bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conceptual and practical considerations for material and data sharing in stem cell research
Authors: Kato Kazuto 
Published: March 2012

AbstractRapid development in the stem cell field, particularly in the field of pluripotent stem cells, resulted in the establishment of many cell lines, including those of ES cells and iPS cells. Some cell lines were made with the help of public funding while others with private money. The way stem cells are used also varies depending on the purpose of the types of research or medical applications. Regardless of the source of funding or the way cells are used, one important question is how to decide policies for sharing materials and data.On one hand, to accelerate innovation and commercialization, one may need to admit that obtaining IPs and not sharing research materials and data need to be prioritized for researchers and companies. On the other hand, to facilitate overall research activities and speed up medical innovation, one can say that sharing materials and data should be encouraged by researchers and even by the business sector.Regarding the latter view, we can learn some lessons from genome research areas, where notions of equity, justice and benefit sharing have been emphasized throughout the history of the field. One well-known example is Bermuda principle formulated in 1996. The principle declared that genome sequence data in the Human Genome Project (HGP) should be released into the public domain as soon as data is produced. One reason behind the principle was to emphasize that human genome data should not be privately owned by a few, but needs to be utilized by all of the researchers around the world. Another reason is a kind of moral consideration – human genome research should give benefit to the people of the society where advanced biomedical science cannot be conducted. The concept has been inherited in many subsequent research activities and has become a basic norm for genome research areas. I would like to argue that stem cell research community needs to learn the same notion of sharing and to pay attention to the concept of global equity and benefit sharing. Moreover, to actually facilitate sharing of materials and data, various points need to be considered. For example, informed consent that enables sharing of cells and data should be obtained. I will talk about conceptual reasoning as well as practical points to facilitate material and data sharing in the stem cell field.
Secreted Noncoding RNAs and Therapeutic Neural Stem Cell Plasticity
Authors: Pluchino Stefano 
Published: March 2012

AbstractCompelling evidence exists that somatic stem cell-based therapies protect the central nervous system (CNS) from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS) and cerebral ischemic/hemorrhagic stroke. However, while it was first assumed that stem cells may act through direct replacement of lost/damaged cells, it has now become clear that they are able to protect the damaged nervous system through a number of ‘bystander’ mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke – both in rodents and non-human primates – others and we have shown that transplanted neural stem/precursor cells (NPCs) possess a constitutive and inducible ability to mediate efficient ‘bystander’ myelin repair and axonal rescue. Yet a comprehensive understanding of the multiple mechanisms by which NPCs exert their therapeutic impact is lacking. We envisage that the remarkable therapeutic plasticity of NPCs results from their capacity to engage highly sophisticated programmes of horizontal cell-to-cell communication at the level of the (micro) environment and we attribute a key role to the transfer of secreted membrane vesicles (MVs) from (donor) NPCs to (recipient) neighbouring cells. We are starting to define whether this form of communication is biologically relevant for NPCs, and look forward to establishing whether it is associated to cell-to-cell trafficking of non-coding RNAs (ncRNAs), and indeed on elucidating its molecular signature and therapeutic significance for MS. We believe that the true innovation of this approach relies in its unique peculiarity to look into an innate cellular mechanism with the visionary focus of translating the knowledge of basal stem cell functions into innovative high-impact clinical therapeutics for MS.
Subependymal zone stem cells and progenitor migration to brain injuries: a critical analysis
Authors: Szele Francis 
Published: March 2012

AbstractAdult neurogenesis in mammals was rediscovered over twenty years ago and has generated a huge amount of interest as a developmental biology system to study stem cells, proliferation, fate determination and migration. It has also raised hope that these cells may be harnessed to help repair brain injury and disease. Indeed subependymal zone (SEZ) progenitors actively migrate to brain injuries and help replace dead cells and provide protective trophic support. Whereas human neurogenesis after infancy is quite minimal it seems to increase after most degenerative brain diseases. I will argue that more post mortem examination of human neurogenesis is needed. I will also present data from my laboratory that has shown the epidermal growth factor receptor and galectin-3 both modulate migration of SEZ cells. These and other molecular mechanisms may be manipulated to increase the reparative response. We are examining SEZ migration with 2-Photon time-lapse microscopy a technique which allows high temporal spatial resolution of dynamic events. This is helping us discern the natural history of these fascinating tissue specific stem and progenitor cells. We believe this is essential for the field to develop their potential clinical use.
Establishing a Legal Foundation for Public Oversight of Clinical Trials
Authors: Frankel Mark 
Published: March 2012

AbstractPublic (government) oversight reflects the way society perceives and responds to risk, which is intrinsic to the conduct of experimental research. Such oversight typically takes the form of regulation, which combines organizations, rules and sanctions intended to produce desired behaviors in support of clear objectives. Ensuring a rigorous clinical trial process that also offers proper protections of research subjects requires a legal framework that features the following qualities: (1) must act, and be seen to act, in the public interest; (2) comprised of clear and explicit objectives and requirements; (3) fairness in its application and enforcement; (4) based on dialogue among regulators, the regulated community, and the beneficiaries of regulation; (5) sustains public confidence and trust; and (6) is more likely than other options to achieve its goals. While these features will be applied to stem cell clinical trials, they are also relevant in other areas where science and technology are perceived as posing risks to individuals and/or the larger society.
What We Need in the GCC States to Catch-up with Evolving Stem Cell and Regenerative Medicine Research
Authors: Al Othman Saleh Fahed 
Published: March 2012

AbstractEvery year we witness the introduction of new drugs and medical technologies that improve the health and lives of individuals around the world. Stem cell research holds an awesome potential for restructuring the way we practise medicine. One day, stem cell researches will dramatically alter the way we treat diseases.Since the first human ES cell lines were derived more than a decade ago, hundreds have been created worldwide, including lines suitable for clinical application. As such, it involves questions of ethics that are commonly raised in research, such as preserving research integrity and the use of human tissue and animals in research. Moreover, there is much to be investigated about the specific characteristics of stem cells and about the efficacy and safety of the new drugs based on this type of cells, both embryonic and adult stem cells, for several therapeutic indications. The current reality is that, although extensive researches are ongoing and encouraging partial results are being achieved, there is still much to do in the GCC states to orchestrate the stem cell and regenerative medicine research.
Attachment of Embryonic Stem Cells-derived Cardiomyocytes in Cultispher-S Microcarriers by using Spinner flask
Authors: Akasha Abdulrhaman Ahmed 
Published: March 2012

AbstractEmbryonic Stem cells have the ability to differentiate under in vitro conditions into cardiomyocytes. A transgenic α-myosin heavy chain (α-MHC+) ES cell line was generated, exhibiting puromycin resistance and expressing enhanced green fluorescent protein (EGFP) under control of the α-MHC+ promoter. A puromycin-resistant, EGFP-positive α-MHC+ cardiomyocyte population was isolated with over 92 percent purity.The cultivation of these cardiomyocytes, in macroporous gelatine microsphere beads in a spinner flask bioreactor has been studied. The average number of cultivated cells per microsphere was optimised after we specified the most suitable agitation conditions and the optimal time frames of cultivation. Our study shows that 80 percent of microspheres were colonised by cardiomyocytes under optimal conditions. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to show that the population of the beads was not limited to the microcarrier surface, but some cells invaded the inner surfaces of the microspheres as well. The present findings demonstrate the successful culture of α-MHC+ cardiomyocytes in macroporous biodegradable microcarriers while maintaining the typical morphological and electrophysiological properties of cardiomyocytes. Our perspective significantly improves survival of grafted cardiomyocytes and thus helps to overcome current limitations of cell replacement approaches
Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra
Authors: Marei Hany , Althani Asma , Afifi Nahla , Michetti Fabricio , Pescatori Mario , Pallini Roberto , Casalbore Patricia , Cenciarelli Carlo , Schwartz Philip , Ahmed Abd-Elmaksoud 
Published: March 2012

AbstractNeural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation.The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells.
Mechanotransduction Modulates the Effect of Mechanical Forces (fluid shear stress and cyclic strain) on Embryonic Stem Cell Differentiation toward Vascular Endothelial and Smooth Muscle Cells
Authors: Nikmanesh Maria , Shi Zhong-Dong , Tarbell John 
Published: March 2012

AbstractIt has been shown that shear stress plays a critical role in promoting endothelial cell (EC) differentiation from embryonic stem cell (ESC)-derived ECs. However, the underlying mechanisms mediating shear stress effects in this process have yet to be investigated. It has been reported that the glycocalyx component heparan sulfate proteoglycan (HSPG) mediates shear stress mechanotransduction in mature EC.In this study, we investigated whether cell surface HSPG plays a role in shear stress modulation of EC phenotype. ESC-derived EC were subjected to shear stress (5 dyn/cm(2) ) for 8h with or without heparinase III (Hep III) that digests heparan sulfate. Immunostaining showed that ESC-derived EC surfaces contain abundant HSPG, which could be cleaved by Hep III. We observed that shear stress significantly increased the expression of vascular EC-specific marker genes (vWF, VE-cadherin, PECAM-1. The effect of shear stress on expression of tight junction protein genes (ZO-1, OCLD, CLD5) was also evaluated. Shear stress increased the expression of ZO-1 and CLD5, while it did not alter the expression of OCLD. Shear stress increased expression of vasodilatory genes (eNOS, COX-2), while it decreased the expression of the vasoconstrictive gene ET1. After reduction of HSPG with Hep III, the shear stress-induced expression of vWF, VE-cadherin, ZO-1, eNOS, and COX-2, were abolished, suggesting that shear stress-induced expression of these genes depends on HSPG. These findings indicate for the first time that HSPG is a mechanosensor mediating shear stress-induced EC differentiation from ESC-derived EC cells.
Comprehensive Transcriptome and Proteome Analysis of Human Embryonic Stem Cells Differentiation to Neural Cells
Authors: Salekdeh Ghasem Hosseini 
Published: March 2012

AbstractHuman embryonic stem cells (hESCs) are pluripotent cells capable of differentiating into other cell lineages in vivo. Global gene expression analysis of hESCs that differentiate into neural cells would help to further define the molecular mechanisms involved in neurogenesis in humans. We performed a comprehensive transcriptome and proteome analysis of hESC differentiation at three different stages: early neural differentiation, neural ectoderm and differentiated neurons. We identified and validated time-dependent gene expression patterns and showed that the gene expression patterns reflect early ESC differentiation. Sets of genes are induced in primary ectodermal lineages and then in differentiated neurons, constituting consecutive waves of known and novel genes. Pathway analysis revealed dynamic expression patterns of members of several signaling pathways, including NOTCH, mTOR and Toll like receptors (TLR), during neural differentiation. Owing to comparative proteomics and transcriptomics analyses, novel genes involved in proliferation of rosette cells, fate specification and neural differentiation were identified. Functional analysis with RNAi figured up that suppression of a protein involved in mRNA processing, MAGOHB, enhanced the neural differentiation of hESCs. Collectively, these results enhance our understanding of the molecular dynamics underlying neural commitment and differentiation.
Selected Common Diagnostic Problems in Urologic Pathology: Perspectives From a Large Consult Service in Genitourinary Pathology
Authors: Brimo Fadi , Epstein Jonathan I. 
Published: March 2012

Context.—Several common differential diagnoses are encountered in urologic pathology, frequently causing patient referrals for a second opinion.Objectives.—To review 3 common differential diagnoses encountered in a large consultation service in genitourinary pathology, including partial atrophy versus prostatic acinar adenocarcinoma, oncocytoma versus chromophobe renal cell carcinoma, and urothelial carcinoma in situ versus normal urothelium and reactive atypia. We will discuss the detailed, morphologically distinctive features and the usefulness of immunohistochemistry.Data Sources.—Personal experience and review of the current literature.Conclusions.—Careful morphologic assessment and awareness of diagnostic pitfalls are fundamental in reaching a definitive diagnosis in most cases. Immunohistochemistry is useful but should be used only in conjunction with the morphologic impression.
Emerging Critical Role of Molecular Testing in Diagnostic Genitourinary Pathology
Authors: Netto George J. , Cheng Liang 
Published: March 2012

Context.—The unprecedented advances in cancer genetics and genomics are rapidly affecting clinical management and diagnostics in solid tumor oncology. Molecular diagnostics is now an integral part of routine clinical management in patients with lung, colon, and breast cancer. In sharp contrast, molecular biomarkers have been largely excluded from current management algorithms of urologic malignancies.Objective.—To discuss promising candidate biomarkers that may soon make their transition to the realm of clinical management of genitourologic malignancies. The need for new treatment alternatives that can improve upon the modest outcome so far in patients with several types of urologic cancer is evident. Well-validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management are lacking. Identifying robust predictive biomarkers that will stratify response to emerging targeted therapeutics is another crucially needed development. A compiled review of salient studies addressing the topic could be helpful in focusing future efforts.Data Sources.—A PubMed (US National Library of Medicine) search for published studies with the following search terms was conducted: molecular, prognostic, targeted therapy, genomics, theranostics and urinary bladder cancer, prostate adenocarcinoma, and renal cell carcinoma. Articles with large cohorts and multivariate analyses were given preference.Conclusions.—Our recent understanding of the complex molecular alterations involved in the development and progression of urologic malignancies is yielding novel diagnostic and prognostic molecular tools and opening the doors for experimental targeted therapies for these prevalent, frequently lethal solid tumors.
Role of Immunohistochemistry in Diagnosing Renal Neoplasms: When Is It Really Useful?
Authors: Shen Steven S. , Truong Luan D. , Scarpelli Marina , Lopez-Beltran Antonio 
Published: March 2012

Context.—With the refinement of molecular and histologic classifications of renal neoplasms and the availability of more-effective molecular targeted therapy for specific renal neoplasms, immunohistochemical techniques will play an increasingly important role in the diagnosis of renal neoplasm. During the past few decades, many markers have been evaluated for their role in the diagnosis, prognosis, and prediction of treatment for renal neoplasms. The number of useful markers in our routine practice continues to increase. The challenge will be to choose among them and to decide in which situations immunohistochemistry will be truly useful.Objectives.—To review the diagnostic utility of molecular markers for renal neoplasms and common diagnostic scenarios that call for immunohistochemistry in routine practice.Data Sources.—This review is based on published literature and personal experience.Conclusions.—Some of the most important and useful markers for the diagnosis of renal neoplasm include cytokeratins, vimentin, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, α-methylacyl coenzyme A racemase, CD117, TFE3, thrombomodulin, uroplakin III, p63, CD57, and carbonic anhydrase IX. Each marker has its diagnostic role in a specific diagnostic setting. The common diagnostic situations that call for immunohistochemical staining are differential diagnoses of renal versus nonrenal neoplasms, histologic subtyping of renal cell carcinoma, diagnosis of rare primary renal neoplasms, diagnosis of renal neoplasms in small core-biopsy specimens, diagnosis of possible metastatic renal carcinomas, and less frequently, molecular prognostication.
Spectrum of Preneoplastic and Neoplastic Cystic Lesions of the Kidney
Authors: Chen Ying-Bei , Tickoo Satish K. 
Published: March 2012

Context.—Cystic lesions of the kidney may be accompanied by a range of neoplasms with distinct prognoses and future risks of developing additional tumors. In addition, some renal tumors, with or without accompanying renal cysts, may show a prominent cystic component. In the adult population, neoplasms occurring in a background of renal cystic diseases and cystic renal neoplasms often pose diagnostic challenges because of their many overlapping features.Objective.—To review the clinicopathologic characteristics of common entities in the spectrum of neoplastic and potential preneoplastic cystic lesions encountered in adults, with an emphasis on renal cystic diseases associated with tumor development and on renal neoplasms with predominantly cystic morphology.Data Sources.—The relevant English-language literature was reviewed, accompanied by the authors' experience at their practicing institution.Conclusions.—The presence of multiple renal cysts, both acquired and syndromic, can be associated with a variety of renal tumors. The morphology of the cysts and associated tumor types can help predict the genetic or acquired basis of the lesions, and particularly in specimens with no accompanying pertinent clinical history, such potential associations should be suggested in surgical pathology reports.
Phosphine‐Catalyzed [3+2] and [4+3] Annulation Reactions of C,N‐Cyclic Azomethine Imines with Allenoates
Authors: Jing Chengfeng , Na Risong , Wang Bo , Liu Honglei , Zhang Lei , Liu Jun , Wang Min , Zhong Jiangchun , Kwon Ohyun , Guo Hongchao 
Published: March 2012

AbstractPhosphine‐catalyzed [3+2] and [4+3] annulation reactions of C,N‐cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two distinct reaction pathways, [3+2] and [4+3] cyclization, depend on the nature of the nucleophilic phosphine and the allenoate. Generally, for α‐alkylallenoates, the reactions always proceed with [3+2] cyclization as the major pathway no matter what phosphine was used; for α‐ArCH2‐substituted allenoates, the reaction pathway was controlled by the phosphine catalyst used.
Click Functionalization of Gold Nanoparticles Using the Very Efficient Catalyst Copper(I) (Hexabenzyl)tris(2‐aminoethyl)‐ amine Bromide
Authors: Zhao Pengxiang , Grillaud Maxime , Salmon Lionel , Ruiz Jaime , Astruc Didier 
Published: March 2012

AbstractWhereas previous “click” functionalization (Huisgen‐type copper‐catalyzed alkyne‐azide cycloaddition, CuAAC) of various gold nanoparticles (AuNP) had systematically proven to be very difficult, tedious, providing low yields with the use of high amounts of copper sulfate+sodium ascorbate – the classic Sharpless catalyst, the new catalyst copper(I) (hexabenzyl)tris(2‐aminoethyl)amine bromide, {[Cu(I)(Hexabenzyl)Tren]Br} is shown here to be very efficient for the introduction of a large variety of organic, organometallic, dendronic and polymeric molecular fragments of various sizes, topologies and hydrophilicities. Indeed, 0.1–0.15 equiv. of this catalyst in toluene was used in each reaction under ambient conditions for 8 to 48 h with good yields without AuNP aggregation. The new functional AuNP have been characterized by 1H NMR, IR and UV‐vis. (plasmon band) spectroscopy, cyclic voltammetry (CV), dynamic light scattering (DLS) and transmission electron microscopy (TEM).