bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primer sets for cloning the human repertoire of T cell Receptor Variable regions
Authors: Boria Ilenia , Cotella Diego , Dianzani Irma , Santoro Claudio , Sblattero Daniele 
Published: August 2008

Abstract

Background
Amplification and cloning of naïve T cell Receptor (TR) repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V) regions are encoded by several genes that recombine during T cell development. The cloning of expressed genes as large diverse libraries from natural sources relies upon the availability of primers able to amplify as many V genes as possible.

Results
Here, we present a list of primers computationally designed on all functional TR V and J genes listed in the IMGT®, the ImMunoGeneTics information system®. The list consists of unambiguous or degenerate primers suitable to theoretically amplify and clone the entire TR repertoire. We show that it is possible to selectively amplify and clone expressed TR V genes in one single RT-PCR step and from as little as 1000 cells.

Conclusion
This new primer set will facilitate the creation of more diverse TR libraries than has been possible using currently available primer sets.
Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
Authors: Luty Agnes A , Kwok John BJ , Thompson Elizabeth M , Blumbergs Peter , Brooks William S , Loy Clement T , Dobson-Stone Carol , Panegyres Peter K , Hecker Jane , Nicholson Garth A , Halliday Glenda M , Schofield Peter R 
Published: August 2008

Abstract

Background
Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND.

Methods
Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing.

Results
Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree.

Conclusion
Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.
Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation
Authors: Lee Jae Woong , Lee Yong Kyung , Yuk Dong Yeon , Choi Dong Young , Ban Sang Bae , Oh Ki Wan , Hong Jin Tae 
Published: August 2008

Abstract

Background
Alzheimer's disease (AD) is characterized by extensive loss of neurons in the brain of AD patients. Intracellular accumulation of beta-amyloid peptide (Aβ) has also shown to occur in AD. Neuro-inflammation has been known to play a role in the pathogenesis of AD.

Methods
In this study, we investigated neuro-inflammation and amyloidogenesis and memory impairment following the systemic inflammation generated by lipopolysaccharide (LPS) using immunohistochemistry, ELISA, behavioral tests and Western blotting.

Results
Intraperitoneal injection of LPS, (250 μg/kg) induced memory impairment determined by passive avoidance and water maze tests in mice. Repeated injection of LPS (250 μg/kg, 3 or 7 times) resulted in an accumulation of Aβ1–42 in the hippocampus and cerebralcortex of mice brains through increased β- and γ-secretase activities accompanied with the increased expression of amyloid precursor protein (APP), 99-residue carboxy-terminal fragment of APP (C99) and generation of Aβ1–42 as well as activation of astrocytes in vivo. 3 weeks of pretreatment of sulindac sulfide (3.75 and 7.5 mg/kg, orally), an anti-inflammatory agent, suppressed the LPS-induced amyloidogenesis, memory dysfunction as well as neuronal cell death in vivo. Sulindac sulfide (12.5–50 μM) also suppressed LPS (1 μg/ml)-induced amyloidogenesis in cultured neurons and astrocytes in vitro.

Conclusion
This study suggests that neuro-inflammatory reaction could contribute to AD pathology, and anti-inflammatory agent could be useful for the prevention of AD.
Video self-observation: a means of improving insight in psychosis
Authors: Vikram Sitara , Yarger Nishi , Coxell Adrian , Maier Michael 
Published: August 2008

Aims and MethodTo improve the level of insight (measured using standardised instruments) using a video interview and self-observation. Changes in levels of insight were measured using the Schedule for Assessing Insight (SAI) at the time of admission, at the time of discharge (both prior to and following the viewing of the videotape) and at follow-up a few months later.ResultsThe comparison of the SAI scores indicated a significant improvement in insight at the time of discharge (P < 0.005), with a further significant improvement after watching the video (P < 0.006). This appeared to be sustained at 3- to 6-month follow-up.Clinical ImplicationsVideo self-observation is a simple, inexpensive procedure that can be used to improve insight in psychosis. This study provides further support for the clinical utility of video self-observation in improving client's insight.
Community model in treating obsessive–compulsive and body dysmorphic disorders
Authors: Drummond L. M. , Pillay A. , Kolb P. J. , Benson S. , Fogg R. , Jones-Thomas E. , Rani S. 
Published: August 2008

Aims and MethodIn November 2005, the National Institute for Health and Clinical Excellence published guidelines for the treatment of obsessive–compulsive disorder (OCD) and body dysmorphic disorder. These guidelines incorporated a stepped care approach with different interventions advised throughout the patient pathway. South West London and St George's Mental Health NHS Trust devised a system of expert clinicians with special expertise in OCD/body dysmorphic disorder to help deliver this model of care. To aid the delivery of service it was decided to operationalise the definitions of severity of OCD/body dysmorphic disorder at each of the stepped-care levels. Examples are given as to how this has been applied in practice. Outcome is presented in terms of clinical hours in the first year of operation.ResultsIn total, 108 patients were referred to the service in the first year. Many of these patients were treated by offering advice and support and joint working with the community mental health team and psychotherapy in primary care teams who had referred. Sixty-eight patients were treated by a member of the specialist service alone and 57 of these suffered from severe OCD. Outcome data from these 57 patients is presented using an intention-to-treat paradigm. They showed a clinically and statistically significant reduction in OCD symptoms after 24 weeks of cognitive–behavioural therapy comprising graded exposure and self-imposed response prevention. the mean Yale–Brown Obsessive Compulsive Scale score dropped from 28 (severe OCD) to 19 (considerable OCD). Depressive symptoms on the Beck Depression Inventory also decreased by an average 24% over the same period.Clinical ImplicationsThe feasibility of extending this model of service organisation to other areas and other diagnoses is discussed.
Part-time working in psychiatry in Northern Ireland
Authors: Donnelly Caroline , McGarry Philip , Mills Heather 
Published: August 2008

Aims and MethodTo establish the proportion of psychiatrists in Northern Ireland who currently work part-time and the proportion of those working fulltime who wish to work part-time. A postal questionnaire was forwarded to psychiatrists and repeated 30 months later.ResultsIn 2004, only 18.3% of respondents were working part-time, and 26.8% in 2006. A great majority stated their intent was to always work part-time, the most frequent reason being to achieve work–life balance.Clinical ImplicationsA significant number of staff working part-time will have implications for the staffing of the service. Policy makers must plan for the adequate provision of part-time working arrangements.
Cyclin-Dependent Kinase 5 Regulates Steroidogenic Acute Regulatory Protein and Androgen Production in Mouse Leydig Cells
Authors: Lin Ho , Chen Mei-Chih , Ku Chien-Te 
Published: August 2008

The roles of cyclin-dependent kinase 5 (Cdk5) in central nervous system and neurodegenerative diseases have been intensely investigated in recent decades. Because protein expressions of Cdk5 and its regulator, p35, have been identified in Leydig cells, it is informative to further explore the novel function of Cdk5/p35 in male reproduction. Here we show that Cdk5/p35 protein expression and kinase activity in mouse Leydig cells are regulated by human chorionic gonadotrophin (hCG) in both dose- and time-dependent manners. Blocking of Cdk5 by molecular inhibitors or small interfering RNA resulted in reduction of testosterone production by Leydig cells. cAMP, a second messenger in LH signaling, was identified as a factor in hCG-dependent regulation of Cdk5/p35. Importantly, Cdk5 protein and kinase activity could support accumulation of steroidogenic acute regulatory (StAR) protein, a crucial component of steroidogenesis. We additionally addressed the protein interaction between Cdk5/p35 and StAR. The Cdk5-dependent serine phosphorylation of StAR indicated a possible mechanism by which Cdk5 induced accumulation of StAR protein. In conclusion, Cdk5 modulates hCG-induced androgen production in mouse Leydig cells, possibly through regulation of StAR protein levels. These results indicate that Cdk5 may play an important role in male reproductive endocrinology and is a potential therapeutic target in androgen-related diseases.The physiological function of cyclin-dependent kinase 5 (Cdk5) in mouse Leydig cells is to regulate androgen production through stabilizing the steroiodogenic acute regulatory (StAR) protein.
Effects of Delayed Sample Processing and Freezing on Serum Concentrations of Selected Nutritional Indicators
Authors: Drammeh Bakary S , Schleicher Rosemary L , Pfeiffer Christine M , Jain Ram B , Zhang Mindy , Nguyen Phuong Hong 
Published: August 2008

Abstract
Background: Environmental conditions during sample processing, shipping, and storage are often suboptimal, particularly in less developed countries. We used samples from US volunteers to investigate the effects of delayed whole blood (WB) processing and delayed freezing of serum on selected nutritional indicators.
Methods: WB tubes (n = 35) were either stored at 32 °C for up to 3 days before serum separation or centrifuged within 2 h of collection; serum samples were stored at 11 °C for up to 14 days to simulate delayed shipping. We assessed analyte stability by comparing results with data from optimally prepared/stored serum samples (&lt;2 h on the clot, frozen at −70 °C) and by using clinical-acceptability criteria based on combined analytical imprecision and intraindividual biologic variability.
Results: Clinically acceptable changes in concentration varied from 3%–15%. Delayed WB processing did not unacceptably affect concentrations of carotenoids and vitamins B12, D, and E; however, we obtained clinically unacceptable changes for ferritin (+9%), soluble transferrin receptor (sTfR) (+5%), and folate (−30%) after 1 day, and for vitamin A (−10%) after 3 days. Delayed freezing of serum did not affect concentrations of ferritin, sTfR, carotenoids, and vitamins A, B12, and E; however, we obtained clinically unacceptable changes for vitamins C (−20%) and D (+7%) after 7 days and for folate after 14 days (−22%).
Conclusions: Despite substantial delays in WB processing or in the freezing of serum samples, most nutritional indicators showed remarkable stability. This information is important for both the design of field studies and the use of residual samples subjected to suboptimal preanalytical factors.
Notch Inhibition Promotes Human Embryonic Stem Cell-Derived Cardiac Mesoderm Differentiation
Authors: Jang Jiho , Ku Seung Yup , Kim Jung Eun , Choi Kyunghee , Kim Yoon Young , Kim Hee Sun , Oh Sun Kyung , Lee Eun Ju , Cho Hyun-Jai , Song Young Hwan , Lee Sang Hun , Lee Suk Ho , Suh Chang Suk , Kim Seok Hyun , Moon Shin Yong , Choi Young Min 
Published: August 2008

Abstract
The roles of Notch signaling in cardiac differentiation from murine embryonic stem cells have been well documented. We investigated whether Notch signaling plays a similar role in human embryonic stem cells (hESCs). Although, as previously reported, blocking Notch signaling via the addition of γ-secretase inhibitor (GSI) alone failed to affect hESC differentiation, we found that GSI plus reduced-volume culture medium (GSI/RVCM) accelerated mesodermal differentiation. GSI/RVCM conditions simultaneously suppressed commitment toward neuroectodermal lineages. Furthermore, sustained inhibition of Notch signaling further enhanced differentiation into cardiac mesoderm. Spontaneous beating activity was typically observed from 12 days after initiation of GSI treatment in RVCM. Moreover, hESC-derived cardiomyocytes expressed connexin 43 and possessed spontaneous calcium oscillations and cardiomyocyte beats coupled to neonatal rat cardiomyocytes when cocultured. These findings strongly suggest a distinct role for Notch signaling in the induction and specification of hESC-derived cardiac mesoderm in vitro.
Disclosure of potential conflicts of interest is found at the end of this article.
The Antitumorigenic Response of Neural Precursors Depends on Subventricular Proliferation and Age
Authors: Walzlein Joo-Hee , Synowitz Michael , Engels Boris , Markovic Darko S. , Gabrusiewicz Konrad , Nikolaev Evgeni , Yoshikawa Kazuaki , Kaminska Bozena , Kempermann Gerd , Uckert Wolfgang , Kaczmarek Leszek , Kettenmann Helmut , Glass Rainer 
Published: August 2008

Abstract
Glioblastomas, the most aggressive primary brain tumors, occur almost exclusively in adult patients. Neural precursor cells (NPCs) are antitumorigenic in mice, as they can migrate to glioblastomas and induce tumor cell death. Here, we show that the antitumor effect of NPCs is age-dependently controlled by cell proliferation in the subventricular zone (SVZ) and that NPCs accumulating at a glioblastoma are diverted from their normal migratory path to the olfactory bulb. Experimentally induced cortical glioblastomas resulted in decreased subventricular proliferation in adult (postnatal day 90) but not in young (postnatal day 30) mice. Adult mice supplied fewer NPCs to glioblastomas and had larger tumors than young mice. Apart from the difference in proliferation, there was neither a change in cell number and death rate in the SVZ nor a change in angiogenesis and immune cell density in the tumors. The ability to kill glioblastomas was similar in NPCs isolated from young and adult mice. The proliferative response of NPCs to glioblastomas depended on the expression of D-type cyclins. In young mice, NPCs express the cyclins D1 and D2, but the expression of cyclin D1 is lost during aging, and in adult NPCs only cyclin D2 remains. In young and adult cyclin D2-deficient mice we observed a reduced supply of NPCs to glioblastomas and the generation of larger tumors compared with wild-type mice. We conclude that cyclin D1 and D2 are nonredundant for the antitumor response of subventricular NPCs. Loss of a single D-type cyclin results in a smaller pool of proliferating NPCs, lower number of NPCs migrating to the tumor, and reduced antitumor activity.
Disclosure of potential conflicts of interest is found at the end of this article.
Secreted Frizzled-Related Protein-1 Enhances Mesenchymal Stem Cell Function in Angiogenesis and Contributes to Neovessel Maturation
Authors: Dufourcq Pascale , Descamps Betty , Tojais Nancy Ferreira , Leroux Lionel , Oses Pierre , Daret Daniéle , Moreau Catherine , Lamazière Jean-Marie Daniel , Couffinhal Thierry , Duplàa Cécile 
Published: August 2008

AbstractMesenchymal stem cell (MSC) transplantation offers a great angiogenic opportunity in vascular regenerative medicine. The canonical Wnt/β-catenin signaling pathway has been demonstrated to play an essential role in stem cell fate. Recently, genetic studies have implicated the Wnt/Frizzled (Fz) molecular pathway, namely Wnt7B and Fz4, in blood growth regulation. Here, we investigated whether MSC could be required in shaping a functional vasculature and whether secreted Frizzled-related protein-1 (sFRP1), a modulator of the Wnt/Fz pathway, could modify MSC capacities, endowing MSC to increase vessel maturation. In the engraftment model, we show that murine bone marrow-derived MSC induced a beneficial vascular effect through a direct cellular contribution to vascular cells. MSC quickly organized into primitive immature vessel tubes connected to host circulation; this organization preceded host endothelial cell (EC) and smooth muscle cell (SMC) recruitment to later form mature neovessel. MSC sustained neovessel organization and maturation. We report here that sFRP1 forced expression enhanced MSC surrounding neovessel, which was correlated with an increase in vessel maturation and functionality. In vitro, sFRP1 strongly increased platelet-derived growth factor-BB (PDGF-BB) expression in MSC and enhanced β-catenin-dependent cell-cell contacts between MSC themselves and EC or SMC. In vivo, sFRP1 increased their functional integration around neovessels and vessel maturation through a glycogen synthase kinase 3 beta (GSK3β)-dependent pathway. sFRP1-overexpressing MSC compared with control MSC were well elongated and in a closer contact with the vascular wall, conditions required to achieve an organized mature vessel wall. We propose that genetically modifying MSC to overexpress sFRP1 may be potentially effective in promoting therapeutic angiogenesis/arteriogenesis processes.Disclosure of potential conflicts of interest is found at the end of this article.
The Transcription Factor Zfp281 Controls Embryonic Stem Cell Pluripotency by Direct Activation and Repression of Target Genes
Authors: Wang Zheng-Xu , Teh Christina Hui-Leng , Chan Caroline Man-Yee , Chu Ci , Rossbach Michael , Kunarso Galih , Allapitchay Tahira Bee , Wong Kee Yew , Stanton Lawrence W. 
Published: August 2008

Abstract
Oct4, Sox2, and Nanog are key components of a core transcriptional regulatory network that controls the ability of embryonic stem cells to differentiate into all cell types. Here we show that Zfp281, a zinc finger transcription factor, is a key component of the network and that it is required to maintain pluripotency. Zfp281 was shown to directly activate Nanog expression by binding to a site in the promoter in very close proximity to the Oct4 and Sox2 binding sites. We present data showing that Zfp281 physically interacts with Oct4, Sox2, and Nanog. Chromatin immunoprecipitation experiments identified 2,417 genes that are direct targets for regulation by Zfp281, including several transcription factors that are known regulators of pluripotency, such as Oct4, Sox2, and Nanog. Gene expression microarray analysis indicated that some Zfp281 target genes were activated, whereas others were repressed, upon knockdown of Zfp281. The identification of both activation and repression domains within Zfp281 suggests that this transcription factor plays bifunctional roles in regulating gene expression within the network.
Disclosure of potential conflicts of interest is found at the end of this article.
A Role for SPE in Meeting Vital Human Needs
Authors: Ebenhack Mary Jeanette , Ebenhack Ben W. 
Published: August 2008

Abstract
Twenty years ago an effort was mounted at the Frederick Douglass Institute for African and Africa-American Studies at the University of Rochester, USA, based on the idea that energy had a critical role to play in assisting developing nations overcome the scourge of poverty. What became the AHEAD Energy Corporation also proposed that locally-available hydrocarbons, especially natural gas, could ignite rapid development.
Although "AHEAD" was an acronym that stood for Access to Hydrocarbon Energy for African Development, it is perhaps serendipitous that these ideas could rightly be said to have been ahead of their time. Until recently, energy's role in development has not been understood. Whereas it is easy for the common person to recognize the need for food, water, housing, education and medical care, it has required long arduous efforts to get international development aid professionals to grasp the idea that energy is perhaps the primary key to economic and social development.

Energy: the invisible need
Energy does not directly feed, house, or clothe people. But energy services facilitate the production of food, construction materials, and textiles. The "causal chain" leading from energy resources to improvements in people's lives can be long and complex, requiring many other non-energy inputs.1 Moreover, energy services often bring improvements in several areas at once. For example, consider all the uses to which electric power can be directed: lighting, refrigeration, communication, use of appliances, cooking, space heating and cooling, and even transportation.
Genetic structure of the Anthyllis vulneraria L. s. l. species complex in Estonia based on AFLPs
Authors: Köster Egle , Bitocchi Elena , Papa Roberto , Pihu Silvia 
Published: August 2008

Abstract
Anthyllis vulneraria L. (Fabaceae) s. lato includes many cryptic taxa, ranging from 25 to 60 subspecies according to different authors. The delimitation of intraspecific taxa of A. vulneraria s. lato has always been complicated and inconsistent. Different data sets (multivariate analyses of morphological variation, allozymes, chloroplast SSRs and ITS) have not resolved the existing problem with distinguishing some subspecies. We used the amplified fragment length polymorphism (AFLP) analysis to describe the differentiation in this species complex and to characterize variation on a geographic scale. Some correlation was found between genetic variability and geographic distribution (western-eastern directional variation), but AFLP data analysis did not reveal clear intraspecific structure of the seven analysed taxa. The analysed specimens did not comprise groups correlated with the subspecies.