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Biomedical Science

This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 9.

Engineering high‐intensity stabilized photoreactive biocomposite materials for gas‐phase carbon capture
(Source: Biotechnology and Bioengineering)
Source: Biotechnology and Bioengineering - August 25, 2014 Category: Biomedical Science Tags: Spotlight Source Type: research

Magnetostrictive particle based biosensors for in situ and real‐time detection of pathogens in water
ABSTRACT Biosensors for in situ detection of pathogenic bacteria in liquid are developed using magnetostrictive particles (MSP) as the sensor platform. The sensing elements used are phage E2 against Salmonella typhimurium, monoclonal antibody against Listeria monocytogenes, polyclonal antibody against Escherichia coli, and polyclonal antibody against Staphylococcus aureus, respectively. These biosensors were characterized in cultures with different populations ranging from 5 × 101 to 5 × 108 cfu/mL. It is found that the MSP‐based biosensors work well in water and have a rapid response with a response time in ...
Source: Biotechnology and Bioengineering - August 25, 2014 Category: Biomedical Science Authors: Kewei Zhang, Liling Fu, Lin Zhang, Z.‐Y. Cheng, Tung‐Shi Huang Tags: Article Source Type: research

A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications.
CONCLUSIONS: Patients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration. PMID: 25181642 [PubMed - as supplied by publisher] (Source: Advances in Medical Sciences)
Source: Advances in Medical Sciences - August 24, 2014 Category: Biomedical Science Authors: Yandrapu H, Marcinkiewicz M, Poplawski C, Namiot Z, Zbroch T, Sarosiek J Tags: Adv Med Sci Source Type: research

Title page/Editorial Board
(Source: Medical Hypotheses)
Source: Medical Hypotheses - August 23, 2014 Category: Biomedical Science Source Type: research

Blocking endocytotic mechanisms to improve heterologous protein titers in Saccharomyces cerevisiae
In this study, we block endocytosis and trafficking to the vacuole using a modified TEV Protease‐Mediated Induction of Protein Instability (mTIPI) system to disrupt the endocytotic and vacuolar complexes. We report that conditional knock‐down of endocytosis gene Rvs161 improved the concentration of α‐amylase in supernatant of S. cerevisiae cultures by 63.7% compared to controls. By adaptive evolution, we obtained knock‐down mutants in Rvs161 and End3 genes with 2‐fold and 3‐fold α‐amylase concentrations compared to controls that were not evolved. Our study demonstrates that genetic blocking of endocytotic m...
Source: Biotechnology and Bioengineering - August 23, 2014 Category: Biomedical Science Authors: William A. Rodríguez‐Limas, Victoria Tannenbaum, Keith E.J. Tyo Tags: Engineering Science of Biological Systems Source Type: research

Computational identification of surrogate genes for prostate cancer phases using machine learning and molecular network analysis
Conclusion: We conclude that the surrogate genes we have selected compose an effective classifier of prostate cancer phases, which corresponds to a minimum characterization of cancer phenotypes on the molecular level. Along with their molecular interaction partners, it is fairly to assume that these genes may have important roles in prostate cancer development; particularly, the un-reported genes may bring new insights for the understanding of the molecular mechanisms. Thus our results may serve as a candidate gene set for further functional studies. (Source: Theoretical Biology and Medical Modelling)
Source: Theoretical Biology and Medical Modelling - August 23, 2014 Category: Biomedical Science Authors: Rudong LiXiao DongChengcheng MaLei Liu Source Type: research

Mangiferin: a promising therapeutic agent for rheumatoid arthritis treatment
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Despite aggressive treatment with anti-rheumatic drugs, progressive destruction of joints continues to occur in RA patients, who subsequently require joint surgery. A lot of evidence suggest that fibroblast-like synovial cells (FLS) play crucial role in joint degradation and the propagation of inflammation in RA. The expansion of fibroblast populations in the joint results primarily from the inhibition of pro-apoptotic pathways, rather than large scale proliferation. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 23, 2014 Category: Biomedical Science Authors: P. Luczkiewicz, A. Kokotkiewicz, Anna Dampc, M. Luczkiewicz Source Type: research

Non-invasive pre-implantation genetic diagnosis of X-linked disorders
Pre-implantation genetic diagnosis (PGD) is a powerful clinical tool to identify embryos with or at risk of specific genetic diseases before implantation in utero after in vitro fertilization (IVF). PGD is performed on embryo biopsies that are obtained by aspiration of one or two cells from pre-implantation embryos at day 3 or day 5/6 of culture. However this is a traumatic method that cannot be avoided because non-invasive procedures to assess the genetic status of pre-implantation embryos are not available yet. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 23, 2014 Category: Biomedical Science Authors: Said Assou, Ounissa Aït-Ahmed, Safia El Messaoudi, Alain R. Thierry, Samir Hamamah Source Type: research

Multi-scale finite element model of growth plate damage during the development of slipped capital femoral epiphysis.
Abstract Slipped capital femoral epiphysis (SCFE) is one of the most common disorders of adolescent hips. A number of works have related the development of SCFE to mechanical factors. Due to the difficulty of diagnosing SCFE in its early stages, the disorder often progresses over time, resulting in serious side effects. Therefore, the development of a tool to predict the initiation of damage in the growth plate is needed. Because the growth plate is a heterogeneous structure, to develop a precise and reliable model, it is necessary to consider this structure from both macro- and microscale perspectives. Thus, the m...
Source: Biomechanics and Modeling in Mechanobiology - August 23, 2014 Category: Biomedical Science Authors: Farzaneh S, Paseta O, Gómez-Benito MJ Tags: Biomech Model Mechanobiol Source Type: research

Manipulation of receptor oligomerization as a strategy to inhibit signaling by TNF superfamily members.
Abstract Signaling by receptor activator of nuclear factor κB (RANK) in response to its ligand RANKL, which is a member of the tumor necrosis factor (TNF) superfamily of cytokines, stimulates osteoclast formation and bone resorption. Thus, this ligand-receptor pair is a therapeutic target for various disorders, such as osteoporosis and metastasis of cancer to bone. RANKL exists as a physiological homotrimer, with each monomer recognizing a single molecule of RANK or the decoy receptor osteoprotegerin (OPG), which inhibits osteoclastogenesis. We engineered a RANKL protein in which all three monomers of RANKL were e...
Source: Science Signaling - August 22, 2014 Category: Biomedical Science Authors: Warren JT, Nelson CA, Decker CE, Zou W, Fremont DH, Teitelbaum SL Tags: Sci Signal Source Type: research

Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells.
Abstract The traditional view of how intracellular effector proteins are recruited to the B cell antigen receptor (BCR) complex at the plasma membrane is based on the occurrence of direct protein-protein interactions, as exemplified by the recruitment of the tyrosine kinase Syk (spleen tyrosine kinase) to phosphorylated motifs in BCR signaling subunits. By contrast, the subcellular targeting of the cytosolic adaptor protein SLP-65 (Src homology 2 domain-containing leukocyte adaptor protein of 65 kD), which serves as a proximal Syk substrate, is unclear. We showed that SLP-65 activation required its association at v...
Source: Science Signaling - August 22, 2014 Category: Biomedical Science Authors: Engelke M, Pirkuliyeva S, Kühn J, Wong L, Boyken J, Herrmann N, Becker S, Griesinger C, Wienands J Tags: Sci Signal Source Type: research

The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance cancer cell motility.
ullick WJ, Yarden Y, Santis G, Winn M, Kholodenko BN, Martin-Fernandez ML, Parker P, Tutt A, Ameer-Beg SM, Ng T Abstract The epidermal growth factor receptor (EGFR) is a member of the ErbB family that can promote the migration and proliferation of breast cancer cells. Therapies that target EGFR can promote the dimerization of EGFR with other ErbB receptors, which is associated with the development of drug resistance. Understanding how interactions among ErbB receptors alter EGFR biology could provide avenues for improving cancer therapy. We found that EGFR interacted directly with the CYT1 and CYT2 variants of ErbB...
Source: Science Signaling - August 22, 2014 Category: Biomedical Science Authors: Kiuchi T, Ortiz-Zapater E, Monypenny J, Matthews DR, Nguyen LK, Barbeau J, Coban O, Lawler K, Burford B, Rolfe DJ, de Rinaldis E, Dafou D, Simpson MA, Woodman N, Pinder S, Gillett CE, Devauges V, Poland SP, Fruhwirth G, Marra P, Boersma YL, Plückthun A, Tags: Sci Signal Source Type: research

Outflanking RANK with a Designer Antagonist Cytokine.
Abstract Members of the tumor necrosis factor (TNF) superfamily of cytokines are noncovalently linked trimers that play important roles in regulating the immune system and have emerged as successful therapeutic targets in various rheumatic and autoimmune conditions. Traditionally, antibodies to cytokines or receptor-Fc fusion proteins have been used to block signaling by TNF family cytokines. In this issue of Science Signaling, Warren et al. have taken a new approach to blocking the action of the TNF superfamily member RANKL [receptor activator of nuclear factor κB (RANK) ligand], which plays an important role in ...
Source: Science Signaling - August 22, 2014 Category: Biomedical Science Authors: Ou-Yang CW, Siegel RM Tags: Sci Signal Source Type: research

Short-term high-fat diet increases macrophage markers in skeletal muscle accompanied by impaired insulin signaling in healthy male subjects
In conclusion, short-term HFHC-diet increases expression of macrophage markers in skeletal muscle of healthy men accompanied by reduced markers of insulin signaling and development of IR. Therefore, recruitment of macrophages into muscle may be an early event in development of insulin resistance in response to short-term HFHC-feeding. (Source: Clinical Science)
Source: Clinical Science - August 22, 2014 Category: Biomedical Science Authors: M R. Boon, L E.H. Bakker, M C. Haks, E Quinten, G Schaart, L van Beek, Y Wang, L van Schinkel, V van Harmelen, A Edo Meinders, T H.M. Ottenhoff, K Willems van Dijk, B Guigas, I M. Jazet, P C.N. Rensen Source Type: research

Folliculo-stellate cells – potential mediators of the inflammaging-induced hyperactivity of the hypothalamic-pituitary-adrenal axis in healthy elderly individuals
Some evidence has suggested that, with age, the hypothalamic-pituitary-adrenal (HPA) axis becomes less resilient, leading to higher glucocorticoids nocturnal levels and a flattening of the circadian profiles. Such age-related changes in the activity of the HPA axis has overexposed the brain and peripheral organs to the effects of the glucocorticoids, increasing the morbidity and mortality rates of the elderly. Debate among scientists regarding the contributions of HPA axis age-related changes of impaired feedback regulation vs. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 22, 2014 Category: Biomedical Science Authors: Ivan Jovanović, Slađana Ugrenović, Miljana Ljubomirović, Ljiljana Vasović, Rade Čukuranović, Vladisav Stefanović Source Type: research

Pathophysiological dilemmas of lipedema
Lipedema is a common, but often underdiagnosed masquerading disease of obesity, which almost exclusively affects females. There are many debates regarding the diagnosis as well as the treatment strategies of the disease. The clinical diagnosis is relatively simple, however knowledge regarding the pathomechanism is less than limited and curative therapy does not exist at all demanding an urgent need for extensive research. According to our hypothesis, lipedema is an estrogen-regulated polygenetic disease, which manifests in parallel with feminine hormonal changes and leads to vasculo- and lymphangiopathy. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 22, 2014 Category: Biomedical Science Authors: E. Szel, L. Kemeny, G. Groma, G. Szolnoky Source Type: research

Research explains how cellular guardians of the gut develop
A specialized class of immune cell inhabits the thin layer of tissue that lines the intestine. New experiments reveal how these cells arise, sometimes from other mature immune cells. More » (Source: The Rockefeller University Newswire)
Source: The Rockefeller University Newswire - August 21, 2014 Category: Biomedical Science Authors: pubaff Tags: Science News Bernardo Reis Daniel Mucida immunity inflammation intraepithelial lymphocytes t cells Source Type: news

Editorial Board
(Source: Prostaglandins, Leukotrienes and Essential Fatty Acids)
Source: Prostaglandins, Leukotrienes and Essential Fatty Acids - August 21, 2014 Category: Biomedical Science Source Type: research

Glycemic Regulation and Insulin Secretion Are Abnormal in Cystic Fibrosis Pigs Despite Sparing of Islet Cell Mass
Diabetes is a common and significant comorbidity in cystic fibrosis (CF). The pathogenesis of CF-related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal,newbornand older CF and non-CF pigsand assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and old...
Source: Clinical Science - August 21, 2014 Category: Biomedical Science Authors: A Uc, A K. Olivier, M A. Griffin, D K. Meyerholz, J Yao, M Abu-El-Haija, K Buchanan, O G Vanegas Calderón, M Abu-El-Haija, A A. Pezzulo, L R. Reznikov, M J. Hoegger, M V. Rector, L S. Ostedgaard, P J. Taft, N D. Gansemer, P S. Ludwig, E E. Hornick, D A. Source Type: research

A robust chromatin immunoprecipitation protocol for studying transcription factor–DNA interactions and histone modifications in wood-forming tissue
Nature Protocols 9, 2180 (2014). doi:10.1038/nprot.2014.146 Authors: Wei Li, Ying-Chung Lin, Quanzi Li, Rui Shi, Chien-Yuan Lin, Hao Chen, Ling Chuang, Guan-Zheng Qu, Ronald R Sederoff & Vincent L Chiang Woody cells and tissues are recalcitrant to standard chromatin immunoprecipitation (ChIP) procedures. However, we recently successfully implemented ChIP in wood-forming tissue of the model woody plant Populus trichocarpa. Here we provide the detailed ChIP protocol optimized for wood-forming tissue that we used in those (Source: Nature Protocols)
Source: Nature Protocols - August 21, 2014 Category: Biomedical Science Authors: Wei LiYing-Chung LinQuanzi LiRui ShiChien-Yuan LinHao ChenLing ChuangGuan-Zheng QuRonald R SederoffVincent L Chiang Tags: Protocol Source Type: research

A simple improved-throughput xylem protoplast system for studying wood formation
Nature Protocols 9, 2194 (2014). doi:10.1038/nprot.2014.147 Authors: Ying-Chung Lin, Wei Li, Hao Chen, Quanzi Li, Ying-Hsuan Sun, Rui Shi, Chien-Yuan Lin, Jack P Wang, Hsi-Chuan Chen, Ling Chuang, Guan-Zheng Qu, Ronald R Sederoff & Vincent L Chiang Isolated protoplasts serve as a transient expression system that is highly representative of stable transgenics in terms of transcriptome responses. They can also be used as a cellular system to study gene transactivation and nucleocytoplasmic protein trafficking. They are particularly useful for systems studies in (Source: Nature Protocols)
Source: Nature Protocols - August 21, 2014 Category: Biomedical Science Authors: Ying-Chung LinWei LiHao ChenQuanzi LiYing-Hsuan SunRui ShiChien-Yuan LinJack P WangHsi-Chuan ChenLing ChuangGuan-Zheng QuRonald R SederoffVincent L Chiang Tags: Protocol Source Type: research

Tethered particle analysis of supercoiled circular DNA using peptide nucleic acid handles
Nature Protocols 9, 2206 (2014). doi:10.1038/nprot.2014.152 Authors: Kamilla Norregaard, Magnus Andersson, Peter Eigil Nielsen, Stanley Brown & Lene B Oddershede This protocol describes how to monitor individual naturally supercoiled circular DNA plasmids bound via peptide nucleic acid (PNA) handles between a bead and a surface. The protocol was developed for single-molecule investigation of the dynamics of supercoiled DNA, and it allows the investigation of both (Source: Nature Protocols)
Source: Nature Protocols - August 21, 2014 Category: Biomedical Science Authors: Kamilla NorregaardMagnus AnderssonPeter Eigil NielsenStanley BrownLene B Oddershede Tags: Protocol Source Type: research

A comparative cross-linking strategy to probe conformational changes in protein complexes
Nature Protocols 9, 2224 (2014). doi:10.1038/nprot.2014.144 Authors: Carla Schmidt & Carol V Robinson Chemical cross-linking, together with mass spectrometry (MS), is a powerful combination for probing subunit interactions within static protein assemblies. To probe conformational changes in response to stimuli, we have developed a comparative cross-linking strategy, using lysine-specific deuterated and nondeuterated bis(sulfosuccinimidyl)suberate cross-linking reagents (BS3 (Source: Nature Protocols)
Source: Nature Protocols - August 21, 2014 Category: Biomedical Science Authors: Carla SchmidtCarol V Robinson Tags: Protocol Source Type: research

Corrigendum to “A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution” Prostaglandins Leukot. Essent. Fatty Acids 88(1) (2013) 5–13
In the article cited above, it has recently come to the authors׳ attention that there was a misprint on p. 10 referring to the mathematical expression (1). The Greek letter α was inexplicably replaced by the word QUOTE. The authors regret this error. (Source: Prostaglandins, Leukotrienes and Essential Fatty Acids)
Source: Prostaglandins, Leukotrienes and Essential Fatty Acids - August 21, 2014 Category: Biomedical Science Authors: Michael A. Crawford, C. Leigh Broadhurst, Martin Guest, Atulya Nagar, Yiqun Wang, Kebreab Ghebremeskel, Walter F. Schmidt Tags: Corrigendum Source Type: research

Biomedical science: Houston has lift-off
Nature (2014). doi:10.1038/nj7514-339a Author: Paul Smaglik Buoyed by state funding, biomedical sciences are booming in the Texan city. (Source: Nature)
Source: Nature - August 20, 2014 Category: Research Authors: Paul Smaglik Tags: Naturejobs Source Type: research

A damage model for the percutaneous triple hemisection technique for tendo-Achilles lengthening
A full understanding of the mechanisms of action in the percutaneous triple hemisection technique for tendo-achilles lengthening has yet to be acquired and therefore, an accurate prediction of the amount of lengthening that occurs is difficult to make. The purpose of this research was to develop a phenomenological damage model that utilizes both matrix and fiber damage and replicates the observed behavior of the tendon tissue during the lengthening process. Matrix damage was triggered and evolved relative to shear strain and the fiber damage was triggered and evolved relative to fiber stretch. (Source: Journal of Biomechanics)
Source: Journal of Biomechanics - August 20, 2014 Category: Biomedical Science Authors: Gregory A. Von Forell, Anton E. Bowden Source Type: research

Primary open-angle glaucoma: neuroendocrine-immune disorder?
Primary open-angle glaucoma (POAG) is an irreversible optic neuropathy characterized by a progressive loss of retinal ganglion cells (RGCs) and an open anterior chamber angle. The intraocular pressure (IOP) is usually but not always elevated. It is the most common form of several types of glaucoma, affecting anestimated44.7 million people worldwide in 2010 [1]. Although the pathogenesis of POAG is still unclear, a variety of hypotheses have been developed to elucidate its pathological mechanism. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 20, 2014 Category: Biomedical Science Authors: Ting Zhang, Xuelu Xie, Fang Lu Source Type: research

Hypothesis about alternative use of redundant regulatory elements was validated by recent results
I recently proposed the hypothesis that there is heritable person-to-person variation in the of use redundant genetic elements [1]. It was also postulated that regulatory regions such as promoters and enhancers are particular cases of the proposed hypothesis [1]. A recent study by Kasowski et al. [2] positively confirmed the hypothesis about the alternative use of regulatory elements. Kasowski et al. [2] assessed chromatin states through measures of histone modifications, and binding of cohesion and CTCF. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 20, 2014 Category: Biomedical Science Authors: Edward A. Ruiz-Narváez Source Type: research

CD146- and CD105- positive phenotypes of retinal ganglion cells. Are these proofs of neuronal regeneration?
The in vivo identity of stem cells is not yet clear. Numerous studies involve the perivascular niches as providers of stem cells during regenerative processes. CD146, in humans, as well as gicerin, at chicken, play roles in neuronal development and neurites extension. CD146 is a marker of stemness but also a pericitary marker. Stem cells in vascular niches can differentiate in neural cells. By applying CD146 and CD105 antibodies on human retinas from glaucomatous eyes, CD146-positive retinal ganglion cells (RGCs) were found, some being placed in perivascular positions; ongoing processes of neurites extension were related t...
Source: Medical Hypotheses - August 20, 2014 Category: Biomedical Science Authors: A.D. Vrapciu, M.C. Rusu, L.M. Voinea, C.G. Corbu Source Type: research

Adiposity is associated with improved neuromuscular reaction time
The development of the central and peripheral nervous system has long been associated with nutritional status [1–3]. This is primarily because the substrates necessary for the effective functioning of the nervous system can be derived only from dietary intake. Numerous studies have highlighted the mechanisms by which the nervous system is affected by malnutrition [4–7]. It is appropriate to determine to what extent malnourishment impairs neuronal performance. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 20, 2014 Category: Biomedical Science Authors: James Grantham, Maciej Henneberg Source Type: research

Glycogenolysis: Is muscle glycogen phosphorylase differentially activated depending on the conditions of hypoxia and exercise ?
Glycogen that is known as a cellular reserve of metabolic energy, is degraded by glycogen phosphorylase [1]. The default state of muscle phosphorylase is the inactive b-form, which is allosterically activated by AMP produced from ATP. The enzyme is also activated by conversion into a-form by the covalent phosphorylation of the subunit. The conversion is initiated by epinephrine or Ca/calmodulin system in muscle [1]. However, it has been uncertain whether the activation of phosphorylase is dependent on the allosteric activation by AMP or on the covalent phosphorylation of the enzyme. (Source: Medical Hypotheses)
Source: Medical Hypotheses - August 20, 2014 Category: Biomedical Science Authors: Masataka Yoshino, Keiko Murakami Source Type: research

A damage model for the percutaneous triple hemisection technique for tendo-achilles lengthening
A full understanding of the mechanisms of action in the percutaneous triple hemisection technique for tendo-achilles lengthening has yet to be acquired and therefore, an accurate prediction of the amount of lengthening that occurs is difficult to make. The purpose of this research was to develop a phenomenological damage model that utilizes both matrix and fiber damage and replicates the observed behavior of the tendon tissue during the lengthening process. Matrix damage was triggered and evolved relative to shear strain and the fiber damage was triggered and evolved relative to fiber stretch. (Source: Journal of Biomechanics)
Source: Journal of Biomechanics - August 20, 2014 Category: Biomedical Science Authors: Gregory A. Von Forell, Anton E. Bowden Source Type: research

Relationships of plasma lipoprotein(a) levels with insulin resistance in hypertensive patients
Lipoprotein(a) [Lp(a)] is an emergent cardiovascular risk factor that is related to the presence and severity of cardiovascular damage in hypertensive patients. In these patients, insulin resistance is frequently detected but its relationship with plasma Lp(a) is not clear. The aim of this study was to examine the relationships between Lp(a) and variables of glucose metabolism in hypertension. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - August 20, 2014 Category: Biomedical Science Authors: Luigi Marzano, GianLuca Colussi, Martina Del Torre, Leonardo A. Sechi, Cristiana Catena Source Type: research

Menin determines K-RAS proliferative outputs in endocrine cells
Endocrine cell proliferation fluctuates dramatically in response to signals that communicate hormone demand. The genetic alterations that override these controls in endocrine tumors often are not associated with oncogenes common to other tumor types, suggesting that unique pathways govern endocrine proliferation. Within the pancreas, for example, activating mutations of the prototypical oncogene KRAS drive proliferation in all pancreatic ductal adenocarcimomas but are never found in pancreatic endocrine tumors. Therefore, we asked how cellular context impacts K-RAS signaling. We found that K-RAS paradoxically suppressed, r...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Chester E. Chamberlain, David W. Scheel, Kathleen McGlynn, Hail Kim, Takeshi Miyatsuka, Juehu Wang, Vinh Nguyen, Shuhong Zhao, Anastasia Mavropoulos, Aswin G. Abraham, Eric O’Neill, Gregory M. Ku, Melanie H. Cobb, Gail R. Martin, Michael S. German Source Type: research

Periderm prevents pathological epithelial adhesions during embryogenesis
Appropriate development of stratified, squamous, keratinizing epithelia, such as the epidermis and oral epithelia, generates an outer protective permeability barrier that prevents water loss, entry of toxins, and microbial invasion. During embryogenesis, the immature ectoderm initially consists of a single layer of undifferentiated, cuboidal epithelial cells that stratifies to produce an outer layer of flattened periderm cells of unknown function. Here, we determined that periderm cells form in a distinct pattern early in embryogenesis, exhibit highly polarized expression of adhesion complexes, and are shed from the outer ...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Rebecca J. Richardson, Nigel L. Hammond, Pierre A. Coulombe, Carola Saloranta, Heidi O. Nousiainen, Riitta Salonen, Andrew Berry, Neil Hanley, Denis Headon, Riitta Karikoski, Michael J. Dixon Source Type: research

Cyclooxygenase-2–dependent lymphangiogenesis promotes nodal metastasis of postpartum breast cancer
Breast involution following pregnancy has been implicated in the high rates of metastasis observed in postpartum breast cancers; however, it is not clear how this remodeling process promotes metastasis. Here, we demonstrate that human postpartum breast cancers have increased peritumor lymphatic vessel density that correlates with increased frequency of lymph node metastases. Moreover, lymphatic vessel density was increased in normal postpartum breast tissue compared with tissue from nulliparous women. In rodents, mammary lymphangiogenesis was upregulated during weaning-induced mammary gland involution. Furthermore, breast ...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Traci R. Lyons, Virginia F. Borges, Courtney B. Betts, Qiuchen Guo, Puja Kapoor, Holly A. Martinson, Sonali Jindal, Pepper Schedin Source Type: research

FGF21 is an endocrine signal of protein restriction
Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Thomas Laeger, Tara M. Henagan, Diana C. Albarado, Leanne M. Redman, George A. Bray, Robert C. Noland, Heike Münzberg, Susan M. Hutson, Thomas W. Gettys, Michael W. Schwartz, Christopher D. Morrison Source Type: research

A human immunodeficiency caused by mutations in the PIK3R1 gene
Recently, patient mutations that activate PI3K signaling have been linked to a primary antibody deficiency. Here, we used whole-exome sequencing and characterized the molecular defects in 4 patients from 3 unrelated families diagnosed with hypogammaglobulinemia and recurrent infections. We identified 2 different heterozygous splice site mutations that affect the same splice site in PIK3R1, which encodes the p85α subunit of PI3K. The resulting deletion of exon 10 produced a shortened p85α protein that lacks part of the PI3K p110-binding domain. The hypothetical loss of p85α-mediated inhibition of p110 activity was suppor...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Marie-Céline Deau, Lucie Heurtier, Pierre Frange, Felipe Suarez, Christine Bole-Feysot, Patrick Nitschke, Marina Cavazzana, Capucine Picard, Anne Durandy, Alain Fischer, Sven Kracker Source Type: research

PAX7 expression defines germline stem cells in the adult testis
Spermatogenesis is a complex, multistep process that maintains male fertility and is sustained by rare germline stem cells. Spermatogenic progression begins with spermatogonia, populations of which express distinct markers. The identity of the spermatogonial stem cell population in the undisturbed testis is controversial due to a lack of reliable and specific markers. Here we identified the transcription factor PAX7 as a specific marker of a rare subpopulation of Asingle spermatogonia in mice. PAX7+ cells were present in the testis at birth. Compared with the adult testis, PAX7+ cells constituted a much higher percentage o...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Gina M. Aloisio, Yuji Nakada, Hatice D. Saatcioglu, Christopher G. Peña, Michael D. Baker, Edward D. Tarnawa, Jishnu Mukherjee, Hema Manjunath, Abhijit Bugde, Anita L. Sengupta, James F. Amatruda, Ileana Cuevas, F. Kent Hamra, Diego H. Castrillon Source Type: research

A selective microRNA-based strategy inhibits restenosis while preserving endothelial function
Drugs currently approved to coat stents used in percutaneous coronary interventions do not discriminate between proliferating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). This lack of discrimination delays reendothelialization and vascular healing, increasing the risk of late thrombosis following angioplasty. We developed a microRNA-based (miRNA-based) approach to inhibit proliferative VSMCs, thus preventing restenosis, while selectively promoting reendothelialization and preserving EC function. We used an adenoviral (Ad) vector that encodes cyclin-dependent kinase inhibitor p27Kip1 (p27) with target s...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Gaetano Santulli, Anetta Wronska, Kunihiro Uryu, Thomas G. Diacovo, Melanie Gao, Steven O. Marx, Jan Kitajewski, Jamie M. Chilton, Kemal Marc Akat, Thomas Tuschl, Andrew R. Marks, Hana Totary-Jain Source Type: research

Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease
CONCLUSION. We demonstrated that IL-1β inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1β plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1β inhibition is warranted.TRIAL REGISTRATION. ClinicalTrials.gov NCT01267994.FUNDING. NIH, Merrill & Phoebe Goodman Otology Research Center, and Long Island Hearing & Speech Society. (Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Andrea Vambutas, Martin Lesser, Virginia Mullooly, Shresh Pathak, Gerald Zahtz, Lisa Rosen, Elliot Goldofsky Source Type: research

IL-1β inhibition in autoimmune inner ear disease: can you hear me now?
Clinical vignette: A 51-year-old man with right-sided sudden hearing loss presents to the otology clinic. He has a 4-year history of episodic vertigo of several hours’ duration and fluctuating, progressive sensorineural hearing loss in his left ear. The vertigo attacks have not occurred for the last 18 months, and the left ear hearing is consistently poor. The patient’s right ear hearing has dropped in the last 36 hours. MRI imaging of brain and temporal bone are normal. A 2-week “burst and taper” of oral prednisone is administered with no effect. Over the next 3 months, serial audiograms show rapidly progressive l...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Steven D. Rauch Source Type: research

Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling
Primary immune deficiency diseases arise due to heritable defects that often involve signaling molecules required for immune cell function. Typically, these genetic defects cause loss of gene function, resulting in primary immune deficiencies such as severe combined immune deficiency (SCID) and X-linked agammaglobulinemia (XLA); however, gain-of-function mutations may also promote immune deficiency. In this issue of the JCI, Deau et al. establish that gain-of-function mutations in PIK3R1, which encodes the p85α regulatory subunit of class IA PI3Ks, lead to immunodeficiency. These observations are consistent with previous ...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Craig M. Walsh, David A. Fruman Source Type: research

Play down protein to play up metabolism?
This study not only sheds new light on the role of FGF21 in systems metabolism, but also on the ways our bodies cope with the ever-changing availability of different dietary macronutrients. (Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Timo D. Müller, Matthias H. Tschöp Source Type: research

Healing the injured vessel wall using microRNA-facilitated gene delivery
Drug-eluting stents have emerged as potent weapons in the treatment of patients with symptomatic coronary artery disease by reducing restenosis rates; however, a significant clinical consequence of these stents is delayed reendothelialization, which may increase the risk of late stent thrombosis. In this issue of the JCI, Santulli and colleagues generated an adenovirus that expresses the cyclin-dependent kinase inhibitor p27Kip1 (p27) and bears four tandem copies of target sequences for the endothelial cell–enriched microRNA (miRNA) miR-126-3p (Ad-p27-126TS) in an attempt to specifically reduce proliferation of vascular ...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Mark W. Feinberg Source Type: research

“RAS”ling β cells to proliferate for diabetes: why do we need MEN?
Adult human pancreatic β cells are refractory to current therapeutic approaches to enhance proliferation. This reluctance to expand is problematic, especially for people with diabetes who lack sufficient numbers of functional insulin-producing β cells and could therefore benefit from therapies for β cell expansion. In this issue of the JCI, Chamberlain et al. describe a surprising series of observations that involve two downstream arms of the RAS signaling pathway, MAPK and RASSF proteins, which also involve the tumor suppressor menin. The findings of this study may help explain the difficulty of inducing β cell prolif...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Adolfo García-Ocaña, Andrew F. Stewart Source Type: research

Inflammatory lymphangiogenesis in postpartum breast tissue remodeling
Like many cancers, mammary carcinomas use lymphatic vessels to disseminate, and numerous clinical and experimental studies have documented a strong correlation between peritumoral lymphangiogenesis and tumor dissemination. At the same time, many other factors can affect the incidence, invasiveness, and mortality of breast cancer, including lactation history. Although lactation reduces overall cancer risk, patients diagnosed within 5 years of pregnancy have an increased incidence of metastatic disease. In this issue of the JCI, Lyons and colleagues demonstrate that postpartum breast tissue remodeling during involution coinc...
Source: Journal of Clinical Investigation - August 19, 2014 Category: Biomedical Science Authors: Melody A. Swartz Source Type: research

Skeletal muscle work efficiency with age: the role of non-contractile processes
Although skeletal muscle work efficiency likely plays a key role in limiting mobility of the elderly, the physiological mechanisms responsible for this diminished function remain incompletely understood. Thus, in the quadriceps of young (n=9) and old (n=10) subjects, we measured the cost of muscle contraction (ATP cost) with 31P-magnetic resonance spectroscopy (31P-MRS) during 1) maximal intermittent contractions to elicit a metabolic demand from both cross-bridge cycling and ion pumping and 2) a continuous maximal contraction to predominantly tax cross-bridge cycling. The ATP cost of the intermittent contractions was sign...
Source: Clinical Science - August 19, 2014 Category: Biomedical Science Authors: G Layec, C R Hart, J Douglas Trinity, Y Le Fur, E Jeong, R S Richardson Source Type: research

Carbohydrate-to-carbohydrate interactions between α2,3- linked sialic acids on α2 integrin subunits and asialo-GM1 underlie the bone metastatic behavior of LNCaP-derivative C4-2B prostate cancer cells.
Abstract Complex interplays between proteins, lipids and carbohydrates can alter the phenotype and are suggested to have a crucial role in tumour metastasis. Our previous studies indicated that a complex of the glycosphingolipids, asialo-GM1, which lacks a2,3-linked sialic acid, and a2b1 integrin receptors is responsible for the metastatic behaviour of C4-2B prostate cancer cells. Herein, we identified and addressed the functional significance of changes in sialylation during prostate cancer progression. We observed an increase in a2,3-linked sialic acid residues on a2 subunits of a2b1 integrin receptors, correlati...
Source: Bioscience Reports - August 19, 2014 Category: Biomedical Science Authors: Van Slambrouck S, Groux-Degroote S, Krzewinski-Recchi MA, Cazet A, Delannoy P, Steelant WF Tags: Biosci Rep Source Type: research

Patient-specific analysis of displacement Forces acting on fenestrated stent Grafts for Endovascular aneurysm repair
Treatment options for Abdominal Aortic Aneurysm (AAA) include highly invasive open surgical repair or minimally invasive Endovascular Aneurysm Repair (EVAR). Despite being minimally invasive, some patients are not suitable for EVAR due to hostile AAA morphology. Fenestrated-EVAR (F-EVAR) was introduced to address these limitations of standard EVAR, where AAA is treated using a Fenestrated Stent Graft (FSG). In order to assess durability of F-EVAR, displacement forces acting on FSGs were analysed in this study, based on patient-specific geometries reconstructed from Computed Tomography (CT) scans. (Source: Journal of Biomechanics)
Source: Journal of Biomechanics - August 19, 2014 Category: Biomedical Science Authors: Harkamaljot Kandail, Mohammad Hamady, Xiao Yun Xu Source Type: research