bluuebunny/crossref_metadata_2025 huggingface dataset:
Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells
Authors: Boitano Anthony E. , Wang Jian , Romeo Russell , Bouchez Laure C. , Parker Albert E. , Sutton Sue E. , Walker John R. , Flaveny Colin A. , Perdew Gary H. , Denison Michael S. , Schultz Peter G. , Cooke Michael P.
Published: August 2010

Stem Cell Expansion

The ability to expand hematopoietic stem cells (HSCs) during ex-vivo culture has been an important goal for over 20 years. Using a high-throughput chemical screen,

Boitano
et al.

(p.
1345
, published online 5 August; see the Perspective by

Sauvageau and Humphries

) found that a purine derivative, StemRegenin1 (SR1), promoted the expansion of human HSCs. Treatment of HSCs with SR1 (which blocked the activity of the aryl hydrocarbon receptor) led to the expansion of CD34
+
cells and a 12 to 17-fold increase in the number of HSCs that engraft immune deficient mice.
Versatile Germline Genes
Authors: Juliano Celina , Wessel Gary
Published: August 2010

When do germ cells establish their separate, independent identity during animal development?
The Power of Two
Authors: Pennisi Elizabeth
Published: August 2010

A University of Florida couple studying the evolution of flowering plants shows the value of doubled genomes—and joined careers.
A Microbe-Dependent Viral Key to Crohn’s Box
Authors: Peterson Daniel A. , Turnbaugh Peter J.
Published: August 2010

New work suggests that multiple facets of the human microbiome must be considered when deciphering complex diseases such as Crohn’s.
The Promise of C-Type Natriuretic Peptide for Weight Loss
Authors: Bentley-Lewis Rhonda
Published: August 2010

A recently described hormone, C-type natriuretic peptide, decreases food intake, and therefore body weight, and increases energy expenditure.
Occupational Asthma Induced by
Chrysonilia sitophila
in a Worker Exposed to Coffee Grounds
Authors: Francuz Beata , Yera Helene , Geraut Laurent , Bensefa-Colas Lynda , Nghiem Zuong Hung , Choudat Dominique
Published: August 2010

A new case of occupational asthma caused by
Chrysonilia sitophila
(asexual state of
Neurospora sitophila
) was diagnosed by molecular identification of the mold and confirmed by skin prick test, peak expiratory flow rate measurements, and experimental immunoglobulin E analysis.
Infectious Lassa Virus, but Not Filoviruses, Is Restricted by BST-2/Tetherin
Authors: Radoshitzky Sheli R. , Dong Lian , Chi Xiaoli , Clester Jeremiah C. , Retterer Cary , Spurgers Kevin , Kuhn Jens H. , Sandwick Sarah , Ruthel Gordon , Kota Krishna , Boltz Dutch , Warren Travis , Kranzusch Philip J. , Whelan Sean P. J. , Bavari Sina
Published: August 2010

Bone marrow stromal antigen 2 (BST-2/tetherin) is a cellular membrane protein that inhibits the release of HIV-1. We show for the first time, using infectious viruses, that BST-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. Specifically, infectious Lassa virus (LASV) release significantly decreased or increased in human cells in which BST-2 was either stably expressed or knocked down, respectively. In contrast, replication and spread of infectious Zaire ebolavirus (ZEBOV) and Lake Victoria marburgvirus (MARV) were not affected by these conditions. Replication of infectious Rift Valley fever virus (RVFV) and cowpox virus (CPXV) was also not affected by BST-2 expression. Elevated cellular levels of human or murine BST-2 inhibited the release of virus-like particles (VLPs) consisting of the matrix proteins of multiple highly virulent NIAID Priority Pathogens, including arenaviruses (LASV and Machupo virus [MACV]), filoviruses (ZEBOV and MARV), and paramyxoviruses (Nipah virus). Although the glycoproteins of filoviruses counteracted the antiviral activity of BST-2 in the context of VLPs, they could not rescue arenaviral (LASV and MACV) VLP release upon BST-2 overexpression. Furthermore, we did not observe colocalization of filoviral glycoproteins with BST-2 during infection with authentic viruses. None of the arenavirus-encoded proteins rescued budding of VLPs in the presence of BST-2. Our results demonstrate that BST-2 might be a broad antiviral factor with the ability to restrict release of a wide variety of human pathogens. However, at least filoviruses, RVFV, and CPXV are immune to its inhibitory effect.
Virulence Determinants of Avian H5N1 Influenza A Virus in Mammalian and Avian Hosts: Role of the C-Terminal ESEV Motif in the Viral NS1 Protein
Authors: Zielecki Florian , Semmler Ilia , Kalthoff Donata , Voss Daniel , Mauel Susanne , Gruber Achim D. , Beer Martin , Wolff Thorsten
Published: August 2010

We assessed the prediction that access of the viral NS1 protein to cellular PDZ domain protein networks enhances the virulence of highly pathogenic avian influenza A viruses. The NS1 proteins of most avian influenza viruses bear the C-terminal ligand sequence Glu-Ser-Glu-Val (ESEV) for PDZ domains present in multiple host proteins, whereas no such motif is found in the NS1 homologues of seasonal human virus strains. Previous analysis showed that a C-terminal ESEV motif increases viral virulence when introduced into the NS1 protein of mouse-adapted H1N1 influenza virus. To examine the role of the PDZ domain ligand motif in avian influenza virus virulence, we generated three recombinants, derived from the prototypic H5N1 influenza A/Vietnam/1203/04 virus, expressing NS1 proteins that either have the C-terminal ESEV motif or the human influenza virus RSKV consensus or bear a natural truncation of this motif, respectively. Cell biological analyses showed strong control of NS1 nuclear migration in infected mammalian and avian cells, with only minor differences between the three variants. The ESEV sequence attenuated viral replication on cultured human, murine, and duck cells but not on chicken fibroblasts. However, all three viruses caused highly lethal infections in mice and chickens, with little difference in viral titers in organs, mean lethal dose, or intravenous pathogenicity index. These findings demonstrate that a PDZ domain ligand sequence in NS1 contributes little to the virulence of H5N1 viruses in these hosts, and they indicate that this motif modulates viral replication in a strain- and host-dependent manner.
Recombinant Soluble, Multimeric HA and NA Exhibit Distinctive Types of Protection against Pandemic Swine-Origin 2009 A(H1N1) Influenza Virus Infection in Ferrets
Authors: Bosch Berend Jan , Bodewes Rogier , de Vries Robert P. , Kreijtz Joost H. C. M. , Bartelink Willem , van Amerongen Geert , Rimmelzwaan Guus F. , de Haan Cornelis A. M. , Osterhaus Albert D. M. E. , Rottier Peter J. M.
Published: August 2010

The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim, we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA
3
) and NA (sNA
4
) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-μg doses of these antigens elicited strong antibody responses, which were adjuvant dependent. Interestingly, coadministration of both antigens strongly enhanced the HA-specific but not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA
3
dramatically reduced virus replication (e.g., by lowering pulmonary titers by about 5 log
10
units), immunization with sNA
4
markedly decreased the clinical effects of infection, such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly, and safely produced in high quantities. In particular, our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.
TO INCREASE RISK AWARENESS AND AVOID REHABILITATION TREATMENT RISK: A CASE REPORT OF THE CERVICAL SPINE DISEASE ASSOCIATED WITH INTRACRANIAL ARTERIAL ANEURYSM DIAGNOSIS AND TREATMENT
Authors: Zhang Jinlong , He Hongchen , Lin Haidan , Luo Qinglu , He Chengqi
Published: August 2010

With socio-economic development, there is growing concern about one's own health problems. The traditional view was that in cases of medical treatment, rehabilitation has a lower risk or even no risk compared to other forms of medication. However, that is not the case. Rehabilitation, like surgery, also has a high risk. The main source of risk comes from nonstandard rehabilitation operation on diseases without clear diagnosis. This article presents a case study of a patient with cervical spine disease with intracranial arterial aneurysm diagnosis and treatment, to explore the potential of rehabilitation medicine and examine the risk of physician–patient conflicts.
The Strigolactone Story
Authors: Xie Xiaonan , Yoneyama Kaori , Yoneyama Koichi
Published: August 2010

Strigolactones (SLs) were originally isolated from plant root exudates as germination stimulants for root parasitic plants of the family Orobanchaceae, including witchweeds (Striga spp.), broomrapes (Orobanche and Phelipanche spp.), and Alectra spp., and so were regarded as detrimental to the producing plants. Their role as indispensable chemical signals for root colonization by symbiotic arbuscular mycorrhizal fungi was subsequently unveiled, and SLs then became recognized as beneficial plant metabolites. In addition to these functions in the rhizosphere, it has been recently shown that SLs or their metabolites are a novel class of plant hormones that inhibit shoot branching. Furthermore, SLs are suggested to have other biological functions in rhizosphere communications and in plant growth and development.
Protein kinase C-δ regulates the subcellular localization of Shc in H2O2-treated cardiomyocytes
Authors: Guo Jianfen , Cong Lin , Rybin Vitalyi O. , Gertsberg Zoya , Steinberg Susan F.
Published: August 2010

Protein kinase C-δ (PKCδ) exerts important cardiac actions as a lipid-regulated kinase. There is limited evidence that PKCδ also might exert an additional kinase-independent action as a regulator of the subcellular compartmentalization of binding partners such as Shc (Src homologous and collagen), a family of adapter proteins that play key roles in growth regulation and oxidative stress responses. This study shows that native PKCδ forms complexes with endogenous Shc proteins in H2O2-treated cardiomyocytes; H2O2 treatment also leads to the accumulation of PKCδ and Shc in a detergent-insoluble cytoskeletal fraction and in mitochondria. H2O2-dependent recruitment of Shc isoforms to cytoskeletal and mitochondrial fractions is amplified by wild-type-PKCδ overexpression, consistent with the notion that PKCδ acts as a signal-regulated scaffold to anchor Shc in specific subcellular compartments. However, overexpression studies with kinase-dead (KD)-PKCδ-K376R (an ATP-binding mutant of PKCδ that lacks catalytic activity) are less informative, since KD-PKCδ-K376R aberrantly localizes as a constitutively tyrosine-phosphorylated enzyme to detergent-insoluble and mitochondrial fractions of resting cardiomyocytes; relatively little KD-PKCδ-K376R remains in the cytosolic fraction. The aberrant localization and tyrosine phosphorylation patterns for KD-PKCδ-K376R do not phenocopy the properties of native PKCδ, even in cells chronically treated with GF109203X to inhibit PKCδ activity. Hence, while KD-PKCδ-K376R overexpression increases Shc localization to the detergent-insoluble and mitochondrial fractions, the significance of these results is uncertain. Our studies suggest that experiments using KD-PKCδ-K376R overexpression as a strategy to competitively inhibit the kinase-dependent actions of native PKCδ or to expose the kinase-independent scaffolding functions of PKCδ should be interpreted with caution.
Blunted IgE-mediated activation of mast cells in mice lacking the serum- and glucocorticoid-inducible kinase SGK3
Authors: Zemtsova Irina M. , Heise Nicole , Fröhlich Henning , Qadri Syed M. , Kucherenko Yuliya , Boini Krishna M. , Pearce David , Shumilina Ekaterina , Lang Florian
Published: August 2010

Previous studies have shown that pharmacological inhibition of the phosphoinositol-3 (PI3) kinase disrupts the activation of mast cells. Through phosphoinositide-dependent kinase PDK1, PI3 kinase activates the serum- and glucocorticoid-inducible kinase 3 (SGK3). The present study explored the role of SGK3 in mast cell function. Mast cells were isolated and cultured from bone marrow (BMMCs) of gene-targeted mice lacking SGK3 ( sgk3 −/−) and their wild-type littermates ( sgk3 +/+). BMMC numbers in the ear conch were similar in both genotypes. Stimulation with IgE and cognate antigen triggered the release of intracellular Ca2+ and entry of extracellular Ca2+. Influx of extracellular Ca2+ but not Ca2+ release from intracellular stores was significantly blunted in sgk3 −/− BMMCs compared with sgk3 +/+ BMMCs. Antigen stimulation further led to a rapid increase of a K+-selective conductance in sgk3 +/+ BMMCs, an effect again blunted in sgk3 −/− BMMCs. In contrast, the Ca2+ ionophore ionomycin activated K+ currents to a similar extent in sgk3 −/− and in sgk3 +/+ BMMCs. β-Hexosaminidase release, triggered by antigen stimulation, was also significantly decreased in sgk3 −/− BMMCs. IgE-dependent anaphylaxis measured as a sharp decrease in body temperature upon injection of DNP-HSA antigen was again significantly blunted in sgk3 −/− compared with sgk3 +/+ mice. Serum histamine levels measured 30 min after induction of an anaphylactic reaction were significantly lower in sgk3 −/− than in sgk3 +/+ mice. In conclusion, both in vitro and in vivo function of BMMCs are impaired in gene targeted mice lacking SGK3. Thus SGK3 is critical for proper mast cell function.
Gas exchange kinetics in obese adolescents. Inferences on exercise tolerance and prescription
Authors: Salvadego Desy , Lazzer Stefano , Busti Carlo , Galli Raffaela , Agosti Fiorenza , Lafortuna Claudio , Sartorio Alessandro , Grassi Bruno
Published: August 2010

A functional evaluation of skeletal muscle oxidative metabolism was performed in a group of obese adolescents (OB). The various components of pulmonary O2uptake (V̇o2) kinetics were evaluated during 10-min constant-load exercises (CLE) on a cycloergometer at different percentages of V̇o2max. The relationships of these components with the gas exchange threshold (GET) were determined. Fourteen male OB [age 16.5 ± 1.0 (SD) yr, body mass index 34.5 ± 3.1 kg·m−2] and 13 normal-weight, age-matched nonathletic male volunteers (control group) were studied. The time-constant (τf) of the fundamental component and the presence, pattern, and relative amplitude of the slow component of V̇o2kinetics were determined at 40, 60, and 80% of V̇o2max, previously estimated during an incremental test. V̇o2max(l/min) was similar in the two groups. GET was lower in OB (55.7 ± 6.7% of V̇o2max) than in control (65.1 ± 5.2%) groups. The τf was higher in OB subjects, indicating a slower fundamental component. At CLE 60% (above GET in OB subjects, below GET in control subjects) a slow component was observed in nine out of fourteen OB subjects, but none in the control group. All subjects developed a slow component at CLE 80% (above GET in both OB and control). Twelve OB subjects did not complete the 10-min CLE 80% due to voluntary exhaustion. In nine OB subjects, the slow component was characterized by a linear increase in V̇o2as a function of time. The slope of this increase was inversely related to the time to exhaustion. The above findings should negatively affect exercise tolerance in obese adolescents and suggest an impairment of skeletal muscle oxidative metabolism. Also in obese adolescents, exercise evaluation and prescription at submaximal loads should be done with respect to GET and not at a given percentage of V̇o2max.
Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF
Authors: Wang Qing , Maillard Marc , Schibler Ueli , Burnier Michel , Gachon Frédéric
Published: August 2010

The cardiovascular system is under the control of the circadian clock, and disturbed circadian rhythms can induce cardiovascular pathologies. This cyclic regulation is probably brought about by the circadian expression of genes encoding enzymes and regulators involved in cardiovascular functions. We have previously shown that the rhythmic transcription of output genes is, in part, regulated by the clock-controlled PAR bZip transcription factors DBP (albumin D-site binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor). The simultaneous deletion of all three PAR bZip transcription factors leads to increased morbidity and shortened life span. In the present study, we demonstrate that Dbp/ Tef/ Hlf triple knockout mice develop cardiac hypertrophy and left ventricular dysfunction associated with a low blood pressure. These dysfunctions are exacerbated by an abnormal response to this low blood pressure characterized by low aldosterone levels. The phenotype of PAR bZip knockout mice highlights the importance of circadian regulators in the modulation of cardiovascular functions.
Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy
Authors: Masuda Shin-ichiro , Tamura Kouichi , Wakui Hiromichi , Maeda Akinobu , Dejima Toru , Hirose Tomonori , Toyoda Masao , Azuma Koichi , Ohsawa Masato , Kanaoka Tomohiko , Yanagi Mai , Yoshida Shin-ichiro , Mitsuhashi Hiroshi , Matsuda Miyuki , Ishigami Tomoaki , Toya Yoshiyuki , Suzuki Daisuke , Nagashima Yoji , Umemura Satoshi
Published: August 2010

The intrarenal renin-angiotensin system plays a crucial role in the regulation of renal circulation and sodium reabsorption through the activation of vascular, glomerular, and tubular angiotensin II type 1 (AT1) receptor signaling. We previously cloned a molecule that specifically interacted with the murine AT1receptor to inhibit AT1receptor signaling, which we named ATRAP (for AT1receptor-associated protein). Since murine ATRAP was shown to be highly expressed in the kidney, in the present study we investigated expression and distribution of human ATRAP in normal kidney and renal biopsy specimens from patients with IgA nephropathy. In the normal human kidney, both ATRAP mRNA and protein were widely and abundantly distributed along the renal tubules from Bowman's capsule to the medullary collecting ducts. In all renal tubular epithelial cells, the ATRAP protein colocalized with the AT1receptor. In renal biopsy specimens with IgA nephropathy, a significant positive correlation between ATRAP and AT1receptor gene expression was observed. There was also a positive relationship between tubulointerstitial ATRAP expression and the estimated glomerular filtration rate in patients with IgA nephropathy. Furthermore, we examined the function of the tubular AT1receptor using an immortalized cell line of mouse distal convoluted tubule cells (mDCT) and found that overexpression of ATRAP by adenoviral gene transfer suppressed the angiotensin II-mediated increases in transforming growth factor-β production in mDCT cells. These findings suggest that ATRAP might play a role in balancing the renal renin-angiotensin system synergistically with the AT1receptor by counterregulatory effects in IgA nephropathy and propose an antagonistic effect of tubular ATRAP on AT1receptor signaling.
Asymmetric superoxide release inside and outside the mitochondria in skeletal muscle under conditions of aging and disuse
Authors: Xu Xin , Chen Chiao-nan (Joyce) , Arriaga Edgar A. , Thompson LaDora V.
Published: August 2010

Superoxide released from mitochondria forms reactive oxygen species that can cause severe oxidative damage and have been associated with aging- and disuse-induced muscle dysfunction. Superoxide is released to both the exterior and the matrix of mitochondria, where oxidative damage is not necessarily the same. This complicates determining the role of mitochondrial superoxide in eliciting oxidative stress in skeletal muscle. A newly developed capillary electrophoretic method analyzes hydroxytriphenylphosphonium ethidium, a superoxide-specific product of triphenylphosphonium hydroethidine, released to outside the mitochondria (supernatant) and retained in the matrix (pellet). In this study, we investigated the mitochondrial superoxide production of soleus (type I) and semimembranosus (type II) muscles of Fischer 344 rats affected by aging (13 vs. 26 mo) and disuse (hindlimb unloading). In agreement with previous studies, overall superoxide production increased with aging and disuse. On the other hand, the new experimental method revealed that superoxide production outside the mitochondria of the soleus does not show a significant age-related increase. Another observation was that the superoxide production increase in the matrix occurs earlier (7 days of disuse) compared with the outside mitochondria (14 days of disuse) in both muscle types. These findings indicate that superoxide release is complex as it occurs asymmetrically at both sides of the mitochondrial inner membrane, and that such release has muscle type and temporal specificity. These findings are important to refine current concepts on oxidative stress associated with muscle aging and disuse.
Muscle dependency of corticomuscular coherence in upper and lower limb muscles and training-related alterations in ballet dancers and weightlifters
Authors: Ushiyama Junichi , Takahashi Yuji , Ushiba Junichi
Published: August 2010

It has been well documented that the 15- to 35-Hz oscillatory activity of the sensorimotor cortex shows coherence with the muscle activity during weak to moderate steady contraction. To investigate the muscle dependency of the corticomuscular coherence and its training-related alterations, we quantified the coherence between electroencephalogram (EEG) from the sensorimotor cortex and rectified electromyogram (EMG) from five upper limb (first dorsal interosseous, flexor carpi radialis, extensor carpi radialis, biceps brachii, triceps brachii) and four lower limb muscles (soleus, tibialis anterior, biceps femoris, rectus femoris), while maintaining a constant force level at 30% of maximal voluntary contraction of each muscle, in 24 untrained, 12 skill-trained (ballet dancers), and 10 strength-trained (weightlifters) individuals. Data from untrained subjects demonstrated the muscle dependency of corticomuscular coherence. The magnitude of the EEG-EMG coherence was significantly greater in the distally located lower limb muscles, such as the soleus and tibialis anterior, than in the upper or other lower limb muscles in untrained subjects ( P < 0.05). These results imply that oscillatory coupling between the sensorimotor cortex and spinal motoneurons during steady contraction differs among muscles, according to the functional role of each muscle. In addition, the ballet dancers and weightlifters showed smaller EEG-EMG coherences than the untrained subjects, especially in the lower limb muscles ( P < 0.05). These results indicate that oscillatory interaction between the sensorimotor cortex and spinal motoneurons can be changed by long-term specialized use of the muscles and that this neural adaptation may lead to finer control of muscle force during steady contraction.
Small-Bowel Capsule Endoscopy in Patients with Suspected Crohn's Disease—Diagnostic Value and Complications
Authors: Figueiredo Pedro , Almeida Nuno , Lopes Sandra , Duque Gabriela , Freire Paulo , Lérias Clotilde , Gouveia Hermano , Sofia Carlos
Published: August 2010

Background. The aim of this work was to assess the value of capsule enteroscopy in the diagnosis of patients with suspected Crohn's Disease (CD). Methods. This was a retrospective study in a single tertiary care centre involving patients undergoing capsule enteroscopy for suspected CD. Patients taking nonsteroidal anti inflammatory drugs during the thirty preceding days or with a follow-up period of less than six months were excluded. Results. Seventy eight patients were included. The endoscopic findings included mucosal breaks in 50%, ulcerated stenosis in 5%, and villous atrophy in 4%. The diagnosis of CD was established in 31 patients. The sensitivity, specificity, positive and negative predictive value of the endoscopic findings were 93%, 80%, 77%, and 94%, respectively. Capsule retention occurred in four patients (5%). The presence of ulcerated stenosis was significantly more frequent in patients with positive inflammatory markers. The diagnostic yield of capsule enteroscopy in patients with negative ileoscopy was 56%, with a diagnostic acuity of 93%. Conclusions. Small bowel capsule endoscopy is a safe and valid technique for assessing patients with suspected CD. Capsule retention is more frequent in patients with positive inflammatory markers. Patients with negative ileoscopy and suspected CD should be submitted to capsule enteroscopy.
Effect of Carcass Size on Feeding Modes of Larvae ofNicrophorus quadripunctatusKraatz (Coleoptera: Silphidae)
Authors: Kishida Ryu , Suzuki Nobuhiko
Published: August 2010

In the parental care of burying beetles ofNicrophorus, the role of males has not been clearly elucidated. To test our hypothesis that the investment in resource manipulation by males influences the feeding of larvae by males, we investigated parental efforts ofN. quadripunctatus. On the small carcasses, the time spent on resource manipulation by males was short, and the males left the carcasses without feeding the larvae (maternal feeding). On the large carcasses, the males spent a long time on resource manipulation, and the male participated in the feeding of larvae (biparental feeding). This suggests that one of the reproductive roles of males in the absence of predators and/or competitors is resource manipulation, and the paternal efforts change depending on carcass size. A longer time spent on resource manipulation by males may be a trigger for the males to participate in the feeding of larvae on large carcasses.
Stochastic Theories and Deterministic Differential Equations
Authors: Moxnes John F. , Hausken Kjell
Published: August 2010

We discuss the concept of “hydrodynamic” stochastic theory, which is not based on the traditional Markovian concept. A Wigner function developed for friction is used for the study of operators in quantum physics, and for the construction of a quantum equation with friction. We compare this theory with the quantum theory, the Liouville process, and the Ornstein‐Uhlenbeck process. Analytical and numerical examples are presented and compared.
Semi‐ and Nonparametric ARCH Processes
Authors: Linton Oliver B. , Yan Yang
Published: August 2010

ARCH/GARCH modelling has been successfully applied in empirical finance for many years. This paper surveys the semiparametric and nonparametric methods in univariate and multivariate ARCH/GARCH models. First, we introduce some specific semiparametric models and investigate the semiparametric and nonparametrics estimation techniques applied to: the error density, the functional form of the volatility function, the relationship between mean and variance, long memory processes, locally stationary processes, continuous time processes and multivariate models. The second part of the paper is about the general properties of such processes, including stationary conditions, ergodic conditions and mixing conditions. The last part is on the estimation methods in ARCH/GARCH processes.
Visual Acuity and Heterogeneities of Retinal Ganglion Cell Densities and the Tapetum Lucidum of the African Elephant (Loxodonta africana)
Authors: Pettigrew John D. , Bhagwandin Adhil , Haagensen Mark , Manger Paul R.
Published: August 2010

The eyes of three adult male African elephants were examined, the retinas were whole-mounted, stained and analyzed to determine visual acuity. A range of small to large ganglion cell types were observed across the retinas. We observed three regions of high ganglion cell density, one in the upper temporal quadrant, a visual or horizontal streak and a smaller region at the nasal end of the horizontal streak. The peak density of ganglion cells observed was 5,280/mm2, and our calculations indicate that the elephant has a maximal visual acuity of between 13.16 and 14.37 cycles/degree. We observed a heterogeneous structure of a tapetum lucidum, the cells of which were found to be most strongly aggregated behind the temporal and nasal densities of retinal ganglion cells. The strength of the tapetum lucidum was weaker posterior to the density of ganglion cells forming the horizontal streak. The morphology of the elephant eye appears to be such that it reflects: (1) the importance of trunk–eye co-ordination for feeding; (2) the importance of 24-hour vigilance for either predators or conspecifics, and (3) the arrhythmic nature of the daily activity of this animal, being useful both diurnally and nocturnally.
Effect of Single-Dose Rituximab on Primary Glomerular Diseases
Authors: Sugiura Hidekazu , Takei Takashi , Itabashi Mitsuyo , Tsukada Misao , Moriyama Takahito , Kojima Chiari , Shiohira Toshiharu , Shimizu Ari , Tsuruta Yuki , Amemiya Nobuyuki , Ogawa Tetsuya , Uchida Keiko , Tsuchiya Ken , Nitta Kosaku
Published: August 2010

Background: A paradigm shift from such toxic ‘nonspecific’ therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. Design: To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. Results: In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. Conclusion: For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.
Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: The blind, prospective CALTHRO study
Authors: Cosmi Benilde , Lessiani Gianfranco , Rodorigo Giuseppina , Guazzaloca Giuliana , Brusi Carlotta , Valdré Lelia , Conti Eleonora , Sartori Michelangelo , Legnani Cristina , Palareti Gualtiero
Published: August 2010

The natural history of calf deep-vein thrombosis (DVT) is still uncertain and it is debated whether it warrants to be diagnosed and treated. We aimed to investigate the complication rate of untreated isolated calf DVT (ICDVT). Symptomatic outpatients were prospectively managed with serial compression ultrasonography (SCUS). Those without proximal DVT and with likely pre-test clinical probability (PCP) or altered D-dimer received immediate subsequent complete examination of calf deep veins (CCUS) by a different operator. The result of CCUS was kept blind both to the managing doctor and the patient and disclosed after three months. Primary outcome was the rate of venous thromboembolism at three months. We examined 431 subjects (196 males; median age 68.0 years) in whom five outcomes were recorded (1.2%; 95% confidence intervals [CI]: 0.4–2.7). If CCUS results had been available, outcomes would have been recorded in 3/424 patients (0.7%; 95% CI: 0.2–2.1) with two events in subjects negative at both serial and complete CUS. ICDVT was diagnosed in 65 subjects (15.3%; 95% CI: 12–19); of whom 59 remained uneventful (one was lost to follow-up). A significant higher rate of outcomes was recorded in subjects with than without ICDVT (5/64; 7.8%; 95% CI: 3–17 vs. 3/351; 0.8%; 95% CI: 0–2; p=0.003). However, after excluding two events picked at serial CUS in subjects with ICDVT, the difference became barely significant (3/64; 4.7%; 95% CI: 1–13; p=0.049). Thrombotic evolution of untreated ICDVT in high-risk subjects may be relevant. Larger studies are needed to address this issue.
Stimulating Entrepreneurial Practices in the Public Sector
Authors: Kim Younhee
Published: August 2010

Unlike the practices of contracting out and privatization, which reduce public sector involvement and responsibility in service provision, public entrepreneurial practices may be one of the best ways to improve government performance and meet citizens’ demand efficiently and effectively. This study examines the relationships between organizational characteristics and public entrepreneurship in order to provide empirical support for entrepreneurial practices in state governments in the United States. The study found that most organizational characteristics influence the entrepreneurial behaviors defined as risk-taking, innovativeness, and proactiveness. The findings suggest that organizational structures and strategies in the public sector need to be adjusted to stimulate entrepreneurial activities and culture through opportunity-driven management.
The new world of biosimilars: what diabetologists need to know about biosimilar insulins
Authors: Krämer Irene , Sauer Thomas
Published: August 2010

Biosimilar pharmaceuticals are emerging as patent protection on the original biopharmaceutical products expires. However, biopharmaceuticals are particularly complex molecules, and biosimilar insulins present special challenges. In part this reflects their structure and chemical modification after synthesis to attain a biologically active form. Their therapeutic window is narrow and the accuracy of their dosing is highly dependent on the formulation and quality of the administration device. For these reasons, the European Medicines Agency has issued stringent guidelines that must be fulfilled in order to receive approval as a biosimilar soluble insulin. Prescribers should therefore consider issues of manufacture, protein quality, formulation, reliability of supply, and other factors that might affect efficacy, safety and tolerability when making choices regarding the selection of biosimilar products.
Use of U-500 insulin in continuous subcutaneous insulin infusion in a patient with severe insulin resistance
Authors: Sennik Devesh , Ward Helen , Naqvi Safdar
Published: August 2010

U-500 insulin (Humulin R; Eli Lilly, Indianapolis, Indiana, USA) is five times as concentrated as conventional U-100 insulins. We report the case of a woman with marked insulin resistance in whom the use of U-500 insulin in continuous subcutaneous insulin infusion (CSII) resulted in a marked improvement. Benefits included improved glycated haemoglobin A1C, decreased volume of insulin required, fewer reservoir changes, greater patient satisfaction and cost savings. We discuss the characteristics of U-500 insulin and how it can be an important option in the treatment of patients on CSII who have marked insulin resistance and a high daily insulin requirement.
SGLT2 inhibitors: glucuretic treatment for type 2 diabetes
Authors: Bailey Clifford J , Day Caroline
Published: August 2010

Sodium glucose co-transporter-2 (SGLT2) inhibitors offer a novel approach to treat diabetes by reducing hyperglycaemia via increased glucosuria. This approach reduces renal glucose reabsorption in the proximal renal tubules providing an insulin-independent mechanism to lower blood glucose. The glucuretics are advanced in clinical development and dapagliflozin has received most extensive study. Once daily dapaglifolozin as monotherapy or as add-on to metformin for 12—24 weeks in type 2 diabetic patients (baseline HbA1C 8—9%) reduced HbA1C by about 0.5—1%, accompanied by weight loss (2—3 kg) and without significant risk of hypoglycaemia. Dapagliflozin has reduced insulin requirement and improved glycaemic control without weight gain in insulin-treated patients. A mild osmotic diuresis associated with glucuretic therapy may account for a small increase in haematocrit (1—2%) and reduced blood pressure (2—5 mmHg). Dehydration and altered electrolyte balance have not been encountered. Urinary tract and genital infections increased in most studies with dapagliflozin, but were typically mild — resolving with self-medication or standard intervention. Thus glucuretics provide a novel insulin-independent approach for control of hyperglycaemia which does not incur hypoglycaemia, promotes weight loss, may reduce blood pressure and offers compatibility with other glucose-lowering agents.
Genetic manipulation of AML1-ETO–induced expansion of hematopoietic precursors in a Drosophila model
Authors: Sinenko Sergey A. , Hung Tony , Moroz Tatiana , Tran Quynh-Minh , Sidhu Sohrab , Cheney Matthew D. , Speck Nancy A. , Banerjee Utpal
Published: August 2010

Among mutations in human Runx1/AML1 transcription factors, the t(8;21)(q22;q22) genomic translocation that creates an AML1-ETO fusion protein is implicated in etiology of the acute myeloid leukemia. To identify genes and components associated with this oncogene we used Drosophila as a genetic model. Expression of AML1-ETO caused an expansion of hematopoietic precursors in Drosophila, which expressed high levels of reactive oxygen species (ROS). Mutations in functional domains of the fusion protein suppress the proliferative phenotype. In a genetic screen, we found that inactivation of EcRB1 or activation of Foxo and superoxide dismutase-2 (SOD2) suppress the AML1-ETO–induced phenotype by reducing ROS expression in the precursor cells. Our studies indicate that ROS is a signaling factor promoting maintenance of normal as well as the aberrant myeloid precursors and suggests the importance of antioxidant enzymes and their regulators as targets for further study in the context of leukemia.
Union of forces advances myeloma care
Authors: Stewart A. Keith
Published: August 2010

In this issue of Blood, Richardson et al report on a landmark treatment regimen for newly diagnosed myeloma patients that for the first time combines lenalidomide and bortezomib. This effort required a team approach comprising 2 competing pharmaceutical companies (joining forces to study this promising regimen) and multiple academic medical centers.1
RoBuST: an integrated genomics resource for the root and bulb crop families Apiaceae and Alliaceae
Authors: Bhasi Ashwini , Senalik Doug , Simon Philipp W , Kumar Brajendra , Manikandan Vinu , Philip Philge , Senapathy Periannan
Published: August 2010

Background

Root and bulb vegetables (RBV) include carrots, celeriac (root celery), parsnips (Apiaceae), onions, garlic, and leek (Alliaceae)—food crops grown globally and consumed worldwide. Few data analysis platforms are currently available where data collection, annotation and integration initiatives are focused on RBV plant groups. Scientists working on RBV include breeders, geneticists, taxonomists, plant pathologists, and plant physiologists who use genomic data for a wide range of activities including the development of molecular genetic maps, delineation of taxonomic relationships, and investigation of molecular aspects of gene expression in biochemical pathways and disease responses. With genomic data coming from such diverse areas of plant science, availability of a community resource focused on these RBV data types would be of great interest to this scientific community.

Description

The RoBuST database has been developed to initiate a platform for collecting and organizing genomic information useful for RBV researchers. The current release of RoBuST contains genomics data for 294 Alliaceae and 816 Apiaceae plant species and has the following features: (1) comprehensive sequence annotations of 3663 genes 5959 RNAs, 22,723 ESTs and 11,438 regulatory sequence elements from Apiaceae and Alliaceae plant families; (2) graphical tools for visualization and analysis of sequence data; (3) access to traits, biosynthetic pathways, genetic linkage maps and molecular taxonomy data associated with Alliaceae and Apiaceae plants; and (4) comprehensive plant splice signal repository of 659,369 splice signals collected from 6015 plant species for comparative analysis of plant splicing patterns.

Conclusions

RoBuST, available athttp://robust.genome.com, provides an integrated platform for researchers to effortlessly explore and analyze genomic data associated with root and bulb vegetables.
Physical activity interventions to improve daily walking activity in cancer survivors
Authors: Knols Ruud H , de Bruin Eling D , Shirato Kei , Uebelhart Daniel , Aaronson Neil K
Published: August 2010

Background

Cancer patients may benefit from physical exercise programs. It is unclear, however, how sustained levels of physical activity are best achieved in this population. A systematic review was performed to summarize the current evidence of the effect of physical activity interventions on daily walking activity enhancement in cancer survivors, and to review the literature for its methodological quality.

Methods

A search in Medline, PEDro and the Cochrane databases was performed for English literature citations (randomized controlled trials; 'RCTs'). In a first step, one reviewer abstracted data from the included studies on patients, physical activity interventions and outcomes. Two independent reviewers reviewed the methodological quality of these studies. Data were pooled using random-effects calculations.

Results

Our search identified 201 citations. Five RCTs that reported changes in daily step activity over time were identified, and were reviewed for methodological quality and substantive results. The median score across studies for methodological quality based on the PEDro criteria was 8. These 5 RCTs evaluated 660 participants with a mean age of 53.6 (SD 4.2) years. The mean change in daily step activity for patients with a physical exercise intervention was 526 daily steps (SD 537), with a range from -92 to 1299 daily steps. The data of three studies reporting the effect of combined physical activity and counseling on daily walking activity in breast cancer survivors were pooled, however; the I2 was 79%, indicating statistical heterogeneity between the three trials.

Conclusion

The 5 RCTs reviewed were of good methodological quality. Together they suggest that combined physical activity and counseling improves daily step activity in (breast) cancer survivors. Studies that define a step goal appear to be more effective in improving daily walking activity than studies that do not do so. However, the current results should be interpreted with caution because of the observed clinical and statistical heterogeneity. Future studies are warranted to evaluate the effects of goal targeted physical activity, with or without counseling, on daily walking in various cancer populations.
Testing the interaction between analytical modules: an example with Roundup Ready®soybean line GTS 40-3-2
Authors: Bellocchi Gianni , De Giacomo Marzia , Foti Nicoletta , Mazzara Marco , Palmaccio Eleonora , Savini Cristian , Di Domenicantonio Chiara , Onori Roberta , Van den Eede Guy
Published: August 2010

Background

The modular approach to analysis of genetically modified organisms (GMOs) relies on the independence of the modules combined (i.e. DNA extraction and GM quantification). The validity of this assumption has to be proved on the basis of specific performance criteria.

Results

An experiment was conducted using, as a reference, the validated quantitative real-time polymerase chain reaction (PCR) module for detection of glyphosate-tolerant Roundup Ready® GM soybean (RRS). Different DNA extraction modules (CTAB, Wizard and Dellaporta), were used to extract DNA from different food/feed matrices (feed, biscuit and certified reference material [CRM 1%]) containing the target of the real-time PCR module used for validation. Purity and structural integrity (absence of inhibition) were used as basic criteria that a DNA extraction module must satisfy in order to provide suitable template DNA for quantitative real-time (RT) PCR-based GMO analysis. When performance criteria were applied (removal of non-compliant DNA extracts), the independence of GMO quantification from the extraction method and matrix was statistically proved, except in the case of Wizard applied to biscuit. A fuzzy logic-based procedure also confirmed the relatively poor performance of the Wizard/biscuit combination.

Conclusions

For RRS, this study recognises that modularity can be generally accepted, with the limitation of avoiding combining highly processed material (i.e. biscuit) with a magnetic-beads system (i.e. Wizard).
What would PCR assessment change in the management of fevers in a malaria endemic area? A school-based study in Benin in children with and without fever
Authors: Faucher Jean-François , Aubouy Agnès , Béhéton Todoégnon , Makoutode Patrick , Abiou Grace , Doritchamou Justin , Houzé Pascal , Ouendo Edgard , Deloron Philippe , Cot Michel
Published: August 2010

Background

A recent school-based study in Benin showed that applying a policy of anti-malarial prescriptions restricted to parasitologically-confirmed cases on the management of fever is safe and feasible. Additional PCR data were analysed in order to touch patho-physiological issues, such as the usefulness of PCR in the management of malaria in an endemic area or the triggering of a malaria attack in children with submicroscopic malaria.

Methods

PCR data were prospectively collected in the setting of an exposed (with fever)/non exposed (without fever) study design. All children had a negative malaria rapid diagnostic test (RDT) at baseline, were followed up to day 14 and did not receive drugs with anti-malarial activity. The index group was defined by children with fever at baseline and the control group by children without fever at baseline. Children with submicroscopic malaria in these two groups were defined by a positive PCR at baseline.

Results

PCR was positive in 66 (27%) children of the index group and in 104 (44%) children of the control group respectively. The only significant factor positively related to PCR positivity at baseline was the clinical status (control group). When definition of malaria attacks included PCR results, no difference of malaria incidence was observed between the index and control groups, neither in the whole cohort, nor in children with submicroscopic malaria. The rate of undiagnosed malaria at baseline was estimated to 3.7% at baseline in the index group.

Conclusions

Treating all children with fever and a positive PCR would have led to a significant increase of anti-malarial consumption, with few benefits in terms of clinical events. Non malarial fevers do not or do not frequently trigger malaria attacks in children with submicroscopic malaria.