bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nidogen 1 and 2 gene promoters are aberrantly methylated in human gastrointestinal cancer
Authors: Ulazzi Linda , Sabbioni Silvia , Miotto Elena , Veronese Angelo , Angusti Angela , Gafà Roberta , Manfredini Stefano , Farinati Fabio , Sasaki Takako , Lanza Giovanni , Negrini Massimo 
Published: February 2007

Abstract

Background
Nidogens are highly conserved proteins of basement membranes. Two nidogen proteins, nidogen 1 and nidogen 2, are known in mammals.

Results
We show that CpG islands of both NID1 and NID2 genes are aberrantly methylated in human cancer samples and cancer cell lines. For both genes, methylation was correlated with loss of gene transcription in human cell lines. Furthermore, demethylation of the NID1 and NID2 promoters restored gene transcription, demonstrating that methylation was responsible for silencing nidogen genes. In primary tumors, we detected NID1 promoter methylation in 67% of colon cancer samples and in 90% of gastric cancers. NID2 promoter was methylated in 29% of colon and 95% of gastric cancers. Immuno-staining for nidogen-2 confirmed the correlation between aberrant methylation and loss of nidogen expression also in primary tumors, implying that aberrant methylation was a mechanism for inhibiting nidogens expression in human gastrointestinal tumors.

Conclusion
These results suggest that loss of nidogens expression has a potential pathogenetic role in colon and stomach tumorigenesis. Nidogens are believed to connect laminin and collagen IV networks, hence stabilizing the basement membrane structure. Nidogens are also important for cell adhesion, as they establish contacts with various cellular integrins. Loss of nidogen expression may favor invasion and metastasis of cancer cells by loosening cell interaction with basal membrane and by weakening the strength of the basement membrane itself, first barrier from the connective vascularized matrix.
Expression of kinin B1 and B2 receptors in immature, monocyte-derived dendritic cells and bradykinin-mediated increase in intracellular Ca2+ and cell migration
Authors: Bertram Cornelia M , Baltic Svetlana , Misso Neil L , Bhoola Kanti D , Foster Paul S , Thompson Philip J , Fogel-Petrovic Mirjana 
Published: February 2007

AbstractThe kinins, bradykinin (BK) and Lys-des[Arg9]-BK, are important inflammatory mediators that act via two specific G protein-coupled kinins, B1 and B2 receptors (B2R). Kinins influence the activity of immune cells by stimulating the synthesis of cytokines, eicosanoids, and chemotactic factors. Whether human dendritic cells (DC) express kinin receptors and whether kinins influence DC function are unknown. Fluorescence immunocytochemistry and RT-PCR were used to demonstrate that immature human monocyte-derived DC (hMo-DC) constitutively expressed kinins B1R and B2R. Kinin receptor expression was induced on the 3rd and 4th days of culture during differentiation of hMo-DC from monocytes and was not dependent on the presence of IL-4 or GM-CSF. Although monocytes also expressed B2R mRNA, the protein was not detected. The kinin agonists BK and Lys-des[Arg9]-BK up-regulated the expression of their respective receptors. BK, acting via the B2R, increased intracellular Ca2+, as visualized by confocal microscopy using the fluorescent Ca2+ dye, Fluor-4 AM. Evaluation of migration in Trans-well chambers demonstrated significant enhancement by BK of migration of immature hMo-DC, which was B2R-dependent. However, kinins did not induce maturation of hMo-DC. The novel finding that kinin receptors are constitutively expressed in immature hMo-DC suggests that these receptors may be expressed in the absence of proinflammatory stimuli. BK, which increases the migration of immature hMo-DC in vitro, may play an important role in the migration of immature DC in noninflammatory conditions and may also be involved in the recruitment of immature DC to sites of inflammation.
Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9
Authors: Marom Barak , Rahat Michal A , Lahat Nitza , Weiss-Cerem Lea , Kinarty Amalia , Bitterman Haim 
Published: February 2007

AbstractMonocytes remodel the extracellular matrix (ECM) by secreting proteins composing the ECM such as fibronectin (FN) and degrading proteases such as matrix metalloproteinase-9 (MMP-9), which cleaves FN into fragments. The effects of FN and its fragmented products on the expression of monocyte MMP-9 are controversial and largely unknown. We showed that in human monocytes, the proinflammatory cytokine TNF-α induced MMP-9 secretion and increased fragmentation of FN into distinct fragments. When primary monocytes or the U937 monocytic cell line were incubated on a plastic substrate, plastic-coated with native FN, and plastic-coated with fragmented FN (frag-FN), native FN inhibited TNF-α-induced proMMP-9 secretion by twofold (P&lt;0.01) compared with plastic or frag-FN. Exploration of the dynamics of inflammation by incubating cells sequentially on the three substrates showed that frag-FN opposed the inhibitory effect of native FN. Inhibition of proMMP-9 by native FN was exerted at the translational level, as no change in MMP-9 mRNA, intracellular protein accumulation, or proteomic degradation was observed, and when degradation was blocked, no de novo translation of MMP-9 could be measured. We also showed that the reduction of MMP-9 secretion by native FN was responsible for attenuated migration of U937 cells (P&lt;0.05). We suggest that in the inflammatory tissue, intact, native FN has a homeostatic role in harnessing MMP-9 activity. However, as fragmented products accumulate locally, they alleviate the inhibition and enable faster migration of the monocytes through the degraded ECM.
Four Novel Mutations of the LHX3 Gene Cause Combined Pituitary Hormone Deficiencies with or without Limited Neck Rotation
Authors: Pfaeffle Roland W. , Savage Jesse J. , Hunter Chad S. , Palme Christina , Ahlmann Martina , Kumar Prasanna , Bellone Jaele , Schoenau Eckhard , Korsch Eckhard , Brämswig Jürgen H. , Stobbe Heike M. , Blum Werner F. , Rhodes Simon J. 
Published: February 2007

AbstractContext: The Lhx3 LIM-homeodomain transcription factor gene is required for development of the pituitary and motoneurons in mice. Human LHX3 gene mutations have been reported in five subjects with a phenotype consisting of GH, prolactin, TSH, LH, and FSH deficiency; abnormal pituitary morphology; and limited neck rotation.Objective: The objective of the study was to determine the frequency and nature of LHX3 mutations in patients with isolated GH deficiency or combined pituitary hormone deficiency (CPHD) and characterize the molecular consequences of mutations.Design: The LHX3 sequence was determined. The biochemical properties of aberrant LHX3 proteins resulting from observed mutations were characterized using reporter gene and DNA binding experiments.Patients: The study included 366 patients with isolated GH deficiency or CPHD.Results: In seven patients with CPHD from four consanguineous pedigrees, four novel, recessive mutations were identified: a deletion of the entire gene (del/del), mutations causing truncated proteins (E173ter, W224ter), and a mutation causing a substitution in the homeodomain (A210V). The mutations were associated with diminished DNA binding and pituitary gene activation, consistent with observed hormone deficiencies. Whereas subjects with del/del, E173ter, and A210V mutations had limited neck rotation, patients with the W224ter mutation did not.Conclusions: LHX3 mutations are a rare cause of CPHD involving deficiencies for GH, prolactin, TSH, and LH/FSH in all patients. Whereas most patients have a severe hormone deficiency manifesting after birth, milder forms can be observed, and limited neck rotation is not a universal feature of patients with LHX3 mutations. This study extends the known molecular defects and range of phenotypes found in LHX3-associated diseases.
Effects of Peroxisome Proliferator-Activated Receptor-α and -γ Agonists on 11β-Hydroxysteroid Dehydrogenase Type 1 in Subcutaneous Adipose Tissue in Men
Authors: Wake Deborah J. , Stimson Roland H. , Tan Garry D. , Homer Natalie Z. M. , Andrew Ruth , Karpe Fredrik , Walker Brian R. 
Published: February 2007

Abstract
Context: In animals, peroxisome proliferator-activated receptor-α (PPARα) and PPARγ agonists down-regulate 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mRNA and activity in liver and adipose tissue, respectively, and PPARγ agonists reduce ACTH secretion from corticotrope cells.
Objective: Our objective was to test whether PPAR agonists alter cortisol secretion and peripheral regeneration by 11β-HSD1 in humans and whether reduced cortisol action contributes to metabolic effects of PPARγ agonists.
Design and Setting: Three randomized placebo-controlled crossover studies were conducted at a clinical research facility.
Patients and Participants: Healthy men and patients with type 2 diabetes participated.
Interventions, Outcome Measures, and Results: In nine healthy men, 7 d of PPARα agonist (fenofibrate) or PPARγ agonist (rosiglitazone) had no effect on cortisol secretion, hepatic cortisol generation after oral cortisone administration, or tracer kinetics during 9,11,12,12-[2H]4-cortisol infusion, although rosiglitazone marginally reduced cortisol generation in sc adipose tissue measured by in vivo microdialysis. In 12 healthy men, 4–5 wk of rosiglitazone increased insulin sensitivity during insulin infusion but did not change 11β-HSD1 mRNA or activity in sc adipose tissue, and insulin sensitization was unaffected by glucocorticoid blockade with a combination of metyrapone and RU38486. In 12 men with type 2 diabetes 12 wk of rosiglitazone reduced arteriovenous cortisone extraction across abdominal sc adipose tissue and reduced 11β-HSD1 mRNA in sc adipose tissue but increased plasma cortisol concentrations.
Conclusions: Neither PPARα nor PPARγ agonists down-regulate 11β-HSD1 or cortisol secretion acutely in humans. The early insulin-sensitizing effect of rosiglitazone is not dependent on reducing intracellular glucocorticoid concentrations. Reduced adipose 11β-HSD1 expression and increased plasma cortisol during longer therapy with rosiglitazone probably reflect indirect effects, e.g. mediated by changes in body fat.
Origin of de Novo KCNJ11 Mutations and Risk of Neonatal Diabetes for Subsequent Siblings
Authors: Edghill Emma L. , Gloyn Anna L. , Goriely Anne , Harries Lorna W. , Flanagan Sarah E. , Rankin Julia , Hattersley Andrew T. , Ellard Sian 
Published: February 2007

Abstract
Context: Activating mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the pancreatic β-cell KATP channel, result in permanent and transient neonatal diabetes. The majority of KCNJ11 mutations are spontaneous, but the parental origin of these mutations is not known.
Objective: Our objective was to determine the parental origin of de novo KCNJ11 mutations and investigate the possibility of mosaicism in transmitting parents.
Design: We identified 68 index cases with a KCNJ11 mutation where neither parent was known to be affected. DNA was available from both parents of 41 probands. The parental origin of the mutation was determined in 18 families by examination of pedigrees, microsatellite analysis, or allele-specific PCR.
Results: A nonsignificant excess of paternally derived mutations was found with 13 of 18 (72%) shown to have arisen on the paternal allele. There was no evidence to suggest an association with increased age at conception. In two families, there were half-siblings with permanent neonatal diabetes born to an unaffected father, suggesting germline mosaicism that was confirmed by the presence of the R201C mutation in one father’s semen. Somatic mosaicism was detected in one unaffected mother, and this mutation will also be present in her germ cells.
Conclusion: De novo KCNJ11 mutations can arise either during gametogenesis or embryogenesis. The possibility of germline mosaicism means that future siblings are at increased risk of neonatal diabetes, and we recommend that molecular genetic testing is routinely offered at birth for subsequent siblings of children with de novo KCNJ11 mutations.
Using Electronic Portfolios to Make Learning Public
Authors: Fahey Kevin , Lawrence Joshua , Paratore Jeanne 
Published: February 2007

Electronic portfolio technology can be used in different contexts to create classroom communities in which everyone, not just the teacher, cares about each student's learning. The authors describe how students in an urban middle school, undergraduate teacher preparation program, and graduate leadership program used an electronic bulletin board and portfolio process to make all of their work public. In these classrooms, student work was not simply handed in to the teacher, graded, and quickly forgotten.The article also reports three preliminary findings:
First, students at every level were able to share their work.
Second, students who had little experience in giving one another feedback learned to reflect on one another's work, share ideas, build on those ideas, and use the feedback to leverage further learning.
Third, the electronic portfolio process encouraged students to generate and focus on ideas that were personally compelling. The middle school students became deeply interested in exploring and reading and writing about community issues, and both the undergraduate and graduate students used the feedback to learn about and change important aspects of their own practice.
10 Rules for Reading
Authors: Litt Deborah G. 
Published: February 2007

In the author's experience, a significant source of reading difficulty for many beginning and struggling readers are misconceptions about print concepts so basic teachers assume their students are aware of them. Many children fail to grasp implicit principles of print such as the following: the reader cannot make up the words, the order of letters within a word makes a difference, and each letter in a word must be considered.Using brief vignettes from her work with beginning and struggling readers, the author draws attention to these often‐overlooked misconceptions. The author explains how she helped students overcome their faulty understandings by providing “rules” about reading, which enabled them to regulate their own reading.
How Do Primary Care Clinicians Manage Childhood Mood and Anxiety Syndromes?
Authors: Wren Frances J. , Scholle Sarah H. , Heo Jungeun , Comer Diane M. 
Published: February 2007

Objective: To describe how primary care clinicians manage children in whom they diagnose mood or anxiety syndromes. Method: This study is a secondary analysis of data from the multi-site Child Behavior Study (CBS)—a cross-sectional survey of primary care management of psychosocial problems. The management of children in whom clinicians identified mood or anxiety syndromes is described and compared with the management of children in whom they identified other psychosocial problems. Recruitment for the CBS occurred in 206 primary care practices in the United States, Puerto Rico, and Canada from October 1994 through June 1997. Participants were 20,861 consecutively sampled primary care attendees aged 4–15 years and 395 clinicians. Primary outcome measures for this report are rates of referral to specialized mental health care and rates of active primary care management (i.e., scheduling a follow-up appointment and/or providing ongoing counseling and/or psychotropic prescription). Results: Identification of a mood or anxiety syndrome was associated with increased rates of referral to mental health compared with rates for children with other psychosocial problems. There was no effect on the proportion of children counseled during the visit. In fact, unless accompanied by a co-morbid behavioral syndrome, children receiving the diagnosis of a mood or anxiety syndrome were less likely to be offered a scheduled follow-up appointment. Rates of prescription of antidepressants or anti-anxiety agents were higher for mood/anxiety groups but this was still uncommon (6.7%). Conclusions: Active management of childhood mood and anxiety syndromes in primary care was uncommon in the United States, Puerto Rico, and Canada in the mid-1990s.
Preparation and characterization of macroporous poly(2‐hydroxyethyl methacrylate)‐based biomaterials: Water sorption property and in vitro blood compatibility
Authors: Bajpai A. K. , Kankane Sanjana 
Published: February 2007

AbstractA semi‐interpenetrating polymer network (IPN) comprising gelatin and poly(2‐hydroxyethyl methacrylate‐co‐acrylamide) was prepared and characterized by FTIR, environmental scanning electron microscopy (ESEM) and differential scanning calorimetry (DSC) techniques. The water sorption potential of the prepared semi‐IPNs was investigated for varying chemical architecture of the IPN, and experimental conditions such as pH, temperature and ionic strength of the swelling media. The semi‐IPNs were also judged for in vitro blood compatibility by performing blood clot, percent hemolysis, protein adsorption and platelet adhesion tests. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1559–1571, 2007
The effect of allylation degree on processing properties, thermal cure, and thermal properties of BMAN resins
Authors: Luo Zhenhua , Wei Liuhe , Liu Feng , Zhao Tong 
Published: February 2007

AbstractA series of allyl‐functional novolac (AN) resins with various allylation degree, from 32.4 to 114.6%, were synthesized and blended reactively with 4,4′‐bismaleimide biphenyl methane (BMI) at a weight ratio of 2.50 : 1 to get BMI‐modified and allyl‐functional novolac (BMAN) resins. Structural characteristics of the resins were determined by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1HNMR) techniques. Processing properties of BMAN resin system was evaluated by solubility, rheology, and thermal gelation, and the results show that processing properties of BMAN resins were excellent and could be tailored by changing allylation degree of AN resins. Differential scanning calorimetry (DSC) was used to evaluate cure reactivity of BMAN resin system, and the results reveal that the resins with higher allylation degree possessed better cure reactivity. Thermal properties were evaluated by means of dynamic mechanical analysis (DMA) and thermogravimetry analysis (TGA) techniques. The results reveal that with increase in allylation degree of resins the thermal stability of BMAN resins increased because of increase in crosslinking density, but char‐yields of the above resins at 800°C decreased in turn. Understanding of the relationship between allylation degree and properties of the resins would be useful to direct the design of material to meet different requirements of applications. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Effect of molecular weight on spherulitic growth rate of poly(ϵ‐caprolactone) and poly(ϵ‐caprolactone)‐b‐poly(ethylene glycol)
Authors: Du Zi‐Xiu , Yang Yong , Xu Jun‐Ting , Fan Zhi‐Qiang 
Published: February 2007

AbstractThe spherulitic growth rates of a series poly (ϵ‐caprolactone) homopolymers and poly(ϵ‐caprolactone)‐b‐ poly(ethylene glycol) (PCL‐b‐PEG) block copolymers with different molecular weights but narrow polydispersity were studied. The results show that for both PCL homopolymers and PCL‐b‐PEG block copolymers, the spherulitic growth rate first increases with molecular weight and reaches a maximum, then decreases as molecular weight increases. Crystallization temperature has greater influence on the spherulitic growth rate of polymers with higher molecular weight. Hoffman–Lauritzen theory was used to analyze spherulitic growth kinetics and the free energy of the folding surface (σe) was derived. It is found that the values of σe decrease with molecular weight at low molecular weight level and become constant for high molecular weight polymers. The chemically linked PEG block does not change the values of σe significantly. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Microstructure‐property relationships in a tissue‐engineering scaffold
Authors: Johnson Jed , Ghosh Anirban , Lannutti John 
Published: February 2007

AbstractElectrospinning can produce tissue‐engineering scaffolds possessing appropriate strength, biomimetic structure, economic appeal, and biocompatibility. To investigate how microstructural changes could potentially affect adherent mammalian cells, tensile samples were strained to 10, 40, and 80% extension, and adhered to double‐sided carbon tape to maintain specific states of strain. While establishing the stress–strain response, we invoked polymer sintering to help verify that the “point bonding” concept is more significant than previously realized at both the macroscopic and microscopic length scales. Sintering successfully established the effects of deliberate, extensive point bonding/localized “notch” generation on mechanical properties and microstructural response without requiring chemical changes within the structure. We also found that fibers experience significant hysteresis in terms of their orientation following exposure to high values of strain. Aligned fibers provide higher strengths (σave = 2.8 ± 0.3 MPa vs. σave = 1.29 ± 0.04 MPa for unaligned fibers) but considerably lower elongation [εave = (30 ± 2)% vs. εave = (102 ± 6)%]. Conversely, when strain occurs perpendicular to the aligned fiber direction total strain increases [εave = (188 ± 6)%] while strength decreases (σave = 0.38 ± 0.01 MPa). Elastic response to low strains appears to estimate ultimate tensile strength. In many ways, electrospun fibers behave similarly to classic interpretations of polymer chains in that when strained in both cases elements can rearrange and translate to align along the direction of loading. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Coral community decline at a remote Caribbean island: marine no‐take reserves are not enough
Authors: Coelho Vânia R. , Manfrino Carrie 
Published: February 2007

Abstract
Coral reefs around the world have been deteriorating over decades owing to anthropogenic pressure. In the Caribbean recent rates of decline are alarming, particularly for coral reefs under high local human impact, many of which are severely degraded, although regions with lower direct anthropogenic influence seem less affected.
Little Cayman is a relatively undeveloped island, with less than 150 permanent residents. About 20% of its reefs have been protected by no‐take marine reserves since the mid‐1980s. We analysed the dynamics of coral communities around the island from 1999 to 2004 in order to test the hypothesis that a lack of major local anthropogenic disturbances is enough to prevent decline of coral populations.
Live hard coral coverage, coral diversity, abundance, mortality, size, and prevalence of disease and bleaching were measured using the Atlantic and Gulf Rapid Reef Assessment methodology (line transects) at nine sites. Despite the apparent undisturbed condition of the island, a 40% relative reduction of mean live coral coverage (from 26% to 16%, absolute change was 10%) was recorded in five years. Mean mortality varied from year to year from 23% to 27%. Overall mean diameter and height have decreased between 6% and 15% on average (from 47 to 40 cm for diameter, and from 31 to 29 cm for height).
The relative abundance of large reef builders of the genus Montastraea decreased, while that of smaller corals of the genera Agaricia and Porites increased. Disease prevalence has increased over time, and at least one relatively large bleaching event (affecting 10% of the corals) took place in 2003.
Mean live coral cover decline was similar inside (from 29% to 19%) and outside (from 24% to 14%) marine no‐take reserves. No significant difference in disease prevalence or clear pattern in bleaching frequency was observed between protected and non‐protected areas. It is concluded that more comprehensive management strategies are needed in order to effectively protect coral communities from degradation.
Copyright © 2007 John Wiley & Sons, Ltd.