetraethylammonium (0.1–1 mM). Both gamma resonance and stuttering were strongly dependent on Kv1 current. Blockade of Kv1 channels with dendrotoxin-I (100 nM) completely abolished the stuttering firing pattern, greatly lowered the minimum firing rate, abolished gamma-band subthreshold oscillations, and slowed spike frequency adaptation. The loss of resonance could be accounted for by a reduction in potassium current near spike threshold and the emergence of a fixed spike threshold. Inactivation of the Kv1 channel combined with the minimum firing rate could account for the stuttering firing pattern. The resonant properties conferred by this channel were shown to be adequate to account for their phase-locking to gamma-frequency inputs as seen in vivo.
Superposition and modulation of muscle synergies for reaching in response to a change in target location
Authors: d'Avella Andrea , Portone Alessandro , Lacquaniti Francesco
Published: September 2011

We have recently shown that the muscle patterns for reaching are well described by the combination of a few time-varying muscle synergies supporting the notion of a modular architecture for arm control. Here we investigated whether the muscle patterns for reaching movements involving online corrections are also generated by the combination of the same set of time-varying muscle synergies used for point-to-point movements. We recorded endpoint kinematics and EMGs from up to 16 arm muscles of 5 subjects reaching from a central location to 8 peripheral targets in the frontal plane, from each peripheral target to 1 of the 2 adjacent targets, and from the central location initially to 1 peripheral target and, after a delay of either 50, 150, or 250 ms from the go signal, to 1 of the 2 adjacent targets. Time-varying muscle synergies were extracted from the averaged, phasic, normalized EMGs of point-to-point movements and fit to the patterns of target change movements using an iterative optimization algorithm. In all subjects, three time-varying muscle synergies explained a large fraction of the data variation of point-to-point movements. The superposition and modulation of the same three synergies reconstructed the muscle patterns for target change movements better than the superposition and modulation of the corresponding point-to-point muscle patterns, appropriately aligned. While at the kinematic level the corrective trajectory for reaching during a change in target location can be obtained by the delayed superposition of the trajectory from the initial to the final target, at the muscle level the underlying phasic muscle patterns are captured by the amplitude and timing modulation of the same time-varying muscle synergies recruited for point-to-point movements. These results suggest that a common modular architecture is used for the control of unperturbed arm movement and for its visually guided online corrections.
Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells
Authors: Giuliani Nicola , Airoldi Irma
Published: September 2011

Multiple myeloma is a monoclonal postgerminal center tumor that has phenotypic features of plasmablasts and/or plasma cells and usually localizes at multiple sites in the bone marrow. The pathogenesis of multiple myeloma is complex and dependent on the interactions between tumor cells and their microenvironment. Different cytokines, chemokines, and proangiogenic factors released in the tumor microenvironment are known to promote multiple myeloma cell growth. Here, we report recent advances on the role of 2 strictly related immunomodulatory cytokines, interleukin-27 (IL-27) and IL-23, in human normal and neoplastic plasma cells, highlighting their ability to (i) act directly against multiple myeloma cells, (ii) influence the multiple myeloma microenvironment by targeting osteoclast and osteoblast cells, and (iii) modulate normal plasma cell function. Finally, the therapeutic implication of these studies is discussed. Clin Cancer Res; 17(22); 6963–70. ©2011 AACR.
Mechanistic Contribution of Ubiquitous 15-Lipoxygenase-1 Expression Loss in Cancer Cells to Terminal Cell Differentiation Evasion
Authors: Moussalli Micheline J. , Wu Yuanqing , Zuo Xiangsheng , Yang Xiu L. , Wistuba Ignacio Ivan , Raso Maria G. , Morris Jeffrey S. , Bowser Jessica L. , Minna John D. , Lotan Reuben , Shureiqi Imad
Published: September 2011

Loss of terminal cell differentiation promotes tumorigenesis. 15-Lipoxygenase-1 (15-LOX-1) contributes to terminal cell differentiation in normal cells. The mechanistic significance of 15-LOX-1 expression loss in human cancers to terminal cell differentiation suppression is unknown. In a screen of 128 cancer cell lines representing more than 20 types of human cancer, we found that 15-LOX-1 mRNA expression levels were markedly lower than levels in terminally differentiated cells. Relative expression levels of 15-LOX-1 (relative to the level in terminally differentiated primary normal human–derived bronchial epithelial cells) were lower in 79% of the screened cancer cell lines than relative expression levels of p16 (INK4A), which promotes terminal cell differentiation and is considered one of the most commonly lost tumor suppressor genes in cancer cells. 15-LOX-1 was expressed during terminal differentiation in three-dimensional air–liquid interface cultures, and 15-LOX-1 expression and terminal differentiation occurred in immortalized nontransformed bronchial epithelial but not in lung cancer cell lines. 15-LOX-1 expression levels were lower in human tumors than in paired normal lung epithelia. Short hairpin RNA–mediated downregulation of 15-LOX-1 in Caco-2 cells blocked enterocyte-like differentiation, disrupted tight junction formation, and blocked E-cadherin and ZO-1 localization to the cell wall membrane. 15-LOX-1 episomal expression in Caco-2 and HT-29 colon cancer cells induced differentiation. Our findings indicate that 15-LOX-1 downregulation in cancer cells is an important mechanism for terminal cell differentiation dysregulation and support the potential therapeutic utility of 15-LOX-1 reexpression to inhibit tumorigenesis. Cancer Prev Res; 4(12); 1961–72. ©2011 AACR.