bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of biometric parameters of a hydromacrophyte habitat on the structure of zooplankton communities in various types of small water bodies
Authors: Kuczyńska-Kippen Natalia , Nagengast Barbara , Joniak Tomasz
Published: June 2009

Hydromacrophyte habitats, which can differ in a multiplicity of biometric parameters, are among the most important factors affecting zooplankton community structure. The main goal of this work was to determine the impact of plant habitat parameters expressed by density, biomass, and plant volume along with chemical features on the composition and dynamics of rotifer and crustacean communities.

A number of small water bodies of different origin (12) located in different catchment areas of the Wielkopolska region were analyzed.

It was found that helophytes and nymphaeids had the highest biomass and the lowest stem density, while elodeids were of the lowest biomass and the greatest stem density. Similarity analysis confirmed this distribution of biometric parameters among particular ecological groups of macrophytes.

The greatest numbers of zooplankton were noted among vegetated zones, which supports the idea of zooplankton using macrophytes as anti-predator refuge. Based on the study of a total of 23 plant stands, it was found that macrophyte biomass and the density of the plant habitat were the strongest predictors of three biometric parameters of zooplankton abundance.
Enzymes for Glycoprotein Synthesis
Authors: Wong Chi-Huey
Published: June 2009

More than 90% of human proteins are glycosylated and since protein glycosylation is understood to play a role in folding, trafficking, stability, immunogenicity, and function there is a need to generate pure protein glycoforms. Pure single protein glycoforms are difficult to obtain
because the cellular machinary produces complex mixtures for any given protein. In this article an overview is given of various approaches used to generate specific single glycoforms of proteins, studies of the role of glycosylation in protein stability and function, and the imaging and identification
of new glycoproteins related to cancer.
Progress of Enantioselective Nitrile Biotransformations in Organic Synthesis
Authors: Wang Mei-Xiang
Published: June 2009

Recent progress of enantioselective biotransformations of nitriles including various functionalized nitriles, ?-hydroxy and ?-amino nitriles, oxirane- and aziridine-containing carbonitriles is summarized in this short review article.
Unraveling the Mechanisms of Isoprenoid Biosynthetic Enzymes: Mechanistic Studies of the Early Stage Enzymes
Authors: Thibodeaux Christopher J. , Liu Hung-wen
Published: June 2009

Isoprenoids (or terpenoids) are a large and structurally diverse class of biomolecules that are essential for the survival of all forms of life. Despite the vast differences in their final structures and functions, the early steps of isoprenoid biosynthesis in all organisms follow one
of only two known biosynthetic pathways: the mevalonate pathway or the methyl erythritol phosphate (MEP) pathway. Interestingly, while humans utilize the mevalonate pathway, many human pathogens rely exclusively on the MEP pathway for the biosynthesis of their isoprenoid compounds. This has
led to a number of mechanistic studies of the MEP-specific pathway enzymes, with the ultimate goal of developing small molecule inhibitors as potential drugs. In addition to their therapeutic value, many of the MEP pathway enzymes also catalyze unusual chemical transformations that are not
well understood. In this review, we will highlight the recent work by us and others towards the elucidation of the catalytic mechanisms of several key enzymes involved in the early stages of isoprenoid biosynthesis. These include 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) and 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate
reductase (IspH) of the MEP pathway, and the type II isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2) from Staphylococcus aureus. The functions of these enzymes are validated or identified as potential drug targets.
In situ Product Recovery Integrated with Biotransformations
Authors: Bechtold Matthias , Panke Sven
Published: June 2009

Biocatalysis constitutes an effective tool for the production of fine chemicals. In order to widen the spectrum of applicable reaction types to reactions that are constrained by inhibitions, product toxicity, or degradation, an unfavorable position of the thermodynamic equilibrium,
or by kinetic control, in situ product removal (ISPR) is an attractive process option to overcome those limitations. To fully exploit the benefits of the ISPR approach, selective removal of the product to an auxiliary phase with high capacity is usually required. Obviously, such an
operation becomes increasingly difficult with decreasing differences in the physical properties of substrate(s) and product(s) as it is arguably frequently the case with biotransformations. In this paper we analyze the possibilities to apply ISPR to biotransformations and identify the most
promising developments supported by simple model considerations to fully exploit the potential of ISPR.
LORD WRIGHT AND INNOVATIVE TRADITIONALISM
Authors: Duxbury Neil
Published: June 2009

This study presents the mid-twentieth-century English lord of appeal, Lord Wright, as an innovative traditionalist judge. Judges have a duty to be creative, Wright believed, but only within the framework of existing legal authority. Wright explained his innovative traditionalist perspective in relation to precedent, public policy, and legislation, and he illustrated his perspective particularly by way of contributions to decisions on worker compensation, commercial contracts, restitution, and international criminal law. He was not always a bold judge, as is especially evident from his contribution to Liversidge v. Anderson. But his efforts to develop the law without undermining established precedents and statutory authority could be subtly effective. In contract and tort decisions, he consistently argued that personal liability should attach only to outcomes that could reasonably have been expected to come about. He was realistic, and believed courts must be realistic, about the tendency of the business world to be guided primarily by its own norms. He incisively criticized implied contract theory and advanced a conception of unjust enrichment that, in England, was considerably ahead of its time. In employment law, he added a twist to freedom-of-contract reasoning, arguing that if it is permissible for individuals to use their economic advantage to impose contractual terms on weaker parties, then it should also be permissible for those parties to combine and gain the upper hand. After World War II, he argued that the positive laws necessary for punishing war criminals already existed. This study draws these arguments together in an effort to capture Wright's judicial style and to show that some of his contributions to legal thought and doctrine run deep and are historically significant.
FREEDOM, LAW, AND NAKED VIOLENCE: A REPLY TO KRAMER
Authors: Simmonds N.E.
Published: June 2009

The essay defends the thesis that law has an inherently moral aspect. To the extent that law governs, one enjoys a degree of freedom (understood as independence from the power of another) which could exist in no other way. The essay responds to Kramer's criticisms of this argument, presented in an earlier issue of the University of Toronto Law Journal. It is suggested that Kramer misrepresents the argument in several respects. Once his misrepresentations are cleared out of the way, his position is revealed as being weak and confused.
JUDICIAL POLITICS IN AUTHORITARIAN REGIMES
Authors: Balasubramaniam Ratna Rueban
Published: June 2009

This review article draws out some of the major jurisprudential lessons that can be learned from a series of case studies of judicial politics in authoritarian regimes. Such regimes need to portray themselves as respectful of the rule of law to prolong their grip on power; they therefore tolerate independent courts, because an independent judiciary is emblematic of a commitment to the rule of law. However, the regime must contend with an unintended side effect of independent courts: judges may use their independence to check the regime, limiting its power. Authoritarian regimes will thus employ strategies to contain judicial power, producing a dialectic of empowerment and constraint with respect to courts. Among the lessons highlighted is that attempts by authoritarian regimes to contain courts strain formal rule of law conditions (conditions requiring, inter alia, that laws comprise rules that are clear, non-contradictory, stable, and generally prospective, and that official action match declared rule), suggesting that the formal conception of the rule of law imposes substantive limits on arbitrary power; and that the dialectic of empowerment and constraint exhibits a problem of domination with respect to courts, as part of a larger problem of domination of legal subjects.
Outcome following decompressive surgery for different histological types of metastatic tumors causing epidural spinal cord compression
Authors: Chaichana Kaisorn L. , Pendleton Courtney , Sciubba Daniel M. , Wolinsky Jean-Paul , Gokaslan Ziya L.
Published: July 2009

Object

Metastatic epidural spinal cord compression (MESCC) is a relatively common and debilitating complication of metastatic disease that often results in neurological deficits. Recent studies have supported decompressive surgery over radiation therapy for patients who present with MESCC. These studies, however, have grouped all patients with different histological types of metastatic disease into the same study population. The differential outcomes for patients with different histological types of metastatic disease therefore remain unknown.

Methods

An institutional database of patients undergoing decompressive surgery for MESCC at an academic tertiary-care institution between 1996 and 2006 was retrospectively reviewed. Patients with primary lung, breast, prostate, kidney, or gastrointestinal (GI) cancer or melanoma were identified. Fisher exact and log-rank analyses were used to compare pre-, peri-, and postoperative variables and survival for patients with these different types of primary cancers.

Results

Twenty-seven patients with primary lung cancer, 26 with breast cancer, 20 with prostate cancer, 21 with kidney cancer, 13 with GI cancer, and 7 with melanoma were identified and categorized. All of these patients were followed up for a mean ± SD of 10.8 ± 3.8 months following surgery. Patients with primary lung and prostate cancers were typically older than patients with other types of primary cancers. Patients with prostate cancer had the shortest duration of symptoms and more commonly presented with motor deficits, while patients with breast cancer more commonly had cervical spine involvement and compression fractures. For all histological types, > 90% of patients retained the ability to ambulate following surgery. However, the group with the highest percentage of patients who regained ambulatory function after decompressive surgery was the lung cancer group. Patients with breast or kidney cancer and those with melanoma had the highest median duration of survival following decompressive surgery.

Conclusions

The present study identifies differences in presenting symptoms, operative course, perioperative complications, long-term ambulatory outcomes, and duration of survival for patients with lung, breast, prostate, kidney, and GI cancers and melanoma. This understanding may allow better risk stratification for patients with MESCC.
Epidemiology of severe cervical spinal trauma in the north area of São Paulo City: a 10-year prospective study
Authors: Santos Egmond Alves Silva , Filho Wenner Jorzino Santos , Possatti Lucas Loss , Bittencourt Lia Rita Azeredo , Fontoura Emílio Afonso França , Botelho Ricardo Vieira
Published: July 2009

Object

The main objective was to study the epidemiological data obtained in patients with cervical spinal trauma (CST) in the north area of São Paulo City between 1997 and 2006.

Methods

All patients with severe CST in the north area of São Paulo City were studied. The data analyzed were age, sex, incidence, causes of trauma, level of trauma, morbidity, deaths, and complications. Analytical tests were performed to study risks of trauma and complications. The chi-square and analysis of variance tests were used for analytical data (significance level p < 0.05).

Results

The study population consisted of 217 patients who were hospitalized for CST. The average incidence rate was 21.6 cases annually or 1.8 cases monthly. The mean patient age was 36.75 years. The 20–40-year-old age bracket was found to be most highly represented, corresponding to 52.6% of total patients. Patients were predominantly male; 191 patients (88.01%) were male compared with only 26 female patients (11.99%). The ratio of men to women was 7.35:1. Injuries in the craniocervical region corresponded to 43 (19.8%) of the cases; injuries in the cervical subaxial region corresponded to 174 (80.2%) of the cases and were associated with worse neurological lesions. Additionally, 40.6% of patients presented with complications in other organs and systems; several patients presented with multiple complications, and 33 patients (15.02%) died. During the hospitalization period, 4 patients presenting as Grade A on the American Spinal Injury Association (ASIA) Scale evolved to Grade C, 1 patient presenting as ASIA Grade A evolved to Grade B, and 2 patients evolved to Grade E. Two patients who had been admitted without neurological lesions evolved to ASIA Grade C (1 patient postsurgery and 1 patient post-traction). Two patients presenting initially as ASIA Grade E evolved to Grade D, and another to central cord syndrome. On average, patients with incomplete lesions improved 1 grade in ASIA classification during hospitalization.

Conclusions

Data from severe CST observed in the current study suggest many differences in the characteristics described in the majority of published epidemiological studies and those found in patients in the north area of São Paulo City. It is likely that these differences reflect the urban and cultural habits and behaviors of the population specific to this area.
Classification of contralateral and ipsilateral finger movements for electrocorticographic brain-computer interfaces
Authors: Scherer Reinhold , Zanos Stavros P. , Miller Kai J. , Rao Rajesh P. N. , Ojemann Jeffrey G.
Published: July 2009

Electrocorticography (ECoG) offers a powerful and versatile platform for developing brain-computer interfaces; it avoids the risks of brain-invasive methods such as intracortical implants while providing significantly higher signal-to-noise ratio than noninvasive techniques such as electroencephalography. The authors demonstrate that both contra- and ipsilateral finger movements can be discriminated from ECoG signals recorded from a single brain hemisphere. The ECoG activation patterns over sensorimotor areas for contra- and ipsilateral movements were found to overlap to a large degree in the recorded hemisphere. Ipsilateral movements, however, produced less pronounced activity compared with contralateral movements. The authors also found that single-trial classification of movements could be improved by selecting patient-specific frequency components in high-frequency bands (> 50 Hz). Their discovery that ipsilateral hand movements can be discriminated from ECoG signals from a single hemisphere has important implications for neurorehabilitation, suggesting in particular the possibility of regaining ipsilateral movement control using signals from an intact hemisphere after damage to the other hemisphere.
Decoding movement-related cortical potentials from electrocorticography
Authors: Reddy Chandan G. , Reddy Goutam G. , Kawasaki Hiroto , Oya Hiroyuki , Miller Lee E. , Howard Matthew A.
Published: July 2009

Object

Control signals for brain-machine interfaces may be obtained from a variety of sources, each with their own relative merits. Electrocorticography (ECoG) provides better spatial and spectral resolution than scalp electroencephalography and does not include the risks attendant upon penetration of the brain parenchyma associated with single and multiunit recordings. For these reasons, subdural electrode recordings have been proposed as useful primary or adjunctive control signals for brain-machine interfaces. The goal of the present study was to determine if 2D control signals could be decoded from ECoG.

Methods

Six patients undergoing invasive monitoring for medically intractable epilepsy using subdural grid electrodes were asked to perform a motor task involving moving a joystick in 1 of 4 cardinal directions (up, down, left, or right) and a fifth condition (“trigger”). Evoked activity was synchronized to joystick movement and analyzed in the theta, alpha, beta, gamma, and high-gamma frequency bands.

Results

Movement-related cortical potentials could be accurately differentiated from rest with very high accuracy (83–96%). Further distinguishing the movement direction (up, down, left, or right) could also be resolved with high accuracy (58–86%) using information only from the high-gamma range, whereas distinguishing the trigger condition from the remaining directions provided better accuracy.

Conclusions

Two-dimensional control signals can be derived from ECoG. Local field potentials as measured by ECoG from subdural grids will be useful as control signals for a brain-machine interface.
An Assessment of Two Methods used to Release Red Kites (Milvus Milvus)
Authors: Murn Campbell , Hunt Samuel
Published: July 2009

Between 2003 and 2005, we released 12 red kites ( Milvus milvus) to the wild in Hampshire, England. Four kites were captive-bred and released as fledglings in artificial nests (‘hacking’). The remaining birds were mature and released from a large aviary. Interaction with electricity power-lines killed two of the captive-bred birds three weeks post-release and a third captive-bred kite died as a result of head injuries six months post-release. One mature kite died 10 days post-release. We suggest that the different release methods of the two groups amplified the behavioural variation between individuals and exposed them to different risk factors. We concluded that releasing mature flight-fit kites from aviaries is likely to be a superior method to hacking pre-fledged kites in artificial nests. The flight skills of the mature kites, developed prior to release, enabled them to avoid potentially lethal interactions with power-lines and aggressive inter-specific encounters. Modifying or adapting release methods to incorporate behavioural variation between individuals within a release population should be a consideration for reintroduction practitioners, particularly where release numbers are small.
The Effects of Systemic Administration of Amylin on the Tibia of Laying Hens
Authors: Akkoç C.G. Özgüden , Güneş N. , Erdost H. , Güzel S.
Published: July 2009

The aim of the present study was to investigate the effects of systemic administration of amylin on the avian tibia using histological, histomorphometrical and biochemical methods. Forty “Super Nick” laying hens 10 weeks of age were used. The experimental groups were injected subcutaneously in the loose skin at the nape of neck every other day with 75 μg kg-1 doses of rat amylin. The morphology of the cells and organic components of bone were studied in standard decalcified preparations at 14, 16, 18 and 20 weeks of age. Cortical bone and tibial growth plate widths were measured from the histological sections. Serum calcium, plasma amylin, parathyroid hormone related peptide (PTHrP) and calcitonin levels were determined at the same ages. Our results suggest that, when administered systemically to laying hens, amylin stimulates the proliferation of chondrocytes and osteoblasts and increases tibial growth plate thickness.
Diet of Cattle Egrets (Bubulcus ibis ibis) in the Flood Valley of the Paraná River, Northern Argentina
Authors: De La Paz Ducommun María , Quiroga Martín A. , Beltzer Adolfo H. , Schnack Juan A.
Published: July 2009

We analysed the feeding ecology of Cattle Egrets ( Bubulcus ibis ibis) based on 30 individuals captured on the Carabajal island, Santa Fe, Argentina (31°39′S, 60°42′W), determining the minimum sample, index of relative importance (IRI), size of prey, feeding efficiency, dietary selectivity, amplitude of the trophic niche, standardisation, circadian rhythm of feeding activity and habitat preference. The trophic spectrum was made up of 17 taxonomic entities, mainly insects (IRI = 15,000), among which orthopterans were the most numerous followed by spiders and amphibians (IRI = 250). The highest percentage of prey size was found in the interval 21-30 mm. The amplitude of the trophic niche ranged between 1.98 and 3.45, and the feeding efficiency between 89 and 92%. In relation to dietary selectivity, the correlation between abundance of prey in stomachs and abundance of prey in the study area yielded no significant results (rs = 0.84, P.0:001). The rhythm of feeding activity responded to the bell-shaped model, which meant a peak in its feeding behaviour pattern at the noon hours. The pastures were the units of vegetation and environment selected more frequently.
Why Were Extinct Gigantic Birds So Small?
Authors: Deeming D. Charles , Birchard Geoffrey F.
Published: July 2009

This review details the six lineages of large flightless birds that evolved in the Late Cretaceous, Tertiary and Quaternary periods of geological time. Estimates of mass for each type of bird suggest that maximal mass is no greater than 500kg with most species attaining only 250–300 kg or less. By contrast, non-avian Archosaurs of the Mesozoic, and many mammal species of the Tertiary, attained great size with many species reaching several tonnes. Size has been limited in flightless birds because of the strength of the eggshell and in the largest species reproduction was only possible if the smaller males incubated. That reproductive characteristics limit mass in flightless birds suggests that truly gigantic non-avian theropods could not contact incubate their eggs and had to rely on environmental sources of heat energy to drive embryonic development. If fossil evidence ever arises to support proper contact incubation in a non-avian theropod then it is predicted that it will only be from a small (<250 kg) species.
Calculation of Residual Electricity Mixes when Accounting for the EECS (European Electricity Certificate System) — the Need for a Harmonised System
Authors: Raadal Hanne Lerche , Nyland Cecilia Askham , Hanssen Ole Jørgen
Published: July 2009

According to the Electricity Directive, suppliers of electricity must disclose their electricity portfolio with regards to energy source and environmental impact. This paper gives some examples of disclosure systems and residual electricity mixes in Norway, Sweden and Finland, compared to an approach based on a common regional disclosure. Disclosures based on the E-TRACK standard are presented, as well as the variation in CO2 emissions from different residual mixes. The results from this study clearly show that there is a need for a harmonised, transparent and reliable system for the accounting of electricity disclosure in Europe.
Differentiation of Murine Embryonic Stem Cells in Skeletal Muscles of Mice
Authors: Tian Chai , Lu Yifan , Gilbert Rénald , Karpati George
Published: June 2009

Possible myogenic differentiation of SSEA-1- and OCT-4-positive murine embryonic stem cells (ESCs) and embryoid bodies (EBs) was studied in vitro and in vivo. In vitro, ESC- or EB-derived ESCs (EBs/ESCs) showed only traces of Pax 3 and 7 expression by immunocytochemistry and Pax 3 expression by immunoblot. By RT-PCR, myogenic determinant molecules (myf5, myoD, and myogenin) were expressed by EBs/ESCs but not by ESCs. However, in such cultures, very rare contracting myotubes were still present. Suspensions of LacZ-labeled ESCs or EBs were injected into anterior tibialis muscles (ATM) of different cohorts of mice for the study of their survival and possible myogenic differentiation. The different cohorts of mice included isogenic adult 129/Sv, nonisogenic CD1 and mdx, as well as mdx immunosuppressed with 2.5 mg/kg daily injections of tacrolimus. Ten to 90 days postinjections, the injected ATM of nonisogenic mice did not contain cells positive for LacZ, SSEA-1, OCT-4, or embryonic myosin heavy chain. The ATM of intact mdx mice contained very rare examples of muscle fibers positive for dystrophin and/or embryonic myosin heavy chain. In the ATM of the isogenic normal and the immunosuppressed mdx mice, as expected, large teratomas developed containing the usual diverse cell types. In some teratomas of immunosuppressed mdx mice, small pockets of muscle fibers expressed dystrophin and myosin heavy chain. Our studies indicated that in muscles of animals nonisogenic with the used ESCs, only very rare ESCs survived with myogenic differentiation. These studies also indicated that ESCs will not undergo significant, selective, and preferential myogenic differentiation in vitro or in vivo in any of the models studied. It is probable that this strain of murine ESC requires some experimentally induced alteration of its gene expression profile to secure significant myogenicity and suppress tumorogenicity.
MR Tracking of Magnetically Labeled Mesenchymal Stem Cells in Rat Kidneys with Acute Renal Failure
Authors: Sun Jun-Hui , Teng Gao-Jun , Ju Sheng-Hong , Ma Zhan-Long , Mai Xiao-Li , Ma Ming
Published: June 2009

Stem cell transplantation is emerging as a potential treatment option for acute renal failure (ARF) because of its capability to regenerate tissues and organs. To better understand the mechanism of cell therapy, in vivo tracking cellular dynamics of the transplanted stem cells is needed. In the present study, in vivo monitored magnetically labeled mesenchymal stem cells (MSCs) were transplanted intravascularly into an ARF rat model using a conventional magnetic resonance imaging (MRI) system. Rat bone marrow MSCs were labeled with home synthesized Fe2O3-PLL, and labeled (n = 6) or unlabeled MSCs (n = 6) were injected into the renal arteries of the rats with ARF induced by the intramuscular injection of glycerol. Using the same technique, labeled MSCs were also injected into the rats assigned to a control group (n = 8). MR images of kidneys were obtained before injection of MSCs as well as immediately, 1, 3, 5, and 8 days afterwards. MR findings were analyzed and compared with histopathological and immunohistochemical results. These results showed that the rat MSCs were successfully labeled with the home synthesized Fe2O3-PLL. In both renal failure and intact rat models, the labeled MSCs demonstrated a loss of signal intensity in the renal cortex on T2*-weighted MR images, which was visible up to 8 days after transplantation. Histological analyses showed that most of the labeled MSCs that tested positive for Prussian blue staining were in glomerular capillaries, corresponding to the areas where a loss in signal intensity was observed in the MRI. A similar signal intensity decrease was not detected in the rats with unlabeled cells. These data demonstrate that the magnetically labeled MSCs in the rat model of ARF were successfully evaluated in vivo by a 1.5 T MRI system, showing that the mechanisms of stem cell therapy have great potential for future ARF treatment recipients.
Multilineage Potential of Side Population Cells from Human Amnion Mesenchymal Layer
Authors: Kobayashi M. , Yakuwa T. , Sasaki K. , Sato K. , Kikuchi A. , Kamo I. , Yokoyama Y. , Sakuragawa N.
Published: June 2009

Side population (SP) cells were isolated by FACS from a human amnion mesenchymal cell (AMC) layer soon after enzyme treatment. The yield of SP cells from AMC layer (AMC-SP cells) was about 0.1–0.2%. AMC-SP cells grew well with cell doublings of 40–80 days of culture. FACS profiles and immunocytostaining showed that AMC-SP cells were composed of two different cells immunologically: HLA I–/II- and HLA I+/II–. Oct-3/4 was detected in the nucleus of AMC-SP cells, when the culture was examined at the third, sixth, and 10th passages. RT-PCR showed that AMC-SP cells expressed the Oct-4, Sox-2, and Rex-1 genes. Immunocytochemistry revealed that all AMC-SP cells were vimentin+, CK19+, and nestin+. In addition, flow cytometry analysis showed that SP cells had high expression of CD13, CD29, CD44, CD46, CD49b, CD49c, CD49e, CD59, CD140a, and CD166 but low expression of CD 49d, and CD51. No evidence of expression was obtained for CD34, CD45, CD49a, CD56, CD90, CD105, CD106, CD117, CD133, CD271, or Flk-1. Upon appropriate differentiation protocols, AMC-SP cells differentiated to several cell lineages such as neuroectodermal, osteogenic, chondrogenic, and adipogenic cells. These results indicate that AMC-SP cells have multilineage potential to several cell lineages with unique immunological characteristics such as HLA I–/II– or HLA I+/II–. AMC-SP cells should be of considerable value for regenerative medicine because they do not induce acute rejection after allotransplantation, they do not cause ethical issues, and there is no limit of supply.
Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice
Authors: Benabdallah Basma F. , Bouchentouf Manaf , Rousseau Joel , Bigey Pascal , Michaud Annick , Chapdelaine Pierre , Scherman Daniel , Tremblay Jacques P.
Published: June 2009

Duchenne muscular dystrophy is a recessive disease due to a mutation in the dystrophin gene. Myoblast transplantation permits to introduce the dystrophin gene in dystrophic muscle fibers. However, the success of this approach is reduced by the short duration of the regeneration following the transplantation, which reduces the number of hybrid fibers. Our aim was to verify whether the success of the myoblast transplantation is enhanced by blocking the myostatin signal with an antagonist, follistatin. Three different approaches were studied to overexpress follistatin in the muscles of mdx mice transplanted with myoblasts. First, transgenic follistatin/mdx mice were generated; second, a follistatin plasmid was electroporated in mdx muscles, and finally, follistatin was induced in mdx mice muscles by a treatment with a histone deacetylase inhibitor. The three approaches improved the success of the myoblast transplantation. Moreover, fiber hypertrophy was also observed in all muscles, demonstrating that myostatin inhibition by follistatin is a good method to improve myoblast transplantation and muscle function. Myostatin inhibition by follistatin in combination with myoblast transplantation is thus a promising novel therapeutic approach for the treatment of muscle wasting in diseases such as Duchenne muscular dystrophy.
Multipotent Menstrual Blood Stromal Stem Cells: Isolation, Characterization, and Differentiation
Authors: Patel Amit N. , Park Eulsoon , Kuzman Michael , Benetti Federico , Silva Francisco J. , Allickson Julie G.
Published: June 2009

The stromal stem cell fraction of many tissues and organs has demonstrated to exhibit stem cell properties such as the capability of self-renewal and multipotency, allowing for multilineage differentiation. In this study, we characterize a population of stromal stem cells derived from menstrual blood (MenSCs). We demonstrate that MenSCs are easily expandable to clinical relevance and express multipotent markers such as Oct-4, SSEA-4, and c-kit at the molecular and cellular level. Moreover, we demonstrate the multipotency of MenSCs by directionally differentiating MenSCs into chondrogenic, adipogenic, osteogenic, neurogenic, and cardiogenic cell lineages. These studies demonstrate the plasticity of MenSCs for potential research in regenerative medicine.
Article Commentary: Tissue Engineering and Biomaterials in Regenerative Medicine
Authors: Nolan Katherine , Millet Yoann , Ricordi Camillo , Stabler Cherie L.
Published: June 2009

The field of regenerative medicine offers the potential to significantly impact a wide spectrum of healthcare issues, from diabetes to cardiovascular disease. In particular, the design of tailored biomaterials, which possess properties desired for their particular application, and the development of superior implant environments, which seek to meet the nutritional needs of the tissue, have yielded promising tissue engineering prototypes. In this commentary, we examine the novel approaches researchers have made in customized biomaterials and promoting angiogenesis that have led to significant advancements in recent years.
Improved Glucose Regulation on a Low Carbohydrate Diet in Diabetic Rats Transplanted with Macroencapsulated Porcine Islets
Authors: Vinerean Horatiu V. , Gazda Lawrence S. , Hall Richard D. , Rubin Albert L. , Barry H. Smith
Published: June 2009

Islet xenografts from porcine donors can reverse diabetes in experimental animal models and may be an alternative to human islet transplantation. We have recently reported the ability of porcine islets encapsulated in a double layer of hydrophilic agarose to maintain in vitro functional ability for >6 months. Although β-cells are capable of adapting their secretory capacity in response to glucose levels, evidence has shown that prolonged hyperglycemia can compromise this ability. The aim of the present study was to determine the effects of diet manipulation on the long-term regulation of blood glucose levels, and the preservation of functional islet in the macrobeads. Twenty-one streptozotocin-induced diabetic Wistar-Furth male rats were randomly assigned to two diets containing 64% carbohydrate (CHO) or 20% CHO. Groups of five to six animals assigned to either diet were implanted with either empty (EM) or porcine islet-containing macrobeads (PIM) and followed for 333 days. Observations included general condition, body weight, blood glucose, and food and water intakes. Monthly blood samples were collected for insulin and C-peptide analysis. The 20% CHO diet significantly lowered blood glucose values when compared with those of the 64% CHO groups for both the empty (14.94 ± 0.41 vs. 16.26 ± 0.42 mmol/L, respectively, p < 0.001) and islet macrobead recipients (12.88 ± 0.39 vs. 15.57 ± 0.85 mmol/L, respectively, p < 0.001). The different diets, however, had no statistically significant effects on the preservation of islet mass in the macrobead. Serum porcine C-peptide was detected throughout the experiment in animals receiving porcine islet macrobeads, regardless of diet. Diabetic rats fed a low carbohydrate level diet and transplanted with porcine islet macrobeads had improved total tissue glucose disposal and improved clinical parameters associated with diabetes.
Efficient Delivery of Human Single Fiber-Derived Muscle Precursor Cells via Biocompatible Scaffold
Authors: Boldrin Luisa , Malerba Alberto , Vitiello Libero , Cimetta Elisa , Piccoli Martina , Messina Chiara , Gamba Pier Giorgio , Elvassore Nicola , De Coppi Paolo
Published: June 2009

The success of cell therapy for skeletal muscle disorders depends upon two main factors: the cell source and the method of delivery. In this work we have explored the therapeutic potential of human muscle precursor cells (hMPCs), obtained from single human muscle fibers, implanted in vivo via micropatterned scaffolds. hMPCs were initially expanded and characterized in vitro by immunostaining and flow cytometric analysis. For in vivo studies, hMPCs were seeded onto micropatterned poly-lactic-glycolic acid 3D-scaffolds fabricated using soft-lithography and thermal membrane lamination. Seeded scaffolds were then implanted in predamaged tibialis anterior muscles of CD1 nude mice; hMPCs were also directly injected in contralateral limbs as controls. Similarly to what we previously described with mouse precursors cells, we found that hMPCs were able to participate in muscle regeneration and scaffold-implanted muscles contained a greater number of human nuclei, as revealed by immunostaining and Western blot analyses. These results indicate that hMPCs derived from single fibers could be a good and reliable cell source for the design of therapeutic protocols and that implantation of cellularized scaffolds is superior to direct injection for the delivery of myogenic cells into regenerating skeletal muscle.
Comparison of Human Serum with Fetal Bovine Serum for Expansion and Differentiation of Human Synovial MSC: Potential Feasibility for Clinical Applications
Authors: Tateishi K. , Ando W. , Higuchi C. , Hart D. A. , Hashimoto J. , Nakata K. , Yoshikawa H. , Nakamura N.
Published: June 2009

The aim of this study was to evaluate the effect of human serum (HS) on growth and differentiation capacity of human synovium-derived mesenchymal stem cells (MSC) in comparison to cells grown in fetal bovine serum (FBS). Human MSCs were isolated from the synovium of knee joints of three donors and the cells were cultured individually in varying concentrations of allogenic HS or FBS. Bovine MSCs were isolated from synovium and cultured in the same manner. Cell proliferation was assessed by the tetrazolium assay after passage 3. The capacity for chondrogenic and osteogenic differentiation was investigated in specific media followed by 1,9-dimethylmethylene blue assay and alcian blue staining, or by alizarin red staining, respectively. Human MSCs proliferated significantly more rapidly in the presence of HS than with equivalent levels of FBS. Chondrogenic or osteogenic differentiation occurred to nearly identical levels in HS or FBS. The results of this study indicate that HS is superior for the culture of human MSCs compared with FBS in terms of cellular expandability, without losing chondrogenic or osteogenic differentiation capacity. Coupled with the advantage in eliminating the potential risk accompanied with the use of xeno-derived materials, pooled, well-characterized HS could be a useful reagent to promote cellular expansion for clinical synovial stem cell-based therapy.
A Preliminary Gene Expression Profile of Acute Graft-Versus-Host Disease
Authors: Buzzeo Matthew P. , Yang Jie , Casella George , Reddy Vijay
Published: June 2009

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for high-risk hematological malignancies, yet a major complication associated with this therapy is acute graft-versus-host disease (GVHD). Despite a well-defined pathophysiological mechanism, there are no definitive markers for predicting acute GVHD development or progression to advanced stages. In the current study, we enrolled four acute GVHD and four acute GVHD-free recipients of allogeneic HSCT and collected peripheral blood just prior to onset of clinical acute GVHD for analysis on Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarrays. We noted significant differences in expression of 1,658 genes between control and acute GVHD patients, based on an analysis of covariance (ANCOVA) by type of transplant, a pooled error estimate, and a false discovery rate (FDR) of 10%. In conclusion, we offer the first report of a preliminary molecular signature of acute GVHD in allogeneic HSCT patients.
Improved Xenogenic Hepatocyte Implantation into Nude Mouse Liver Parenchyma with Acute Liver Failure when Followed by Repeated Anti-Fas Antibody (Jo2) Treatment
Authors: Vidal Isabelle , Blanchard Nadège , Alexandre Eliane , Gandillet Arnaud , Chenard-Neu Marie-Pierre , Staedtler Frank , Schumacher Martin , Bachellier Philippe , Jaeck Daniel , Firat Huseyin , Heyd Bruno , Richert Lysiane
Published: June 2009

Hepatocyte transplantation is a promising therapy for acute liver failure in humans. Recently, we succeeded in inducing various acute and chronic liver failures in nude mice. Engraftment of transplanted xenogeneic rat hepatocytes, visualized in the host liver by anti-MHC class I immunohistochemistry, revealed that liver repopulation was limited, and equivalent in nude mice with and without acute liver failure. In the present study, acute liver failure was induced in nude mice by a single injection of sublethal anti-Fas antibody Jo2, followed 24 h later by rat hepatocyte transplantation and than by a weekly repeated injection of Jo2. Rat hepatocyte engraftment into the recipient liver parenchyma 3 weeks following hepatocyte transplantation was about sevenfold increased when nude mice were subsequently subjected to weekly repeated Jo2 injection. Genomic analysis of these mice showed an overall transcriptome profile of upregulation of cellular cycle blocking transcripts, activation of liver injury inducing IFN-γ/STAT1 pathway, and circadian transcript signature of antiproliferative cell status compared to mice submitted to hepatocyte transplantation only. The findings of the present study suggest that the induction of cell proliferation blockade in recipient livers could promote sufficient engraftment of transplanted hepatocytes to allow transient or definitive treatment of liver failure in humans.
Riboflavin Inhibits IL-6 Expression and p38 Activation in Islet Cells
Authors: Cobianchi Lorenzo , Fornoni Alessia , Pileggi Antonello , Molano R. Damaris , Sanabria Nahir Y. , Gonzalez-Quintana Jorge , Bocca Nicola , Marzorati Simona , Zahr Elsie , Hogan Anthony R. , Ricordi Camillo , Inverardi Luca
Published: June 2009

Riboflavin is a water-soluble vitamin that reduces the production of proinflammatory mediators and oxygen radicals. Because islet β-cells are very sensitive to oxidative stress and to cytokines, we investigated the possible cytoprotective effects of riboflavin on insulinoma NIT-1 cells and on isolated rodent islets. NIT-1 cells and islets cultured in the presence or absence of 10 μM riboflavin were studied at baseline and after exposure to cytokines (TNF-α, IL-1β, INF-γ). Riboflavin treatment did not affect islet cell viability as assessed by flow cytometry for caspases activation. However, riboflavin prevented the cytokine-induced increase in IL-6 mRNA expression and p38 phosphorylation analyzed by real-time PCR and immunoassay, respectively. In summary, nontoxic doses of riboflavin prevent cytokines-induced p38 phosphorylation and IL-6 upregulation in islet cells. This observation, together with the safety profile of riboflavin in the clinical setting, makes it an appealing agent for islet cytoprotection in islet transplantation protocols.
Ex Vivo Nanofiber Expansion and Genetic Modification of Human Cord Blood-Derived Progenitor/Stem Cells Enhances Vasculogenesis
Authors: Das Hiranmoy , Abdulhameed Nasreen , Joseph Matthew , Sakthivel Ramasamy , Mao Hai-Quan , Pompili Vincent J.
Published: June 2009

The stem cell therapy for treating ischemic diseases is promising; however, the limited availability and compromised quality of progenitor cells in aged and diseased patients limit its therapeutic use. Here we report a nanofiber-based ex vivo stem cell expansion technology and proangiogenic growth factors overexpression of human umbilical cord blood (UCB)-derived progenitor cells to enhance angiogenic potential of therapeutic stem cells. The progenitor cells were expanded ~225-fold on nanofiber-based serum-free ex vivo expansion culture technique without inducing differentiation. The expanded cells express high levels of stem cell homing receptor, CXCR4, and adhesion molecule, LFA-1. The nanofiber-expanded stem cells uptake AcLDL effectively, and migrate efficiently in an in vitro transmigration assay. These expanded cells can also differentiate into endothelial and smooth muscle cells in vitro. In a NOD/SCID mouse hind limb vascular injury model, nanofiber-expanded cells were more effective in blood flow restoration and this effect was further augmented by VEGF164 and PDGF-BB, growth factor overexpression. The data indicate that nanofiber-based ex vivo expansion technology can provide an essential number of therapeutic stem cells. Additionally, proangiogenic growth factors overexpression in progenitor cells can potentially improve autologous or allogeneic stem cell therapy for ischemic diseases.
Early Translation of Adipose-Derived Cell Therapy for Cardiovascular Disease
Authors: Sanz-Ruiz Ricardo , Fernández-Santos Eugenia , Domínguez-Muñoa Marta , Parma Radoslaw , Villa Adolfo , Fernández Lucía , Sánchez Pedro L. , Fernández-Avilés Francisco
Published: June 2009

Over the past decade, cell therapy has emerged as a new approach to reversing myocardial ischemia. Several types of adult stem cells have been studied in both preclinical and clinical conditions for this purpose: bone marrow cells, circulating cells, and myoblasts. Nevertheless, the quest for the ideal “anti-ischemic” cell is still ongoing. Recently, the existence of a population of stem cells located in adipose tissue (adipose-derived stem cells) has been observed. These are able to differentiate into multiple cell lineages including cardiomyocytic differentiation. In this review we discuss the basic principles of adipose-derived stem cells (types and characteristics, harvesting, and expansion), the initial experimental studies, and the currently ongoing clinical trials.
Evaluation of a Peritoneal-Generated Cardiac Patch in a Rat Model of Heterotopic Heart Transplantation
Authors: Amir Gabriel , Miller Liron , Shachar Michal , Feinberg Micha S. , Holbova Radka , Cohen Smadar , Leor Jonathan
Published: June 2009

Tissue engineering holds the promise of providing new solutions for heart transplant shortages and pediatric heart transplantation. The aim of this study was to evaluate the ability of a peritoneal-generated, tissue-engineered cardiac patch to replace damaged myocardium in a heterotopic heart transplant model. Fetal cardiac cells (1 × 106/scaffold) from syngeneic Lewis rats were seeded into highly porous alginate scaffolds. The cell constructs were cultured in vitro for 4 days and then they were implanted into the rat peritoneal cavity for 1 week. During this time the peritoneal-implanted patches were vascularized and populated with myofibroblasts. They were harvested and their performance in an infrarenal heterotopic abdominal heart transplantation model was examined ( n = 15). After transplantation and before reperfusion of the donor heart, a 5-mm left ( n = 6) or right ( n = 9) ventriculotomy was performed and the patch was sutured onto the donor heart to repair the defect. Echocardiographical studies carried out 1–2 weeks after transplantation showed normal LV function in seven of the eight hearts studied. After 1 month, visual examination of the grafted patch revealed no aneurysmal dilatation. Microscopic examination revealed, in most of the cardiac patches, a complete disappearance of the scaffold and its replacement by a consistent tissue composed of myofibroblasts embedded in collagen bundles. The cardiac patch was enriched with a relatively large number of infiltrating blood vessels. In conclusion, cardiac patches generated in the peritoneum were developed into consistent tissue patches with properties to seal and correct myocardial defects. Our study also offers a viable rat model for screening and evaluating new concepts in cardiac reconstruction and engineering.