bluuebunny/crossref_metadata_2025 huggingface dataset:
Alfred Kühn (1885–1968) and developmental evolution
Authors: Laubichler Manfred D. , Rheinberger Hans‐Jörg
Published: March 2004

Alfred Kühn (1885–1968) was known as one of the most comprehensive zoologists of his time. His research program in developmental physiological genetics was one of the first successful attempts to integrate the experimental study of development and heredity. It led him to discover the first known reaction chain from gene to phenotype. Kühn also foresaw many elements of modern evolutionary developmental biology and as a student of Weismann and mentor to many developmental geneticists of the late 20th century directly connects Weismann with molecular developmental genetics. J. Exp. Zool. (Mol. Dev. Evol.) 302B:103–110, 2004. © 2004 Wiley‐Liss, Inc.
Portal branch ligation induces efficient retrovirus‐mediated gene delivery in rat liver
Authors: Lorand Isabelle , Vons Corinne , Nguyen Tuan , Di Rico Virginie , Coulomb Aurore , Franco Dominique , Capron Frédérique , Weber Anne
Published: March 2004

Background

The in vivo transduction of hepatocytes with conventional retrovirus vectors requires the induction of cell division and this can currently only be achieved by invasive surgery or by inducing severe liver damage. We hypothesised that partial portal branch ligation (PBL) could induce hepatocyte proliferation and efficient gene transfer in the rat.

Methods

We ligated the portal branch serving 70% of the liver and measured the kinetics of liver mass restoration and cell proliferation and the distribution of dividing hepatocytes after administration of 5‐bromo‐2′‐deoxyuridine. The efficiency of retrovirus‐mediated gene transfer after PBL was tested by use of β‐galactosidase‐expressing recombinant retroviruses. The viruses were administered in a single injection via the portal vein at different times after PBL and the livers of transduced animals were analysed 4 days later.

Results

We found that the number of cycling hepatocytes remained stable between 24 and 44 h after PBL (∼12.5%). Although there was a high level of inter‐animal variability, hepatocyte proliferation was always initiated in the same lobe of the liver. In animals that had undergone PBL, 19% of hepatocytes were transduced 28 h after the administration of a single high‐titre injection of retroviruses, mainly around the portal spaces.

Conclusions

PBL can mediate the efficient transduction of hepatocytes in vivo after a single intravenous injection of recombinant retroviruses. This approach is feasible in humans. Copyright © 2004 John Wiley & Sons, Ltd.
5‐Fluorouracil or gemcitabine combined with adenoviral‐mediated reintroduction of p16INK4A greatly enhanced cytotoxicity in Panc‐1 pancreatic adenocarcinoma cells
Authors: Halloran Christopher M. , Ghaneh Paula , Shore Susannah , Greenhalf William , Zumstein Lou , Wilson Deborah , Neoptolemos John P. , Costello Eithne
Published: March 2004

Background

Pancreatic cancer is one of the most lethal of all the common gastrointestinal malignancies. Although surgery offers the best chance for survival, it is not appropriate for all cases. The only adjuvant treatment to show promise is chemotherapy. Hence new treatments are urgently sought. We previously reported that adenoviral (Ad)‐mediated delivery of p53 (Adp53) and p16INK4A (Adp16) significantly inhibited the growth of pancreatic cancer cell lines and established subcutaneous pancreatic tumours in nude mice (Ghaneh P, et al. Adenovirus mediated transfer of p53 and p16INK4A results in pancreatic cancer regression in vitro and in vivo. Gene Ther 2001; 8: 199–208). In this study we examine whether combining Ad‐mediated delivery of p53 or p16INK4A with clinically relevant chemotherapeutic drugs has therapeutic potential for pancreatic cancer.

Methods and results

Four pancreatic adenocarcinoma cell lines were evaluated for their sensitivity to 5‐fluorouracil (5‐FU) and gemcitabine and two of these, Suit‐2 and Panc‐1, were chosen for combination experiments because they showed moderate and poor sensitivity, respectively, to 5‐FU and gemcitabine. We found no evidence for enhanced cytotoxicity when either cell line was transduced with Adp53 before or after incubation with chemotherapeutic drugs. In contrast, incubation of Panc‐1 cells with either 5‐FU or gemcitabine followed by Ad‐mediated overexpression of p16INK4A resulted in a substantial reduction in cell viability under conditions where the drugs alone had minimal cytotoxicity. Incubation of Suit‐2 cells with 5‐FU followed by Ad‐mediated overexpression of p16INK4A also resulted in a significant reduction in cell viability. This, however, was observed only with higher concentrations of 5‐FU and viral vector. Cell cycle analysis of Panc‐1 cells showed that the combination of cytotoxic drugs and Adp16 resulted in an increase in the sub‐G1 population suggesting an increase in apoptosis. Dual labelling of these cells with annexin V and propidium iodide (PI) confirmed that the combination of 5‐FU and Adp16 resulted in a significant increase in early apoptotic cells (annexin V positive and PI negative) compared with controls. Moreover, overexpression of p16INK4A was associated with a reduction in pRb levels in these cells—high levels of pRb have been proposed to contribute to chemoresistance in pancreatic cancer cells.

Conclusions

We have shown that the currently used chemotherapeutic drugs for pancreatic adenocarcinoma combined with restoration of p16INK4A expression hold promise for the adjuvant treatment of this disease. Importantly, the combination facilitated the use of chemotherapeutic drugs at lower concentrations than would otherwise be effective. Copyright © 2004 John Wiley & Sons, Ltd.
Identification of a replication‐defective herpes simplex virus for recombinant adeno‐associated virus type 2 (rAAV2) particle assembly using stable producer cell lines
Authors: Toublanc Estelle , Benraiss Abdellatif , Bonnin Delphine , Blouin Véronique , Brument Nicole , Cartier Nathalie , Epstein Alberto L. , Moullier Philippe , Salvetti Anna
Published: March 2004

Background

The development of stable producer cell lines for recombinant adeno‐associated virus (rAAV) assembly is a strategy followed by many groups to develop scalable production methods suitable for good manufacturing practice (GMP) requirements. The major drawback of this method lies in the requirement for replicating adenovirus (Ad) for rAAV assembly. In the present study, we analyzed the ability of several replication‐defective herpes simplex type 1 (HSV‐1) helper viruses to induce rAAV2 particle production from stable producer cell lines.

Methods

Several stable rAAV producer cell clones were infected with wild‐type and replication‐defective HSV strains and analyzed for rep‐cap gene amplification, viral protein synthesis and rAAV titers achieved. In vivo analysis following rAAV injection in the murine brain was also conducted to evaluate the toxicity and biopotency of the rAAV stocks.

Results

We demonstrated that an HSV strain mutated in the UL30 polymerase gene could efficiently be used in this context, resulting in rAAV titers similar to those measured with wild‐type HSV or Ad. Importantly, with respect to clinical developments, the use of this mutant resulted in rAAV stocks which were consistently devoid of contaminating HSV particles and fully active in vivo in the murine central nervous system with no detectable toxicity.

Conclusions

This study, together with our previous report describing a rAAV chromatography‐based purification process, contributes to the definition of an entirely scalable process for the generation of rAAV particles. Copyright © 2004 John Wiley & Sons, Ltd.
Hepatocyte growth factor stimulates adenoviral‐mediated gene transfer across the apical membrane of epithelial cells
Authors: Burrus Jason K. , Matheson William D. , Hong Jeong S. , Sorscher Eric J. , Balkovetz Daniel F.
Published: March 2004

Background

The apical surface of polarized epithelial cells is relatively resistant to gene delivery by various agents including adenoviral vectors. Hepatocyte growth factor (HGF) dedifferentiates previously well‐polarized Madin‐Darby canine kidney (MDCK) cell monolayers by altering cell‐surface polarity and inhibiting tight junction function.

Methods

We used an in vitro model of polarized MDCK cells grown on permeable supports to examine the effects of HGF pretreatment on adenoviral (Ad)‐mediated gene delivery through the apical surface of epithelial cell monolayers.

Results

HGF pretreatment of MDCK cell monolayers for 72 h increased Ad‐mediated gene transfer and expression of enhanced green fluorescent protein (EGFP) and luciferase in a dose‐dependent fashion. Time‐course analysis of HGF‐induced stimulation of Ad‐mediated gene transfer was seen after 24 h and increased further with pretreatment periods extending to 72 h. HGF pretreatment increased Ad‐mediated gene transfer at varying multiplicity of infection (MOI; ranging from 0.2–2000). PCR analysis for adenoviral DNA in control and HGF‐pretreated MDCK cells suggested increased entry of viral constructs into HGF‐pretreated MDCK cell monolayers. HGF‐induced alterations in cell polarity are reversible upon removal of HGF.

Conclusions

These data demonstrate that HGF pretreatment of MDCK cells increases the sensitivity of the cells to Ad‐mediated gene delivery. The mechanism by which this occurs appears to be through increased entry of adenovirus into epithelial cells. These data provide evidence that biological agents that transiently alter epithelial cell polarity and tight junction function can be used to augment Ad‐mediated gene delivery into epithelial cells from the apical surface. Copyright © 2004 John Wiley & Sons, Ltd.
Thirteen days: Joseph Delboeuf versus Pierre Janet on the nature of hypnotic suggestion
Authors: LeBlanc André
Published: March 2004

The problem of post‐hypnotic suggestion was introduced in 1884. Give a hypnotic subject the
post‐hypnotic command to return in 13 days. Awake, the subject remembers nothing yet nonetheless fulfills
the command to return. How then does the subject count 13 days without knowing it? In 1886, Pierre Janet
proposed the concept of dissociation as a solution, arguing that a second consciousness kept track of time
outside of the subject's main consciousness. Joseph Delboeuf, in 1885, and Hippolyte Bernheim, in 1886,
proposed an alternative solution, arguing that subjects occasionally drifted into a hypnotic state in which they
were reminded of the suggestion. This article traces the development of these competing solutions and describes
some of Delboeuf's final reflections on the problem of simulation and the nature of hypnosis. © 2004
Wiley Periodicals, Inc.
A four‐fold humanity: Margaret Mead and psychological types
Authors: Sullivan Gerald
Published: March 2004

Beginning in 1933, while working in New Guinea, Margaret Mead developed her so‐called squares hypothesis. Mead never published its terms, though she made a brief comment on it in her autobiography,Blackberry Winter(1972), and the arguments found inSex and Temperament in Three Primitive Societies(1935) and the research leading toBalinese Character(Bateson & Mead, 1942) bore its imprint. Beginning with William McDougall's distinction between temperament (innate predispositions) and character (learned organization of habit), Mead articulated a morphological approach to the interplay between biology and culture that yielded four primary and four intermediary personality types. Under specified but not inevitable circumstances, the conscious choices of a given people could render one or another of these types characteristic or predominantly stable within their population, giving each of the other types a definite relation to the dominant type and thereby the cultural ethos of its society. Persons of each type followed a developmental path specific to their type different both from that of other types and in its manifestations given the various relations of the individual's type to the dominant type. Mead's hypothesis was, therefore, a vision of the unity and diversity of a single human species as well as an approach to the differing psychological positioning of individuals in cultures. In examining Mead's hypothesis, this essay also takes up Mead's debts to several leading psychologists (McDougall, C. G. Jung, and Erik Erikson), and (provisionally) how her vision differed from that of Ruth Benedict. © 2004 Wiley Periodicals, Inc.
Théodule Ribot's ambiguous positivism: Philosophical and epistemological strategies in the founding of French scientific psychology
Authors: Guillin Vincent
Published: March 2004

Théodule Ribot (1839–1916) is regarded by many historians of psychology as the
“father” of the discipline in France. Ribot contributed to the development of a “new
psychology” independent from philosophy, relying on the methods of the natural sciences. However, such an
epistemological transition encountered fierce opposition from both the champions of the old‐fashioned
metaphysical psychology and the representatives of the “scientific spirit.” This article focuses on
the objections raised by the latter, and especially philosophers of science, against the possibility of a
scientific psychology. For instance, according to Auguste Comte, psychology does not satisfy certain basic
methodological requirements. To overcome these objections, Ribot, in his La Psychologie Anglaise
Contemporaine (1870/1914), devised an epistemological strategy that amounted to invoking
criticisms of Comte's views made by other representatives of the positivist school, such as John Stuart Mill
and Herbert Spencer. © 2004 Wiley Periodicals, Inc.
What is the canonical theory of assimilation?
Authors: Kivisto Peter
Published: March 2004

Throughout the past century, assimilation has been the hegemonic theory of ethnic group relations in
sociology, and Robert E. Park is generally considered to be the key figure associated with the articulation of
assimilation's canonical formulation. Based on a careful reading of Park's main essays on
assimilation, this article argues that those who associate his position with the melting pot (with its
assumption of the eradication of ethnic traits and ties), the race‐relations cycle, or a
straight‐line process of incorporation misconstrue his views. This article is in part corrective and in
part revisionist insofar as it is intended to indicate aspects of Park's theory that have particular
relevance to current sociological efforts to understand the implications of assimilation in multiethnic liberal
democracies. © 2004 Wiley Periodicals, Inc.
Cheiron's origins: Personal recollections and a photograph
Authors: Scarborough Elizabeth
Published: March 2004

When the Cheiron Society convened at the University of New Hampshire for its thirty‐fifth annual
meeting in June 2003, members were returning to the site where the proposal to establish a new scholarly
organization to promote research in the history of the behavioral and social sciences originated in the summer of
1968. I was witness to Cheiron's birthing and have been closely involved in its evolution over the years,
and so was asked to comment on the circumstances that produced what has become a vibrant source of stimulation
and support for those of us interested in the field. (For other published accounts of the Institute and
Cheiron's founding see Brozek, Watson, & Ross, 1969, 1970; Goodman, 1979, 1982; Watson, 1972,
1975; and Weyant, 1968.) © 2004 Wiley Periodicals, Inc.
Taking stock and planning for the next decade: Realistic prospects for stem cell therapies for the nervous system
Authors: Snyder Evan Y. , Daley George Q. , Goodell Margaret
Published: March 2004

In thinking about the practical application of stem cell biology to clinical situations—particularly for the central nervous system (CNS)—it is instructive to remember that the neural stem cell (NSC) field—as a prototype for somatic stem cells in general—emerged as the unanticipated byproduct of investigations by developmental neurobiologists into fundamental aspects of neural determination, commitment, and plasticity. Stem cell behavior is ultimately an expression of developmental principles, an alluring vestige from the more plastic and generative stages of organogenesis. In attempting to apply stem cell biology therapeutically, it is instructive always to bear in mind what role the stem cell plays in development and to what cues it was “designed” to respond in trying to understand the “logic” behind its behavior (both what investigators want to see and what investigators do not want to see). Furthermore, in transplantation paradigms, the interaction between engrafted NSCs and recipient host is a dynamic, complex, ongoing reciprocal interaction where both entities are constantly in flux. In this review, we propose a “roadmap” to the clinic, with a particular emphasis on flagging the “potholes” and “speed bumps” through which we must navigate. Despite the admonitions to be circumspect, we also suggest disease processes that may be within the grasp of proven stem cell properties and might be approachable in the relatively near future. © 2004 Wiley‐Liss, Inc.
The “brainy side” of human embryonic stem cells
Authors: Hornstein Eran , Benvenisty Nissim
Published: March 2004

The recent isolation of human embryonic stem (ES) cells is evoking great hopes for their future utilization in cell‐replacement therapies and human development research. The hallmarks of ES cells, pluripotency and self‐renewal capacity, suggest an infinite source for tissues of virtually all desired types. Specifically, human ES cells may potentially be the basis for effective treatments of a wide range of human neurodegenerative disorders. To enable the translation of this novel biomedical field into the clinic, mechanisms that control the differentiation of human embryonic stem cells into fully functional neuronal cells should be analyzed and controlled. © 2004 Wiley‐Liss, Inc.
PACAP promotes neural stem cell proliferation in adult mouse brain
Authors: Mercer Alex , Rönnholm Harriet , Holmberg Johan , Lundh Hanna , Heidrich Jessica , Zachrisson Olof , Ossoinak Amina , Frisén Jonas , Patrone Cesare
Published: March 2004

In recent years, it has become evident that neural stem cells in the adult mammalian brain continuously generate new neurons, mainly in the hippocampus and olfactory bulb. Although different growth factors have been shown to stimulate neurogenesis in the adult brain, very little is known about the role of neuropeptides in this process. Pituitary adenylate cyclase‐activating polypeptide (PACAP) is a neuropeptide with pleiotropic effects acting through three receptors to which it has high affinity, namely, PACAP receptor 1 (PAC1), vasoactive intestinal peptide (VIP) receptor 1, and VIP receptor 2. We show that PAC1 is expressed in the neurogenic regions of the adult mouse brain, namely the ventricular zone of the lateral ventricle and the hippocampal dentate gyrus. Cultured neural stem cells isolated from the lateral ventricle wall of adult mice express PAC1 and proliferate in vitro in response to two PAC1 agonists, PACAP and Maxadilan, but not VIP at physiologic concentrations, indicating PAC1 as a mediator of neural stem cell proliferation. Pharmacologic and biochemical characterization of PACAP‐induced neural stem cell proliferation revealed the protein kinase C pathway as the principal signaling pathway, whereas addition of epidermal growth factor synergistically enhanced the proliferating effect of PACAP. Further in vitro characterization of the effect of PACAP on neural stem cells showed PACAP capable of stimulating ex novo in vitro formation of multipotent neurospheres with the capacity to generate both neuronal and glial cells. Finally, intracerebroventricular infusion of PACAP increases cell proliferation in the ventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus. We conclude that PACAP, through PAC1, is a potent mediator of adult neural stem cell proliferation. © 2004 Wiley‐Liss, Inc.
Adult hippocampal neurogenesis and voluntary running activity: Circadian and dose‐dependent effects
Authors: Holmes Melissa M. , Galea Liisa A.M. , Mistlberger Ralph E. , Kempermann Gerd
Published: March 2004

Running activity increases cell proliferation and neurogenesis in the dentate gyrus of adult mice. The present experiment was designed to investigate whether the effect of activity on adult neurogenesis is dependent on the time of day (circadian phase) and the amount of activity. Mice received restricted access to a running wheel (0, 1, or 3 hr) at one of three times of day: the middle of the light phase (i.e., when mice are normally inactive), dark onset (i.e., when mice begin their nocturnal activity), and the middle of the dark period (i.e., when mice are in the middle of their active period). Cell proliferation and net neurogenesis were assessed after incorporation of the thymidine analog bromodeoxyuridine (BrdU) and immunohistochemical detection of BrdU and neuronal markers. Running activity significantly increased cell proliferation, cell survival, and total number of new neurons only in animals with 3 hr of wheel access during the middle of the dark period. Although activity was positively correlated with increased neurogenesis at all time points, the effects were not statistically significant in animals with wheel access at the beginning of the dark period or during the middle of the light period. These data suggest that the influence of exercise on cell proliferation and neurogenesis is modulated by both circadian phase and the amount of daily exercise, thus providing new insight into the complex relationship between physiological and behavioral factors that can mediate adult neuroplasticity. © 2004 Wiley‐Liss, Inc.
Endogenous adult neural stem cells: Limits and potential to repair the injured central nervous system
Authors: Picard‐Riera Nathalie , Nait‐Oumesmar Brahim , Baron‐Van Evercooren Anne
Published: March 2004

Mitotic activity persists in various regions of the adult mammal CNS. While evidences of neurogenesis appeared, many studies focused on the features of the adult stem cells from germinative areas such as the subventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, the cortex, the fourth ventricle and the central canal of the spinal cord. In the present paper, we review the potentialities of the adult germinative areas in terms of proliferation, migration and differentiation in non pathological situation and in response to different type of CNS injury. Adult endogenous stem cells are activated in response to various injuries but their capacities to migrate and to undergo either neurogenesis or gliogenesis differ according to the lesion‐type and the germinative zone from which they arise. Different works demonstrated that epigenic factors such as growth factors can enhance the repair potential of the adult stem cells. Reactivation and mobilization of endogenous stem cells as well as demonstration of their long‐term survival and functionality appear to be interesting strategies to investigate in order to promote endogenous repair of the adult CNS. © 2004 Wiley‐Liss, Inc.
Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?
Authors: Walczak P. , Chen N. , Hudson J.E. , Willing A.E. , Garbuzova‐Davis S.N. , Song S. , Sanberg P.R. , Sanchez‐Ramos J. , Bickford P.C. , Zigova T.
Published: March 2004

Hematopoietic progenitors are cells, which under challenging experimental conditions can develop unusual phenotypic properties, rather distant from their original mesodermal origin. As previously reported, cells derived from human umbilical cord blood (HUCB) or human bone marrow (BM) under certain in vivo or in vitro conditions can manifest neural features that resemble features of neural‐derived cells, immunocytochemically and in some instances also morphologically. The present study explored how hematopoietic‐derived cells would respond to neurogenic signals from the subventricular zone (SVZ) of adult and aged (6 and 16 months old) rats. The mononuclear fraction of HUCB cells was transplanted into the SVZ of immunosuppressed (single cyclosporin or three‐drug treatment) animals. The triple‐suppression paradigm allowed us to protect transplanted human cells within the brain and to explore further their phenotypic and migratory properties. One week after implantation, many surviving HUCB cells were located within the SVZ and the vertical limb of the rostral migratory stream (RMS). The migration of HUCB cells was restricted exclusively to the pathway leading to the olfactory bulb. In younger animals, grafted cells navigated almost halfway through the vertical limb, whereas, in the older animals, the migration was less pronounced. The overall cell survival was greater in younger animals than in older ones. Immunocytochemistry for surface CD antigen expression showed that many HUCB cells, either cultured or within the brain parenchyma, retained their hematopoietic identity. A few cells, identified by using human‐specific antibodies (anti‐human nuclei, or mitochondria) expressed nestin and doublecortin, markers of endogenous neural progenitors. Therefore, it is believed that the environment of the neurogenic SVZ, even in aged animals, was able to support survival, “neuralization,” and migratory features of HUCB‐derived cells. © 2004 Wiley‐Liss, Inc.
Green fluorescent protein bone marrow cells express hematopoietic and neural antigens in culture and migrate within the neonatal rat brain
Authors: Hudson J.E. , Chen N. , Song S. , Walczak P. , Jendelová P. , Sykova E. , Willing A.E. , Saporta S. , Bickford P. , Sanchez‐Ramos J. , Zigova T.
Published: March 2004

Finding a reliable source of alternative neural stem cells for treatment of various diseases and injuries affecting the central nervous system is a challenge. Numerous studies have shown that hematopoietic and nonhematopoietic progenitors derived from bone marrow (BM) under specific conditions are able to differentiate into cells of all three germ layers. Recently, it was reported that cultured, unfractionated (whole) adult BM cells form nestin‐positive spheres that can later initiate neural differentiation (Kabos et al., 2002). The identity of the subpopulation of BM cells that contributes to neural differentiation remains unknown. We therefore analyzed the hematopoietic and neural features of cultured, unfractionated BM cells derived from a transgenic mouse that expresses green fluorescent protein (GFP) in all tissues. We also transplanted the BM cells into the subventricular zone (SVZ), a region known to support postnatal neurogenesis. After injection of BM cells into the neurogenic SVZ in neonatal rats, we found surviving GFP+ BM cells close to the injection site and in various brain regions, including corpus callosum and subcortical white matter. Many of the grafted cells were detected within the rostral migratory stream (RMS), moving toward the olfactory bulb (OB), and some cells reached the subependymal zone of the OB. Our in vitro experiments revealed that murine GFP+ BM cells retained their proliferation and differentiation potential and predominantly preserved their hematopoietic identity (CD45, CD90, CD133), although a few expressed neural antigens (nestin, glial fibrillary acdiic protein, TuJ1). © 2004 Wiley‐Liss, Inc.
Blockade of interleukin‐6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury
Authors: Okada S. , Nakamura M. , Mikami Y. , Shimazaki T. , Mihara M. , Ohsugi Y. , Iwamoto Y. , Yoshizaki K. , Kishimoto T. , Toyama Y. , Okano H.
Published: March 2004

Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the cells that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of the spinal cord, especially the inflammatory cytokines that dramatically increase in the acute phase at the injury site, is considered to be an important cause of inhibitory mechanism of neuronal differentiation following SCI. Interleukin‐6 (IL‐6), which has been demonstrated to induce NSPCs to undergo astrocytic differentiation selectively through the JAK/STAT pathway in vitro, has also been demonstrated to play a critical role as a proinflammatory cytokine and to be associated with secondary tissue damage in SCI. In this study, we assessed the efficacy of rat anti‐mouse IL‐6 receptor monoclonal antibody (MR16‐1) in the treatment of acute SCI in mice. Immediately after contusive SCI with a modified NYU impactor, mice were intraperitoneally injected with a single dose of MR16‐1 (100 μg/g body weight), the lesions were assessed histologically, and the functional recovery was evaluated. MR16‐1 not only suppressed the astrocytic diffentiation‐promoting effect of IL‐6 signaling in vitro but inhibited the development of astrogliosis after SCI in vivo. MR16‐1 also decreased the number of invading inflammatory cells and the severity of connective tissue scar formation. In addition, we observed significant functional recovery in the mice treated with MR16‐1 compared with control mice. These findings suggest that neutralization of IL‐6 signaling in the acute phase of SCI represents an attractive option for the treatment of SCI. © 2004 Wiley‐Liss, Inc.
Role of calcium and kinases on the neurotrophic effect induced by γ‐aminobutyric acid
Authors: Fiszman Mónica L. , Schousboe Arne
Published: March 2004

An increasing body of evidence supports a trophic action of γ‐aminobutyric acid (GABA) during nervous system development. The purported mediator of these trophic effects is a depolarizing response triggered by GABA, which elicits a calcium influx in immature CNS cells. This Mini‐Review focuses on the neurotrophic role of neural activity and GABA and some of the most common intracellular cascades activated by depolarization and trophic factors. Several biological effects induced by GABA in the developing nervous system are reviewed, with particular emphasis on what is known about calcium‐dependent neurotrophic effects induced by GABA and its intracellular mechanisms. © 2004 Wiley‐Liss, Inc.
How types of carbonate rock assemblages constrain the distribution of karst rocky desertified land in Guizhou Province, PR China: phenomena and mechanisms
Authors: Wang S.‐J. , Li R.‐L. , Sun C.‐X. , Zhang D.‐F. , Li F.‐Q. , Zhou D.‐Q. , Xiong K.‐N. , Zhou Z.‐F.
Published: March 2004

In southwestern China karst rocky desertification (a process of land degradation involving serious soil erosion, extensive exposure of basement rocks, drastic decrease of soil productivity and the appearance of a desert‐like landscape) results from irrational land use on the fragile, thin karst soil. Soil particles in the Guizhou karst plateau were accumulated predominantly from residues left behind after the dissolution of carbonate rocks, and the thickness of the soil layer is related to the amount of argillaceous substances in the lost carbonate rock. This paper examines the spatial distribution of karst rocky desertified (KRD) land in Guizhou Province, and relates it to the different assemblages of basement carbonate rocks.

Types of carbonate rock assemblages are discussed using a 1 : 500000 scale digital‐distribution map. Their distribution and sensitivity to erosion are analysed, demonstrating that the occurrence of KRD land is positively correlated to homogeneous carbonate rocks. Differences in physical and chemical properties of limestone and dolomite rocks lead to differences in dissolution, accumulation rate of soil particles and relief on the surface, and these factors influence land‐use potential. Copyright © 2004 John Wiley & Sons, Ltd.
Local versus expert knowledge in forest management in a semi‐arid part of India
Authors: Sekhar N. Udaya
Published: March 2004

This study analyzes the differences between the villagers' and the Forest Department's preferences in the choice of tree species to be planted in eastern Rajasthan, India. Locals learned to manage the tree resources in a sustainable manner before the formal knowledge perspectives started to dominate through various state forestry programmes in which decision making is dominated by expert perspectives in a given political context. The study also attempts to identify the problems of complementary relationships between local and expert knowledge and the resulting management implications. Copyright © 2004 John Wiley & Sons, Ltd.
AM fungi inoculation and addition of microbially‐treated dry olive cake‐enhanced afforestation of a desertified Mediterranean site
Authors: Caravaca F. , Alguacil M. M. , Vassileva M. , Díaz G. , Roldán A.
Published: March 2004

A field experiment was carried out to compare the effectiveness of inoculation with three arbuscular mycorrhizal (AM) fungi, namelyGlomus intraradicesSchenck & Smith,Glomus deserticola(Trappe, Bloss. & Menge) andGlomus mosseae(Nicol & Gerd.) Gerd. & Trappe, and the addition ofAspergillus niger‐treated dry olive cake (DOC) in the presence of rock phosphate, in increasing root nitrate reductase (NR) and acid phosphatase activities, mycorrhizal colonization, plant growth and nutrient uptake inDorycnium pentaphyllumL. seedlings afforested in a semiarid degraded soil. Three months after planting, both the addition of fermented DOC and the mycorrhizal inoculation treatments had increased root NR activity significantly, particularly the inoculation withG. deserticola(by 75 per cent with respect to non‐inoculated plants), but they had no effect on root acid phosphatase. Mycorrhizal inoculation treatments withG. deserticolaorG. mosseaeon their own were even more effective than the addition of fermented DOC alone in improving the growth and (NPK) foliar nutrients ofD. pentaphyllumplants. The combined treatment involving the application of microbially‐treated agrowastes and mycorrhizal inoculation with AM fungi, particularly withG. mosseae, can be proposed as a successful revegetation strategy forD. pentaphyllumin P‐deficient soils under semiarid Mediterranean conditions. Copyright © 2004 John Wiley & Sons, Ltd.
Desertification problems in the Yangtze River source area, China
Authors: Yan P. , Dong G. R. , Su Z. Z. , Zhang D. S.
Published: March 2004

Desertification in the source area of Yangtze River is discussed in the paper. Under the conditions of the cold climate and permafrost, the freeze–thaw processes have significant effects on the different kinds of desertification. The classification, distribution, development, formation and control measurements of desertification in the source area are in particular compared with other desertified regions in east China. Furthermore, suggestions for desertification research and control in the source area are put forward. Copyright © 2004 John Wiley & Sons, Ltd.
Cementite transformation in low carbon steel under the influence of sulphur
Authors: Hucińska J.
Published: March 2004

Cementite/Fe3C carbide in a commercial low carbon steel after prolonged service in naphtha environment with traces of sulphur of 0.3 ppm and at a temperature of 200–220°C has been examined. It has been stated that under the influence of sulphur, cementite at the steel surface and inside the steel is transformed into an unstable quasi‐crystalline phase enriched with sulphur/tramp elements and iron depletion. Cementite transformation and disintegration of the degraded carbide phase is connected with a release of carbon that diffuses into the steel in front of the sulphur diffusion zone. Beneath the steel surface a layer of low carbon content forms, followed by a zone of higher carbon content.
Optical detection methods for mass spectrometry of macroions
Authors: Peng Wen‐Ping , Cai Yong , Chang Huan‐Cheng
Published: March 2004

I.
Introduction
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 II.
Macroion Detection Methods
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A.  Energy‐Sensitive Detection
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B.  Charge‐Sensitive Detection
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C.  Photon‐Sensitive Detection
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    1.  ELS
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    2.   LIF
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III
Applications to Micron‐Sized and Nano‐Sized Particles
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A.  Ion Sources
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B.  Mass Analyzers
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C.  Detectors
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    1.  ELS/Ellipsoidal Reflector
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    2.  LIF/Ion Trap
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IV.
Conclusions and Outlook
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Acknowledgments
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References
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Detection of macroions has been a challenge in the field of mass spectrometry. Conventional ionization‐based detectors, relying on production and multiplication of secondary electrons, are restricted to detection for charged particles of m/z < 1 × 106. While both energy‐sensitive and charge‐sensitive detectors have been developed recently to overcome the limitation, they are not yet in common use. Photon‐sensitive detectors are suggested to be an alternative, with which detection of macroions (or charged particles) by either elastic light scattering (ELS) or laser‐induced fluorescence (LIF) has been possible. In this article, we provide a critical review on the developments of novel optical detection methods for mass spectrometry of macroions, including both micron‐sized and nano‐sized synthetic polymers as well as high‐mass biomolecules. Design and development of new spectrometers making possible observations of the mass spectra of macroions with sizes in the range of 10–103 nm or masses in the range of 1–106 MDa are illustrated. The potential and promise of this optical approach toward macroion detection with high efficiency are discussed in practical aspects. © 2004 Wiley Periodicals, Inc.,Mass Spec Rev
Dynamic Density Functional Theory for Sheared Polymeric Systems
Authors: Zvelindovsky A. V. , Sevink G. J. A. , Lyakhova K. S. , Altevogt P.
Published: March 2004

Summary:Details of the dynamic density functional theory for sheared polymer systems are presented. The method is illustrated on polymer blends with and without compatibilizers. Shearing slows down coarsening of structures at later stages of phase separation, trapping the system in kineticly driven metastable states. Under certain conditions the system is found trapped in a metastable multiple sphere morphology, while under other conditions a sphere‐to‐string transition is observed. The results are sensitive to the (block co)polymer architecture.

The morphology of a symmetric polymer blend in a 32 × 32 box.

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The morphology of a symmetric polymer blend in a 32 × 32 box.
A Protocol for the Estimation of Parameters in Process Models: Case Studies with Polymerization Scenarios
Authors: Polic A. Loui , Lona Liliane M. F. , Duever Thomas A. , Penlidis Alexander
Published: March 2004

Summary: As our understanding of chemical processes increases, the complexity of the models developed to describe them also increases. In most cases the equations are nonlinear in the inputs and parameters, and must be solved numerically. At present in estimating parameters for large process models, there are two shortcomings in the existing knowledge about (multiresponse) parameter estimation. The first is, how effective is the present parameter estimation methodology when applied to large models, and the second is, can any advantage be gained from considering the parameter estimation problem as a whole. This paper will address these questions, by revisiting the various steps of a parameter estimation protocol. There is little discussion in the literature as to how all the steps for parameter estimation are related. In the development of this protocol all of the steps for parameter estimation will be revisited: parameter sensitivity analysis, statistical design of experiments, estimation of parameters and confidence regions. By considering all these steps as a whole the overall parameter estimation procedure can be more efficient and some pitfalls, such as local optima and incorrect confidence regions, may be dealt with in an appropriate manner. To illustrate the application of the protocol, two case studies related to polymerization models are presented. These case studies illustrate some of the problems that may be encountered in the parameter estimation process and how the proposed protocol can aid in overcoming them.

Plot of conversion versus time for the copolymerization of styrene/methyl methacrylate.

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Plot of conversion versus time for the copolymerization of styrene/methyl methacrylate.
Measurement of fat/water ratios in rat liver using 3D three‐point dixon MRI
Authors: Zhang Xiaowei , Tengowski Mark , Fasulo Lisa , Botts Suzanne , Suddarth Steve A. , Johnson G. Allan
Published: March 2004

Hepatic steatosis, or fatty liver, is commonly observed during the animal phase of drug safety studies. A noninvasive three‐dimensional (3D) three‐point Dixon method was used to quantitatively evaluate the fatty livers of rats induced by an experimental microsomal transfer protein (MTP) inhibitor, in an effort to develop a safety biomarker that could be translated to human studies. The method was implemented at 2.0 T for in vivo studies, and at 7.1 T for higher‐resolution magnetic resonance (MR) histologic studies. In three separate protocols to study dose response and longitudinal evolution, intrahepatic fatty accumulation was detected by this method and confirmed by chemical and histologic assessments. Consistent with the pathologic changes, the fat/water ratios estimated by the MR technique increased significantly at doses of 1 mg/kg and 100 mg/kg of MTP inhibitor after 14 days of continuous administration. Among the more important findings were: 1) with the 3D three‐point Dixon method, in vivo longitudinal studies of liver fat distribution can be conducted at significantly higher resolution than has previously been reported; 2) MR histology allows delineation of distribution at the microscopic scale of 0.0024 mm3 resolution; and 3) the 3D three‐point Dixon technique provides relative estimates of liver fat content and distribution at a high confidence level. This technique will be applicable in future studies in which fatty liver is a potential safety issue. Magn Reson Med 51:697–702, 2004. © 2004 Wiley‐Liss, Inc.
Cardiac SSFP imaging at 3 Tesla
Authors: Schär Michael , Kozerke Sebastian , Fischer Stefan E. , Boesiger Peter
Published: March 2004

Balanced steady‐state free precession (SSFP) techniques provide excellent contrast between myocardium and blood at a high signal‐to‐noise ratio (SNR). Hence, SSFP imaging has become the method of choice for assessing cardiac function at 1.5T. The expected improvement in SNR at higher field strength prompted us to implement SSFP at 3.0T. In this work, an optimized sequence protocol for cardiac SSFP imaging at 3.0T is derived, taking into account several partly adverse effects at higher field, such as increased field inhomogeneities, longer T1, and power deposition limitations. SSFP contrast is established by optimizing the maximum amplitude of the radiofrequency (RF) field strength for shortest TR, as well as by localized linear or second‐order shimming and local optimization of the resonance frequency. Given the increased SNR, sensitivity encoding (SENSE) can be employed to shorten breath‐hold times. Short‐axis, long‐axis, and four‐chamber cine views obtained in healthy adult subjects are presented, and three different types of artifacts are discussed along with potential methods for reducing them. Magn Reson Med 51:799–806, 2004. © 2004 Wiley‐Liss, Inc.
Dynamic estimation of the myocardial oxygen extraction ratio during dipyridamole stress by MRI: A preliminary study in canines
Authors: Zheng Jie , Wang Jinghua , Nolte Mark , Li Debiao , Gropler Robert J. , Woodard Pamela K.
Published: March 2004

The myocardial oxygen extraction fraction (OEF) reflects the balance between myocardial oxygen supply and demand. The feasibility of quantifying myocardial OEF was demonstrated with MRI during pharmacologic vasodilation in dogs. Dipyridamole was infused intravenously to increase blood flow and change in myocardial oxygen content. Arterial and coronary sinus blood sampling was performed during dipyridamole‐induced vasodilation to measure the myocardial blood oxygen content. Myocardial T2 was measured dynamically during the vasodilation, and quantified with a simplified diffusion model as a function of myocardial OEF and blood volume. The results showed a strong correlation (R2 = 0.89) between myocardial OEF values measured by MRI and those measured by blood sampling. Regional differences in the OEF were demonstrated by direct infusion of dipyridamole into coronary arteries in dogs. Combined with vasodilator stress, dynamic assessments of the OEF may provide a putative measurement of myocardial flow reserve and allow consecutive monitoring of myocardial dose and response. Magn Reson Med 51:718–726, 2004. © 2004 Wiley‐Liss, Inc.
Automatic tuning and matching of a small multifrequency saddle coil at 4.7 T
Authors: Pérez de Alejo Rigoberto , Garrido Carlos , Villa Palmira , Rodriguez Ignacio , Vaquero Juan José , Ruiz‐Cabello Jesús , Cortijo Manuel
Published: March 2004

A new circuit design for automatically tuning and matching a saddle coil for small animal imaging is presented. This design allows working at 1H, 19F, and 3He resonance frequencies in a 4.7 T spectrometer. It is based on a balanced circuit with commercial variable capacity diodes controlled by a computer using digital potentiometers. The change between two different frequencies can be accurately performed in a few seconds. System Q is compared, between 140–210 MHz, to the same coil tuned and matched with high Q variable capacitors. Differences lower than 5% were found with a loaded coil. The proposed design has initially been evaluated in 19F and 1H NMR images acquired with a five‐tube phantom. An application is also shown for the acquisition of 3He, 19F, and 1H lung images in a control rat. Magn Reson Med 51:869–873, 2004. © 2004 Wiley‐Liss, Inc.
Intramuscular innervation of upper‐limb skeletal muscles
Authors: Lim Aymeric Y.T. , Pereira Barry P. , Kumar V. Prem , de Coninck Christine , Taki Christina , Baudet Jacques , Merle Michel
Published: March 2004

We studied 150 skeletal muscles from 8 upper limbs using the modified Sihler's staining technique. Based on the pattern of the intramuscular innervation and shape, the muscles were grouped into trapezoidal‐shaped (Class I), spindle‐shaped (Class II), and muscles that were combinations of these two classes (Class III). Such distinctions are clinically important for limb reconstruction procedures. Bipennate, spindle‐shaped muscles with the aponeurosis of the tendons of insertion extending proximally into the muscle belly and Class III muscles with multiple tendons of origin may be split for separate independent functional transfers. Muscle Nerve 29: 523–530, 2004
Multifocal slowing of nerve conduction in metachromatic leukodystrophy
Authors: Cameron Carol L. , Kang Peter B. , Burns Ted M. , Darras Basil T. , Jones H. Royden
Published: March 2004

Polyneuropathy is invariably associated with the late‐infantile form of metachromatic leukodystrophy (MLD), and occurs frequently in the early juvenile, juvenile, and adult variants. Uniform slowing of nerve conduction velocity is the neurophysiologic hallmark of metachromatic leukodystrophy and other inherited demyelinating polyneuropathies. To evaluate the consistency of this principle, we reviewed nerve conduction studies in 9 children with late‐infantile or early‐juvenile metachromatic leukodystrophy. Each child had significant slowing of motor nerve conduction velocity (NCV). The compound muscle action potentials showed abnormal temporal dispersion in 3 of the 9 children, which is usually regarded as the hallmark of acquired demyelinating polyneuropathies. There are reports of multifocal slowing in other hereditary processes including X‐linked Charcot–Marie–Tooth disease, hereditary neuropathy with liability to pressure palsies, and adrenomyeloneuropathy. Although multifocal NCV slowing in a child with polyneuropathy is seen most commonly in acquired conditions, a hereditary process, including MLD, cannot always be excluded in this setting. Muscle Nerve 29: 531–536, 2004