bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferative Lesions of Serous Membranes in Ovariectomised Female and Entire Male Dogs After Stilboestrol Administration
Authors: O'Shea J. D. , Jabara Anne G. 
Published: January 2017

It was shown previously that ovarian tumours, which frequently metastasise to serous surfaces, can be produced in dogs by prolonged administration of stilboestrol. The ability of non-ovarian serous surfaces to proliferate in response to stilboestrol, independently of ovarian metastases, was studied in 5 ovariectomised females and 4 entire males. Papillary proliferations occurred on the uterine serosae in 3 females and on the testicular and cpididymal serosae in 2 males. In no case was there papillary proliferation on serous membranes of non-genital organs. One of 2 entire females given stillboestrol had proliferations regarded as metastases of ovarian origin on non-genital serous membranes. It is concluded that, in addition to ovarian changes, stilboestrol can cause primary proliferative lesions in the serous membranes of certain genital organs in both sexes. There is no evidence that serous membranes of non-genital organs be capable of a primary proliferative response to stilboestrol.
Nasal Rhinosporidiosis in the Dog
Authors: Easley J. R. , Meuten D. J. , Levy M. G. , Dykstra M. J. , Breitschwerdt E. B. , Holzinger E. A. , Cattley R. C. 
Published: January 2017

Rhinosporidiosis was diagnosed in six dogs from the southeastern United States. All six dogs had unilateral nasal polyps with multiple small white sporangia visible beneath the surface. Microscopically, the polyps consisted of organisms and fibrovascular tissue with a surface of columnar or squamous epithelium. Juvenile sporangia were unilamellar, 15-75 in diameter, nucleated, and accounted for about 65% of sporangia seen. Approximately 5% of the sporangia were in intermediate stages of maturation, were bilamellar, 100-150 μm in diameter, and contained immature endospores. Mature sporangia comprised about 30% of the total, were usually unilamellar, 100-400 μm in diameter, and contained a mixture of immature and mature endospores. The inner layer of the wall of the intermediate sporangia and the single wall of the mature sporangia were argyrophilic and carminophilic. Ultrastructurally. the earliest stage contained a nucleus and many ribosomes, lipid droplets, and phagolysosomes. Maturing sporangia contained discrete membrane-bound, round clevage products. These structures subsequently matured to spores, each of which had a wall and contained a nucleus and many lipid droplets. The organism from one dog was cultured and grown in vitro for 7 months and is the first successful cultivation of Rhinosporidium seeberi.
Castration prevents calcium channel blocker-induced gingival hyperplasia in beagle dogs
Authors: Dayan Dan , Kozlovsky Avital , Tal Haim , Kariv Noam , Shemesh Mordechai , Nyska Abraham 
Published: January 2017

1 The purpose of this study was to investigate testosterone's role on the calcium channel antagonist oxodi-pine-inducing gingival hyperplasia in a dog model. 2 Two experiments were conducted using castrated and intact male dogs. Oxodipine was administered orally for 90 days, at a dose of 24 mg/kg/day. In the first experiment, the occurrence of gingival hyperplasia was evaluated. In the second, the gingival index (GI) and gingival hyperplasia index (GHI) were recorded and correlated with serum levels of testosterone. 3 A significant positive correlation between GI, GHI and plasma testosterone was noted. Castrated dogs were injected with testosterone, 4 months after the start of oxodipine treatment, while in the non-castrated dogs, administration of oxodipine was stopped. Castration correlated with lack of GH, while testosterone injection to the same dogs was associated with an increase of GI and GHI. 4 Since it is known that testosterone receptors are present in the gingiva, it is proposed that oxodipine-induced gingival hyperplasia could be mediated by the calcium channel blocker on plasma testosterone levels.
An estrogen receptor β-selective agonist inhibits non-alcoholic steatohepatitis in preclinical models by regulating bile acid and xenobiotic receptors
Authors: Ponnusamy Suriyan , Tran Quynh T , Thiyagarajan Thirumagal , Miller Duane D , Bridges Dave , Narayanan Ramesh 
Published: January 2017

Non-alcoholic steatohepatitis (NASH) affects 8–10 million people in the US and up to 75% of obese individuals. Despite this, there are no approved oral therapeutics to treat NASH and therefore the need for novel approaches exists. The estrogen receptor β (ER-β)-selective agonist, β-LGND2, inhibits body weight and white adipose tissue, and increases metabolism, resulting in higher energy expenditure and thermogenesis. Due to favorable effects of β-LGND2 on obesity, we hypothesized that β-LGND2 will prevent NASH directly by reducing lipid accumulation in the liver or indirectly by favorably changing body composition. Male C57BL/6 mice fed with high fat diet (HFD) for 10 weeks or methionine choline-deficient diet for four weeks and treated with vehicle exhibited altered liver weights by twofold and increased serum transaminases by 2–6-folds. These changes were not observed in β-LGND2-treated animals. Infiltration of inflammatory cells and collagen deposits, an indication of fibrosis, were observed in the liver of mice fed with HFD for 10 weeks, which were effectively blocked by β-LGND2. Gene expression studies in the liver indicate that pregnane X receptor target genes were significantly increased by HFD, and the increase was inhibited by β-LGND2. On the other hand, metabolomics indicate that bile acid metabolites were significantly increased by β-LGND2. These studies demonstrate that an ER-β agonist might provide therapeutic benefits in NASH by directly modulating the function of xenobiotic and bile acid receptors in the liver, which have important functions in the liver, and indirectly, as demonstrated before, by inhibiting adiposity.Impact statementOver 75–90% of those classified as clinically obese suffer from co-morbidities, the most common of which is non-alcoholic steatohepatitis (NASH). While there are currently no effective treatment approaches for NASH, data presented here provide preliminary evidence that an estrogen receptor β-selective ligand could have the potential to reduce lipid accumulation and inflammation, and protect liver from NASH.
Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model
Authors: Roh Kangsan , Cho Sungrae , Park Jae-hyun , Yoo Byong Chul , Kim Won-Ki , Kim Seok-ki , Park Kyewon , Kang Hee , Ku Jin-mo , Yeom Chang-Hwan , Lee Kyunghoon , Lee Sukchan 
Published: January 2017

Acquired lymphedema is one of the most dreaded side effects of cancer treatment, such as surgical treatment or irradiation. However, due to the lack of appropriate animal models, there is no effective therapeutic method to cure acquired lymphedema. To develop a reproducible acquired lymphedema animal model, we devised a mouse hind limb model by removing a superficial inguinal lymph node, a popliteal lymph node, a deep inguinal lymph node, and the femoral lymphatic vessel. We measured the volume of lymphedematous leg and observed the change in level of hyaluronic acid (HA) and lymphangiogenic factors after injecting hyaluronidase. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that HA, a major component of extracellular matrix, accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating hyaluronidase. Following hyaluronidase injection, the lymphedematous region of our model resembled a normal hind limb. Our findings indicated that hyaluronidase promoted lymphangiogenesis on the lymphedematous limb. Based on hyaluronidase treatment in the lymphedematous region, this could potentially be a new therapeutic approach for acquired lymphedema mediated through the modification of the size of HA fragments. Impact statement In this manuscript, the essence of the work described in this manuscript involves the development of (1) a mouse limb model showing acquired lymphedema and (2) a potent therapeutic treatment using hyaluronidase to remedy acquired lymphedema in our model. In order to develop a reproducible acquired lymphedema animal model that reflects the most common symptoms experienced by lymphedema patients, we devised a mouse hind limb model by removing lymph nodes and lymphatics. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that hyaluronic acid (HA) accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating the lymphedematous leg with hyaluronidase, which also degraded high molecular weight HA to low molecular weight HA. Immunohistochemical analysis, quantitative real-time PCR analysis and lymphangioscintigraphy showed that hyaluronidase enhanced lymphangiogenesis in the lymphedematous limb.
Diffuse large B-cell lymphoma genotyping on the liquid biopsy
Authors: Rossi Davide , Diop Fary , Spaccarotella Elisa , Monti Sara , Zanni Manuela , Rasi Silvia , Deambrogi Clara , Spina Valeria , Bruscaggin Alessio , Favini Chiara , Serra Roberto , Ramponi Antonio , Boldorini Renzo , Foà Robin , Gaidano Gianluca 
Published: January 2017

Key Points
Plasma cfDNA genotyping is as accurate as genotyping of the diagnostic biopsy in detecting clonal somatic mutations in DLBCL. Plasma cfDNA genotyping is a real-time, noninvasive tool that can be used to track clonal evolution in DLBCL.
Initiation of acute graft-versus-host disease by angiogenesis
Authors: Riesner Katarina , Shi Yu , Jacobi Angela , Kräter Martin , Kalupa Martina , McGearey Aleixandria , Mertlitz Sarah , Cordes Steffen , Schrezenmeier Jens-Florian , Mengwasser Jörg , Westphal Sabine , Perez-Hernandez Daniel , Schmitt Clemens , Dittmar Gunnar , Guck Jochen , Penack Olaf 
Published: January 2017

Key PointsAngiogenesis preceded infiltration of inflammatory leukocytes during GVHD as well as during experimental colitis. Metabolic alterations and cytoskeleton changes occurred during early angiogenesis, but classical endothelial activation signs were absent.
Exploring surface cleaning strategies in hospital to prevent contact transmission of methicillin-resistant Staphylococcus aureus
Authors: Lei Hao , Jones Rachael M. , Li Yuguo 
Published: January 2017

Abstract

Background
Cleaning of environmental surfaces in hospitals is important for the control of methicillin-resistant Staphylococcus aureus (MRSA) and other hospital-acquired infections transmitted by the contact route. Guidance regarding the best approaches for cleaning, however, is limited.

Methods
In this study, a mathematical model based on ordinary differential equations was constructed to study MRSA concentration dynamics on high-touch and low-touch surfaces, and on the hands and noses of two patients (in two hospitals rooms) and a health care worker in a hypothetical hospital environment. Two cleaning interventions – whole room cleaning and wipe cleaning of touched surfaces – were considered. The performance of the cleaning interventions was indicated by a reduction in MRSA on the nose of a susceptible patient, relative to no intervention.

Results
Whole room cleaning just before first patient care activities of the day was more effective than whole room cleaning at other times, but even with 100% efficiency, whole room cleaning only reduced the number of MRSA transmitted to the susceptible patient by 54%. Frequent wipe cleaning of touched surfaces was shown to be more effective that whole room cleaning because surfaces are rapidly re-contaminated with MRSA after cleaning. Wipe cleaning high-touch surfaces was more effective than wipe cleaning low-touch surfaces for the same frequency of cleaning. For low wipe cleaning frequency (≤3 times per hour), high-touch surfaces should be targeted, but for high wipe cleaning frequency (>3 times per hour), cleaning should target high- and low-touch surfaces in proportion to the surface touch frequency. This study reproduces the observations from a field study of room cleaning, which provides support for the validity of our findings.

Conclusions
Daily whole room cleaning, even with 100% cleaning efficiency, provides limited reduction in the number of MRSA transmitted to susceptible patients via the contact route; and should be supplemented with frequent targeted cleaning of high-touch surfaces, such as by a wipe or cloth containing disinfectant.
Phosphoinositol 3-phosphate acts as a timer for reactive oxygen species production in the phagosome
Authors: Song Zhi Min , Bouchab Leïla , Hudik Elodie , Le Bars Romain , Nüsse Oliver , Dupré-Crochet Sophie 
Published: January 2017

Abstract
Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40phox by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40phox and p67phox at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils. It also releases p67phox, the key cytosolic subunit of the oxidase, and p40phox from the phagosome. The knockdown of the PI(3)P phosphatase MTM1 or Rubicon or both increases the level of PI(3)P at the phagosome. That increase enhances ROS production inside the phagosome and triggers an extended accumulation of p67phox at the phagosome. Furthermore, the overexpression of MTM1 at the phagosomal membrane induces the disappearance of PI(3)P from the phagosome and prevents sustained ROS production. In conclusion, PI(3)P, indeed, regulates ROS production by maintaining p40phox and p67phox at the phagosomal membrane.
MFG-E8-derived peptide attenuates adhesion and migration of immune cells to endothelial cells
Authors: Hirano Yohei , Yang Weng-Lang , Aziz Monowar , Zhang Fangming , Sherry Barbara , Wang Ping 
Published: January 2017

Abstract
Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) plays an immunomodulatory role in inflammatory diseases. MFG-E8-derived short peptide (MSP68) greatly reduces neutrophil infiltration and injury in the lung during sepsis. In this study, we examined the effect of MSP68 on chemotaxis of various immune cells and its regulatory mechanism. Bone marrow-derived neutrophils (BMDNs) from C57BL/6 mice, human monocyte THP-1 cell line, and human T lymphocyte Jurkat cell line were used for adhesion and migration assays using a Transwell method in the presence of MSP68. Treatment with MSP68 significantly inhibited the BMDN and THP-1 cell but not Jurkat cell adhesion on the TNF-α-stimulated pulmonary artery endothelial cell (PAEC) monolayer dose-dependently. MSP68 also significantly reduced BMDN adhesion on VCAM-1-coated wells dose dependently. Surface plasmon resonance (SPR) analysis revealed that MSP68 efficiently recognized integrin α4β1 (receptor for VCAM-1) at the dissociation constant (KD) of 1.53 × 10−7 M. These findings implicate that MSP68 prevents neutrophil adhesion to the activated endothelial cells by interfering with the binding between integrin α4β1 on neutrophils and VCAM-1 on endothelial cells. Moreover, MSP68 significantly attenuated the migration of BMDN and THP-1 cells but not Jurkat cells to their chemoattractants. Pretreatment with MSP68 inhibited the transmigration of BMDNs across the PAECs toward chemoattractants, fMLP, MIP-2, and complement fragment 5a (C5a) dose-dependently. Finally, we identified that the activation of p38 MAPK in BMDNs by fMLP was inhibited by MSP68. Thus, MSP68 attenuates extravasation of immune cells through the endothelial cell lining into inflamed tissue, implicating MSP68 to be a novel, therapeutic agent for inflammatory diseases caused by excessive immune cell infiltration.
Exosomes from eosinophils autoregulate and promote eosinophil functions
Authors: Cañas José Antonio , Sastre Beatriz , Mazzeo Carla , Fernández-Nieto Mar , Rodrigo-Muñoz José Manuel , González-Guerra Andrés , Izquierdo Manuel , Barranco Pilar , Quirce Santiago , Sastre Joaquín , del Pozo Victoria 
Published: January 2017

Abstract
Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n = 58) and healthy volunteers (n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma.
Frontline Science: Tumor necrosis factor-α stimulation and priming of human neutrophil granule exocytosis
Authors: McLeish Kenneth R , Merchant Michael L , Creed T Michael , Tandon Shweta , Barati Michelle T , Uriarte Silvia M , Ward Richard A 
Published: January 2017

Abstract
Neutrophil granule exocytosis plays an important role in innate and adaptive immune responses. The present study examined TNF-α stimulation or priming of exocytosis of the 4 neutrophil granule subsets. TNF-α stimulated exocytosis of secretory vesicles and gelatinase granules and primed specific and azurophilic granule exocytosis to fMLF stimulation. Both stimulation and priming of exocytosis by TNF-α were dependent on p38 MAPK activity. Bioinformatic analysis of 1115 neutrophil proteins identified by mass spectrometry as being phosphorylated by TNF-α exposure found that actin cytoskeleton regulation was a major biologic function. A role for p38 MAPK regulation of the actin cytoskeleton was confirmed experimentally. Thirteen phosphoproteins regulated secretory vesicle quantity, formation, or release, 4 of which—Raf1, myristoylated alanine-rich protein kinase C (PKC) substrate (MARCKS), Abelson murine leukemia interactor 1 (ABI1), and myosin VI—were targets of the p38 MAPK pathway. Pharmacologic inhibition of Raf1 reduced stimulated exocytosis of gelatinase granules and priming of specific granule exocytosis. We conclude that differential regulation of exocytosis by TNF-α involves the actin cytoskeleton and is a necessary component for priming of the 2 major neutrophil antimicrobial defense mechanisms: oxygen radical generation and release of toxic granule contents.
Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
Authors: Jiu Yaming , Peränen Johan , Schaible Niccole , Cheng Fang , Eriksson John E. , Krishnan Ramaswamy , Lappalainen Pekka 
Published: January 2017

ABSTRACT
The actin and intermediate filament cytoskeletons contribute to numerous cellular processes, including morphogenesis, cytokinesis and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms of this interaction are incompletely understood. Here, we show that inactivation of vimentin leads to increased actin stress fiber assembly and contractility, and consequent elevation of myosin light chain phosphorylation and stabilization of tropomyosin-4.2 (see Geeves et al., 2015). The vimentin-knockout phenotypes can be rescued by re-expression of wild-type vimentin, but not by the non-filamentous ‘unit length form’ vimentin, demonstrating that intact vimentin intermediate filaments are required to facilitate the effects on the actin cytoskeleton. Finally, we provide evidence that the effects of vimentin on stress fibers are mediated by activation of RhoA through its guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2). Vimentin depletion induces phosphorylation of the microtubule-associated GEF-H1 on Ser886, and thereby promotes RhoA activity and actin stress fiber assembly. Taken together, these data reveal a new mechanism by which intermediate filaments regulate contractile actomyosin bundles, and may explain why elevated vimentin expression levels correlate with increased migration and invasion of cancer cells.
Role of the different eyes in the visual odometry in the wolf spider Lycosa tarantula (Araneae, Lycosidae)
Authors: Ortega-Escobar Joaquin , Ruiz Miguel A. 
Published: January 2017

ABSTRACT
The wolf spider Lycosa tarantula returns home by means of path integration. Previous studies demonstrated: (i) that the angular component of the outbound run is measured using a polarized-light compass associated with the anterior median eyes; (ii) changes in direction of the substratum are detected by the anterior lateral eyes (ALEs); and (iii) in relation to the linear component of the outbound run, an increase of optic flow, in either the lateral or ventral fields of view, caused spiders to search for the burrow at a point nearer to the goal. However, the role of the secondary eyes [ALEs, posterior lateral eyes (PLEs) and posterior median eyes (PMEs)] in the perception of this optic flow and the importance of them for gauging the distance walked is still unknown. In this study, lateral or ventral gratings of wavelength λ=1 cm were used, with two groups of spiders in each setup: (1) PLEs+PMEs covered and (2) ALEs covered. The largest reduction in the distance walked to return to the burrow was observed with the ventral grating/ALEs covered. These results show the importance of the previously neglected ALEs for the visual behavior of these spiders. The possibility of gathering information for locomotion from the three pairs of secondary eyes in the mushroom bodies is discussed.