bluuebunny/crossref_metadata_2025 huggingface dataset:
Foam fractionation of α‐lactalbumin and β‐lactoglobulin from a whey solution
Authors: Shea A. P. , Crofcheck C. L. , Payne F. A. , Xiong Y. L.
Published: March 2009

Whey, a byproduct of cheese production, is often considered a waste stream. Separation and purification of whey proteins is a difficult and expensive task. Occasionally, it is transported out of the dairy plant for a per volume charge. One possible method to reduce the waste volume and disposal cost is to concentrate whey by foam fractionation and potentially produce a valuable coproduct, a concentrated whey protein solution. Foam fractionation is an adsorptive bubble separation method based on the hydrophobic/hydrophilic properties of proteins. In this study, foam fractionation was evaluated for the concentration of whey proteins, specifically α‐lactalbumin and β‐lactoglobulin, from a dilute whey protein solution. The effects of initial whey protein concentration (0.075 and 0.15 mg/ml), pH (3.8–5.5), superficial gas velocity (0.85 and 0.95 cm/s) and temperature (4 and 65 °C) on protein enrichment and recovery were examined. Higher enrichment was achieved with the lower initial protein concentration (0.075 mg/ml), and at pH values that were near the isoelectric points (pI) of α‐lactalbumin and β‐lactoglobulin (pH 3.8, 4.2, 4.5, and 5.2). Higher superficial gas velocity enhanced the amount of proteins recovered with a decrease in the enrichment. Cold temperature treatment and partial heat denaturation of whey proteins reduced enrichment and increased protein recovery simultaneously. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.
Enhancement of oil droplet removal from o/w emulsion by adding methylated milk casein in flotation technique
Authors: Maruyama Hideo , Tada Yuhsuke , Seki Hideshi
Published: March 2009

To clarify oil‐in‐water (o/w) emulsion, flotation experiments were conducted by adding methylated milk casein (MeCS), which is a biodegradable flocculant. Emulsion used in this study was prepared by ultrasonic emulsification of heavy oil (bunker‐A) and sodium dodecyl sulfate (SDS) solution. It was found that addition of MeCS enhanced clarification of oil droplets from o/w emulsion solution due to floc formation by adding MeCS. An optimum dosage of MeCS to form effective floc was determined by the relative turbidity in a clarification experiment. In flotation experiments, clarification ability was evaluated by removal rate constant, k, obtained by fitting of turbidity data to a pseudo‐first‐order kinetic equation. In case of varying dosage of MeCS and keeping superficial gas velocity, Ug, at constant value (5.48 × 10−2 cm/s), removal rate was greatly influenced by amount of MeCS dosage. The maximum value of k was also obtained at the most optimum dosage of MeCS, and k decreased with adding lesser or larger amount of MeCS than the optimum dosage. On the other hand, in case of keeping the dosage of MeCS at the optimum dosage, and varying superficial gas velocity, up to Ug < ca. 0.2 cm/s, k was increased with increasing superficial gas velocity, and increase in removal rate of oil droplets was mostly proportional with increase in bubble surface area production rate. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.
Removal of Basic Blue 3 by sorption onto a weak acid acrylic resin
Authors: Bârsănescu Adriana , Buhăceanu Rodica , Dulman Viorica
Published: March 2009

A weak acid acrylic resin was used as an adsorbent for the investigation of Basic Blue 3 (BB3) adsorption kinetics, isotherms, and thermodynamic parameters. Batch adsorption studies were carried out to evaluate the effect of pH, contact time, initial concentration (28–100 mg/g), adsorbent dose (0.05–0.3 g), and temperature (290–323 K) on the removal of BB3. The adsorption equilibrium data were analyzed by the Langmuir, Temkin, and Freundlich isotherm models, with the best fitting being the first one. The adsorption capacity (Qo) increased with increasing initial dye concentration, adsorbent dose, and temperature; the highest maximum Qo (59.53 mg/g) was obtained at 323 K. Pseudo‐first‐order and pseudo‐second‐order kinetic models and intraparticle diffusion models were used to analyze the kinetic data; good agreement between the experimental and calculated amounts of dye adsorbed at equilibrium were obtained for the pseudo‐second‐order kinetic models for the entire investigated concentrations domain. Various thermodynamic parameters, such as standard enthalpy of adsorption (ΔHo = 88.817 kJ/mol), standard entropy of adsorption (ΔSo = 0.307 kJ mol−1 K−1), and Gibbs free energy (ΔGo < 0, for all temperatures investigated), were evaluated and revealed that the adsorption process was endothermic and favorable. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Adsorption of anionic textile dye Acid Green 9 from aqueous solution onto weak or strong base anion exchangers
Authors: Dulman Viorica , Simion Catinca , Bârsănescu Adriana , Bunia Ion , Neagu Violeta
Published: March 2009

The aim of this work is to study the thermodynamic and kinetic studies with regard to the adsorption of Acid Green 9 (AG9) on the most efficient resin, namely, acrylic weak base anion exchange resin with ethylenediamine‐functional groups (A1) selected from several anion exchange resins. The influence of the various experimental parameters such as, pH, initial dye concentration, contact time, temperature, and adsorbent dose was investigated by batch experiments. The extent of the dye adsorption increased with the decrease of the initial dye concentration and the increase of the contact time, temperature, and amount of the adsorbent. Adsorption process was quantitative and very fast at low concentrations of the dye. To investigate the mechanism of the adsorption and potential rate‐controlling steps, pseudo first‐ and second‐order, as well as intraparticle diffusion kinetic equations have been used. The adsorption kinetic of AG9 dye from aqueous solution onto A1 could be described by the pseudo second‐order reaction model. The obtained results are in agreement with the Langmuir and Freundlich models. In the optimum conditions established, an adsorption capacity of 500 mg textile dye (72% purity) g−1 adsorbent (at 293 K) was reached. Desorption experiments by batch and dynamic methods were performed using a solution of 0.05 mol L−1 NaOH. A series of 13 adsorption–desorption cycles were carried out by the dynamic method with a quantitative adsorption and the desorption efficiency higher than 95%. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Normal Right Ventricular Three‐Dimensional Architecture, as Assessed with Diffusion Tensor Magnetic Resonance Imaging, is Preserved During Experimentally Induced Right Ventricular Hypertrophy
Authors: Nielsen Eva , Smerup Morten , Agger Peter , Frandsen Jesper , Ringgard Steffen , Pedersen Michael , Vestergaard Peter , Nyengaard Jens R. , Andersen Johnnie B. , Lunkenheimer Paul P. , Anderson Robert H. , Hjortdal Vibeke
Published: March 2009

The three‐dimensional architecture of the right ventricular myocardium is a major determinant of function, but as yet no investigator‐independent methods have been used to characterize either the normal or hypertrophied state. We aimed to assess and compare, using diffusion tensor magnetic resonance imaging, the normal architecture with the arrangement induced by chronic hypertrophy. We randomized 20 female 5 kg piglets into pulmonary trunk banding (N = 16) and sham operation (N = 4). Right ventricular hypertrophy was assessed after 8 weeks. The excised and fixed hearts were subject to diffusion tensor imaging to determine myocyte helical angles, and the presence of any reproducible tracks formed by the aggregated myocytes. All banding animals developed significant right ventricular hypertrophy, albeit that no difference was observed in terms of helical angles or myocardial pathways between the banded animals and sham group animals. Helical angles varied from ∼70 degrees endocardially to −50 degrees epicardially. Very few tracks were circular, with helical angles approximating zero. Reproducible patterns of chains of aggregated myocytes were observed in all hearts, regardless of group. The architecture of the myocytes aggregated in the walls of the right ventricle is comparable to that found in the left ventricle in terms of endocardial and epicardial helical angles, however the right ventricle both in the normal and the hypertrophied state lacks the extensive zone of circular myocytes seen in the mid‐portion of the left ventricular walls. Without such beneficial architectural remodelling, the porcine right ventricle seems unsuited structurally to sustain a permanent increase in afterload. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.
Angioarchitecture of the venous and capillary system in heart defects induced by retinoic acid in mice
Authors: Ratajska Anna , Ciszek Bogdan , Zajączkowska Agnieszka , Jabłońska Anna , Juszyński Michał
Published: March 2009

BACKGROUND: Corrosion casting and immunohistochemical staining with anti‐alpha smooth muscle actin and anti‐CD34 was utilized to demonstrate the capillary plexus and venous system in control and malformed mouse hearts. METHODS: Outflow tract malformations (e.g., double outlet right ventricle, transposition of the great arteries, and common truncus arteriosus) were induced in progeny of pregnant mice by retinoic acid administration at day 8.5 of pregnancy. RESULTS: Although control hearts exhibited areas in which capillaries tended to be oriented in parallel arrays, the orientation of capillaries in the respective areas of malformed hearts was chaotic and disorganized. The major branch of a conal vein in control hearts runs usually from the left side of the conus to its right side at the root of the pulmonary trunk and opens to the right atrium below the right auricle; thus, it has a curved course. On the other hand, a conal vein in malformed hearts courses from the left side or from the anterior side of the conus and tends to traverse straight upwards along the dextroposed aorta or along the aortopulmonary groove with its proximal part located outside of the heart. Other cardiac veins in outflow tract malformations are positioned in the same locations as in control hearts. CONCLUSIONS: We postulate that the changed location of the conal vein and disorganized capillary plexus result from malformed morphogenesis of the outflow tract and/or a disturbed regulation of angiogenic growth factor release from the adjacent environment. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.
Developmental and reproductive toxicity studies on artemisone
Authors: Schmuck G. , Klaus A.‐M. , Krötlinger F. , Langewische F.W.
Published: March 2009

BACKGROUND: In order to justify clinical studies in women of child‐bearing age with artemisone, a new artimisinin derivative, studies to assess fertility and early embryonic development in rats, developmental toxicity in rats and rabbits, and peri‐post natal development in rats were performed. METHODS AND RESULTS: In the study on fertility and early embryonic development (dose levels 0‐5‐20‐80 mg/kg bw/day), doses inducing clinical and organ toxicity were used. Only in severe toxicity conditions, a reduction of the number of estruses, a prolonged time to insemination, decreased numbers of corpora lutea, implantation sites, and viable fetuses were found. Two developmental toxicity studies were performed in rats (dose levels 0‐1‐2 mg/kg bw/day) and rabbits (dose levels 0‐2.5‐5.0‐7.5 mg/kg bw/day). It was shown that rats were about 5 times more sensitive than rabbits. In rats, artemisone induced total litter loss (late resorptions) at 2 mg/kg body weight and above with an increased incidence of a common vascular variation and retarded ossification at this dose. In rabbits, maternal toxicity, abortion and a slightly increased incidence of cardiac ventricular septal defects was observed at 7.5 mg/kg body weight. In a pre‐ and postnatal developmental toxicity study in rats (dose levels 0‐1‐2‐4 mg/kg bw/day), 4 mg/kg body weight artemisone induced clinical symptoms and affected postnatal survival, body weight gain in the F1 pups, and motor activity. CONCLUSIONS: In summary, artemisone was shown to be embryo‐ and fetotoxic and induced cardiac ventricular septal defects and retarded ossification in dosages where total litter loss and abortions were observed. However, no effect on reproductive and developmental parameters below severe toxic dosages could be observed. Birth Defects Res (Part B)86: 131‐143, 2009. © 2009 Wiley‐Liss, Inc.
Recent developments in testicular germ cell tumor research
Authors: van de Geijn Gert‐Jan M. , Hersmus Remko , Looijenga Leendert H. J.
Published: March 2009

Testicular germ cell tumors of adolescents and adults (TGCTs; the so‐called type II variant) are the most frequent malignancies found in Caucasian males between 20 and 40 years of age. The incidence has increased over the last decades. TGCTs are divided into seminomas and nonseminomas, the latter consisting of the subgroups embryonal carcinoma, yolk‐sac tumor, teratoma, and choriocarcinoma. The pathogenesis starts in utero, involving primordial germ cells/gonocytes that are blocked in their differentiation, and develops via the precursor lesion carcinoma in situ toward invasiveness. TGCTs are totipotent and can be considered as stem cell tumors. The developmental capacity of their cell of origin, the primordial germ cells/gonocyte, is demonstrated by the different tumor histologies of the invasive TGCTs. Seminoma represents the germ cell lineage, and embryonal carcinoma is the undifferentiated component, being the stem cell population of the nonseminomas. Somatic differentiation is seen in the teratomas (all lineages), whereas yolk‐sac tumors and choriocarcinoma represent extra‐embryonal differentiation. Seminomas are highly sensitive to irradiation and (DNA damaging) chemotherapy, whereas most nonseminomatous elements are less susceptible to radiation, although still sensitive to chemotherapy, with the exception of teratoma. To allow early diagnosis and follow up, appropriate markers are mandatory to discriminate between the different subgroups. In this review, a summary will be given related to several recent developments in TGCT research, especially selected because of their putative clinical impact. Birth Defects Research (Part C) 87:96–113, 2009. © 2009 Wiley‐Liss, Inc.
Gonocytes, the forgotten cells of the germ cell lineage
Authors: Culty Martine
Published: March 2009

Male germ cells, the repository cells of the genome, comprise several successive developmental stages starting in the embryo and ending up with the spermatozoon. Gonocytes represent the fetal and neonatal stages preceding the formation of spermatogonial stem cells. Recent findings shows that germline stem cells can be driven to pluripotency and used as alternative for embryonic stem cells prompted more effort in identifying the processes regulating the development of their precursors, the testicular gonocytes. Also called pre‐ or pro‐spermatogonia, gonocytes represent not one, but several successive developmental stages between the time at which the germ cell becomes resident in the forming fetal testis to the time it migrates to the basement membrane of the seminiferous cord to adopt a spermatogonial phenotype. This review summarizes the findings regarding the genetic identity of gonocytes, providing a description of the “common” gene expression profiles of fetal and neonatal gonocytes, as well as information on the main regulatory factors of gonocyte functions. A better comprehension of gonocyte development should help in the understanding of how germline stem cells are formed, possibly providing valuable clues on the origins of germ cell tumors or infertility. Birth Defects Research (Part C) 87:1–26, 2009. © 2009 Wiley‐Liss, Inc.
Gonadoblastoma locus and the TSPY gene on the human Y chromosome
Authors: Lau Yun‐Fai Chris , Li Yunmin , Kido Tatsuo
Published: March 2009

The gonadoblastoma (GBY) locus is the only oncogenic locus on the human Y chromosome. It is postulated to serve a normal function in the testis, but could exert oncogenic effects in dysgenetic gonads of individuals with intersex and/or dysfunctional testicular phenotypes. Recent studies establish the testis‐specific protein Y‐encoded (TSPY) gene to be the putative gene for GBY. TSPY serves normal functions in male stem germ cell proliferation and differentiation, but is ectopically expressed in early and late stages of gonadoblastomas, testicular carcinoma in situ (the premalignant precursor for all testicular germ cell tumors), seminomas, and selected nonseminomas. Aberrant TSPY expression stimulates protein synthetic activities, accelerates cell proliferation, and promotes tumorigenicity in athymic mice. TSPY binds to type B cyclins, enhances an activated cyclin B‐CDK1 kinase activity, and propels a rapid G2/M transition in the cell cycle. TSPY also counteracts the normal functions of its X‐homologue, TSPX, which also binds to cyclin B and modulates the cyclin B‐CDK1 activity to insure a proper G2/M transition in the cell cycle. Hence, ectopic expression and actions of the Y‐located TSPY gene in incompatible germ cells, such as those in dysgenetic or ovarian environments and dysfunctional testis, disrupt the normal cell cycle regulation and predispose the host cells to tumorigenesis. The contrasting properties of TSPY and TSPX suggest that somatic cancers, such as intracranial germ cell tumors, melanoma, and hepatocellular carcinoma, with detectable TSPY expression could exhibit sexual dimorphisms in the initiation and/or progression of the respective oncogenesis. Birth Defects Research (Part C) 87:114–122, 2009. © 2009 Wiley‐Liss, Inc.
Immune physiology and oogenesis in fetal and adult humans, ovarian infertility, and totipotency of adult ovarian stem cells
Authors: Bukovsky Antonin , Caudle Michael R. , Virant‐Klun Irma , Gupta Satish K. , Dominguez Roberto , Svetlikova Marta , Xu Fei
Published: March 2009

It is still widely believed that while oocytes in invertebrates and lower vertebrates are periodically renewed throughout life, oocytes in humans and higher vertebrates are formed only during the fetal/perinatal period. However, this dogma is questioned, and clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal from ovarian stem cells (OSCs) in adult human ovaries, and of the role of third‐party bone marrow‐derived cells (monocyte‐derived tissue macrophages and T lymphocytes) could help provide a better understanding of the causes of ovarian infertility, its prevention, and potential treatment. We have reported differentiation of distinct cell types from OSC and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. OSCs are also capable of producing neural/neuronal cells in vitro after sequential stimulation with sex steroid combinations. Hence, OSC represent a unique type of totipotent adult stem cells, which could be utilized for autologous treatment of premature ovarian failure and also for autologous stem cell therapy of neurodegenerative diseases without use of allogeneic embryonic stem cells or somatic cell nuclear transfer. The in vivo application of sex steroid combinations may augment the proliferation of existing neural stem cells and their differentiation into mature neuronal cells (systemic regenerative therapy). Such treatment may also stimulate the transdifferentiation of autologous neural stem cell precursors into neural stem cells useful for topical or systemic regenerative treatment. Birth Defects Research (Part C) 87:64–89, 2009. © 2009 Wiley‐Liss, Inc.
Genomic landscape of developing male germ cells
Authors: Lee Tin‐Lap , Pang Alan Lap‐Yin , Rennert Owen M. , Chan Wai‐Yee
Published: March 2009

Spermatogenesis is a highly orchestrated developmental process by which spermatogonia develop into mature spermatozoa. This process involves many testis‐ or male germ cell‐specific gene products whose expressions are strictly regulated. In the past decade the advent of high‐throughput gene expression analytical techniques has made functional genomic studies of this process, particularly in model animals such as mice and rats, feasible and practical. These studies have just begun to reveal the complexity of the genomic landscape of the developing male germ cells. Over 50% of the mouse and rat genome are expressed during testicular development. Among transcripts present in germ cells, 40% ‐ 60% are uncharacterized. A number of genes, and consequently their associated biological pathways, are differentially expressed at different stages of spermatogenesis. Developing male germ cells present a rich repertoire of genetic processes. Tissue‐specific as well as spermatogenesis stage‐specific alternative splicing of genes exemplifies the complexity of genome expression. In addition to this layer of control, discoveries of abundant presence of antisense transcripts, expressed psuedogenes, non‐coding RNAs (ncRNA) including long ncRNAs, microRNAs (miRNAs) and Piwi‐interacting RNAs (piRNAs), and retrogenes all point to the presence of multiple layers of expression and functional regulation in male germ cells. It is anticipated that application of systems biology approaches will further our understanding of the regulatory mechanism of spermatogenesis. Birth Defects Research (Part C) 87:43–63, 2009. Published by Wiley‐Liss, Inc.
Variations in the MRI appearance of the insertion of the tendon of subscapularis
Authors: Cash C.J.C. , MacDonald K.J. , Dixon A.K. , Bearcroft P.W.P. , Constant C.R.
Published: March 2009

Standard anatomical textbooks describe the insertion of the subscapularis tendon on to the lesser tuberosity of the humerus. The transverse humeral ligament is also described at this level, as a band of tissue attached to the greater and lesser tuberosities, overlying the long tendon of biceps as it emerges from the capsule of the shoulder joint. The shoulder is a notorious site for anatomical variation but until recently little has been published with regard to the tendon of subscapularis. In this study, we illustrate that considerable variation in the insertion site of the tendon of subscapularis can be demonstrated using magnetic resonance imaging and that only 20% conform to the classic textbook description. In addition, a distinct transverse humeral ligament was identifiable in only a minority of shoulders examined (36%). Clin. Anat. 22:489–494, 2009. © 2009 Wiley‐Liss, Inc.
Centrioles to basal bodies in the spermiogenesis of Mastotermes darwiniensis (Insecta, Isoptera)
Authors: Riparbelli Maria Giovanna , Callaini Giuliano , Mercati David , Hertel Horst , Dallai Romano
Published: March 2009

In addition to their role in centrosome organization, the centrioles have another distinct function as basal bodies for the formation of cilia and flagella. Centriole duplication has been reported to require two alternate assembly pathways: template or de novo. Since spermiogenesis in the termite Mastotermes darwiniensis lead to the formation of multiflagellate sperm, this process represents a useful model system in which to follow basal body formation and flagella assembly. We present evidence of a possible de novo pathway for basal body formation in the differentiating germ cell. This cell also contains typical centrosomal proteins, such as centrosomin, pericentrin‐like protein, γ‐tubulin, that undergo redistribution as spermatid differentiation proceeds. The spermatid centrioles are long structures formed by nine doublet rather than triplet microtubules provided with short projections extending towards the surrounding cytoplasm and with links between doublets. The sperm basal bodies are aligned in parallel beneath the nucleus. They consist of long regions close to the nucleus showing nine doublets in a cartwheel array devoid of any projections; on the contrary, the short region close to the plasma membrane, where the sperm flagella emerge, is characterized by projections similar to those observed in the centrioles linking the basal body to the plasma membrane. It is hypothesized that this appearance is in connection with the centriole elongation and further with the flagellar axonemal organization. Microtubule doublets of sperm flagellar axonemes are provided with outer dynein arms, while inner arms are rarely visible. Cell Motil. Cytoskeleton 2009. © 2009 Wiley‐Liss, Inc.
A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer
Authors: Amato Robert J. , Jac Jaroslaw , Giessinger Sarah , Saxena Somyata , Willis James P.
Published: March 2009

BACKGROUND:

Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, affects tumor growth by blocking growth factor stimulation, arresting cell cycle progression, and inhibiting angiogenesis. mTOR inhibitors and agents with primarily antiangiogenic activity have been shown to have efficacy in renal cell cancer (RCC). This phase 2 study assessed the efficacy of daily oral dosing with everolimus in patients with RCC.

METHODS:

Patients had confirmed predominantly clear cell RCC; had received ≤1 prior therapy; and had progressive, measurable metastatic disease. Everolimus was given at a dose of 10 mg daily orally without interruption (28‐day cycle), with dose modifications for toxicity (graded according to National Cancer Institute Common Toxicity Criteria, version 3.0). Patients were evaluated every 2 cycles (8 weeks) using Response Evaluation Criteria in Solid Tumors (RECIST).

RESULTS:

Of 41 enrolled patients, 39 were treated and evaluable for safety, 37 of whom were evaluable for response (2 patients withdrew after the first week of therapy). Approximately 78% of the patients were male, the median age was 60 years, 93% had a Zubrod performance status of 0 to 1, and 83% had received prior therapy. The median progression‐free survival (PFS) was 11.2 months and the median overall survival was 22.1 months. Partial responses were observed in 5 (14%) patients, stable disease lasting ≥3 months was reported in 27 (73%) patients, and stable disease lasting ≥6 months was reported in 21 (57%) patients. Nausea (38% of patients), anorexia (38% of patients), diarrhea (31% of patients), stomatitis (31% of patients), pneumonitis (31% of patients), and rash (26% of patients) were common. Grade 3 of 4 adverse events included pneumonitis (18% of patients); transaminase elevations (10% of patients); thrombocytopenia, hyperglycemia, and alkaline phosphatase elevations (8% each of patients); and hyperlipidemia (5% of patients).

CONCLUSIONS:

In the current study, everolimus demonstrated encouraging antitumor activity against metastatic RCC as indicated by a PFS ≥ 6 months for approximately 70% of patients. Cancer 2009. © 2009 American Cancer Society.
Intravenous administration of human umbilical cord blood cells in an animal model of MPS III B
Authors: Garbuzova‐Davis Svitlana , Klasko Stephen K. , Sanberg Paul R.
Published: March 2009

Sanfilippo syndrome type B (MPS III B) is caused by a deficiency of α‐N‐acetylglucosaminidase enzyme (Naglu), leading to accumulation of heparan sulfate (HS), a glycosaminoglycan (GAG), within lysosomes and to eventual progressive cerebral and systemic multiple organ abnormalities. Treatment of MPS patients is mainly supportive and enzyme replacement cell therapy shows promise for treating this disease. One new approach for potential treatment of MPS III B is human umbilical cord blood (hUCB) cell transplantation. Recently, we demonstrated that administration of hUCB cells into the cerebral ventricle of presymptomatic Naglu mice had a beneficial effect, probably due to enzyme delivery into the enzyme‐deficient mutant mice. However, administration of these cells into the systemic circulation of mutant mice could be more advantageous and may lead to new strategies of enzyme replacement for Sanfilippo. The aim of this study was to determine the effect of intravenous administration of hUCB cells into a mouse model of Sanfilippo Syndrome type B. The major findings in our study were that hUCB cell administration improved behavioral outcomes (decreased hyper/stereotypical activity and improved cognitive function). Cells widely distribute within and outside the CNS and intraparenchymally migrate. Administered cells have an antiinflammatory effect (Th2‐associated cytokines) in the brain and reduce heparan sulfate accumulation in the liver and spleen. Our results demonstrate the advantages of intravenously administering hUCB cells into a mouse model of Sanfilippo Syndrome type B, the advantages probably a result of Naglu delivery to enzyme‐deficient organs. J. Comp. Neurol. 515:93–101, 2009. © 2009 Wiley‐Liss, Inc.
The dynamics of long‐term transgene expression in engrafted neural stem cells
Authors: Lee Jean‐Pyo , Tsai David J. , In Park Kook , Harvey Alan R. , Snyder Evan Y.
Published: March 2009

To assess the dynamics and confounding variables that influence transgene expression in neural stem cells (NSCs), we generated distinct NSC clones from the same pool of cells, carrying the same reporter gene transcribed from the same promoter, transduced by the same retroviral vector, and transplanted similarly at the same differentiation state, at the same time and location, into the brains of newborn mouse littermates, and monitored in parallel for over a year in vivo (without immunosuppression). Therefore, the sole variables were transgene chromosomal insertion site and copy number. We then adapted and optimized a technique that tests, at the single cell level, persistence of stem cell‐mediated transgene expression in vivo based on correlating the presence of the transgene in a given NSC's nucleus (by fluorescence in situ hybridization [FISH]) with the frequency of that transgene's product within the same cell (by combined immunohistochemistry [IHC]). Under the above‐stated conditions, insertion site is likely the most contributory variable dictating transgene downregulation in an NSC after 3 months in vivo. We also observed that this obstacle could be effectively and safely counteracted by simple serial infections (as few as three) inserting redundant copies of the transgene into the prospective donor NSC. (The preservation of normal growth control mechanisms and an absence of tumorigenic potential can be readily screened and ensured ex vivo prior to transplantation.) The combined FISH/IHC strategy employed here for monitoring the dynamics of transgene expression at the single cell level in vivo may be used for other types of therapeutic and housekeeping genes in endogenous and exogenous stem cells of many organs and lineages. J. Comp. Neurol. 515:83–92, 2009. © 2009 Wiley‐Liss, Inc.
Beneficial effects of antioxidant‐enriched diet for tyrosine hydroxylase‐positive neurons in ventral mesencephalic tissue in oculo grafts
Authors: Berglöf Elisabet , Small Brent J. , Bickford Paula C. , Strömberg Ingrid
Published: March 2009

Supplementation of antioxidants to the diet has been proved to be beneficial in aging and after brain injury. Furthermore, it has been postulated that the locus coeruleus promotes survival of dopamine neurons. Thus, this study was performed to elucidate the effects of a blueberry‐enriched diet on fetal ventral mesencephalic tissue in the presence or absence of locus coeruleus utilizing the in oculo grafting method. Sprague‐Dawley rats were given control diet or diet supplemented with 2% blueberries, and solid tissue pieces of fetal locus coeruleus and ventral mesencephalon were implanted as single and co‐grafts. The results revealed that the presence of locus coeruleus tissue or the addition of blueberries enhanced the survival of ventral mesencephalic tyrosine hydroxylase (TH)‐positive neurons, whereas no additive effects were observed for the two treatments. The density of TH‐positive nerve fibers in ventral mesencephalic tissue was significantly elevated when it was attached to the locus coeruleus or by blueberry treatment, whereas the innervation of dopamine‐β‐hydroxylase‐positive nerve fibers was not altered. The presence of locus coeruleus tissue or bluberry supplementation reduced the number of Iba‐1‐positive microglia in the ventral mesencephalic portion of single and co‐grafts, respectively, whereas almost no OX6 immunoreactivity was found. Furthermore, neither the attachment of ventral mesencephalic tissue nor the addition of blueberries improved the survival of TH‐positive neurons in the locus coerulean grafts. To conclude, locus coeruleus and blueberries are beneficial for the survival of fetal ventral mesencephalic tissue, findings that could be useful when grafting tissue in Parkinson's disease. J. Comp. Neurol. 515:72–82, 2009. © 2009 Wiley‐Liss, Inc.
Mesencephalic astrocyte‐derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats
Authors: Airavaara Mikko , Shen Hui , Kuo Chi‐Chung , Peränen Johan , Saarma Mart , Hoffer Barry , Wang Yun
Published: March 2009

Mesencephalic astrocyte‐derived neurotrophic factor (MANF), also known as arginine‐rich, mutated in early stage of tumors (ARMET), is a secreted protein that reduces endoplasmic reticulum (ER) stress. Previous studies have shown that MANF mRNA expression and protein levels are increased in the cerebral cortex after brain ischemia, a condition that induces ER stress. The function of MANF during brain ischemia is still not known. The purpose of this study was to examine the protective effect of MANF after ischemic brain injury. Recombinant human MANF was administrated locally to the cerebral cortex before a 60‐min middle cerebral artery occlusion (MCAo) in adult rats. Triphenyltetrazolium chloride (TTC) staining indicated that pretreatment with MANF significantly reduced the volume of infarction at 2 days after MCAo. MANF also attenuated TUNEL labeling, a marker of cell necrosis/apoptosis, in the ischemic cortex. Animals receiving MANF pretreatment demonstrated a decrease in body asymmetry and neurological score as well as an increase in locomotor activity after MCAo. Taken together, these data suggest that MANF has neuroprotective effects against cerebral ischemia, possibly through the inhibition of cell necrosis/apoptosis in cerebral cortex. J. Comp. Neurol. 515:116–124, 2009. Published 2009 Wiley‐Liss, Inc.
Differential expression and regulation of olig genes in zebrafish
Authors: Tiso Natascia , Filippi Alida , Benato Francesca , Negrisolo Enrico , Modena Nicola , Vaccari Enrico , Driever Wolfgang , Argenton Francesco
Published: March 2009

The members of the Olig gene family encode for basic helix‐loop‐helix (bHLH) transcription factors involved in neural cell type specification. Three Olig genes (Olig1, Olig2 and Olig3) have been identified in all known vertebrate models and a fourth one in anamniotes (olig4). Here we have performed a global analysis of olig genes during zebrafish embryonic development and determined which signaling pathways control their induction and regionalization in the CNS. Interestingly, zebrafish olig3 and olig4 together establish most of the expression domains corresponding to mouse Olig3. According to our data, olig1 is specifically confined to the oligodendrocyte lineage, whereas the other members display stratified expression in diencephalon, hindbrain, and spinal cord. We observed differential expression of olig genes within specific motoneuron and interneuron domains of the spinal cord. olig2, olig3, and olig4 expression appears to be regulated by nodal and FGF signaling during gastrulation and early somitogenesis, by RA signaling in the hindbrain, and by BMP and Hh signals along the dorsoventral axis of the embryonic CNS. Our findings suggest a role for olig genes in CNS patterning as well as in multiple cell fate decisions during neural differentiation. J. Comp. Neurol. 515:378–396, 2009. © 2009 Wiley‐Liss, Inc.
Intrinsic connections of the macaque monkey hippocampal formation: II. CA3 connections
Authors: Kondo Hideki , Lavenex Pierre , Amaral David G.
Published: March 2009

We examined the topographic organization of the connections of the CA3 field of the macaque monkey hippocampus. Discrete anterograde and retrograde tracer injections were made at various positions within CA3 and CA1. The projections from CA3 to CA1 (Schaffer collaterals), which terminate in the strata radiatum, pyramidale, and oriens, are present throughout the entire transverse extent of CA1. Projections extend both rostrally and caudally from the injection site for as much as three‐fourths of the longitudinal extent of the hippocampus. The associational projections from CA3 to CA3 also travel extensively along the longitudinal axis. CA3 gives rise to more substantial projections to CA1 than to CA3. CA3 projections that originate at the level of the uncus tend to be more restricted to the rostral portions of CA1 and CA3. As in the rodent brain, projections from CA3 to CA1 are distributed along a radial gradient, depending on the transverse location of the cells of origin. CA3 cells located near the dentate gyrus generate projections that more densely terminate superficially in the terminal zone of CA1, whereas CA3 cells located closer to CA1 give rise to projections that more heavily terminate deeply in the terminal zone of CA1. The present results indicate that in the monkey, as in the rat, CA3 cells give rise to extensive projections to CA1 and CA3. Interestingly, radial, transverse, and longitudinal gradients of CA3 fiber distribution, so clear in the rat, are much more subtle in the nonhuman primate brain. J. Comp. Neurol. 515:349–377, 2009. © 2009 Wiley‐Liss, Inc.
Immunohistochemical localization of calbindin‐D28k and calretinin in the brainstem of anuran and urodele amphibians
Authors: Morona Ruth , González Agustin
Published: March 2009

Calbindin‐D28k (CB) and calretinin (CR) are calcium binding proteins present in distinct sets of neurons; they act as buffers regulating the concentration of intracellular calcium. CB and CR immunohistochemistry was studied in the brainstem of anuran and urodele amphibians in combination with other markers (choline acetyltransferase, tyrosine hydroxylase, and nitric oxide synthase), which served to clarify the localization and signature of many cell groups. CR labeled the retinorecipient layers of the optic tectum, and CB and CR labeled distinct tectal cell populations. The two proteins were largely complementary in the torus semicircularis and marked auditory and lateral line sensory regions, depending on the species. CB and CR in the mesencephalic and isthmic tegmentum specified the boundaries of basal and medial longitudinal bands. In the cerebellum, CB labeled Purkinje cells in all species, whereas CR was mainly found in fibers and labeled Purkinje cells only inRana. In the parabrachial region, CB and CR allowed the distinction of the laterodorsal tegmental nucleus, isthmic nucleus, locus coeruleus, and rostral octavolateral nuclei. The distribution of CB‐ and CR‐immunoreactive cells in the reticular formation and central gray was consistent with the current models of brainstem segmentation in amphibians. CR was found in the auditory fibers and nuclei inRanaand in mechanosensory lateral line fibers inXenopusand urodeles, whereas CB mainly labeled vestibular fibers and nuclei in all species. These results highlight the anatomical complexity of the amphibian brainstem and help in an understanding of its regional organization that is not cytoarchitectonically evident. J. Comp. Neurol. 515:503–537, 2009. © 2009 Wiley‐Liss, Inc.
Functional and topographic segregation of glomeruli revealed by local staining of antennal sensory neurons in the honeybee Apis mellifera
Authors: Nishino Hiroshi , Nishikawa Michiko , Mizunami Makoto , Yokohari Fumio
Published: March 2009

In the primary olfactory center of animals, glomeruli are the relay stations where sensory neurons expressing cognate odorant receptors converge onto interneurons. In cockroaches, moths, and honeybees, sensory afferents from sensilla on the anterodorsal surface and the posteroventral surface of the flagellum form two nerves of almost equal thicknesses. In this study, double labeling of the two nerves, or proximal/distal regions of the nerves, with fluorescent dyes was used to investigate topographic organization of sensory afferents in the honeybee. The sensory neurons of ampullaceal sensilla responsive to CO2, coelocapitular sensilla responsive to hygrosensory, and thermosensory stimuli and coeloconic sensilla of unknown function were characterized with large somata and supplied thick axons exclusively to the ventral nerve. Correspondingly, all glomeruli innervated by sensory tract (T) 4 received thick axonal processes exclusively from the ventral nerve. Almost all T1–3 glomeruli received a similar number of sensory afferents from the two nerves. In the macroglomerular complexes of the drone, termination fields of afferents from the two nerves almost completely overlapped; this differs from moths and cockroaches, which show heterogeneous terminations in the glomerular complex. In T1–3 glomeruli, sensory neurons originating from more distal flagellar segments tended to terminate within the inner regions of the cortical layer. These results suggest that some degree of somatotopic organization of sensory afferents exist in T1–3 glomeruli, and part of T4 glomeruli serve for processing of hygro‐ and thermosensory signals. J. Comp. Neurol. 515:161–180, 2009. © 2009 Wiley‐Liss, Inc.
Large‐conductance calcium‐activated potassium channels in purkinje cell plasma membranes are clustered at sites of hypolemmal microdomains
Authors: Kaufmann Walter A. , Ferraguti Francesco , Fukazawa Yugo , Kasugai Yu , Shigemoto Ryuichi , Laake Petter , Sexton Joseph A. , Ruth Peter , Wietzorrek Georg , Knaus Hans‐Günther , Storm Johan F. , Ottersen Ole Petter
Published: March 2009

Calcium‐activated potassium channels have been shown to be critically involved in neuronal function, but an elucidation of their detailed roles awaits identification of the microdomains where they are located. This study was undertaken to unravel the precise subcellular distribution of the large‐conductance calcium‐activated potassium channels (called BK, KCa1.1, or Slo1) in the somatodendritic compartment of cerebellar Purkinje cells by means of postembedding immunogold cytochemistry and SDS‐digested freeze‐fracture replica labeling (SDS‐FRL). We found BK channels to be unevenly distributed over the Purkinje cell plasma membrane. At distal dendritic compartments, BK channels were scattered over the plasma membrane of dendritic shafts and spines but absent from postsynaptic densities. At the soma and proximal dendrites, BK channels formed two distinct pools. One pool was scattered over the plasma membrane, whereas the other pool was clustered in plasma membrane domains overlying subsurface cisterns. The labeling density ratio of clustered to scattered channels was about 60:1, established in SDS‐FRL. Subsurface cisterns, also called hypolemmal cisterns, are subcompartments of the endoplasmic reticulum likely representing calciosomes that unload and refill Ca2+ independently. Purkinje cell subsurface cisterns are enriched in inositol 1,4,5‐triphosphate receptors that mediate the effects of several neurotransmitters, hormones, and growth factors by releasing Ca2+ into the cytosol, generating local Ca2+ sparks. Such increases in cytosolic [Ca2+] may be sufficient for BK channel activation. Clustered BK channels in the plasma membrane may thus participate in building a functional unit (plasmerosome) with the underlying calciosome that contributes significantly to local signaling in Purkinje cells. J. Comp. Neurol. 515:215–230, 2009. © 2009 Wiley‐Liss, Inc.
A multiplicative Schwarz method with active subdomains for transient convection–diffusion problems
Authors: Sandoval M. L. , Rodríguez‐Ferran A.
Published: March 2009

An efficient algorithm to find the solution of transient convection–diffusion problems with dominant convection is presented. The main idea is to follow the solution front and activate those subdomains where the solution satisfies a given threshold value. We call this novel method ‘the multiplicative Schwarz method with active subdomains’, and it is motivated by the solution of a problem from activated‐carbon filters used in the automotive industry to reduce emissions. Numerical experiments show that this method is more efficient than the preconditioned conjugate gradient method with an incomplete Cholesky factorization. Copyright © 2009 John Wiley & Sons, Ltd.
Market‐based grid resource co‐allocation and reservation for applications with hard deadlines
Authors: Vanmechelen Kurt , Depoorter Wim , Broeckhove Jan
Published: March 2009

Grid computing technology enables the creation of large‐scale IT infrastructures that are shared across organizational boundaries. In such shared infrastructures, conflicts between user requirements are common and originate from the selfish actions that users perform when formulating their service requests. The introduction of economic principles in grid resource management offers a promising way of dealing with these conflicts. We develop and analyze both a centralized and a decentralized algorithm for economic grid resource management in the context of compute bound applications with deadline‐based quality of service requirements and non‐migratable workloads. Through the use of reservations, we co‐allocate resources across multiple providers in order to ensure that applications finish within their deadline. An evaluation of both algorithms is presented and their performance in terms of realized user value is compared with an existing market‐based resource management algorithm. We establish that our algorithms, which operate under a more realistic workload model, can closely approximate the performance of this algorithm. We also quantify the effect of allowing local workload preemption and different scheduling heuristics on the realized user value. Copyright © 2009 John Wiley & Sons, Ltd.
Cytomorphologic manifestations of Alzheimer's disease using brain squash smears: An autopsy study with histology–cytology correlation
Authors: Takei Hidehiro , Kosarac Ognjen , Powell Suzanne Z.
Published: March 2009

Alzheimer's disease (AD) is the most common form of dementia. The cardinal histopathologic features include senile plaques (SPs) and neurofibrillary tangles (NFTs), and in addition, granulovacuolar degeneration (GVD) and Hirano bodies (HBs) are frequently observed in the hippocampus. We studied hippocampal cytological features of AD, compared with controls. Hippocampal squash smears were prepared from 26 autopsy brains and stained with three different solutions, including Papanicolaou stain (Pap‐s). The smears were evaluated for the aforementioned four structures and gliosis, and their frequency was compared between AD (n = 15) and control (n = 11) groups. Hippocampal smears of all AD cases revealed NFTs and gliosis. NFTs were light gray with thick flame‐like structures on Pap‐s. GVD was identified in the majority of AD cases and was most easily observed on Pap‐s. SPs were difficult to identify and were seen only in AD cases. HBs were rarely identified as long light eosinophilic hyaline structures on Pap‐s. Cytological findings of hippocampi reflect the characteristic histological features of AD with the exception of HBs, which are difficult to identify on smears. NFTs and gliosis, and SPs seem to be sensitive and specific cytologic markers in hippocampal smears for AD, respectively. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.