bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between MRI T1rho value and histological findings of intact and radially incised menisci in microminipigs
Authors: Nakagawa Yusuke , Sekiya Ichiro , Kondo Shimpei , Tabuchi Takashi , Ichinose Shizuko , Koga Hideyuki , Tsuji Kunikazu , Muneta Takeshi 
Published: July 2015

PurposeTo examine whether the T1rho value reflects histological changes in menisci we analyzed the relationship between T1rho value and histological findings in intact and radially incised menisci of pigs.Materials and MethodsSeven microminipigs were used for this experiment. A radial incision was created and repaired in the medial meniscus, which was evaluated 4 weeks after surgery. Sagittal T1rho mapping images were taken by 3.0T magnetic resonance imaging (MRI). The region of interest was set by dividing the meniscus into six zones (from zone 1 to zone 6). For histological evaluation of intact menisci, characteristics of each zone were determined. In incised menisci, a histological score was used to evaluate pathological change.ResultsIn intact lateral menisci, the zone where histological findings indicated fibrocartilage showed a lower T1rho value (34.2 ± 2.3 msec) than hyaline‐like cartilage (38.2 ± 2.5 msec) or fibrous tissue (37.2 ± 2.0 msec). In incised medial menisci, T1rho values increased (about 50–90 msec) in the zone where histological findings indicated that synovial ingrowth, scar tissue formation, and degenerative changes had occurred. There were correlations between T1rho values and histological scores in all zones (r = 0.62–0.92, P = 0.001–0.026).ConclusionZonal variations of the T1rho value were observed in intact menisci due to varying structure in each zone. T1rho values were correlated with histological changes such as collagen fiber organization and safranin‐o stainability in incised menisci. This study supports T1rho mapping as useful for evaluating ultrastructural composition in menisci. J. Magn. Reson. Imaging 2016;43:434–445.
Longitudinal study of the substantia nigra in Parkinson disease: A high‐field 1H‐MR spectroscopy imaging study
Authors: Seraji‐Bozorgzad Navid , Bao Fen , George Edwin , Krstevska Shana , Gorden Veronica , Chorostecki Jessica , Santiago Carla , Zak Imad , Caon Christina , Khan Omar 
Published: July 2015

AbstractIntroductionThe value of biomarkers in early diagnosis and development of therapeutics in Parkinson's disease (PD) is well established.MethodsWe used proton magnetic resonance spectroscopy in a prospective, longitudinal study of 23 patients with early PD, naïve to dopaminergic therapy, and six age‐matched healthy controls to examine the temporal changes in metabolic profile of substantia nigra over a period of 3 months.ResultsN‐acetyl aspartate to creatine ratio at month 3 was compared with baseline values in the PD and control groups, as well as the side‐to‐side difference of the ratio at baseline. By month 3, n‐acetyl aspartate to creatine ratio had decreased by 4.4% in patients with PD (P = 0.024), without a concomitant change in healthy controls. The side‐to‐side asymmetry was significantly higher in the PD group (16.7%) vs. healthy controls (1.6%, P = 0.0024).ConclusionEstimation of change in the n‐acetyl aspartate to creatine ratio appears to be a fast, quantifiable, and reliable marker of dopaminergic neuronal viability in PD. © 2015 International Parkinson and Movement Disorder Society
A Rebuttal to Comments on ‘Sacrifice of the Social Outsider’
Authors: Kieffer C. L. 
Published: July 2015

AbstractA recent publication by the author documented two probable cases of Klippel–Feil Syndrome at the site of Midnight Terror Cave in the Cayo District of Belize. Radiographic images recently taken of the multiple congenital fused vertebrae from these two individuals raised discussion regarding the initial assessment of Klippel–Feil Syndrome. This commentary further discusses the topic by dealing with researcher assumptions of the syndrome and indicates radiographic data do not provide enough evidence to change the initial assessment. Copyright © 2015 John Wiley & Sons, Ltd.
The perilous leap between exploration and exploitation
Authors: Swift Tim 
Published: July 2015

Research summary: R&D‐based exploration and exploitation are necessary in order for firms to have sustainable competitive advantage. Yet, transitioning between these orthogonal types of R&D is considered profound organizational change. Building on recent research showing that compact, significant changes in R&D expenditure is an antecedent to the transition between explorative and exploitative R&D, I show that this leap between exploration and exploitation is quite hazardous. The magnitude of changes in R&D expenditure, whether increases or decreases, is positively associated with organizational failure. Firms maintaining higher levels of absorptive capacity are more capable of surviving the leap from R&D‐based exploitation to exploration, and firms that do not use reductions in R&D expenditure to manipulate short‐term earnings performance are more likely to survive the leap from exploration to exploitation.Managerial summary: In order to survive and thrive, innovative companies must be able to exploit their existing competencies, and to explore for new ones once those current competencies decline in value. However, transiting from one form of innovation to the other is difficult because the skills required to explore are fundamentally opposed to those required to exploit. In this article, I describe how difficult this leap between exploration and exploitation can be. I show that the move between R&D‐based exploration and exploitation is related to organizational failure. In addition, firms that are superior learners are more likely to survive the leap from exploitation to exploration, and firms that are not cutting R&D expenditure to manipulate earnings are more likely to survive the leap from exploration to exploitation. Copyright © 2015 John Wiley & Sons, Ltd.
Concise Review: Patient-Derived Stem Cell Research for Monogenic Disorders
Authors: Qin Yiren , Gao Wei-Qiang 
Published: July 2015

Abstract
Monogenic disorders (MGDs) are caused by a single gene mutation and have a serious impact on human health. At present, there are no effective therapeutic methods for MGDs. Stem cell techniques provide insights into potential treatments for MGDs. With the development of patient-derived stem cells, we can begin to progressively understand the molecular mechanism of MGDs and identify new drugs for MGD treatment. Using powerful genome editing tools, such as zinc finger nucleases, transcriptional activator-like effector nucleases, and the clustered regulatory interspaced short palindromic repeat/Cas9 system, MGD-associated gene mutations can be corrected in MGD stem cells in vitro and then transplanted into MGD animal models to assess their safety and therapeutic effects. Despite the continued challenges surrounding potential pluripotent stem cell tumorigenicity and concerns regarding the genetic modification of stem cells, the extensive clinical application of MGD patient-specific stem cells will be pursued through further advances in basic research in the MGD field. In this review, we will summarize the latest progress in research into the use of patient-derived stem cells for the potential treatment of MGDs and provide predictions regarding the direction of future investigations.
In Vitro T-Cell Generation From Adult, Embryonic, and Induced Pluripotent Stem Cells: Many Roads to One Destination
Authors: Smith Michelle J. , Webber Beau R. , Mohtashami Mahmood , Stefanski Heather E. , Zún˜iga-Pflücker Juan Carlos , Blazar Bruce R. 
Published: July 2015

Abstract
T lymphocytes are critical mediators of the adaptive immune system and have the capacity to serve as therapeutic agents in the areas of transplant and cancer immunotherapy. While T cells can be isolated and expanded from patients, T cells derived in vitro from both hematopoietic stem/progenitor cells (HSPCs) and human pluripotent stem cells (hPSCs) offer great potential advantages in generating a self-renewing source of T cells that can be readily genetically modified. T-cell differentiation in vivo is a complex process requiring tightly regulated signals; providing the correct signals in vitro to induce T-cell lineage commitment followed by their development into mature, functional, single positive T cells, is similarly complex. In this review, we discuss current methods for the in vitro derivation of T cells from murine and human HSPCs and hPSCs that use feeder-cell and feeder-cell-free systems. Furthermore, we explore their potential for adoption for use in T-cell-based therapies. Stem Cells 2015;33:3174–3180
Autocrine Action of Thrombospondin-2 Determines the Chondrogenic Differentiation Potential and Suppresses Hypertrophic Maturation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells
Authors: Jeong Sang Young , Ha Jueun , Lee Miyoung , Jin Hye Jin , Kim Dong Hyun , Choi Soo Jin , Oh Wonil , Yang Yoon Sun , Kim Jae-Sung , Kim Byung-Gyu , Chang Jeong Ho , Cho Dong-Hyung , Jeon Hong Bae 
Published: July 2015

AbstractPrevious studies have shown that mesenchymal stem cell (MSC)-based therapies have varying efficacies for the treatment of various diseases, including cartilage defects. In this study, we demonstrated that the chondrogenic differentiation potential of human umbilical cord blood-derived MSCs (hUCB-MSCs) obtained from different individual donors varies, and we investigated the molecular basis for this variation. Microarray gene expression analysis identified thrombospondin-2 (TSP2) as a candidate gene underlying the interindividual variation in the chondrogenic differentiation potential of hUCB-MSCs. To assess the association between TSP-2 and the differentiation potential, we evaluated chondrogenic differentiation of hUCB-MSCs treated with TSP2 siRNA. In addition, we studied the effect of supplementing exogenous recombinant TSP-2 on TSP2 siRNA-treated hUCB-MSCs. We found that TSP-2 autocrinally promoted chondrogenic differentiation of hUCB-MSCs via the Notch signaling pathway, which was confirmed in MSCs from other sources such as bone marrow and adipose tissue. Interestingly, we observed that TSP-2 attenuated hypertrophy, which inevitably occurs during chondrogenic differentiation of hUCB-MSCs. Our findings indicated that the variable chondrogenic differentiation potential of MSCs obtained from different donors is influenced by the TSP-2 level in the differentiating cells. Thus, the TSP-2 level can be used as a marker to select MSCs with superior chondrogenic differentiation potential for use in cartilage regeneration therapy. Stem Cells 2015;33:3291–3303
Negative Regulation of miR-375 by Interleukin-10 Enhances Bone Marrow-Derived Progenitor Cell-Mediated Myocardial Repair and Function After Myocardial Infarction
Authors: Garikipati Venkata Naga Srikanth , Krishnamurthy Prasanna , Verma Suresh Kumar , Khan Mohsin , Abramova Tatiana , Mackie Alexander R. , Qin Gangjian , Benedict Cynthia , Nickoloff Emily , Johnson Jennifer , Gao Ehre , Losordo Douglas W. , Houser Steven R. , Koch Walter J. , Kishore Raj 
Published: July 2015

Abstract
Poor survival and function of transplanted cells in ischemic and inflamed myocardium likely compromises the functional benefit of stem cell-based therapies. We have earlier reported that co-administration of interleukin (IL)−10 and BMPAC enhances cell survival and improves left ventricular (LV) functions after acute myocardial infarction (MI) in mice. We hypothesized that IL-10 regulates microRNA-375 (miR-375) signaling in BMPACs to enhance their survival and function in ischemic myocardium after MI and attenuates left ventricular dysfunction after MI. miR-375 expression is significantly upregulated in BMPACs upon exposure to inflammatory/hypoxic stimulus and also after MI. IL-10 knockout mice display significantly elevated miR-375 levels. We report that ex vivo miR-375 knockdown in BMPAC before transplantation in the ischemic myocardium after MI significantly improve the survival and retention of transplanted BMPACs and also BMPAC-mediated post-infarct repair, neovascularization, and LV functions. Our in vitro studies revealed that knockdown of miR-375-enhanced BMPAC proliferation and tube formation and inhibited apoptosis; over expression of miR-375 in BMPAC had opposite effects. Mechanistically, miR-375 negatively regulated 3-phosphoinositide-dependent protein kinase-1 (PDK-1) expression and PDK-1-mediated activation of PI3kinase/AKT signaling. Interestingly, BMPAC isolated from IL-10-deficient mice showed elevated basal levels of miR-375 and exhibited functional deficiencies, which were partly rescued by miR-375 knockdown, enhancing BMPAC function in vitro and in vivo. Taken together, our studies suggest that miR-375 is negatively associated with BMPAC function and survival and IL-10-mediated repression of miR-375 enhances BMPAC survival and function. Stem Cells 2015;33:3519–3529
Transcriptome Dynamics of Developing Photoreceptors in Three-Dimensional Retina Cultures Recapitulates Temporal Sequence of Human Cone and Rod Differentiation Revealing Cell Surface Markers and Gene Networks
Authors: Kaewkhaw Rossukon , Kaya Koray Dogan , Brooks Matthew , Homma Kohei , Zou Jizhong , Chaitankar Vijender , Rao Mahendra , Swaroop Anand 
Published: July 2015

Abstract
The derivation of three-dimensional (3D) stratified neural retina from pluripotent stem cells has permitted investigations of human photoreceptors. We have generated a H9 human embryonic stem cell subclone that carries a green fluorescent protein (GFP) reporter under the control of the promoter of cone-rod homeobox (CRX), an established marker of postmitotic photoreceptor precursors. The CRXp-GFP reporter replicates endogenous CRX expression in vitro when the H9 subclone is induced to form self-organizing 3D retina-like tissue. At day 37, CRX+ photoreceptors appear in the basal or middle part of neural retina and migrate to apical side by day 67. Temporal and spatial patterns of retinal cell type markers recapitulate the predicted sequence of development. Cone gene expression is concomitant with CRX, whereas rod differentiation factor neural retina leucine zipper protein (NRL) is first observed at day 67. At day 90, robust expression of NRL and its target nuclear receptor NR2E3 is evident in many CRX+ cells, while minimal S-opsin and no rhodopsin or L/M-opsin is present. The transcriptome profile, by RNA-seq, of developing human photoreceptors is remarkably concordant with mRNA and immunohistochemistry data available for human fetal retina although many targets of CRX, including phototransduction genes, exhibit a significant delay in expression. We report on temporal changes in gene signatures, including expression of cell surface markers and transcription factors; these expression changes should assist in isolation of photoreceptors at distinct stages of differentiation and in delineating coexpression networks. Our studies establish the first global expression database of developing human photoreceptors, providing a reference map for functional studies in retinal cultures. Stem Cells 2015;33:3504–3518
Azide Chemistry – An Inorganic Perspective, Part II[‡][3+2]‐Cycloaddition Reactions of Metal Azides and Related Systems
Authors: Fehlhammer Wolf Peter , Beck Wolfgang 
Published: July 2015

AbstractIn whatever state of bonding – whether covalent to an organic residue or a heteroatom, or polar to ionic in contact with a metal – the azide moiety N3is characterized by its high potential of reactivity which essentially manifests itself in two basic processes: the elimination of dinitrogen and the entry into 1, 3‐dipolar cycloadditions with suitable dipolarophiles, the latter of which clearly predominates the chemistry of azide, also that of its metal compounds. In a preceding review entitled“Part I – Metal Azides: Overview, General Trends and Recent Developments”which was meant to lay the foundations for the present paper, these and other reactions have already been touched upon. The present review – Part II – now focusses in great detail on the formation of five‐membered heterocycles – tetrazol(at)es, triazol(at)es, triazolin(at)es, thiatriazol(at)es, etc. as well as various consecutive products – from azide and nitriles, isocyanides, alkynes, alkenes and heteroallenes (CS2, RN=C=S) in the ligand sphere of the metal. Generally, these [3+2]‐cycloadditions are found to proceed under much milder conditions in comparison with the strictly organic case whose triumphant progress since the 1960s is intimately bound up with the name of Huisgen. Mechanistic considerations on the matter are presented. A secondary aspect still occupying quite a part of the discussion is concerned with the role of metals in [3+2]‐cycloadditions particularly of the highly topical “click”‐type, e.g. (CuAAC), (RuAAC). Likewise, a short chapter deals with the question of pentazol(at)e (N5–) which according to numerous theoretical studies could well be stabilized and isolated in combination with metals, e.g., in the form of azametallocenes. A last chapter is devoted to a cursory survey of related systems, in particular fulminato complexes, metallonitrile ylides and metallonitrile imines, in which the metal acts as a substituent on the 1, 3‐dipole (metallo‐1, 3‐dipole). Other systems with a metal substituent on the dipolarophile (metallo‐dipolarophile), or, with metal itself in the three‐ (two‐) atom arrangement constituting the dipole (dipolarophile) [metalla‐1, 3‐dipole, metalla‐dipolarophile] are only quoted by way of example.
Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice
Authors: Gupta Sapna , Wang Liqun , Kruger Warren D. 
Published: July 2015

AbstractCystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other treatments such as methionine restriction and supplemental B‐vitamins. However, the effectiveness of betaine supplementation by itself in the treatment of CBS deficiency has not been well explored. Here, we have examined the effect of a betaine supplemented diet on the Tg‐I278T Cbs−/− mouse model of CBS deficiency and compared its effectiveness to our previously published data using a methionine restricted diet. Tg‐I278T Cbs−/− mice on betaine, from the time of weaning until for 240 days of age, had a 40 % decrease in mean tHcy level and a 137 % increase in serum methionine levels. Betaine‐treated Tg‐I278T Cbs−/− mice also exhibited increased levels of betaine‐dependent homocysteine methyl transferase (BHMT), increased levels of the lipogenic enzyme stearoyl‐coenzyme A desaturase (SCD‐1), and increased lipid droplet accumulation in the liver. Betaine supplementation largely reversed the hair loss phenotype in Tg‐I278T Cbs−/− animals, but was far less effective than methionine restriction in reversing the weight‐loss, fat‐loss, and osteoporosis phenotypes. Surprisingly, betaine supplementation had several negative effects in control Tg‐I278T Cbs+/− mice including decreased weight gain, lean mass, and bone mineral density. Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice.
The Swedish Adoption Twin Study of Aging: An Update
Authors: Pedersen N.L. , McClearn G.E. , Plomin R. , Nesselroade J.R. , Berg S. , DeFaire U. 
Published: July 2015

AbstractThe Swedish Adoption/Twin Study of Aging (SATSA) is a longitudinal program of research in gerontological genetics which is currently in its fifth year. The base population is comprised of 351 pairs of twins reared apart and 407 matched control pairs of twins reared together who responded to a questionnaire (Q1) in 1984. Two additional stages of SATSA have recently been completed: a longitudinal follow-up questionnaire mailed out in 1987 (Q2) and extensive in-person testing (IPT1) which included a health examination and cognitive battery. A second wave of IPT was started in January 1989. A summary of some of the major findings from Q1 and a description of IPT1 are reported.
Polyphenol-rich juices reduce blood pressure measures in a randomised controlled trial in high normal and hypertensive volunteers
Authors: Tjelle Torunn Elisabeth , Holtung Linda , Bøhn Siv Kjølsrud , Aaby Kjersti , Thoresen Magne , Wiik Siv Åshild , Paur Ingvild , Karlsen Anette Solli , Retterstøl Kjetil , Iversen Per Ole , Blomhoff Rune 
Published: July 2015

Intake of fruits and berries may lower blood pressure (BP), most probably due to the high content of polyphenols. In the present study, we tested whether consumption of two polyphenol-rich juices could lower BP. In a randomised, double-blinded, placebo-controlled trial of 12 weeks, 134 healthy individuals, aged 50–70 years, with high normal range BP (130/85–139/89 mmHg, seventy-two subjects) or stage 1-2 hypertension (140/90–179/109 mmHg, sixty-two subjects), were included. They consumed 500 ml/d of one of either (1) a commercially available polyphenol-rich juice based on red grapes, cherries, chokeberries and bilberries; (2) a juice similar to (1) but enriched with polyphenol-rich extracts from blackcurrant press-residue or (3) a placebo juice (polyphenol contents 245·5, 305·2 and 76 mg/100 g, respectively). Resting BP was measured three times, with a 1 min interval, at baseline and after 6 and 12 weeks of intervention. Systolic BP significantly reduced over time (6 and 12 weeks, respectively) in the pooled juice group compared with the placebo group in the first of the three measurements, both for the whole study group (6·9 and 3·4 mmHg; P= 0·01) and even more pronounced in the hypertensive subjects when analysed separately (7·3 and 6·8 mmHg; P= 0·04). The variation in the BP measurements was significantly reduced in the pooled juice group compared with the placebo group (1·4 and 1·7 mmHg; P= 0·03). In conclusion, the present findings suggest that polyphenol-rich berry juice may contribute to a BP- and BP variability lowering effect, being more pronounced in hypertensive than in normotensive subjects.
Conodont biostratigraphy of the Little Cedar and Lower Coralville Formations of the Cedar Valley Group (Middle Devonian) of Iowa and significance of a new species of Polygnathus
Authors: Rogers Frederick S. 
Published: July 2015

The Little Cedar and lower Coralville formations of the Cedar Valley Group (Middle Devonian) of Iowa were deposited on a cratonic, shallow-water, carbonate and evaporite shelf during the Taghanic onlap. Four conodont subzones, zones, or cratonic biofacies faunas can be recognized in this sequence of strata. They are, in ascending order, the Middle varcus Subzone (recognized in the lower Little Cedar Formation), the hermanni zone (recognized in the middle Little Cedar Formation), the Lower subterminus Fauna (recognized in the upper Little Cedar Formation), and the Upper subterminus Fauna (recognized in the lower Coralville Formation). The Lower subterminus Fauna and the Upper subterminus Fauna represent a possible zonal span from the Lower hermanni Zone to the Upper disparilis Zone of the standard conodont zonation.In the Polygnathus- and Icriodus-dominated conodont faunas studied is a biostratigraphically useful new species. Polygnathus klugi new species is a Polygnathus dubius-like form that occurs sporadically and in small numbers in the Middle varcus Subzone, the hermanni Zone, and the Upper subterminus Fauna. However, it occurs consistently and in large numbers in the Lower subterminus Fauna, where it is the characterizing species. It has also been recovered from core samples both in central Alberta, Canada, and the Russian Platform. In both areas, it is associated with conodonts of the subterminus faunal interval.