tbuckley/cabot-search huggingface dataset:
Role of neural tension in stretch-induced strength loss
Authors: J Tallent, B Greene, C D Johnson, M P McHugh
Journal: British Journal of Sports Medicine (2010)

The aim of the study was to examine whether increased neural tension during passive hamstring stretching contributes to stretch-induced strength loss. Eleven healthy subjects performed maximal isometric knee flexion contractions (100°, 80°, 60° and 20°) before and after a series of hamstring stretches (six 1-min stretches), performed in either a spinal neutral position or a neural tension position. Effect of stretch technique (neutral or neural tension) on passive resistance to stretch, strength-induced strength loss and electromyography activity during strength tests was assessed with repeated measures analysis of variance. Passive resistance to stretch was reduced by 19% after the series of stretches (p=0.001) with no difference between neutral or neural tension stretches (p=0.41). Stretch-induced strength loss was greater (p=0.043) after the neural tension stretches (13%) vs the neutral stretches (5%). There was an apparent rightward shift in the length tension curve after neutral stretches with a 15% strength loss at muscle lengths shorter than optimum, and a 10% gain in strength at muscle lengths longer than optimum (p&lt;0.001). This effect was not apparent after neural tension stretches where strength loss was 21% at muscle lengths shorter than optimum and 9% at muscle lengths longer than optimum. The addition of neural tension to hamstring stretching increased stretch-induced strength loss but this was not associated with observable neural inhibition. The absence of a rightward shift in the length-tension curve after neural tension stretching indicates that muscle fibre shortening during isometric contractions was unaffected, presumably because tendon-aponeurosis compliance was not increased.
The Response of CD24 −/low /CD44 + Breast Cancer–Initiating Cells to Radiation
Authors: Tiffany M. Phillips, William H. McBride, Frank Pajonk
Journal: JNCI Journal of the National Cancer Institute (2006)

If cancer arises and is maintained by a small population of cancer-initiating cells within every tumor, understanding how these cells react to cancer treatment will facilitate improvement of cancer treatment in the future. Cancer-initiating cells can now be prospectively isolated from breast cancer cell lines and tumor samples and propagated as mammospheres in vitro under serum-free conditions.CD24(-/low)/CD44+ cancer-initiating cells were isolated from MCF-7 and MDA-MB-231 breast cancer monolayer cultures and propagated as mammospheres. Their response to radiation was investigated by assaying clonogenic survival and by measuring reactive oxygen species (ROS) levels, phosphorylation of the replacement histone H2AX, CD44 levels, CD24 levels, and Notch-1 activation using flow cytometry. All statistical tests were two-sided.Cancer-initiating cells were more resistant to radiation than cells grown as monolayer cultures (MCF-7: monolayer cultures, mean surviving fraction at 2 Gy [SF(2Gy)] = 0.2, versus mammospheres, mean SF(2Gy) = 0.46, difference = 0.26, 95% confidence interval [CI] = 0.05 to 0.47; P = .026; MDA-MB-231: monolayer cultures, mean SF(2Gy) = 0.5, versus mammospheres, mean SF(2Gy) = 0.69, difference = 0.19, 95% CI = -0.07 to 0.45; P = .09). Levels of ROS increased in both mammospheres and monolayer cultures after irradiation with a single dose of 10 Gy but were lower in mammospheres than in monolayer cultures (MCF-7 monolayer cultures: 0 Gy, mean = 1.0, versus 10 Gy, mean = 3.32, difference = 2.32, 95% CI = 0.67 to 3.98; P = .026; mammospheres: 0 Gy, mean = 0.58, versus 10 Gy, mean = 1.46, difference = 0.88, 95% CI = 0.20 to 1.56; P = .031); phosphorylation of H2AX increased in irradiated monolayer cultures, but no change was observed in mammospheres. Fractionated doses of irradiation increased activation of Notch-1 (untreated, mean = 10.7, versus treated, mean = 15.1, difference = 4.4, 95% CI = 2.7 to 6.1, P = .002) and the percentage of the cancer stem/initiating cells in the nonadherent cell population of MCF-7 monolayer cultures (untreated, mean = 3.52%, versus treated, mean = 7.5%, difference = 3.98%, 95% CI = 1.67% to 6.25%, P = .009).Breast cancer-initiating cells are a relatively radioresistant subpopulation of breast cancer cells and increase in numbers after short courses of fractionated irradiation. These findings offer a possible mechanism for the accelerated repopulation of tumor cells observed during gaps in radiotherapy.
A Mitogenomic Timescale for Birds Detects Variable Phylogenetic Rates of Molecular Evolution and Refutes the Standard Molecular Clock
Authors: Sergio L Pereira, Allan J Baker
Journal: Molecular Biology and Evolution (2006)

Current understanding of the diversification of birds is hindered by their incomplete fossil record and uncertainty in phylogenetic relationships and phylogenetic rates of molecular evolution. Here we performed the first comprehensive analysis of mitogenomic data of 48 vertebrates, including 35 birds, to derive a Bayesian timescale for avian evolution and to estimate rates of DNA evolution. Our approach used multiple fossil time constraints scattered throughout the phylogenetic tree and accounts for uncertainties in time constraints, branch lengths, and heterogeneity of rates of DNA evolution. We estimated that the major vertebrate lineages originated in the Permian; the 95% credible intervals of our estimated ages of the origin of archosaurs (258 MYA), the amniote–amphibian split (356 MYA), and the archosaur–lizard divergence (278 MYA) bracket estimates from the fossil record. The origin of modern orders of birds was estimated to have occurred throughout the Cretaceous beginning about 139 MYA, arguing against a cataclysmic extinction of lineages at the Cretaceous/Tertiary boundary. We identified fossils that are useful as time constraints within vertebrates. Our timescale reveals that rates of molecular evolution vary across genes and among taxa through time, thereby refuting the widely used mitogenomic or cytochrome b molecular clock in birds. Moreover, the 5-Myr divergence time assumed between 2 genera of geese (Branta and Anser) to originally calibrate the standard mitochondrial clock rate of 0.01 substitutions per site per lineage per Myr (s/s/l/Myr) in birds was shown to be underestimated by about 9.5 Myr. Phylogenetic rates in birds vary between 0.0009 and 0.012 s/s/l/Myr, indicating that many phylogenetic splits among avian taxa also have been underestimated and need to be revised. We found no support for the hypothesis that the molecular clock in birds “ticks” according to a constant rate of substitution per unit of mass-specific metabolic energy rather than per unit of time, as recently suggested. Our analysis advances knowledge of rates of DNA evolution across birds and other vertebrates and will, therefore, aid comparative biology studies that seek to infer the origin and timing of major adaptive shifts in vertebrates.
Exploring the Material-Induced Transcriptional Landscape of Osteoblasts on Bone Graft Materials
Authors: Nathalie Groen, Niloofar Tahmasebi, Fumitaka Shimizu, Yasuteru Sano, Takashi Kanda, Davide Barbieri, Huipin Yuan, Pamela Habibovic, Clemens A van Blitterswijk, Jan de Boer
Journal: Advanced Healthcare Materials (2015)

During the past decades, there have been major advances in the field of biomaterials, thereby generating a vast variety of materials for a broad range of tissue engineering and regeneration applications. Although gene expression profiling has been used occasionally in biomaterial research, its usefulness for understanding cell–biomaterial interactions should be further explored for it to fulfill its promise as a tool to assess and improve material properties. Here, the transcriptional landscape induced by 23 materials is explored with a variety of properties within the scope of bone regeneration. An osteoblast cell line is used to identify the gene expression profiles that can be adopted in response to biophysical and chemical cues. It is shown that TGF‐β and WNT signaling may be involved in the cellular response to osteoinductive materials along with differential cell adhesion kinetics via attenuated FAK signaling. The previously reported effect of calcium and phosphate on BMP2 and TGF‐β signaling is confirmed and the biological effect of the addition of nanohydroxyapatite in poly ( d , l ‐lactic acid) polymer particles is studied. Together with future applications, this approach will help researchers understand cellular responses in relation to material properties, which will promote the development of more effective biomaterials for applications in tissue regeneration.
TARGET LESION THIN-CAP FIBROATHEROMA DETECTED BY VIRTUAL HISTOLOGY INTRAVASCULAR ULTRASOUND AFFECTS MICROVASCULAR INJURY DURING PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH ANGINA PECTORIS
Authors: Ryotaro Yamada, Hiroyuki Okura, Teruyoshi Kume, Yoji Neishi, Takahiro Kawamoto, Akihiro Hayashida, Tetsuo Tsuchiya, Ken Saito, Koichiro Imai, Kiyoshi Yoshida
Journal: Journal of the American College of Cardiology (2010)
Xenobiotic Metabolizing Gene Variants, Dietary Heterocyclic Amine Intake, and Risk of Prostate Cancer
Authors: Stella Koutros, Sonja I. Berndt, Rashmi Sinha, Xiaomei Ma, Nilanjan Chatterjee, Michael C.R. Alavanja, Tongzhang Zheng, Wen-Yi Huang, Richard B. Hayes, Amanda J. Cross
Journal: Cancer Research (2009)

Abstract We recently reported that heterocyclic amines (HCA) are associated with prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We now use extensive genetic data from this resource to determine if risks associated with dietary HCAs {2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx); and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)} from cooked meat are modified by single nucleotide polymorphisms (SNP) in genes involved in HCA metabolism (CYP1A1, CYP1A2, CYP1B1, GSTA1, GSTM1, GSTM3, GSTP1, NAT1, NAT2, SULT1A1, SULT1A2, and UGT1A locus). We conducted a nested case-control study that included 1,126 prostate cancer cases and 1,127 controls selected for a genome-wide association study for prostate cancer. Unconditional logistic regression was used to estimate odds ratios (OR), 95% confidence intervals (95% CI), and P values for the interaction between SNPs, HCA intake, and risk of prostate cancer. The strongest evidence for an interaction was noted between DiMeIQx and MeIQx and the polymorphism rs11102001 downstream of the GSTM3 locus (Pinteraction = 0.001 for both HCAs; statistically significant after correction for multiple testing). Among men carrying the A variant, the risk of prostate cancer associated with high DiMeIQx intake was 2-fold greater than that with low intake (OR, 2.3; 95% CI, 1.2–4.7). The SNP rs11102001, which encodes a nonsynonymous amino acid change P356S in EPS8L3, is a potential candidate modifier of the effect of HCAs on prostate cancer risk. The observed effect provides evidence to support the hypothesis that HCAs may act as promoters of malignant transformation by altering mitogenic signaling. [Cancer Res 2009;69(5):1877–84]
TGF-β1 Regulates the PINCH-1–Integrin-Linked Kinase–α-Parvin Complex in Glomerular Cells
Authors: Kyu Yong Jung, Ka Chen, Matthias Kretzler, Chuanyue Wu
Journal: Journal of the American Society of Nephrology (2006)

Glomerular damage is a major cause of renal failure. Recent studies suggest that a ternary protein complex that consists of PINCH-1, integrin-linked kinase, and alpha-parvin, cytoplasmic components of cell-extracellular matrix adhesions, plays pivotal roles in regulation of glomerular cell behavior. It is reported here that TGF-beta1, a key factor in the progression of glomerular failure, regulates the PINCH-1-integrin-linked kinase-alpha-parvin (PIP) complex formation in glomerular podocytes and mesangial cells. Treatment of podocytes with TGF-beta1 inhibited the PIP complex formation. Forced disruption of the PIP complex in podocytes activated p38 mitogen-activated protein kinase and promoted apoptosis. Importantly, inhibition of p38 mitogen-activated protein kinase, either with a chemical p38 inhibitor (SB202190) or with a dominant negative form of p38alpha, alleviates podocyte apoptosis that is induced by the disruption of the PIP complex. In contrast to an inhibitory role in podocytes, TGF-beta1 promotes the PIP complex formation in mesangial cells. Thus, TGF-beta1 regulates the PIP complex in a cell type-dependent manner. Because the PIP complex promotes glomerular mesangial matrix deposition and protects podocytes from apoptosis, the TGF-beta1-induced up- and downregulation of the PIP complex likely contribute to the pleiotropic effects of TGF-beta1 on different glomerular cell types and hence the progression of glomerular failure.
Protein Expansion Is Primarily due to Indels in Intrinsically Disordered Regions
Authors: S. Light, R. Sagit, O. Sachenkova, D. Ekman, A. Elofsson
Journal: Molecular Biology and Evolution (2013)

Proteins evolve not only through point mutations but also by insertion and deletion events, which affect the length of the protein. It is well known that such indel events most frequently occur in surface-exposed loops. However, detailed analysis of indel events in distantly related and fast-evolving proteins is hampered by the difficulty involved in correctly aligning such sequences. Here, we circumvent this problem by first only analyzing homologous proteins based on length variation rather than pairwise alignments. Using this approach, we find a surprisingly strong relationship between difference in length and difference in the number of intrinsically disordered residues, where up to three quarters of the length variation can be explained by changes in the number of intrinsically disordered residues. Further, we find that disorder is common in both insertions and deletions. A more detailed analysis reveals that indel events do not induce disorder but rather that already disordered regions accrue indels, suggesting that there is a lowered selective pressure for indels to occur within intrinsically disordered regions.
Reconstructing the Duplication History of Tandemly Repeated Genes
Authors: Olivier Elemento, Olivier Gascuel, Marie-Paule Lefranc
Journal: Molecular Biology and Evolution (2002)

We present a novel approach to deal with the problem of reconstructing the duplication history of tandemly repeated genes that are supposed to have arisen from unequal recombination. We first describe the mathematical model of evolution by tandem duplication and introduce duplication histories and duplication trees. We then provide a simple recursive algorithm which determines whether or not a given rooted phylogeny can be a duplication history and another algorithm that simulates the unequal recombination process and searches for the best duplication trees according to the maximum parsimony criterion. We use real data sets of human immunoglobulins and T-cell receptors to validate our methods and algorithms. Identity between most parsimonious duplication trees and most parsimonious phylogenies for the same data, combined with the agreement with additional knowledge about the sequences, such as the presence of polymorphisms, shows strong evidence that our reconstruction procedure provides good insights into the duplication histories of these loci.
A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter.
Authors: G Melillo, T Musso, A Sica, L S Taylor, G W Cox, L Varesio
Journal: The Journal of Experimental Medicine (1995)

Picolinic acid, a catabolite of L-tryptophan, activates the transcription of the inducible nitric oxide synthase gene (iNOS) in IFN-gamma-treated murine macrophages. We performed functional studies on the 5' flanking region of the iNOS gene linked to a CAT reporter gene to identify the cis-acting element(s) responsible for the activation of iNOS transcription by picolinic acid. Transient transfection assays showed that the full-length iNOS promoter in the murine macrophage cell line ANA-1 was activated by the synergistic interaction between IFN-gamma and picolinic acid. Deletion or mutation of the iNOS promoter region from -227 to -209, containing a sequence homology to a hypoxia-responsive enhancer (iNOS-HRE), decreased picolinic acid- but not LPS-induced CAT activity by more than 70%. Functional studies using a tk promoter-CAT reporter gene plasmid demonstrated that the iNOS-HRE was sufficient to confer inducibility by picolinic acid but not by IFN-gamma or LPS. Electrophoretic mobility shift assays confirmed that picolinic acid alone induced a specific binding activity to the iNOS-HRE. Furthermore, we found that the iNOS-HRE activity was inducible by hypoxia and that hypoxia in combination with IFN-gamma activated the iNOS promoter in transient transfection assays and induced iNOS transcription and mRNA expression. These data establish that the iNOS-HRE is a novel regulatory element of the iNOS promoter activity in murine macrophages and provide the first evidence that iNOS is a hypoxia-inducible gene.
A household epidemic of tropical sprue.
Authors: V I Mathan, M Ignatius, S J Baker
Journal: Gut (1966)

EDITORIAL COMMENT This study focuses on an Indian family unit in which 16 out of 27 members developed a malabsorption syndrome: seven were studied in detail and the possible epidemiological factors are analysed.The possibility of a virus infection is discussed.FIG. 1.The house and some of the family.
Injuries in Swedish skydiving
Authors: Anton Westman, Ulf Björnstig
Journal: British Journal of Sports Medicine (2007)

To create a basis for prevention of modern skydiving injuries.Descriptive epidemiological study.National total material.Data on all reported injury events (n = 257) in Swedish skydiving 1999-2003 (total 539,885 jumps) were retrieved from the Swedish Parachute Association. Non-fatally injured skydivers were sent a questionnaire asking for event and injury details (response rate 89%), and supplementary hospital records were retrieved for the most serious injuries (n = 85). Human, equipment and environmental factors were assessed for risk.Frequency and severity of injuries.Incidence of non-fatal injury events was 48 per 100,000 jumps. The lower extremities, spine and shoulders were important regions of injury. The most serious injuries were experienced by licensed skydivers, but students in training had a higher injury rate and more often left the sport because of the injury. Of two student-training systems, one had an incidence less than half that of the other.A basis for prevention was created, showing a potential for reduction of frequency and severity of injuries with training and technical interventions.
Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer
Authors: Jolanta F. Kukowska-Latallo, Kimberly A. Candido, Zhengyi Cao, Shraddha S. Nigavekar, Istvan J. Majoros, Thommey P. Thomas, Lajos P. Balogh, Mohamed K. Khan, James R. Baker
Journal: Cancer Research (2005)

Abstract Prior studies suggested that nanoparticle drug delivery might improve the therapeutic response to anticancer drugs and allow the simultaneous monitoring of drug uptake by tumors. We employed modified PAMAM dendritic polymers &amp;lt;5 nm in diameter as carriers. Acetylated dendrimers were conjugated to folic acid as a targeting agent and then coupled to either methotrexate or tritium and either fluorescein or 6-carboxytetramethylrhodamine. These conjugates were injected i.v. into immunodeficient mice bearing human KB tumors that overexpress the folic acid receptor. In contrast to nontargeted polymer, folate-conjugated nanoparticles concentrated in the tumor and liver tissue over 4 days after administration. The tumor tissue localization of the folate-targeted polymer could be attenuated by prior i.v. injection of free folic acid. Confocal microscopy confirmed the internalization of the drug conjugates into the tumor cells. Targeting methotrexate increased its antitumor activity and markedly decreased its toxicity, allowing therapeutic responses not possible with a free drug.
Increased function of pronociceptive TRPV1 at the level of the joint in a rat model of osteoarthritis pain
Authors: S Kelly, R J Chapman, S Woodhams, D R Sagar, J Turner, J J Burston, C Bullock, K Paton, J Huang, A Wong, D F McWilliams, B N Okine, D A Barrett, G J Hathway, D A Walsh, V Chapman
Journal: Annals of the Rheumatic Diseases (2013)

Objectives Blockade of transient receptor potential vanilloid 1 (TRPV1) with systemic antagonists attenuates osteoarthritis (OA) pain behaviour in rat models, but on-target-mediated hyperthermia has halted clinical trials. The present study investigated the potential for targeting TRPV1 receptors within the OA joint in order to produce analgesia. Methods The presence of TRPV1 receptors in human synovium was detected using western blotting and immunohistochemistry. In a rat model of OA, joint levels of an endogenous ligand for TRPV1, 12-hydroxy-eicosatetraenoic acid (12-HETE), were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Effects of peripheral administration of the TRPV1 receptor antagonist JNJ-17203212 on afferent fibre activity, pain behaviour and core body temperature were investigated. Effects of a spinal administration of JNJ-17203212 on dorsal horn neuronal responses were studied. Results We demonstrate increased TRPV1 immunoreactivity in human OA synovium, confirming the diseased joint as a potential therapeutic target for TRPV1-mediated analgesia. In a model of OA pain, we report increased joint levels of 12-HETE, and the sensitisation of joint afferent neurones to mechanical stimulation of the knee. Local administration of JNJ-17203212 reversed this sensitisation of joint afferents and inhibited pain behaviour (weight-bearing asymmetry), to a comparable extent as systemic JNJ-17203212, in this model of OA pain, but did not alter core body temperature. There was no evidence for increased TRPV1 function in the spinal cord in this model of OA pain. Conclusions Our data provide a clinical and mechanistic rationale for the future investigation of the therapeutic benefits of intra-articular administration of TRPV1 antagonists for the treatment of OA pain.