bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained parenting and college drinking in first‐year students
Authors: Turrisi Rob , Ray Anne E. 
Published: March 2010

AbstractResearch indicates that for many students excessive drinking in college is a continuation of high school drinking tendencies. However, there have been limited theory‐driven, systematic interventions targeting students so as to prevent alcohol misuse in their transition to college. Almost all current prevention approaches tend to be focused on younger populations and college‐drinking interventions are typically delivered to students when they are already on campus. These analyses draw from a novel program of research involving parents of college freshmen based on the work of Turrisi et al. [Turrisi et al. [2001] Psychology of Addictive Behaviors, 15(4), 366–372; Turrisi, et al. [2009] Journal of Applied Social Psychology, 7, 315–326] and focuses on examining: (1) the relationship between parenting and student drinking tendencies during the transitional period between high school and college and into the first year of college, and (2) the mediation process by which sustained parenting throughout the first year is related to college‐drinking outcomes and consequences so as to inform future intervention efforts. The empirical evidence from this study suggests that sustained parental efforts have a beneficial effect on reducing high‐risk drinking and preventing harm even at this late stage of late adolescent/early adult development. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 286–294, 2010
Psychobiological models of adolescent risk: Implications for prevention and intervention
Authors: Calkins Susan D. 
Published: March 2010

AbstractThe papers in this special section address the phenomena of observed increases in risky behavior during the adolescent period of development. Authors provide well‐documented evidence that adolescents are at greater risk for a range of psychological and behavioral problems during this period than at any other time in development. The papers share a developmental and psychobiological perspective on this period, noting that biological, social, and contextual factors interact to produce heightened risk for problematic behavior during this period. This perspective suggests several points of entry for intervention and prevention efforts aimed at reducing both mental and behavioral health problems. Gaps in current research efforts are noted, as is the need for more research focusing on mechanisms of change prior to and during adolescence. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 213–215, 2010
α‐Dystroglycan is essential for the induction of Egr3, a transcription factor important in muscle spindle formation
Authors: Williams Stacey , Jacobson Christian 
Published: March 2010

AbstractMuscle spindle fibers are specialized stretch receptors that allow the perception and coordination of limb movement. The differentiation of these specialized structures is initiated by signals derived from the in growing Ia sensory neurons during development. While the direct molecular signaling mechanisms between sensory neurons and developing muscle at nascent spindle fibers have been well documented in past studies the roles of muscle basal lamina components on this process have not previously been described. As such, our initial experiments addressed potential roles for agrin (AGRN) and laminin (LN) in the expression of the transcription factor Egr3. Levels of Egr3 were monitored using immunoblot analysis and both basal lamina molecules proved effective in inducing Erg3 expression. Previous work had established neuregulin (NRG) as a critical signaling component in spindle fiber development so blocking experiments with NRG and ErbB inhibitors were then used to determine if LN‐induced Egr3 expression was occurring as a result of NRG‐ErbB signaling and not via other, novel pathway. Inhibiting signaling through this pathway did indeed reduce the expression of Egr3. Finally, we looked at α‐dystrogylcan, a shared receptor for AGRN and LN at neuromuscular junctions. Using a α‐dystroglycan (α‐DG) silenced muscle cell line and an anti‐α‐DG antibody we attempted to block basal lamina/α‐DG interactions. Again, and in both instances, Egr3 expression was significantly decreased. Taken together, analysis of the results from these experiments revealed that indeed AGRN, LN, and α‐DG influence Egr3 levels and therefore may play an important role in spindle fiber differentiation. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:498–507, 2010
Altered effector functions of virus‐specific and virus cross‐reactive CD8+ T cells in mice immunized with related flaviviruses
Authors: Trobaugh Derek W. , Yang Liyan , Ennis Francis A. , Green Sharone 
Published: March 2010

AbstractMemory cross‐reactive CD8+ T‐cell responses may induce protection or immunopathology upon secondary viral challenge. To elucidate the potential role of T cells in sequential flavivirus infection, we characterized cross‐reactive CD4+ and CD8+ T‐cell responses between attenuated and pathogenic Japanese encephalitis virus (JEV) and pathogenic West Nile virus (WNV). A previously reported WNV NS4b CD8+ T‐cell epitope and its JEV variant elicited CD8+ T‐cell responses in both JEV‐ and WNV‐infected mice. The peptide variant homologous to the immunizing virus induced greater cytokine secretion and activated higher frequencies of epitope‐specific CD8+ T cells. However, there was a virus‐dependent, peptide variant‐independent pattern of cytokine secretion; the IFNγ+‐to‐IFNγ+TNFα+ CD8+ T‐cell ratio was greater in JEV‐ than in WNV‐infected mice. Despite similarities in viral burden for pathogenic WNV and JEV viruses, CD8+ T cells from pathogenic JEV‐immunized mice exhibited functional and phenotypic profiles similar to those seen for the attenuated JEV strain. Patterns of killer cell lectin‐like receptor G1 (KLRG1) and CD127 expression differed by virus type, with a rapid expansion and contraction of short‐lived effector cells in JEV infection and persistence of high levels of short‐lived effector cells in WNV infection. Such cross‐reactive T‐cell responses to primary infection may affect the outcomes of sequential flavivirus infections.
The synthetic TLR2 agonist BPPcysMPEG leads to efficient cross‐priming against co‐administered and linked antigens
Authors: Prajeeth Chittappen K. , Jirmo Adan Chari , Krishnaswamy Jayendra Kumar , Ebensen Thomas , Guzman Carlos A. , Weiss Siegfried , Constabel Hannelore , Schmidt Reinhold E. , Behrens Georg M. N. 
Published: March 2010

AbstractThe property of DC to generate effective CTL responses is influenced by TLR signaling. TLR ligands contain molecular signatures associated with pathogens, have an impact on the antigen processing and presentation by DC, and are being exploited as potential adjuvants. We hypothesized that the TLR2/6 heterodimer agonist S‐[2,3‐bispalmitoyiloxy‐(2R)‐propyl]‐R‐cysteinyl‐amido‐monomethoxyl polyethylene glycol (BPP), a synthetic derivative of the Mycoplasma macrophage activating lipopeptide‐2, is a potent adjuvant for cross‐priming against cellular antigens. Systemic administration of BPP‐induced maturation of CD8α+ DC and CD8α− DC in the spleen and resulted in enhanced cross‐presentation of intravenously co‐administered antigen in mice. In addition, administration of BPP and cell‐associated OVA generated an effective CTL response against OVA in vivo in a CD4+ T helper cell‐dependent manner, but independent of IFN‐α. Delivering antigenic peptides directly linked to BPP led to superior CTL immunity as compared to giving antigens and adjuvants admixed. In contrast to other TLR ligands, such as CpG, systemic activation of DC with BPP did not result in shut‐down of antigen presentation by splenic DC subsets, although cross‐priming against subsequently encountered antigens was reduced. Together, our data provide evidence that BPP is a potent stimulus to generate CTL via cross‐priming.
Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance
Authors: Baruah Paramita , Simpson Elizabeth , Dumitriu Ingrid E. , Derbyshire Katy , Coe David , Addey Caroline , Dyson Julian , Chai Jian‐Guo , Cook Terence , Scott Diane , Botto Marina 
Published: March 2010

AbstractComplement activation is known to have deleterious effects on organ transplantation. On the other hand, the complement system is also known to have an important role in regulating immune responses. The balance between these two opposing effects is critical in the context of transplantation. Here, we report that female mice deficient in C1q (C1qa−/−) or C3 (C3−/−) reject male syngeneic grafts (HY incompatible) at an accelerated rate compared with WT mice. Intranasal HY peptide administration, which induces tolerance to syngeneic male grafts in WT mice, fails to induce tolerance in C1qa−/− or C3−/− mice. The rejection of the male grafts correlated with the presence of HY DbUty‐specific CD8+ T cells. Consistent with this, peptide‐treated C1qa−/− and C3−/− female mice rejecting male grafts exhibited more antigen‐specific CD8+IFN‐γ+ and CD8+IL‐10+ cells compared with WT females. This suggests that accumulation of IFN‐γ‐ and IL‐10‐producing T cells may play a key role in mediating the ongoing inflammatory process and graft rejection. Interestingly, within the tolerized male skin grafts of peptide‐treated WT mice, IFN‐γ, C1q and C3 mRNA levels were higher compared to control female grafts. These results suggest that C1q and C3 facilitate the induction of intranasal tolerance.
Nonlinear analysis of the deformation and breakup of viscous microjets using the method of lines
Authors: Furlani E. P. , Hanchak M. S. 
Published: March 2010

AbstractWe present a numerical model for predicting the instability and breakup of viscous microjets of Newtonian fluid. We adopt a one‐dimensional slender‐jet approximation and obtain the equations of motion in the form of a pair of coupled nonlinear partial differential equations (PDEs). We solve these equations using the method of lines, wherein the PDEs are transformed to a system of ordinary differential equations for the nodal values of the jet variables on a uniform staggered grid. We use the model to predict the instability and satellite formation in infinite microthreads of fluid and continuous microjets that emanate from an orifice. For the microthread analysis, we take into account arbitrary initial perturbations of the free‐surface and jet velocity, as well as Marangoni instability that is due to an arbitrary variation in the surface tension. For the continuous nozzle‐driven jet analysis, we take into account arbitrary time‐dependent perturbations of the free‐surface, velocity and/or surface tension as boundary conditions at the nozzle orifice. We validate the model using established computational data, as well as axisymmetric, volume of fluid (VOF) computational fluid dynamic (CFD) simulations. The key advantages of the model are its ease of implementation and speed of computation, which is several orders of magnitude faster than the VOF CFD simulations. The model enables rapid parametric analysis of jet breakup and satellite formation as a function of jet dimensions, modulation parameters, and fluid rheology. Copyright © 2010 John Wiley & Sons, Ltd.
Potential role of micro‐RNAs in head and neck tumorigenesis
Authors: Tran Nham , O'Brien Christopher J. , Clark Jonathan , Rose Barbara 
Published: March 2010

AbstractA new class of regulatory molecules known as microRNAs (miRNAs) is redefining our understanding of the molecular pathways associated with tumorigenesis. These miRNAs are small noncoding RNA (ncRNA) sequences with potent regulatory potential. The aberrant expression of miRNAs has been associated with the development of various tumors. It has been suggested that miRNAs can both regulate and act as tumor‐suppressor genes and oncogenes. Our understanding of the role of miRNAs in head and neck tumorigenesis is in its infancy. However, several recent studies have revealed extensive dysregulation of miRNA in head and neck tumors and have highlighted the potential of certain miRNAs to act as diagnostic and prognostic markers and targets for new therapeutic agents. The intent of this review is to discuss and summarize current findings that point to a significant role for miRNAs in head and neck tumorigenesis. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging
Authors: Ren Pei‐Gen , Huang Zhinong , Ma Ting , Biswal Sandip , Smith Robert L. , Goodman Stuart B. 
Published: March 2010

AbstractMacrophages constitute a major part of the cell response to wear particles produced at articulating and nonarticulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra‐high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by noninvasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/mL UHMWPE suspension or saline alone. Reporter RAW264.7 macrophages that stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection and at 2‐day intervals. Compared with the nonoperated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 ± 0.09‐, 2.36 ± 0.92‐, and 10.32 ± 7.61‐fold, respectively. The values at same time points for saline‐injected control group were 1.08 ± 0.07‐, 1.14 ± 0.27‐, and 1.14 ± 0.35‐fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all postinjection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle‐induced periprosthetic osteolysis. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways
Authors: Gunnell Lea M , Jonason Jennifer H , Loiselle Alayna E , Kohn Anat , Schwarz Edward M , Hilton Matthew J , O'Keefe Regis J 
Published: March 2010

Abstract
The importance of canonical transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling during cartilage and joint development is well established, but the necessity for noncanonical (SMAD-independent) signaling during these processes is largely unknown. TGF-β activated kinase 1 (TAK1) is a MAP3K activated by TGF-β, BMP, and other mitogen-activated protein kinase (MAPK) signaling components. We set out to define the potential role for noncanonical, TAK1-mediated signaling in cartilage and joint development via deletion of Tak1 in chondrocytes (Col2Cre;Tak1f/f) and the developing limb mesenchyme (Prx1Cre;Tak1f/f). Deletion of Tak1 in chondrocytes resulted in novel embryonic developmental cartilage defects including decreased chondrocyte proliferation, reduced proliferating chondrocyte survival, delayed onset of hypertrophy, reduced Mmp13 expression, and a failure to maintain interzone cells of the elbow joint, which were not observed previously in another Col2Cre;Tak1f/f model. Deletion of Tak1 in limb mesenchyme resulted in widespread joint fusions likely owing to the differentiation of interzone cells to the chondrocyte lineage. The Prx1Cre;Tak1f/f model also allowed us to identify novel columnar chondrocyte organization and terminal maturation defects owing to the interplay between chondrocytes and the surrounding mesenchyme. Furthermore, both our in vivo models and in vitro cell culture studies demonstrate that loss of Tak1 results in impaired activation of the downstream MAPK target p38, as well as diminished activation of the BMP/SMAD signaling pathway. Taken together, these data demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling and is necessary for proper cartilage and joint development. © 2010 American Society for Bone and Mineral Research
The evolutionary mechanism of cancer
Authors: Heng Henry H.Q. , Stevens Joshua B. , Bremer Steven W. , Ye Karen J. , Liu Guo , Ye Christine J. 
Published: March 2010

AbstractIdentification of the general molecular mechanism of cancer is the Holy Grail of cancer research. Since cancer is believed to be caused by a sequential accumulation of cancer gene mutations, the identification, characterization, and targeting of common genetic alterations and their defined pathways have dominated the field for decades. Despite the impressive data accumulated from studies of gene mutations, epigenetic dysregulation, and pathway alterations, an overwhelming amount of diverse molecular information has offered limited understanding of the general mechanisms of cancer. To solve this paradox, the newly established genome theory is introduced here describing how somatic cells evolve within individual patients. The evolutionary mechanism of cancer is characterized using only three key components of somatic cell evolution that include increased system dynamics induced by stress, elevated genetic and epigenetic heterogeneity, and genome alteration mediated natural selection. Cancer progression represents a macro‐evolutionary process where karyotype change or genome replacement plays the key dominant role. Furthermore, the recently identified relationship between the evolutionary mechanism and a large number of diverse individual molecular mechanisms is discussed. The total sum of all the individual molecular mechanisms is equal to the evolutionary mechanism of cancer. Individual molecular mechanisms including all the molecular mechanisms described to date are stochastically selected and unpredictable and are therefore clinically impractical. Recognizing the fundamental importance of the underlying basis of the evolutionary mechanism of cancer mandates the development of new strategies in cancer research. J. Cell. Biochem. 109: 1072–1084, 2010. © 2010 Wiley‐Liss, Inc.
Oxygen tension differentially influences osteogenic differentiation of human adipose stem cells in 2D and 3D cultures
Authors: He Jiawei , Genetos Damian C. , Yellowley Clare E. , Leach J. Kent 
Published: March 2010

AbstractSkeletal defects commonly suffer from poor oxygen microenvironments resulting from compromised vascularization associated with injury or disease. Adipose stem cells (ASCs) represent a promising cell population for stimulating skeletal repair by differentiating toward the osteogenic lineage or by secreting trophic factors. However, the osteogenic or trophic response of ASCs to reduced oxygen microenvironments is poorly understood. Moreover, a direct comparison between 2D and 3D response of ASCs to hypoxia is lacking. Thus, we characterized the osteogenic and angiogenic potential of human ASCs under hypoxic (1%), normoxic (5%), and atmospheric (21%) oxygen tensions in both 2D and 3D over 4 weeks in culture. We detected greatest alkaline phosphatase activity and extracellular calcium deposition in cells cultured in both 2D and 3D under 21% oxygen, and reductions in enzyme activity corresponded to reductions in oxygen tension. ASCs cultured in 1% oxygen secreted more vascular endothelial growth factor (VEGF) over the 4‐week period than cells cultured in other conditions, with cells cultured in 2D secreting VEGF in a more sustained manner than those in 3D. Expression of osteogenic markers revealed temporal changes under different oxygen conditions with peak expression occurring earlier in 3D. In addition, the increase of most osteogenic markers was significantly higher in 2D compared to 3D cultures at 1% and 5% oxygen. These results suggest that oxygen, in conjunction with dimensionality, affects the timing of the differentiation program in ASCs. These findings offer new insights for the use of ASCs in bone repair while emphasizing the importance of the culture microenvironment. J. Cell. Biochem. 110: 87–96, 2010. © 2010 Wiley‐Liss, Inc.
CDK5 phosphorylates eNOS at Ser‐113 and regulates NO production
Authors: Lee Chien‐Hsing , Wei Yin‐Win , Huang Yi‐Ting , Lin Yuh‐Te , Lee Yu‐Cheng , Lee Kuen‐Haur , Lu Pei‐Jung 
Published: March 2010

AbstractPhosphorylation of endothelial nitric oxide synthase (eNOS) is key mechanism in response to various forms of cellular stimulation. Through protein nitration by peroxynitrite, eNOS is believed to be responsible for the major abnormalities in several important neurodegenerative diseases including Alzheimer's (AD) and Parkinson's diseases (PD). Recent studies provide important in vivo evidence that hyperactivation of Cdk5 by p25 plays an essential role in the cell death of neurons in experimental models of AD and PD. This study focuses on the functional regulation of eNOS by Cdk5/p35 complex in a phosphorylation dependent manner. Our results showed that Cdk5 can phosphorylate eNOS both in vitro and in vivo. In vitro kinase assay together with the bioinformatic analysis and site direct mutagenesis revealed that Ser‐113 is the major phosphorylation site for Cdk5. Most interestingly, the nitrite production was significantly reduced in eNOS and Cdk5/p35 co‐transfected SH‐SY5Y cells when compared with co‐transfection of Cdk5/p35 and S113A. Together, our data suggest that Cdk5 can phosphorylate eNOS at the Ser‐113 site and down‐regulate eNOS‐derived NO levels. J. Cell. Biochem. 110: 112–117, 2010. © 2010 Wiley‐Liss, Inc.
Concurrent inhibition of NF‐κB, cyclooxygenase‐2, and epidermal growth factor receptor leads to greater anti‐tumor activity in pancreatic cancer
Authors: Ali Shadan , Banerjee Sanjeev , Schaffert Jacqueline M. , El‐Rayes Bassel F. , Philip Philip A. , Sarkar Fazlul H. 
Published: March 2010

AbstractInactivation of survival pathways such as NF‐κB, cyclooxygenase (COX‐2), or epidermal growth factor receptor (EGFR) signaling individually may not be sufficient for the treatment of advanced pancreatic cancer (PC) as suggested by recent clinical trials. 3,3′‐Diindolylmethane (B‐DIM) is an inhibitor of NF‐κB and COX‐2 and is a well‐known chemopreventive agent. We hypothesized that the inhibition of NF‐κB and COX‐2 by B‐DIM concurrently with the inhibition of EGFR by erlotinib will potentiate the anti‐tumor effects of cytotoxic drug gemcitabine, which has been tested both in vitro and in vivo. Inhibition of viable cells in seven PC cell lines treated with B‐DIM, erlotinib, or gemcitabine alone or their combinations was evaluated using 3‐(4,5‐dimetylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Significant inhibition in cell viability was observed in PC cells expressing high levels of COX‐2, EGFR, and NF‐κB proteins. The observed inhibition was associated with an increase in apoptosis as assessed by ELISA. A significant down‐regulation in the expression of COX‐2, NF‐κB, and EGFR in BxPC‐3, COLO‐357, and HPAC cells was observed, suggesting that simultaneous targeting of EGFR, NF‐κB, and COX‐2 is more effective than targeting either signaling pathway separately. Our in vitro results were further supported by in vivo studies showing that B‐DIM in combination with erlotinib and gemcitabine was significantly more effective than individual agents. Based on our preclinical in vitro and in vivo results, we conclude that this multi‐targeted combination could be developed for the treatment of PC patients whose tumors express high levels of COX‐2, EGFR, and NF‐κB. J. Cell. Biochem. 110: 171–181, 2010. © 2010 Wiley‐Liss, Inc.