Central talar dome lesions: a unique surgical approach with incorporation of a talar allograft for joint reconstitution and restoration of function.

PubMed

Dobbs, Bruce M; Cazzell, Shawn M; Dini, Monara

2011-01-01

Osteochondral lesions of the talus have been documented, reported, and studied since as early as the 19th century. The evolution of classification systems has allowed surgeons to better manage osseous lesions. Most osteochondral lesions of the talus have been categorized as anterolateral, posteromedial, or central with respect to the talar dome and its articulating surface. The complexity of the aforementioned lesions each present their own set of obstacles and, hence, management. Specifically, surgery on a central talar dome lesion is complicated by poor exposure and limited access, proving to be a challenging operation. Preoperative planning, including exhaustive imaging before any talar dome surgery, is imperative. We present a case study that involves the need for a distal tibial chevron (wedge) talus, with incorporation of a cadaveric allograft to fill the defect.

Central nervous system integration of sensorimotor signals in oral and pharyngeal structures: oropharyngeal kinematics response to recurrent laryngeal nerve lesion.

PubMed

Gould, Francois D H; Ohlemacher, Jocelyn; Lammers, Andrew R; Gross, Andrew; Ballester, Ashley; Fraley, Luke; German, Rebecca Z

2016-03-01

Safe, efficient liquid feeding in infant mammals requires the central coordination of oropharyngeal structures innervated by multiple cranial and spinal nerves. The importance of laryngeal sensation and central sensorimotor integration in this system is poorly understood. Recurrent laryngeal nerve lesion (RLN) results in increased aspiration, though the mechanism for this is unclear. This study aimed to determine the effect of unilateral RLN lesion on the motor coordination of infant liquid feeding. We hypothesized that 1) RLN lesion results in modified swallow kinematics, 2) postlesion oropharyngeal kinematics of unsafe swallows differ from those of safe swallows, and 3) nonswallowing phases of the feeding cycle show changed kinematics postlesion. We implanted radio opaque markers in infant pigs and filmed them pre- and postlesion with high-speed videofluoroscopy. Markers locations were digitized, and swallows were assessed for airway protection. RLN lesion resulted in modified kinematics of the tongue relative to the epiglottis in safe swallows. In lesioned animals, safe swallow kinematics differed from unsafe swallows. Unsafe swallow postlesion kinematics resembled prelesion safe swallows. The movement of the tongue was reduced in oral transport postlesion. Between different regions of the tongue, response to lesion was similar, and relative timing within the tongue was unchanged. RLN lesion has a pervasive effect on infant feeding kinematics, related to the efficiency of airway protection. The timing of tongue and hyolaryngeal kinematics in swallows is a crucial locus for swallow disruption. Laryngeal sensation is essential for the central coordination in feeding of oropharyngeal structures receiving motor inputs from different cranial nerves. Copyright © 2016 the American Physiological Society.

A case of tactile agnosia with a lesion restricted to the post-central gyrus.

PubMed

Estañol, Bruno; Baizabal-Carvallo, José Fidel; Sentíes-Madrid, Horacio

2008-01-01

Tactile agnosia has been described after lesions of the primary sensory cortex but the exact location and extension of those lesions is not clear. We report the clinical features and imaging findings in a patient with an acute ischemic stroke restricted to the primary sensory area (S1). A 73-year-old man had a sudden onset of a left alien hand, without left hemiparesis. Neurological examination showed intact primary sensory functions, but impaired recognition of shape, size (macrogeometrical) and texture (microgeometrical) of objects; damage confined to the post-central gyrus, sparing the posterior parietal cortex was demonstrated on MRI. An embolic occlusion of the anterior parietal artery was suspected as mechanism of stroke. Tactile agnosia with impaired microgeometrical and macrogeometrical features' recognition can result from a single lesion in the primary sensory cortex (S1) in the right parietal hemisphere, sparing other regions of the cerebral cortex which presumably participate in tactile object recognition.

Surgical Treatment, Oral Rehabilitation, and Orthognathic Surgery After Failure of Pharmacologic Treatment of Central Giant Cell Lesion: A Case Report.

PubMed

Maia Nogueira, Renato Luiz; Osterne, Rafael Lima Verde; Cavalcante, Roberta Barroso; Abreu, Ricardo Teixeira

2016-12-01

Although pharmacologic treatments for central giant cell lesions have gained much emphasis, these treatment modalities do not always have successful outcomes, and surgical treatment may be necessary. The purpose of the present study was to report a case of aggressive central giant cell lesion initially treated by nonsurgical methods without satisfactory results, necessitating segmental mandibular resection for definitive treatment and oral rehabilitation. A 20-year-old woman was diagnosed with an aggressive central giant cell lesion in the mandible. The patient was first treated with intralesional corticosteroid injections. Subsequently, the lesion increased in size. Therefore, a second pharmacologic treatment was proposed with salmon calcitonin nasal spray, but no signs of a treatment response were noted. Because of the lack of response, surgical excision was performed, and a mandibular reconstruction plate was installed. At 12 months after surgical resection, the patient underwent mandibular reconstruction with bone grafts. After 6 months, 7 dental implants were installed, and fixed prostheses were made. After installation of the prostheses, the patient experienced persistent mandibular laterognathism, and a mandibular orthognathic surgery was performed to correct the laterognathia. The follow-up examination 4 years after orthognathic surgery showed no signs of recurrence and good facial symmetry. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Similar mandibular osseous lesions in Tyrannosaurus rex and man.

PubMed

Neiburger, E J

2005-01-01

This report identifies several cases of similar-appearing multiple lesions in the mandibles of both humans and the dinosaur Tyrannosaurus rex (T. rex). A diagnosis and potential etiologies are discussed. The appearance of these lesions in prehistoric fossils suggests that this pathology is an ancient affliction which predates humans and our mammalian ancestors. Lytic lesions of the oral structures have occurred in man and higher animals throughout time. The causes range from congenital anomalies, trauma, and infections to benign and metastatic neoplasms. Not only mammals suffer from these conditions; reptiles and birds experience similar diseases.

Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

PubMed Central

Baer, Matthew L.; Henderson, Scott C.; Colello, Raymond J.

2015-01-01

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

Lesions of the amygdala central nucleus abolish lipoprivic-enhanced responding during oil-predicting conditioned stimuli.

PubMed

Benoit, S C; Morell, J R; Davidson, T L

1999-12-01

T. L. Davidson, A. M. Altizer, S. C. Benoit, E. K. Walls, and T. L. Powley (1997) reported that rats show facilitated responding to conditioned stimuli (CSs) that predict oil, after administration of the lipoprivic agent, Na-2-mercaptoacetate (MA). This facilitation was blocked by vagal deafferentation. The present article extends that investigation to another structure, the amygdala central nucleus (CN). The CN receives inputs from dorsal vagal nuclei, and neurotoxic lesions of this nucleus are reported to abolish feeding in response to lipoprivic challenges. In Experiment 1, rats with ibotenic acid (IBO) lesions of the CN failed to show enhanced appetitive responding during oil-predicting CSs after administration of MA. Experiment 2 used a conditioned taste-aversion procedure to establish that rats with IBO lesions of the CN were able to discriminate the tastes of sucrose and peanut oil and had intact CS-US representations. It is concluded that the amygdala CN is a necessary structure for the detection of lipoprivic challenges.

Histopathological Study of Central Nervous System Lesions: Emphasizing Association of Neoplasms with ABO Blood Groups.

PubMed

Kumarguru, B N; Pallavi, P; Sunila; Manjunath, G V; Vasan, T S; Rajalakshmi, B R

2017-04-01

The Central Nervous System (CNS) lesions show considerable geographic and racial variations with respect to the incidence and the pattern of distribution of lesions. The ABO blood status is a readily accessible factor in genetic constitution of the patients. It has been shown to be associated with many diseases. But the influence of blood group status on the pathogenesis of brain tumours is still unclear. To study various histopathological patterns of CNS lesions and to evaluate the association of CNS tumours with the distribution of ABO blood groups in documented cases. In the present study, 147 cases were analyzed. It was an analytical type of study, done at JSS Medical College, Mysore, over a period of 2 years and 8 months from January 2009 to August 2011. Histopathology slides were routinely stained by Haematoxylin and Eosin (H&E) stain. Special stains were performed in selected cases. Blood group of the patients and the control group were documented. Blood group distribution pattern was assessed in relation to histopathological diagnosis of various CNS tumours. Histopathological diagnosis of 147 cases included neoplastic lesions (84.35%) and non-neoplastic lesions (15.64%). Neoplastic lesions (84.35%) constituted the majority, which included neuroepithelial tumours (29.25%) as predominant pattern. Non-neoplastic lesions constituted only 15.64%, which included inflammatory lesion (8.16%) as the predominant pattern. ABO blood group data was available in 92 cases (84.4%) of neoplastic lesions, which included 71 cases (48.29%) of primary CNS neoplasms categorized according to WHO grades. The control group constituted 21,067 healthy voluntary donors. Blood group O was the most frequent blood group in neoplastic lesions (40.21%) and primary CNS neoplasms categorized according to WHO grades (45.07%). The association between the CNS neoplasms and ABO blood groups was not statistically significant (p = 0.055). But a definite change in the pattern of distribution of ABO

Central giant cell lesion of the jaws: An updated analysis of 2270 cases reported in the literature.

PubMed

Chrcanovic, Bruno Ramos; Gomes, Carolina Cavalieri; Gomez, Ricardo Santiago

2018-05-11

To review all available data published on central giant cell lesion (CGCL) of the jaws into a comprehensive analysis of its clinical/radiological features, with emphasis on the predictive factors associated with its recurrence. An electronic search was undertaken in 5 databases (February/2018), looking for reporting cases of CGCLs. A total of 365 publications were included, comprising 2270 lesions. CGCLs were more prevalent in women and the mandible. Cortical bone perforation occurred in 50% of the cases. Marginal/segmental resection was more often performed in larger lesions, and drug therapy was more frequent in small lesions. Recurrence was reported in 232 of 1316 cases (17.6%). The recurrence rate of the aggressive lesions (22.8%) after surgical treatment was higher than non-aggressive lesions (7.8%). Four of 5 CGCLs showed partial/total regression with pharmacological treatment. Aggressive lesions showed a worse response to corticosteroids than non-aggressive lesions. For the lesions submitted to surgery as the first treatment, curettage, enucleation, or marginal resection in relation to segmental resection, aggressive lesions, cortical bone perforation, and tooth root resorption were associated with increased recurrence rate. Recurrence related to a combination of surgical/pharmacological treatment could not be evaluated due to the variety of protocols. Aggressive CGCLs recur more often than the non-aggressive ones. Despite sometimes showing poor response to corticosteroid injection or surgical curettage, a combination of both treatment strategies should be considered in aggressive cases to reduce morbidities associated with radical surgery. The best protocol to manage aggressive and non-aggressive lesions remains to be determined. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Primary Angiitis of the Central Nervous System: Magnetic Resonance Imaging Spectrum of Parenchymal, Meningeal, and Vascular Lesions at Baseline.

PubMed

Boulouis, Grégoire; de Boysson, Hubert; Zuber, Mathieu; Guillevin, Loïc; Meary, Eric; Costalat, Vincent; Pagnoux, Christian; Naggara, Olivier

2017-05-01

Primary angiitis of the central nervous system remains challenging. To report an overview and pictorial review of brain magnetic resonance imaging findings in adult primary angiitis of the central nervous system and to determine the distribution of parenchymal, meningeal, and vascular lesions in a large multicentric cohort. Adult patients from the French COVAC cohort (Cohort of Patients With Primary Vasculitis of the Central Nervous System), with biopsy or angiographically proven primary angiitis of the central nervous system and brain magnetic resonance imaging available at the time of diagnosis were included. A systematic imaging review was performed blinded to clinical data. Sixty patients met inclusion criteria. Mean age was 45 years (±12.9). Patients initially presented focal deficit(s) (83%), headaches (53%), cognitive disorder (40%), and seizures (38.3%). The most common magnetic resonance imaging finding observed in 42% of patients was multiterritorial, bilateral, distal acute stroke lesions after small to medium artery distribution, with a predominant carotid circulation distribution. Hemorrhagic infarctions and parenchymal hemorrhages were also frequently found in the cohort (55%). Acute convexity subarachnoid hemorrhage was found in 26% of patients and 42% demonstrated pre-eminent leptomeningeal enhancement, which is found to be significantly more prevalent in biopsy-proven patients (60% versus 28%; P =0.04). Seven patients had tumor-like presentations. Seventy-seven percent of magnetic resonance angiographic studies were abnormal, revealing proximal/distal stenoses in 57% and 61% of patients, respectively. Adult primary angiitis of the central nervous system is a heterogenous disease, with multiterritorial, distal, and bilateral acute stroke being the most common pattern of parenchymal lesions found on magnetic resonance imaging. Our findings suggest a higher than previously thought prevalence of hemorrhagic transformation and other hemorrhagic

DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes.

PubMed

Cohen, Isadora S; Bar, Carmit; Paz-Elizur, Tamar; Ainbinder, Elena; Leopold, Karoline; de Wind, Niels; Geacintov, Nicholas; Livneh, Zvi

2015-02-18

DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells.

Cholesterol Regulates Multiple Forms of Vesicle Endocytosis at a Mammalian Central Synapse

PubMed Central

Yue, Hai-Yuan; Xu, Jianhua

2015-01-01

Endocytosis in synapses sustains neurotransmission by recycling vesicle membrane and maintaining the homeostasis of synaptic membrane. A role of membrane cholesterol in synaptic endocytosis remains controversial because of conflicting observations, technical limitations in previous studies, and potential interference from nonspecific effects after cholesterol manipulation. Furthermore, it is unclear whether cholesterol participates in distinct forms of endocytosis that function under different activity levels. In this study, applying the whole-cell membrane capacitance measurement to monitor endocytosis in real time at the rat calyx of Held terminals, we found that disrupting cholesterol with dialysis of cholesterol oxidase (COase) or methyl-β-cyclodextrin (MCD) impaired three different forms of endocytosis, i.e., slow endocytosis, rapid endocytosis, and endocytosis of the retrievable membrane that exists at the surface before stimulation. The effects were observed when disruption of cholesterol was mild enough not to change Ca2+ channel current or vesicle exocytosis, indicative of stringent cholesterol requirement in synaptic endocytosis. Extracting cholesterol with high concentrations of MCD reduced exocytosis, mainly by decreasing the readily releasable pool (RRP) and the vesicle replenishment after RRP depletion. Our study suggests that cholesterol is an important, universal regulator in multiple forms of vesicle endocytosis at mammalian central synapses. PMID:25893258

Cholesterol regulates multiple forms of vesicle endocytosis at a mammalian central synapse.

PubMed

Yue, Hai-Yuan; Xu, Jianhua

2015-07-01

Endocytosis in synapses sustains neurotransmission by recycling vesicle membrane and maintaining the homeostasis of synaptic membrane. A role of membrane cholesterol in synaptic endocytosis remains controversial because of conflicting observations, technical limitations in previous studies, and potential interference from non-specific effects after cholesterol manipulation. Furthermore, it remains unclear whether cholesterol participates in distinct forms of endocytosis that function under different activity levels. In this study, applying the whole-cell membrane capacitance measurement to monitor endocytosis in real time at the rat calyx of Held terminals, we found that disrupting cholesterol with dialysis of cholesterol oxidase or methyl-β-cyclodextrin impaired three different forms of endocytosis, including slow endocytosis, rapid endocytosis, and endocytosis of the retrievable membrane that exists at the surface before stimulation. The effects were observed when disruption of cholesterol was mild enough not to change Ca(2+) channel current or vesicle exocytosis, indicative of stringent cholesterol requirement in synaptic endocytosis. Extracting cholesterol with high concentrations of methyl-β-cyclodextrin reduced exocytosis, mainly by decreasing the readily releasable pool and the vesicle replenishment after readily releasable pool depletion. Our study suggests that cholesterol is an important, universal regulator in multiple forms of vesicle endocytosis at mammalian central synapses. © 2015 International Society for Neurochemistry.

Quantitative genetic-interaction mapping in mammalian cells

PubMed Central

Roguev, Assen; Talbot, Dale; Negri, Gian Luca; Shales, Michael; Cagney, Gerard; Bandyopadhyay, Sourav; Panning, Barbara; Krogan, Nevan J

2013-01-01

Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ~11,000 pairwise knockdowns in mouse fibroblasts, focusing on 130 factors involved in chromatin regulation to create a GI map. Comparison of the GI and protein-protein interaction (PPI) data revealed that pairs of genes exhibiting positive GIs and/or similar genetic profiles were predictive of the corresponding proteins being physically associated. The mammalian GI map identified pathways and complexes but also resolved functionally distinct submodules within larger protein complexes. By integrating GI and PPI data, we created a functional map of chromatin complexes in mouse fibroblasts, revealing that the PAF complex is a central player in the mammalian chromatin landscape. PMID:23407553

Regional patterns of postglacial changes in the Palearctic mammalian diversity indicate retreat to Siberian steppes rather than extinction

PubMed Central

Řičánková, Věra Pavelková; Robovský, Jan; Riegert, Jan; Zrzavý, Jan

2015-01-01

We examined the presence of possible Recent refugia of Pleistocene mammalian faunas in Eurasia by analysing regional differences in the mammalian species composition, occurrence and extinction rates between Recent and Last Glacial faunas. Our analyses revealed that most of the widespread Last Glacial species have survived in the central Palearctic continental regions, most prominently in Altai–Sayan (followed by Kazakhstan and East European Plain). The Recent Altai–Sayan and Kazakhstan regions show species compositions very similar to their Pleistocene counterparts. The Palearctic regions have lost 12% of their mammalian species during the last 109,000 years. The major patterns of the postglacial changes in Palearctic mammalian diversity were not extinctions but rather radical shifts of species distribution ranges. Most of the Pleistocene mammalian fauna retreated eastwards, to the central Eurasian steppes, instead of northwards to the Arctic regions, considered Holocene refugia of Pleistocene megafauna. The central Eurasian Altai and Sayan mountains could thus be considered a present-day refugium of the Last Glacial biota, including mammals. PMID:26246136

DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes

PubMed Central

Cohen, Isadora S.; Bar, Carmit; Paz-Elizur, Tamar; Ainbinder, Elena; Leopold, Karoline; de Wind, Niels; Geacintov, Nicholas; Livneh, Zvi

2015-01-01

DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells. PMID:25589543

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

PubMed

Jesus, Tito T; Oliveira, Pedro F; Sousa, Mário; Cheng, C Yan; Alves, Marco G

2017-06-01

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermatogenesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

PubMed Central

Jesus, Tito T.; Oliveira, Pedro F.; Sousa, M ario; Cheng, C. Yan; Alves, Marco G.

2017-01-01

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermato-genesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system. PMID:28124577

Contrast enhancement of central nervous system lesions: multicenter intraindividual crossover comparative study of two MR contrast agents.

PubMed

Maravilla, Kenneth R; Maldjian, Joseph A; Schmalfuss, Ilona M; Kuhn, Matthew J; Bowen, Brian C; Wippold, Franz J; Runge, Val M; Knopp, Michael V; Kremer, Stephane; Wolansky, Leo J; Anzalone, Nicoletta; Essig, Marco; Gustafsson, Lars

2006-08-01

To prospectively compare gadobenate dimeglumine with gadopentetate dimeglumine (0.1 mmol per kilogram body weight) for enhanced magnetic resonance (MR) imaging of central nervous system (CNS) lesions. This study was HIPAA-compliant at U.S. centers and was conducted at all centers according to the Good Clinical Practice standard. Institutional review board and regulatory approval were granted; written informed consent was obtained. Seventy-nine men and 78 women (mean age, 50.5 years +/- 14.4 [standard deviation]) were randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed by gadopentetate was administered in group A; order of administration was reversed in group B. Contrast agent administration (volume, speed of injection), imaging parameters before and after injection, and time between injections and postinjection acquisitions were identical for both examinations. Three blinded neuroradiologists evaluated images by using objective image interpretation criteria for diagnostic information end points (lesion border delineation, definition of disease extent, visualization of internal morphologic features of the lesion, enhancement of the lesion) and quantitative parameters (percentage of lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference in terms of lesion conspicuity, detectability, and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test. Readers 1, 2, and 3 demonstrated overall preference for gadobenate in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10, and six patients, respectively (P < .0001). Significant (P < .0001) preference for gadobenate was demonstrated for diagnostic information end points, percentage of lesion enhancement, and CNR. Superiority of gadobenate was significant (P < .001) in patients with intraaxial and extraaxial lesions

Mammalian Homologs of Yeast Checkpoint Genes

DTIC Science & Technology

2002-07-01

pathway is sensitive to various forms of DNA damage Developmental Biology throughout the cell cycle . The DNA replication check- Yale University point...components would be ordered into pathways for mammalian checkpoint function, with emphasis on p53 regulation, cell cycle regulation, and complementation...structurally related to the human tumor suppressor ATM. MEC1 and RAD53, two essential genes, play a central role in DNA damage checkpoints at all cell cycle

Gross and microscopic morphology of lesions in Cnidaria from Palmyra Atoll, Central Pacific

USGS Publications Warehouse

Williams, Gareth J.; Work, Thierry M.; Aeby, Greta S.; Knapp, Ingrid S.; Davy, Simon K.

2011-01-01

We conducted gross and microscopic characterizations of lesions in Cnidaria from Palmyra Atoll, Central Pacific. We found growth anomalies (GA) to be the most commonly encountered lesion. Cases of discoloration and tissue loss were rare. GAs had a focal or multi-focal distribution and were predominantly nodular, exophytic, and umbonate. In scleractinians, the majority of GAs manifested as hyperplasia of the basal body wall (52% of cases), with an associated absence or reduction of polyp structure (mesenteries and filaments, actinopharynx and tentacles), and depletion of zooxanthellae in the gastrodermis of the upper body wall. In the soft corals Sinularia sp. and Lobophytum sp., GAs exclusively manifested as prominent hyperplasia of the coenenchyme with an increased density of solenia. In contrast to scleractinians, soft coral GAs displayed an inflammatory and necrotizing component with marked edema of the mesoglea, accompanied by infiltrates of variably-sized granular amoebocytes. Fungi, algae, sponges, and Crustacea were present in some scleractinian GAs, but absent in soft coral GAs. Fragmentation of tissues was a common finding in Acropora acuminata and Montipora cf. dilatata colonies with tissue loss, although no obvious causative agents were seen. Discoloration in the zoanthid, Palythoa tuberculosa, was found to be the result of necrosis, while in Lobophytum sp. discoloration was the result of zooxanthellar depletion (bleaching). Soft corals with discoloration or tissue loss showed a marked inflammatory response, however no obvious causative organisms were seen. Lesions that appeared similar at the gross level were revealed to be distinct by microscopy, emphasizing the importance of histopathology.

Gross and microscopic morphology of lesions in Cnidaria from Palmyra Atoll, Central Pacific.

PubMed

Williams, Gareth J; Work, Thierry M; Aeby, Greta S; Knapp, Ingrid S; Davy, Simon K

2011-02-01

We conducted gross and microscopic characterizations of lesions in Cnidaria from Palmyra Atoll, Central Pacific. We found growth anomalies (GA) to be the most commonly encountered lesion. Cases of discoloration and tissue loss were rare. GAs had a focal or multi-focal distribution and were predominantly nodular, exophytic, and umbonate. In scleractinians, the majority of GAs manifested as hyperplasia of the basal body wall (52% of cases), with an associated absence or reduction of polyp structure (mesenteries and filaments, actinopharynx and tentacles), and depletion of zooxanthellae in the gastrodermis of the upper body wall. In the soft corals Sinularia sp. and Lobophytum sp., GAs exclusively manifested as prominent hyperplasia of the coenenchyme with an increased density of solenia. In contrast to scleractinians, soft coral GAs displayed an inflammatory and necrotizing component with marked edema of the mesoglea, accompanied by infiltrates of variably-sized granular amoebocytes. Fungi, algae, sponges, and Crustacea were present in some scleractinian GAs, but absent in soft coral GAs. Fragmentation of tissues was a common finding in Acropora acuminata and Montipora cf. dilatata colonies with tissue loss, although no obvious causative agents were seen. Discoloration in the zoanthid, Palythoa tuberculosa, was found to be the result of necrosis, while in Lobophytum sp. discoloration was the result of zooxanthellar depletion (bleaching). Soft corals with discoloration or tissue loss showed a marked inflammatory response, however no obvious causative organisms were seen. Lesions that appeared similar at the gross level were revealed to be distinct by microscopy, emphasizing the importance of histopathology. Copyright © 2010 Elsevier Inc. All rights reserved.

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

PubMed

Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

Voxel-based lesion mapping of meningioma: a comprehensive lesion location mapping of 260 lesions.

PubMed

Hirayama, Ryuichi; Kinoshita, Manabu; Arita, Hideyuki; Kagawa, Naoki; Kishima, Haruhiko; Hashimoto, Naoya; Fujimoto, Yasunori; Yoshimine, Toshiki

2018-06-01

OBJECTIVE In the present study the authors aimed to determine preferred locations of meningiomas by avoiding descriptive analysis and instead using voxel-based lesion mapping and 3D image-rendering techniques. METHODS Magnetic resonance images obtained in 248 treatment-naïve meningioma patients with 260 lesions were retrospectively and consecutively collected. All images were registered to a 1-mm isotropic, high-resolution, T1-weighted brain atlas provided by the Montreal Neurological Institute (the MNI152), and a lesion frequency map was created, followed by 3D volume rendering to visualize the preferred locations of meningiomas in 3D. RESULTS The 3D lesion frequency map clearly showed that skull base structures such as parasellar, sphenoid wing, and petroclival regions were commonly affected by the tumor. The middle one-third of the superior sagittal sinus was most commonly affected in parasagittal tumors. Substantial lesion accumulation was observed around the leptomeninges covering the central sulcus and the sylvian fissure, with very few lesions observed at the frontal, parietal, and occipital convexities. CONCLUSIONS Using an objective visualization method, meningiomas were shown to be located around the middle third of the superior sagittal sinus, the perisylvian convexity, and the skull base. These observations, which are in line with previous descriptive analyses, justify further use of voxel-based lesion mapping techniques to help understand the biological nature of this disease.

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

PubMed

Maggi, Pietro; Absinta, Martina; Grammatico, Matteo; Vuolo, Luisa; Emmi, Giacomo; Carlucci, Giovanna; Spagni, Gregorio; Barilaro, Alessandro; Repice, Anna Maria; Emmi, Lorenzo; Prisco, Domenico; Martinelli, Vittorio; Scotti, Roberta; Sadeghi, Niloufar; Perrotta, Gaetano; Sati, Pascal; Dachy, Bernard; Reich, Daniel S; Filippi, Massimo; Massacesi, Luca

2018-02-01

In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS). In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed. MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%. The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294. © 2018 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

PubMed Central

KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

Oxidative Stress and DNA Lesions: The Role of 8-Oxoguanine Lesions in Trypanosoma cruzi Cell Viability

PubMed Central

Aguiar, Pedro H. N.; Furtado, Carolina; Repolês, Bruno M.; Ribeiro, Grazielle A.; Mendes, Isabela C.; Peloso, Eduardo F.; Gadelha, Fernanda R.; Macedo, Andrea M.; Franco, Glória R.; Pena, Sérgio D. J.; Teixeira, Santuza M. R.; Vieira, Leda Q.; Guarneri, Alessandra A.; Andrade, Luciana O.; Machado, Carlos R.

2013-01-01

The main consequence of oxidative stress is the formation of DNA lesions, which can result in genomic instability and lead to cell death. Guanine is the base that is most susceptible to oxidation, due to its low redox potential, and 8-oxoguanine (8-oxoG) is the most common lesion. These characteristics make 8-oxoG a good cellular biomarker to indicate the extent of oxidative stress. If not repaired, 8-oxoG can pair with adenine and cause a G:C to T:A transversion. When 8-oxoG is inserted during DNA replication, it could generate double-strand breaks, which makes this lesion particularly deleterious. Trypanosoma cruzi needs to address various oxidative stress situations, such as the mammalian intracellular environment and the triatomine insect gut where it replicates. We focused on the MutT enzyme, which is responsible for removing 8-oxoG from the nucleotide pool. To investigate the importance of 8-oxoG during parasite infection of mammalian cells, we characterized the MutT gene in T. cruzi (TcMTH) and generated T. cruzi parasites heterologously expressing Escherichia coli MutT or overexpressing the TcMTH enzyme. In the epimastigote form, the recombinant and wild-type parasites displayed similar growth in normal conditions, but the MutT-expressing cells were more resistant to hydrogen peroxide treatment. The recombinant parasite also displayed significantly increased growth after 48 hours of infection in fibroblasts and macrophages when compared to wild-type cells, as well as increased parasitemia in Swiss mice. In addition, we demonstrated, using western blotting experiments, that MutT heterologous expression can influence the parasite antioxidant enzyme protein levels. These results indicate the importance of the 8-oxoG repair system for cell viability. PMID:23785540

Acid-$beta$-glycerophosphatase reaction products in the central nervous system mitochondria following x-ray irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roizin, L.; Orlovskaja, D.; Liu, J.C.

A survey of the literature to date on the enzyme histochemistry of intracellular organelles has not yielded any reference to the presence of acid phosphatase reaction products in the mammalian mitochondria of the central nervous system. A combination of Gomori's acid phosphatase method, however, with standard electron microscopy has disclosed the presence of enzyme reaction products in the mitochondria of the central nervous system of rats from 2 hr to 22 weeks after x-ray irradiation, as well as in a cerebral biopsy performed on a patient affected by Huntington's chorea. No enzyme reaction products, on the other hand, were observedmore » in serial sections that had been incubated in substrates either containing sodium fluoride or lacking in $beta$- glycerophosphate. The abnormal mitochondrial enzyme reaction (chemical lesion) is considered to be the consequence of the pathologic process affecting the ultrastructural-chemical organization of the organelle. (auth)« less

Heavy ion induced DNA-DSB in yeast and mammalian cells

NASA Technical Reports Server (NTRS)

Loebrich, M.; Ikpeme, S.; Kiefer, J.

1994-01-01

Molecular changes at the DNA are assumed to be the main cause for radiation effects in a number of organisms. During the course of the last decades techniques have been developed for measuring DNA double-strand breaks (dsb), generally assumed to be the most critical DNA lesions. The outcome of all those different approaches portrays a collection of data useful for a theoretical description of radiation action mechanisms. However, in the case of heavy ion induced DNA dsb the picture is not quite clear yet and further projects and strategies have to be developed. The biological systems studied in our group are yeast and mammalian cells. While in the case of yeast cells technical and methodical reasons highlight these organisms mammalian cells reach greater importance when dsb repair studies are performed. In both types of organisms the technique of pulsed-field gel electrophoresis (PFGE) is applied, although with different modifications and evaluation procedures mainly due to the different genome sizes.

Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping

PubMed Central

Duffau, H

2001-01-01

OBJECTIVES—Brain plasticity is supposed to allow the compensation of motor function in cases of rolandic lesion. The aim was to analyse the mechanisms of functional reorganisation during surgery in the central area.
METHODS—A motor brain mapping was performed in three right handed patients without any neurological deficit, operated on for a slow growing lesion near the rolandic region (two precentral resected under general anaesthesia and one retrocentral removed under local anaesthesia to allow also sensory mapping) using intraoperative direct electrical stimulations (5 mm space tips bipolar stimulator probe, biphasic square wave pulse current: 1 ms/phase, 60 Hz, 4 to 18mA).
RESULTS—For each patient, the motor areas of the hand and forearm in the primary motor cortex (M1) were identified before and after lesion removal with the same stimulation parameters: the same eloquent sites were found, plus the appearance after resection of additional sites in M1 inducing the same movement during stimulations as the previous areas.
CONCLUSIONS—Multiple cortical representations for hand and forearm movements in M1 seem to exist. In addition, the results demonstrate the short term capacity of the brain to make changes in local motor maps, by sudden unmasking after tumour resection of a second redundant site participating in the same movement. Finally, it seems not necessary for the whole of the redundant sites to be functional to provide normal movement, a concept with potential implications for surgery within the central region.

 PMID:11254775

Control of Cell Survival in Adult Mammalian Neurogenesis.

PubMed

Kuhn, H Georg

2015-10-28

The fact that continuous proliferation of stem cells and progenitors, as well as the production of new neurons, occurs in the adult mammalian central nervous system (CNS) raises several basic questions concerning the number of neurons required in a particular system. Can we observe continued growth of brain regions that sustain neurogenesis? Or does an elimination mechanism exist to maintain a constant number of cells? If so, are old neurons replaced, or are the new neurons competing for limited network access among each other? What signals support their survival and integration and what factors are responsible for their elimination? This review will address these and other questions regarding regulatory mechanisms that control cell-death and cell-survival mechanisms during neurogenesis in the intact adult mammalian brain. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Functional noncoding sequences derived from SINEs in the mammalian genome.

PubMed

Nishihara, Hidenori; Smit, Arian F A; Okada, Norihiro

2006-07-01

Recent comparative analyses of mammalian sequences have revealed that a large number of nonprotein-coding genomic regions are under strong selective constraint. Here, we report that some of these loci have been derived from a newly defined family of ancient SINEs (short interspersed repetitive elements). This is a surprising result, as SINEs and other transposable elements are commonly thought to be genomic parasites. We named the ancient SINE family AmnSINE1, for Amniota SINE1, because we found it to be present in mammals as well as in birds, and some copies predate the mammalian-bird split 310 million years ago (Mya). AmnSINE1 has a chimeric structure of a 5S rRNA and a tRNA-derived SINE, and is related to five tRNA-derived SINE families that we characterized here in the coelacanth, dogfish shark, hagfish, and amphioxus genomes. All of the newly described SINE families have a common central domain that is also shared by zebrafish SINE3, and we collectively name them the DeuSINE (Deuterostomia SINE) superfamily. Notably, of the approximately 1000 still identifiable copies of AmnSINE1 in the human genome, 105 correspond to loci phylogenetically highly conserved among mammalian orthologs. The conservation is strongest over the central domain. Thus, AmnSINE1 appears to be the best example of a transposable element of which a significant fraction of the copies have acquired genomic functionality.

Functional noncoding sequences derived from SINEs in the mammalian genome

PubMed Central

Nishihara, Hidenori; Smit, Arian F.A.; Okada, Norihiro

2006-01-01

Recent comparative analyses of mammalian sequences have revealed that a large number of nonprotein-coding genomic regions are under strong selective constraint. Here, we report that some of these loci have been derived from a newly defined family of ancient SINEs (short interspersed repetitive elements). This is a surprising result, as SINEs and other transposable elements are commonly thought to be genomic parasites. We named the ancient SINE family AmnSINE1, for Amniota SINE1, because we found it to be present in mammals as well as in birds, and some copies predate the mammalian-bird split 310 million years ago (Mya). AmnSINE1 has a chimeric structure of a 5S rRNA and a tRNA-derived SINE, and is related to five tRNA-derived SINE families that we characterized here in the coelacanth, dogfish shark, hagfish, and amphioxus genomes. All of the newly described SINE families have a common central domain that is also shared by zebrafish SINE3, and we collectively name them the DeuSINE (Deuterostomia SINE) superfamily. Notably, of the ∼1000 still identifiable copies of AmnSINE1 in the human genome, 105 correspond to loci phylogenetically highly conserved among mammalian orthologs. The conservation is strongest over the central domain. Thus, AmnSINE1 appears to be the best example of a transposable element of which a significant fraction of the copies have acquired genomic functionality. PMID:16717141

Histogenesis of splenic lesions in Hodgkin's disease.

PubMed

Yam, L T; Li, C Y

1976-12-01

Histochemical markers were used to identify the various cellular and structural components of the human spleen, and to investigate the histogenesis of the splenic lesions of Hodgkin's disease. The early lesions appear in areas near the central artery (periarterial lymphatic sheath) in the white pulp. The white pulp becomes hypertrophic. The lesions enlarge, extend into the red pulp, and compress the sinuses and the cords of Billroth. The derivations of various "histiocytes" contained with the lesions are differentiated by using cytochemical stains for lysosomal enzymes and for granulocytes. The epithelioid cells in the granulomas are rich in those lysosomal enzymes typically seen in phagocytic histiocytes, suggesting that they are indeed true histiocytes. The malignant "histiocytes," including the mononuclear Hodgkin cells, the binucleated Sternberg-Reed cells, and the multinucleated giant cells, do not contain significant amounts of lysosomal enzymes and more closely resemble stimulated lymphocytes. The splenic lesions in Hodkin's disease may be the result of a lymphocytic and histiocytic cellular response to an unknown agent, which reaches the spleen through the central artery in the white pulp.

Astrocytic TYMP and VEGFA drive blood–brain barrier opening in inflammatory central nervous system lesions

PubMed Central

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M.; Mariani, John N.; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S.

2015-01-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood–brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood–brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood–brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood–brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood–brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood–brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP

Generation and Repair of AID-initiated DNA Lesions in B Lymphocytes

PubMed Central

Chen, Zhangguo; Wang, Jing H.

2014-01-01

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions. PMID:24748462

The muscular dystrophies associated with central nervous system lesions: a brief review from a standpoint of the localization and function of causative genes.

PubMed

Yamamoto, Tomoko; Hiroi, Atsuko; Osawa, Makiko; Shibata, Noriyuki

2014-01-01

The muscular dystrophies have been traditionally classified based mainly on clinical manifestation and mode of inheritance. Owing to the discoveries of causative genes, new terminologies derived from each gene, such as dystrophinopathy, α-dystroglycanopathy, sarcoglycanopathy and fukutinopathy, have also become common. Mutations of each gene may cause several clinical phenotypes. Some muscular dystrophies accompany central nervous system (CNS) lesions, especially in the congenital muscular dystrophies. Cobblestone lissencephaly (type II lissencephaly) is a well-known CNS malformation observed in severe forms of α-dystroglycanopathy. Moreover, CNS involvement has been reported in other muscular dystrophies, such as Duchenne muscular dystrophy. In this review, genes related to the muscular dystrophies associated with CNS lesions are briefly described along with the molecular characteristics of each gene and the pathomechanism of the CNS lesions. Understanding of both the clinicopathological characteristics of these CNS lesions and their molecular mechanisms is important for the diagnosis, care of patients, and development of new therapeutic strategies.

Characterization of the mammalian miRNA turnover landscape

PubMed Central

Guo, Yanwen; Liu, Jun; Elfenbein, Sarah J.; Ma, Yinghong; Zhong, Mei; Qiu, Caihong; Ding, Ye; Lu, Jun

2015-01-01

Steady state cellular microRNA (miRNA) levels represent the balance between miRNA biogenesis and turnover. The kinetics and sequence determinants of mammalian miRNA turnover during and after miRNA maturation are not fully understood. Through a large-scale study on mammalian miRNA turnover, we report the co-existence of multiple cellular miRNA pools with distinct turnover kinetics and biogenesis properties and reveal previously unrecognized sequence features for fast turnover miRNAs. We measured miRNA turnover rates in eight mammalian cell types with a combination of expression profiling and deep sequencing. While most miRNAs are stable, a subset of miRNAs, mostly miRNA*s, turnovers quickly, many of which display a two-step turnover kinetics. Moreover, different sequence isoforms of the same miRNA can possess vastly different turnover rates. Fast turnover miRNA isoforms are enriched for 5′ nucleotide bias against Argonaute-(AGO)-loading, but also additional 3′ and central sequence features. Modeling based on two fast turnover miRNA*s miR-222-5p and miR-125b-1-3p, we unexpectedly found that while both miRNA*s are associated with AGO, they strongly differ in HSP90 association and sensitivity to HSP90 inhibition. Our data characterize the landscape of genome-wide miRNA turnover in cultured mammalian cells and reveal differential HSP90 requirements for different miRNA*s. Our findings also implicate rules for designing stable small RNAs, such as siRNAs. PMID:25653157

Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

PubMed

Cardinal, Rudolf N; Parkinson, John A; Lachenal, Guillaume; Halkerston, Katherine M; Rudarakanchana, Nung; Hall, Jeremy; Morrison, Caroline H; Howes, Simon R; Robbins, Trevor W; Everitt, Barry J

2002-08-01

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.

The herb community of a tropical forest in central Panamá: dynamics and impact of mammalian herbivores.

PubMed

Royo, Alejandro A; Carson, Walter P

2005-08-01

Mammals are hypothesized to either promote plant diversity by preventing competitive exclusion or limit diversity by reducing the abundance of sensitive plant species through their activities as browsers or disturbance agents. Previous studies of herbivore impacts in plant communities have focused on tree species and ignored the herbaceous community. In an experiment in mature-phase, tropical moist forest sites in central Panamá, we studied the impact of excluding ground-dwelling mammals on the richness and abundance of herbs in 16, 30x45-m plots. Within each plot, we censused the herbaceous community in 28, 2x2-m subplots (1,792 m2 total area sampled). We identified over 54 species of herbs averaging 1.21 ramets m-2 and covering approximately 4.25% of the forest floor. Excluding mammals for 5 years had no impact on overall species richness. Within exclosures, however, there was a significant two-fold increase in the density of rare species. Overall herbaceous density and percent cover did not differ between exclosures and adjacent control plots, although cover did increase over time. Mammalian exclusion significantly increased the total cover of three-dominant herb species, Pharus latifolius, Calathea inocephala, and Adiantum lucidum, but did not affect their density. This study represents one of the most extensive herbaceous community censuses conducted in tropical forests and is among a few that quantify herbaceous distribution and abundance in terms of both density and cover. Additionally, this work represents the first community level test of mammalian impacts on the herbaceous community in a tropical forest to date. Our results suggest that ground dwelling mammals do not play a key role in altering the relative abundance patterns of tropical herbs in the short term. Furthermore, our results contrast sharply with prior studies on similar temporal and spatial scales that demonstrate mammals strongly alter tree seedling composition and reduce seedling density

Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

PubMed

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R

2015-06-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an

Histone underacetylation is an ancient component of mammalian X chromosome inactivation

PubMed Central

Wakefield, Matthew J.; Keohane, Ann M.; Turner, Bryan M.; Graves, Jennifer A. Marshall

1997-01-01

Underacetylation of histone H4 is thought to be involved in the molecular mechanism of mammalian X chromosome inactivation, which is an important model system for large-scale genetic control in eukaryotes. However, it has not been established whether histone underacetylation plays a critical role in the multistep inactivation pathway. Here we demonstrate differential histone H4 acetylation between the X chromosomes of a female marsupial, Macropus eugenii. Histone underacetylation is the only molecular aspect of X inactivation known to be shared by marsupial and eutherian mammals. Its strong evolutionary conservation implies that, unlike DNA methylation, histone underacetylation was a feature of dosage compensation in a common mammalian ancestor, and is therefore likely to play a central role in X chromosome inactivation in all mammals. PMID:9275180

Contrasting expressions of aggressive behavior released by lesions of the central nucleus of the amygdala during wakefulness and rapid eye movement sleep without atonia in cats.

PubMed

Zagrodzka, J; Hedberg, C E; Mann, G L; Morrison, A R

1998-06-01

Whether damage to the central nucleus of the amygdala (Ace) contributes to the predatorylike attack sometimes observed in rapid eye movement sleep without atonia (REM-A), created in cats by bilateral pontine lesions, was examined. Such lesions eliminate REM sleep skeletal muscle atonia and release elaborate behavior. Unilateral damage to the Ace alone increased affective defensive aggressive behavior toward humans and conspecifics without altering predatory behavior in wakefulness. Pontine lesions added at loci normally not leading to aggression induced predatorylike attacks in REM-A as well as the waking affective defense. Alterations of autonomic activity, the absence of relevant environmental stimuli in REM-A, or both may explain the state-related differences.

PI3K-GSK3 signalling regulates mammalian axon regeneration by inducing the expression of Smad1

NASA Astrophysics Data System (ADS)

Saijilafu; Hur, Eun-Mi; Liu, Chang-Mei; Jiao, Zhongxian; Xu, Wen-Lin; Zhou, Feng-Quan

2013-10-01

In contrast to neurons in the central nervous system, mature neurons in the mammalian peripheral nervous system (PNS) can regenerate axons after injury, in part, by enhancing intrinsic growth competence. However, the signalling pathways that enhance the growth potential and induce spontaneous axon regeneration remain poorly understood. Here we reveal that phosphatidylinositol 3-kinase (PI3K) signalling is activated in response to peripheral axotomy and that PI3K pathway is required for sensory axon regeneration. Moreover, we show that glycogen synthase kinase 3 (GSK3), rather than mammalian target of rapamycin, mediates PI3K-dependent augmentation of the growth potential in the PNS. Furthermore, we show that PI3K-GSK3 signal is conveyed by the induction of a transcription factor Smad1 and that acute depletion of Smad1 in adult mice prevents axon regeneration in vivo. Together, these results suggest PI3K-GSK3-Smad1 signalling as a central module for promoting sensory axon regeneration in the mammalian nervous system.

Secondary osteons scale allometrically in mammalian humerus and femur

PubMed Central

Phillips, C.; Cornish, H.; Cooke, M.; Hutchinson, J. R.; Doube, M.

2017-01-01

Intra-cortical bone remodelling is a cell-driven process that replaces existing bone tissue with new bone tissue in the bone cortex, leaving behind histological features called secondary osteons. While the scaling of bone dimensions on a macroscopic scale is well known, less is known about how the spatial dimensions of secondary osteons vary in relation to the adult body size of the species. We measured the cross-sectional area of individual intact secondary osteons and their central Haversian canals in transverse sections from 40 stylopodal bones of 39 mammalian species (body mass 0.3–21 000 kg). Scaling analysis of our data shows that mean osteonal resorption area (negative allometry, exponent 0.23,R2 0.54,p<0.005) and Haversian canal area (negative allometry, exponent 0.31,R2 0.45,p<0.005) are significantly related to body mass, independent of phylogeny. This study is the most comprehensive of its kind to date, and allows us to describe overall trends in the scaling behaviour of secondary osteon dimensions, supporting the inference that the osteonal resorption area may be limited by the need to avoid fracture in smaller mammalian species, but the need to maintain osteocyte viability in larger mammalian species. PMID:29291052

Mitochondrial transcription in mammalian cells

PubMed Central

Shokolenko, Inna N.; Alexeyev, Mikhail F.

2017-01-01

As a consequence of recent discoveries of intimate involvement of mitochondria with key cellular processes, there has been a resurgence of interest in all aspects of mitochondrial biology, including the intricate mechanisms of mitochondrial DNA maintenance and expression. Despite four decades of research, there remains a lot to be learned about the processes that enable transcription of genetic information from mitochondrial DNA to RNA, as well as their regulation. These processes are vitally important, as evidenced by the lethality of inactivating the central components of mitochondrial transcription machinery. Here, we review the current understanding of mitochondrial transcription and its regulation in mammalian cells. We also discuss key theories in the field and highlight controversial subjects and future directions as we see them. PMID:27814650

Coyote (Canis latrans) mammalian prey diet shifts in response to seasonal vegetation change.

PubMed

Seamster, Virginia A; Waits, Lisette P; Macko, Stephen A; Shugart, Herman H

2014-01-01

Drylands typically have strong seasonal variation in rainfall and primary productivity. This study examines the effects of seasonal change in grass-derived resource availability on the base of the food chain of a mammalian predator. Seasonal changes in live grass cover were measured in two vegetation types at the Sevilleta National Wildlife Refuge in central New Mexico, USA. Non-invasive genetic sampling of scat was used to identify individuals in the local coyote (Canis latrans) population. Stable carbon and nitrogen isotope analysis of hair removed from scats of 45 different coyotes was used to assess seasonal variation in the diet of mammalian coyote prey that came from C4 grasses. Live grass cover increased from the spring to the summer and fall; contribution of C4 grasses to the diet of mammalian coyote prey increased from the summer to the fall and was higher in grassland areas. There were significant differences in the seasonal patterns in the prey diet between grassland and shrubland areas.

Live cell imaging of Argonaute proteins in mammalian cells.

PubMed

Pare, Justin M; Lopez-Orozco, Joaquin; Hobman, Tom C

2011-01-01

The central effector of mammalian RNA interference (RNAi) is the RNA-induced silencing complex (RISC). Proteins of the Argonaute family are the core components of RISC. Recent work from multiple laboratories has shown that Argonaute family members are associated with at least two types of cytoplasmic RNA granules: GW/Processing bodies and stress granules. These Argonaute-containing granules harbor proteins that function in mRNA degradation and translational repression in response to stress. The known role of Argonaute proteins in miRNA-mediated translational repression and siRNA-directed mRNA cleavage (i.e., Argonaute 2) has prompted speculation that the association of Argonautes with these granules may reflect the activity of RNAi in vivo. Accordingly, studying the dynamic association between Argonautes and RNA granules in living cells will undoubtedly provide insight into the regulatory mechanisms of RNA-based silencing. This chapter describes a method for imaging fluorescently tagged Argonaute proteins in living mammalian cells using spinning disk confocal microscopy.

Clinical evaluation of acute phase nystagmus associated with cerebellar lesions.

PubMed

Ogawa, Y; Otsuka, K; Hagiwara, A; Inagaki, T; Shimizu, S; Nagai, N; Konomi, U; Itani, S; Kondo, T; Suzuki, M

2016-06-01

To determine the characteristics of acute phase nystagmus in patients with cerebellar lesions, and to identify a useful indicator for differentiating central lesions from peripheral lesions. Acute phase nystagmus and the appearance of neurological symptoms were retrospectively investigated in 11 patients with cerebellar stroke. At the initial visit, there were no patients with vertical nystagmus, direction-changing gaze evoked nystagmus or pure rotatory nystagmus. There were four cases with no nystagmus and seven cases with horizontal nystagmus at the initial visit. There were no neurological symptoms, except for vertigo and hearing loss, in any cases at the initial visit. The direction and type of nystagmus changed with time, and neurological symptoms other than vertigo appeared subsequently to admission. It is important to observe the changes in nystagmus and other neurological findings for the differential diagnosis of central lesions.

Soft Tissue Surgery for Adults With Nonfunctional, Spastic Hands Following Central Nervous System Lesions: A Retrospective Study.

PubMed

Gatin, Laure; Schnitzler, Alexis; Calé, Fabien; Genêt, Guillaume; Denormandie, Philippe; Genêt, François

2017-12-01

Soft tissue surgery for upper extremity contractures can improve hygiene, pain, and appearance in adults with central nervous system lesions. The goal of such interventions is highly individual; thus, goal attainment scaling (GAS; a method of scoring the extent to which patient's individual goals are achieved [5 levels] in the course of intervention and using T score values) is pertinent to evaluate outcome. The objective of this study was to assess the effect of soft tissue surgery for upper extremity muscle contractures in patients with central nervous system lesions using GAS. Retrospective data from 70 interventions were included (63 patients; 23 women). The mean age was 51.3 ± 16.2 years (range, 24.2-87.0 years). The primary goal was to improve hygiene (n = 58), pain (n = 10), or appearance (n = 2). The etiologies were stroke (n = 35), traumatic brain injury (n = 16), cerebral anoxia (n = 4), neurodegenerative disease (n = 6), and cerebral palsy (n = 2). The GAS score was calculated before surgery and 3 months after surgery. The T score (which took into account the weight of each goal) was 52.3 at 3 months (38.5 before surgery), corresponding to a "better than expected" outcome. The mean of the differences of the GAS score for each goal before and after surgery increased by 1.27 for hygiene, 1.06 for pain, and 1.00 for appearance. Soft tissue surgery can safely and effectively improve hygiene, pain, and appearance in adults with cerebral damage. The preoperative evaluation should be multidisciplinary. The GAS is a useful tool to assess the effectiveness of orthopedic surgery for these patients. Therapeutic IV. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Central Dogma Goes Digital.

PubMed

Lin, Yihan; Elowitz, Michael B

2016-03-17

In this issue of Molecular Cell, Tay and colleagues (Albayrak et al., 2016) describe a new technique to digitally quantify the numbers of protein and mRNA in the same mammalian cell, providing a new way to look at the central dogma of molecular biology. Copyright © 2016 Elsevier Inc. All rights reserved.

The response of mammalian cells to UV-light reveals Rad54-dependent and independent pathways of homologous recombination.

PubMed

Eppink, Berina; Tafel, Agnieszka A; Hanada, Katsuhiro; van Drunen, Ellen; Hickson, Ian D; Essers, Jeroen; Kanaar, Roland

2011-11-10

Ultraviolet (UV) radiation-induced DNA lesions can be efficiently repaired by nucleotide excision repair (NER). However, NER is less effective during replication of UV-damaged chromosomes. In contrast, translesion DNA synthesis (TLS) and homologous recombination (HR) are capable of dealing with lesions in replicating DNA. The core HR protein in mammalian cells is the strand exchange protein RAD51, which is aided by numerous proteins, including RAD54. We used RAD54 as a cellular marker for HR to study the response of mammalian embryonic stem (ES) cells to UV irradiation. In contrast to yeast, ES cells lacking RAD54 are not UV sensitive. Here we show that the requirement for mammalian RAD54 is masked by active NER. By genetically inactivating NER and HR through disruption of the Xpa and Rad54 genes, respectively, we demonstrate the contribution of HR to chromosomal integrity upon UV irradiation. We demonstrate using chromosome fiber analysis at the individual replication fork level, that HR activity is important for the restart of DNA replication after induction of DNA damage by UV-light in NER-deficient cells. Furthermore, our data reveal RAD54-dependent and -independent contributions of HR to the cellular sensitivity to UV-light, and they uncover that RAD54 can compensate for the loss of TLS polymerase η with regard to UV-light sensitivity. In conclusion, we show that HR is important for the progression of UV-stalled replication forks in ES cells, and that protection of the fork is an interplay between HR and TLS. Copyright © 2011 Elsevier B.V. All rights reserved.

In Vivo Imaging of the Central and Peripheral Effects of Sleep Deprivation and Suprachiasmatic Nuclei Lesion on PERIOD-2 Protein in Mice

PubMed Central

Curie, Thomas; Maret, Stephanie; Emmenegger, Yann; Franken, Paul

2015-01-01

Study Objectives: That sleep deprivation increases the brain expression of various clock genes has been well documented. Based on these and other findings we hypothesized that clock genes not only underlie circadian rhythm generation but are also implicated in sleep homeostasis. However, long time lags have been reported between the changes in the clock gene messenger RNA levels and their encoded proteins. It is therefore crucial to establish whether also protein levels increase within the time frame known to activate a homeostatic sleep response. We report on the central and peripheral effects of sleep deprivation on PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice. Design: In vivo and in situ PER2 imaging during baseline, sleep deprivation, and recovery. Settings: Mouse sleep-recording facility. Participants: Per2::Luciferase knock-in mice. Interventions: N/A. Measurements and Results: Six-hour sleep deprivation increased PER2 not only in the brain but also in liver and kidney. Remarkably, the effects in the liver outlasted those observed in the brain. Within the brain the increase in PER2 concerned the cerebral cortex mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver PER2 levels did increase in these mice similar to the sham and partially lesioned controls. Conclusions: Our results stress the importance of considering both sleep-wake dependent and circadian processes when quantifying clock-gene levels. Because sleep deprivation alters PERIOD-2 in the brain as well as in the periphery, it is tempting to speculate that clock genes constitute a common pathway mediating the shared and well-known adverse effects of both chronic sleep loss and disrupted circadian rhythmicity on metabolic health. Citation: Curie T, Maret S, Emmenegger Y, Franken P. In

Putrescine biosynthesis in mammalian tissues.

PubMed Central

Coleman, Catherine S; Hu, Guirong; Pegg, Anthony E

2004-01-01

L-ornithine decarboxylase provides de novo putrescine biosynthesis in mammals. Alternative pathways to generate putrescine that involve ADC (L-arginine decarboxylase) occur in non-mammalian organisms. It has been suggested that an ADC-mediated pathway may generate putrescine via agmatine in mammalian tissues. Published evidence for a mammalian ADC is based on (i) assays using mitochondrial extracts showing production of 14CO2 from [1-14C]arginine and (ii) cloned cDNA sequences that have been claimed to represent ADC. We have reinvestigated this evidence and were unable to find any evidence supporting a mammalian ADC. Mitochondrial extracts prepared from freshly isolated rodent liver and kidney using a metrizamide/Percoll density gradient were assayed for ADC activity using L-[U-14C]-arginine in the presence or absence of arginine metabolic pathway inhibitors. Although 14CO2 was produced in substantial amounts, no labelled agmatine or putrescine was detected. [14C]Agmatine added to liver extracts was not degraded significantly indicating that any agmatine derived from a putative ADC activity was not lost due to further metabolism. Extensive searches of current genome databases using non-mammalian ADC sequences did not identify a viable candidate ADC gene. One of the putative mammalian ADC sequences appears to be derived from bacteria and the other lacks several residues that are essential for decarboxylase activity. These results indicate that 14CO2 release from [1-14C]arginine is not adequate evidence for a mammalian ADC. Although agmatine is a known constituent of mammalian cells, it can be transported from the diet. Therefore L-ornithine decarboxylase remains the only established route for de novo putrescine biosynthesis in mammals. PMID:14763899

α-Synuclein in Central Nervous System and from Erythrocytes, Mammalian Cells, and Escherichia coli Exists Predominantly as Disordered Monomer*

PubMed Central

Fauvet, Bruno; Mbefo, Martial K.; Fares, Mohamed-Bilal; Desobry, Carole; Michael, Sarah; Ardah, Mustafa T.; Tsika, Elpida; Coune, Philippe; Prudent, Michel; Lion, Niels; Eliezer, David; Moore, Darren J.; Schneider, Bernard; Aebischer, Patrick; El-Agnaf, Omar M.; Masliah, Eliezer; Lashuel, Hilal A.

2012-01-01

Since the discovery and isolation of α-synuclein (α-syn) from human brains, it has been widely accepted that it exists as an intrinsically disordered monomeric protein. Two recent studies suggested that α-syn produced in Escherichia coli or isolated from mammalian cells and red blood cells exists predominantly as a tetramer that is rich in α-helical structure (Bartels, T., Choi, J. G., and Selkoe, D. J. (2011) Nature 477, 107–110; Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L. T. T., Liao, J., Auclair, J. R., Johnson, D., Landeru, A., Simorellis, A. K., Ju, S., Cookson, M. R., Asturias, F. J., Agar, J. N., Webb, B. N., Kang, C., Ringe, D., Petsko, G. A., Pochapsky, T. C., and Hoang, Q. Q. (2011) Proc. Natl. Acad. Sci. 108, 17797–17802). However, it remains unknown whether or not this putative tetramer is the main physiological form of α-syn in the brain. In this study, we investigated the oligomeric state of α-syn in mouse, rat, and human brains. To assess the conformational and oligomeric state of native α-syn in complex mixtures, we generated α-syn standards of known quaternary structure and conformational properties and compared the behavior of endogenously expressed α-syn to these standards using native and denaturing gel electrophoresis techniques, size-exclusion chromatography, and an oligomer-specific ELISA. Our findings demonstrate that both human and rodent α-syn expressed in the central nervous system exist predominantly as an unfolded monomer. Similar results were observed when human α-syn was expressed in mouse and rat brains as well as mammalian cell lines (HEK293, HeLa, and SH-SY5Y). Furthermore, we show that α-syn expressed in E. coli and purified under denaturing or nondenaturing conditions, whether as a free protein or as a fusion construct with GST, is monomeric and adopts a disordered conformation after GST removal. These results do not rule out the possibility that α-syn becomes structured upon interaction

Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

PubMed

Kossard, S; Collins, A; McCrossin, I

1987-05-01

Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

Germicidal Efficacy and Mammalian Skin Safety of 222-nm UV Light

PubMed Central

Buonanno, Manuela; Ponnaiya, Brian; Welch, David; Stanislauskas, Milda; Randers-Pehrson, Gerhard; Smilenov, Lubomir; Lowy, Franklin D.; Owens, David M.; Brenner, David J.

2017-01-01

We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200–222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues. We used a krypton-chlorine (Kr-Cl) excimer lamp that produces 222-nm UV light with a bandpass filter to remove the lower- and higher-wavelength components. Relative to respective controls, we measured: 1. in vitro killing of methicillin-resistant Staphylococcus aureus (MRSA) as a function of UV fluence; 2. yields of the main UV-associated premutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) in a 3D human skin tissue model in vitro; 3. eight cellular and molecular skin damage endpoints in exposed hairless mice in vivo. Comparisons were made with results from a conventional 254-nm UV germicidal lamp used as positive control. We found that 222-nm light kills MRSA efficiently but, unlike conventional germicidal UV lamps (254 nm), it produces almost no premutagenic UV-associated DNA lesions in a 3D human skin model and it is not cytotoxic to exposed mammalian skin. As predicted by biophysical considerations and in agreement with our previous findings, far-UVC light in the range of 200–222 nm kills bacteria efficiently regardless of their drug-resistant proficiency, but without the skin damaging effects associated with conventional germicidal UV exposure. PMID:28225654

Germicidal Efficacy and Mammalian Skin Safety of 222-nm UV Light.

PubMed

Buonanno, Manuela; Ponnaiya, Brian; Welch, David; Stanislauskas, Milda; Randers-Pehrson, Gerhard; Smilenov, Lubomir; Lowy, Franklin D; Owens, David M; Brenner, David J

2017-04-01

We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200-222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues. We used a krypton-chlorine (Kr-Cl) excimer lamp that produces 222-nm UV light with a bandpass filter to remove the lower- and higher-wavelength components. Relative to respective controls, we measured: 1. in vitro killing of methicillin-resistant Staphylococcus aureus (MRSA) as a function of UV fluence; 2. yields of the main UV-associated premutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) in a 3D human skin tissue model in vitro; 3. eight cellular and molecular skin damage endpoints in exposed hairless mice in vivo. Comparisons were made with results from a conventional 254-nm UV germicidal lamp used as positive control. We found that 222-nm light kills MRSA efficiently but, unlike conventional germicidal UV lamps (254 nm), it produces almost no premutagenic UV-associated DNA lesions in a 3D human skin model and it is not cytotoxic to exposed mammalian skin. As predicted by biophysical considerations and in agreement with our previous findings, far-UVC light in the range of 200-222 nm kills bacteria efficiently regardless of their drug-resistant proficiency, but without the skin damaging effects associated with conventional germicidal UV exposure.

Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

PubMed Central

Safi, Yaser; Jafari, Soudeh

2017-01-01

Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated) and rough (squamous epithelium-originated). Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic), and mesenchymal lesions (benign and malignant neoplasms). In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method. PMID:28757870

Effects of surgical lesions on choline acetyltransferase activity in the cat cochlea.

PubMed

Frilling, Mark J; Wiet, Gregory J; Godfrey, Donald A; Parli, Judy A; Dunn, Jon D; Ross, C David

2017-12-01

Although it is well established that the choline acetyltransferase (ChAT, the enzyme for acetylcholine synthesis) in the mammalian cochlea is associated with its olivocochlear innervation, the distribution of this innervation in the cochlea varies somewhat among mammalian species. The quantitative distribution of ChAT activity in the cochlea has been reported for guinea pigs and rats. The present study reports the distribution of ChAT activity within the organ of Corti among the three turns of the cat cochlea and the effects of removing olivocochlear innervation either by a lateral cut aimed to totally transect the left olivocochlear bundle or a more medial cut additionally damaging the superior olivary complex on the same side. Similarly to results for guinea pig and rat, the distribution of ChAT activity in the cat outer hair cell region showed a decrease from base to apex, but, unlike in the guinea pig and rat, the cat inner hair cell region did not. As in the rat, little ChAT activity was measured in the outer supporting cell region. As previously reported for whole cat cochlea and for rat cochlear regions, transection of the olivocochlear bundle resulted in almost total loss of ChAT activity in the hair cell regions of the cat cochlea. Lesions of the superior olivary complex resulted in loss of ChAT activity in the inner hair cell region of all cochlear turns only on the lesion side but bilateral losses in the outer hair cell region of all turns. The results are consistent with previous evidence that virtually all cholinergic synapses in the mammalian cochlea are associated with its olivocochlear innervation, that the olivocochlear innervation to the inner hair cell region is predominantly ipsilateral, and that the olivocochlear innervation to the outer hair cells is bilateral. Copyright © 2017 Elsevier B.V. All rights reserved.

Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits

PubMed Central

Meyer, Sarah; Kessner, Simon S.; Cheng, Bastian; Bönstrup, Marlene; Schulz, Robert; Hummel, Friedhelm C.; De Bruyn, Nele; Peeters, Andre; Van Pesch, Vincent; Duprez, Thierry; Sunaert, Stefan; Schrooten, Maarten; Feys, Hilde; Gerloff, Christian; Thomalla, Götz; Thijs, Vincent; Verheyden, Geert

2015-01-01

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand. PMID:26900565

Scar modulation in subacute and chronic CNS lesions: Effects on axonal regeneration.

PubMed

Stichel, Christine C.; Lausberg, Friederike; Hermanns, Susanne; Müller, Hans Werner

1999-01-01

After injury of the adult mammalian CNS axonal regeneration across or around the lesion scar is negligible. Previously, we have shown that the lesion-induced basal membrane (BM) within the lesion center participates in a growth barrier for axon regeneration and that its reduction by means of pharmacological or immunochemical treatment is a prerequisite and sufficient condition for regrowing axons to cross the lesion site. The present study was designed to further investigate this observation by analyzing the effect of a delayed treatment on the regeneration of both subacutely and chronically lesioned axons.Adult rats underwent unilateral transection of the postcommissural fornix. At one to five days after transection one group of animals received a local injection of 2, 2'-dipyridyl (DPY), an inhibitor of collagen triple helix formation and synthesis. Another group received a second transection within the former lesion site followed by an immediate DPY-injection at five days or 4 weeks after transection. Six weeks after the last surgery BM deposition and axonal regeneration were analysed using immunocytochemical methods.A local injection of DPY clearly reduced the lesion-induced BM deposition when applied within the first 3 days after transection. Under these conditions regrowing axons still crossed the former impermeable lesion site and regenerated within their normal pathway up to their former target, the mammillary body. However, in late subacute (5 d) and chronic stages (4 w) the double transection+injection paradigm failed to reduce BM deposition and, in consequence, also to induce axonal regeneration.These results demonstrate the potential of the collagen IV-reducing strategy to promote axonal regeneration across the lesion scar not only in acute but also in early subacute traumatic injuries.

Baroreflex failure in a patient with central nervous system lesions involving the nucleus tractus solitarii

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Whetsell, W. O.; Jobe, J.; Nadeau, J. H.

1994-01-01

Animal studies have shown the importance of the nucleus tractus solitarii, a collection of neurons in the brain stem, in the acute regulation of blood pressure. Impulses arising from the carotid and aortic baroreceptors converge in this center, where the first synapse of the baroreflex is located. Stimulation of the nucleus tractus solitarii provides an inhibitory signal to other brain stem structures, particularly the rostral ventrolateral medulla, resulting in a reduction in sympathetic outflow and a decrease in blood pressure. Conversely, experimental lesions of the nucleus tractus solitarii lead to loss of baroreflex control of blood pressure, sympathetic activation, and severe hypertension in animals. In humans, baroreflex failure due to deafferentation of baroreceptors has been previously reported and is characterized by episodes of severe hypertension and tachycardia. We present a patient with an undetermined process of the central nervous system characterized pathologically by ubiquitous infarctions that were particularly prominent in the nucleus tractus solitarii bilaterally but spared the rostral ventrolateral medulla. Absence of a functioning baroreflex was evidenced by the lack of reflex tachycardia to the hypotensive effects of sodium nitroprusside, exaggerated pressor responses to handgrip and cold pressor test, and exaggerated depressor responses to meals and centrally acting alpha 2-agonists. This clinicopathological correlate suggests that the patient's baroreflex failure can be explained by the unique combination of the destruction of sympathetic inhibitory centers (ie, the nucleus tractus solitarii) and preservation of centers that exert a positive modulation on sympathetic tone (ie, the rostral ventrolateral medulla).

Central xanthoma of the jaw in association with Noonan syndrome.

PubMed

Olson, Nicholas J; Addante, Rocco R; de Abreu, Francine B; Memoli, Vincent A

2018-05-01

Xanthomas are histiocytic lesions of the skin, soft tissue and bone and are generally considered to be reactive in nature. When they arise in the bones of the jaw, they are referred to as central xanthomas. New evidence supports the hypothesis that central xanthomas are a separate and distinct entity from their extragnathic counterparts. Noonan syndrome (NS) is an autosomal dominant disorder that has been associated with giant cell lesions which also commonly occur in the jaw. We present a case of a 15year-old-male with NS who presented with a radiolucent lesion of the mandible that on excision, was found to be a central xanthoma. Although giant cell lesions have been well described in NS, xanthomas of the jaw have not been reported. We will also discuss the entities that must be excluded prior to making a diagnosis of central xanthoma, as this can affect both treatment and follow up. Copyright © 2018. Published by Elsevier Inc.

Intraventricular mass lesions at magnetic resonance imaging: iconographic essay - part 1*

PubMed Central

de Castro, Felipe Damásio; Reis, Fabiano; Guerra, José Guilherme Giocondo

2014-01-01

The present essay is illustrated with magnetic resonance images obtained at the authors' institution over the past 15 years and discusses the main imaging findings of intraventricular tumor-like lesions (ependymoma, pilocytic astrocytoma, central neurocytoma, ganglioglioma, choroid plexus papilloma, primitive neuroectodermal tumors, meningioma, epidermoid tumor). Such lesions represent a subgroup of intracranial lesions with unique characteristics and some image patterns that may facilitate the differential diagnosis. PMID:25741075

Nitric oxide negatively regulates mammalian adult neurogenesis

NASA Astrophysics Data System (ADS)

Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

2003-08-01

Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

Effects of Pleistocene environmental changes on the distribution and community structure of the mammalian fauna of Mexico

NASA Astrophysics Data System (ADS)

Ceballos, Gerardo; Arroyo-Cabrales, Joaquín; Ponce, Eduardo

2010-05-01

Biological communities in Mexico experienced profound changes in species composition and structure as a consequence of the environmental fluctuations during the Pleistocene. Based on the recent and fossil Mexican mammal checklists, we determine the distribution, composition, diversity, and community structure of late Pleistocene mammalian faunas, and analyze extinction patterns and response of individual species to environmental changes. We conclude that (1) differential extinctions occurred at family, genus, and species level, with a major impact on species heavier than 100 kg, including the extinction all proboscideans and several ruminants; (2) Pleistocene mammal communities in Mexico were more diverse than recent ones; and (3) the current assemblages of species are relatively young. Furthermore, Pleistocene relicts support the presence of biogeographic corridors; important refugia existed as well as centers of speciation in isolated regions. We identified seven corridors: eastern USA-Sierra Madre Oriental corridor, Rocky Mountains-Sierra Madre Occidental corridor, Central United States-Northern Mexico corridor, Transvolcanic Belt-Sierra Madre del Sur corridor, western USA-Baja California corridor, Tamaulipas-Central America gulf lowlands corridor, and Sonora-Central America Pacific lowlands corridor. Our study suggests that present mammalian assemblages are very different than the ones in the late Pleistocene.

Mammalian Cell-Based Sensor System

NASA Astrophysics Data System (ADS)

Banerjee, Pratik; Franz, Briana; Bhunia, Arun K.

Use of living cells or cellular components in biosensors is receiving increased attention and opens a whole new area of functional diagnostics. The term "mammalian cell-based biosensor" is designated to biosensors utilizing mammalian cells as the biorecognition element. Cell-based assays, such as high-throughput screening (HTS) or cytotoxicity testing, have already emerged as dependable and promising approaches to measure the functionality or toxicity of a compound (in case of HTS); or to probe the presence of pathogenic or toxigenic entities in clinical, environmental, or food samples. External stimuli or changes in cellular microenvironment sometimes perturb the "normal" physiological activities of mammalian cells, thus allowing CBBs to screen, monitor, and measure the analyte-induced changes. The advantage of CBBs is that they can report the presence or absence of active components, such as live pathogens or active toxins. In some cases, mammalian cells or plasma membranes are used as electrical capacitors and cell-cell and cell-substrate contact is measured via conductivity or electrical impedance. In addition, cytopathogenicity or cytotoxicity induced by pathogens or toxins resulting in apoptosis or necrosis could be measured via optical devices using fluorescence or luminescence. This chapter focuses mainly on the type and applications of different mammalian cell-based sensor systems.

Mammalian synthetic biology: emerging medical applications

PubMed Central

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

2015-01-01

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

Focusing on RISC assembly in mammalian cells.

PubMed

Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

2008-04-11

RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

Stem Cells in Mammalian Gonads.

PubMed

Wu, Ji; Ding, Xinbao; Wang, Jian

Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

PubMed Central

Nowlin, Brian T.; Burdo, Tricia H.; Midkiff, Cecily C.; Salemi, Marco; Alvarez, Xavier; Williams, Kenneth C.

2016-01-01

Macrophage recruitment to the central nervous system (CNS) during AIDS pathogenesis is poorly understood. We measured the accumulation of brain perivascular (CD163+) and inflammatory (MAC387+) macrophages in SIV-infected monkeys. Monocyte progenitors were 5-bromo-2′-deoxyuridine (BrdU) labeled in bone marrow, and CNS macrophages were labeled serially with fluorescent dextrans injected into the cisterna magna. MAC387+ macrophages accumulated in the meninges and choroid plexus in early inflammation and in the perivascular space and SIV encephalitis (SIVE) lesions late. CD163+ macrophages accumulated in the perivascular space and SIVE lesions with late inflammation. Most of the BrdU+ cells were MAC387+; however, CD163+BrdU+ macrophages were present in the meninges and choroid plexus with AIDS. Most (81.6% ± 1.8%) of macrophages in SIVE lesions were present in the CNS before SIVE lesion formation. There was a 2.9-fold increase in SIVp28+ macrophages entering the CNS late compared with those entering early (P < 0.05). The rate of CD163+ macrophage recruitment to the CNS inversely correlated with time to death (P < 0.03) and increased with SIVE. In SIVE animals, soluble CD163 correlated with CD163+ macrophage recruitment (P = 0.02). Most perivascular macrophages that comprise SIVE lesions and multinucleated giant cells are present in the CNS early, before SIVE lesions are formed. Most SIV-infected macrophages traffic to the CNS terminally with AIDS. PMID:25963554

Mammalian synthetic biology: emerging medical applications.

PubMed

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

2015-05-06

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Mammalian development in space

NASA Technical Reports Server (NTRS)

Ronca, April E.

2003-01-01

Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

Generating mammalian stable cell lines by electroporation.

PubMed

A Longo, Patti; Kavran, Jennifer M; Kim, Min-Sung; Leahy, Daniel J

2013-01-01

Expression of functional, recombinant mammalian proteins often requires expression in mammalian cells (see Single Cell Cloning of a Stable Mammalian Cell Line). If the expressed protein needs to be made frequently, it can be best to generate a stable cell line instead of performing repeated transient transfections into mammalian cells. Here, we describe a method to generate stable cell lines via electroporation followed by selection steps. This protocol will be limited to the CHO dhfr-Urlaub et al. (1983) and LEC1 cell lines, which in our experience perform the best with this method. Copyright © 2013 Elsevier Inc. All rights reserved.

Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

PubMed Central

Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

2012-01-01

Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

Dental cervical lesions associated with occlusal erosion and attrition.

PubMed

Khan, F; Young, W G; Shahabi, S; Daley, T J

1999-09-01

Acid demineralization of teeth causes occlusal erosion and attrition, and shallow and wedge-shaped cervical lesions putatively involving abfraction. From 250 patients with tooth wear, 122 with cervical lesions were identified. From epoxy resin replicas of their dentitions, associations of occlusal attrition or erosion or no wear with cervical lesions were recorded at 24 tooth sites (total 2928 sites). Criteria used to discriminate occlusal attrition from erosion, and shallow from grooved, wedge-shaped or restored cervical lesions were delineated by scanning electron microscopy. A 96 per cent association was found between occlusal and cervical pathology. Shallow cervical lesions were more commonly found in association with occlusal erosion. Wedge-shaped lesions were found equally commonly in association with occlusal erosion, as with attrition. Grooved and restored cervical lesions were uncommon. Differences were appreciated in the associations within incisor, canine, premolar and molar tooth sites which related more to the site-specificity of dental erosion than to attrition from occlusal forces. Non-carious lesions on teeth then have multifactorial aetiology and pathogenesis in which erosion and salivary protection play central roles. Dentists should primarily consider erosion in the diagnosis, prevention and treatment of tooth wear.

Autoimmune control of lesion growth in CNS with minimal damage

NASA Astrophysics Data System (ADS)

Mathankumar, R.; Mohan, T. R. Krishna

2013-07-01

Lesions in central nervous system (CNS) and their growth leads to debilitating diseases like Multiple Sclerosis (MS), Alzheimer's etc. We developed a model earlier [1, 2] which shows how the lesion growth can be arrested through a beneficial auto-immune mechanism. We compared some of the dynamical patterns in the model with different facets of MS. The success of the approach depends on a set of control parameters and their phase space was shown to have a smooth manifold separating the uncontrolled lesion growth region from the controlled. Here we show that an optimal set of parameter values exist in the model which minimizes system damage while, at once, achieving control of lesion growth.

Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells

PubMed Central

Osawa, T; Davies, D; Hartley, J A

2011-01-01

DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced cell death is unclear. Here, we show a novel mechanism of p53-independent apoptotic cell death involving prolonged cell-cycle (G2) arrest, ICL repair involving HR, transient mitosis, incomplete cytokinesis, and gross chromosomal abnormalities resulting from ICLs in mammalian cells. This characteristic ‘giant' cell death, observed by using time-lapse video microscopy, was reduced in ICL repair ERCC1- and XRCC3-deficient cells. Collectively, the results illustrate the coordination of ICL-induced cellular responses, including cell-cycle arrest, DNA damage repair, and cell death. PMID:21814285

Novel snake papillomavirus does not cluster with other non-mammalian papillomaviruses.

PubMed

Lange, Christian E; Favrot, Claude; Ackermann, Mathias; Gull, Jessica; Vetsch, Elisabeth; Tobler, Kurt

2011-09-12

Papillomaviruses (PVs) are associated with the development of neoplasias and have been found in several different species, most of them in humans and other mammals. We identified, cloned and sequenced PV DNA from pigmented papilloma-like lesions of a diamond python (Morelia spilota spilota). This represents the first complete PV genome discovered in a Squamata host (MsPV1). It consists of 7048 nt and contains the characteristic open reading (ORF) frames E6, E7, E1, E2, L1 and L2. The L1 ORF sequence showed the highest percentage of sequence identities to human PV5 (57.9%) and Caribbean manatee (Trichechus manatus) PV1 (55.4%), thus, establishing a new clade. According to phylogenetic analysis, the MsPV1 genome clusters with PVs of mammalian rather than sauropsid hosts.

Nasopalatine duct cyst mimicking an endodontic periapical lesion: a case report.

PubMed

Bains, Rhythm; Verma, Promila; Chandra, Anil; Tikku, A P; Singh, Nimisha

2016-01-01

Lesions of nonendodontic origin, such as nasopalatine or globulomaxillary cysts, may mimic periapical radiolucencies associated with pulpal pathosis, and incorrect diagnosis may lead to unnecessary endodontic treatment. Horizontal root fractures most commonly affect the maxillary central and lateral incisors. Prognosis depends largely on the level of fracture; fractures in the apical third have the best prognosis, and those in the cervical third have the worst. This case report discusses surgical and restorative management of a patient who had a nasopalatine cyst that had been misdiagnosed and treated as an endodontic lesion of the maxillary right central incisor as well as a midroot horizontal fracture of the adjacent lateral incisor.

Digital Quantification of Proteins and mRNA in Single Mammalian Cells.

PubMed

Albayrak, Cem; Jordi, Christian A; Zechner, Christoph; Lin, Jing; Bichsel, Colette A; Khammash, Mustafa; Tay, Savaş

2016-03-17

Absolute quantification of macromolecules in single cells is critical for understanding and modeling biological systems that feature cellular heterogeneity. Here we show extremely sensitive and absolute quantification of both proteins and mRNA in single mammalian cells by a very practical workflow that combines proximity ligation assay (PLA) and digital PCR. This digital PLA method has femtomolar sensitivity, which enables the quantification of very small protein concentration changes over its entire 3-log dynamic range, a quality necessary for accounting for single-cell heterogeneity. We counted both endogenous (CD147) and exogenously expressed (GFP-p65) proteins from hundreds of single cells and determined the correlation between CD147 mRNA and the protein it encodes. Using our data, a stochastic two-state model of the central dogma was constructed and verified using joint mRNA/protein distributions, allowing us to estimate transcription burst sizes and extrinsic noise strength and calculate the transcription and translation rate constants in single mammalian cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Roles of epigenome in mammalian spermatogenesis.

PubMed

Song, Ning; Endo, Daisuke; Koji, Takehiko

2014-04-01

Mammalian spermatogenesis is a successive process consisting of spermatogonial proliferation, spermatocytic meiosis, and spermiogenesis, representing the maturation of haploid spermatids. During the process, 25-75 % of the expected sperm yield is thought to be lost through apoptosis. In addition, spermatogenesis is considered to be a process undergoing successive heterochromatinization, finally reaching a complete condensed form in the sperm head. Thus, cell proliferation, differentiation and death may be strictly regulated by epigenetic factors in this process. This review describes the current understanding of the role of epigenome in spermatogenesis, especially focusing on the following aspects; DNA methylation, modification of histones, and small RNA function. These epigenetic factors affect each other and play a central role in events essential for spermatogenesis, fertilization and embryogenesis, through the regulation of gene expression, transposon activities, meiotic sex chromosome inactivation, histone remodeling and genome imprinting. Finally, a brief discussion of future avenues of study is highlighted.

Reactive oral lesions associated with dental implants. A systematic review.

PubMed

Atarbashi-Moghadam, Fazele; Atarbashi-Moghadam, Saede; Namdari, Mahshid; Shahrabi-Farahani, Shokoufeh

2018-05-11

Reactive lesion formation around dental implants a complication that has been given much consideration. These lesions can lead to marginal bone loss, and consequently, implant failure. In the present systematic review, all reported reactive lesions associated with dental implants in the literature were assessed. An electronic search was performed using PubMed Central, Scopus, Google Scholar, and Science Direct. The search strategy was limited to human studies (case reports and case series), full-text English language articles, published until May 2017. A total of 19 articles reporting 27 lesions in 25 cases were included. Peripheral giant cell granuloma and pyogenic granuloma were the most reactive lesions found around dental implants. The mean age of the patients was 51.28 ± 14.48 years, with a slight female predilection. Posterior mandibular gingiva was the most common location for these lesions. The recurrence rate of lesions was 33.33%, and the chance of implant removal was 29.62%. Due to the clinical significance of these lesions, early histopathologic examination is recommended to exclude the presence of such pathological lesions. © 2018 John Wiley & Sons Australia, Ltd.

Mixed periapical lesion: differential diagnosis of a case.

PubMed

Krithika, C; Kota, S; Gopal, K S; Koteeswaran, D

2011-03-01

A radicular cyst associated with carious teeth is a very common odontogenic lesion in the oral cavity, but calcifications in residual radicular cysts are quite rare. We report one such case where a routine pre-implant radiographic assessment revealed a mixed periapical radiopaque radiolucent lesion in the right maxillary central incisor region. Histological and radiographic studies show that there is a slow increase in the mineralized deposits within the cyst lumen with time. This becomes prominent histochemically in cysts more than 8 years old and radiographically 6 years later, as seen in our case. In this paper we would like to highlight the importance of a residual radicular cyst with calcifications in the differential diagnosis of a mixed periapical radiopaque radiolucent lesion.

Mixed periapical lesion: differential diagnosis of a case

PubMed Central

Krithika, C; Kota, S; Gopal, KS; Koteeswaran, D

2011-01-01

A radicular cyst associated with carious teeth is a very common odontogenic lesion in the oral cavity, but calcifications in residual radicular cysts are quite rare. We report one such case where a routine pre-implant radiographic assessment revealed a mixed periapical radiopaque radiolucent lesion in the right maxillary central incisor region. Histological and radiographic studies show that there is a slow increase in the mineralized deposits within the cyst lumen with time. This becomes prominent histochemically in cysts more than 8 years old and radiographically 6 years later, as seen in our case. In this paper we would like to highlight the importance of a residual radicular cyst with calcifications in the differential diagnosis of a mixed periapical radiopaque radiolucent lesion. PMID:21346087

A compact light-sheet microscope for the study of the mammalian central nervous system

PubMed Central

Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

2016-01-01

Investigation of the transient processes integral to neuronal function demands rapid and high-resolution imaging techniques over a large field of view, which cannot be achieved with conventional scanning microscopes. Here we describe a compact light sheet fluorescence microscope, featuring a 45° inverted geometry and an integrated photolysis laser, that is optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We demonstrate the utility of this design for three-dimensional morphological reconstruction, activation of a single synapse with localized photolysis, and fast imaging of neuronal Ca2+ signalling across a large field of view. The developed system opens up a host of novel applications for the neuroscience community. PMID:27215692

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka.

PubMed

Nanayakkara, Shanika; Komiya, Toshiyuki; Ratnatunga, Neelakanthi; Senevirathna, S T M L D; Harada, Kouji H; Hitomi, Toshiaki; Gobe, Glenda; Muso, Eri; Abeysekera, Tilak; Koizumi, Akio

2012-05-01

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.

Simulation of spread and control of lesions in brain.

PubMed

Thamattoor Raman, Krishna Mohan

2012-01-01

A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios.

Mammalian Pheromones

PubMed Central

Liberles, Stephen D.

2015-01-01

Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d ) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors. PMID:23988175

Endogenous formation and repair of oxidatively induced G[8-5 m]T intrastrand cross-link lesion

PubMed Central

Wang, Jin; Cao, Huachuan; You, Changjun; Yuan, Bifeng; Bahde, Ralf; Gupta, Sanjeev; Nishigori, Chikako; Niedernhofer, Laura J.; Brooks, Philip J.; Wang, Yinsheng

2012-01-01

Exposure to reactive oxygen species (ROS) can give rise to the formation of various DNA damage products. Among them, d(G[8-5 m]T) can be induced in isolated DNA treated with Fenton reagents and in cultured human cells exposed to γ-rays, d(G[8-5m]T) can be recognized and incised by purified Escherichia coli UvrABC nuclease. However, it remains unexplored whether d(G[8-5 m]T) accumulates in mammalian tissues and whether it is a substrate for nucleotide excision repair (NER) in vivo. Here, we found that d(G[8-5 m]T) could be detected in DNA isolated from tissues of healthy humans and animals, and elevated endogenous ROS generation enhanced the accumulation of this lesion in tissues of a rat model of Wilson’s disease. Additionally, XPA-deficient human brain and mouse liver as well as various types of tissues of ERCC1-deficient mice contained higher levels of d(G[8-5 m]T) but not ROS-induced single-nucleobase lesions than the corresponding normal controls. Together, our studies established that d(G[8-5 m]T) can be induced endogenously in mammalian tissues and constitutes a substrate for NER in vivo. PMID:22581771

In Vitro Lesion Bypass Studies of O(4)-Alkylthymidines with Human DNA Polymerase η.

PubMed

Williams, Nicole L; Wang, Pengcheng; Wu, Jiabin; Wang, Yinsheng

2016-04-18

Environmental exposure and endogenous metabolism can give rise to DNA alkylation. Among alkylated nucleosides, O(4)-alkylthymidine (O(4)-alkyldT) lesions are poorly repaired in mammalian systems and may compromise the efficiency and fidelity of cellular DNA replication. To cope with replication-stalling DNA lesions, cells are equipped with translesion synthesis DNA polymerases that are capable of bypassing various DNA lesions. In this study, we assessed human DNA polymerase η (Pol η)-mediated bypass of various O(4)-alkyldT lesions, with the alkyl group being Me, Et, nPr, iPr, nBu, iBu, (R)-sBu, or (S)-sBu, in template DNA by conducting primer extension and steady-state kinetic assays. Our primer extension assay results revealed that human Pol η, but not human polymerases κ and ι or yeast polymerase ζ, was capable of bypassing all O(4)-alkyldT lesions and extending the primer to generate full-length replication products. Data from steady-state kinetic measurements showed that Pol η preferentially misincorporated dGMP opposite O(4)-alkyldT lesions with a straight-chain alkyl group. The nucleotide misincorporation opposite most lesions with a branched-chain alkyl group was, however, not selective, where dCMP, dGMP, and dTMP were inserted at similar efficiencies opposite O(4)-iPrdT, O(4)-iBudT, and O(4)-(R)-sBudT. These results provide important knowledge about the effects of the length and structure of the alkyl group in O(4)-alkyldT lesions on the fidelity and efficiency of DNA replication mediated by human Pol η.

Enhancer Evolution across 20 Mammalian Species

PubMed Central

Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

2015-01-01

Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

Protein and genome evolution in Mammalian cells for biotechnology applications.

PubMed

Majors, Brian S; Chiang, Gisela G; Betenbaugh, Michael J

2009-06-01

Mutation and selection are the essential steps of evolution. Researchers have long used in vitro mutagenesis, expression, and selection techniques in laboratory bacteria and yeast cultures to evolve proteins with new properties, termed directed evolution. Unfortunately, the nature of mammalian cells makes applying these mutagenesis and whole-organism evolution techniques to mammalian protein expression systems laborious and time consuming. Mammalian evolution systems would be useful to test unique mammalian cell proteins and protein characteristics, such as complex glycosylation. Protein evolution in mammalian cells would allow for generation of novel diagnostic tools and designer polypeptides that can only be tested in a mammalian expression system. Recent advances have shown that mammalian cells of the immune system can be utilized to evolve transgenes during their natural mutagenesis processes, thus creating proteins with unique properties, such as fluorescence. On a more global level, researchers have shown that mutation systems that affect the entire genome of a mammalian cell can give rise to cells with unique phenotypes suitable for commercial processes. This review examines the advances in mammalian cell and protein evolution and the application of this work toward advances in commercial mammalian cell biotechnology.

Central Nervous System Cancers, Version 2.2014

PubMed Central

Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C.; DeAngelis, Lisa M.; Fenstermaker, Robert A.; Friedman, Allan; Gilbert, Mark R.; Hattangadi-Gluth, Jona; Hesser, Deneen; Holdhoff, Matthias; Junck, Larry; Lawson, Ronald; Loeffler, Jay S.; Moots, Paul L.; Mrugala, Maciej M.; Newton, Herbert B.; Raizer, Jeffrey J.; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C.; Sills, Allen K.; Swinnen, Lode J.; Tran, David; Tran, Nam; Vrionis, Frank D.; Wen, Patrick Yung; McMillian, Nicole R.; Ho, Maria

2015-01-01

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases. PMID:25361798

The central domain of yeast transcription factor Rpn4 facilitates degradation of reporter protein in human cells.

PubMed

Morozov, A V; Spasskaya, D S; Karpov, D S; Karpov, V L

2014-10-16

Despite high interest in the cellular degradation machinery and protein degradation signals (degrons), few degrons with universal activity along species have been identified. It has been shown that fusion of a target protein with a degradation signal from mammalian ornithine decarboxylase (ODC) induces fast proteasomal degradation of the chimera in both mammalian and yeast cells. However, no degrons from yeast-encoded proteins capable to function in mammalian cells were identified so far. Here, we demonstrate that the yeast transcription factor Rpn4 undergoes fast proteasomal degradation and its central domain can destabilize green fluorescent protein and Alpha-fetoprotein in human HEK 293T cells. Furthermore, we confirm the activity of this degron in yeast. Thus, the Rpn4 central domain is an effective interspecies degradation signal. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Magnetic resonance imaging characteristics in four dogs with central nervous system neosporosis.

PubMed

Parzefall, Birgit; Driver, Colin J; Benigni, Livia; Davies, Emma

2014-01-01

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs. © 2014 American College of Veterinary Radiology.

Novel snake papillomavirus does not cluster with other non-mammalian papillomaviruses

PubMed Central

2011-01-01

Papillomaviruses (PVs) are associated with the development of neoplasias and have been found in several different species, most of them in humans and other mammals. We identified, cloned and sequenced PV DNA from pigmented papilloma-like lesions of a diamond python (Morelia spilota spilota). This represents the first complete PV genome discovered in a Squamata host (MsPV1). It consists of 7048 nt and contains the characteristic open reading (ORF) frames E6, E7, E1, E2, L1 and L2. The L1 ORF sequence showed the highest percentage of sequence identities to human PV5 (57.9%) and Caribbean manatee (Trichechus manatus) PV1 (55.4%), thus, establishing a new clade. According to phylogenetic analysis, the MsPV1 genome clusters with PVs of mammalian rather than sauropsid hosts. PMID:21910860

Selection of filamentous fungi of the Beauveria genus able to metabolize quercetin like mammalian cells

PubMed Central

de M. B. Costa, Eula Maria; Pimenta, Fabiana Cristina; Luz, Wolf Christian; de Oliveira, Valéria

2008-01-01

Microbial biotransformations constitute an important alternative as models for drug metabolism study in mammalians and have been used for the industrial synthesis of chemicals with pharmaceutical purposes. Several microorganisms with unique biotransformation ability have been found by intensive screening and put in commercial applications. Ten isolates of Beauveria sp genus filamentous fungi, isolated from soil in the central Brazil, and Beauveria bassiana ATCC 7159 were evaluated for their capability of quercetin biotransformation. Biotransformation processes were carried out for 24 up to 96 hours and monitored by mass spectrometry analyses of the culture broth. All strains were able to metabolize quercetin, forming mammalian metabolites. The results were different from those presented by other microorganisms previously utilized, attrackting attention because of the great diversity of reactions. Methylated, sulphated, monoglucuronidated, and glucuronidated conjugated metabolites were simultaneously detected. PMID:24031237

The mammalian circadian clock and its entrainment by stress and exercise.

PubMed

Tahara, Yu; Aoyama, Shinya; Shibata, Shigenobu

2017-01-01

The mammalian circadian clock regulates day-night fluctuations in various physiological processes. The circadian clock consists of the central clock in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks in peripheral tissues. External environmental cues, including light/dark cycles, food intake, stress, and exercise, provide important information for adjusting clock phases. This review focuses on stress and exercise as potent entrainment signals for both central and peripheral clocks, especially in regard to the timing of stimuli, types of stressors/exercises, and differences in the responses of rodents and humans. We suggest that the common signaling pathways of clock entrainment by stress and exercise involve sympathetic nervous activation and glucocorticoid release. Furthermore, we demonstrate that physiological responses to stress and exercise depend on time of day. Therefore, using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective for preventing obesity, diabetes, and cardiovascular disease.

Wnt signalling pathway parameters for mammalian cells.

PubMed

Tan, Chin Wee; Gardiner, Bruce S; Hirokawa, Yumiko; Layton, Meredith J; Smith, David W; Burgess, Antony W

2012-01-01

Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated with the parameters

Microanalyses of lesions and lymph nodes from coalminers' lungs.

PubMed

Chapman, J S; Ruckley, V A

1985-08-01

The dust content and composition of lesions and hilar lymph nodes from the lungs of British coalworkers have been examined. Samples of macules, fibrotic nodules, and massive fibrosis (both peripheral and central sites) were dissected from 49 lungs. The highest mean dust concentrations (about 20%) were found in nodules and massive fibrosis. Overall there were no significant differences between the selected lesion types and their respective whole lung dust composition, although the central sites of massive fibrosis were found to contain on average a higher proportion of coal and a lower proportion of ash and its measured constituents, quartz and kaolin plus mica, than the edge of the lesion (p less than 0.001 for each component). There were striking differences between recovered lung and lymph node dusts. An examination of 180 specimens showed a mean quartz in lymph node dust of 20.3% compared with 6.1% in lung dust. As expected the proportion of quartz was greater in lymph nodes and lungs from men who had worked "low" rank (high ash) coal. By contrast with the corresponding figures for lung dusts, however, the mean proportion of quartz in nodes did not increase over the pathological range of pneumoconiotic lung disease. On average the proportions of kaolin and mica in lymph nodes reflect those found in lungs. The lymphotrophic nature of quartz was clearly shown although it was not possible to show an association between this clearance pathway and any particular type of lesion.

Dedifferentiated adenoid cystic carcinoma of the trachea: a case report with respect to the immunohistochemical analyses of mammalian target of rapamycin pathway proteins.

PubMed

Ishida, Mitsuaki; Okabe, Hidetoshi

2013-08-01

Dedifferentiated adenoid cystic carcinoma is an extremely rare and highly aggressive tumor. We describe the first reported case of dedifferentiated adenoid cystic carcinoma of the trachea and analyze the expression profiles of mammalian target of rapamycin pathway proteins. A 66-year-old Japanese man was incidentally found to have stenosis of the trachea, and a bronchial biopsy revealed low-grade adenoid cystic carcinoma. The resected specimen revealed dedifferentiated adenoid cystic carcinoma, which was composed of conventional low-grade adenoid cystic carcinoma with tubular and cribriform patterns, and a dedifferentiated carcinoma component (poorly differentiated adenocarcinoma). Immunohistochemical study showed that mammalian target of rapamycin and 4E-BP1 were expressed in both components; however, phosphorylated 4E-BP1 was expressed only in the dedifferentiated carcinoma component. This report clearly demonstrates that mammalian target of rapamycin pathway proteins were activated in dedifferentiated carcinoma. Mammalian target of rapamycin is a central protein involved in carcinogenesis, and administration of its inhibitors prolonged survival in some types of carcinoma. Therefore, mammalian target of rapamycin inhibitors may be a potential candidate for treatment of this highly aggressive carcinoma. Copyright © 2013 Elsevier Inc. All rights reserved.

Multi-output decision trees for lesion segmentation in multiple sclerosis

NASA Astrophysics Data System (ADS)

Jog, Amod; Carass, Aaron; Pham, Dzung L.; Prince, Jerry L.

2015-03-01

Multiple Sclerosis (MS) is a disease of the central nervous system in which the protective myelin sheath of the neurons is damaged. MS leads to the formation of lesions, predominantly in the white matter of the brain and the spinal cord. The number and volume of lesions visible in magnetic resonance (MR) imaging (MRI) are important criteria for diagnosing and tracking the progression of MS. Locating and delineating lesions manually requires the tedious and expensive efforts of highly trained raters. In this paper, we propose an automated algorithm to segment lesions in MR images using multi-output decision trees. We evaluated our algorithm on the publicly available MICCAI 2008 MS Lesion Segmentation Challenge training dataset of 20 subjects, and showed improved results in comparison to state-of-the-art methods. We also evaluated our algorithm on an in-house dataset of 49 subjects with a true positive rate of 0.41 and a positive predictive value 0.36.

Esterified Trehalose Analogues Protect Mammalian Cells from Heat Shock.

PubMed

Bragg, Jack T; D'Ambrosio, Hannah K; Smith, Timothy J; Gorka, Caroline A; Khan, Faraz A; Rose, Joshua T; Rouff, Andrew J; Fu, Terence S; Bisnett, Brittany J; Boyce, Michael; Khetan, Sudhir; Paulick, Margot G

2017-09-19

Trehalose is a disaccharide produced by many organisms to better enable them to survive environmental stresses, including heat, cold, desiccation, and reactive oxygen species. Mammalian cells do not naturally biosynthesize trehalose; however, when introduced into mammalian cells, trehalose provides protection from damage associated with freezing and drying. One of the major difficulties in using trehalose as a cellular protectant for mammalian cells is the delivery of this disaccharide into the intracellular environment; mammalian cell membranes are impermeable to the hydrophilic sugar trehalose. A panel of cell-permeable trehalose analogues, in which the hydrophilic hydroxyl groups of trehalose are masked as esters, have been synthesized and the ability of these analogues to load trehalose into mammalian cells has been evaluated. Two of these analogues deliver millimolar concentrations of free trehalose into a variety of mammalian cells. Critically, Jurkat cells incubated with these analogues show improved survival after heat shock, relative to untreated Jurkat cells. The method reported herein thus paves the way for the use of esterified analogues of trehalose as a facile means to deliver high concentrations of trehalose into mammalian cells for use as a cellular protectant. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Predicting improvement of postorthodontic white spot lesions.

PubMed

Kim, Susan; Katchooi, Mina; Bayiri, Burcu; Sarikaya, Mehmet; Korpak, Anna M; Huang, Greg J

2016-05-01

Patients undergoing orthodontic treatment are at greater risk for developing white spot lesions (WSLs). Although prevention is always the goal, WSLs continue to be a common sequela. For this reason, understanding the patterns of WSL improvement, if any, has great importance. Previous studies have shown that some lesions exhibit significant improvement, whereas others have limited or no improvement. Our aim was to identify specific patient-related and tooth-related factors that are most predictive of improvement with treatment. Patients aged 12 to 20 years with at least 1 WSL that developed during orthodontic treatment were recruited from private dental and orthodontic offices. They had their fixed appliances removed 2 months or less before enrollment. Photographs were taken at enrollment and 8 weeks later. Paired photographs of the maxillary incisors, taken at each time point, were blindly assessed for changes in surface area and appearance at the individual tooth level using visual inspection. One hundred one subjects were included in this study. Patient age, brushing frequency, and greater percentage of surface area affected were associated with increased improvement. Central incisors exhibited greater improvements than lateral incisors. Longer time since appliance removal and longer length of orthodontic treatment were associated with decreased levels of improvement. Sex, oral hygiene status, retainer type, location of the lesion (gingival, middle, incisal), staining, and lesion diffuseness were not found to be predictive of improvement. Of the various patient-related and tooth-related factors examined, age, time since appliance removal, length of orthodontic treatment, tooth type (central or lateral incisor), WSL surface area, and brushing frequency had significant associations with WSL improvement. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Effect of Microgravity on Mammalian Lymphocytes

NASA Technical Reports Server (NTRS)

Banerjee, H.; Blackshear, M.; Mahaffey, K.; Knight, C.; Khan, A. A.; Delucas, L.

2004-01-01

The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization.The Astronauts will be exposed to microgravity environment for a long duration of time during these flights.Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system.We did our preliminary investigations by exposing mammalian lymphocytes to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon Inc (USA).Our initial results showed no significant change in cytokine expression in these cells for a time period of forty eight hours exposure.Our future experiments will involve exposure for a longer period of time.

An autopsy case of chronic active Epstein-Barr virus infection (CAEBV): distribution of central nervous system (CNS) lesions.

PubMed

Kobayashi, Zen; Tsuchiya, Kuniaki; Takahashi, Makoto; Yokota, Osamu; Sasaki, Atsushi; Bhunchet, Ekapot; Arai, Tetsuaki; Akiyama, Haruhiko; Kamoshita, Masaharu; Kotera, Minoru; Mizusawa, Hidehiro

2008-12-15

A 27-year-old Japanese man developed recurrent respiratory and central nervous system (CNS) symptoms, and hemophagocytic syndromes with a clinical course of 6 years. CT demonstrated multiple nodular lesions in the bilateral lungs, and MRI revealed multiple abnormal intensity areas in the brain and spinal cord. Cerebrospinal fluid (CSF) examination disclosed mild pleocytosis and the presence of Epstein-Barr virus (EBV)-DNA detected by polymerase chain reaction (PCR). The patient died of a hemorrhagic shock associated with a hemophagocytic syndrome. A postmortem study revealed massive hemorrhage in the abdominal cavity and iliopsoas muscles, as well as diffuse infiltration of lymphocytes and/or macrophages into the lungs, liver, kidneys, spleen, cardiac muscle, bone marrow, and CNS. The severe involvement was demonstrated in the CNS, especially in the spinal cord and brainstem. The CD3 positive cells of the brainstem were EBV-encoded RNA 1 positive. This is the first autopsy case of chronic active EBV infection (CAEBV) in which severe and extensive CNS involvement was demonstrated.

Mammalian Fe-S cluster biogenesis and its implication in disease.

PubMed

Beilschmidt, Lena K; Puccio, Hélène M

2014-05-01

Iron-sulfur (Fe-S) clusters are inorganic cofactors that are ubiquitous and essential. Due to their chemical versatility, Fe-S clusters are implicated in a wide range of protein functions including mitochondrial respiration and DNA repair. Composed of iron and sulfur, they are sensible to oxygen and their biogenesis requires a highly conserved protein machinery that facilitates assembly of the cluster as well as its insertion into apoproteins. Mitochondria are the central cellular compartment for Fe-S cluster biogenesis in eukaryotic cells and the importance of proper function of this biogenesis for life is highlighted by a constantly increasing number of human genetic diseases that are associated with dysfunction of this Fe-S cluster biogenesis pathway. Although these disorders are rare and appear dissimilar, common aspects are found among them. This review will give an overview on what is known on mammalian Fe-S cluster biogenesis today, by putting it into the context of what is known from studies from lower model organisms, and focuses on the associated diseases, by drawing attention to the respective mutations. Finally, it outlines the importance of adequate cellular and murine models to uncover not only each protein function, but to resolve their role and requirement throughout the mammalian organism. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A magnetic resonance imaging finding in children with cerebral palsy: Symmetrical central tegmental tract hyperintensity.

PubMed

Derinkuyu, Betul Emine; Ozmen, Evrim; Akmaz-Unlu, Havva; Altinbas, Namik Kemal; Gurkas, Esra; Boyunaga, Oznur

2017-03-01

Central tegmental tract is an extrapyramidal tract between red nucleus and inferior olivary nucleus which is located in the tegmentum pontis bilaterally and symmetrically. The etiology of the presence of central tegmental tract hyperintensity on MRI is unclear. In this study our aim is to evaluate the frequency of central tegmental tract lesions in patients with cerebral palsy and control group, as well as to determine whether there is an association between central tegmental tract lesions and cerebral palsy types. Clinical and MRI data of 200 patients with cerebral palsy in study group (87 female, 113 male; mean age, 5.81years; range, 0-16years) and 258 patients in control group (114 female, 144 male; mean age, 6.28years; range, 0-16years) were independently evaluated by two reader for presence of central tegmental tract hyperintensity and other associated abnormalities. Central tegmental tract hyperintensities on T2WI were detected in 19% of the study group (38/200) and 3.5% of the control group (9/258) (p<0.0001). Among the total of 38 central tegmental tract lesions in study group, the frequency of central tegmental tract hyperintensity was 16% (24/150) in spastic cerebral palsy and 35% (14/40) in dyskinetic cerebral palsy (p=0.0131). The prevalence of central tegmental tract hyperintensity is higher in patients with cerebral palsy particularly in dyskinetic type. We suggest that there is an increased association of the tegmental lesions with dyskinetic CP. Patients with cerebral palsy and ischemic changes were more likely to have central tegmental tract lesions. According to our results we advocate that an ischemic process may have a role in the etiopathogenesis. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases.

PubMed

Matyszak, M K; Perry, V H

1996-09-01

We have studied the effect of an inhibitor of matrix metalloproleinases, BB-1101, on a delayed-type hypersensitivity (DTH) response in the CNS. We used a recently described model in which heat-killed bacillus Calmette-Guérin (BCG) sequestered behind the blood-brain barrier (BBB) is targeted by a T-cell mediated response after subcutaneous injection of BCG (Matyszak and Perry, 1995). The DTH lesions are characterised by breakdown of the BBB, macrophage and lymphocyte infiltration and tissue damage including myelin loss. Treatment with BB-1101, which is not only a potent inhibitor of matrix metalloproteinases but also strongly inhibits TNF-alpha release, dramatically attenuated the CNS lesions. Breakdown of the BBB and the recruitment of T-cells into the site of the lesion were significantly reduced. There were many fewer inflammatory macrophages in DTH lesions than in comparable lesions from untreated animals. There was also significantly less myelin damage (assessed by staining with anti-MBP antibody). The DTH response in animals treated with dexamethasone was also reduced, but to a lesser degree. No significant effect was seen after administration of pentoxifylline, a phosphodiesterase inhibitor with effects including the inhibition of TNF-alpha production. Our results suggest that inhibitors of matrix metalloproteinases may be of considerable therapeutic benefit in neuroinflammatory diseases.

Clinico-morphological features of BRAF inhibition-induced proliferative skin lesions in cancer patients.

PubMed

Belum, Viswanath Reddy; Rosen, Alyx C; Jaimes, Natalia; Dranitsaris, George; Pulitzer, Melissa P; Busam, Klaus J; Marghoob, Ashfaq A; Carvajal, Richard D; Chapman, Paul B; Lacouture, Mario E

2015-01-01

The use of BRAF inhibitors may lead to the development of cutaneous toxicities such as rashes, photosensitivity, alopecia, palmoplantar erythrodysesthesia, and proliferative skin lesions, including keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs). The latter are noteworthy for their potential to exhibit malignant features, and they may necessitate invasive treatment. Their prompt identification is of primary importance for directing supportive care efforts and maintaining dose intensity while minimizing the morbidity associated with supportive care interventions. Because such lesions are less familiar to oncologists, this study was designed to characterize their clinico-morphological features, which have not been hitherto described. The clinical and dermoscopic characteristics and risk factors of new-onset proliferative skin lesions (benign verrucous lesions and KAs/cuSCCs) developing after the initiation of treatment with vemurafenib, dabrafenib, and XL281 were analyzed; the histopathological diagnoses were ascertained. The majority of the lesions were benign verrucous lesions (78%, n = 87), whereas KAs/cuSCCs represented 22% (n = 25). The median times to biopsy for the initial verrucous lesions and KAs/cuSCCs were 4.8 and 10.5 weeks, respectively. The clinico-morphological features significant for KAs/cuSCCs included a larger size (P < .001), a nodular appearance (P < .001), a central keratin plug (P < .001), a central ulceration or crust (P = .04), an adherent scale (P = .02), an erythematous halo (P = .03), and a scaly ring (collarette; P < .001) at the periphery. Our findings represent the first detailed description of the clinico-morphological characteristics that permit distinction between the benign and malignant skin lesions induced by BRAF inhibitors. They are valuable for the recognition of lesions that require intervention and/or a dermatology referral versus those that permit provisional

Crossroads between Bacterial and Mammalian Glycosyltransferases

PubMed Central

Brockhausen, Inka

2014-01-01

Bacterial glycosyltransferases (GT) often synthesize the same glycan linkages as mammalian GT; yet, they usually have very little sequence identity. Nevertheless, enzymatic properties, folding, substrate specificities, and catalytic mechanisms of these enzyme proteins may have significant similarity. Thus, bacterial GT can be utilized for the enzymatic synthesis of both bacterial and mammalian types of complex glycan structures. A comparison is made here between mammalian and bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and those found in the O antigens of Gram-negative bacteria. These epitopes include Thomsen–Friedenreich (TF or T) antigen, blood group O, A, and B, type 1 and 2 chains, Lewis antigens, sialylated and fucosylated structures, and polysialic acids. Many different approaches can be taken to investigate the substrate binding and catalytic mechanisms of GT, including crystal structure analyses, mutations, comparison of amino acid sequences, NMR, and mass spectrometry. Knowledge of the protein structures and functions helps to design GT for specific glycan synthesis and to develop inhibitors. The goals are to develop new strategies to reduce bacterial virulence and to synthesize vaccines and other biologically active glycan structures. PMID:25368613

Mosaic evolution of the mammalian auditory periphery.

PubMed

Manley, Geoffrey A

2013-01-01

The classical mammalian auditory periphery, i.e., the type of middle ear and coiled cochlea seen in modern therian mammals, did not arise as one unit and did not arise in all mammals. It is also not the only kind of auditory periphery seen in modern mammals. This short review discusses the fact that the constituents of modern mammalian auditory peripheries arose at different times over an extremely long period of evolution (230 million years; Ma). It also attempts to answer questions as to the selective pressures that led to three-ossicle middle ears and the coiled cochlea. Mammalian middle ears arose de novo, without an intermediate, single-ossicle stage. This event was the result of changes in eating habits of ancestral animals, habits that were unrelated to hearing. The coiled cochlea arose only after 60 Ma of mammalian evolution, driven at least partly by a change in cochlear bone structure that improved impedance matching with the middle ear of that time. This change only occurred in the ancestors of therian mammals and not in other mammalian lineages. There is no single constellation of structural features of the auditory periphery that characterizes all mammals and not even all modern mammals.

Lesion progression in post-treatment persistent endodontic lesions.

PubMed

Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

2012-10-01

Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Pigmented skin lesion detection using random forest and wavelet-based texture

NASA Astrophysics Data System (ADS)

Hu, Ping; Yang, Tie-jun

2016-10-01

The incidence of cutaneous malignant melanoma, a disease of worldwide distribution and is the deadliest form of skin cancer, has been rapidly increasing over the last few decades. Because advanced cutaneous melanoma is still incurable, early detection is an important step toward a reduction in mortality. Dermoscopy photographs are commonly used in melanoma diagnosis and can capture detailed features of a lesion. A great variability exists in the visual appearance of pigmented skin lesions. Therefore, in order to minimize the diagnostic errors that result from the difficulty and subjectivity of visual interpretation, an automatic detection approach is required. The objectives of this paper were to propose a hybrid method using random forest and Gabor wavelet transformation to accurately differentiate which part belong to lesion area and the other is not in a dermoscopy photographs and analyze segmentation accuracy. A random forest classifier consisting of a set of decision trees was used for classification. Gabor wavelets transformation are the mathematical model of visual cortical cells of mammalian brain and an image can be decomposed into multiple scales and multiple orientations by using it. The Gabor function has been recognized as a very useful tool in texture analysis, due to its optimal localization properties in both spatial and frequency domain. Texture features based on Gabor wavelets transformation are found by the Gabor filtered image. Experiment results indicate the following: (1) the proposed algorithm based on random forest outperformed the-state-of-the-art in pigmented skin lesions detection (2) and the inclusion of Gabor wavelet transformation based texture features improved segmentation accuracy significantly.

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

PubMed

Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

2017-10-12

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

Effect of Microgravity on Mammalian Lymphocytes

NASA Technical Reports Server (NTRS)

Banerjee, H.; Blackshear, M.; Mahaffey, K.; Khan, A. A.; Delucas, L.

2004-01-01

The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization. The Astronauts will be exposed to microgravity environment for a long duration of time during these flights. Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system and nervous system. We did our preliminary investigations by exposing mammalian lymphocytes and astrocyte cells to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon, Inc. (USA).Our initial results showed no significant change in cytokine expression in these cells up to a time period of 120 hours exposure. Our future experiments will involve exposure for a longer period of time.

DNA Damage by Ionizing Radiation: Tandem Double Lesions by Charged Particles

NASA Technical Reports Server (NTRS)

Huo, Winifred M.; Chaban, Galina M.; Wang, Dunyou; Dateo, Christopher E.

2005-01-01

Oxidative damages by ionizing radiation are the source of radiation-induced carcinogenesis, damage to the central nervous system, lowering of the immune response, as well as other radiation-induced damages to human health. Monte Carlo track simulations and kinetic modeling of radiation damages to the DNA employ available molecular and cellular data to simulate the biological effect of high and low LET radiation io the DNA. While the simulations predict single and double strand breaks and base damages, so far all complex lesions are the result of stochastic coincidence from independent processes. Tandem double lesions have not yet been taken into account. Unlike the standard double lesions that are produced by two separate attacks by charged particles or radicals, tandem double lesions are produced by one single attack. The standard double lesions dominate at the high dosage regime. On the other hand, tandem double lesions do not depend on stochastic coincidences and become important at the low dosage regime of particular interest to NASA. Tandem double lesions by hydroxyl radical attack of guanine in isolated DNA have been reported at a dosage of radiation as low as 10 Gy. The formation of two tandem base lesions was found to be linear with the applied doses, a characteristic of tandem lesions. However, tandem double lesions from attack by a charged particle have not been reported.

Chronic systemic IL-1β exacerbates central neuroinflammation independently of the blood-brain barrier integrity.

PubMed

Murta, Verónica; Farías, María Isabel; Pitossi, Fernando Juan; Ferrari, Carina Cintia

2015-01-15

Peripheral circulating cytokines are involved in immune to brain communication and systemic inflammation is considered a risk factor for flaring up the symptoms in most neurodegenerative diseases. We induced both central inflammatory demyelinating lesion, and systemic inflammation with an interleukin-1β expressing adenovector. The peripheral pro-inflammatory stimulus aggravated the ongoing central lesion independently of the blood-brain barrier (BBB) integrity. This model allows studying the role of specific molecules and cells (neutrophils) from the innate immune system, in the relationship between central and peripheral communication, and on relapsing episodes of demyelinating lesions, along with the role of BBB integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

A pediatric renal lymphoma case presenting with central nervous system findings.

PubMed

Baran, Ahmet; Küpeli, Serhan; Doğru, Omer

2013-06-01

In pediatric patients renal lymphoma frequently presents in the form of multiple, bilateral mass lesions, infrequently as a single or retroperitoneal mass, and rarely as diffuse infiltrative lesions. In patients with apparent central nervous system involvement close attention to other physical and laboratory findings are essential for preventing a delay in the final diagnosis. Herein we present a pediatric patient with renal lymphoma that presented with central nervous system findings that caused a delay in diagnosis. None declared.

A Novel Counter Sheet-flow Sandwich Cell Culture Device for Mammalian Cell Growth in Space

NASA Astrophysics Data System (ADS)

Sun, Shujin; Gao, Yuxin; Shu, Nanjiang; Tang, Zemei; Tao, Zulai; Long, Mian

2008-08-01

Cell culture and growth in space is crucial to understand the cellular responses under microgravity. The effects of microgravity were coupled with such environment restrictions as medium perfusion, in which the underlying mechanism has been poorly understood. In the present work, a customer-made counter sheet-flow sandwich cell culture device was developed upon a biomechanical concept from fish gill breathing. The sandwich culture unit consists of two side chambers where the medium flow is counter-directional, a central chamber where the cells are cultured, and two porous polycarbonate membranes between side and central chambers. Flow dynamics analysis revealed the symmetrical velocity profile and uniform low shear rate distribution of flowing medium inside the central culture chamber, which promotes sufficient mass transport and nutrient supply for mammalian cell growth. An on-orbit experiment performed on a recovery satellite was used to validate the availability of the device.

Pre-pharyngeal Swallow Effects of Recurrent Laryngeal Nerve Lesion on Bolus Shape and Airway Protection in an Infant Pig Model.

PubMed

Gould, Francois D H; Yglesias, B; Ohlemacher, J; German, R Z

2017-06-01

Recurrent laryngeal nerve (RLN) damage in infants leads to increased dysphagia and aspiration pneumonia. Recent work has shown that intraoral transport and swallow kinematics change following RLN lesion, suggesting potential changes in bolus formation prior to the swallow. In this study, we used geometric morphometrics to understand the effect of bolus shape on penetration and aspiration in infants with and without RLN lesion. We hypothesized (1) that geometric bolus properties are related to airway protection outcomes and (2) that in infants with RLN lesion, the relationship between geometric bolus properties and dysphagia is changed. In five infant pigs, dysphagia in 188 swallows was assessed using the Infant Mammalian Penetration-Aspiration Scale (IMPAS). Using images from high-speed VFSS, bolus shape, bolus area, and tongue outline were quantified digitally. Bolus shape was analyzed using elliptical Fourier analysis, and tongue outline using polynomial curve fitting. Despite large inter-individual differences, significant within individual effects of bolus shape and bolus area on airway protection exist. The relationship between penetration-aspiration score and both bolus area and shape changed post lesion. Tongue shape differed between pre- and post-lesion swallows, and between swallows with different IMPAS scores. Bolus shape and area affect airway protection outcomes. RLN lesion changes that relationship, indicating that proper bolus formation and control by the tongue require intact laryngeal sensation. The impact of RLN lesion on dysphagia is pervasive.

Quantitative EEG abnormalities in major depressive disorder with basal ganglia stroke with lesions in different hemispheres.

PubMed

Wang, Chunfang; Chen, Yuanyuan; Zhang, Ying; Chen, Jin; Ding, Xiaojing; Ming, Dong; Du, Jingang

2017-06-01

This study aimed to examine the aberrant EEG oscillation in major depressive subjects with basal ganglia stroke with lesions in different hemispheres. Resting EEG of 16 electrodes in 58 stroke subjects, 26 of whom had poststroke depression (13 with left-hemisphere lesion and 13 with right) and 32 of whom did not (18 with left lesion and 14 with right), was recorded to obtain spectral power analysis for several frequency bands. Multiple analysis of variance and receiver operating characteristic (ROC) curves were used to identify differences between poststroke depression (PSD) and poststroke non-depression (PSND), treating the different lesion hemispheres separately. Moreover, Pearson linear correlation analysis was conducted to test the severity of depressive symptoms and EEG indices. PSD with left-hemisphere lesion showed increased beta2 power in frontal and central areas, but PSD with right-hemisphere lesion showed increased theta and alpha power mainly in occipital and temporal regions. Additionally, for left-hemisphere lesions, beta2 power in central and right parietal regions provided high discrimination between PSD and PSND, and for right-hemisphere lesions, theta power was similarly discriminative in most regions, especially temporal regions. We also explored the association between symptoms of depression and the power of abnormal bands, but we found no such relationship. The sample size was relatively small and included subjects with different lesions of the basal ganglia. The aberrant EEG oscillation in subjects with PSD differs between subjects with lesions of the left and right hemispheres, suggesting a complex association between depression and lesion location in stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Mammalian touch catches up

PubMed Central

Walsh, Carolyn M.; Bautista, Diana M.; Lumpkin, Ellen A.

2015-01-01

An assortment of touch receptors innervate the skin and encode different tactile features of the environment. Compared with invertebrate touch and other sensory systems, our understanding of the molecular and cellular underpinnings of mammalian touch lags behind. Two recent breakthroughs have accelerated progress. First, an arsenal of cell-type-specific molecular markers allowed the functional and anatomical properties of sensory neurons to be matched, thereby unraveling a cellular code for touch. Such markers have also revealed key roles of non-neuronal cell types, such as Merkel cells and keratinocytes, in touch reception. Second, the discovery of Piezo genes as a new family of mechanically activated channels has fueled the discovery of molecular mechanisms that mediate and mechanotransduction in mammalian touch receptors. PMID:26100741

Homogenization of Mammalian Cells.

PubMed

de Araújo, Mariana E G; Lamberti, Giorgia; Huber, Lukas A

2015-11-02

Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells. © 2015 Cold Spring Harbor Laboratory Press.

Base Excision Repair and Lesion-Dependent Subpathways for Repair of Oxidative DNA Damage

PubMed Central

Svilar, David; Goellner, Eva M.; Almeida, Karen H.

2011-01-01

Abstract Nuclear and mitochondrial genomes are under continuous assault by a combination of environmentally and endogenously derived reactive oxygen species, inducing the formation and accumulation of mutagenic, toxic, and/or genome-destabilizing DNA lesions. Failure to resolve these lesions through one or more DNA-repair processes is associated with genome instability, mitochondrial dysfunction, neurodegeneration, inflammation, aging, and cancer, emphasizing the importance of characterizing the pathways and proteins involved in the repair of oxidative DNA damage. This review focuses on the repair of oxidative damage–induced lesions in nuclear and mitochondrial DNA mediated by the base excision repair (BER) pathway in mammalian cells. We discuss the multiple BER subpathways that are initiated by one of 11 different DNA glycosylases of three subtypes: (a) bifunctional with an associated β-lyase activity; (b) monofunctional; and (c) bifunctional with an associated β,δ-lyase activity. These three subtypes of DNA glycosylases all initiate BER but yield different chemical intermediates and hence different BER complexes to complete repair. Additionally, we briefly summarize alternate repair events mediated by BER proteins and the role of BER in the repair of mitochondrial DNA damage induced by ROS. Finally, we discuss the relation of BER and oxidative DNA damage in the onset of human disease. Antioxid. Redox Signal. 14, 2491–2507. PMID:20649466

Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats.

PubMed

Renzi, A; De Luca, L A; Menani, J V

2002-09-15

In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

Evolutionary Patterns of RNA-Based Duplication in Non-Mammalian Chordates

PubMed Central

Li, Xin; Vibranovski, Maria D.; Gan, Xiaoni; Wang, Dengqiang; Wang, Wen; Long, Manyuan; He, Shunping

2011-01-01

The role of RNA-based duplication, or retroposition, in the evolution of new gene functions in mammals, plants, and Drosophila has been widely reported. However, little is known about RNA-based duplication in non-mammalian chordates. In this study, we screened ten non-mammalian chordate genomes for retrocopies and investigated their evolutionary patterns. We identified numerous retrocopies in these species. Examination of the age distribution of these retrocopies revealed no burst of young retrocopies in ancient chordate species. Upon comparing these non-mammalian chordate species to the mammalian species, we observed that a larger fraction of the non-mammalian retrocopies was under strong evolutionary constraints than mammalian retrocopies are, as evidenced by signals of purifying selection and expression profiles. For the Western clawed frog, Medaka, and Sea squirt, many retrogenes have evolved gonad and brain expression patterns, similar to what was observed in human. Testing of retrogene movement in the Medaka genome, where the nascent sex chrosomes have been well assembled, did not reveal any significant gene movement. Taken together, our analyses demonstrate that RNA-based duplication generates many functional genes and can make a significant contribution to the evolution of non-mammalian genomes. PMID:21779328

The impact of transposable elements on mammalian development

PubMed Central

Garcia-Perez, Jose L.; Widmann, Thomas J.; Adams, Ian R.

2018-01-01

Summary Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that significantly impact on mammalian development and genome regulation. In recent years, our understanding of how pre-existing TEs affect genome architecture, gene regulatory networks and protein function during mammalian embryogenesis has dramatically expanded. In addition, the mobilization of active TEs in selected cell types has been shown to generate genetic variation during development and in fully differentiated tissues. Importantly, the ongoing domestication and evolution of TEs appears to provide a rich source of regulatory elements, functional modules and genetic variation that fuels the evolution of mammalian developmental processes. Here, we review the functional impact that TEs exert on mammalian developmental processes and how the somatic activity of TEs can influence gene regulatory networks. PMID:27875251

Evaluation of sarolaner and spinosad oral treatments to eliminate fleas, reduce dermatologic lesions and minimize pruritus in naturally infested dogs in west Central Florida, USA.

PubMed

Dryden, Michael W; Canfield, Michael S; Niedfeldt, Emily; Kinnon, Amanda; Kalosy, Kimberly; Smith, Amber; Foley, Kaitlin M; Smith, Vicki; Bress, Todd S; Smith, Nicole; Endrizzi, Mike; Login, Joyce

2017-08-17

An in-home investigation of naturally flea infested dogs was conducted in West Central Florida, USA to evaluate and compare the effectiveness of two different oral flea adulticides to control flea infestations, minimize dermatologic lesions and reduce pruritus over an 8-week period. Twenty-nine dogs living in 19 homes and another 26 dogs residing in 16 different homes were orally administered either a sarolaner or spinosad chewable, respectively on day 0 and once between days 28-30. Products were administered by study personnel according to label directions. Flea populations on dogs were estimated using visual area counts and flea infestations in the indoor premises were assessed using intermittent-light flea traps on days 0, 7, 14, 21 and once between days 28-30, 40-45, and 56-60. Assessments of dermatologic lesions were conducted monthly during the study and severity of pruritus was evaluated throughout the study on the same schedule as flea counts were conducted. Concurrent treatments for existing skin disease were not allowed. The administration of sarolaner or spinosad reduced flea populations on dogs by 99.0% and 97.3%, respectively within 7 days. Flea infestations on the sarolaner- and spinosad-treated dogs were reduced by > 99% at every counting period from day 14 post-treatment through the end of the 8-week study. At the end of the study 96.4 and 92.0% of the dogs treated with sarolaner and spinosad, respectively were flea-free. Flea populations in the indoor premises were also markedly reduced the end of the study, with 100 and 99.8% reductions in flea trap counts in the sarolaner and spinosad treatment groups, respectively. FAD lesion scores, atopic dermatitis lesions scores (CADESI-4) and pruritus severity scores were also markedly improved with both formulations. An in-home clinical field study conducted during the summer of 2016 in subtropical Florida demonstrated that two-monthly administrations of either sarolaner or spinosad chewables almost

Estimating the Global Incidence of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review for Central Nervous System Vascular Lesions and Meta-Analysis of Ruptured Aneurysms.

PubMed

Hughes, Joshua D; Bond, Kamila M; Mekary, Rania A; Dewan, Michael C; Rattani, Abbas; Baticulon, Ronnie; Kato, Yoko; Azevedo-Filho, Hildo; Morcos, Jacques J; Park, Kee B

2018-04-09

There is increasing acknowledgement that surgical care is important in global health initiatives. In particular, neurosurgical care is as limited as 1 per 10 million people in parts of the world. We performed a systematic literature review to examine the worldwide incidence of central nervous system vascular lesions and a meta-analysis of aneurysmal subarachnoid hemorrhage (aSAH) to define the disease burden and inform neurosurgical global health efforts. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to estimate the global epidemiology of central nervous system vascular lesions, including unruptured and ruptured aneurysms, arteriovenous malformations, cavernous malformations, dural arteriovenous fistulas, developmental venous anomalies, and vein of Galen malformations. Results were organized by World Health Organization regions. After literature review, because of a lack of data from particular World Health Organization regions, we determined we could only provide an estimate of aSAH. Using data from studies with aSAH and 12 high-quality stroke studies from regions lacking data, we meta-analyzed the yearly crude incidence of aSAH per 100,000 persons. Estimates were generated via random-effects models. From an initial yield of 1492 studies, 46 manuscripts on aSAH incidence were included. The final meta-analysis included 58 studies from 31 different countries. We estimated the global crude incidence for aSAH to be 6.67 per 100,000 persons with a wide variation across WHO regions from 0.71 to 12.38 per 100,000 persons. Worldwide, almost 500,000 individuals will suffer from aSAH each year, with almost two-thirds in low- and middle-income countries. Copyright © 2018 Elsevier Inc. All rights reserved.

Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grollman, A.P.; Takeshita, Masaru

1995-12-31

More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura`s discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10{sup 5} guanine residues in mammalian DNA are oxidized atmore » the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA.« less

[Anorexia nervosa and nervus peronaeus lesions].

PubMed

Weber, Peter; Rost, Barbara

2009-09-01

Anorexia nervosa could be associated with numerous medical complications. In addition, malnutrition can cause different problems of central nervous system, whereas reports on periphere nerve lesions are rare. We report a case of a 14 8/12 years old girl suffering from anorexia nervosa since five months, who presented with peroneal nerve palsy. In association to anorexia nervosa the prognosis of this mononeuropathy seems to be good. Anorectic patients with neurological complications need an interdisciplinary medical treatment.

Mammalian diversity: gametes, embryos and reproduction.

PubMed

Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

2006-01-01

The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

Chemical sensing in mammalian host-bacterial commensal associations

USDA-ARS?s Scientific Manuscript database

The mammalian gastrointestinal (GI) tract is colonized by a complex consortium of bacterial species. Bacteria engage in chemical signaling to coordinate population-wide behavior. However, it is unclear if chemical sensing plays a role in establishing mammalian host–bacterial commensal relationships....

Mesozoic mammals from Arizona: new evidence on Mammalian evolution.

PubMed

Jenkins, F A; Crompton, A W; Downs, W R

1983-12-16

Knowledge of early mammalian evolution has been based on Old World Late Triassic-Early Jurassic faunas. The discovery of mammalian fossils of approximately equivalent age in the Kayenta Formation of northeastern Arizona gives evidence of greater diversity than known previously. A new taxon documents the development of an angular region of the jaw as a neomorphic process, and represents an intermediate stage in the origin of mammalian jaw musculature.

Hybrid radioguided occult lesion localization (hybrid ROLL) of (18)F-FDG-avid lesions using the hybrid tracer indocyanine green-(99m)Tc-nanocolloid.

PubMed

KleinJan, G H; Brouwer, O R; Mathéron, H M; Rietbergen, D D D; Valdés Olmos, R A; Wouters, M W; van den Berg, N S; van Leeuwen, F W B

2016-01-01

To assess if combined fluorescence- and radio-guided occult lesion localization (hybrid ROLL) is feasible in patients scheduled for surgical resection of non-palpable (18)F-FDG-avid lesions on PET/CT. Four patients with (18)F-FDG-avid lesions on follow-up PET/CT that were not palpable during physical examination but were suspected to harbor metastasis were enrolled. Guided by ultrasound, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was injected centrally in the target lesion. SPECT/CT imaging was used to confirm tracer deposition. Intraoperatively, lesions were localized using a hand-held gamma ray detection probe, a portable gamma camera, and a fluorescence camera. After excision, the gamma camera was used to check the wound bed for residual activity. A total of six (18)F-FDG-avid lymph nodes were identified and scheduled for hybrid ROLL. Comparison of the PET/CT images with the acquired SPECT/CT after hybrid tracer injection confirmed accurate tracer deposition. No side effects were observed. Combined radio- and fluorescence-guidance enabled localization and excision of the target lesion in all patients. Five of the six excised lesions proved tumor-positive at histopathology. The hybrid ROLL approach appears to be feasible and can facilitate the intraoperative localization and excision of non-palpable lesions suspected to harbor tumor metastases. In addition to the initial radioguided detection, the fluorescence component of the hybrid tracer enables high-resolution intraoperative visualization of the target lesion. The procedure needs further evaluation in a larger cohort and wider range of malignancies to substantiate these preliminary findings. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

PubMed Central

Parker, David

2017-01-01

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where

The impact of transposable elements on mammalian development.

PubMed

Garcia-Perez, Jose L; Widmann, Thomas J; Adams, Ian R

2016-11-15

Despite often being classified as selfish or junk DNA, transposable elements (TEs) are a group of abundant genetic sequences that have a significant impact on mammalian development and genome regulation. In recent years, our understanding of how pre-existing TEs affect genome architecture, gene regulatory networks and protein function during mammalian embryogenesis has dramatically expanded. In addition, the mobilization of active TEs in selected cell types has been shown to generate genetic variation during development and in fully differentiated tissues. Importantly, the ongoing domestication and evolution of TEs appears to provide a rich source of regulatory elements, functional modules and genetic variation that fuels the evolution of mammalian developmental processes. Here, we review the functional impact that TEs exert on mammalian developmental processes and discuss how the somatic activity of TEs can influence gene regulatory networks. © 2016. Published by The Company of Biologists Ltd.

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

PubMed Central

Fu, Zhenxing; Powell, Frank L.

2011-01-01

During ventilatory acclimatization to hypoxia (VAH), time-dependent increases in ventilation lower Pco2 levels, and this persists on return to normoxia. We hypothesized that plasticity in the caudal nucleus tractus solitarii (NTS) contributes to VAH, as the NTS receives the first synapse from the carotid body chemoreceptor afferents and also contains CO2-sensitive neurons. We lesioned cells in the caudal NTS containing the neurokinin-1 receptor by microinjecting the neurotoxin saporin conjugated to substance P and measured ventilatory responses in awake, unrestrained rats 18 days later. Lesions did not affect hypoxic or hypercapnic ventilatory responses in normoxic control rats, in contrast to published reports for similar lesions in other central chemosensitive areas. Also, lesions did not affect the hypercapnic ventilatory response in chronically hypoxic rats (inspired Po2 = 90 Torr for 7 days). These results suggest functional differences between central chemoreceptor sites. However, lesions significantly increased ventilation in normoxia or acute hypoxia in chronically hypoxic rats. Hence, chronic hypoxia increases an inhibitory effect of neurokinin-1 receptor neurons in the NTS on ventilatory drive, indicating that these neurons contribute to plasticity during chronic hypoxia, although such plasticity does not explain VAH. PMID:21593425

Simplified Bioreactor For Growing Mammalian Cells

NASA Technical Reports Server (NTRS)

Spaulding, Glenn F.

1995-01-01

Improved bioreactor for growing mammalian cell cultures developed. Designed to support growth of dense volumes of mammalian cells by providing ample, well-distributed flows of nutrient solution with minimal turbulence. Cells relatively delicate and, unlike bacteria, cannot withstand shear forces present in turbulent flows. Bioreactor vessel readily made in larger sizes to accommodate greater cell production quantities. Molding equipment presently used makes cylinders up to 30 centimeters long. Alternative sintered plastic techniques used to vary pore size and quantity, as necessary.

Endoscopic analysis of colorectal serrated lesions with cancer.

PubMed

Nagata, Shuichiro; Mitsuyama, Keiichi; Kawano, Hiroshi; Noda, Tetsuhiro; Maeyama, Yasuhiko; Mukasa, Michita; Takedatsu, Hidetoshi; Yoshioka, Shinichiro; Kuwaki, Kotaro; Akiba, Jun; Tsuruta, Osamu; Torimura, Takuji

2018-06-01

Serrated lesions, including hyperplastic polyps (HPs), traditional serrated adenomas (TSAs) and sessile serrated adenomas/polyps (SSA/Ps), are important contributors to colorectal carcinogenesis. The aim of the present study was to analyze the potential of conventional endoscopy and advanced endoscopic imaging techniques to delineate the characteristic features of serrated lesions with cancer. The present study was a retrospective analysis of the data of 168 patients who had undergone colonoscopy, and a total of 228 serrated lesions (77 HPs, 58 TSAs, 84 SSA/Ps, 9 SSA/P plus TSAs) have been identified in these patients. A cancer component was identified in 2.6% of HPs, 13.8% of TSAs and 10.7% of SSA/Ps, but none of SSA/P plus TSAs. Compared with the lesions without cancer, the lesions with cancer exhibited a larger size (HP, TSA and SSA/P), a reddish appearance (SSA/P), a two-tier raised appearance (HP and SSA/P), a central depression (HP, TSA and SSA/P), the type V pit pattern (HP, TSA and SSA/P), and/or the type III capillary pattern (TSA and SSA/P). Deep invasion was identified in 50.0% of HPs, 12.5% of TSAs and 55.6% of SSA/Ps with cancer. The Ki-67 proliferative zone was distributed diffusely within the area of the cancer, but partially within the non-cancer area of HPs, TSAs and SSA/Ps. The lesion types were also analyzed on the basis of mucin phenotype. The present study suggested that a detailed endoscopic analysis of serrated lesions with cancer is useful for delineating characteristic features, and the analysis aids treatment selection.

In Vivo Imaging of the Central and Peripheral Effects of Sleep Deprivation and Suprachiasmatic Nuclei Lesion on PERIOD-2 Protein in Mice.

PubMed

Curie, Thomas; Maret, Stephanie; Emmenegger, Yann; Franken, Paul

2015-09-01

That sleep deprivation increases the brain expression of various clock genes has been well documented. Based on these and other findings we hypothesized that clock genes not only underlie circadian rhythm generation but are also implicated in sleep homeostasis. However, long time lags have been reported between the changes in the clock gene messenger RNA levels and their encoded proteins. It is therefore crucial to establish whether also protein levels increase within the time frame known to activate a homeostatic sleep response. We report on the central and peripheral effects of sleep deprivation on PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice. In vivo and in situ PER2 imaging during baseline, sleep deprivation, and recovery. Mouse sleep-recording facility. Per2::Luciferase knock-in mice. N/A. Six-hour sleep deprivation increased PER2 not only in the brain but also in liver and kidney. Remarkably, the effects in the liver outlasted those observed in the brain. Within the brain the increase in PER2 concerned the cerebral cortex mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver PER2 levels did increase in these mice similar to the sham and partially lesioned controls. Our results stress the importance of considering both sleep-wake dependent and circadian processes when quantifying clock-gene levels. Because sleep deprivation alters PERIOD-2 in the brain as well as in the periphery, it is tempting to speculate that clock genes constitute a common pathway mediating the shared and well-known adverse effects of both chronic sleep loss and disrupted circadian rhythmicity on metabolic health. © 2015 Associated Professional Sleep Societies, LLC.

Medial Amygdala Lesions Selectively Block Aversive Pavlovian–Instrumental Transfer in Rats

PubMed Central

McCue, Margaret G.; LeDoux, Joseph E.; Cain, Christopher K.

2014-01-01

Pavlovian conditioned stimuli (CSs) play an important role in the reinforcement and motivation of instrumental active avoidance (AA). Conditioned threats can also invigorate ongoing AA responding [aversive Pavlovian–instrumental transfer (PIT)]. The neural circuits mediating AA are poorly understood, although lesion studies suggest that lateral, basal, and central amygdala nuclei, as well as infralimbic prefrontal cortex, make key, and sometimes opposing, contributions. We recently completed an extensive analysis of brain c-Fos expression in good vs. poor avoiders following an AA test (Martinez et al., 2013, Learning and Memory). This analysis identified medial amygdala (MeA) as a potentially important region for Pavlovian motivation of instrumental actions. MeA is known to mediate defensive responding to innate threats as well as social behaviors, but its role in mediating aversive Pavlovian–instrumental interactions is unknown. We evaluated the effect of MeA lesions on Pavlovian conditioning, Sidman two-way AA conditioning (shuttling) and aversive PIT in rats. Mild footshocks served as the unconditioned stimulus in all conditioning phases. MeA lesions had no effect on AA but blocked the expression of aversive PIT and 22 kHz ultrasonic vocalizations in the AA context. Interestingly, MeA lesions failed to affect Pavlovian freezing to discrete threats but reduced freezing to contextual threats when assessed outside of the AA chamber. These findings differentiate MeA from lateral and central amygdala, as lesions of these nuclei disrupt Pavlovian freezing and aversive PIT, but have opposite effects on AA performance. Taken together, these results suggest that MeA plays a selective role in the motivation of instrumental avoidance by general or uncertain Pavlovian threats. PMID:25278858

Gravitational Study of the Central Nervous System

NASA Technical Reports Server (NTRS)

Horowitz, J. M.

1983-01-01

A series of experiments conducted at 1G are discussed with reference to the role of calcium ions in information processing by the central nervous system. A technique is described which allows thin sections of a mammalian hippocampus to be isolated while maintaining neural activity. Two experiments carried out in hypergravic fields are also addressed; one investigating altered stimulation in the auditory system, the other determining temperature regulation responses in hypergravic fields.

Central oculomotor disturbances and nystagmus: a window into the brainstem and cerebellum.

PubMed

Strupp, Michael; Hüfner, Katharina; Sandmann, Ruth; Zwergal, Andreas; Dieterich, Marianne; Jahn, Klaus; Brandt, Thomas

2011-03-01

Oculomotor disturbances and nystagmus are seen in many diseases of the nervous system, the vestibular apparatus, and the eyes, as well as in toxic and metabolic disorders. They often indicate a specific underlying cause. The key to diagnosis is systematic clinical examination of the patient's eye movements. This review deals mainly with central oculomotor disturbances, i.e., those involving smooth pursuit, saccades, gaze-holding, and central types of nystagmus. We searched the current literature for relevant publications on the diagnosis and treatment of oculomotor disturbances and nystagmus, and discuss them selectively in this review along with the German Neurological Society's guidelines on the topic. A detailed knowledge of the anatomy and physiology of eye movements usually enables the physician to localize the disturbance to a specific area in the brainstem or cerebellum. The examination of eye movements is an even more sensitive method than magnetic resonance imaging for the diagnosis of acute vestibular syndromes and for the differentiation of peripheral from central lesions. For example, isolated dysfunction of horizontal saccades is due to a pontine lesion, while isolated dysfunction of vertical saccades is due to a midbrain lesion. Generalized gaze-evoked nystagmus (GEN) has multiple causes; purely vertical GEN is due to a midbrain lesion, while purely horizontal GEN is due to a pontomedullary lesion. Internuclear ophthalmoplegia involves a constellation of findings, the most prominent of which is impaired adduction to the side of the causative lesion in the ipsilateral medial longitudinal fasciculus. The most common pathological types of central nystagmus are downbeat and upbeat nystagmus (DBN, UBN). DBN is generally due to cerebellar dysfunction, e.g., because of a neurodegenerative disease. This short review focuses on the clinical characteristics, pathophysiology and current treatment of oculomotor disorders and nystagmus.

High-speed atomic force microscopy imaging of live mammalian cells

PubMed Central

Shibata, Mikihiro; Watanabe, Hiroki; Uchihashi, Takayuki; Ando, Toshio; Yasuda, Ryohei

2017-01-01

Direct imaging of morphological dynamics of live mammalian cells with nanometer resolution under physiological conditions is highly expected, but yet challenging. High-speed atomic force microscopy (HS-AFM) is a unique technique for capturing biomolecules at work under near physiological conditions. However, application of HS-AFM for imaging of live mammalian cells was hard to be accomplished because of collision between a huge mammalian cell and a cantilever during AFM scanning. Here, we review our recent improvements of HS-AFM for imaging of activities of live mammalian cells without significant damage to the cell. The improvement of an extremely long (~3 μm) AFM tip attached to a cantilever enables us to reduce severe damage to soft mammalian cells. In addition, a combination of HS-AFM with simple fluorescence microscopy allows us to quickly locate the cell in the AFM scanning area. After these improvements, we demonstrate that developed HS-AFM for live mammalian cells is possible to image morphogenesis of filopodia, membrane ruffles, pits open-close formations, and endocytosis in COS-7, HeLa cells as well as hippocampal neurons. PMID:28900590

Network localization of neurological symptoms from focal brain lesions

PubMed Central

Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S.; Fox, Michael D.

2015-01-01

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10−5) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had

Network localization of neurological symptoms from focal brain lesions.

PubMed

Boes, Aaron D; Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S; Fox, Michael D

2015-10-01

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had

Tick-induced allergies: mammalian meat allergy, tick anaphylaxis and their significance

PubMed Central

2015-01-01

Serious tick-induced allergies comprise mammalian meat allergy following tick bites and tick anaphylaxis. Mammalian meat allergy is an emergent allergy, increasingly prevalent in tick-endemic areas of Australia and the United States, occurring worldwide where ticks are endemic. Sensitisation to galactose-α-1,3-galactose (α-Gal) has been shown to be the mechanism of allergic reaction in mammalian meat allergy following tick bite. Whilst other carbohydrate allergens have been identified, this allergen is unique amongst carbohydrate food allergens in provoking anaphylaxis. Treatment of mammalian meat anaphylaxis involves avoidance of mammalian meat and mammalian derived products in those who also react to gelatine and mammalian milks. Before initiating treatment with certain therapeutic agents (e.g., cetuximab, gelatine-containing substances), a careful assessment of the risk of anaphylaxis, including serological analysis for α-Gal specific-IgE, should be undertaken in any individual who works, lives, volunteers or recreates in a tick endemic area. Prevention of tick bites may ameliorate mammalian meat allergy. Tick anaphylaxis is rare in countries other than Australia. Tick anaphylaxis is secondarily preventable by prevention and appropriate management of tick bites. Analysis of tick removal techniques in tick anaphylaxis sufferers offers insights into primary prevention of both tick and mammalian meat anaphylaxis. Recognition of the association between mammalian meat allergy and tick bites has established a novel cause and effect relationship between an environmental exposure and subsequent development of a food allergy, directing us towards examining environmental exposures as provoking factors pivotal to the development of other food allergies and refocusing our attention upon causation of allergy in general. PMID:25653915

Radiological analysis of cystic lesion in osteonecrosis of the femoral head.

PubMed

Gao, Fuqiang; Han, Jun; He, Zike; Li, Zirong

2018-04-27

Cystic lesions are a common complication in osteonecrosis of the femoral head (ONFH). This study will discuss the cause of cystic lesion formation and the feature of cystic lesion distribution in ONFH. According to the feature of cystic lesion in ONFH, we will discuss the possible mechanisms of cystic lesions and their  influence on collapse of the femoral head. We retrospectively gathered 102 ONFH patients (168 hips) from November in 2015 to August in 2016 on China-Japan Friendship Hospital. Three categories of patients' medical information were collected: demographic characteristics, bone cystic lesion location, and pathological finding on CT and MRI imaging (microfracture, collapse, crescent sign). On mid-coronal and mid-axial CT section, the femoral head was divided into four quadrants for locating the cystic lesion. And we classified the location relationship of cystic lesion and sclerosis rim as G1 type, G2 type, and G3 type on coronal CT section. A significant difference was found between ONFH group with cystic lesion and ONFH group without cystic lesion in terms of microfracture (P < 0.001), collapse (P < 0.001), and crescent sign (P < 0.001). Forty-four cystic lesions (70%) are located in anterior hip area and 19 cystic lesions (30%) are located in posterior hip area. There were 14, 24, and seven cystic lesions (31, 53, 16%) locating in lateral, central, and medial pillars of the femoral head. G2 type was the most common pattern of location relationship between cystic lesion and sclerosis rim. Cystic lesions are often found near sclerosis rim in ONFH. The femoral head with osteonecrosis complicating by cystic lesions is more likely to accompany microfracture, collapse, and crescent sign which indicate structural instability in the femoral head. Cystic lesion in ONFH plays an important role in aggravating the progression of femoral head collapse. The peak stress from sclerosis rim may be a main factor inducing the formation of cystic lesion in

Headache in acute ischaemic stroke: a lesion mapping study.

PubMed

Seifert, Christian L; Schönbach, Etienne M; Magon, Stefano; Gross, Elena; Zimmer, Claus; Förschler, Anette; Tölle, Thomas R; Mühlau, Mark; Sprenger, Till; Poppert, Holger

2016-01-01

Headache is a common symptom in acute ischaemic stroke, but the underlying mechanisms are incompletely understood. The aim of this lesion mapping study was to identify brain regions, which are related to the development of headache in acute ischaemic stroke. Patients with acute ischaemic stroke (n = 100) were assessed by brain MRI at 3 T including diffusion weighted imaging. We included 50 patients with stroke and headache as well as 50 patients with stroke but no headache symptoms. Infarcts were manually outlined and images were transformed into standard stereotaxic space using non-linear warping. Voxel-wise overlap and subtraction analyses of lesions as well as non-parametric statistics were conducted. The same analyses were carried out by flipping of left-sided lesions, so that all strokes were transformed to the same hemisphere. Between the headache group as well as the non-headache there was no difference in infarct volumes, in the distribution of affected vascular beds or in the clinical severity of strokes. The headache phenotype was tension-type like in most cases. Subtraction analysis revealed that in headache sufferers infarctions were more often distributed in two well-known areas of the central pain matrix: the insula and the somatosensory cortex. This result was confirmed in the flipped analysis and by non-parametric statistical testing (whole brain corrected P-value < 0.01). To the best of our knowledge, this is the first lesion mapping study investigating potential lesional patterns associated with headache in acute ischaemic stroke. Insular strokes turned out to be strongly associated with headache. As the insular cortex is a well-established region in pain processing, our results suggest that, at least in a subgroup of patients, acute stroke-related headache might be centrally driven. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multi-cellular, three-dimensional living mammalian tissue

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor)

1994-01-01

The present invention relates to a multicellular, three-dimensional, living mammalian tissue. The tissue is produced by a co-culture process wherein two distinct types of mammalian cells are co-cultured in a rotating bioreactor which is completely filled with culture media and cell attachment substrates. As the size of the tissue assemblies formed on the attachment substrates changes, the rotation of the bioreactor is adjusted accordingly.

Prognosis of a mandibular incisor with apical and periodontal lesion: an 18-month follow-up.

PubMed

Yilmaz, Burak; Er, Serkan; Sonbay, Burcin Hilal

2009-01-01

Oral habits that are performed daily, can be a factor in the progression of periodontal and/or endodontic diseases. The purpose of this clinical report was to describe the treatment of a wide periodontal lesion and 18-month follow-up of a 13-year-old male patient's permanent mandibular central incisor that was traumatized due to chronic pencil biting. The lesion was curreted surgically while the compromised mandibular central incisor was endodontically and periodontally treated. The interdisciplinary approach showed a successful clinical outcome, as the survival of the infected tooth and the recovery of the soft tissues and the alveolar bone could have been achieved.

Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

NASA Astrophysics Data System (ADS)

Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

2016-10-01

Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

Pre-pharyngeal swallow effects of recurrent laryngeal nerve lesion on bolus shape and airway protection in an infant pig model

PubMed Central

Gould, Francois D. H.; Yglesias, B.; Ohlemacher, J.; German, R. Z.

2016-01-01

Recurrent laryngeal nerve (RLN) damage in infants leads to increased dysphagia and aspiration pneumonia. Recent work has shown that intra oral transport and swallow kinematics change following RLN lesion, suggesting potential changes in bolus formation prior to the swallow. In this study we used geometric morphometrics to understand the effect of bolus shape on penetration and aspiration in infants with and without RLN lesion. We hypothesized 1) that geometric bolus properties are related to airway protection outcomes and 2) that in infants with RLN lesion, the relationship between geometric bolus properties and dysphagia is changed. In five infant pigs, dysphagia in 188 swallows was assessed using the Infant Mammalian Penetration Aspiration Score (IMPAS). Using images from high-speed VFSS, bolus shape, bolus area, and tongue outline were quantified digitally. Bolus shape was analyzed using elliptical Fourier analysis, and tongue outline using polynomial curve fitting. Despite large inter-individual differences, significant within individual effects of bolus shape and bolus area on airway protection exist. The relationship between penetration-aspiration score and both bolus area and shape changed post lesion. Tongue shape differed between pre and post lesion swallows, and between swallows with different IMPAS scores. Bolus shape and area affect airway protection outcomes. RLN lesion changes that relationship, indicating that proper bolus formation and control by the tongue requires intact laryngeal sensation. The impact of RLN lesion on dysphagia is pervasive. PMID:27873091

Surgical manipulation of mammalian embryos in vitro.

PubMed

Naruse, I; Keino, H; Taniguchi, M

1997-04-01

Whole-embryo culture systems are useful in the fields of not only embryology but also teratology, toxicology, pharmacology, and physiology. Of the many advantages of whole-embryo culture, we focus here on the surgical manipulation of mammalian embryos. Whole-embryo culture allows us to manipulate mammalian embryos, similarly to fish, amphibian and avian embryos. Many surgical experiments have been performed in mammalian embryos in vitro. Such surgical manipulation alters the destiny of morphogenesis of the embryos and can answer many questions concerning developmental issues. As an example of surgical manipulation using whole-embryo culture systems, one of our experiments is described. Microsurgical electrocauterization of the deep preaxial mesodermal programmed cell death zone (fpp) in the footplate prevented the manifestation of polydactyly in genetic polydactyly mouse embryos (Pdn/Pdn), in which fpp was abolished.

The soft mechanical signature of glial scars in the central nervous system

NASA Astrophysics Data System (ADS)

Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James; Franze, Kristian

2017-03-01

Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

That liver lesion on MDCT in the oncology patient: is it important?

PubMed Central

Thakrar, Kiran H.; Wenzke, Daniel R.; Newmark, Geraldine M.; Mehta, Uday K.; Berlin, Jonathan W.

2012-01-01

Abstract Multidetector-row computed tomography (MDCT) has become the primary imaging test for the staging and follow-up of most malignancies that originate outside of the central nervous system. Technical advances in this imaging technique have led to significant improvement in the detection of metastatic disease to the liver. An unintended by-product of this improving diagnostic acumen is the discovery of incidental hepatic lesions in oncology patients that in the past remained undetected. These ubiquitous, incidentally identified hepatic lesions have created a management dilemma for both clinicians and radiologists: are these lesions benign or do they represent metastases? Naturally, the answer to this question has profound prognostic and therapeutic implications. In this review, guidelines concerning the diagnosis and management of some of the more common hepatic incidental lesions detected in patients with extrahepatic malignancies are presented. PMID:23023318

Conservative Management of Central Cemento-Ossifying Fibroma.

PubMed

Gomes-Ferreira, Pedro Henrique Silva; Carrasco, Leandro Carlos; de Oliveira, Danila; Pereira, Járede Carvalho; Alcalde, Luis Fernando Azambuja; Faverani, Leonardo Perez

2017-01-01

Central cemento-ossifying fibroma is characterized by the combined production of osteoid and cementoid tissue. Radiographically, this lesion is presented as an outlined cortical and variable radiopaque spots, also can be present complete radiolucent or different degrees of radiopacity. The recommended treatment is curettage or enucleation, and the recurrence rate is less than 5%. Considering that surgical treatment is invasive, mainly in large lesions, this study aims to report a patient in whom conservative treatment was carried out by involving the preservation of teeth, with a long-term follow-up. A 48-year-old black female patient, diagnosed with central cemento-ossifying fibroma in mandible, treated conservatively and a 2 years of follow-up. It was concluded that the conservative treatment with a long term of follow-up for maintaining teeth was satisfactory.

Involvement of Escherichia coli DNA Polymerase IV in Tolerance of Cytotoxic Alkylating DNA Lesions in Vivo

PubMed Central

Bjedov, Ivana; Dasgupta, Chitralekha Nag; Slade, Dea; Le Blastier, Sophie; Selva, Marjorie; Matic, Ivan

2007-01-01

Escherichia coli PolIV, a DNA polymerase capable of catalyzing synthesis past replication-blocking DNA lesions, belongs to the most ubiquitous branch of Y-family DNA polymerases. The goal of this study is to identify spontaneous DNA damage that is bypassed specifically and accurately by PolIV in vivo. We increased the amount of spontaneous DNA lesions using mutants deficient for different DNA repair pathways and measured mutation frequency in PolIV-proficient and -deficient backgrounds. We found that PolIV performs an error-free bypass of DNA damage that accumulates in the alkA tag genetic background. This result indicates that PolIV is involved in the error-free bypass of cytotoxic alkylating DNA lesions. When the amount of cytotoxic alkylating DNA lesions is increased by the treatment with chemical alkylating agents, PolIV is required for survival in an alkA tag-proficient genetic background as well. Our study, together with the reported involvement of the mammalian PolIV homolog, Polκ, in similar activity, indicates that Y-family DNA polymerases from the DinB branch can be added to the list of evolutionarily conserved molecular mechanisms that counteract cytotoxic effects of DNA alkylation. This activity is of major biological relevance because alkylating agents are continuously produced endogenously in all living cells and are also present in the environment. PMID:17483416

Presence of abscisic acid, a phytohormone, in the mammalian brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le Page-Degivry, M.T.; Bidard, J.N.; Rouvier, E.

1986-02-01

This paper reports the presence of abscisic acid, one of the most important phytohormones, in the central nervous system of pigs and rats. The identification of this hormone in brain was made after extensive purification by using a radioimmunoassay that is very specific for (+)-cis-abscisic acid. The final product of purification from mammalian brain has the same properties as authentic abscisic acid: it crossreacts in the radioimmunoassay for the phytohormone and it has the same retention properties and the same gas chromatography/mass spectrometry characteristics. Moreover, like (+)-cis-abscisic acid itself, the brain factor inhibits stomatal apertures of abaxial epidermis strips ofmore » Setcreasea purpurea Boom (Commelinaceae). The presence of abscisic acid conjugates that are present in plants has also been identified in brain.« less

Computational modeling of the cell-autonomous mammalian circadian oscillator.

PubMed

Podkolodnaya, Olga A; Tverdokhleb, Natalya N; Podkolodnyy, Nikolay L

2017-02-24

This review summarizes various mathematical models of cell-autonomous mammalian circadian clock. We present the basics necessary for understanding of the cell-autonomous mammalian circadian oscillator, modern experimental data essential for its reconstruction and some special problems related to the validation of mathematical circadian oscillator models. This work compares existing mathematical models of circadian oscillator and the results of the computational studies of the oscillating systems. Finally, we discuss applications of the mathematical models of mammalian circadian oscillator for solving specific problems in circadian rhythm biology.

Critical Structure Sparing in Stereotactic Ablative Radiotherapy for Central Lung Lesions: Helical Tomotherapy vs. Volumetric Modulated Arc Therapy

PubMed Central

Chi, Alexander; Ma, Pan; Fu, Guishan; Hobbs, Gerry; Welsh, James S.; Nguyen, Nam P.; Jang, Si Young; Dai, Jinrong; Jin, Jing; Komaki, Ritsuko

2013-01-01

Background Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are both advanced techniques of delivering intensity-modulated radiotherapy (IMRT). Here, we conduct a study to compare HT and partial-arc VMAT in their ability to spare organs at risk (OARs) when stereotactic ablative radiotherapy (SABR) is delivered to treat centrally located early stage non-small-cell lung cancer or lung metastases. Methods 12 patients with centrally located lung lesions were randomly chosen. HT, 2 & 8 arc (Smart Arc, Pinnacle v9.0) plans were generated to deliver 70 Gy in 10 fractions to the planning target volume (PTV). Target and OAR dose parameters were compared. Each technique’s ability to meet dose constraints was further investigated. Results HT and VMAT plans generated essentially equivalent PTV coverage and dose conformality indices, while a trend for improved dose homogeneity by increasing from 2 to 8 arcs was observed with VMAT. Increasing the number of arcs with VMAT also led to some improvement in OAR sparing. After normalizing to OAR dose constraints, HT was found to be superior to 2 or 8-arc VMAT for optimal OAR sparing (meeting all the dose constraints) (p = 0.0004). All dose constraints were met in HT plans. Increasing from 2 to 8 arcs could not help achieve optimal OAR sparing for 4 patients. 2/4 of them had 3 immediately adjacent structures. Conclusion HT appears to be superior to VMAT in OAR sparing mainly in cases which require conformal dose avoidance of multiple immediately adjacent OARs. For such cases, increasing the number of arcs in VMAT cannot significantly improve OAR sparing. PMID:23577071

Oxidized Base Damage and Single-Strand Break Repair in Mammalian Genomes: Role of Disordered Regions and Posttranslational Modifications in Early Enzymes

PubMed Central

Hegde, Muralidhar L.; Izumi, Tadahide; Mitra, Sankar

2012-01-01

Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/ SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed. PMID:22749145

The In Vivo PDGF Response During Remyelination in Mouse Spinal Cord Following Murine Hepatitis Virus Strain AS9-Induced Transient Demyelination

DTIC Science & Technology

1998-09-14

repopulation. These and other growth factors interacting with cell adhesion molecules andlor matrix molecules would be expected to mediate oligodendrocyte...oligodendrocyte lineage, along with a closely related CCHC zinc finger, is expressed in developing neurons in the mammalian central nervous system. J...repopulate and remyelinate demyelinated lesions. In vitro studies have shown that platelet- derived growth factor (PDGF) induces proliferation

Advanced Stoichiometric Analysis of Metabolic Networks of Mammalian Systems

PubMed Central

Orman, Mehmet A.; Berthiaume, Francois; Androulakis, Ioannis P.; Ierapetritou, Marianthi G.

2013-01-01

Metabolic engineering tools have been widely applied to living organisms to gain a comprehensive understanding about cellular networks and to improve cellular properties. Metabolic flux analysis (MFA), flux balance analysis (FBA), and metabolic pathway analysis (MPA) are among the most popular tools in stoichiometric network analysis. Although application of these tools into well-known microbial systems is extensive in the literature, various barriers prevent them from being utilized in mammalian cells. Limited experimental data, complex regulatory mechanisms, and the requirement of more complex nutrient media are some major obstacles in mammalian cell systems. However, mammalian cells have been used to produce therapeutic proteins, to characterize disease states or related abnormal metabolic conditions, and to analyze the toxicological effects of some medicinally important drugs. Therefore, there is a growing need for extending metabolic engineering principles to mammalian cells in order to understand their underlying metabolic functions. In this review article, advanced metabolic engineering tools developed for stoichiometric analysis including MFA, FBA, and MPA are described. Applications of these tools in mammalian cells are discussed in detail, and the challenges and opportunities are highlighted. PMID:22196224

Glutamate-dependent phosphorylation of the mammalian target of rapamycin (mTOR) in Bergmann glial cells.

PubMed

Zepeda, Rossana C; Barrera, Iliana; Castelán, Francisco; Suárez-Pozos, Edna; Melgarejo, Yaaziel; González-Mejia, Elba; Hernández-Kelly, Luisa C; López-Bayghen, Esther; Aguilera, José; Ortega, Arturo

2009-09-01

Glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, plays an important role in neuronal development and synaptic plasticity. It activates a variety of signaling pathways that regulate gene expression at the transcriptional and translational levels. Within glial cells, besides transcription, glutamate also regulates translation initiation and elongation. The mammalian target of rapamycin (mTOR), a key participant in the translation process, represents an important regulatory locus for translational control. Therefore, in the present communication we sought to characterize the mTOR phosphorylation pattern after glutamate treatment in chick cerebellar Bergmann glia primary cultures. A time- and dose-dependent increase in mTOR Ser 2448 phosphorylation was found. Pharmacological tools established that the glutamate effect is mediated through ionotropic and metabotropic receptors and interestingly, the glutamate transporter system is also involved. The signaling cascade triggered by glutamate includes an increase in intracellular Ca2+ levels, and the activation of the p60(Src)/PI-3K/PKB pathway. These results suggest that glia cells participate in the activity-dependent change in the brain protein repertoire.

Rheotaxis guides mammalian sperm

PubMed Central

Miki, Kiyoshi; Clapham, David E

2013-01-01

Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

Hyperintense white matter lesions in 50 high-altitude pilots with neurologic decompression sickness.

PubMed

McGuire, Stephen A; Sherman, Paul M; Brown, Anthony C; Robinson, Andrew Y; Tate, David F; Fox, Peter T; Kochunov, Peter V

2012-12-01

Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation. We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups. The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant. A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions.

Hyperintense White Matter Lesions in 50 High-Altitude Pilots With Neurologic Decompression Sickness

PubMed Central

McGuire, Stephen A.; Sherman, Paul M.; Brown, Anthony C.; Robinson, Andrew Y.; Tate, David F.; Fox, Peter T.; Kochunov, Peter V.

2013-01-01

Introduction Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation. Methods We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups. Results The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant. Conclusion A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions. PMID:23316539

Amino acids in the cultivation of mammalian cells.

PubMed

Salazar, Andrew; Keusgen, Michael; von Hagen, Jörg

2016-05-01

Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure.

Low-grade central osteosarcoma of distal femur, resembling fibrous dysplasia

PubMed Central

Vasiliadis, Haris S; Arnaoutoglou, Christina; Plakoutsis, Sotiris; Doukas, Michalis; Batistatou, Anna; Xenakis, Theodoros A

2013-01-01

We report a case of a 32 year-old male, admitted for a lytic lesion of the distal femur. One month after the first X-ray, clinical and imaging deterioration was evident. Open biopsy revealed fibrous dysplasia. Three months later, the lytic lesion had spread to the whole distal third of the femur reaching the articular cartilage. The malignant clinical and imaging features necessitated excision of the lesion and reconstruction with a custom-made total knee arthroplasty. Intra-operatively, no obvious soft tissue infiltration was evident. Nevertheless, an excision of the distal 15.5 cm of the femur including 3.0 cm of the surrounding muscles was finally performed. The histological examination of the excised specimen revealed central low-grade osteosarcoma. Based on the morphological features of the excised tumor, allied to the clinical findings, the diagnosis of low-grade central osteosarcoma was finally made although characters of a fibrous dysplasia were apparent. Central low-grade osteosarcoma is a rare, well-differentiated sub-type of osteosarcoma, with clinical, imaging, and histological features similar to benign tumours. Thus, initial misdiagnosis is usual with the condition commonly mistaken for fibrous dysplasia. Central low-grade osteosarcoma is usually treated with surgery alone, with rare cases of distal metastases. However, regional recurrence is quite frequent after close margin excision. PMID:24147271

Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina.

PubMed

Beier, Corinne; Palanker, Daniel; Sher, Alexander

2018-06-04

Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring. Copyright © 2018 Elsevier Ltd. All rights reserved.

Visualizing Inhibition of Nucleosome Mobility and Transcription by Cisplatin-DNA Interstrand Crosslinks in Live Mammalian Cells

PubMed Central

Zhu, Guangyu; Song, Lina; Lippard, Stephen J.

2013-01-01

Cisplatin is a widely used anticancer drug that acts by binding DNA and causing the formation of intrastrand and interstrand (ICL) cross-links, but the precise downstream effects of the latter damage are not well understood. In this study, we investigated the influence of cisplatin ICLs on synthetic nucleosomes that were platinated in a site-specific manner in vitro and on gene transcription in live mammalian cells. Nucleosome core particles (NCPs) that we constructed contained site-specific cisplatin 5′-d(G*pC)/5′-d(G*pC) ICLs, where the asterisk denotes the platinated nucleoside, to examine the influence of platinum lesions on the dynamic behavior of nucleosomes in solution. A cisplatin ICL, but not a 1,2-d(GpG) cross-link, significantly inhibited ATP-independent histone octamer-DNA sliding. We also used a novel linearization-recircularization strategy described here to synthesize mammalian expression vectors containing site-specific cisplatin ICLs. Plasmid vectors were tested in live mammalian cellsto study the transcription inhibition effects of cisplatin ICLs in the context of two different repair backgrounds. Cisplatin ICLs inhibit transcription as effectively as 1,2-d(GpG) cross-links. We determined that nucleotide excision repair plays a key role in the removal of cisplatin ICLs, acting in a replication-independent fashion. We also found that loss of mismatch repair function dramatically attenuatesthe transcription inhibition effects by cisplatin ICLs but not 1,2-d(GpG) intrastrand cross-links. Our results revealed the unique properties of cisplatin ICLs on nucleosome mobility and on transcription, and they defined how these adducts act in a manner completely different from that used for cisplatin 1,2-d(GpG) cross-links. These new findings provide direct support for a role of ICLs in the pharmacological activities of cisplatin, despite the lower frequency of their formation. PMID:23695549

Involvement of opsins in mammalian sperm thermotaxis

PubMed Central

Pérez-Cerezales, Serafín; Boryshpolets, Sergii; Afanzar, Oshri; Brandis, Alexander; Nevo, Reinat; Kiss, Vladimir; Eisenbach, Michael

2015-01-01

A unique characteristic of mammalian sperm thermotaxis is extreme temperature sensitivity, manifested by the capacity of spermatozoa to respond to temperature changes of <0.0006 °C as they swim their body-length distance. The identity of the sensing system that confers this exceptional sensitivity on spermatozoa is not known. Here we show that the temperature-sensing system of mammalian spermatozoa involves opsins, known to be G-protein-coupled receptors that act as photosensors in vision. We demonstrate by molecular, immunological, and functional approaches that opsins are present in human and mouse spermatozoa at specific sites, which depend on the species and the opsin type, and that they are involved in sperm thermotaxis via two signalling pathways—the phospholipase C and the cyclic-nucleotide pathways. Our results suggest that, depending on the context and the tissue, mammalian opsins act not only as photosensors but also as thermosensors. PMID:26537127

[The Role of Imaging in Central Nervous System Infections].

PubMed

Yokota, Hajime; Tazoe, Jun; Yamada, Kei

2015-07-01

Many infections invade the central nervous system. Magnetic resonance imaging (MRI) is the main tool that is used to evaluate infectious lesions of the central nervous system. The useful sequences on MRI are dependent on the locations, such as intra-axial, extra-axial, and spinal cord. For intra-axial lesions, besides the fundamental sequences, including T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery (FLAIR) images, advanced sequences, such as diffusion-weighted imaging, diffusion tensor imaging, susceptibility-weighted imaging, and MR spectroscopy, can be applied. They are occasionally used as determinants for quick and correct diagnosis. For extra-axial lesions, understanding the differences among 2D-conventional T1-weighted images, 2D-fat-saturated T1-weighted images, 3D-Spin echo sequences, and 3D-Gradient echo sequence after the administration of gadolinium is required to avoid wrong interpretations. FLAIR plus gadolinium is a useful tool for revealing abnormal enhancement on the brain surface. For the spinal cord, the sequences are limited. Evaluating the distribution and time course of the spinal cord are essential for correct diagnoses. We summarize the role of imaging in central nervous system infections and show the pitfalls, key points, and latest information in them on clinical practices.

Is central dogma a global property of cellular information flow?

PubMed

Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

2012-01-01

The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale, and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.

La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts.

PubMed

Blakqori, Gjon; Delhaye, Sophie; Habjan, Matthias; Blair, Carol D; Sánchez-Vargas, Irma; Olson, Ken E; Attarzadeh-Yazdi, Ghassem; Fragkoudis, Rennos; Kohl, Alain; Kalinke, Ulrich; Weiss, Siegfried; Michiels, Thomas; Staeheli, Peter; Weber, Friedemann

2007-05-01

La Crosse virus (LACV) is a mosquito-transmitted member of the Bunyaviridae family that causes severe encephalitis in children. For the LACV nonstructural protein NSs, previous overexpression studies with mammalian cells had suggested two different functions, namely induction of apoptosis and inhibition of RNA interference (RNAi). Here, we demonstrate that mosquito cells persistently infected with LACV do not undergo apoptosis and mount a specific RNAi response. Recombinant viruses that either express (rLACV) or lack (rLACVdelNSs) the NSs gene similarly persisted and were prone to the RNAi-mediated resistance to superinfection. Furthermore, in mosquito cells overexpressed LACV NSs was unable to inhibit RNAi against Semliki Forest virus. In mammalian cells, however, the rLACVdelNSs mutant virus strongly activated the antiviral type I interferon (IFN) system, whereas rLACV as well as overexpressed NSs suppressed IFN induction. Consequently, rLACVdelNSs was attenuated in IFN-competent mouse embryo fibroblasts and animals but not in systems lacking the type I IFN receptor. In situ analyses of mouse brains demonstrated that wild-type and mutant LACV mainly infect neuronal cells and that NSs is able to suppress IFN induction in the central nervous system. Thus, our data suggest little relevance of the NSs-induced apoptosis or RNAi inhibition for growth or pathogenesis of LACV in the mammalian host and indicate that NSs has no function in the insect vector. Since deletion of the viral NSs gene can be fully complemented by inactivation of the host's IFN system, we propose that the major biological function of NSs is suppression of the mammalian innate immune response.

Next-generation mammalian genetics toward organism-level systems biology.

PubMed

Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

2017-01-01

Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

Jaw Intraosseous Lesions Biopsied Extracted From 1998 to 2010 in an Iranian Population

PubMed Central

Jamshidi, Shokoofeh; Shojaei, Setareh; Roshanaei, Ghodratollah; Modabbernia, Shirin; Bakhtiary, Esmaeel

2015-01-01

Background: Jaw bones might be potential locations for different lesions. Differences in prevalence and the type of lesions can help in designing and programming prevention procedures in health care centers. Objectives: The aim of the present study was to evaluate the prevalence of intraosseous lesions in the jaws of patients referred to diagnostic and therapeutic centers in Hamadan during 1990-2010. Patients and Methods: This cross-sectional descriptive analytical study was carried out in Hamadan in 2011. Data sheets of the subjects were used to collect all the data of patients with intraosseous lesions, including their age, gender, location of the lesion, the radiographic view of lesions, and their type and histopathological diagnoses. Data were analyzed with SPSS, using means and frequencies. Results: A total of 284 intraosseous lesions were reported in our study. The mean age of the subjects was 28.8 ± 15.2 years. The lesions were distributed in males and females almost similarly. The most prevalent lesions were cystic lesions (54.58%), manifestations of systemic conditions in jaw bones (18.3%), benign tumors (15.5%), malignant lesions (6.7%), and inflammatory lesions (4.92%), in a descending order. The most common cystic lesion was radicular cyst; the most common manifestation of systemic conditions in jaw bones was central giant cell granuloma; the most common benign tumor was ameloblastoma; the most common malignant lesion was osteosarcoma; and the most common inflammatory lesion was periapical granuloma. Conclusions: Our data provided information on the prevalence and types of intraosseous lesions among an Iranian population. This study provided baseline information to help in designing and programming procedures in health care centers in every community so that preventive therapeutic measures can be adopted. PMID:26328061

Multispectral near-infrared reflectance and transillumination imaging of occlusal carious lesions: variations in lesion contrast with lesion depth

NASA Astrophysics Data System (ADS)

Simon, Jacob C.; Curtis, Donald A.; Darling, Cynthia L.; Fried, Daniel

2018-02-01

In vivo and in vitro studies have demonstrated that near-infrared (NIR) light at λ=1300-1700-nm can be used to acquire high contrast images of enamel demineralization without interference of stains. The objective of this study was to determine if a relationship exists between the NIR image contrast of occlusal lesions and the depth of the lesion. Extracted teeth with varying amounts of natural occlusal decay were measured using a multispectral-multimodal NIR imaging system which captures λ=1300-nm occlusal transillumination, and λ=1500-1700-nm cross-polarized reflectance images. Image analysis software was used to calculate the lesion contrast detected in both images from matched positions of each imaging modality. Samples were serially sectioned across the lesion with a precision saw, and polarized light microscopy was used to measure the respective lesion depth relative to the dentinoenamel junction. Lesion contrast measured from NIR crosspolarized reflectance images positively correlated (p<0.05) with increasing lesion depth and a statistically significant difference between inner enamel and dentin lesions was observed. The lateral width of pit and fissures lesions measured in both NIR cross-polarized reflectance and NIR transillumination positively correlated with lesion depth.

Targeting RNA in mammalian systems with small molecules.

PubMed

Donlic, Anita; Hargrove, Amanda E

2018-05-03

The recognition of RNA functions beyond canonical protein synthesis has challenged the central dogma of molecular biology. Indeed, RNA is now known to directly regulate many important cellular processes, including transcription, splicing, translation, and epigenetic modifications. The misregulation of these processes in disease has led to an appreciation of RNA as a therapeutic target. This potential was first recognized in bacteria and viruses, but discoveries of new RNA classes following the sequencing of the human genome have invigorated exploration of its disease-related functions in mammals. As stable structure formation is evolving as a hallmark of mammalian RNAs, the prospect of utilizing small molecules to specifically probe the function of RNA structural domains and their interactions is gaining increased recognition. To date, researchers have discovered bioactive small molecules that modulate phenotypes by binding to expanded repeats, microRNAs, G-quadruplex structures, and RNA splice sites in neurological disorders, cancers, and other diseases. The lessons learned from achieving these successes both call for additional studies and encourage exploration of the plethora of mammalian RNAs whose precise mechanisms of action remain to be elucidated. Efforts toward understanding fundamental principles of small molecule-RNA recognition combined with advances in methodology development should pave the way toward targeting emerging RNA classes such as long noncoding RNAs. Together, these endeavors can unlock the full potential of small molecule-based probing of RNA-regulated processes and enable us to discover new biology and underexplored avenues for therapeutic intervention in human disease. This article is categorized under: RNA Methods > RNA Analyses In Vitro and In Silico RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA in Disease and Development > RNA in Disease. © 2018 Wiley Periodicals, Inc.

Phylogenetic Analysis of Genome Rearrangements among Five Mammalian Orders

PubMed Central

Luo, Haiwei; Arndt, William; Zhang, Yiwei; Shi, Guanqun; Alekseyev, Max; Tang, Jijun; Hughes, Austin L.; Friedman, Robert

2015-01-01

Evolutionary relationships among placental mammalian orders have been controversial. Whole genome sequencing and new computational methods offer opportunities to resolve the relationships among 10 genomes belonging to the mammalian orders Primates, Rodentia, Carnivora, Perissodactyla and Artiodactyla. By application of the double cut and join distance metric, where gene order is the phylogenetic character, we computed genomic distances among the sampled mammalian genomes. With a marsupial outgroup, the gene order tree supported a topology in which Rodentia fell outside the cluster of Primates, Carnivora, Perissodactyla, and Artiodactyla. Results of breakpoint reuse rate and synteny block length analyses were consistent with the prediction of random breakage model, which provided a diagnostic test to support use of gene order as an appropriate phylogenetic character in this study. We the influence of rate differences among lineages and other factors that may contribute to different resolutions of mammalian ordinal relationships by different methods of phylogenetic reconstruction. PMID:22929217

Mammalian Synthetic Biology: Engineering Biological Systems.

PubMed

Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

2017-06-21

The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

PubMed

Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

2016-09-11

A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription

PubMed Central

Aydin, Özge Z.; Marteijn, Jurgen A.; Ribeiro-Silva, Cristina; Rodríguez López, Aida; Wijgers, Nils; Smeenk, Godelieve; van Attikum, Haico; Poot, Raymond A.; Vermeulen, Wim; Lans, Hannes

2014-01-01

Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving lesion-stalled transcription. Human ISWI isoform SMARCA5/SNF2H and its binding partners ACF1 and WSTF are rapidly recruited to UV-C induced DNA damage to specifically facilitate CSB binding and to promote transcription recovery. SMARCA5 targeting to UV-C damage depends on transcription and histone modifications and requires functional SWI2/SNF2-ATPase and SLIDE domains. After initial recruitment to UV damage, SMARCA5 re-localizes away from the center of DNA damage, requiring its HAND domain. Our studies support a model in which SMARCA5 targeting to DNA damage-stalled transcription sites is controlled by an ATP-hydrolysis-dependent scanning and proofreading mechanism, highlighting how SWI2/SNF2 chromatin remodelers identify and bind nucleosomes containing damaged DNA. PMID:24990377

Structure and Function of Mammalian Carbohydrate-Lectin Interactions

NASA Astrophysics Data System (ADS)

Anderson, Kevin; Evers, David; Rice, Kevin G.

Over the past three decades the field of glycobiology has expanded beyond a basic understanding of the structure and biosynthesis of glycoprotein, proteoglycans, and glycolipids toward a more detailed picture of how these molecules afford communication through binding to mammalian lectins. Although the number of different mammalian lectin domains appears to be finite and even much smaller than early estimates predicated based on the diversity of glycan structures, nature appears capable of using these in numerous combinations to fine tune specificity. The following provides an overview of the major classes of mammalian lectins and discusses their glycan binding specificity. The review provides a snapshot of the field of glycobiology that continues to grow providing an increasing number of examples of biological processes that rely upon glycan-lectin binding.

Brain vascular lesions: a clinicopathologic, immunohistochemistry, and ultrastructural approach.

PubMed

Navarrete, Marisol Galván; Hernández, Alma Dalia; Collado-Ortiz, Miguel Angel; Salinas-Lara, Citlaltepetl; Tena-Suck, Martha Lilia

2014-08-01

Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor β (β-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood. Copyright © 2014 Elsevier Inc. All rights reserved.

Design and performance test of NIRS-based spinal cord lesion detector

NASA Astrophysics Data System (ADS)

Li, Nanxi; Li, Ting

2018-02-01

Spinal cord lesions can cause a series of severe complications, which can even lead to paralysis with high mortality. However, the traditional diagnosis of spinal cord lesion relies on complicated imaging modalities and other invasive and dangerous methods. Here, we have designed a small monitor based on NIRS technology for noninvasive monitoring for spinal cord lesions. The development of the instrument system includes the design of hardware circuits and the program of software. In terms of hardware, OPT1011 is selected as the light detector, and the appropriate probe distribution structure is selected according to the simulation result of Monte Carlo Simulation. At the same time, the powerful controller is selected as our system's central processing chip for the circuit design, and the data is transmitted by serial port to the host computer for post processing. Finally, we verify the stability and feasibility of the instrument system. It is found that the spinal signal could be obviously detected in the system, which indicates that our monitor based on NIRS technology has the potential to monitor the spinal lesion.

Diagnostic Features of Common Oral Ulcerative Lesions: An Updated Decision Tree

PubMed Central

Safi, Yaser

2016-01-01

Diagnosis of oral ulcerative lesions might be quite challenging. This narrative review article aims to introduce an updated decision tree for diagnosing oral ulcerative lesions on the basis of their diagnostic features. Various general search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of MeSH keywords such as “oral ulcer,” “stomatitis,” and “mouth diseases.” Thereafter, English-language articles published since 1983 to 2015 in both medical and dental journals including reviews, meta-analyses, original papers, and case reports were appraised. Upon compilation of the relevant data, oral ulcerative lesions were categorized into three major groups: acute, chronic, and recurrent ulcers and into five subgroups: solitary acute, multiple acute, solitary chronic, multiple chronic, and solitary/multiple recurrent, based on the number and duration of lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by stepwise progression. PMID:27781066

CT-Guided Biopsy of Small Liver Lesions: Visibility, Artifacts, and Corresponding Diagnostic Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stattaus, Joerg, E-mail: joerg.stattaus@uni-due.de; Kuehl, Hilmar; Ladd, Susanne

2007-09-15

Purpose. Our study aimed to determine the visibility of small liver lesions during CT-guided biopsy and to assess the influence of lesion visibility on biopsy results. Material and Methods. Fifty patients underwent CT-guided core biopsy of small focal liver lesions (maximum diameter, 3 cm); 38 biopsies were performed using noncontrast CT, and the remaining 12 were contrast-enhanced. Visibility of all lesions was graded on a 4-point-scale (0 = not visible, 1 = poorly visible, 2 = sufficiently visible, 3 = excellently visible) before and during biopsy (with the needle placed adjacent to and within the target lesion). Results. Forty-three biopsiesmore » (86%) yielded diagnostic results, and seven biopsies were false-negative. In noncontrast biopsies, the rate of insufficiently visualized lesions (grades 0-1) increased significantly during the procedure, from 10.5% to 44.7%, due to needle artifacts. This resulted in more (17.6%) false-negative biopsy results compared to lesions with good visualization (4.8%), although this difference lacks statistical significance. Visualization impairment appeared more often with an intercostal or subcostal vs. an epigastric access and with a subcapsular vs. a central lesion location, respectively. With contrast-enhanced biopsy the visibility of hepatic lesions was only temporarily improved, with a risk of complete obscuration in the late phase. Conclusion. In conclusion, visibility of small liver lesions diminished significantly during CT-guided biopsy due to needle artifacts, with a fourfold increased rate of insufficiently visualized lesions and of false-negative histological results. Contrast enhancement did not reveal better results.« less

Characteristics of Rosai-Dorfman Disease Primarily Involved in the Central Nervous System: 3 Case Reports and Review of Literature.

PubMed

Luo, Zhengxiang; Zhang, Yansong; Zhao, Penglai; Lu, Hucheng; Yang, Kun; Zhang, Yuhai; Zeng, Yanjun

2017-01-01

This study aimed to summarize the clinical characteristics of Rosai-Dorfman disease primarily involving the central nervous system and to explore diagnosis and treatment. We analyzed the clinical, imaging, and pathologic characteristics; treatment; and prognosis in 3 cases of Rosai-Dorfman disease primarily involving the central nervous system. We also performed a literature review. The largest of multiple intracranial lesions was totally resected, and steroid administration and radiotherapy were performed in phases for the remaining lesions. During the 1-year follow-up period, the excised lesion did not recur, and no obvious variations were observed in the other lesions. Subtotal resection was performed of the largest of another group of multiple intracranial lesions, and the residual did not show any obvious variations during the 1-year follow-up period. The isolated lesion was totally resected and did not recur during a 2-year follow-up period. Rosai-Dorfman disease with multiple lesions primarily involving the central nervous system is rare. Imaging characteristics are similar to meningiomas, and the pathological features include lymphocytes and plasma cells reaching tissue cells with large volume and abundant cytoplasm. Surgery is the preferred treatment, as the effects of steroid administration and radiotherapy are not apparent. Copyright © 2016 Elsevier Inc. All rights reserved.

[Healing process of claw lesions in dairy cows in alpine mountain pastures].

PubMed

Lischer, C J; Wehrle, M; Geyer, H; Lutz, B; Ossent, P

2000-07-01

The field study investigated severity, localisation and incidence of claw lesions of dairy cows and their healing process during a period of three months on selected mountain pastures in the central part of Switzerland. In 60 cows, which were at least 120 days in their lactation, the healing process was compared with the biochemical profiles. In 141 cows 197 claw lesions were recorded. Diagnosed were only sole ulcers (38%) and white line lesions (62%). In the first and second half of the summer term, the number of claw lesions was equal, although more severe lesions occurred mainly during the second half (89%). The lesions were treated surgically and the affected claw was elevated on a wood block or a plastic shoe. Average time for formation of a close layer of horn was 14 days. A delayed healing process was observed in dairy cows with an milk yield over 5500 kg per lactation, as well as in the second half of the summer term. Cows with a delayed healing process had significantly higher concentrations of free fatty acids and beta-hydroxybutyrate, and higher plasma enzyme activities for AST than cows with adequate healing process. This indicates that cows with a relatively high milk production touch upon the limits of their physical capacity under harder conditions on alpine pastures, which may affect also the healing process of claw lesions.

Applications of CRISPR/Cas9 in the Mammalian Central Nervous System



PubMed Central

Savell, Katherine E.; Day, Jeremy J.

2017-01-01

Within the central nervous system, gene regulatory mechanisms are crucial regulators of cellular development and function, and dysregulation of these systems is commonly observed in major neuropsychiatric and neurological disorders. However, due to a lack of tools to specifically modulate the genome and epigenome in the central nervous system, many molecular and genetic mechanisms underlying cognitive function and behavior are still unknown. Although genome editing tools have been around for decades, the recent emergence of inexpensive, straightforward, and widely accessible CRISPR/Cas9 systems has led to a revolution in gene editing. The development of the catalytically dead Cas9 (dCas9) expanded this flexibility even further by acting as an anchoring system for fused effector proteins, structural scaffolds, and RNAs. Together, these advances have enabled robust, modular approaches for specific targeting and modification of the local chromatin environment at a single gene. This review highlights these advancements and how the combination of powerful modulatory tools paired with the versatility of CRISPR-Cas9-based systems offer great potential for understanding the underlying genetic and epigenetic contributions of neuronal function, behavior, and neurobiological diseases. PMID:29259522

Maturation of the mammalian secretome

PubMed Central

Simpson, Jeremy C; Mateos, Alvaro; Pepperkok, Rainer

2007-01-01

A recent use of quantitative proteomics to determine the constituents of the endoplasmic reticulum and Golgi complex is discussed in the light of other available methodologies for cataloging the proteins associated with the mammalian secretory pathway. PMID:17472737

Gene transfer and gene mapping in mammalian cells in culture.

PubMed

Shows, T B; Sakaguchi, A Y

1980-01-01

The ability to transfer mammalian genes parasexually has opened new possibilities for gene mapping and fine structure mapping and offers great potential for contributing to several aspects of mammalian biology, including gene expression and genetic engineering. The DNA transferred has ranged from whole genomes to single genes and smaller segments of DNA. The transfer of whole genomes by cell fusion forms cell hybrids, which has promoted the extensive mapping of human and mouse genes. Transfer, by cell fusion, of rearranged chromosomes has contributed significantly to determining close linkage and the assignment of genes to specific chromosomal regions. Transfer of single chromosomes has been achieved utilizing microcells fused to recipient cells. Metaphase chromosomes have been isolated and used to transfer single-to-multigenic DNA segments. DNA-mediated gene transfer, simulating bacterial transformation, has achieved transfer of single-copy genes. By utilizing DNA cleaved with restriction endonucleases, gene transfer is being empolyed as a bioassay for the purification of genes. Gene mapping and the fate of transferred genes can be examined now at the molecular level using sequence-specific probles. Recently, single genes have been cloned into eucaryotic and procaryotic vectors for transfer into mammalian cells. Moreover, recombinant libraries in which entire mammalian genomes are represented collectively are a rich new source of transferable genes. Methodology for transferring mammalian genetic information and applications for mapping mammalian genes is presented and prospects for the future discussed.

The mammalian blastema: regeneration at our fingertips

PubMed Central

Simkin, Jennifer; Sammarco, Mimi C.; Dawson, Lindsay A.; Schanes, Paula P.; Yu, Ling

2015-01-01

Abstract In the mouse, digit tip regeneration progresses through a series of discrete stages that include inflammation, histolysis, epidermal closure, blastema formation, and redifferentiation. Recent studies reveal how each regenerative stage influences subsequent stages to establish a blastema that directs the successful regeneration of a complex mammalian structure. The focus of this review is on early events of healing and how an amputation wound transitions into a functional blastema. The stepwise formation of a mammalian blastema is proposed to provide a model for how specific targeted treatments can enhance regenerative performance in humans. PMID:27499871

Better Smelling Through Genetics: Mammalian Odor Perception

PubMed Central

Keller, Andreas; Vosshall, Leslie B.

2008-01-01

SUMMARY The increasing availability of genomic and genetic tools to study olfaction—the sense of smell—has brought important new insights into how this chemosensory modality functions in different species. Newly sequenced mammalian genomes—from platypus to dog—have made it possible to infer how smell has evolved to suit the needs of a given species and how variation within a species may affect individual olfactory perception. This review will focus on recent advances in the genetics and genomics of mammalian smell, with a primary focus on rodents and humans. PMID:18938244

Recovery from retinal lesions: molecular plasticity mechanisms in visual cortex far beyond the deprived zone.

PubMed

Hu, Tjing-Tjing; Van den Bergh, Gert; Thorrez, Lieven; Heylen, Kevin; Eysel, Ulf T; Arckens, Lutgarde

2011-12-01

In cats with central retinal lesions, deprivation of the lesion projection zone (LPZ) in primary visual cortex (area 17) induces remapping of the cortical topography. Recovery of visually driven cortical activity in the LPZ involves distinct changes in protein expression. Recent observations, about molecular activity changes throughout area 17, challenge the view that its remote nondeprived parts would not be involved in this recovery process. We here investigated the dynamics of the protein expression pattern of remote nondeprived area 17 triggered by central retinal lesions to explore to what extent far peripheral area 17 would contribute to the topographic map reorganization inside the visual cortex. Using functional proteomics, we identified 40 proteins specifically differentially expressed between far peripheral area 17 of control and experimental animals 14 days to 8 months postlesion. Our results demonstrate that far peripheral area 17 is implicated in the functional adaptation to the visual deprivation, involving a meshwork of interacting proteins, operating in diverse pathways. In particular, endocytosis/exocytosis processes appeared to be essential via their intimate correlation with long-term potentiation and neurite outgrowth mechanisms.

COMPARATIVE ANALYSIS OF MAMMALIAN SPERM MOTILITY

PubMed Central

Phillips, David M.

1972-01-01

Spermatozoa of several mammalian species were studied by means of high-speed cinematography and electron microscopy. Three types of motile patterns were observed in mouse spermatozoa. The first type involved an asymmetrical beat which seemed to propel the sperm in circular paths. The second type involved rotation of the sperm and appeared to allow them to maintain straight paths. In the third type of pattern, the sperm appeared to move by crawling on surfaces in a snakelike manner. Spermatozoa of rabbit and Chinese hamster also had an asymmetrical beat which sometimes caused them to swim in circles. In spite of the asymmetry of the beat, these spermatozoa were also able to swim in straight paths by rotating around a central axis as they swam. Spermatozoa of some species appeared very flexible; their flagella formed arcs with a very small radius of curvature as they beat. Spermatozoa of other species appeared very stiff, and their flagella formed arcs with a very large radius of curvature. The stiffness of the spermatozoan appeared to correlate positively with the cross-sectional area of the dense fibers. This suggests that the dense fibers may be stiff elastic elements. Opossum sperm become paired as they pass through the epididymis. Pairs of opossum spermatozoa beat in a coordinated, alternating manner. PMID:5025110

Baculovirus GP64-mediated entry into mammalian cells.

PubMed

Kataoka, Chikako; Kaname, Yuuki; Taguwa, Shuhei; Abe, Takayuki; Fukuhara, Takasuke; Tani, Hideki; Moriishi, Kohji; Matsuura, Yoshiharu

2012-03-01

The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) serves as an efficient viral vector, not only for abundant gene expression in insect cells, but also for gene delivery into mammalian cells. Lentivirus vectors pseudotyped with the baculovirus envelope glycoprotein GP64 have been shown to acquire more potent gene transduction than those with vesicular stomatitis virus (VSV) envelope glycoprotein G. However, there are conflicting hypotheses about the molecular mechanisms of the entry of AcMNPV. Moreover, the mechanisms of the entry of pseudotyped viruses bearing GP64 into mammalian cells are not well characterized. Determination of the entry mechanisms of AcMNPV and the pseudotyped viruses bearing GP64 is important for future development of viral vectors that can deliver genes into mammalian cells with greater efficiency and specificity. In this study, we generated three pseudotyped VSVs, NPVpv, VSVpv, and MLVpv, bearing envelope proteins of AcMNPV, VSV, and murine leukemia virus, respectively. Depletion of membrane cholesterol by treatment with methyl-β-cyclodextrin, which removes cholesterol from cellular membranes, inhibited GP64-mediated internalization in a dose-dependent manner but did not inhibit attachment to the cell surface. Treatment of cells with inhibitors or the expression of dominant-negative mutants for dynamin- and clathrin-mediated endocytosis abrogated the internalization of AcMNPV and NPVpv into mammalian cells, whereas inhibition of caveolin-mediated endocytosis did not. Furthermore, inhibition of macropinocytosis reduced GP64-mediated internalization. These results suggest that cholesterol in the plasma membrane, dynamin- and clathrin-dependent endocytosis, and macropinocytosis play crucial roles in the entry of viruses bearing baculovirus GP64 into mammalian cells.

Example based lesion segmentation

NASA Astrophysics Data System (ADS)

Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

2014-03-01

Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

Is central dogma a global property of cellular information flow?

PubMed Central

Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

2012-01-01

The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale, and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information. PMID:23189060

Treating vascular lesions.

PubMed

Astner, Susanne; Anderson, R Rox

2005-01-01

The treatment of acquired vascular lesions is one of the most commonly requested and performed cutaneous laser procedures. Furthermore, every year, 40,000 children are born in the United States each with congenital vascular lesions and malformations. Laser treatment of vascular lesion is based on the principle of selective photothermolysis, conceived in the 1980s. A variety of different lasers and light sources have since been used in the treatment of vascular lesions: lasers with wavelengths between green and yellow, near infrared lasers, and broadband light sources. Despite limitations, this remains the treatment of choice today. This publication addresses acquired and congenital vascular lesions as different entities and proposes a separation of vascular lesions into those that can easily be treated from those where clearance is difficult. Different treatment modalities and the various endpoints of individual vascular lesions will be discussed.

Anaplastic ganglioglioma arising from a Lhermitte-Duclos-like lesion. Case report.

PubMed

Takei, Hidehiro; Dauser, Robert; Su, Jack; Chintagumpala, Murali; Bhattacharjee, Meenakshi B; Jones, Jeremy; Adesina, Adekunle M

2007-08-01

The authors report the case of a 7-year-old boy with a history of developmental delay who presented with aggressive behavior. A magnetic resonance (MR) image showed a mass lesion originating from the cerebellar vermis with an atypical folial pattern and contrast enhancement. Histologically, the subtotally resected specimen consisted mostly of neuropil with nodular foci of ganglion cells. Lhermitte-Duclos disease (LDD) was diagnosed in the patient. A retrospective review of the tissue sections showed a nidus of associated astrocytic proliferation, suggesting a diagnosis of ganglioglioma. Five years later, the patient experienced an altered mental state and a facial droop. An MR image revealed a cerebellar mass with cystic areas and an enhancing nodule. The resected tissue specimen consisted primarily of a mixed proliferation of glial and ganglion cells consistent with a ganglioglioma. Two years later, a third craniectomy was performed in the patient for worsening headache and ataxia. Histologically, the tumor showed progressive anaplasia and was most accurately classified as an anaplastic ganglioglioma. Immunohistochemically, most of the tumor cells were immunoreactive for anti-phospho-mammalian target of rapamycin (mTOR) and phospho-S6 ribosomal protein antibodies. In contrast, the subpopulation of neoplastic ganglion cells in the tissue, particularly from the first surgery, did not express phosphatase and tensin homolog deleted from chromosome 10 (PTEN). This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD. This case represents the first report of an anaplastic ganglioglioma arising in an LDD-like lesion.

Architecture of the Mammalian Golgi

PubMed Central

Klumperman, Judith

2011-01-01

Since its first visualization in 1898, the Golgi has been a topic of intense morphological research. A typical mammalian Golgi consists of a pile of stapled cisternae, the Golgi stack, which is a key station for modification of newly synthesized proteins and lipids. Distinct stacks are interconnected by tubules to form the Golgi ribbon. At the entrance site of the Golgi, the cis-Golgi, vesicular tubular clusters (VTCs) form the intermediate between the endoplasmic reticulum and the Golgi stack. At the exit site of the Golgi, the trans-Golgi, the trans-Golgi network (TGN) is the major site of sorting proteins to distinct cellular locations. Golgi functioning can only be understood in light of its complex architecture, as was revealed by a range of distinct electron microscopy (EM) approaches. In this article, a general concept of mammalian Golgi architecture, including VTCs and the TGN, is described. PMID:21502307

Diagnosis and management of premalignant penile lesions

PubMed Central

Shabbir, Majid; Minhas, Suks; Muneer, Asif

2011-01-01

Diagnosing premalignant penile lesions from benign penile dermatoses presents a unique challenge. The rarity of these conditions and the low incidence of penile cancer mean that the majority of our knowledge is based on small, non-randomized, retrospective studies. The introduction of specialist penile cancer centres in the UK has resulted in the centralization of expertise and resources, and has furthered our understanding of the biological behaviour and management of this rare malignancy. We review the current trends in the approach to diagnosing and treating various premalignant penile conditions. PMID:21904571

Central neuropathic pain in MS is due to distinct thoracic spinal cord lesions.

PubMed

Okuda, Darin T; Melmed, Kara; Matsuwaki, Takashi; Blomqvist, Anders; Craig, Arthur D Bud

2014-08-01

To determine a neuro-anatomic cause for central neuropathic pain (CNP) observed in multiple sclerosis (MS) patients. Parallel clinical and neuro-anatomical studies were performed. A clinical investigation of consecutively acquired MS patients with and without CNP (i.e. cold allodynia or deep hyperesthesia) within a single MS center was pursued. A multivariate logistic regression model was used to assess the relationship between an upper central thoracic spinal cord focus to central pain complaints. To identify the hypothesized autonomic interneurons with bilateral descending projections to lumbosacral sensory neurons, retrograde single- and double-labeling experiments with CTb and fluorescent tracers were performed in three animal species (i.e. rat, cat, and monkey). Clinical data were available in MS patients with (n = 32; F:23; median age: 34.6 years (interquartile range [IQR]: 27.4-45.5)) and without (n = 30; F:22; median age: 36.6 years [IQR: 31.6-47.1]) CNP. The value of a central focus between T1-T6 in relation to CNP demonstrated a sensitivity of 96.9% (95% confidence interval [CI]: 83.8-99.9) and specificity of 83.3% (95% CI: 65.3-94.4). A significant relationship between CNP and a centrally located focus within the thoracic spine was also observed (odds ratio [OR]: 155.0 [95% CI lower limit: 16.0]; P < 0.0001, two-tailed Fisher exact test). In all animal models, neurons with bilateral descending projections to the lumbosacral superficial dorsal horn were concentrated in the autonomic intermediomedial nucleus surrounding the mid-thoracic central canal. Our observations provide the first evidence for the etiology of CNP. These data may assist with the development of refined symptomatic therapies and allow for insights into unique pain syndromes observed in other demyelinating subtypes.

Computed tomography-magnetic resonance image fusion: a clinical evaluation of an innovative approach for improved tumor localization in primary central nervous system lesions.

PubMed

Lattanzi, J P; Fein, D A; McNeeley, S W; Shaer, A H; Movsas, B; Hanks, G E

1997-01-01

We describe our initial experience with the AcQSim (Picker International, St. David, PA) computed tomography-magnetic resonance imaging (CT-MRI) fusion software in eight patients with intracranial lesions. MRI data are electronically integrated into the CT-based treatment planning system. Since MRI is superior to CT in identifying intracranial abnormalities, we evaluated the precision and feasibility of this new localization method. Patients initially underwent CT simulation from C2 to the most superior portion of the scalp. T2 and post-contrast T1-weighted MRI of this area was then performed. Patient positioning was duplicated utilizing a head cup and bridge of nose to forehead angle measurements. First, a gross tumor volume (GTV) was identified utilizing the CT (CT/GTV). The CT and MRI scans were subsequently fused utilizing a point pair matching method and a second GTV (CT-MRI/GTV) was contoured with the aid of both studies. The fusion process was uncomplicated and completed in a timely manner. Volumetric analysis revealed the CT-MRI/GTV to be larger than the CT/GTV in all eight cases. The mean CT-MRI/GTV was 28.7 cm3 compared to 16.7 cm3 by CT alone. This translated into a 72% increase in the radiographic tumor volume by CT-MRI. A simulated dose-volume histogram in two patients revealed that marginal portions of the lesion, as identified by CT and MRI, were not included in the high dose treatment volume as contoured with the use of CT alone. Our initial experience with the fusion software demonstrated an improvement in tumor localization with this technique. Based on these patients the use of CT alone for treatment planning purposes in central nervous system (CNS) lesions is inadequate and would result in an unacceptable rate of marginal misses. The importation of MRI data into three-dimensional treatment planning is therefore crucial to accurate tumor localization. The fusion process simplifies and improves precision of this task.

Enzymatic Removal of Ribonucleotides from DNA Is Essential for Mammalian Genome Integrity and Development

PubMed Central

Reijns, Martin A.M.; Rabe, Björn; Rigby, Rachel E.; Mill, Pleasantine; Astell, Katy R.; Lettice, Laura A.; Boyle, Shelagh; Leitch, Andrea; Keighren, Margaret; Kilanowski, Fiona; Devenney, Paul S.; Sexton, David; Grimes, Graeme; Holt, Ian J.; Hill, Robert E.; Taylor, Martin S.; Lawson, Kirstie A.; Dorin, Julia R.; Jackson, Andrew P.

2012-01-01

Summary The presence of ribonucleotides in genomic DNA is undesirable given their increased susceptibility to hydrolysis. Ribonuclease (RNase) H enzymes that recognize and process such embedded ribonucleotides are present in all domains of life. However, in unicellular organisms such as budding yeast, they are not required for viability or even efficient cellular proliferation, while in humans, RNase H2 hypomorphic mutations cause the neuroinflammatory disorder Aicardi-Goutières syndrome. Here, we report that RNase H2 is an essential enzyme in mice, required for embryonic growth from gastrulation onward. RNase H2 null embryos accumulate large numbers of single (or di-) ribonucleotides embedded in their genomic DNA (>1,000,000 per cell), resulting in genome instability and a p53-dependent DNA-damage response. Our findings establish RNase H2 as a key mammalian genome surveillance enzyme required for ribonucleotide removal and demonstrate that ribonucleotides are the most commonly occurring endogenous nucleotide base lesion in replicating cells. PMID:22579044

THE SIGNIFICANCE OF LESIONS IN PERIPHERAL GANGLIA IN CHIMPANZEE AND IN HUMAN POLIOMYELITIS

PubMed Central

Bodian, David; Howe, Howard A.

1947-01-01

1. The peripheral ganglia of eighteen inoculated chimpanzees and thirteen uninoculated controls, and of eighteen fatal human poliomyelitis cases, were studied for histopathological evidence of the route of transmission of virus from the alimentary tract to the CNS. 2. Lesions thought to be characteristic of poliomyelitis in inoculated chimpanzees could not be sharply differentiated from lesions of unknown origin in uninoculated control animals. Moreover, although the inoculated animals as a group, in comparison with the control animals, had a greater number of infiltrative lesions in sympathetic as well as in sensory ganglia, it was not possible to make satisfactory correlations between the distribution of these lesions and the routes of inoculation. 3. In sharp contrast with chimpanzees, the celiac and stellate ganglia of the human poliomyelitis cases were free of any but insignificant infiltrative lesions. Lesions in human trigeminal and spinal sensory ganglia included neuronal damage as well as focal and perivascular inflitrative lesions, as is well known. In most ganglia, as in monkey and chimpanzee sensory ganglia, these were correlated in intensify with the degree of severity of lesions in the region of the CNS receiving their axons. This suggested that lesions in sensory ganglia probably resulted from spread of virus centrifugally from the CNS, in accord with considerable experimental evidence. 4. Two principal difficulties in the interpretation of histopathological findings in peripheral ganglia were revealed by this study. The first is that the specificity of lesions in sympathetic ganglia has not been established beyond doubt as being due to poliomyelitis. The second is that the presence of characteristic lesions in sensory ganglia does not, and cannot, reveal whether the virus reached the ganglia from the periphery or from the central nervous system, except in very early preparalytic stages or in exceptional cases of early arrest of virus spread and of

[Central nervous system involvement in systemic diseases: Spectrum of MRI findings].

PubMed

Drier, A; Bonneville, F; Haroche, J; Amoura, Z; Dormont, D; Chiras, J

2010-12-01

Central nervous system (CNS) involvement in systemic disease (SD) is unusual. MRI features of such lesions are unfamiliar to most radiologists. The diagnosis of SD is still based on clinical features and laboratory findings but some characteristic MRI findings exist for each SD: micronodular leptomeningeal enhancement in sarcoidosis, diffuse or focal pachymeningeal involvement in Wegener disease, dentate nuclei and brain stem lesions in Langerhans cell histiocytosis, meningeal masses, dentate nuclei lesions and periarterial infiltration in Erdheim-Chester disease, meningeal masses in Rosai-Dorfman disease, veinular pontic lesions and cerebral vein thrombosis in Behçet, supratentorial microvascular lesions in lupus and antiphospholipid and Gougerot-Sjögren syndrome. In this work, we explain, describe and illustrate the most characteristic MRI findings for each disease. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Rapid adaptation to microgravity in mammalian macrophage cells.

PubMed

Thiel, Cora S; de Zélicourt, Diane; Tauber, Svantje; Adrian, Astrid; Franz, Markus; Simmet, Dana M; Schoppmann, Kathrin; Hauschild, Swantje; Krammer, Sonja; Christen, Miriam; Bradacs, Gesine; Paulsen, Katrin; Wolf, Susanne A; Braun, Markus; Hatton, Jason; Kurtcuoglu, Vartan; Franke, Stefanie; Tanner, Samuel; Cristoforetti, Samantha; Sick, Beate; Hock, Bertold; Ullrich, Oliver

2017-02-27

Despite the observed severe effects of microgravity on mammalian cells, many astronauts have completed long term stays in space without suffering from severe health problems. This raises questions about the cellular capacity for adaptation to a new gravitational environment. The International Space Station (ISS) experiment TRIPLE LUX A, performed in the BIOLAB laboratory of the ISS COLUMBUS module, allowed for the first time the direct measurement of a cellular function in real time and on orbit. We measured the oxidative burst reaction in mammalian macrophages (NR8383 rat alveolar macrophages) exposed to a centrifuge regime of internal 0 g and 1 g controls and step-wise increase or decrease of the gravitational force in four independent experiments. Surprisingly, we found that these macrophages adapted to microgravity in an ultra-fast manner within seconds, after an immediate inhibitory effect on the oxidative burst reaction. For the first time, we provided direct evidence of cellular sensitivity to gravity, through real-time on orbit measurements and by using an experimental system, in which all factors except gravity were constant. The surprisingly ultra-fast adaptation to microgravity indicates that mammalian macrophages are equipped with a highly efficient adaptation potential to a low gravity environment. This opens new avenues for the exploration of adaptation of mammalian cells to gravitational changes.

Ancient genomic architecture for mammalian olfactory receptor clusters

PubMed Central

Aloni, Ronny; Olender, Tsviya; Lancet, Doron

2006-01-01

Background Mammalian olfactory receptor (OR) genes reside in numerous genomic clusters of up to several dozen genes. Whole-genome sequence alignment nets of five mammals allow their comprehensive comparison, aimed at reconstructing the ancestral olfactory subgenome. Results We developed a new and general tool for genome-wide definition of genomic gene clusters conserved in multiple species. Syntenic orthologs, defined as gene pairs showing conservation of both genomic location and coding sequence, were subjected to a graph theory algorithm for discovering CLICs (clusters in conservation). When applied to ORs in five mammals, including the marsupial opossum, more than 90% of the OR genes were found within a framework of 48 multi-species CLICs, invoking a general conservation of gene order and composition. A detailed analysis of individual CLICs revealed multiple differences among species, interpretable through species-specific genomic rearrangements and reflecting complex mammalian evolutionary dynamics. One significant instance involves CLIC #1, which lacks a human member, implying the human-specific deletion of an OR cluster, whose mouse counterpart has been tentatively associated with isovaleric acid odorant detection. Conclusion The identified multi-species CLICs demonstrate that most of the mammalian OR clusters have a common ancestry, preceding the split between marsupials and placental mammals. However, only two of these CLICs were capable of incorporating chicken OR genes, parsimoniously implying that all other CLICs emerged subsequent to the avian-mammalian divergence. PMID:17010214

Understanding and utilising mammalian venom via a platypus venom transcriptome.

PubMed

Whittington, Camilla M; Koh, Jennifer M S; Warren, Wesley C; Papenfuss, Anthony T; Torres, Allan M; Kuchel, Philip W; Belov, Katherine

2009-03-06

Only five mammalian species are known to be venomous, and while a large amount of research has been carried out on reptile venom, mammalian venom has been poorly studied to date. Here we describe the status of current research into the venom of the platypus, a semi-aquatic egg-laying Australian mammal, and discuss our approach to platypus venom transcriptomics. We propose that such construction and analysis of mammalian venom transcriptomes from small samples of venom gland, in tandem with proteomics studies, will allow the identification of the full range of mammalian venom components. Functional studies and pharmacological evaluation of the identified toxins will then lay the foundations for the future development of novel biomedical substances. A large range of useful molecules have already been identified in snake venom, and many of these are currently in use in human medicine. It is therefore hoped that this basic research to identify the constituents of platypus venom will eventually yield novel drugs and new targets for painkillers.

Multispectral near-IR reflectance imaging of simulated early occlusal lesions: Variation of lesion contrast with lesion depth and severity

PubMed Central

Simon, Jacob C.; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

2014-01-01

Background and Objectives Early demineralization appears with high contrast at near-IR wavelengths due to a ten to twenty fold difference in the magnitude of light scattering between sound and demineralized enamel. Water absorption in the near-IR has a significant effect on the lesion contrast and the highest contrast has been measured in spectral regions with higher water absorption. The purpose of this study was to determine how the lesion contrast changes with lesion severity and depth for different spectral regions in the near-IR and compare that range of contrast with visible reflectance and fluorescence. Materials and Methods Forty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4×4 mm window on the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the unprotected windows after 12–48 hr exposure to a demineralizing solution at pH-4.5. Near-IR reflectance images were acquired over several near-IR spectral distributions, visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Cross polarization optical coherence tomography (CP-OCT) was used to non-destructively assess the depth and severity of demineralization in each sample window. Matching two dimensional CP-OCT images of the lesion depth and integrated reflectivity were compared with the reflectance and fluorescence images to determine how accurately the variation in the lesion contrast represents the variation in the lesion severity. Results Artificial lesions appear more uniform on tooth surfaces exposed to an acid challenge at visible wavelengths than they do in the near-IR. Measurements of the lesion depth and severity using CP-OCT show that the lesion severity varies markedly across the sample windows and that the lesion

Is Ghrelin Synthesized in the Central Nervous System?

PubMed Central

Cabral, Agustina; López Soto, Eduardo J.; Epelbaum, Jacques; Perelló, Mario

2017-01-01

Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals. PMID:28294994

Is Ghrelin Synthesized in the Central Nervous System?

PubMed

Cabral, Agustina; López Soto, Eduardo J; Epelbaum, Jacques; Perelló, Mario

2017-03-15

Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.

Correlation of the erectile dysfunction with lesions of cerebrovascular accidents.

PubMed

Jeon, Sang-Wohn; Yoo, Koo Han; Kim, Tae-Hwan; Kim, Jin Il; Lee, Choong-Hyun

2009-01-01

The recent human and animal studies indicate that the central supraspinal systems controlling penile erection, which are localized predominantly in the parts of the frontal lobe and limbic system, are reported to be involved in erection. The purpose of this study was to elucidate the correlation of the erectile dysfunction (ED) with lesions of cerebrovascular accidents (CVA). Forty-four men were selected among the CVA patients who had visited our hospital between March and July 2006. The audiovisual sexual stimulation (AVSS) test was conducted using Rigiscan device on the patients, whose erectile domain score of the International Index of Erectile Function Questionnaire (IIEF) was less than 22. The criteria for adequate erectile function was the erectile events of > 60% rigidity for > or = 5 minutes. The CVA lesions were classified into frontal lobe, cortex except frontal lobe, basal ganglia, thalamus, and other area. Each CVA lesions of ED group and non-ED group were compared. IIEF, AVSS using Rigiscan. Thirty-eight patients' erectile domain score of IIEF were less than 22, and the AVSS test was conducted on them. Eighteen patients showed no ED, and 20 patients showed ED. The mean age of the ED group was 60.40 +/- 2.2, and the mean age of non-ED group was 55.29 +/- 1.85. There was no statistically significant difference between the mean age of both groups (P = 0.081). As each CVA lesions of both groups were compared, the CVA lesions of the thalamic area in the ED group were significantly more than in the non-ED group (P = 0.010). Patients (47.4%) who were suggestive of ED in the IIEF has no ED in the AVSS test. The patients who had CVA lesions in the thalamic area more commonly showed ED than the patients with CVA lesions of any other areas.

Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.

PubMed

Bilic, I; Zoricic, I; Anic, T; Separovic, J; Stancic-Rokotov, D; Mikus, D; Buljat, G; Ivankovic, D; Aralica, G; Prkacin, I; Perovic, D; Mise, S; Rotkvic, I; Petek, M; Rucman, R; Seiwerth, S; Sikiric, P

2001-03-09

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

ERIC Educational Resources Information Center

Drew, Liam J.; Fusi, Stefano; Hen, René

2013-01-01

In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

Possible involvement of SINEs in mammalian-specific brain formation

PubMed Central

Sasaki, Takeshi; Nishihara, Hidenori; Hirakawa, Mika; Fujimura, Koji; Tanaka, Mikiko; Kokubo, Nobuhiro; Kimura-Yoshida, Chiharu; Matsuo, Isao; Sumiyama, Kenta; Saitou, Naruya; Shimogori, Tomomi; Okada, Norihiro

2008-01-01

Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor. PMID:18334644

Possible involvement of SINEs in mammalian-specific brain formation.

PubMed

Sasaki, Takeshi; Nishihara, Hidenori; Hirakawa, Mika; Fujimura, Koji; Tanaka, Mikiko; Kokubo, Nobuhiro; Kimura-Yoshida, Chiharu; Matsuo, Isao; Sumiyama, Kenta; Saitou, Naruya; Shimogori, Tomomi; Okada, Norihiro

2008-03-18

Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.

The development of an MRI lesion quantifying system for multiple sclerosis patients undergoing treatment

NASA Astrophysics Data System (ADS)

Moin, Paymann; Ma, Kevin; Amezcua, Lilyana; Gertych, Arkadiusz; Liu, Brent

2009-02-01

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that affects approximately 2.5 million people worldwide. Magnetic resonance imaging (MRI) is an established tool for the assessment of disease activity, progression and response to treatment. The progression of the disease is variable and requires routine follow-up imaging studies. Currently, MRI quantification of multiple sclerosis requires a manual approach to lesion measurement and yields an estimate of lesion volume and interval change. In the setting of several prior studies and a long treatment history, trends related to treatment change quickly become difficult to extrapolate. Our efforts seek to develop an imaging informatics based MS lesion computer aided detection (CAD) package to quantify and track MS lesions including lesion load, volume, and location. Together, with select clinical parameters, this data will be incorporated into an MS specific e- Folder to provide decision support to evaluate and assess treatment options for MS in a manner tailored specifically to an individual based on trends in MS presentation and progression.

Mechanisms of mammalian iron homeostasis

PubMed Central

Pantopoulos, Kostas; Porwal, Suheel Kumar; Tartakoff, Alan; Devireddy, L.

2012-01-01

Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iron. Disruption of iron homeostasis is associated with various human diseases: iron deficiency resulting from defects in acquisition or distribution of the metal causes anemia; whereas iron surfeit resulting from excessive iron absorption or defective utilization causes abnormal tissue iron deposition, leading to oxidative damage. Mammals utilize distinct mechanisms to regulate iron homeostasis at the systemic and cellular levels. These involve the hormone hepcidin and iron regulatory proteins, which collectively ensure iron balance. This review outlines recent advances in iron regulatory pathways, as well as in mechanisms underlying intracellular iron trafficking, an important but less-studied area of mammalian iron homeostasis. PMID:22703180

Bioenergetics of Mammalian Sperm Capacitation

PubMed Central

Ferramosca, Alessandra; Zara, Vincenzo

2014-01-01

After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods. PMID:24791005

Bioenergetics of mammalian sperm capacitation.

PubMed

Ferramosca, Alessandra; Zara, Vincenzo

2014-01-01

After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

Molecular sled sequences are common in mammalian proteins.

PubMed

Xiong, Kan; Blainey, Paul C

2016-03-18

Recent work revealed a new class of molecular machines called molecular sleds, which are small basic molecules that bind and slide along DNA with the ability to carry cargo along DNA. Here, we performed biochemical and single-molecule flow stretching assays to investigate the basis of sliding activity in molecular sleds. In particular, we identified the functional core of pVIc, the first molecular sled characterized; peptide functional groups that control sliding activity; and propose a model for the sliding activity of molecular sleds. We also observed widespread DNA binding and sliding activity among basic polypeptide sequences that implicate mammalian nuclear localization sequences and many cell penetrating peptides as molecular sleds. These basic protein motifs exhibit weak but physiologically relevant sequence-nonspecific DNA affinity. Our findings indicate that many mammalian proteins contain molecular sled sequences and suggest the possibility that substantial undiscovered sliding activity exists among nuclear mammalian proteins. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Rheotaxis facilitates upstream navigation of mammalian sperm cells

PubMed Central

Kantsler, Vasily; Dunkel, Jörn; Blayney, Martyn; Goldstein, Raymond E

2014-01-01

A major puzzle in biology is how mammalian sperm maintain the correct swimming direction during various phases of the sexual reproduction process. Whilst chemotaxis may dominate near the ovum, it is unclear which cues guide spermatozoa on their long journey towards the egg. Hypothesized mechanisms range from peristaltic pumping to temperature sensing and response to fluid flow variations (rheotaxis), but little is known quantitatively about them. We report the first quantitative study of mammalian sperm rheotaxis, using microfluidic devices to investigate systematically swimming of human and bull sperm over a range of physiologically relevant shear rates and viscosities. Our measurements show that the interplay of fluid shear, steric surface-interactions, and chirality of the flagellar beat leads to stable upstream spiralling motion of sperm cells, thus providing a generic and robust rectification mechanism to support mammalian fertilisation. A minimal mathematical model is presented that accounts quantitatively for the experimental observations. DOI: http://dx.doi.org/10.7554/eLife.02403.001 PMID:24867640

Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export.

PubMed

Li, Ping; Noegel, Angelika A

2015-11-16

Nuclear export of messenger ribonucleoproteins (mRNPs) through the nuclear pore complex (NPC) can be roughly classified into two forms: bulk and specific export, involving an nuclear RNA export factor 1 (NXF1)-dependent pathway and chromosome region maintenance 1 (CRM1)-dependent pathway, respectively. SUN proteins constitute the inner nuclear envelope component of the l I: nker of N: ucleoskeleton and C: ytoskeleton (LINC) complex. Here, we show that mammalian cells require SUN1 for efficient nuclear mRNP export. The results indicate that both SUN1 and SUN2 interact with heterogeneous nuclear ribonucleoprotein (hnRNP) F/H and hnRNP K/J. SUN1 depletion inhibits the mRNP export, with accumulations of both hnRNPs and poly(A)+RNA in the nucleus. Leptomycin B treatment indicates that SUN1 functions in mammalian mRNA export involving the NXF1-dependent pathway. SUN1 mediates mRNA export through its association with mRNP complexes via a direct interaction with NXF1. Additionally, SUN1 associates with the NPC through a direct interaction with Nup153, a nuclear pore component involved in mRNA export. Taken together, our results reveal that the inner nuclear envelope protein SUN1 has additional functions aside from being a central component of the LINC complex and that it is an integral component of the mammalian mRNA export pathway suggesting a model whereby SUN1 recruits NXF1-containing mRNP onto the nuclear envelope and hands it over to Nup153. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells.

PubMed

Moore, Darcie L; Jessberger, Sebastian

2017-01-01

Accumulating evidence suggests that mammalian cells asymmetrically segregate cellular components ranging from genomic DNA to organelles and damaged proteins during cell division. Asymmetric inheritance upon mammalian cell division may be specifically important to ensure cellular fitness and propagate cellular potency to individual progeny, for example in the context of somatic stem cell division. We review here recent advances in the field and discuss potential effects and underlying mechanisms that mediate asymmetric segregation of cellular components during mammalian cell division. Copyright © 2016 Elsevier Ltd. All rights reserved.

Magnetochronology of the Oligocene mammalian faunas in the Lanzhou Basin, Northwest China

NASA Astrophysics Data System (ADS)

Zhang, Peng; Ao, Hong; Dekkers, Mark J.; An, Zhisheng; Wang, Lijuan; Li, Yongxiang; Liu, Shihang; Qiang, Xiaoke; Chang, Hong; Zhao, Hui

2018-06-01

The fluvio-lacustrine sequence in the Lanzhou Basin, located at the northeastern margin of the Tibetan Plateau, is a rich source of Oligocene-Miocene mammalian fossils, critical to our understanding of the terrestrial Asian mammal and environmental evolution. While the Miocene mammalian faunas have been dated with magnetostratigraphy, the numerical age of the Oligocene faunas remains controversial. Here, we present new high-resolution magnetostratigraphic records from two fluvio-lacustrine sections in the central Lanzhou Basin, which provide age constraints for two Oligocene mammal assemblages in the Lower Xianshuihe Formation, the Nanpoping and Xiagou Faunas. The Lower Xianshuihe Formation is suggested to span from polarity chrons C12r to C7n, ranging from ca 31 Ma to 24 Ma. The Early Oligocene Nanpoping Fauna correlates to the C12r-C11n.2n polarity chron intervals, yielding an age of ∼31-30 Ma, while the Late Oligocene Xiagou Fauna correlates to chrons C7An-C8n.2n, with an age of ∼26-25 Ma. This magnetostratigraphy provides a more accurate age than biochronology for the Oligocene giant mammal Indricotheriinae contained in the Nanpoping Fauna and sheds new light on the chronology and distribution of Indricotheriinae in Eurasia. The faunas, in particular the Nanpoping Fauna, suggest a mixed setting of woodlands and grasslands associated with a humid environment in the Lanzhou Basin during Early Oligocene, in contrast to its present arid environment with few woodlands.

Odor Coding by a Mammalian Receptor Repertoire

PubMed Central

Saito, Harumi; Chi, Qiuyi; Zhuang, Hanyi; Matsunami, Hiro; Mainland, Joel D.

2009-01-01

Deciphering olfactory encoding requires a thorough description of the ligands that activate each odorant receptor (OR). In mammalian systems, however, ligands are known for fewer than 50 of over 1400 human and mouse ORs, greatly limiting our understanding of olfactory coding. We performed high-throughput screening of 93 odorants against 464 ORs expressed in heterologous cells and identified agonists for 52 mouse and 10 human ORs. We used the resulting interaction profiles to develop a predictive model relating physicochemical odorant properties, OR sequences, and their interactions. Our results provide a basis for translating odorants into receptor neuron responses and unraveling mammalian odor coding. PMID:19261596

Membrane penetrating peptides greatly enhance baculovirus transduction efficiency into mammalian cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Hong-Zhang; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, ROC; Wu, Carol P.

2011-02-11

Research highlights: {yields} Ligation of CTP with GP64 enhances baculovirus transduction into mammalian cells. {yields} Fusion of PTD with VP39 enhances baculovirus transduction into mammalian cells. {yields} CTP and PTD-carrying viruses improve the transduction of co-transduced baculoviruses. {yields} Virus entry and gene expression can be separate events in different cell types. -- Abstract: The baculovirus group of insect viruses is widely used for foreign gene introduction into mammalian cells for gene expression and protein production; however, the efficiency of baculovirus entry into mammalian cells is in general still low. In this study, two recombinant baculoviruses were engineered and their abilitymore » to improve viral entry was examined: (1) cytoplasmic transduction peptide (CTP) was fused with baculovirus envelope protein, GP64, to produce a cytoplasmic membrane penetrating baculovirus (vE-CTP); and (2) the protein transduction domain (PTD) of HIV TAT protein was fused with the baculovirus capsid protein VP39 to form a nuclear membrane penetrating baculovirus (vE-PTD). Transduction experiments showed that both viruses had better transduction efficiency than vE, a control virus that only expresses EGFP in mammalian cells. Interestingly, vE-CTP and vE-PTD were also able to improve the transduction efficiency of a co-transduced baculovirus, resulting in higher levels of gene expression. Our results have described new routes to further enhance the development of baculovirus as a tool for gene delivery into mammalian cells.« less

Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species

PubMed Central

Rosselló, Ricardo Antonio; Chen, Chun-Chun; Dai, Rui; Howard, Jason T; Hochgeschwender, Ute; Jarvis, Erich D

2013-01-01

Cells are fundamental units of life, but little is known about evolution of cell states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that have been re-programmed to an embryonic stem cell-like state, providing a powerful platform for biology and medicine. However, they have been limited to a few mammalian species. Here we found that a set of four mammalian transcription factor genes used to generate iPSCs in mouse and humans can induce a partially reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. These findings are one of the first to show cross-lineage stem cell-like induction, and to generate pluripotent-like cells for several of these species with in vivo chimeras. We suggest that the stem-cell state may be highly conserved across a wide phylogenetic range. DOI: http://dx.doi.org/10.7554/eLife.00036.001 PMID:24015354

Epidemiology of Ocular Toxoplasmosis in Three Community Surveys in the Central Region of Ghana, West Africa.

PubMed

Abu, Emmanuel Kwasi; Boampong, Johnson Nyarko; Amoabeng, Joseph Kwame; Ilechie, Alex A; Kyei, Samuel; Owusu-Ansah, Andrew; Boadi-Kusi, Samuel Bert; Amoani, Benjamin; Ayi, Irene

2016-01-01

To conduct the first ever population-based survey on ocular toxoplasmosis in the Central Region of Ghana. A cross-sectional population-based study was conducted in three randomly selected communities in the Central Region, Ghana. Visual acuity (VA) measurement, dilated fundus examination by indirect ophthalmoscopy and serology testing were performed on all participants. Ocular toxoplasmosis was diagnosed based on characteristic retinal lesions and supported by positive serologic testing using commercial enzyme-linked immunosorbent assay (ELISA) kits. A total of 390 subjects aged 10-100 years (mean age 47 years) were examined; 118 (30.3%) were male and 272 (69.7%) female. Ten subjects (6 females and 4 males) had toxoplasmic ocular lesions (prevalence 2.6%). Of these, two had bilateral lesions and eight had unilateral lesions. Subjects with toxoplasmic ocular lesions were older than those without lesions (p = 0.028). The development of ocular toxoplasmosis was not associated with rural dwelling, sex, keeping cats, or consumption of meat. The prevalence of ocular toxoplasmosis in our Ghanaian study population was lower than findings from Southern Brazil, where there is a similar prevalence of infection in the general population.

Synaptic Mechanisms of Action of Convulsion-Producing Anticholinesterases. Characterization of Di-Isopropyl Phosphorofluoridate-Induced Epileptiform Activity in the Mammalian Hippocampus.

DTIC Science & Technology

1983-10-01

O ) OV6 ISOBSLET *SECURITY CLASSIFICATION OF THIS PAGE (Oc~ Dt. Entered) - 4 .. I,3...* %%S& P 4. A I IUN U ,13 ’ A ^II t~,.. I. f ltnew- A "viously...Abstr. 8:558, 1982. 73. Gustafsson, B., Galvan, M., Grafe, P . and Wigstrom, H. A transient outward current in a mammalian central neurone blocked by 4...TEST CHART N4ATIONAL BUREAU CF STANAROS -963 - A ............ ............ AD _ _ _ Report No. 1 SYNAPTIC MECHANISMS OF ACTION OF CONVULSION-PRODUCING

Postoperative MRI Evaluation of a Radiofrequency Cordotomy Lesion for Intractable Cancer Pain

PubMed Central

Vedantam, A.; Hou, P.; Chi, T.L.; Hess, K.R; Dougherty, P.M.; Bruera, E.; Viswanathan, A.

2017-01-01

BACKGROUND AND PURPOSE There are limited data on the use of postoperative imaging to evaluate the cordotomy lesion. We aimed to describe the cordotomy lesion by using postoperative MR imaging in patients after percutaneous cordotomy for intractable cancer pain. MATERIALS AND METHODS Postoperative MR imaging and clinical outcomes were prospectively obtained for 10 patients after percutaneous cordotomy for intractable cancer pain. Area, signal intensity, and location of the lesion were recorded. Clinical outcomes were measured by using the Visual Analog Scale and the Brief Pain Inventory–Short Form, and correlations with MR imaging metrics were evaluated. RESULTS Ten patients (5 men, 5 women; mean age, 58.5 ± 9.6 years) were included in this study. The cordotomy lesion was hyperintense with central hypointense foci on T2-weighted MR imaging, and it was centered in the anterolateral quadrant at the C1–C2 level. The mean percentage of total cord area lesioned was 24.9% ± 7.9%, and most lesions were centered in the dorsolateral region of the anterolateral quadrant (66% of the anterolateral quadrant). The number of pial penetrations correlated with the percentage of total cord area that was lesioned (r = 0.78; 95% CI, 0.44–0.89; P = .008) and the length of T2-weighted hyperintensity (r = 0.85; 95% CI, 0.54–0.89; P = .002). No significant correlations were found between early clinical outcomes and quantitative MR imaging metrics. CONCLUSIONS We describe qualitative and quantitative characteristics of a cordotomy lesion on early postoperative MR imaging. The size and length of the lesion on MR imaging correlate with the number of pial penetrations. Larger studies are needed to further investigate the clinical correlates of MR imaging metrics after percutaneous cordotomy. PMID:28209581

Evaluation of fluralaner and afoxolaner treatments to control flea populations, reduce pruritus and minimize dermatologic lesions in naturally infested dogs in private residences in west central Florida USA.

PubMed

Dryden, Michael W; Canfield, Michael S; Kalosy, Kimberly; Smith, Amber; Crevoiserat, Lisa; McGrady, Jennifer C; Foley, Kaitlin M; Green, Kathryn; Tebaldi, Chantelle; Smith, Vicki; Bennett, Tashina; Heaney, Kathleen; Math, Lisa; Royal, Christine; Sun, Fangshi

2016-06-28

A study was conducted to evaluate and compare the effectiveness of two different oral flea and tick products to control flea infestations, reduce pruritus and minimize dermatologic lesions over a 12 week period on naturally infested dogs in west central FL USA. Thirty-four dogs with natural flea infestations living in 17 homes were treated once with a fluralaner chew on study day 0. Another 27 dogs living in 17 different homes were treated orally with an afoxolaner chewable on day 0, once between days 28-30 and once again between days 54-60. All products were administered according to label directions by study investigators. Flea populations on pets were assessed using visual area counts and premise flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between days 28-30, 40-45, 54-60 and 82-86. Dermatologic assessments were conducted on day 0 and once monthly. Pruritus assessments were conducted by owners throughout the study. No concurrent treatments for existing skin disease (antibiotics, anti-inflammatories, anti-fungals) were allowed. Following the first administration of fluralaner or afoxolaner, flea populations on pets were reduced by 99.0 % and 99.3 %, respectively within 7 days. Flea populations on the fluralaner treated dogs were 0 (100 % efficacy) on days 54-60 and 82-86 after the administration of a single dose on day 0. Administration of 3 monthly doses of afoxolaner reduced flea populations by 100 % on days 82-86. Flea numbers in indoor-premises were markedly reduced in both treatment groups by days 82-86, with 100 % and 98.9 % reductions in flea trap counts in the fluralaner and afoxolaner treatment groups, respectively. Marked improvement was observed in FAD lesion scoring, Atopic Dermatitis lesions scoring (CADESI-4) and pruritus scores with both formulations. In a clinical field investigation conducted during the summer of 2015 in subtropical Florida, a single administration of an oral

Histopathological observations of human periimplantitis lesions.

PubMed

Berglundh, Tord; Gislason, Orn; Lekholm, Ulf; Sennerby, Lars; Lindhe, Jan

2004-05-01

The aim of the present study was to analyze some characteristics of advanced and progressive periimplantitis lesions in man. Soft tissue biopsies were obtained from 12 implants in six patients. The implants had been in function between 4 and 21 years and were, with one exception, located in the maxilla. The radiographic examination performed prior to biopsy revealed that all sites exhibited advanced bone loss. Further, clinical signs of severe inflammation, such as suppuration, swelling and/or fistula formation were detected in the majority of sites and seven of the 12 implants were found to be mobile at biopsy. Each biopsy was following fixation embedded in epoxy resin and sections were prepared for histometric and morphometric analysis. It was demonstrated (i). that all soft tissue units harbored large inflammatory cell infiltrates (ICT) that extended to a position apical of a pocket epithelium and (ii). that about 60% of the lesions were occupied by inflammatory cells, among which plasma cells dominated. Numerous amounts of PMN cells occurred not only in the pocket epithelium and adjacent connective tissue areas, but were also present in peri-vascular compartments in more central areas of the ICT.

THE EFFECT OF PHOTOPIGMENT BLEACHING ON FUNDUS AUTOFLUORESCENCE IN ACUTE CENTRAL SEROUS CHORIORETINOPATHY.

PubMed

Choi, Kwang-Eon; Yun, Cheolmin; Kim, Young-Ho; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

2017-03-01

To evaluate the effect of photobleaching on fundus autofluorescence (FAF) images in acute central serous chorioretinopathy. We obtained prephotobleaching and postphotobleaching images using an Optomap 200Tx, and photobleaching was induced with a Heidelberg Retina Angiograph 2. Degrees of photobleaching were assessed as grayscale values in Optomap images. Concordances among the three kinds of images were analyzed. Hyper-AF lesions in prephotobleaching images were classified as Type 1 (changed to normal-AF after photobleaching) and Type 2 (unchanged after photobleaching). The FAF composite patterns of central serous chorioretinopathy lesions were classified as diffuse or mottled. Initial and final best-corrected visual acuity, central retinal thickness, and disease duration were compared according to fovea FAF type. Forty-one eyes of 41 patients were analyzed. The lesion brightness of postphotobleaching Optomap FAF showed greater concordance with Heidelberg Retina Angiograph 2 FAF (94.74%) than the prephotobleaching Optomap FAF (80.49%). Eyes with Type 1 fovea had greater initial and final best-corrected visual acuity (20/23 vs. 20/41, 20/21 vs. 20/32, P < 0.0001, P = 0.001, respectively) and shorter disease duration (19.68 ± 12.98 vs. 51.55 ± 44.98 days, P = 0.043) than those with Type 2 fovea. However, eyes with diffuse Type 2 fovea had only lower initial and final best-corrected visual acuity (20/23 vs. 20/45, 20/21 vs. 20/36, P < 0.0001, P < 0.0001, respectively) than those with Type 1 fovea. Understanding the photobleaching effect is necessary for the accurate interpretation of FAF images. Furthermore, comparing prephotobleaching and postphotobleaching FAF images may be helpful for estimation of lesion status in central serous chorioretinopathy.

Differential signatures of bacterial and mammalian IMP dehydrogenase enzymes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, R.; Evans, G.; Rotella, F.

1999-06-01

IMP dehydrogenase (IMPDH) is an essential enzyme of de novo guanine nucleotide synthesis. IMPDH inhibitors have clinical utility as antiviral, anticancer or immunosuppressive agents. The essential nature of this enzyme suggests its therapeutic applications may be extended to the development of antimicrobial agents. Bacterial IMPDH enzymes show bio- chemical and kinetic characteristics that are different than the mammalian IMPDH enzymes, suggesting IMPDH may be an attractive target for the development of antimicrobial agents. We suggest that the biochemical and kinetic differences between bacterial and mammalian enzymes are a consequence of the variance of specific, identifiable amino acid residues. Identification ofmore » these residues or combination of residues that impart this mammalian or bacterial enzyme signature is a prerequisite for the rational identification of agents that specifically target the bacterial enzyme. We used sequence alignments of IMPDH proteins to identify sequence signatures associated with bacterial or eukaryotic IMPDH enzymes. These selections were further refined to discern those likely to have a role in catalysis using information derived from the bacterial and mammalian IMPDH crystal structures and site-specific mutagenesis. Candidate bacterial sequence signatures identified by this process include regions involved in subunit interactions, the active site flap and the NAD binding region. Analysis of sequence alignments in these regions indicates a pattern of catalytic residues conserved in all enzymes and a secondary pattern of amino acid conservation associated with the major phylogenetic groups. Elucidation of the basis for this mammalian/bacterial IMPDH signature will provide insight into the catalytic mechanism of this enzyme and the foundation for the development of highly specific inhibitors.« less

Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patient.

PubMed

Bernal-Cano, F; Joseph, J T; Koralnik, I J

2007-10-01

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. This disease is caused by a reactivation of the polyomavirus JC (JCV). Clinical presentation can be variable from patient to patient as lesions can occur anywhere in the CNS white matter; however, they appear to spare the optic nerves and the spinal cord. The authors present a case of PML in the setting of acquired immunodeficiency syndrome (AIDS) who developed PML lesions in the spinal cord, discovered during the postmortem examination. This finding is significant because PML has recently been diagnosed in patients with multiple sclerosis (MS) treated with the novel immunomodulatory medication natalizumab. Indeed, spinal cord lesions are frequent in MS. Therefore clinicians should be aware that in addition to the brain, PML may also affect the spinal cord white matter.

Regulation of Mammalian Gene Dosage by Long Noncoding RNAs

PubMed Central

Hung, Ko-Hsuan; Wang, Yang; Zhao, Jing Crystal

2013-01-01

Recent transcriptome studies suggest that long noncoding RNAs (lncRNAs) are key components of the mammalian genome, and their study has become a new frontier in biomedical research. In fact, lncRNAs in the mammalian genome were identified and studied at particular epigenetic loci, including imprinted loci and X-chromosome inactivation center, at least two decades ago—long before development of high throughput sequencing technology. Since then, researchers have found that lncRNAs play essential roles in various biological processes, mostly during development. Since much of our understanding of lncRNAs originates from our knowledge of these well-established lncRNAs, in this review we will focus on lncRNAs from the X-chromosome inactivation center and the Dlk1-Dio3 imprinted cluster as examples of lncRNA mechanisms functioning in the epigenetic regulation of mammalian genes. PMID:24970160

DNA Replication Origins and Fork Progression at Mammalian Telomeres

PubMed Central

Higa, Mitsunori; Fujita, Masatoshi; Yoshida, Kazumasa

2017-01-01

Telomeres are essential chromosomal regions that prevent critical shortening of linear chromosomes and genomic instability in eukaryotic cells. The bulk of telomeric DNA is replicated by semi-conservative DNA replication in the same way as the rest of the genome. However, recent findings revealed that replication of telomeric repeats is a potential cause of chromosomal instability, because DNA replication through telomeres is challenged by the repetitive telomeric sequences and specific structures that hamper the replication fork. In this review, we summarize current understanding of the mechanisms by which telomeres are faithfully and safely replicated in mammalian cells. Various telomere-associated proteins ensure efficient telomere replication at different steps, such as licensing of replication origins, passage of replication forks, proper fork restart after replication stress, and dissolution of post-replicative structures. In particular, shelterin proteins have central roles in the control of telomere replication. Through physical interactions, accessory proteins are recruited to maintain telomere integrity during DNA replication. Dormant replication origins and/or homology-directed repair may rescue inappropriate fork stalling or collapse that can cause defects in telomere structure and functions. PMID:28350373

Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

PubMed

Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C; DeAngelis, Lisa M; Fenstermaker, Robert A; Friedman, Allan; Gilbert, Mark R; Hattangadi-Gluth, Jona; Hesser, Deneen; Holdhoff, Matthias; Junck, Larry; Lawson, Ronald; Loeffler, Jay S; Moots, Paul L; Mrugala, Maciej M; Newton, Herbert B; Raizer, Jeffrey J; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tran, David; Tran, Nam; Vrionis, Frank D; Wen, Patrick Yung; McMillian, Nicole R; Ho, Maria

2014-11-01

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases. Copyright © 2014 by the National Comprehensive Cancer Network.

Mammalian evolution may not be strictly bifurcating.

PubMed

Hallström, Björn M; Janke, Axel

2010-12-01

The massive amount of genomic sequence data that is now available for analyzing evolutionary relationships among 31 placental mammals reduces the stochastic error in phylogenetic analyses to virtually zero. One would expect that this would make it possible to finally resolve controversial branches in the placental mammalian tree. We analyzed a 2,863,797 nucleotide-long alignment (3,364 genes) from 31 placental mammals for reconstructing their evolution. Most placental mammalian relationships were resolved, and a consensus of their evolution is emerging. However, certain branches remain difficult or virtually impossible to resolve. These branches are characterized by short divergence times in the order of 1-4 million years. Computer simulations based on parameters from the real data show that as little as about 12,500 amino acid sites could be sufficient to confidently resolve short branches as old as about 90 million years ago (Ma). Thus, the amount of sequence data should no longer be a limiting factor in resolving the relationships among placental mammals. The timing of the early radiation of placental mammals coincides with a period of climate warming some 100-80 Ma and with continental fragmentation. These global processes may have triggered the rapid diversification of placental mammals. However, the rapid radiations of certain mammalian groups complicate phylogenetic analyses, possibly due to incomplete lineage sorting and introgression. These speciation-related processes led to a mosaic genome and conflicting phylogenetic signals. Split network methods are ideal for visualizing these problematic branches and can therefore depict data conflict and possibly the true evolutionary history better than strictly bifurcating trees. Given the timing of tectonics, of placental mammalian divergences, and the fossil record, a Laurasian rather than Gondwanan origin of placental mammals seems the most parsimonious explanation.

Mammalian Evolution May not Be Strictly Bifurcating

PubMed Central

Hallström, Björn M.; Janke, Axel

2010-01-01

The massive amount of genomic sequence data that is now available for analyzing evolutionary relationships among 31 placental mammals reduces the stochastic error in phylogenetic analyses to virtually zero. One would expect that this would make it possible to finally resolve controversial branches in the placental mammalian tree. We analyzed a 2,863,797 nucleotide-long alignment (3,364 genes) from 31 placental mammals for reconstructing their evolution. Most placental mammalian relationships were resolved, and a consensus of their evolution is emerging. However, certain branches remain difficult or virtually impossible to resolve. These branches are characterized by short divergence times in the order of 1–4 million years. Computer simulations based on parameters from the real data show that as little as about 12,500 amino acid sites could be sufficient to confidently resolve short branches as old as about 90 million years ago (Ma). Thus, the amount of sequence data should no longer be a limiting factor in resolving the relationships among placental mammals. The timing of the early radiation of placental mammals coincides with a period of climate warming some 100–80 Ma and with continental fragmentation. These global processes may have triggered the rapid diversification of placental mammals. However, the rapid radiations of certain mammalian groups complicate phylogenetic analyses, possibly due to incomplete lineage sorting and introgression. These speciation-related processes led to a mosaic genome and conflicting phylogenetic signals. Split network methods are ideal for visualizing these problematic branches and can therefore depict data conflict and possibly the true evolutionary history better than strictly bifurcating trees. Given the timing of tectonics, of placental mammalian divergences, and the fossil record, a Laurasian rather than Gondwanan origin of placental mammals seems the most parsimonious explanation. PMID:20591845

Central giant cell granuloma in pediatric maxilla: surgical management.

PubMed

Faverani, Leonardo Perez; Ferreira, Sabrina; Ferreira, Gabriel Ramalho; Coléte, Juliana Zorzi; Aranega, Alessandra Marcondes; Garcia Júnior, Idelmo Rangel

2014-07-01

Central giant cell granuloma (CGCG) is an intraosseous lesion consisting of fibrous cellular tissue that contains multiple foci of hemorrhage, multinucleated giant cells, and occasional trabeculae of woven bone. An 8-year-old boy presented himself complaining of a painless swelling in the left maxilla that had started 1 year. Computed tomography (CT) scan confirmed a poorly defined multilocular radiolucent lesion in the left maxilla crossing the midline. The patient underwent enucleation through an intraoral approach of the lesion. The biopsy revealed multinucleated giant cells in a fibrous stroma. A CT was taken approximately 1 year postoperatively. There was no clinical or radiographic evidence of recurrence. Therefore, surgical treatment of CGCG can be performed, trying to preserve the surrounding anatomic structures, which can be maintained in case the lesion does not show an aggressive clinical behavior, avoiding large surgical defects which are undesirable in children.

Comparison of amphibian and mammalian thyroperoxidase ...

EPA Pesticide Factsheets

Thyroperoxidase (TPO) catalyzes the production of thyroid hormones in the vertebrate thyroid gland by oxidizing iodide (I- ) to produce iodinated tyrosines on thyroglobulin, and further coupling of specific mono- or di-iodinated tyrosines to generate the triiodo- and tetra-iodothyronine, precursors to thyroid hormone. This enzyme is a target for thyroid disrupting chemicals. TPO-inhibition by xenobiotics is a molecular initiating event that is known to perturb the thyroid axis by preventing synthesis of thyroid hormone. Previous work on TPO-inhibition has been focused on mammalian TPO; specifically, the rat and pig. A primary objective of this experiment was to directly measure TPO activity in a non-mammalian system, in this case a thyroid gland homogenate from Xenopus laevis; as well as compare chemical inhibition from past mammalian studies to the amphibian data generated. Thyroid glands obtained from X. laevis tadpoles at NF stages 58-60, were pooled and homogenized by sonication in phosphate buffer. This homogenate was then used to test 24 chemicals for inhibition of TPO as measured by conversion of Amplex UltraRed (AUR) substrate to its fluorescent product. The test chemicals were selected based upon previous results from rat in vitro TPO assays, and X. laevis in vitro and in vivo studies for thyroid disrupting endpoints, and included both positive and negative chemicals in these assays. An initial screening of the chemicals was done at a single high con

Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay

PubMed Central

Cortés-Gutiérrez, Elva I.; López-Fernández, Carmen; Fernández, José Luis; Dávila-Rodríguez, Martha I.; Johnston, Stephen D.; Gosálvez, Jaime

2014-01-01

Key Concepts The two-dimensional Two-Tailed Comet assay (TT-comet) protocol is a valuable technique to differentiate between single-stranded (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell.Protein lysis inherent with the TT-comet protocol accounts for differences in sperm protamine composition at a species-specific level to produce reliable visualization of sperm DNA damage.Alkaline treatment may break the sugar–phosphate backbone in abasic sites or at sites with deoxyribose damage, transforming these lesions into DNA breaks that are also converted into ssDNA. These lesions are known as Alkali Labile Sites “ALSs.”DBD–FISH permits the in situ visualization of DNA breaks, abasic sites or alkaline-sensitive DNA regions.The alkaline comet single assay reveals that all mammalian species display constitutive ALS related with the requirement of the sperm to undergo transient changes in DNA structure linked with chromatin packing.Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome.The TT is a valuable tool for identifying SSBs or DSBs in sperm cells with DNA fragmentation and can be therefore used for the purposes of fertility assessment. Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome. A series of methodologies to assess DNA damage in spermatozoa have been developed but most are unable to differentiate between single-stranded DNA breaks (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell. The two-dimensional Two-Tailed Comet assay (TT-comet) protocol highlighted in this review overcomes this limitation and emphasizes the importance in accounting for the difference in sperm protamine composition at a species-specific level for the appropriate preparation of the assay. The TT-comet is a modification of the original comet assay that uses a two dimensional electrophoresis to

Spectrum of MRI brain lesion patterns in neuromyelitis optica spectrum disorder: a pictorial review.

PubMed

Wang, Kevin Yuqi; Chetta, Justin; Bains, Pavit; Balzer, Anthony; Lincoln, John; Uribe, Tomas; Lincoln, Christie M

2018-06-01

Neuromyelitis optica is a neurotropic autoimmune inflammatory disease of the central nervous system traditionally thought to exclusively involve the optic nerves and spinal cord. With the discovery of the disease-specific aquaporin-4 antibody and the increasing recognition of clinical and characteristic imaging patterns of brain involvement in what is now termed neuromyelitis optica spectrum disorder (NMOSD), MRI now plays a greater role in diagnosis of NMOSD based on the 2015 consensus criteria and in distinguishing it from other inflammatory disorders, particularly multiple sclerosis (MS). Several brain lesion patterns are highly suggestive of NMOSD, whereas others may serve as red flags. Specifically, long corticospinal lesions, hemispheric cerebral white matter lesions and periependymal lesions in the diencephalon, dorsal brainstem and white matter adjacent to lateral ventricles are typical of NMOSD. In contrast, juxtacortical, cortical, or lesions perpendicularly oriented to the surface of the lateral ventricle suggests MS as the diagnosis. Ultimately, a strong recognition of the spectrum of MRI brain findings in NMOSD is essential for accurate diagnosis, and particularly in differentiating from MS. This pictorial review highlights the spectrum of characteristic brain lesion patterns that may be seen in NMOSD and further delineates findings that may help distinguish it from MS.

Reticuloendotheliosis virus: detection of immunological relationship to mammalian type C retroviruses.

PubMed Central

Charman, H P; Gilden, R V; Oroszlan, S

1979-01-01

Reticuloendotheliosis virus (REV) p30 shares cross-reactive determinants and a common NH2-terminal tripeptide with mammalian type C viral p30's. An interspecies competition radioimmunoassay was developed, using iodinated REV p30 and a broadly reactive antiserum to mammalian virus p30's. The avian leukosis-sarcoma viruses and mammalian non-type C retroviruses did not compete in this assay. Previous data indicating that the REV group is not represented completely in normal avian cell DNA lead us to speculate that this may be the first example of interclass transmission, albeit in the remote past, among the Retroviridae. PMID:87519

Proteins improving recombinant antibody production in mammalian cells.

PubMed

Nishimiya, Daisuke

2014-02-01

Mammalian cells have been successfully used for the industrial manufacture of antibodies due to their ability to synthesize antibodies correctly. Nascent polypeptides must be subjected to protein folding and assembly in the ER and the Golgi to be secreted as mature proteins. If these reactions do not proceed appropriately, unfolded or misfolded proteins are degraded by the ER-associated degradation (ERAD) pathway. The accumulation of unfolded proteins or intracellular antibody crystals accompanied by this failure triggers the unfolded protein response (UPR), which can considerably attenuate the levels of translation, folding, assembly, and secretion, resulting in reduction of antibody productivity. Accumulating studies by omics-based analysis of recombinant mammalian cells suggest that not only protein secretion processes including protein folding and assembly but also translation are likely to be the rate-limiting factors for increasing antibody production. Here, this review describes the mechanism of antibody folding and assembly and recent advantages which could improve recombinant antibody production in mammalian cells by utilizing proteins such as ER chaperones or UPR-related proteins.

Acute abdominal pain as the only symptom of a thoracic demyelinating lesion in multiple sclerosis.

PubMed

Nomura, Shohei; Shimakawa, Shuichi; Kashiwagi, Mitsuru; Tanabe, Takuya; Fukui, Miho; Tamai, Hiroshi

2015-11-01

Multiple sclerosis (MS) is a syndrome characterized by complex neurological symptoms resulting from demyelinating lesions in the central nervous system. We report a child with a relapse of MS whose only presenting symptom was severe abdominal pain. Dysfunctional intestinal mobility was assessed by abdominal computed tomography. Findings resembled paralytic ileus resulting from peritonitis. However, the patient demonstrated no other symptoms of peritonitis. A T2-weighted magnetic resonance image revealed a new demyelinating lesion localized to thoracic segments T4-T12. The lesion presumably affected autonomic efferents involved in intestinal mobility. Treatment with a pulse of methylprednisolone reduced both abdominal pain and lesion size. To our knowledge, this is the first reported case of a pediatric MS patient with a demyelinating lesion associated with an autonomic symptom of altered intestinal mobility in the absence of neurological symptoms. This atypical presentation of MS highlights the need for physicians' vigilance when treating this patient population. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Rab-NANOPS: FRET biosensors for Rab membrane nanoclustering and prenylation detection in mammalian cells.

PubMed

Najumudeen, Arafath Kaja; Guzmán, Camilo; Posada, Itziar M D; Abankwa, Daniel

2015-01-01

Rab proteins constitute the largest subfamily of Ras-like small GTPases. They are central to vesicular transport and organelle definition in eukaryotic cells. Unlike their Ras counterparts, they are not a hallmark of cancer. However, a number of diseases, including cancer, show a misregulation of Rab protein activity. As for all membrane-anchored signaling proteins, correct membrane organization is critical for Rabs to operate. In this chapter, we provide a detailed protocol for the use of a flow cytometry-based Fluorescence Resonance Energy Transfer (FRET)-biosensors assay, which allows to detect changes in membrane anchorage, subcellular distribution, and of the nanoscale organization of Rab-GTPases in mammalian cell lines. This assay is high-throughput amenable and can therefore be utilized in chemical-genomic and drug discovery efforts.

Where hearing starts: the development of the mammalian cochlea.

PubMed

Basch, Martin L; Brown, Rogers M; Jen, Hsin-I; Groves, Andrew K

2016-02-01

The mammalian cochlea is a remarkable sensory organ, capable of perceiving sound over a range of 10(12) in pressure, and discriminating both infrasonic and ultrasonic frequencies in different species. The sensory hair cells of the mammalian cochlea are exquisitely sensitive, responding to atomic-level deflections at speeds on the order of tens of microseconds. The number and placement of hair cells are precisely determined during inner ear development, and a large number of developmental processes sculpt the shape, size and morphology of these cells along the length of the cochlear duct to make them optimally responsive to different sound frequencies. In this review, we briefly discuss the evolutionary origins of the mammalian cochlea, and then describe the successive developmental processes that lead to its induction, cell cycle exit, cellular patterning and the establishment of topologically distinct frequency responses along its length. © 2015 Anatomical Society.

Structural differences between yeast and mammalian microtubules revealed by cryo-EM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howes, Stuart C.; Geyer, Elisabeth A.; LaFrance, Benjamin

Microtubules are polymers of αβ-tubulin heterodimers essential for all eukaryotes. Despite sequence conservation, there are significant structural differences between microtubules assembled in vitro from mammalian or budding yeast tubulin. Yeast MTs were not observed to undergo compaction at the interdimer interface as seen for mammalian microtubules upon GTP hydrolysis. Lack of compaction might reflect slower GTP hydrolysis or a different degree of allosteric coupling in the lattice. The microtubule plus end–tracking protein Bim1 binds yeast microtubules both between αβ-tubulin heterodimers, as seen for other organisms, and within tubulin dimers, but binds mammalian tubulin only at interdimer contacts. At the concentrationsmore » used in cryo-electron microscopy, Bim1 causes the compaction of yeast microtubules and induces their rapid disassembly. In conclusion, our studies demonstrate structural differences between yeast and mammalian microtubules that likely underlie their differing polymerization dynamics. These differences may reflect adaptations to the demands of different cell size or range of physiological growth temperatures.« less

Chemosignals, Hormones and Mammalian Reproduction

PubMed Central

Petrulis, Aras

2013-01-01

Many mammalian species use chemosignals to coordinate reproduction by altering the physiology and behavior of both sexes. Chemosignals prime reproductive physiology so that individuals become sexually mature and active at times when mating is most probable and suppress it when it is not. Once in reproductive condition, odors produced and deposited by both males and females are used to find and select individuals for mating. The production, dissemination and appropriate responses to these cues are modulated heavily by organizational and activational effects of gonadal sex steroids and thereby intrinsically link chemical communication to the broader reproductive context. Many compounds have been identified as “pheromones” but very few have met the expectations of that term: a unitary, species-typical substance that is both necessary and sufficient for an experience-independent behavioral or physiological response. In contrast, most responses to chemosignals are dependent or heavily modulated by experience, either in adulthood or during development. Mechanistically, chemosignals are perceived by both main and accessory (vomeronasal) olfactory systems with the importance of each system tied strongly to the nature of the stimulus rather than to the response. In the central nervous system, the vast majority of responses to chemosignals are mediated by cortical and medial amygdala connections with hypothalamic and other forebrain structures. Despite the importance of chemosignals in mammals, many details of chemical communication differ even among closely related species and defy clear categorization. Although generating much research and public interest, strong evidence for the existence of a robust chemical communication among humans is lacking. PMID:23545474

Short latency compound action potentials from mammalian gravity receptor organs

NASA Technical Reports Server (NTRS)

Jones, T. A.; Jones, S. M.

1999-01-01

Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

Imaging of the central skull base.

PubMed

Borges, Alexandra

2009-08-01

The central skull base (CSB) constitutes a frontier between the extracranial head and neck and the middle cranial fossa. The anatomy of this region is complex, containing most of the bony foramina and canals of the skull base traversed by several neurovascular structures that can act as routes of spread for pathologic processes. Lesions affecting the CSB can be intrinsic to its bony-cartilaginous components; can arise from above, within the intracranial compartment; or can arise from below, within the extracranial head and neck. Crosssectional imaging is indispensable in the diagnosis, treatment planning, and follow-up of patients with CSB lesions. This review focuses on a systematic approach to this region based on an anatomic division that takes into account the major tissue constituents of the CSB.

Imaging of the central skull base.

PubMed

Borges, Alexandra

2009-11-01

The central skull base (CSB) constitutes a frontier between the extracranial head and neck and the middle cranial fossa. The anatomy of this region is complex, containing most of the bony foramina and canals of the skull base traversed by several neurovascular structures that can act as routes of spread for pathologic processes. Lesions affecting the CSB can be intrinsic to its bony-cartilaginous components; can arise from above, within the intracranial compartment; or can arise from below, within the extracranial head and neck. Crosssectional imaging is indispensable in the diagnosis, treatment planning, and follow-up of patients with CSB lesions. This review focuses on a systematic approach to this region based on an anatomic division that takes into account the major tissue constituents of the CSB.

The Mammalian Cervical Vertebrae Blueprint Depends on the T (brachyury) Gene

PubMed Central

Kromik, Andreas; Ulrich, Reiner; Kusenda, Marian; Tipold, Andrea; Stein, Veronika M.; Hellige, Maren; Dziallas, Peter; Hadlich, Frieder; Widmann, Philipp; Goldammer, Tom; Baumgärtner, Wolfgang; Rehage, Jürgen; Segelke, Dierck; Weikard, Rosemarie; Kühn, Christa

2015-01-01

A key common feature of all but three known mammalian genera is the strict seven cervical vertebrae blueprint, suggesting the involvement of strong conserving selection forces during mammalian radiation. This is further supported by reports indicating that children with cervical ribs die before they reach reproductive age. Hypotheses were put up, associating cervical ribs (homeotic transformations) to embryonal cancer (e.g., neuroblastoma) or ascribing the constraint in cervical vertebral count to the development of the mammalian diaphragm. Here, we describe a spontaneous mutation c.196A > G in the Bos taurus T gene (also known as brachyury) associated with a cervical vertebral homeotic transformation that violates the fundamental mammalian cervical blueprint, but does not preclude reproduction of the affected individual. Genome-wide mapping, haplotype tracking within a large pedigree, resequencing of target genome regions, and bioinformatic analyses unambiguously confirmed the mutant c.196G allele as causal for this previously unknown defect termed vertebral and spinal dysplasia (VSD) by providing evidence for the mutation event. The nonsynonymous VSD mutation is located within the highly conserved T box of the T gene, which plays a fundamental role in eumetazoan body organization and vertebral development. To our knowledge, VSD is the first unequivocally approved spontaneous mutation decreasing cervical vertebrae number in a large mammal. The spontaneous VSD mutation in the bovine T gene is the first in vivo evidence for the hypothesis that the T protein is directly involved in the maintenance of the mammalian seven-cervical vertebra blueprint. It therefore furthers our knowledge of the T-protein function and early mammalian notochord development. PMID:25614605

Radiolucent rim as a possible diagnostic aid for differentiating jaw lesions

PubMed Central

Mortazavi, Hamed; Rahmani, Somayeh; Jafari, Soudeh; Parvaei, Parvin

2015-01-01

In this study, we formulate a new proposal that complements previous classifications in order to assist dental practitioners in performing a differential diagnosis based on patients' radiographs. We used general search engines and specialized databases such as Google Scholar, PubMed, PubMed Central, MedLine Plus, Science Direct, Scopus, and well-recognized textbooks to find relevant studies by using keywords such as "jaw disease," "jaw lesions," "radiolucent rim," "radiolucent border," and "radiolucent halo." More than 200 articles were found, of which 70 were broadly relevant to the topic. We ultimately included 50 articles that were closely related to the topic of interest. When the relevant data were compiled, the following eight lesions were identified as having a radiolucent rim: periapical cemento-osseous dysplasia, focal cemento-osseous dysplasia, florid cemento-osseous dysplasia, cemento-ossifying fibroma, osteoid osteoma, osteoblastoma, odontoma, and cementoblastoma. We propose a novel subcategory, jaw lesions with a radiolucent rim, which includes eight entities. The implementation of this new category can help improve the diagnoses that dental practitioners make based on patients' radiographs. PMID:26730374

The oxidation of cystamine and homocystamine by mammalian enzymes

PubMed Central

Bergeret, Bernadette; Blaschko, H.

1957-01-01

The oxidative deamination of cystamine and homocystamine by mammalian oxidases has been studied. The histaminase of pig kidney oxidizes homocystamine much more slowly than cystamine. The amine oxidase of mammalian liver (guinea-pig, rabbit) oxidizes homocystamine more rapidly than cystamine. Both amines are oxidized by plasma (or serum) of ruminants (ox, sheep, goat) and of the horse. In the enzymatic oxidation of homocystamine both aminogroups are removed; there is no evidence that a ring compound analogous to cystaldimine is accumulating. PMID:13489183

Rotation of single live mammalian cells using dynamic holographic optical tweezers

NASA Astrophysics Data System (ADS)

Bin Cao; Kelbauskas, Laimonas; Chan, Samantha; Shetty, Rishabh M.; Smith, Dean; Meldrum, Deirdre R.

2017-05-01

We report on a method for rotating single mammalian cells about an axis perpendicular to the optical system axis through the imaging plane using dynamic holographic optical tweezers (HOTs). Two optical traps are created on the opposite edges of a mammalian cell and are continuously transitioned through the imaging plane along the circumference of the cell in opposite directions, thus providing the torque to rotate the cell in a controlled fashion. The method enables a complete 360° rotation of live single mammalian cells with spherical or near-to spherical shape in 3D space, and represents a useful tool suitable for the single cell analysis field, including tomographic imaging.

Vertebrate brains and evolutionary connectomics: on the origins of the mammalian ‘neocortex’

PubMed Central

Karten, Harvey J.

2015-01-01

The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated ‘cortical’ manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple ‘subcortical’ groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as ‘evolutionary connectomics’, revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian ‘neocortex’, hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial ‘columns’ in the mammalian sensory and motor cortices. The molecular properties of these ‘nuclei’ in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae. PMID:26554047

FRET sensor-based quantification of intracellular trehalose in mammalian cells.

PubMed

Kikuta, Shingo; Hou, Bi-Huei; Sato, Ryoichi; Frommer, Wolf B; Kikawada, Takahiro

2016-01-01

Trehalose acts as a stress protectant and an autophagy inducer in mammalian cells. The molecular mechanisms of action remain obscure because intracellular trehalose at micromolar level is difficult to quantitate. Here, we show a novel trehalose monitoring technology based on FRET. FLIP-suc90μ∆1Venus sensor expressed in mammalian cells enables to quickly and non-destructively detect an infinitesimal amount of intracellular trehalose.

Intermolecular Interactions of Homologs of Germ Plasm Components in Mammalian Germ Cells

PubMed Central

Fox, Mark S.; Clark, Amander T.; El Majdoubi, Mohammed; Vigne, Jean-Louis; Urano, Jun; Hostetler, Chris E.; Griswold, Michael D.; Weiner, Richard I.; Pera, Renee A. Reijo

2007-01-01

In some species such as flies, worms, frogs, and fish the key to forming and maintaining early germ cell populations is the assembly of germ plasm, microscopically-distinct egg cytoplasm that is rich in RNAs, RNA-binding proteins and ribosomes. Cells which inherit germ plasm are destined for the germ cell lineage. In contrast, in mammals, germ cells are formed and maintained later in development as a result of inductive signaling from one embryonic cell type to another. Research advances, using complementary approaches, including identification of key signaling factors that act during the initial stages of germ cell development, differentiation of germ cells in vitro from mouse and human embryonic stem cells and the demonstration, that homologs of germ plasm components are conserved in mammals, have shed light on key elements in the early development of mammalian germ cells. Here, we use FRET (Fluorescence Resonance Energy Transfer) to demonstrate that living mammalian germ cells possess specific RNA/protein complexes that contain germ plasm homologs, beginning in the earliest stages of development examined. Moreover, we demonstrate that although both human and mouse germ cells and embryonic stem cells express the same proteins, germ cell specific protein/protein interactions distinguish germ cells from precursor embryonic stem cells in vitro; interactions also determine sub-cellular localization of complex components. Finally, we suggest that assembly of similar protein complexes may be central to differentiation of diverse cell lineages and provide useful diagnostic tools for isolation of specific cell types from the assorted types differentiated from embryonic stem cells. PMID:16996493

1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1999-02-12

This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conferencemore » sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.« less

Combined Palmer Type 1A and 1B Traumatic Lesions of the Triangular Fibrocartilage Complex A New Category.

PubMed

Nance, Erin; Ayalon, Omri; Yang, Steven

2016-06-01

We present a series of eight patients who underwent wrist arthroscopy for presumed solitary tears of the triangular fibrocartilage (TFC) and were, instead, found to have combined 1A (central tear) and 1B (ulnar avulsion) tears. The Palmer Classification does not currently categorize this combined pattern. All but one patient had a traumatic injury. Each subject had preoperative radiographs and MRI scans. TFC tears were evident on all MRI scans, though only one was suggestive of a combined tear pat - tern. Surgical management included arthroscopic central tear debridement and ulnar peripheral repair. Average follow-up was 22 months. Grip strength in the affected hand improved from 16% deficit as compared to the unaffected side, to 3.5% deficit postoperatively (p = 0.003), and visual analog scores (VAS) decreased from an average of 7.1/10 preoperatively to 2.3/10 postoperatively (p < 0.001). There was no statistically significant change in wrist range of motion (ROM), however. Arthroscopic debridement of the central perforation (1A lesion) with concomitant repair of the ulnar detachment (1B lesion) resulted in functional and symptomatic improvement. This combined 1A/1B TFC injury is not reliably diagnosed preoperatively and should be considered a new subset in the Palmer classification, as this will raise awareness of its presence and assist in preoperative planning of such lesions.

Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase.

PubMed

Simonicova, Lucia; Dudekova, Henrieta; Ferenc, Jaroslav; Prochazkova, Katarina; Nebohacova, Martina; Dusinsky, Roman; Nosek, Jozef; Tomaska, Lubomir

2015-11-01

The experimental evidence from the last decade made telomerase a prominent member of a family of moonlighting proteins performing different functions at various cellular loci. However, the study of extratelomeric functions of the catalytic subunit of mammalian telomerase (TERT) is often complicated by the fact that it is sometimes difficult to distinguish them from its role(s) at the chromosomal ends. Here, we present an experimental model for studying the extranuclear function(s) of mammalian telomerase in the yeast Saccharomyces cerevisiae. We demonstrate that the catalytic subunit of mammalian telomerase protects the yeast cells against oxidative stress and affects the stability of the mitochondrial genome. The advantage of using S. cerevisiae to study of mammalian telomerase is that (1) mammalian TERT does not interfere with its yeast counterpart in the maintenance of telomeres, (2) yeast telomerase is not localized in mitochondria and (3) it does not seem to be involved in the protection of cells against oxidative stress and stabilization of mtDNA. Thus, yeast cells can be used as a 'test tube' for reconstitution of mammalian TERT extranuclear function(s).

Exploring the read-write genome: mobile DNA and mammalian adaptation.

PubMed

Shapiro, James A

2017-02-01

The read-write genome idea predicts that mobile DNA elements will act in evolution to generate adaptive changes in organismal DNA. This prediction was examined in the context of mammalian adaptations involving regulatory non-coding RNAs, viviparous reproduction, early embryonic and stem cell development, the nervous system, and innate immunity. The evidence shows that mobile elements have played specific and sometimes major roles in mammalian adaptive evolution by generating regulatory sites in the DNA and providing interaction motifs in non-coding RNA. Endogenous retroviruses and retrotransposons have been the predominant mobile elements in mammalian adaptive evolution, with the notable exception of bats, where DNA transposons are the major agents of RW genome inscriptions. A few examples of independent but convergent exaptation of mobile DNA elements for similar regulatory rewiring functions are noted.

Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popescu, Bogdan F.; Frischer, Josa M.; Webb, Samuel M.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis. We found that the distributionmore » of iron and zinc is heterogeneous in MS plaques, and with few remarkable exceptions they do not accumulate in chronic MS lesions. We show that brain iron tends to decrease with increasing age and disease duration of MS patients; reactive astrocytes organized in large astrogliotic areas in a subset of smoldering and inactive plaques accumulate iron and safely store it in ferritin; a subset of smoldering lesions do not contain a rim of iron-loaded macrophages/microglia; and the iron content of shadow plaques varies with the stage of remyelination. Zinc in MS lesions was generally decreased, paralleling myelin loss. Iron accumulates concentrically in a subset of chronic inactive lesions suggesting that not all iron rims around MS lesions equate with smoldering plaques. Furthermore, upon degeneration of iron-loaded microglia/macrophages, astrocytes may form an additional protective barrier that may prevent iron-induced oxidative damage.« less

Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions

DOE PAGES

Popescu, Bogdan F.; Frischer, Josa M.; Webb, Samuel M.; ...

2017-03-22

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis. We found that the distributionmore » of iron and zinc is heterogeneous in MS plaques, and with few remarkable exceptions they do not accumulate in chronic MS lesions. We show that brain iron tends to decrease with increasing age and disease duration of MS patients; reactive astrocytes organized in large astrogliotic areas in a subset of smoldering and inactive plaques accumulate iron and safely store it in ferritin; a subset of smoldering lesions do not contain a rim of iron-loaded macrophages/microglia; and the iron content of shadow plaques varies with the stage of remyelination. Zinc in MS lesions was generally decreased, paralleling myelin loss. Iron accumulates concentrically in a subset of chronic inactive lesions suggesting that not all iron rims around MS lesions equate with smoldering plaques. Furthermore, upon degeneration of iron-loaded microglia/macrophages, astrocytes may form an additional protective barrier that may prevent iron-induced oxidative damage.« less

Comparisons of lesion detectability in ultrasound images acquired using time-shift compensation and spatial compounding.

PubMed

Lacefield, James C; Pilkington, Wayne C; Waag, Robert C

2004-12-01

The effects of aberration, time-shift compensation, and spatial compounding on the discrimination of positive-contrast lesions in ultrasound b-scan images are investigated using a two-dimensional (2-D) array system and tissue-mimicking phantoms. Images were acquired within an 8.8 x 12-mm2 field of view centered on one of four statistically similar 4-mm diameter spherical lesions. Each lesion was imaged in four planes offset by successive 45 degree rotations about the central scan line. Images of the lesions were acquired using conventional geometric focusing through a water path, geometric focusing through a 35-mm thick distributed aberration phantom, and time-shift compensated transmit and receive focusing through the aberration phantom. The views of each lesion were averaged to form sets of water path, aberrated, and time-shift compensated 4:1 compound images and 16:1 compound images. The contrast ratio and detectability index of each image were computed to assess lesion differentiation. In the presence of aberration representative of breast or abdominal wall tissue, time-shift compensation provided statistically significant improvements of contrast ratio but did not consistently affect the detectability index, and spatial compounding significantly increased the detectability index but did not alter the contrast ratio. Time-shift compensation and spatial compounding thus provide complementary benefits to lesion detection.

Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.

PubMed

Lyu, Zhe; Whitman, William B

2017-01-01

Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems.

The contribution of oxytocin and vasopressin to mammalian social behavior: potential role in autism spectrum disorder.

PubMed

Harony, Hala; Wagner, Shlomo

2010-01-01

Oxytocin (OT) and arginine-vasopressin (AVP) are 2 peptides that are produced in the brain and released via the pituitary gland to the peripheral blood, where they have diverse physiological functions. In the last 2 decades it has become clear that these peptides also play a central role in the modulation of mammalian social behavior by their actions within the brain. Several lines of evidence suggest their involvement in autism spectrum disorder (ASD), which is known to be associated with impaired social cognition and behavior. Recent clinical trials using OT administration to autistic patients have reported promising results. Here, we aim to describe the main data that suggest a connection between these peptides and ASD. Following a short illustration of several major topics in ASD biology we will (a) briefly describe the oxytocinergic and vasopressinergic systems in the brain, (b) discuss a few compelling cases manifesting the involvement of OT and AVP in mammalian social behavior, (c) describe data supporting the role of these peptides in human social cognition and behavior, and (d) discuss the possibility of the involvement of OT and AVP in ASD etiology, as well as the prospect of using these peptides as a treatment for ASD patients. Copyright © 2010 S. Karger AG, Basel.

Discharge rates in electromyography distinguish early between peripheral and central paresis.

PubMed

Jürgens, Tim P; Puchner, Christoph; Schulte-Mattler, Wilhelm J

2012-10-01

Abnormally increased discharge rates (DRs) of motor unit potentials on concentric needle electromyography (CNEMG) indicate a loss of motor units in peripheral neurogenic lesions. To determine when increased DRs occur during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG recordings of 19 patients with acute weakness of peripheral origin. The initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the lesion. Abnormally increased DRs (≥20/s) were found in all but 1 of the muscles in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all patients thereafter. The DRs depended on neither the kind of lesion nor the time between onset and CNEMG examination. The measurement of DRs of motor unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or worse to differentiate between a central and a peripheral lesion. Copyright © 2012 Wiley Periodicals, Inc.

Evolutionary history of mammalian sucking lice (Phthiraptera: Anoplura)

PubMed Central

2010-01-01

Background Sucking lice (Phthiraptera: Anoplura) are obligate, permanent ectoparasites of eutherian mammals, parasitizing members of 12 of the 29 recognized mammalian orders and approximately 20% of all mammalian species. These host specific, blood-sucking insects are morphologically adapted for life on mammals: they are wingless, dorso-ventrally flattened, possess tibio-tarsal claws for clinging to host hair, and have piercing mouthparts for feeding. Although there are more than 540 described species of Anoplura and despite the potential economical and medical implications of sucking louse infestations, this study represents the first attempt to examine higher-level anopluran relationships using molecular data. In this study, we use molecular data to reconstruct the evolutionary history of 65 sucking louse taxa with phylogenetic analyses and compare the results to findings based on morphological data. We also estimate divergence times among anopluran taxa and compare our results to host (mammal) relationships. Results This study represents the first phylogenetic hypothesis of sucking louse relationships using molecular data and we find significant conflict between phylogenies constructed using molecular and morphological data. We also find that multiple families and genera of sucking lice are not monophyletic and that extensive taxonomic revision will be necessary for this group. Based on our divergence dating analyses, sucking lice diversified in the late Cretaceous, approximately 77 Ma, and soon after the Cretaceous-Paleogene boundary (ca. 65 Ma) these lice proliferated rapidly to parasitize multiple mammalian orders and families. Conclusions The diversification time of sucking lice approximately 77 Ma is in agreement with mammalian evolutionary history: all modern mammal orders are hypothesized to have diverged by 75 Ma thus providing suitable habitat for the colonization and radiation of sucking lice. Despite the concordant timing of diversification events

Accurate GM atrophy quantification in MS using lesion-filling with co-registered 2D lesion masks☆

PubMed Central

Popescu, V.; Ran, N.C.G.; Barkhof, F.; Chard, D.T.; Wheeler-Kingshott, C.A.; Vrenken, H.

2014-01-01

Background In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images. Aim To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white matter volumes comparable to precise lesion masks. Methods 2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS patients, with nearest-neighbor (NNI), and tri-linear interpolation. As gold-standard, lesion masks were manually outlined on 3DT1-images. LEAP and FSL-lesion_filling were applied with each lesion mask. Grey (GM) and white matter (WM) volumes were quantified with FSL-FAST, and deep gray matter (DGM) volumes using FSL-FIRST. Volumes were compared between lesion mask types using paired Wilcoxon tests. Results Lesion-filling with gold-standard lesion masks compared to native images reduced GM overestimation by 1.93 mL (p < .001) for LEAP, and 1.21 mL (p = .002) for FSL-lesion_filling. Similar effects were achieved with NNI lesion masks from 2DT2. Global WM underestimation was not significantly influenced. GM and WM volumes from NNI, did not differ significantly from gold-standard. GM segmentation differed between lesion masks in the lesion area, and also elsewhere. Using the gold-standard, FSL-FAST quantified as GM on average 0.4% of the lesion area with LEAP and 24.5% with FSL-lesion_filling. Lesion-filling did not influence DGM volumes from FSL-FIRST. Discussion These results demonstrate that for global GM volumetry, precise lesion masks on 3DT1 images can be replaced by co-registered 2DT2 lesion masks. This makes lesion-filling a feasible method for GM atrophy measurements in MS. PMID:24567908

Amino acids as central synaptic transmitters or modulators in mammalian thermoregulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bligh, J.

1981-11-01

Of the amino acids that affect the activity of central neurons, aspartate and glutamate (which exert generally excitatory influences) and glycine, taurine, and ..gamma..-aminobutyric acid (GABA) (which generally exert inhibitory influences) are the strongest neurotransmitter candidates. As with other putative transmitter substances, their effects on body temperature when injected into the cerebral ventricles or the preoptic hypothalamus tend to vary within and between species. These effects are uninterpretable without accompanying information regarding effector activity changes and the influences of dose and ambient temperature. Observations necessary for analysis of apparent action have been made in studies of the effects of intracerebroventricularmore » injections of these amino acids into sheep. Aspartate and glutamate have similar excitatory effects on the pathway from cold sensors, whereas taurine and GABA exert inhibitory influences on the neural pathways that activate both heat production and heat loss effectors. Glycine appears to be without effect.« less

Sleep patterning and behaviour in cats with pontine lesions creating REM without atonia.

PubMed

Sanford; Morrison; Mann; Harris; Yoo; Ross

1994-12-01

Lesions of the dorsal pontine tegmentum release muscle tone and motor behaviour, much of it similar to orienting during wakefulness, into rapid eye movement sleep (REM), a state normally characterized by paralysis. Sleep after pontine lesions may be altered, with more REM-A episodes of shorter duration compared to normal REM. We examined behaviour, ponto-geniculo-occipital (PGO) waves (which may be central markers of orienting) and sleep in lesioned cats: (i) to characterize the relationship of PGO waves to behaviour in REM-A; (ii) to determine whether post-lesion changes in the timing and duration of REM-A episodes were due to activity-related awakenings: and (iii) to determine whether alterations in sleep changed the circadian sleep/wake cycle in cats. Behavioural release in REM-A was generally related to episode length, but episode length was not necessarily shorter than normal REM in cats capable of full locomotion in REM-A. PGO wave frequency was reduced overall during REM-A, but was higher during REM-A with behaviour than during quiet REM-A without overt behaviour. Pontine lesions did not significantly alter the circadian sleep/wake cycle: REM-A had approximately the same Light/Dark distribution as normal REM. Differences in the patterning of normal REM and REM-A within sleep involve more than mere movement-induced awakenings. Brainstem lesions that eliminate the atonia of REM may damage neural circuitry involved in REM initiation and maintenance; this circuitry is separate from circadian control mechanisms.

Diagnostic Pitfalls in Papillary Lesions of the Breast: Experience from a Single Tertiary Care Center

PubMed Central

Basavaiah, Sridevi Hanaganahalli; Sreeram, Saraswathy; Suresh, Pooja Kundapur; Kini, Hema; Adiga, Deepa; Sahu, Kausalya Kumari; Pai, Radha R

2016-01-01

Introduction Papillary neoplasms are a group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant. Aims This study was conducted to analyse the clinicopathological characteristics of papillary lesions of the breast. Materials and Methods A retrospective and prospective analysis of 34 cases of papillary lesions received over a period of 7 years from 2009 to 2015 was done. The patient’s clinical details were collected from medical archives and the histopathological findings were reviewed. The lesions were classified into benign, atypical and malignant categories. Results During the study period, there were 34 cases of papillary lesions of breast. The mean age was 58 years. The central quadrant was the most common location (66.6%). The most common presenting complaint was lump (76.5% cases). Papillary lesions presented more commonly as solitary lump (82.4%) rather than multifocal disease. Benign papillary lesions were more common than the atypical and malignant lesions. The most common papillary lesion accounting for 43% of the cases was intraductal papilloma. Malignant lesions accounted for 41.2% cases with intraductal papillary carcinoma and invasive papillary carcinoma constituting 14.7% cases each. Conclusion Diagnosis of papillary carcinoma is challenging and its classification includes different entities that have specific diagnostic criteria. Due to their heterozygosity in morphology with benign, atypical and malignant subtypes, morphological features such as type of fibrovascular core and continuity of myoepithelial layer along with immunohistochemical stains for myoepithelial cells should be considered for proper and accurate diagnosis. PMID:27656446

The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration.

PubMed

Cartoni, Romain; Norsworthy, Michael W; Bei, Fengfeng; Wang, Chen; Li, Siwei; Zhang, Yiling; Gabel, Christopher V; Schwarz, Thomas L; He, Zhigang

2016-12-21

Mitochondrial transport is crucial for neuronal and axonal physiology. However, whether and how it impacts neuronal injury responses, such as neuronal survival and axon regeneration, remain largely unknown. In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition. Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs). Importantly, Armcx1 also promotes both neuronal survival and axon regeneration after injury, and these effects depend on its mitochondrial localization. Furthermore, Armcx1 knockdown undermines both neuronal survival and axon regeneration in the high regenerative capacity model, further supporting a key role of Armcx1 in regulating neuronal injury responses in the adult central nervous system (CNS). Our findings suggest that Armcx1 controls mitochondrial transport during neuronal repair. Copyright © 2016 Elsevier Inc. All rights reserved.

Mammalian lipoxygenases and their biological relevance

PubMed Central

Kuhn, Hartmut; Banthiya, Swathi; van Leyen, Klaus

2015-01-01

Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. PMID:25316652

Mammalian polycistronic mRNAs and disease

PubMed Central

Karginov, Timofey A.; Hejazi Pastor, Daniel Parviz; Semler, Bert L.; Gomez, Christopher M.

2016-01-01

Our understanding of gene expression has come far since the “one-gene one-polypeptide” hypothesis proposed by Beadle and Tatum. This review addresses the gradual recognition that a growing number of polycistronic genes, originally discovered in viruses, are being identified within the mammalian genome, and that these may provide new insights into disease mechanisms and treatment. We have carried out a systematic literature review identifying 13 mammalian genes for which there is evidence for polycistronic expression via translation through an Internal Ribosome Entry Site (IRES). Although the canonical mechanism of translation initiation has been studied extensively, this review highlights a process of non-canonical translation, IRES-mediated translation, that is a growing source of understanding complex inheritance, elucidation of disease mechanisms, and discovery of novel therapeutic targets. Identification of additional polycistronic genes may provide new insights into disease therapy and allow for new discoveries of translational and disease mechanisms. PMID:28012572

Pluripotency and lineages in the mammalian blastocyst: an evolutionary view.

PubMed

Cañon, Susana; Fernandez-Tresguerres, Beatriz; Manzanares, Miguel

2011-06-01

Early mammalian development is characterized by a highly specific stage, the blastocyst, by which embryonic and extraembryonic lineages have been determined, but pattern formation has not yet begun. The blastocyst is also of interest because cell precursors of the embryo proper retain for a certain time the capability to generate all the cell types of the adult animal. This embryonic pluripotency is established and maintained by a regulatory network under the control of a small set of transcription factors, comprising Oct4, Sox2 and Nanog. This network is largely conserved in eutherian mammals, but there is scarce information about how it arose in vertebrates. We have analysed the conservation of gene regulatory networks controlling blastocyst lineages and pluripotency in the mouse by comparison with the chick. We found that few of elements of the network are novel to mammals; rather, most of them were present before the separation of the mammalian lineage from other amniotes, but acquired novel expression domains during early mammalian development. Our results strongly support the hypothesis that mammalian blastocyst regulatory networks evolved through rewiring of pre-existing components, involving the co-option and duplication of existing genes and the establishment of new regulatory interactions among them.

Uterine Vascular Lesions

PubMed Central

Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

2013-01-01

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.

PubMed

Johnson, S A; Lampert-Etchells, M; Pasinetti, G M; Rozovsky, I; Finch, C E

1992-01-01

This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

Programmable single-cell mammalian biocomputers.

PubMed

Ausländer, Simon; Ausländer, David; Müller, Marius; Wieland, Markus; Fussenegger, Martin

2012-07-05

Synthetic biology has advanced the design of standardized control devices that program cellular functions and metabolic activities in living organisms. Rational interconnection of these synthetic switches resulted in increasingly complex designer networks that execute input-triggered genetic instructions with precision, robustness and computational logic reminiscent of electronic circuits. Using trigger-controlled transcription factors, which independently control gene expression, and RNA-binding proteins that inhibit the translation of transcripts harbouring specific RNA target motifs, we have designed a set of synthetic transcription–translation control devices that could be rewired in a plug-and-play manner. Here we show that these combinatorial circuits integrated a two-molecule input and performed digital computations with NOT, AND, NAND and N-IMPLY expression logic in single mammalian cells. Functional interconnection of two N-IMPLY variants resulted in bitwise intracellular XOR operations, and a combinatorial arrangement of three logic gates enabled independent cells to perform programmable half-subtractor and half-adder calculations. Individual mammalian cells capable of executing basic molecular arithmetic functions isolated or coordinated to metabolic activities in a predictable, precise and robust manner may provide new treatment strategies and bio-electronic interfaces in future gene-based and cell-based therapies.

Ribosomal protein S6 kinase 1 signaling regulates mammalian lifespan

PubMed Central

Selman, Colin; Tullet, Jennifer M.A.; Wieser, Daniela; Irvine, Elaine; Lingard, Steven J.; Choudhury, Agharul I.; Claret, Marc; Al-Qassab, Hind; Carmignac, Danielle; Ramadani, Faruk; Woods, Angela; Robinson, Iain C.A.; Schuster, Eugene; Batterham, Rachel L.; Kozma, Sara C.; Thomas, George; Carling, David; Okkenhaug, Klaus; Thornton, Janet M.; Partridge, Linda; Gems, David; Withers, Dominic J.

2016-01-01

Caloric restriction (CR) protects against aging and disease but the mechanisms by which this affects mammalian lifespan are unclear. We show in mice that deletion of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway component ribosomal S6 protein kinase 1 (S6K1) led to increased lifespan and resistance to age-related pathologies such as bone, immune and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian lifespan, and suggest therapeutic manipulation of S6K1 and AMPK might mimic CR and provide broad protection against diseases of aging. PMID:19797661

Expression of recombinant sea urchin cellulase SnEG54 using mammalian cell lines.

PubMed

Okumura, Fumihiko; Kameda, Hiroyuki; Ojima, Takao; Hatakeyama, Shigetsugu

2010-05-07

We previously identified the cellulase SnEG54 from Japanese purple sea urchin Strongylocentrotus nudus, the molecular mass of which is about 54kDa on SDS-PAGE. It is difficult to express and purify a recombinant cellulase protein using bacteria such as Escherichia coli or yeast. In this study, we generated mammalian expression vectors encoding SnEG54 to transiently express SnEG54 in mammalian cells. Both SnEG54 expressed in mammalian cells and SnEG54 released into the culture supernatant showed hydrolytic activity toward carboxymethyl cellulose. By using a retroviral expression system, we also established a mammalian cell line that constitutively produces SnEG54. Unexpectedly, SnEG54 released into the culture medium was not stable, and the peak time showing the highest concentration was approximately 1-2days after seeding into fresh culture media. These findings suggest that non-mammalian sea urchin cellulase can be generated in human cell lines but that recombinant SnEG54 is unstable in culture medium due to an unidentified mechanism. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Structure of the Deactive State of Mammalian Respiratory Complex I.

PubMed

Blaza, James N; Vinothkumar, Kutti R; Hirst, Judy

2018-02-06

Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase

PubMed Central

Simonicova, Lucia; Dudekova, Henrieta; Ferenc, Jaroslav; Prochazkova, Katarina; Nebohacova, Martina; Dusinsky, Roman; Nosek, Jozef; Tomaska, Lubomir

2015-01-01

The experimental evidence from the last decade made telomerase a prominent member of a family of moonlighting proteins performing different functions at various cellular loci. However, the study of extratelomeric function(s) of the catalytic subunit of mammalian telomerase (TERT) is often complicated by the fact that it is sometimes difficult to distinguish them from its role(s) at chromosomal ends. Here we describe an experimental model for studying extranuclear function(s) of mammalian telomerase in the yeast Saccharomyces cerevisiae. We demonstrate that the catalytic subunit of mammalian telomerase protects the yeast cells against oxidative stress and affect the stability of mitochondrial genome. The advantage of using S. cerevisiae for the study of mammalian telomerase is that (i) mammalian TERT does not interfere with its yeast counterpart in the maintenance of telomeres, (ii) yeast telomerase is not localized in mitochondria and (iii) it does not seem to be involved in the protection of the cells against oxidative stress and in the stabilization of mtDNA. Thus yeast cells can be used as a ‘test tube’ for reconstitution of mammalian TERT extranuclear function(s). PMID:25567623

Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes.

PubMed

Middleton, Ryan C; Rogers, Russell G; De Couto, Geoffrey; Tseliou, Eleni; Luther, Kristin; Holewinski, Ronald; Soetkamp, Daniel; Van Eyk, Jennifer E; Antes, Travis J; Marbán, Eduardo

2018-01-01

Newts can regenerate amputated limbs and cardiac tissue, unlike mammals which lack broad regenerative capacity. Several signaling pathways involved in cell proliferation, differentiation and survival during newt tissue regeneration have been elucidated, however the factors that coordinate signaling between cells, as well as the conservation of these factors in other animals, are not well defined. Here we report that media conditioned by newt limb explant cells (A1 cells) protect mammalian cardiomyocytes from oxidative stress-induced apoptosis. The cytoprotective effect of A1-conditioned media was negated by exposing A1 cells to GW4869, which suppresses the generation of extracellular vesicles (EVs). A1-EVs are similar in diameter (~100-150 nm), structure, and share several membrane surface and cargo proteins with mammalian exosomes. However, isolated A1-EVs contain significantly higher levels of both RNA and protein per particle than mammalian EVs. Additionally, numerous cargo RNAs and proteins are unique to A1-EVs. Of particular note, A1-EVs contain numerous mRNAs encoding nuclear receptors, membrane ligands, as well as transcription factors. Mammalian cardiomyocytes treated with A1-EVs showed increased expression of genes in the PI3K/AKT pathway, a pivotal player in survival signaling. We conclude that newt cells secrete EVs with diverse, distinctive RNA and protein contents. Despite ~300 million years of evolutionary divergence between newts and mammals, newt EVs confer cytoprotective effects on mammalian cardiomyocytes.

Long-Term Modulation of Electrical Synapses in the Mammalian Thalamus

NASA Astrophysics Data System (ADS)

Landisman, Carole E.; Connors, Barry W.

2005-12-01

Electrical synapses are common between inhibitory neurons in the mammalian thalamus and neocortex. Synaptic modulation, which allows flexibility of communication between neurons, has been studied extensively at chemical synapses, but modulation of electrical synapses in the mammalian brain has barely been examined. We found that the activation of metabotropic glutamate receptors, via endogenous neurotransmitter or by agonist, causes long-term reduction of electrical synapse strength between the inhibitory neurons of the rat thalamic reticular nucleus.

Hypergravity signal transduction and gene expression in cultured mammalian cells

NASA Technical Reports Server (NTRS)

Kumei, Y.; Whitson, P. A.

1994-01-01

A number of studies have been conducted during space flight and with clinostats and centrifuges, suggesting that gravity effects the proliferation and differentiation of mammalian cells in vitro. However, little is known about the mechanisms by which mammalian cells respond to changes in gravitational stress. This paper summarizes studies designed to clarify the effects of hypergravity on the cultured human HeLa cells and to investigate the mechanism of hypergravity signal transduction in these cells.

Droplet size influences division of mammalian cell factories in droplet microfluidic cultivation.

PubMed

Periyannan Rajeswari, Prem Kumar; Joensson, Haakan N; Andersson-Svahn, Helene

2017-01-01

The potential of using droplet microfluidics for screening mammalian cell factories has been limited by the difficulty in achieving continuous cell division during cultivation in droplets. Here, we report the influence of droplet size on mammalian cell division and viability during cultivation in droplets. Chinese Hamster Ovary (CHO) cells, the most widely used mammalian host cells for biopharmaceuticals production were encapsulated and cultivated in 33, 180 and 320 pL droplets for 3 days. Periodic monitoring of the droplets during incubation showed that the cell divisions in 33 pL droplets stopped after 24 h, whereas continuous cell division was observed in 180 and 320 pL droplets for 72 h. The viability of the cells cultivated in the 33 pL droplets also dropped to about 50% in 72 h. In contrast, the viability of the cells in the larger droplets was above 90% even after 72 h of cultivation, making them a more suitable droplet size for 72-h cultivation. This study shows a direct correlation of microfluidic droplet size to the division and viability of mammalian cells. This highlights the importance of selecting suitable droplet size for mammalian cell factory screening assays. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anteroventral Third Ventricle Lesions Attenuate Pressor Responses to Serotonin in Anesthetized Rats

NASA Technical Reports Server (NTRS)

Muntzel, Martin S.; Lewis, Stephen J.; Johnson, Alan Kim

1996-01-01

When administered intravenously, serotonin (5-hydroxytryptamine; 5-HT) evokes a triphasic blood pressure response, consisting of the Bezold-Jarisch-associated depressor response, a pressor action, and long-lasting depressor response. Because the pressor response may, in part, be caused by central nervous system (CNS) activation by 5-HT, we predicted that destruction of the anteroventral third ventricle (AV3V) region, an area rich in 5-HT receptors, would attenuate increases in blood pressure to intravenous 5-HT. In anesthetized sham-lesioned and AV3V-lesioned Sprague-Dawley rats. we measured mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (SNA) to increasing bolus doses of intravenous 5-HT (1, 2.5, 5, 10, 25 microg/kg), before and after blockade of bradycardia using methylatropine (200 microg/kg). In all rats, bolus injections of 5-HT elicited bradycardia accompanied by a fall in lumbar SNA and an initial hypotension followed by a pressor response and a longer lasting hypotensive response. The bradycardia, reduction in lumbar SNA, and both depressor responses were equivalent in sham-lesioned and AV3V-lesioned groups. Importantly, AV3V lesions attenuated pressor responses to increasing doses of 5-HT (3 +/- 1, 6 +/- 4, 6 +/- 4, 17 +/- 4, 35 +/- 3 mmHg) compared to sham-lesioned controls (6 +/- 3, 16 +/- 7, 33 +/- 5, 54 +/- 4, 51 +/- 6 mmHg; P < 0.0001). This attenuation was conserved following blockade of bradycardia with methylatropine (P < 0.01). In summary, pressor responses to intravenous 5-HT are diminished by AV3V lesions. These data indicate that the pressor component of the blood pressure response to intravenous 5-HT is partly dependent upon interaction with the CNS.

Nucleus prepositus hypoglossi lesions produce a unique ocular motor syndrome

PubMed Central

Kim, Sung-Hee; Zee, David S.; du Lac, Sascha; Kim, Hyo Jung

2016-01-01

Objective: To describe the ocular motor abnormalities in 9 patients with a lesion involving the nucleus prepositus hypoglossi (NPH), a key constituent of a vestibular-cerebellar-brainstem neural network that ensures that the eyes are held steady in all positions of gaze. Methods: We recorded eye movements, including the vestibulo-ocular reflex during head impulses, in patients with vertigo and a lesion involving the NPH. Results: Our patients showed an ipsilesional-beating spontaneous nystagmus, horizontal gaze-evoked nystagmus more intense on looking toward the ipsilesional side, impaired pursuit more to the ipsilesional side, central patterns of head-shaking nystagmus, contralateral eye deviation, and decreased vestibulo-ocular reflex gain during contralesionally directed head impulses. Conclusions: We attribute these findings to an imbalance in the NPH–inferior olive–flocculus–vestibular nucleus loop, and the ocular motor abnormalities provide a new brainstem localization for patients with acute vertigo. PMID:27733568

KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.

PubMed

Rhodes, Kenneth J; Carroll, Karen I; Sung, M Amy; Doliveira, Lisa C; Monaghan, Michael M; Burke, Sharon L; Strassle, Brian W; Buchwalder, Lynn; Menegola, Milena; Cao, Jie; An, W Frank; Trimmer, James S

2004-09-08

Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family alpha subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family alpha subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP2, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 alpha subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.

Functional Significance of Hormonal Changes in Mammalian Fathers

PubMed Central

Saltzman, Wendy; Ziegler, Toni E.

2016-01-01

In the 5–10% of mammals in which both parents routinely provide infant care, fathers as well as mothers undergo systematic endocrine changes as they transition into parenthood. Although fatherhood-associated changes in such hormones and neuropeptides as prolactin, testosterone, glucocorticoids, vasopressin, and oxytocin have been characterised in only a small number of biparental rodents and primates, they appear to be more variable than corresponding changes in mothers, and experimental studies typically have not provided strong or consistent evidence that these endocrine shifts play causal roles in the activation of paternal care. Consequently, their functional significance remains unclear. We propose that endocrine changes in mammalian fathers may enable males to meet the species-specific demands of fatherhood by influencing diverse aspects of their behaviour and physiology, similar to many effects of hormones and neuropeptides in mothers. We review the evidence for such effects, focusing on recent studies investigating whether mammalian fathers in biparental species undergo systematic changes in 1) energetics and body composition, 2) neural plasticity, cognition, and sensory physiology, and 3) stress responsiveness and emotionality, all of which may be mediated by endocrine changes. The few published studies, based on a small number of rodent and primate species, suggest that hormonal and neuropeptide alterations in mammalian fathers might mediate shifts in paternal energy balance, body composition, and neural plasticity, but do not appear to have major effects on stress responsiveness or emotionality. Further research is needed on a wider variety of biparental mammals, under more naturalistic conditions, to more fully elucidate the functional significance of hormone and neuropeptide profiles of mammalian fatherhood and to clarify how fatherhood may trade off with, or perhaps enhance, aspects of organismal function in biparental mammals. PMID:25039657

Erythropoietin binding protein from mammalian serum

DOEpatents

Clemons, Gisela K.

1997-01-01

Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

InXy and SeXy, compact heterologous reporter proteins for mammalian cells.

PubMed

Fluri, David A; Kelm, Jens M; Lesage, Guillaume; Baba, Marie Daoud-El; Fussenegger, Martin

2007-10-15

Mammalian reporter proteins are essential for gene-function analysis, drugscreening initiatives and as model product proteins for biopharmaceutical manufacturing. Bacillus subtilis can maintain its metabolism by secreting Xylanase A (XynA), which converts xylan into shorter xylose oligosaccharides. XynA is a family 11 xylanase monospecific for D-xylose containing substrates. Mammalian cells transgenic for constitutive expression of wild-type xynA showed substantial secretion of this prokaryotic enzyme. Deletion analysis confirmed that a prokaryotic signal sequence encoded within the first 81 nucleotides was compatible with the secretory pathway of mammalian cells. Codon optimization combined with elimination of the prokaryotic signal sequence resulted in an exclusively intracellular mammalian Xylanase A variant (InXy) while replacement by an immunoglobulin-derived secretion signal created an optimal secreted Xylanase A derivative (SeXy). A variety of chromogenic and fluorescence-based assays adapted for use with mammalian cells detected InXy and SeXy with high sensitivity and showed that both reporter proteins resisted repeated freeze/thaw cycles, remained active over wide temperature and pH ranges, were extremely stable in human serum stored at room temperature and could independently be quantified in samples also containing other prominent reporter proteins such as the human placental alkaline phosphatase (SEAP) and the Bacillus stearothermophilus-derived secreted alpha-amylase (SAMY). Glycoprofiling revealed that SeXy produced in mammalian cells was N- glycosylated at four different sites, mutation of which resulted in impaired secretion. SeXy was successfully expressed in a variety of mammalian cell lines and primary cells following transient transfection and transduction with adeno-associated virus particles (AAV) engineered for constitutive SeXy expression. Intramuscular injection of transgenic AAVs into mice showed significant SeXy levels in the bloodstream

Mammalian Cell Tissue Culture.

PubMed

Phelan, Katy; May, Kristin M

2017-07-11

Cultured mammalian cells are used extensively in the field of human genetics. It requires a number of special skills in order to be able to preserve the structure, function, behavior, and biology of the cells in culture. This unit describes the basic skills required to maintain and preserve cell cultures: maintaining aseptic technique, preparing media with the appropriate characteristics, passaging, freezing and storage, recovering frozen stocks, and counting viable cells. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Direct Capture of Functional Proteins from Mammalian Plasma Membranes into Nanodiscs.

PubMed

Roy, Jahnabi; Pondenis, Holly; Fan, Timothy M; Das, Aditi

2015-10-20

Mammalian plasma membrane proteins make up the largest class of drug targets yet are difficult to study in a cell free system because of their intransigent nature. Herein, we perform direct encapsulation of plasma membrane proteins derived from mammalian cells into a functional nanodisc library. Peptide fingerprinting was used to analyze the proteome of the incorporated proteins in nanodiscs and to further demonstrate that the lipid composition of the nanodiscs directly affects the class of protein that is incorporated. Furthermore, the functionality of the incorporated membrane proteome was evaluated by measuring the activity of membrane proteins: Na(+)/K(+)-ATPase and receptor tyrosine kinases. This work is the first report of the successful establishment and characterization of a cell free functional library of mammalian membrane proteins into nanodiscs.

Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina.

PubMed

Sparrow, Janet R; Duncker, Tobias; Woods, Russell; Delori, François C

2016-01-01

Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina.

Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.

PubMed

Zakhari, N; Taccone, M S; Torres, C; Chakraborty, S; Sinclair, J; Woulfe, J; Jansen, G H; Nguyen, T B

2018-02-01

Centrally restricted diffusion has been demonstrated in recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess the accuracy of centrally restricted diffusion in the diagnosis of radiation necrosis in high-grade gliomas not treated with bevacizumab. In this prospective study, we enrolled patients with high-grade gliomas who developed a new ring-enhancing necrotic lesion and who underwent re-resection. The presence of a centrally restricted diffusion within the ring-enhancing lesion was assessed visually on diffusion trace images and by ADC measurements on 3T preoperative diffusion tensor examination. The percentage of tumor recurrence and radiation necrosis in each surgical specimen was defined histopathologically. The association between centrally restricted diffusion and radiation necrosis was assessed using the Fisher exact test. Differences in ADC and the ADC ratio between the groups were assessed via the Mann-Whitney U test, and receiver operating characteristic curve analysis was performed. Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation necrosis and 9 cases of tumor recurrence. There was significant association between centrally restricted diffusion by visual assessment and radiation necrosis ( P = .015) with a sensitivity of 75% and a specificity of 88.9%, a positive predictive value 85.7%, and a negative predictive value of 80% for the diagnosis of radiation necrosis. There was a statistically significant difference in the ADC and ADC ratio between radiation necrosis and tumor recurrence ( P = .027). The presence of centrally restricted diffusion in a new ring-enhancing lesion might indicate radiation necrosis rather than tumor recurrence in high-grade gliomas previously treated with standard chemoradiation without bevacizumab. © 2018 by American Journal of Neuroradiology.

Current perspectives of CASA applications in diverse mammalian spermatozoa.

PubMed

van der Horst, Gerhard; Maree, Liana; du Plessis, Stefan S

2018-03-26

Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.

Screening Mammalian Cells on a Hydrogel: Functionalized Small Molecule Microarray.

PubMed

Zhu, Biwei; Jiang, Bo; Na, Zhenkun; Yao, Shao Q

2017-01-01

Mammalian cell-based microarray technology has gained wide attention, for its plethora of promising applications. The platform is able to provide simultaneous information on multiple parameters for a given target, or even multiple target proteins, in a complex biological system. Here we describe the preparation of mammalian cell-based microarrays using selectively captured of human prostate cancer cells (PC-3). This platform was then used in controlled drug release and measuring the associated drug effects on these cancer cells.

Amygdala Lesions Reduce Cataplexy in Orexin KO mice

PubMed Central

Burgess, C.R.; Oishi, Y.; Mochizuki, T.; Peever, J.H.; Scammell, T.E.

2013-01-01

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of REM sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal grey, lateral pontine tegmentum, locus coeruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knockout mice, a model of narcolepsy. These lesions did not alter basic sleep/wake behavior, but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia. PMID:23739970

Micro-optical coherence tomography of the mammalian cochlea

PubMed Central

Iyer, Janani S.; Batts, Shelley A.; Chu, Kengyeh K.; Sahin, Mehmet I.; Leung, Hui Min; Tearney, Guillermo J.; Stankovic, Konstantina M.

2016-01-01

The mammalian cochlea has historically resisted attempts at high-resolution, non-invasive imaging due to its small size, complex three-dimensional structure, and embedded location within the temporal bone. As a result, little is known about the relationship between an individual’s cochlear pathology and hearing function, and otologists must rely on physiological testing and imaging methods that offer limited resolution to obtain information about the inner ear prior to performing surgery. Micro-optical coherence tomography (μOCT) is a non-invasive, low-coherence interferometric imaging technique capable of resolving cellular-level anatomic structures. To determine whether μOCT is capable of resolving mammalian intracochlear anatomy, fixed guinea pig inner ears were imaged as whole temporal bones with cochlea in situ. Anatomical structures such as the tunnel of Corti, space of Nuel, modiolus, scalae, and cell groupings were visualized, in addition to individual cell types such as neuronal fibers, hair cells, and supporting cells. Visualization of these structures, via volumetrically-reconstructed image stacks and endoscopic perspective videos, represents an improvement over previous efforts using conventional OCT. These are the first μOCT images of mammalian cochlear anatomy, and they demonstrate μOCT’s potential utility as an imaging tool in otology research. PMID:27633610

Space radiation effects on plant and mammalian cells

NASA Astrophysics Data System (ADS)

Arena, C.; De Micco, V.; Macaeva, E.; Quintens, R.

2014-11-01

The study of the effects of ionizing radiation on organisms is related to different research aims. The current review emphasizes the studies on the effects of different doses of sparsely and densely ionizing radiation on living organisms, with the final purpose of highlighting specific and common effects of space radiation in mammals and plants. This topic is extremely relevant in the context of radiation protection from space environment. The response of different organisms to ionizing radiation depends on the radiation quality/dose and/or the intrinsic characteristics of the living system. Macromolecules, in particular DNA, are the critical targets of radiation, even if there is a strong difference between damages encountered by plant and mammalian cells. The differences in structure and metabolism between the two cell types are responsible for the higher resistance of the plant cell compared with its animal counterpart. In this review, we report some recent findings from studies performed in Space or on Earth, simulating space-like levels of radiation with ground-based facilities, to understand the effect of ionizing radiation on mammalian and plant cells. In particular, our attention is focused on genetic alterations and repair mechanisms in mammalian cells and on structures and mechanisms conferring radioresistance to plant cells.

Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities.

PubMed

Ley, C J; Ekman, S; Hansson, K; Björnsdóttir, S; Boyde, A

2014-03-25

Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.

Musculoskeletal networks reveal topological disparity in mammalian neck evolution.

PubMed

Arnold, Patrick; Esteve-Altava, Borja; Fischer, Martin S

2017-12-13

The increase in locomotor and metabolic performance during mammalian evolution was accompanied by the limitation of the number of cervical vertebrae to only seven. In turn, nuchal muscles underwent a reorganization while forelimb muscles expanded into the neck region. As variation in the cervical spine is low, the variation in the arrangement of the neck muscles and their attachment sites (i.e., the variability of the neck's musculoskeletal organization) is thus proposed to be an important source of neck disparity across mammals. Anatomical network analysis provides a novel framework to study the organization of the anatomical arrangement, or connectivity pattern, of the bones and muscles that constitute the mammalian neck in an evolutionary context. Neck organization in mammals is characterized by a combination of conserved and highly variable network properties. We uncovered a conserved regionalization of the musculoskeletal organization of the neck into upper, mid and lower cervical modules. In contrast, there is a varying degree of complexity or specialization and of the integration of the pectoral elements. The musculoskeletal organization of the monotreme neck is distinctively different from that of therian mammals. Our findings reveal that the limited number of vertebrae in the mammalian neck does not result in a low musculoskeletal disparity when examined in an evolutionary context. However, this disparity evolved late in mammalian history in parallel with the radiation of certain lineages (e.g., cetartiodactyls, xenarthrans). Disparity is further facilitated by the enhanced incorporation of forelimb muscles into the neck and their variability in attachment sites.

[Neuroimaging of Langerhans cell histiocytosis in the central nervous system of children].

PubMed

De La Hoz Polo, M; Rebollo Polo, M; Fons Estupiña, C; Muchart López, J; Cruz Martinez, O

2015-01-01

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the accumulation within tissues of anomalous dendritic cells similar to Langerhans cells. The clinical presentation varies, ranging from the appearance of a single bone lesion to multisystemic involvement. Central nervous system (CNS) involvement, manifesting as diabetes insipidus secondary to pituitary involvement, has been known since the original description of the disease. Two types of CNS lesions are currently differentiated. The first, pseudotumoral lesions with infiltration by Langerhans cells, most commonly manifests as pituitary infiltration. The second, described more recently, consists of neurodegenerative lesions of the CNS associated with neurologic deterioration. This second type of lesion constitutes a complication of the disease; however, there is no consensus about the cause of this complication. Our objective was to describe the radiologic manifestations of LCH in the CNS in pediatric patients. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration

PubMed Central

Lu, Li; Finegold, Milton J; Johnson, Randy L

2018-01-01

The mammalian liver has a remarkable capacity for repair following injury. Removal of up to two-third of liver mass results in a series of events that include extracellular matrix remodeling, coordinated hepatic cell cycle re-entry, restoration of liver mass and tissue remodeling to return the damaged liver to its normal state. Although there has been considerable advancement of our knowledge concerning the regenerative capacity of the mammalian liver, many outstanding questions remaining, such as: how does the regenerating liver stop proliferating when appropriate mass is restored and how do these mechanisms relate to normal regulation of organ size during development? Hippo pathway has been proposed to be central in mediating both events: organ size control during development and following regeneration. In this report, we examined the role of Yap and Taz, key components of the Hippo pathway in liver organ size regulation, both in the context of development and homeostasis. Our studies reveal that contrary to the current paradigms that Yap/Taz are not required for developmental regulation of liver size but are required for proper liver regeneration. In livers depleted of Yap and Taz, liver mass is elevated in neonates and adults. However, Yap/Taz-depleted livers exhibit profound defects in liver regeneration, including an inability to restore liver mass and to properly coordinate cell cycle entry. Taken together, our results highlight requirements for the Hippo pathway during liver regeneration and indicate that there are additional pathways that cooperate with Hippo signaling to control liver size during development and in the adult. PMID:29303509

Energy independent uptake and release of polystyrene nanoparticles in primary mammalian cell cultures.

PubMed

Fiorentino, Ilaria; Gualtieri, Roberto; Barbato, Vincenza; Mollo, Valentina; Braun, Sabrina; Angrisani, Alberto; Turano, Mimmo; Furia, Maria; Netti, Paolo A; Guarnieri, Daniela; Fusco, Sabato; Talevi, Riccardo

2015-01-15

Nanoparticle (NPs) delivery systems in vivo promises to overcome many obstacles associated with the administration of drugs, vaccines, plasmid DNA and RNA materials, making the study of their cellular uptake a central issue in nanomedicine. The uptake of NPs may be influenced by the cell culture stage and the NPs physical-chemical properties. So far, controversial data on NPs uptake have been derived owing to the heterogeneity of NPs and the general use of immortalized cancer cell lines that often behave differently from each other and from primary mammalian cell cultures. Main aims of the present study were to investigate the uptake, endocytosis pathways, intracellular fate and release of well standardized model particles, i.e. fluorescent 44 nm polystyrene NPs (PS-NPs), on two primary mammalian cell cultures, i.e. bovine oviductal epithelial cells (BOEC) and human colon fibroblasts (HCF) by confocal microscopy and spectrofluorimetric analysis. Different drugs and conditions that inhibit specific internalization routes were used to understand the mechanisms that mediate PS-NP uptake. Our data showed that PS-NPs are rapidly internalized by both cell types 1) with similar saturation kinetics; 2) through ATP-independent processes, and 3) quickly released in the culture medium. Our results suggest that PS-NPs are able to rapidly cross the cell membrane through passive translocation during both uptake and release, and emphasize the need to carefully design NPs for drug delivery, to ensure their selective uptake and to optimize their retainment in the targeted cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Erythropoietin binding protein from mammalian serum

DOEpatents

Clemons, G.K.

1997-04-29

Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

Argonaute identity defines the length of mature mammalian microRNAs.

PubMed

Juvvuna, Prasanna Kumar; Khandelia, Piyush; Lee, Li Ming; Makeyev, Eugene V

2012-08-01

MicroRNAs (miRNAs) are 19- to 25-nt-long non-coding RNAs that regulate gene expression by base-pairing with target mRNAs and reducing their stability or translational efficiency. Mammalian miRNAs function in association with four closely related Argonaute proteins, AGO1-4. All four proteins contain the PAZ and the MID domains interacting with the miRNA 3' and 5' termini, respectively, as well as the PIWI domain comprising an mRNA 'slicing' activity in the case of AGO2 but not AGO1, AGO3 and AGO4. However, the slicing mode of the miRNA-programmed AGO2 is rarely realized in vivo and the four Argonautes are thought to play largely overlapping roles in the mammalian miRNA pathway. Here, we show that the average length of many miRNAs is diminished during nervous system development as a result of progressive shortening of the miRNA 3' ends. We link this modification with an increase in the fractional abundance of Ago2 in the adult brain and identify a specific structural motif within the PAZ domain that enables efficient trimming of miRNAs associated with this but not the other three Argonautes. Taken together, our data suggest that mammalian Argonautes may define the length and possibly biological activity of mature mammalian miRNAs in a developmentally controlled manner.

Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

PubMed

Shimano, Y; Kumazaki, M; Sakurai, T; Hida, H; Fujimoto, I; Fukuda, A; Nishino, H

1995-12-01

Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

Infection studies of nontarget mammalian cell lines with Bombyx mori macula-like virus.

PubMed

Innami, Katsuhisa; Aizawa, Takahiro; Tsukui, Toshihiro; Katsuma, Susumu; Imanishi, Shigeo; Kawasaki, Hideki; Iwanaga, Masashi

2016-03-01

Bombyx mori-derived cell lines are generally used for Bombyx mori nucleopolyhedrovirus (BmNPV)-based baculovirus expression vector system (BEVS). However, almost all of the B. mori-derived cell lines are persistently infected with Bombyx mori macula-like virus (BmMLV). In this study, nontarget mammalian cell lines were exposed to BmMLV, and their susceptibility was investigated. Real-time PCR showed that viral RNA in virus-inoculated nine mammalian cell lines decreased sharply at 7 days postinfection. Also, there was no significant effect on cell viability of mammalian cells after inoculation with BmMLV. These findings indicate that mammalian cell lines used in this study are not permissive to BmMLV, and BmMLV contamination might not affect the safety aspect of BmNPV-based BEVS. Copyright © 2015 Elsevier B.V. All rights reserved.

Hollow fibers - Their applications to the study of mammalian cell function

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Angeline, M.; Harkness, J.; Chu, M.; Grindleland, R.

1984-01-01

The use of hollow fiber technology in cell culture and transplantation is examined. The morphologies of encapsulated pituitary cells before and after implantation into the rat are defined. Implantation experiments using hollow fibers to study mammalian cell functions are described. Consideration is given to examining somatotroph, prolactin, prostrate, fibroblast, and retinal cell functions. These experiments demonstrate that hollow fiber technology is applicable for studying mammalian cell functions.

Ventromedial hypothalamic nucleus lesions disrupt olfactory mate recognition and receptivity in female ferrets

PubMed Central

Robarts, Daniel W.; Baum, Michael J.

2008-01-01

Previous research showed that ferrets of both sexes rely on the perception of conspecifics’ body odors to identify and motivate approach towards opposite-sex mating partners, and exposure to male body odors stimulated Fos expression in an olfactory projection circuit of female, but not male, ferrets that terminates in the ventromedial hypothalamic nucleus (VMH). We asked whether the female-typical preference of ferrets to approach male as opposed to female body odors in Y-maze tests would be disrupted by VMH lesions. Sexually experienced female ferrets were ovo-hysterectomized prior to receiving bilateral electrolytic lesions of the VMH, the preoptic area/anterior hypothalamus (POA/AH) or a sham operation. Subsequently, while receiving estradiol benzoate, females that received either complete or partial bilateral lesions of the VMH approached volatile odors from an anesthetized male on significantly fewer trials than females given POA/AH lesions or a sham operation. Both groups of ferrets with VMH lesion damage reliably discriminated between volatile anal scents as well as urinary odors from the 2 sexes in home cage habituation/dishabituation tests, suggesting that their odor-based sex discrimination remained intact. Females with complete bilateral VMH lesions showed significantly lower acceptance of neck gripping from a stimulus male (receptivity) and more aggression towards the male than all other groups of female subjects. Estrogen-sensitive neurons in the VMH appear to play a central role in female-typical neural processing of odor inputs leading to a preference to seek out a male sex partner, in addition to facilitating females’ sexual receptivity. PMID:17011561

Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vazquez-Iglesias, Lorena; Lostale-Seijo, Irene; Martinez-Costas, Jose

2012-10-25

A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasmmore » sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cells.« less

Nucleus caudalis lesioning: Case report of chronic traumatic headache relief

PubMed Central

Sandwell, Stephen E.; El-Naggar, Amr O.

2011-01-01

Background: The nucleus caudalis dorsal root entry zone (DREZ) surgery is used to treat intractable central craniofacial pain. This is the first journal publication of DREZ lesioning used for the long-term relief of an intractable chronic traumatic headache. Case Description: A 40-year-old female experienced new-onset bi-temporal headaches following a traumatic head injury. Despite medical treatment, her pain was severe on over 20 days per month, 3 years after the injury. The patient underwent trigeminal nucleus caudalis DREZ lesioning. Bilateral single-row lesions were made at 1-mm interval between the level of the obex and the C2 dorsal nerve roots, using angled radiofrequency electrodes, brought to 80°C for 15 seconds each, along a path 1 to 1.2 mm posterior to the accessory nerve rootlets. The headache improved, but gradually returned. Five years later, her headaches were severe on over 24 days per month. The DREZ surgery was then repeated. Her headaches improved and the relief has continued for 5 additional years. She has remained functional, with no limitation in instrumental activities of daily living. Conclusions: The nucleus caudalis DREZ surgery brought long-term relief to a patient suffering from chronic traumatic headache. PMID:22059123

18-F-FDG PET/CT in Localizing Additional CNS Lesion in a Case of Langerhans Cell Histiocytosis: Determining Accurate Extent of the Disease

PubMed Central

Shamim, Shamim Ahmed; Tripathy, Sarthak; Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi

2017-01-01

Central nervous system involvement is a rare manifestation of Langerhans cell histiocytosis (LCH), with bone and skin lesions being more frequent. MR remains the investigation of choice for localizing brain lesions. However, due to poor sensitivity of MRI in detecting osseous and pulmonary lesions, it is not used routinely in staging purposes until and unless indicated. We hereby discuss a case of 6-year-old boy of LCH who was referred for 18-F-FDG PET/CT for staging and knowing the extent of the disease, but a lesion in hypothalamus was picked up incidentally on FDG PET-CT study that was confirmed by MRI. PMID:28533655

18-F-FDG PET/CT in Localizing Additional CNS Lesion in a Case of Langerhans Cell Histiocytosis: Determining Accurate Extent of the Disease.

PubMed

Shamim, Shamim Ahmed; Tripathy, Sarthak; Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi

2017-01-01

Central nervous system involvement is a rare manifestation of Langerhans cell histiocytosis (LCH), with bone and skin lesions being more frequent. MR remains the investigation of choice for localizing brain lesions. However, due to poor sensitivity of MRI in detecting osseous and pulmonary lesions, it is not used routinely in staging purposes until and unless indicated. We hereby discuss a case of 6-year-old boy of LCH who was referred for 18-F-FDG PET/CT for staging and knowing the extent of the disease, but a lesion in hypothalamus was picked up incidentally on FDG PET-CT study that was confirmed by MRI.

Imaging review of lipomatous musculoskeletal lesions

PubMed Central

Burt, Ashley M.; Huang, Brady K.

2017-01-01

Lipomatous lesions are common musculoskeletal lesions that can arise within the soft tissues, bone, neurovascular structures, and synovium. The majority of these lesions are benign, and many of the benign lesions can be diagnosed by radiologic evaluation. However, radiologic differences between benign and malignant lipomatous lesions may be subtle and pathologic correlation is often needed. The use of sonography, computed tomography (CT), and magnetic resonance imaging (MRI) is useful not only in portraying fat within the lesion, but also for evaluating the presence and extent of soft tissue components. Lipomas make up most soft tissue lipomatous lesions, but careful evaluation must be performed to distinguish these lesions from a low-grade liposarcoma. In addition to the imaging appearance, the location of the lesion and the patient demographics can be utilized to help diagnose other soft tissue lipomatous lesions, such as elastofibroma dorsi, angiolipoma, lipoblastoma, and hibernoma. Osseous lipomatous lesions such as a parosteal lipoma and intraosseous lipoma occur less commonly as their soft tissue counterpart, but are also benign. Neurovascular and synovial lipomatous lesions are much rarer lesions but demonstrate more classic radiologic findings, particularly on MRI. A review of the clinical, radiologic, and pathologic characteristics of these lesions is presented. PMID:28474576

Tick-borne encephalitis virus and the immune response of the mammalian host.

PubMed

Dörrbecker, Bastian; Dobler, Gerhard; Spiegel, Martin; Hufert, Frank T

2010-07-01

Tick-borne encephalitis (TBE) is caused by Tick-borne encephalitis virus (TBEV), one of the most prevalent arboviruses in Europe and in many parts of Asia. Transmission of TBEV to humans usually occurs by bite of an infected tick or rarely by ingestion of unpasteurized milk products of infected livestock. TBEV infection induces an innate and adaptive immune response, nevertheless it is able to replicate in several cell types of the immune system at the same time which probably contributes to the spread of the virus in the human host. Furthermore, TBEV can enter the central nervous system (CNS) by yet not well understood mechanisms via the blood brain barrier (BBB) or the olfactory neurons which leads to serious neurological disorders like meningitis, encephalitis or even meningoencephalitis. In this article we review the known facts and possible hypotheses of interaction of TBEV with components of the mammalian immune system and their implications for TBEV-mediated pathogenesis. Copyright © 2010 Elsevier Ltd. All rights reserved.

Mammalian niche conservation through deep time.

PubMed

DeSantis, Larisa R G; Beavins Tracy, Rachel A; Koontz, Cassandra S; Roseberry, John C; Velasco, Matthew C

2012-01-01

Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas) are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of terminal Pleistocene

Mammalian Niche Conservation through Deep Time

PubMed Central

DeSantis, Larisa R. G.; Beavins Tracy, Rachel A.; Koontz, Cassandra S.; Roseberry, John C.; Velasco, Matthew C.

2012-01-01

Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas) are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ∼2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of terminal Pleistocene

Hock lesions and free-stall design.

PubMed

Weary, D M; Taszkun, I

2000-04-01

We compared the prevalence and severity of skin lesions on the hocks of lactating dairy cows in southern British Columbia, comparing 20 farms using three common bedding surfaces: sawdust, sand, and geotextile mattresses. Skin lesions were scored at five positions on the hock. For each position we noted if the lesion showed inflammatory attributes, and then assigned a severity score. Of the 1752 lactating cows scored, 1267 cows (73%) had at least one hock lesion. Of those cows with lesions, 87% had lesions on both legs, 76% had lesions on more than one location on the hock, and 78% had a lesion of at least moderate severity (i.e., evidence of skin breakage or an area of hair loss >10 cm2). Lesions were most prevalent on farms that used geotextile mattresses (91% of cows) and least common on farms that used sand (24% of cows). Moreover, lesions on cows from farms using mattresses were more numerous and more severe than those on cows from sand-bedded farms. The prevalence and severity of lesions on farms using sawdust was intermediate. Lesions also varied in relation to location on the hock. For farms using geotextile mattresses, lesions were more common and more severe on the lateral surfaces of both the tuber calcis and the tarsal joint. On farms using sawdust, lesions were common on the dorsal surface of the tuber calcis and the lateral surfaces of both the tuber calcis and the tarsal joint. Lesions were rare on all five positions for cows from sand-bedded farms. Among the 10 farms sampled using sawdust, we found a significant negative relationship between the length of the stall and severity of lesions. For cows with lesions, the number and severity of lesions increased with age.

Ecology and evolution of mammalian biodiversity

PubMed Central

Jones, Kate E.; Safi, Kamran

2011-01-01

Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future. PMID:21807728

Ecology and evolution of mammalian biodiversity.

PubMed

Jones, Kate E; Safi, Kamran

2011-09-12

Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future.

Mammalian lipoxygenases and their biological relevance.

PubMed

Kuhn, Hartmut; Banthiya, Swathi; van Leyen, Klaus

2015-04-01

Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated not only in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOXs oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in the regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". Copyright © 2014 Elsevier B.V. All rights reserved.

Repair-Resistant DNA Lesions

PubMed Central

2017-01-01

The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the major mechanism that removes most bulky and some nonbulky lesions from cellular DNA. There is growing evidence that certain DNA lesions are repaired slowly or are entirely resistant to repair in cells, tissues, and in cell extract model assay systems. It is well established that the eukaryotic DNA lesion-sensing proteins do not detect the damaged nucleotide, but recognize the distortions/destabilizations in the native DNA structure caused by the damaged nucleotides. In this article, the nature of the structural features of certain bulky DNA lesions that render them resistant to NER, or cause them to be repaired slowly, is compared to that of those that are good-to-excellent NER substrates. Understanding the structural features that distinguish NER-resistant DNA lesions from good NER substrates may be useful for interpreting the biological significance of biomarkers of exposure of human populations to genotoxic environmental chemicals. NER-resistant lesions can survive to replication and cause mutations that can initiate cancer and other diseases. Furthermore, NER diminishes the efficacy of certain chemotherapeutic drugs, and the design of more potent pharmaceuticals that resist repair can be advanced through a better understanding of the structural properties of DNA lesions that engender repair-resistance. PMID:28750166

Unraveling the processes shaping mammalian gut microbiomes over evolutionary time

PubMed Central

Groussin, Mathieu; Mazel, Florent; Sanders, Jon G.; Smillie, Chris S.; Lavergne, Sébastien; Thuiller, Wilfried; Alm, Eric J.

2017-01-01

Whether mammal–microbiome interactions are persistent and specific over evolutionary time is controversial. Here we show that host phylogeny and major dietary shifts have affected the distribution of different gut bacterial lineages and did so on vastly different bacterial phylogenetic resolutions. Diet mostly influences the acquisition of ancient and large microbial lineages. Conversely, correlation with host phylogeny is mostly seen among more recently diverged bacterial lineages, consistent with processes operating at similar timescales to host evolution. Considering microbiomes at appropriate phylogenetic scales allows us to model their evolution along the mammalian tree and to infer ancient diets from the predicted microbiomes of mammalian ancestors. Phylogenetic analyses support co-speciation as having a significant role in the evolution of mammalian gut microbiome compositions. Highly co-speciating bacterial genera are also associated with immune diseases in humans, laying a path for future studies that probe these co-speciating bacteria for signs of co-evolution. PMID:28230052

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid.

PubMed Central

Nistér, M.; Enblad, P.; Bäckström, G.; Söderman, T.; Persson, L.; Heldin, C. H.; Westermark, B.

1994-01-01

The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentration of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and beta-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier. PMID:8180030

Studying non-mammalian models? Not a fool's ERRand!

PubMed Central

Bardet, Pierre-Luc; Laudet, Vincent; Vanacker, Jean-Marc

2006-01-01

Through studies in mammalian model systems, the orphan nuclear receptor Estrogen- Receptor Related (ERR) α has been shown to interfere with estrogen signaling and may therefore be an interesting pharmaceutical target in estrogen-related pathologies. ERRα is also involved in energy storage and consumption and its modulation may be of relevance in the treatment of obesity and diabetes. Recent data have also been published studying the effects of this receptor, as well as other members of the ERR family, in non-mammalian animal model systems. Besides indications concerning their mechanisms of action, this analysis demonstrated a role for ERRα in controlling cellular movements and suggested that ERR receptors may be implicated in a more subtle range of processes than originally envisioned. PMID:16580224

Prdm9 controls activation of mammalian recombination hotspots.

PubMed

Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

2010-02-12

Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

Proteomic identification of plant proteins probed by mammalian nitric oxide synthase antibodies.

PubMed

Butt, Yoki Kwok-Chu; Lum, John Hon-Kei; Lo, Samuel Chun-Lap

2003-03-01

Several studies suggest that a mammalian-like nitric oxide synthase (NOS) exists in plants. Researchers have attempted to verify its presence using two approaches: (i) determination of NOS functional activity and (ii) probing with mammalian NOS antibodies. However, up to now, neither a NOS-like gene nor a protein has been found in plants. While there is still some controversy over whether the NOS functional activity seen is due to nitrate reductase, using the mammalian NOS antibodies in western blot analysis, several groups have reported the presence of immunoreactive protein bands in plant homogenates. Based on these results, immunohistochemical studies using these antibodies have also been used to localize NOS in plant tissues. However, plant NOS has never been positively identified or characterized. Thus, we used a proteomic approach to verify the identities of plant proteins that cross-reacted with the mammalian NOS antibodies. Proteins extracted from maize (Zea mays L.) embryonic axes were separated by two-dimensional gel electrophoresis and subjected to western blot analysis with the mammalian neuronal NOS and inducible NOS antibodies. Twenty immunoreactive protein spots recognized on a corresponding Coomassie blue-stained two-dimensional gel were subjected to tryptic digestion, followed by identification using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Fifteen proteins were successfully identified and they have described functions that are unrelated to NO metabolism. The remaining five proteins could not be identified. The amino acid sequences of these identified proteins and those used to raise the antibodies were aligned. However, no homologous region could be found. Our results demonstrate that the mammalian NOS antibodies recognize many NOS-unrelated plant proteins. Therefore, it is inappropriate to infer the presence of plant NOS using this immunological technique.

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

PubMed Central

Chambers, Emily V.; Bickmore, Wendy A.; Semple, Colin A.

2013-01-01

Several recent studies have examined different aspects of mammalian higher order chromatin structure – replication timing, lamina association and Hi-C inter-locus interactions — and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin

CONCENTRIC DECILE SEGMENTATION OF WHITE AND HYPOPIGMENTED AREAS IN DERMOSCOPY IMAGES OF SKIN LESIONS ALLOWS DISCRIMINATION OF MALIGNANT MELANOMA

PubMed Central

Dalal, Ankur; Moss, Randy H.; Stanley, R. Joe; Stoecker, William V.; Gupta, Kapil; Calcara, David A.; Xu, Jin; Shrestha, Bijaya; Drugge, Rhett; Malters, Joseph M.; Perry, Lindall A.

2011-01-01

Dermoscopy, also known as dermatoscopy or epiluminescence microscopy (ELM), permits visualization of features of pigmented melanocytic neoplasms that are not discernable by examination with the naked eye. White areas, prominent in early malignant melanoma and melanoma in situ, contribute to early detection of these lesions. An adaptive detection method has been investigated to identify white and hypopigmented areas based on lesion histogram statistics. Using the Euclidean distance transform, the lesion is segmented in concentric deciles. Overlays of the white areas on the lesion deciles are determined. Calculated features of automatically detected white areas include lesion decile ratios, normalized number of white areas, absolute and relative size of largest white area, relative size of all white areas, and white area eccentricity, dispersion, and irregularity. Using a back-propagation neural network, the white area statistics yield over 95% diagnostic accuracy of melanomas from benign nevi. White and hypopigmented areas in melanomas tend to be central or paracentral. The four most powerful features on multivariate analysis are lesion decile ratios. Automatic detection of white and hypopigmented areas in melanoma can be accomplished using lesion statistics. A neural network can achieve good discrimination of melanomas from benign nevi using these areas. Lesion decile ratios are useful white area features. PMID:21074971

The association of mammalian DREAM complex and HPV16 E7 proteins

PubMed Central

Rashid, Nurshamimi Nor; Rothan, Hussin A; Yusoff, Mohd Shahrizal Mohd

2015-01-01

The mammalian DREAM (Drosophila, RB, E2F, and Myb) complex was discovered in 2004 by several research groups. It was initially identified in Drosophila followed by Caenorhaditis elegans and later in mammalian cells. The composition of DREAM is temporally regulated during cell cycle; being associated with E2F-4 and either p107 or p130 in G0/G1 (repressive DREAM complexes) and with B-myb transcription factor in S/G2 (activator DREAM complex). High risk human papillomavirus (HPV) E6 and E7 oncoproteins expression are important for malignant transformation of cervical cancer cells. In particular, the E7 of high risk HPV binds to pRB family members (pRB, p107 and p130) for degradation. It has recently been discovered that the p107 and p130 ‘pocket proteins’ are members of mammalian DREAM complexes. With this understanding, we would like to hypothesise the mammalian DREAM complex could plays a critical role for malignant transformation in cervical cancer cells. PMID:26885443

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice.

PubMed

Yue, Yunshuang; Wang, Yi; Li, Dan; Song, Zhigang; Jiao, Hongchao; Lin, Hai

2015-01-01

Bacterial lipopolysaccharide (LPS), also known as endotoxin, induces profound anorexia. However, the LPS-provoked pro-inflammatory signaling cascades and the neural mechanisms underlying the development of anorexia are not clear. Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. This study aimed to determine whether the mTOR pathway is involved in LPS-induced anorexia. Effects of LPS on hypothalamic gene/protein expression in mice were measured by RT-PCR or western blotting analysis. To determine whether inhibition of mTOR signaling could attenuate LPS-induced anorexia, we administered an i.c.v. injection of rapamycin, an mTOR inhibitor, on LPS-treated male mice. In this study, we showed that LPS stimulates the mTOR signaling pathway through the enhanced phosphorylation of mTOR(Ser2448) and p70S6K(Thr389). We also showed that LPS administration increased the phosphorylation of FOXO1(Ser256), the p65 subunit of nuclear factor kappa B (P<0.05), and FOXO1/3a(Thr) (24) (/) (32) (P<0.01). Blocking the mTOR pathway significantly attenuated the LPS-induced anorexia by decreasing the phosphorylation of p70S6K(Thr389), FOXO1(Ser256), and FOXO1/3a(Thr) (24) (/) (32). These results suggest promising approaches for the prevention and treatment of LPS-induced anorexia. © 2015 Society for Endocrinology.

Cultured normal mammalian tissue and process

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor); Prewett, Tacey L. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor)

1993-01-01

Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cell aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

Reverse Genetics for Mammalian Orthoreovirus.

PubMed

Stuart, Johnasha D; Phillips, Matthew B; Boehme, Karl W

2017-01-01

Reverse genetics allows introduction of specific alterations into a viral genome. Studies performed with mutant viruses generated using reverse genetics approaches have contributed immeasurably to our understanding of viral replication and pathogenesis, and also have led to development of novel vaccines and virus-based vectors. Here, we describe the reverse genetics system that allows for production and recovery of mammalian orthoreovirus, a double-stranded (ds) RNA virus, from plasmids that encode the viral genome.

Loiasis with Peripheral Nerve Involvement and Spleen Lesions

PubMed Central

Gobbi, Federico; Boussinesq, Michel; Mascarello, Marta; Angheben, Andrea; Gobbo, Maria; Rossanese, Andrea; Corachán, Manuel; Bisoffi, Zeno

2011-01-01

Loiasis, which is caused by the filarial nematode Loa loa, affects millions of persons living in the rainforest areas and savannah regions of central Africa. Typical manifestations are calabar swellings and the eyeworm. We report a case of loiasis with unusual clinical complications: a peripheral neuropathy and focal hypo-echogenic lesions of the spleen, which disappeared after treatment with albendazole and ivermectin. The literature reports that L. loa infection can be associated with various manifestations, some of them being serious. More information is needed to better characterize the protean manifestations of the disease in loiasis-endemic areas to evaluate the true incidence of loiasis. PMID:21540382

[Managing focal incidental renal lesions].

PubMed

Nicolau, C; Paño, B; Sebastià, C

2016-01-01

Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina

PubMed Central

Duncker, Tobias; Woods, Russell; Delori, François C.

2018-01-01

Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina. PMID:26427423

Light-dark cycle memory in the mammalian suprachiasmatic nucleus.

PubMed

Ospeck, Mark C; Coffey, Ben; Freeman, Dave

2009-09-16

The mammalian circadian oscillator, or suprachiasmatic nucleus (SCN), contains several thousand clock neurons in its ventrolateral division, many of which are spontaneous oscillators with period lengths that range from 22 to 28 h. In complete darkness, this network synchronizes through the exchange of action potentials that release vasoactive intestinal polypeptide, striking a compromise, free-running period close to 24 h long. We entrained Siberian hamsters to various light-dark cycles and then tracked their activity into constant darkness to show that they retain a memory of the previous light-dark cycle before returning to their own free-running period. Employing Leloup-Goldbeter mammalian clock neurons we model the ventrolateral SCN network and show that light acting weakly upon a strongly rhythmic vasoactive intestinal polypeptide oscillation can explain the observed light-dark cycle memory. In addition, light is known to initiate a mitogen-activated protein kinase signaling cascade that induces transcription of both per and mkp1 phosphatase. We show that the ensuing phosphatase-kinase interaction can account for the dead zone in the mammalian phase response curve and hypothesize that the SCN behaves like a lock-in amplifier to entrain to the light edges of the circadian day.

Studies toward birth and early mammalian development in space

NASA Astrophysics Data System (ADS)

Ronca, April E.

2003-10-01

Sustaining life beyond Earth on either space stations or other planets will require a clear understanding of how the space environment affects key phases of mammalian reproduction and development. Pregnancy, parturition (birth) and the early development of offspring are complex processes essential for successful reproduction and the proliferation of mammalian species. While no mammal has yet undergone birth within the space environment, studies spanning the gravity continuum from 0- to 2-g are revealing startling insights into how reproduction and development may proceed under gravitational conditions deviating from those typically experienced on Earth. In this report, I review studies of pregnant Norway rats and their offspring flown in microgravity (μg) onboard the NASA Space Shuttle throughout the period corresponding to mid- to late gestation, and analogous studies of pregnant rats exposed to hypergravity ( ht) onboard the NASA Ames Research Center 24-ft centrifuge. Studies of postnatal rats flown in space or exposed to centrifugation are reviewed. Although many important questions remain unanswered, the available data suggest that numerous aspects of pregnancy, birth and early mammalian development can proceed under altered gravity conditions. Published by Elsevier Ltd on behalf of COSPAR.

Quantitative assessment of multiple sclerosis lesion load using CAD and expert input

NASA Astrophysics Data System (ADS)

Gertych, Arkadiusz; Wong, Alexis; Sangnil, Alan; Liu, Brent J.

2008-03-01

Multiple sclerosis (MS) is a frequently encountered neurological disease with a progressive but variable course affecting the central nervous system. Outline-based lesion quantification in the assessment of lesion load (LL) performed on magnetic resonance (MR) images is clinically useful and provides information about the development and change reflecting overall disease burden. Methods of LL assessment that rely on human input are tedious, have higher intra- and inter-observer variability and are more time-consuming than computerized automatic (CAD) techniques. At present it seems that methods based on human lesion identification preceded by non-interactive outlining by CAD are the best LL quantification strategies. We have developed a CAD that automatically quantifies MS lesions, displays 3-D lesion map and appends radiological findings to original images according to current DICOM standard. CAD is also capable to display and track changes and make comparison between patient's separate MRI studies to determine disease progression. The findings are exported to a separate imaging tool for review and final approval by expert. Capturing and standardized archiving of manual contours is also implemented. Similarity coefficients calculated from quantities of LL in collected exams show a good correlation of CAD-derived results vs. those incorporated as expert's reading. Combining the CAD approach with an expert interaction may impact to the diagnostic work-up of MS patients because of improved reproducibility in LL assessment and reduced time for single MR or comparative exams reading. Inclusion of CAD-generated outlines as DICOM-compliant overlays into the image data can serve as a better reference in MS progression tracking.

Lesion detection in ultra-wide field retinal images for diabetic retinopathy diagnosis

NASA Astrophysics Data System (ADS)

Levenkova, Anastasia; Sowmya, Arcot; Kalloniatis, Michael; Ly, Angelica; Ho, Arthur

2018-02-01

Diabetic retinopathy (DR) leads to irreversible vision loss. Diagnosis and staging of DR is usually based on the presence, number, location and type of retinal lesions. Ultra-wide field (UWF) digital scanning laser technology provides an opportunity for computer-aided DR lesion detection. High-resolution UWF images (3078×2702 pixels) may allow detection of more clinically relevant retinopathy in comparison with conventional retinal images as UWF imaging covers a 200° retinal area, versus 45° by conventional cameras. Current approaches to DR diagnosis that analyze 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) retinal images provide similar results to UWF imaging. However, in 40% of cases, more retinopathy was found outside the 7- field ETDRS fields by UWF and in 10% of cases, retinopathy was reclassified as more severe. The reason is that UWF images examine both the central retina and more peripheral regions. We propose an algorithm for automatic detection and classification of DR lesions such as cotton wool spots, exudates, microaneurysms and haemorrhages in UWF images. The algorithm uses convolutional neural network (CNN) as a feature extractor and classifies the feature vectors extracted from colour-composite UWF images using a support vector machine (SVM). The main contribution includes detection of four types of DR lesions in the peripheral retina for diagnostic purposes. The evaluation dataset contains 146 UWF images. The proposed method for detection of DR lesion subtypes in UWF images using two scenarios for transfer learning achieved AUC ≈ 80%. Data was split at the patient level to validate the proposed algorithm.

Association between right-to-left shunts and brain lesions in sport divers.

PubMed

Gerriets, Tibo; Tetzlaff, Kay; Hutzelmann, Alfred; Liceni, Thomas; Kopiske, Gerrit; Struck, Niklas; Reuter, Michael; Kaps, Manfred

2003-10-01

Recent studies suggest that healthy sport divers may develop clinically silent brain damage, based on the association between a finding of multiple brain lesions on MRI and the presence of right-to-left shunt, a pathway for venous gas bubbles to enter the arterial system. We performed echocontrast transcranial Doppler sonography in 42 sport divers to determine the presence of a right-to-left shunt. Cranial MRI was carried out using a 1.5 T magnet. A lesion was counted if it was hyperintense on both T2-weighted and T2-weighted fluid attenuated inversion recovery sequences. To test the hypothesis that the occurrence of postdive arterial gas emboli is related to brain lesions on MRI, we measured postdive intravascular bubbles in a subset of 15 divers 30 min after open water scuba dives. Echocontrast transcranial Doppler sonography revealed a right-to-left shunt in 16 of the divers (38%). Only one hyperintensive lesion of the central white matter was found and that was in a diver with no evidence of a right-to-left shunt. Postdive arterial gas emboli were detected in 3 out of 15 divers; they had a right-to-left shunt, but no pathologic findings on cranial magnetic resonance imaging. Our data support the theory that right-to-left shunts can serve as a pathway for venous gas bubbles into the arterial circulation. However, we could not confirm an association between brain lesions and the presence of a right-to-left shunt in sport divers.

Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin.

PubMed

Vázquez-Iglesias, Lorena; Lostalé-Seijo, Irene; Martínez-Costas, José; Benavente, Javier

2012-10-25

A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasm sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Lesion network localization of criminal behavior

PubMed Central

Darby, R. Ryan; Horn, Andreas; Fox, Michael D.

2018-01-01

Following brain lesions, previously normal patients sometimes exhibit criminal behavior. Although rare, these cases can lend unique insight into the neurobiological substrate of criminality. Here we present a systematic mapping of lesions with known temporal association to criminal behavior, identifying 17 lesion cases. The lesion sites were spatially heterogeneous, including the medial prefrontal cortex, orbitofrontal cortex, and different locations within the bilateral temporal lobes. No single brain region was damaged in all cases. Because lesion-induced symptoms can come from sites connected to the lesion location and not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has recently identified regions involved in symptom generation across a variety of lesion-induced disorders. All lesions were functionally connected to the same network of brain regions. This criminality-associated connectivity pattern was unique compared with lesions causing four other neuropsychiatric syndromes. This network includes regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Finally, we replicated our results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was implied but not definitive. Our results suggest that lesions in criminals occur in different brain locations but localize to a unique resting state network, providing insight into the neurobiology of criminal behavior. PMID:29255017

Ghrelin: an emerging player in the regulation of reproduction in non-mammalian vertebrates.

PubMed

Unniappan, Suraj

2010-07-01

The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of multiple endocrine factors mainly produced from the brain, pituitary, and gonads. In addition to these, several other tissues including the fat and gut produce factors that have reproductive effects. Ghrelin is one such gut/brain hormone with species-specific effects in the regulation of mammalian reproduction. Recent studies have shown that ghrelin and ghrelin receptor mRNAs, and protein are expressed in the ovary and testis of mammals, indicating a direct effect for ghrelin in the control of reproduction. Ghrelin regulates mammalian reproduction by modulating hormone secretion from the brain and pituitary, and by acting directly on the gonads to influence reproductive tissue development and steroid hormone release. Based on the studies reported so far, ghrelin seems to have a predominantly inhibitory role on mammalian reproduction. The presence of ghrelin and ghrelin receptor has been found in the brain, pituitary and gonads of several non-mammalian vertebrates. In contrast to mammals, ghrelin seems to have a stimulatory role in the regulation of non-mammalian reproduction. The main objective of this review is to do a perspective analysis of the comparative aspects of ghrelin regulation of reproduction. (c) 2009 Elsevier Inc. All rights reserved.

Inter-algorithm lesion volumetry comparison of real and 3D simulated lung lesions in CT

NASA Astrophysics Data System (ADS)

Robins, Marthony; Solomon, Justin; Hoye, Jocelyn; Smith, Taylor; Ebner, Lukas; Samei, Ehsan

2017-03-01

The purpose of this study was to establish volumetric exchangeability between real and computational lung lesions in CT. We compared the overall relative volume estimation performance of segmentation tools when used to measure real lesions in actual patient CT images and computational lesions virtually inserted into the same patient images (i.e., hybrid datasets). Pathologically confirmed malignancies from 30 thoracic patient cases from Reference Image Database to Evaluate Therapy Response (RIDER) were modeled and used as the basis for the comparison. Lesions included isolated nodules as well as those attached to the pleura or other lung structures. Patient images were acquired using a 16 detector row or 64 detector row CT scanner (Lightspeed 16 or VCT; GE Healthcare). Scans were acquired using standard chest protocols during a single breath-hold. Virtual 3D lesion models based on real lesions were developed in Duke Lesion Tool (Duke University), and inserted using a validated image-domain insertion program. Nodule volumes were estimated using multiple commercial segmentation tools (iNtuition, TeraRecon, Inc., Syngo.via, Siemens Healthcare, and IntelliSpace, Philips Healthcare). Consensus based volume comparison showed consistent trends in volume measurement between real and virtual lesions across all software. The average percent bias (+/- standard error) shows -9.2+/-3.2% for real lesions versus -6.7+/-1.2% for virtual lesions with tool A, 3.9+/-2.5% and 5.0+/-0.9% for tool B, and 5.3+/-2.3% and 1.8+/-0.8% for tool C, respectively. Virtual lesion volumes were statistically similar to those of real lesions (< 4% difference) with p >.05 in most cases. Results suggest that hybrid datasets had similar inter-algorithm variability compared to real datasets.

Imaging of cerebellopontine angle lesions: an update. Part 2: intra-axial lesions, skull base lesions that may invade the CPA region, and non-enhancing extra-axial lesions.

PubMed

Bonneville, Fabrice; Savatovsky, Julien; Chiras, Jacques

2007-11-01

Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions responsible for cerebellopontine angle (CPA) syndrome. However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion- and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion's site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Non-enhancing extra-axial CPA masses are cystic (epidermoid cyst, arachnoid cyst, neurenteric cyst) or contain fat (dermoid cyst, lipoma). Tumours can also extend into the CPA by extension from the skull base (paraganglioma, chondromatous tumours, chordoma, cholesterol granuloma, endolymphatic sac tumour). Finally, brain stem or ventricular tumours can present with a significant exophytic component in the CPA that may be difficult to differentiate from an extra-axial lesion (lymphoma, hemangioblastoma, choroid plexus papilloma, ependymoma, glioma, medulloblastoma, dysembryoplastic neuroepithelial tumour).

Identification of the convulsant opiate thebaine in mammalian brain.

PubMed Central

Kodaira, H; Lisek, C A; Jardine, I; Arimura, A; Spector, S

1989-01-01

The convulsant opiate thebaine, an intermediate of morphine biosynthesis, was purified from bovine brain to homogeneity by gel filtration and high-performance liquid chromatography (HPLC) monitored by a radioimmunoassay. The immunoreactive material behaved identically to standard thebaine in two HPLC systems and was confirmed to be thebaine by combined gas chromatography/mass spectrometry. To our knowledge, the presence of thebaine in mammalian tissue has not been demonstrated previously. Codeine and morphine were also found to exist in ovine brain. The presence of thebaine in ovine brain provides strong evidence that morphine and codeine, in various mammalian tissues, are of endogenous origin and actually biosynthesized from a precursor. Images PMID:2911601

Retention of the Native Epigenome in Purified Mammalian Chromatin

PubMed Central

Ehrensberger, Andreas H.; Franchini, Don-Marc; East, Philip; George, Roger; Matthews, Nik; Maslen, Sarah L.; Svejstrup, Jesper Q.

2015-01-01

A protocol is presented for the isolation of native mammalian chromatin as fibers of 25–250 nucleosomes under conditions that preserve the natural epigenetic signature. The material is composed almost exclusively of histones and DNA and conforms to the structure expected by electron microscopy. All sequences probed for were retained, indicating that the material is representative of the majority of the genome. DNA methylation marks and histone marks resembled the patterns observed in vivo. Importantly, nucleosome positions also remained largely unchanged, except on CpG islands, where nucleosomes were found to be unstable. The technical challenges of reconstituting biochemical reactions with native mammalian chromatin are discussed. PMID:26248330

A role for carbohydrate recognition in mammalian sperm-egg binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, Gary F., E-mail: clarkgf@health.missouri.edu

Highlights: • Mammalian sperm-egg binding as a carbohydrate dependent species recognition event. • The role of carbohydrate recognition in human, mouse and pig sperm-egg binding. • Historical perspective and future directions for research focused on gamete binding. - Abstract: Mammalian fertilization usually requires three sequential cell–cell interactions: (i) initial binding of sperm to the specialized extracellular matrix coating the egg known as the zona pellucida (ZP); (ii) binding of sperm to the ZP via the inner acrosomal membrane that is exposed following the induction of acrosomal exocytosis; and (iii) adhesion of acrosome-reacted sperm to the plasma membrane of the eggmore » cell, enabling subsequent fusion of these gametes. The focus of this review is on the initial binding of intact sperm to the mammalian ZP. Evidence collected over the past fifty years has confirmed that this interaction relies primarily on the recognition of carbohydrate sequences presented on the ZP by lectin-like egg binding proteins located on the plasma membrane of sperm. There is also evidence that the same carbohydrate sequences that mediate binding also function as ligands for lectins on lymphocytes that can inactivate immune responses, likely protecting the egg and the developing embryo up to the stage of blastocyst hatching. The literature related to initial sperm-ZP binding in the three major mammalian models (human, mouse and pig) is discussed. Historical perspectives and future directions for research related to this aspect of gamete adhesion are also presented.« less

Transplantation of prokaryotic two-component signaling pathways into mammalian cells.

PubMed

Hansen, Jonathan; Mailand, Erik; Swaminathan, Krishna Kumar; Schreiber, Joerg; Angelici, Bartolomeo; Benenson, Yaakov

2014-11-04

Signaling pathway engineering is a promising route toward synthetic biological circuits. Histidine-aspartate phosphorelays are thought to have evolved in prokaryotes where they form the basis for two-component signaling. Tyrosine-serine-threonine phosphorelays, exemplified by MAP kinase cascades, are predominant in eukaryotes. Recently, a prokaryotic two-component pathway was implemented in a plant species to sense environmental trinitrotoluene. We reasoned that "transplantation" of two-component pathways into mammalian host could provide an orthogonal and diverse toolkit for a variety of signal processing tasks. Here we report that two-component pathways could be partially reconstituted in mammalian cell culture and used for programmable control of gene expression. To enable this reconstitution, coding sequences of histidine kinase (HK) and response regulator (RR) components were codon-optimized for human cells, whereas the RRs were fused with a transactivation domain. Responsive promoters were furnished by fusing DNA binding sites in front of a minimal promoter. We found that coexpression of HKs and their cognate RRs in cultured mammalian cells is necessary and sufficient to strongly induce gene expression even in the absence of pathways' chemical triggers in the medium. Both loss-of-function and constitutive mutants behaved as expected. We further used the two-component signaling pathways to implement two-input logical AND, NOR, and OR gene regulation. Thus, two-component systems can be applied in different capacities in mammalian cells and their components can be used for large-scale synthetic gene circuits.

Argonaute identity defines the length of mature mammalian microRNAs

PubMed Central

Juvvuna, Prasanna Kumar; Khandelia, Piyush; Lee, Li Ming; Makeyev, Eugene V.

2012-01-01

MicroRNAs (miRNAs) are 19- to 25-nt-long non-coding RNAs that regulate gene expression by base-pairing with target mRNAs and reducing their stability or translational efficiency. Mammalian miRNAs function in association with four closely related Argonaute proteins, AGO1–4. All four proteins contain the PAZ and the MID domains interacting with the miRNA 3′ and 5′ termini, respectively, as well as the PIWI domain comprising an mRNA ‘slicing’ activity in the case of AGO2 but not AGO1, AGO3 and AGO4. However, the slicing mode of the miRNA-programmed AGO2 is rarely realized in vivo and the four Argonautes are thought to play largely overlapping roles in the mammalian miRNA pathway. Here, we show that the average length of many miRNAs is diminished during nervous system development as a result of progressive shortening of the miRNA 3′ ends. We link this modification with an increase in the fractional abundance of Ago2 in the adult brain and identify a specific structural motif within the PAZ domain that enables efficient trimming of miRNAs associated with this but not the other three Argonautes. Taken together, our data suggest that mammalian Argonautes may define the length and possibly biological activity of mature mammalian miRNAs in a developmentally controlled manner. PMID:22505576

Transient pituitary enlargement with central hypogonadism secondary to bilateral cavernous sinus thrombosis: pituitary oedema?

PubMed

Joubert, Michael; Verdon, Renaud; Reznik, Yves

2009-05-01

Design We report the case of an incidental pituitary mass discovered in the context of bilateral cavernous sinus thrombosis due to a bacterial pansinusitis. Conclusions Magnetic resonance imaging features of the pituitary lesion, together with transient central hypogonadism and total regression of the mass after anticoagulation and antimicrobial therapy, suggest that this lesion is a pituitary oedema of vascular mechanism. Other possible causes of pituitary mass in such a situation are also discussed.

Periapical lesions are not always a sequelae of pulpal necrosis: a retrospective study of 1521 biopsies.

PubMed

Kontogiannis, T G; Tosios, K I; Kerezoudis, N P; Krithinakis, S; Christopoulos, P; Sklavounou, A

2015-01-01

To record the incidence of lesions that were not the sequelae of pulpal necrosis (non-SPN) amongst 1521 biopsies of periapical lesions submitted with a clinical diagnosis of a sequelae of pulpal necrosis (SPN). A retrospective study of 1521 biopsy request forms of specimens submitted for histopathological examination with a clinical diagnosis 'periapical inflammation', 'periapical abscess', 'periapical granuloma' or 'periapical cyst' during an arbitrarily selected 14-year period was undertaken. Gender and age of the patient, site and maximum diameter of the lesion, symptoms, inclusion of the final diagnosis in the differential diagnosis and specialty of the clinician submitting the biopsy material were recorded in each case. The final diagnosis for each case was extracted from the pathology report, and two groups were formed, SPN and non-SPN lesions. Differences between the respective features of SPN and non-SPN cases were analysed with Yate's chi-square test and t-test (significance level P < 0.05) RESULTS: In 52 of the 1521 cases examined (3.42%), the histological diagnosis was not consistent with a SPN. In most non-SPN cases, the histopathological diagnosis was not included in the differential diagnosis. The keratocystic odontogenic tumour [odontogenic keratocyst (OKC)] was the most frequent non-SPN lesion (34.62%). Other, yet less frequent, non-SPN lesions included glandular odontogenic cysts, lateral periodontal cysts, central ossifying fibromas as well as malignancies (metastatic carcinomas and Langerhans cell histiocytosis). Non-SPN lesions appeared in the periapical region mimicking a SPN, although rarely. Most of them were developmental cysts, in particular OKCs, but odontogenic tumours, such as ameloblastoma, or malignant lesions were also diagnosed. Histological examination of tissue harvested from periapical lesions should be performed, in particular when those lesions are large. © 2014 International Endodontic Journal. Published by John Wiley & Sons

Ranavirus infections associated with skin lesions in lizards

PubMed Central

2013-01-01

Ranaviral disease in amphibians has been studied intensely during the last decade, as associated mass-mortality events are considered to be a global threat to wild animal populations. Several studies have also included other susceptible ectothermic vertebrates (fish and reptiles), but only very few cases of ranavirus infections in lizards have been previously detected. In this study, we focused on clinically suspicious lizards and tested these animals for the presence of ranaviruses. Virological screening of samples from lizards with increased mortality and skin lesions over a course of four years led to the detection of ranaviral infections in seven different groups. Affected species were: brown anoles (Anolis sagrei), Asian glass lizards (Dopasia gracilis), green anoles (Anolis carolinensis), green iguanas (Iguana iguana), and a central bearded dragon (Pogona vitticeps). Purulent to ulcerative-necrotizing dermatitis and hyperkeratosis were diagnosed in pathological examinations. All animals tested positive for the presence of ranavirus by PCR and a part of the major capsid protein (MCP) gene of each virus was sequenced. Three different ranaviruses were isolated in cell culture. The analyzed portions of the MCP gene from each of the five different viruses detected were distinct from one another and were 98.4-100% identical to the corresponding portion of the frog virus 3 (FV3) genome. This is the first description of ranavirus infections in these five lizard species. The similarity in the pathological lesions observed in these different cases indicates that ranaviral infection may be an important differential diagnosis for skin lesions in lizards. PMID:24073785

Ranavirus infections associated with skin lesions in lizards.

PubMed

Stöhr, Anke C; Blahak, Silvia; Heckers, Kim O; Wiechert, Jutta; Behncke, Helge; Mathes, Karina; Günther, Pascale; Zwart, Peer; Ball, Inna; Rüschoff, Birgit; Marschang, Rachel E

2013-09-27

Ranaviral disease in amphibians has been studied intensely during the last decade, as associated mass-mortality events are considered to be a global threat to wild animal populations. Several studies have also included other susceptible ectothermic vertebrates (fish and reptiles), but only very few cases of ranavirus infections in lizards have been previously detected. In this study, we focused on clinically suspicious lizards and tested these animals for the presence of ranaviruses. Virological screening of samples from lizards with increased mortality and skin lesions over a course of four years led to the detection of ranaviral infections in seven different groups. Affected species were: brown anoles (Anolis sagrei), Asian glass lizards (Dopasia gracilis), green anoles (Anolis carolinensis), green iguanas (Iguana iguana), and a central bearded dragon (Pogona vitticeps). Purulent to ulcerative-necrotizing dermatitis and hyperkeratosis were diagnosed in pathological examinations. All animals tested positive for the presence of ranavirus by PCR and a part of the major capsid protein (MCP) gene of each virus was sequenced. Three different ranaviruses were isolated in cell culture. The analyzed portions of the MCP gene from each of the five different viruses detected were distinct from one another and were 98.4-100% identical to the corresponding portion of the frog virus 3 (FV3) genome. This is the first description of ranavirus infections in these five lizard species. The similarity in the pathological lesions observed in these different cases indicates that ranaviral infection may be an important differential diagnosis for skin lesions in lizards.

Skull base lesions: extracranial origins.

PubMed

Mosier, Kristine M

2013-10-01

A number of extracranial anatomical sites, including the nasopharynx, paranasal sinuses, and masticator space, may give rise to lesions involving the skull base. Implicit in the nature of an invasive lesion, the majority of these lesions are malignant. Accordingly, for optimal patient outcomes and treatment planning, it is imperative to include a search pattern for extracranial sites and to assess accurately the character and extent of these diverse lesions. Of particular importance to radiologists are lesions arising from each extracranial site, the search patterns, and relevant information important to convey to the referring clinician. Copyright © 2013 Elsevier Inc. All rights reserved.

SNARE interactions in membrane trafficking: a perspective from mammalian central synapses.

PubMed

Kavalali, Ege T

2002-10-01

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are a large family of proteins that are present on all organelles involved in intracellular vesicle trafficking and secretion. The interaction of complementary SNAREs found on opposing membranes presents an attractive lock-and-key mechanism, which may underlie the specificity of vesicle trafficking. Moreover, formation of the tight complex between a vesicle membrane SNARE and corresponding target membrane SNAREs could drive membrane fusion. In synapses, this tight complex, also referred to as the synaptic core complex, is essential for neurotransmitter release. However, recent observations in knockout mice lacking major synaptic SNAREs challenge the prevailing notion on the executive role of these proteins in fusion and open up several questions about their exact role(s) in neurotransmitter release. Persistence of a form of regulated neurotransmitter release in these mutant mice also raises the possibility that other cognate or non-cognate SNAREs may partially compensate for the loss of a particular SNARE. Future analysis of SNARE function in central synapses will also have implications for the role of these molecules in other vesicle trafficking events such as endocytosis and vesicle replenishment. Such analysis can provide a molecular basis for synaptic processes including certain forms of short-term synaptic plasticity. Copyright 2002 Wiley Periodicals, Inc.

Effects of amygdala lesions on overexpectation phenomena in food cup approach and autoshaping procedures

PubMed Central

Holland, Peter C.

2016-01-01

Prediction error (PE) plays a critical role in most modern theories of associative learning, by determining the effectiveness of conditioned or unconditioned stimuli (CS or USs). Here, we examined the effects of lesions of central (CeA) or basolateral (BLA) amygdala on performance in overexpectation tasks. In two experiments, after two CSs were separately paired with the US, they were combined and followed by the same US. In a subsequent test, we observed losses in strength of both CSs, as expected if the negative PE generated on reinforced compound trials encouraged inhibitory learning. CeA lesions, known to interfere with PE-induced enhancements in CS effectiveness, reduced those losses, suggesting that normally the negative PE also enhances cue associability in this task. BLA lesions had no effect. When a novel cue accompanied the reinforced compound, it acquired net conditioned inhibition, despite its consistent pairings with the US, consonant with US effectiveness models. That acquisition was unaffected by either CeA or BLA lesions, suggesting different rules for assignment of credit of changes in cue strength and cue associability. Finally, we examined a puzzling autoshaping phenomenon previously attributed to overexpectation effects. When a previously-food-paired auditory cue was combined with the insertion of a lever and paired with the same food US, the auditory cue not only failed to block conditioning to the lever, but also lost strength, as in an overexpectation experiment. This effect was abolished by BLA lesions but unaffected by CeA lesions, suggesting it was unrelated to other overexpectation effects. PMID:27176564

Where language meets meaningful action: a combined behavior and lesion analysis of aphasia and apraxia.

PubMed

Weiss, Peter H; Ubben, Simon D; Kaesberg, Stephanie; Kalbe, Elke; Kessler, Josef; Liebig, Thomas; Fink, Gereon R

2016-01-01

It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca's region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24% (n = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare (n = 2, 4%). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.

Imaging of cerebellopontine angle lesions: an update. Part 1: enhancing extra-axial lesions.

PubMed

Bonneville, Fabrice; Savatovsky, Julien; Chiras, Jacques

2007-10-01

Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions in the cerebellopontine angle (CPA). However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion's site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Part 1 describes the different enhancing extra-axial CPA masses primarily arising from the cerebellopontine cistern and its contents, including vestibular and non-vestibular schwannomas, meningioma, metastasis, aneurysm, tuberculosis and other miscellaneous meningeal lesions.

A Comparative Study of Airflow and Odorant Deposition in the Mammalian Nasal Cavity

NASA Astrophysics Data System (ADS)

Richter, Joseph; Rumple, Christopher; Ranslow, Allison; Quigley, Andrew; Pang, Benison; Neuberger, Thomas; Krane, Michael; van Valkenburgh, Blaire; Craven, Brent

2013-11-01

The complex structure of the mammalian nasal cavity provides a tortuous airflow path and a large surface area for respiratory air conditioning, filtering of inspired contaminants, and olfaction. Due to the small and contorted structure of the nasal turbinals, nasal anatomy and function remains poorly understood in most mammals. Here, we utilize high-resolution MRI scans to reconstruct anatomically-accurate models of the mammalian nasal cavity. These data are used to compare the form and function of the mammalian nose. High-fidelity computational fluid dynamics (CFD) simulations of nasal airflow and odorant deposition are presented and used to compare olfactory function across species (primate, rodent, canine, feline, ungulate).

Non-mammalian models in behavioral neuroscience: consequences for biological psychiatry

PubMed Central

Maximino, Caio; Silva, Rhayra Xavier do Carmo; da Silva, Suéllen de Nazaré Santos; Rodrigues, Laís do Socorro dos Santos; Barbosa, Hellen; de Carvalho, Tayana Silva; Leão, Luana Ketlen dos Reis; Lima, Monica Gomes; Oliveira, Karen Renata Matos; Herculano, Anderson Manoel

2015-01-01

Current models in biological psychiatry focus on a handful of model species, and the majority of work relies on data generated in rodents. However, in the same sense that a comparative approach to neuroanatomy allows for the identification of patterns of brain organization, the inclusion of other species and an adoption of comparative viewpoints in behavioral neuroscience could also lead to increases in knowledge relevant to biological psychiatry. Specifically, this approach could help to identify conserved features of brain structure and behavior, as well as to understand how variation in gene expression or developmental trajectories relates to variation in brain and behavior pertinent to psychiatric disorders. To achieve this goal, the current focus on mammalian species must be expanded to include other species, including non-mammalian taxa. In this article, we review behavioral neuroscientific experiments in non-mammalian species, including traditional “model organisms” (zebrafish and Drosophila) as well as in other species which can be used as “reference.” The application of these domains in biological psychiatry and their translational relevance is considered. PMID:26441567

Amygdala lesions reduce cataplexy in orexin knock-out mice.

PubMed

Burgess, Christian R; Oishi, Yo; Mochizuki, Takatoshi; Peever, John H; Scammell, Thomas E

2013-06-05

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of rapid eye movement sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal gray, lateral pontine tegmentum, locus ceruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knock-out mice, a model of narcolepsy. These lesions did not alter basic sleep-wake behavior but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia.

Evolution and functional divergence of NLRP genes in mammalian reproductive systems

PubMed Central

2009-01-01

Background NLRPs (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing Proteins) are members of NLR (Nod-like receptors) protein family. Recent researches have shown that NLRP genes play important roles in both mammalian innate immune system and reproductive system. Several of NLRP genes were shown to be specifically expressed in the oocyte in mammals. The aim of the present work was to study how these genes evolved and diverged after their duplication, as well as whether natural selection played a role during their evolution. Results By using in silico methods, we have evaluated the evolution and functional divergence of NLRP genes, in particular of mouse reproduction-related Nlrp genes. We found that (1) major NLRP genes have been duplicated before the divergence of mammals, with certain lineage-specific duplications in primates (NLRP7 and 11) and in rodents (Nlrp1, 4 and 9 duplicates); (2) tandem duplication events gave rise to a mammalian reproduction-related NLRP cluster including NLRP2, 4, 5, 7, 8, 9, 11, 13 and 14 genes; (3) the function of mammalian oocyte-specific NLRP genes (NLRP4, 5, 9 and 14) might have diverged during gene evolution; (4) recent segmental duplications concerning Nlrp4 copies and vomeronasal 1 receptor encoding genes (V1r) have been undertaken in the mouse; and (5) duplicates of Nlrp4 and 9 in the mouse might have been subjected to adaptive evolution. Conclusion In conclusion, this study brings us novel information on the evolution of mammalian reproduction-related NLRPs. On the one hand, NLRP genes duplicated and functionally diversified in mammalian reproductive systems (such as NLRP4, 5, 9 and 14). On the other hand, during evolution, different lineages adapted to develop their own NLRP genes, particularly in reproductive function (such as the specific expansion of Nlrp4 and Nlrp9 in the mouse). PMID:19682372

Accuracy in clinically evaluating pigmented lesions.

PubMed Central

Curley, R. K.; Cook, M. G.; Fallowfield, M. E.; Marsden, R. A.

1989-01-01

OBJECTIVE--To determine the ability of three doctors experienced in managing melanocytic lesions to diagnose correctly melanoma, dysplastic naevi, and various benign pigmented lesions. DESIGN--Independent clinical evaluation and histopathological assessment. SETTING--Pigmented lesion clinic, which patients attend without an appointment for early diagnosis of melanoma. PATIENTS--86 Patients with lesions that were judged to be benign by at least one of the three doctors. INTERVENTIONS--The lesions were excised under local anaesthesia and sent for histopathological examination in coded bottles without clinical details. MAIN OUTCOME MEASURE--Comparison of clinical with histopathological diagnosis for each lesion. RESULTS--A total of 120 lesions were evaluated by at least two of the three doctors. The histopathological diagnoses were made by the same pathologist. The overall sensitivity (diagnostic accuracy) for the three doctors for all types of lesion was 50%. Of the 39 dysplastic naevi, only 19 were identified correctly by all observers, and a further 24 banal lesions were wrongly diagnosed as dysplastic by at least one doctor. Particular difficulty was experienced with small (less than 5 mm), flat lesions, which can be banal or potentially malignant. CONCLUSIONS--Critical diagnosis and management decisions concerning pigmented lesions should always be based on a combination of clinical and histopathological assessments and the history of the patient. PMID:2503192

The effect of aniracetam on cerebral glucose metabolism in rats after lesioning of the basal forebrain measured by PET.

PubMed

Ouchi, Y; Kakiuchi, T; Okada, H; Nishiyama, S; Tsukada, H

1999-03-15

To evaluate the effect of aniracetam, a potent modulator of the glutamatergic and cholinergic systems, on the altered cerebral glucose metabolism after lesioning of the basal forebrain, we measured the cerebral metabolic rate of glucose (CMRGlc) with positron emission tomography and the choline acetyltransferase (ChAT) activity in the frontal cortex of the lesioned rats after treating them with aniracetam. Continuous administration of aniracetam for 7 days after the surgery prevented CMRGlc reduction in the frontal cortex ipsilateral to the lesion while the lesioned rats without aniracetam showed significant CMRGlc reduction in the frontal cortex. The level of CMRGlc in the lesion-side basal forebrain was lower in all rats regardless of the aniracetam treatment. Biochemical studies showed that aniracetam did not alter the reduction in the frontal ChAT activity. These results showed that aniracetam prevents glucose metabolic reduction in the cholinergically denervated frontal cortex with little effect on the cortical cholinergic system. The present study suggested that a neurotransmitter system other than the cholinergic system, e.g. the glutamatergic system, plays a central role in the cortical metabolic recovery after lesioning of the basal forebrain.

Breast lesion characterization using whole-lesion histogram analysis with stretched-exponential diffusion model.

PubMed

Liu, Chunling; Wang, Kun; Li, Xiaodan; Zhang, Jine; Ding, Jie; Spuhler, Karl; Duong, Timothy; Liang, Changhong; Huang, Chuan

2018-06-01

Diffusion-weighted imaging (DWI) has been studied in breast imaging and can provide more information about diffusion, perfusion and other physiological interests than standard pulse sequences. The stretched-exponential model has previously been shown to be more reliable than conventional DWI techniques, but different diagnostic sensitivities were found from study to study. This work investigated the characteristics of whole-lesion histogram parameters derived from the stretched-exponential diffusion model for benign and malignant breast lesions, compared them with conventional apparent diffusion coefficient (ADC), and further determined which histogram metrics can be best used to differentiate malignant from benign lesions. This was a prospective study. Seventy females were included in the study. Multi-b value DWI was performed on a 1.5T scanner. Histogram parameters of whole lesions for distributed diffusion coefficient (DDC), heterogeneity index (α), and ADC were calculated by two radiologists and compared among benign lesions, ductal carcinoma in situ (DCIS), and invasive carcinoma confirmed by pathology. Nonparametric tests were performed for comparisons among invasive carcinoma, DCIS, and benign lesions. Comparisons of receiver operating characteristic (ROC) curves were performed to show the ability to discriminate malignant from benign lesions. The majority of histogram parameters (mean/min/max, skewness/kurtosis, 10-90 th percentile values) from DDC, α, and ADC were significantly different among invasive carcinoma, DCIS, and benign lesions. DDC 10% (area under curve [AUC] = 0.931), ADC 10% (AUC = 0.893), and α mean (AUC = 0.787) were found to be the best metrics in differentiating benign from malignant tumors among all histogram parameters derived from ADC and α, respectively. The combination of DDC 10% and α mean , using logistic regression, yielded the highest sensitivity (90.2%) and specificity (95.5%). DDC 10% and α mean derived from

Topical delivery of a preformed photosensitizer for photodynamic therapy of cutaneous lesions

NASA Astrophysics Data System (ADS)

Oleinick, Nancy L.; Kenney, Malcolm E.; Lam, Minh; McCormick, Thomas; Cooper, Kevin D.; Baron, Elma D.

2012-02-01

Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 μL/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.

Mammalian Synthetic Biology: Time for Big MACs.

PubMed

Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

2016-10-21

The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

Cross-referencing yeast genetics and mammalian genomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hieter, P.; Basset, D.; Boguski, M.

1994-09-01

We have initiated a project that will systematically transfer information about yeast genes onto the genetic maps of mice and human beings. Rapidly expanding human EST data will serve as a source of candidate human homologs that will be repeatedly searched using yeast protein sequence queries. Search results will be automatically reported to participating labs. Human cDNA sequences from which the ESTs are derived will be mapped at high resolution in the human and mouse genomes. The comparative mapping information cross-references the genomic position of novel human cDNAs with functional information known about the cognate yeast genes. This should facilitatemore » the initial identification of genes responsible for mammalian mutant phenotypes, including human disease. In addition, the identification of mammalian homologs of yeast genes provides reagents for determining evolutionary conservation and for performing direct experiments in multicellular eukaryotes to enhance study of the yeast protein`s function. For example, ESTs homologous to CDC27 and CDC16 were identified, and the corresponding cDNA clones were obtained from ATTC, completely sequenced, and mapped on human and mouse chromosomes. In addition, the CDC17hs cDNA has been used to raise antisera to the CDC27Hs protein and used in subcellular localization experiments and junctional studies in mammalian cells. We have received funding from the National Center for Human Genome Research to provide a community resource which will establish comprehensive cross-referencing among yeast, human, and mouse loci. The project is set up as a service and information on how to communicate with this effort will be provided.« less

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions

PubMed Central

Gillen, Kelly M.; Mubarak, Mayyan; Nguyen, Thanh D.; Pitt, David

2018-01-01

Microglia are resident immune cells that fulfill protective and homeostatic functions in the central nervous system (CNS) but may also promote neurotoxicity in the aged brain and in chronic disease. In multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS, microglia and macrophages contribute to the development of white matter lesions through myelin phagocytosis, and possibly to disease progression through diffuse activation throughout myelinated white matter. In this review, we discuss an additional compartment of myeloid cell activation in MS, i.e., the rim and normal adjacent white matter of chronic active lesions. In chronic active lesions, microglia and macrophages may contain high amounts of iron, express markers of proinflammatory polarization, are activated for an extended period of time (years), and drive chronic tissue damage. Iron-positive myeloid cells can be visualized and quantified with quantitative susceptibility mapping (QSM), a magnetic resonance imaging technique. Thus, QSM has potential as an in vivo biomarker for chronic inflammatory activity in established white matter MS lesions. Reducing chronic inflammation associated with iron accumulation using existing or novel MS therapies may impact disease severity and progression. PMID:29515576

Congenital lesions of epithelial origin.

PubMed

Hills, Susannah E; Maddalozzo, John

2015-02-01

Defects of embryologic development give rise to a variety of congenital lesions arising from the epithelium and are among the most common congenital lesions of the head and neck in the pediatric population. This article presents several congenital lesions of epithelial origin, including congenital midline cervical cleft, pilomatrixoma, dermoid, foregut duplication cysts, and preauricular sinuses and pits. In addition, the management of these lesions is reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

An automatic quantification system for MS lesions with integrated DICOM structured reporting (DICOM-SR) for implementation within a clinical environment

NASA Astrophysics Data System (ADS)

Jacobs, Colin; Ma, Kevin; Moin, Paymann; Liu, Brent

2010-03-01

Multiple Sclerosis (MS) is a common neurological disease affecting the central nervous system characterized by pathologic changes including demyelination and axonal injury. MR imaging has become the most important tool to evaluate the disease progression of MS which is characterized by the occurrence of white matter lesions. Currently, radiologists evaluate and assess the multiple sclerosis lesions manually by estimating the lesion volume and amount of lesions. This process is extremely time-consuming and sensitive to intra- and inter-observer variability. Therefore, there is a need for automatic segmentation of the MS lesions followed by lesion quantification. We have developed a fully automatic segmentation algorithm to identify the MS lesions. The segmentation algorithm is accelerated by parallel computing using Graphics Processing Units (GPU) for practical implementation into a clinical environment. Subsequently, characterized quantification of the lesions is performed. The quantification results, which include lesion volume and amount of lesions, are stored in a structured report together with the lesion location in the brain to establish a standardized representation of the disease progression of the patient. The development of this structured report in collaboration with radiologists aims to facilitate outcome analysis and treatment assessment of the disease and will be standardized based on DICOM-SR. The results can be distributed to other DICOM-compliant clinical systems that support DICOM-SR such as PACS. In addition, the implementation of a fully automatic segmentation and quantification system together with a method for storing, distributing, and visualizing key imaging and informatics data in DICOM-SR for MS lesions improves the clinical workflow of radiologists and visualizations of the lesion segmentations and will provide 3-D insight into the distribution of lesions in the brain.

Hypothyroid-associated central vestibular disease in 10 dogs: 1999-2005.

PubMed

Higgins, Michael A; Rossmeisl, John H; Panciera, David L

2006-01-01

With the exception of myxedema coma, central nervous system signs are rare in hypothyroid dogs. Central vestibular dysfunction is a possible and reversible manifestation of hypothyroidism. Medical records of dogs with vestibular dysfunction and hypothyroidism were reviewed. Of 113 records identified, 10 dogs with at least 2 concurrent clinical neurologic abnormalities localizable to the central vestibular system were included. Retrospective, descriptive study. Median age at diagnosis was 7 years (range, 5-10 years). All dogs were referred for progressive neurologic disease. Lesions were localized to the myelencephalic region in 5 dogs and to the vestibulocerebellum in 5 dogs. Two dogs had evidence of multifocal intracranial disease. Non-neurologic physical abnormalities suggestive of hypothyroidism were absent in 7 of 10 dogs. Hypercholesterolemia was the only consistent clinicopathologic abnormality detected, and was present in 7 of 10 dogs. All dogs had total thyroxine (TT4) and free thyroxine (fT4) concentrations below reference ranges, and 9 of 10 had increased TSH concentrations. Intracranial imaging studies were normal in 5 of 8 dogs, and identified lesions consistent with infarctions in 3 of 8 dogs. Albuminocytologic dissociation was detected in 5 of 6 CSF analyses. Brainstem auditory-evoked responses disclosed prolonged wave V latencies in 3 of 4 dogs tested. No other causes of central vestibular dysfunction were identified during other diagnostic investigations. The median time from initiation of treatment to clinical improvement was 4 days. Vestibular signs resolved in 9 of 10 dogs within 4 weeks. Although the pathogenesis in dogs without evidence of infarction is unknown, central vestibular dysfunction appears to be a rare but reversible neurologic sequelae of hypothyroidism.

Effects of simulated weightlessness on mammalian development. Part 1: Development of clinostat for mammalian tissue culture and use in studies on meiotic maturation of mouse oocytes

NASA Technical Reports Server (NTRS)

Wolegemuth, D. J.; Grills, G. S.

1984-01-01

The effects of weightlessness on three aspects of mammalian reproduction: oocyte development, fertilization, and early embryogenesis was studied. Zero-gravity conditions within the laboratory by construction of a clinostat designed to support in vitro tissue culture were simulated and the effects of simulated weightlessness on meiotic maturation in mammalian oocytes using mouse as the model system were studied. The timing and frequency of germinal vesicule breakdown and polar body extrusion, and the structural and numerical properties of meiotic chromosomes at Metaphase and Metaphase of meiosis are assessed.

Concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation.

PubMed

Li, John; Weissberg, Zoe; Bevilacqua, Thomas A; Yu, Gordon; Weber, Kristy; Sebro, Ronnie

2018-04-01

To compare the concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation. Retrospective review of 215 FNAs of osseous lesions performed in conjunction with core biopsy at our institution over a 6-year period (2011-2016). FNAs were interpreted independently of core biopsies. We assessed if FNA in conjunction with core biopsy increased diagnostic accuracy compared to core biopsy alone. We also calculated the concordance between FNA and core biopsy by lesion appearance, lesion CT attenuation, lesion histology, lesion location and FNA needle gauge size. Core biopsy alone provided the diagnosis in 207/215 cases (96.3%), however, the FNA provided the diagnosis in the remaining 8/215 cases (3.7%) where the core biopsy was non-diagnostic. There were 154 (71.6%) lytic lesions, 21 (9.8%) blastic lesions, 25 (11.6%) mixed lytic and blastic lesions and 15 (7.0%) lesions that were neither lytic nor blastic. The concordance between FNA and core biopsy for lytic osseous lesions (136/154 cases, 88.3%) was statistically significantly higher than that for blastic osseous lesions (13/21 cases, 61.9%) [P = 4.2 × 10 -3 ; 95% CI (0.02, 0.50)]. The concordance between FNA and core biopsy was higher for low-attenuation- (110/126) than high-attenuation (58/77) lesions (P = 0.028). The concordance between FNA and core biopsy was also higher for metastases (102/119 cases, 85.7%) than non-metastases (78/96, 81.3%) [P = 0.487; 95% CI (- 0.15, 0.065)]. There was no difference in the rate of concordance between FNA and core biopsy by lesion location or FNA needle gauge size (P > 0.05). FNA with core biopsy increases diagnostic rate compared to core biopsy alone or FNA alone. The concordance between FNA and core biopsy is higher for lytic lesions than for blastic lesions; and higher for low-attenuation lesions than for high-attenuation lesions.

Mammalian Polyamine Metabolism and Function

PubMed Central

Pegg, Anthony E.

2009-01-01

Summary Polyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism. PMID:19603518

Epidermal hydrogen peroxide is not increased in lesional and non-lesional skin of vitiligo.

PubMed

Zailaie, Mohammad Z

2017-01-01

It is widely believed that the loss of the epidermal melanocytes in vitiligo is basically due to excessive oxidative stress. Previous research work described abnormal elevation of the absolute concentration of the epidermal hydrogen peroxide (H 2 O 2 ) in lesional and non-lesional skin of vitiligo. Based on this finding, our primary research objective was to use this feature as a screening marker in individuals at a great risk of developing vitiligo. Ninety-six patients of non-segmental vitiligo (NSV) of varying durations, skin phototypes, and treatment modalities (psoralen UVA-, narrow band UVB-treated) were recruited for this study. Raman spectroscopic measurements, using an external probehead, of the lesional and non-lesional skin were obtained, and the resulting spectra were analyzed using the Opus software package of the MultiRam spectrometer and the intensity of the peak at 875 cm -1 that represents the absolute concentration of H 2 O 2 was calculated. Contrary to previous reports, in patients of skin phototype IV, the absolute concentrations of H 2 O 2 in non-lesional and lesional NSV of all groups were non-significantly decreased compared to normal control. In patients of NSV of skin phototype V, the decrease in the absolute concentrations of H 2 O 2 was not significant in the untreated group, and a slight non-significant increase in the NBUVB-treated group was noted. However, in the PUVA-treated group, the non-lesional skin demonstrated significant increase in the absolute concentration of H 2 O 2 , whereas the lesional skin showed only a slight non-significant increase compared to normal control. In NSV patients of skin phototype VI who were previously treated with PUVA, the non-lesional skin showed a slight non-significant increase in the absolute concentration of H 2 O 2 ; however, the lesional skin showed a marked significant decrease compared to normal control and the non-lesional skin. Thereof, one can conclude that the epidermal H 2 O 2 is not

Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic protein in mammalian cells

PubMed Central

Miyazaki, Yusuke; Chen, Ling-chun; Chu, Bernard W; Swigut, Tomek; Wandless, Thomas J

2015-01-01

Eukaryotic cells possess a variety of signaling pathways that prevent accumulation of unfolded and misfolded proteins. Chief among these is the heat shock response (HSR), which is assumed to respond to unfolded proteins in the cytosol and nucleus alike. In this study, we probe this axiom further using engineered proteins called ‘destabilizing domains’, whose folding state we control with a small molecule. The sudden appearance of unfolded protein in mammalian cells elicits a robust transcriptional response, which is distinct from the HSR and other known pathways that respond to unfolded proteins. The cellular response to unfolded protein is strikingly different in the nucleus and the cytosol, although unfolded protein in either compartment engages the p53 network. This response provides cross-protection during subsequent proteotoxic stress, suggesting that it is a central component of protein quality control networks, and like the HSR, is likely to influence the initiation and progression of human pathologies. DOI: http://dx.doi.org/10.7554/eLife.07687.001 PMID:26314864

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão’s legacy

PubMed Central

Shuttleworth, C William; Kirov, Sergei A; Ayata, Cenk; Hinzman, Jason M; Foreman, Brandon; Andrew, R David; Boutelle, Martyn G; Brennan, KC; Carlson, Andrew P; Dahlem, Markus A; Drenckhahn, Christoph; Dohmen, Christian; Fabricius, Martin; Farkas, Eszter; Feuerstein, Delphine; Graf, Rudolf; Helbok, Raimund; Lauritzen, Martin; Major, Sebastian; Oliveira-Ferreira, Ana I; Richter, Frank; Rosenthal, Eric S; Sakowitz, Oliver W; Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Strong, Anthony J; Urbach, Anja; Westover, M Brandon; Winkler, Maren KL; Witte, Otto W; Woitzik, Johannes; Dreier, Jens P

2016-01-01

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão’s historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage. PMID:27328690

Covalently Linked Tandem Lesions in DNA

PubMed Central

Patrzyc, Helen B.; Dawidzik, Jean B.; Budzinski, Edwin E.; Freund, Harold G.; Wilton, John H.; Box, Harold C.

2013-01-01

Reactive oxygen species (ROS) generate a type of DNA damage called tandem lesions, two adjacent nucleotides both modified. A subcategory of tandem lesions consists of adjacent nucleotides linked by a covalent bond. Covalently linked tandem lesions generate highly characteristic liquid chromotography-tandem mass spectrometry (LC-MS/MS) elution profiles. We have used this property to comprehensively survey X-irradiated DNA for covalently linked tandem lesions. A total of 15 tandem lesions were detected in DNA irradiated in deoxygenated aqueous solution, five tandem lesions were detected in DNA that was irradiated in oxygenated solution. PMID:23106212

H5N1 pathogenesis studies in mammalian models

PubMed Central

Belser, Jessica A.; Tumpey, Terrence M.

2017-01-01

H5N1 influenza viruses are capable of causing severe disease and death in humans, and represent a potential pandemic subtype should they acquire a transmissible phenotype. Due to the expanding host and geographic range of this virus subtype, there is an urgent need to better understand the contribution of both virus and host responses following H5N1 virus infection to prevent and control human disease. The use of mammalian models, notably the mouse and ferret, has enabled the detailed study of both complex virus–host interactions as well as the contribution of individual viral proteins and point mutations which influence virulence. In this review, we describe the behavior of H5N1 viruses which exhibit high and low virulence in numerous mammalian species, and highlight the contribution of inoculation route to virus pathogenicity. The involvement of host responses as studied in both inbred and outbred mammalian models is discussed. The roles of individual viral gene products and molecular determinants which modulate the severity of H5N1 disease in vivo are presented. This research contributes not only to our understanding of influenza virus pathogenesis, but also identifies novel preventative and therapeutic targets to mitigate the disease burden caused by avian influenza viruses. PMID:23458998

Prevalence of most commonly reported tobacco-associated lesions in central Gujarat: A hospital-based cross-sectional study.

PubMed

Joshi, Manjiri; Tailor, Mansi

2016-01-01

Oral cancer is a major health problem in tobacco users worldwide and is one of the ten most common cancers. India alone accounts for 1/3 rd of the world's oral cancer and has a high rate of potentially malignant disorders (PMDs). The most common predisposing factors are smoking, smokeless tobacco, betel nut in quid form (pan), alcohol, spicy food, and sharp broken tooth. There are various tobacco-associated lesions (TALs) which can be diagnosed at very early stage. This study was conducted to rule out association of smoking and smokeless tobacco with occurrence of TALs and its dose-response relationship. Total of 60,018 patients attending the Department of Oral Medicine and Radiology from January 2013 to December 2014 with different oral and dental symptoms were screened. Of these, 4795 patients satisfying inclusion and exclusion criteria formed the cohort of the present study. All the patients were informed regarding the study and an informed verbal consent was obtained, following which they were interviewed for tobacco-related habits and examined by the trained dental professionals for the presence of any lesion. Along with patients' demographic details, information regarding the type of habit, duration, and frequency was recorded. Statistical analysis was performed using STATA 13.1 software (STATA 13.1 software by Stata Corp Ltd India Continent) by applying Pearson's Chi-square test with Fisher's exact test, Independent t-test, and ANOVA test. The overall study population showed maximum cases having habit of smokeless tobacco (37.9%) and smoking tobacco (36.5%). The overall prevalence of TALs was found to be 7.98%. Our study found strong relation of duration and frequency of habit with respect to occurrence of the lesions. TALs are often subtle and asymptomatic. Therefore, it is important for the clinician to maintain a high index of suspicion, especially if risk factors such as tobacco habits are present.

Enamel formation and growth in non-mammalian cynodonts

PubMed Central

Dirks, Wendy; Martinelli, Agustín G.

2018-01-01

The early evolution of mammals is associated with the linked evolutionary origin of diphyodont tooth replacement, rapid juvenile growth and determinate adult growth. However, specific relationships among these characters during non-mammalian cynodont evolution require further exploration. Here, polarized light microscopy revealed incremental lines, resembling daily laminations of extant mammals, in histological sections of enamel in eight non-mammalian cynodont species. In the more basal non-probainognathian group, enamel extends extremely rapidly from cusp to cervix. By contrast, the enamel of mammaliamorphs is gradually accreted, with slow rates of crown extension, more typical of the majority of non-hypsodont crown mammals. These results are consistent with the reduction in dental replacement rate across the non-mammalian cynodont lineage, with greater rates of crown extension required in most non-probainognathians, and slower crown extension rates permitted in mammaliamorphs, which have reduced patterns of dental replacement in comparison with many non-probainognathians. The evolution of mammal-like growth patterns, with faster juvenile growth and more abruptly terminating adult growth, is linked with this reduction in dental replacement rates and may provide an additional explanation for the observed pattern in enamel growth rates. It is possible that the reduction in enamel extension rates in mammaliamorphs reflects an underlying reduction in skeletal growth rates at the time of postcanine formation, due to a more abruptly terminating pattern of adult growth in these more mammal-like, crownward species. PMID:29892415

MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

PubMed

Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

2017-03-15

Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

AV3V lesions attenuate the cardiovascular responses produced by blood-borne excitatory amino acid analogs

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Beltz, T. G.; Lewis, S. J.; Johnson, A. K.

1999-01-01

Systemic injections of the excitatory amino acid (EAA) analogs, kainic acid (KA) and N-methyl-D-aspartate (NMDA), produce a pressor response in conscious rats that is caused by a centrally mediated activation of sympathetic drive and the release of arginine vasopressin (AVP). This study tested the hypothesis that the tissue surrounding the anteroventral part of the third ventricle (AV3V) plays a role in the expression of the pressor responses produced by systemically injected EAA analogs. Specifically, we examined whether prior electrolytic ablation of the AV3V region would affect the pressor responses to KA and NMDA (1 mg/kg iv) in conscious rats. The KA-induced pressor response was smaller in AV3V-lesioned than in sham-lesioned rats (11 +/- 2 vs. 29 +/- 2 mmHg; P < 0.05). After ganglion blockade, KA produced a pressor response in sham-lesioned but not AV3V-lesioned rats (+27 +/- 3 vs. +1 +/- 2 mmHg; P < 0.05). The KA-induced pressor response in ganglion-blocked sham-lesioned rats was abolished by a vasopressin V1-receptor antagonist. Similar results were obtained with NMDA. The pressor response to AVP (10 ng/kg iv) was slightly smaller in AV3V-lesioned than in sham-lesioned ganglion-blocked rats (45 +/- 3 vs. 57 +/- 4 mmHg; P < 0.05). This study demonstrates that the pressor responses to systemically injected EAA analogs are smaller in AV3V-lesioned rats. The EAA analogs may produce pressor responses by stimulation of EAA receptors in the AV3V region, or the AV3V region may play an important role in the expression of these responses.

Emergence of mammalian cell-adapted vesicular stomatitis virus from persistent infections of insect vector cells.

PubMed

Novella, Isabel S; Ebendick-Corpus, Bonnie E; Zárate, Selene; Miller, Eric L

2007-06-01

Arboviruses (arthropod-borne viruses) represent quintessential generalists, with the ability to infect and perform well in multiple hosts. However, antagonistic pleiotropy imposed a cost during the adaptation to persistent replication of vesicular stomatitis virus in sand fly cells and resulted in strains that initially replicated poorly in hamster cells, even when the virus was allowed to replicate periodically in the latter. Once a debilitated strain started replicating continuously in mammalian cells, fitness increased significantly. Fitness recovery did not entail back mutations or compensatory mutations, but instead, we observed the replacement of persistence-adapted genomes by mammalian cell-adapted strains with a full set of new, unrelated sequence changes. These mammalian cell-adapted genomes were present at low frequencies in the populations with a history of persistence for up to a year and quickly became dominant during mammalian infection, but coexistence was not stable in the long term. Periodic acute replication in mammalian cells likely contributed to extending the survival of minority genomes, but these genomes were also found in strictly persistent populations.

Involvement of mast cells and microvessels density in reactive lesions of oral cavity: A comparative immunohistochemical study.

PubMed

Ferreira, Stephany Vasco; Xavier, Flávia Caló Aquino; Freitas, Maria da Conceição Andrade de; Nunes, Fábio Daumas; Gurgel, Clarissa Araújo; Cangussu, Maria Cristina Teixeira; Martins, Manoela Domingues; Freitas, Valéria Souza; Dos Santos, Jean Nunes

2016-09-01

In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effect of Lesion Baseline Severity and Mineral Distribution on Remineralization and Progression of Human and Bovine Dentin Caries Lesions.

PubMed

Lippert, Frank; Churchley, David; Lynch, Richard J

2015-01-01

The aims of this laboratory study were to compare the effects of lesion baseline severity, mineral distribution and substrate on remineralization and progression of caries lesions created in root dentin. Lesions were formed in dentin specimens prepared from human and bovine dentin using three protocols, each utilizing three demineralization periods to create lesions of different mineral distributions (subsurface, moderate softening, extreme softening) and severity within each lesion type. Lesions were then either remineralized or demineralized further and analyzed using transverse microradiography. At lesion baseline, no differences were found between human and bovine dentin for integrated mineral loss (x0394;Z). Differences in mineral distribution between lesion types were apparent. Human dentin lesions were more prone to secondary demineralization (x0394;x0394;Z) than bovine dentin lesions, although there were no differences in x0394;L. Likewise, smaller lesions were more susceptible to secondary demineralization than larger ones. Subsurface lesions were more acid-resistant than moderately and extremely softened lesions. After remineralization, differences between human and bovine dentin lesions were not apparent for x0394;x0394;Z although bovine dentin lesions showed greater reduction in lesion depth L. For lesion types, responsiveness to remineralization (x0394;x0394;Z) was in the order extremely softened>moderately softened>subsurface. More demineralized lesions exhibited greater remineralization than shallower ones. In summary, some differences exist between human and bovine dentin and their relative responsiveness to de- and remineralization. These differences, however, were overshadowed by the effects of lesion baseline mineral distribution and severity. Thus, bovine dentin appears to be a suitable substitute for human dentin in mechanistic root caries studies. © 2015 S. Karger AG, Basel.

Staged marginal contoured and central excision technique in the surgical management of perianal Paget's disease.

PubMed

Möller, Mecker G; Lugo-Baruqui, Jose Alejandro; Milikowski, Clara; Salgado, Christopher J

2014-04-01

Extramammary Paget's disease (EMPD) is an adenocarcinoma of the apocrine glands with unknown exact prevalence and obscure etiology. It has been divided into primary EMPD and secondary EMPD, in which an internal malignancy is usually associated. Treatment for primary EMPD usually consists of wide lesion excision with negative margins. Multiple methods have been proposed to obtain free-margin status of the disease. These include visible border lesion excision, punch biopsies, and micrographic and frozen-section surgery, with different results but still high recurrence rates. The investigators propose a method consisting of a staged contoured marginal excision using "en face" permanent pathologic analysis preceding the steps of central excision of the lesion and the final reconstruction of the surgical defect. Advantages of this method include adequate margin control allowing final reconstruction and tissue preservation, while minimizing patient discomfort. The staged contoured marginal and central excision technique offers a new alternative to the armamentarium for surgical oncologists for the management of EMPD in which margin control is imperative for control of recurrence rates. Copyright © 2014 Elsevier Inc. All rights reserved.

Influences of Different Large Mammalian Fauna on Dung Beetle Diversity in Beech Forests

PubMed Central

Enari, Hiroto; Koike, Shinsuke; Sakamaki, Haruka

2013-01-01

This paper focuses on biological relationships between mammalian species richness and the community structure of dung beetles in cool-temperate forests in the northernmost part of mainland Japan. The composition of beetle assemblages was evaluated at 3 sites in undisturbed beech forests with different mammalian fauna. In spring and summer 2009, beetles were collected at each site using pitfall traps baited with feces from Japanese macaques, Macaca fuscata Blyth (Primates: Cercopithecidae); Asiatic black bears, Ursus thibetanus Cuvier (Carnivora: Ursidae); Japanese serows, Capricornis crispus Temminck (Artiodactyla: Bovidae); and cattle. In the present study, 1,862 dung beetles representing 14 species were collected, and most dung beetles possessed the ecological characteristic of selecting specific mammalian feces. The present findings indicated that although species diversity in dung beetle assemblages was not necessarily positively correlated with mammalian species richness in cool-temperate forests, the absence of the macaque population directly resulted in the marked reduction of the beetle abundance, with the loss of the most frequent species, Aphodius eccoptus Bates (Coleoptera: Scarabaeidae) during spring. PMID:23909510

Design and construction of targeted AAVP vectors for mammalian cell transduction.

PubMed

Hajitou, Amin; Rangel, Roberto; Trepel, Martin; Soghomonyan, Suren; Gelovani, Juri G; Alauddin, Mian M; Pasqualini, Renata; Arap, Wadih

2007-01-01

Bacteriophage (phage) evolved as bacterial viruses, but can be adapted to transduce mammalian cells through ligand-directed targeting to a specific receptor. We have recently reported a new generation of hybrid prokaryotic-eukaryotic vectors, which are chimeras of genetic cis-elements of recombinant adeno-associated virus and phage (termed AAVP). This protocol describes the design and construction of ligand-directed AAVP vectors, production of AAVP particles and the methodology to transduce mammalian cells in vitro and to target tissues in vivo after systemic administration. Targeted AAVP particles are made in a two-step process. First, a ligand peptide of choice is displayed on the coat protein to generate a targeted backbone phage vector. Then, a recombinant AAV carrying a mammalian transgene cassette is inserted into an intergenomic region. High-titer suspensions (approximately 10(10)-10(11) transducing units per microl) can be produced within 3 days after vector construction. Transgene expression by targeted AAVP usually reaches maximum levels within 1 week.

Mammalian basal metabolic rate is proportional to body mass2/3

PubMed Central

White, Craig R.; Seymour, Roger S.

2003-01-01

The relationship between mammalian basal metabolic rate (BMR, ml of O2 per h) and body mass (M, g) has been the subject of regular investigation for over a century. Typically, the relationship is expressed as an allometric equation of the form BMR = aMb. The scaling exponent (b) is a point of contention throughout this body of literature, within which arguments for and against geometric (b = 2/3) and quarter-power (b = 3/4) scaling are made and rebutted. Recently, interest in the topic has been revived by published explanations for quarter-power scaling based on fractal nutrient supply networks and four-dimensional biology. Here, a new analysis of the allometry of mammalian BMR that accounts for variation associated with body temperature, digestive state, and phylogeny finds no support for a metabolic scaling exponent of 3/4. Data encompassing five orders of magnitude variation in M and featuring 619 species from 19 mammalian orders show that BMR ∝ M2/3. PMID:12637681

Neuronal network-based mathematical modeling of perceived verticality in acute unilateral vestibular lesions: from nerve to thalamus and cortex.

PubMed

Glasauer, S; Dieterich, M; Brandt, T

2018-05-29

Acute unilateral lesions of vestibular graviceptive pathways from the otolith organs and semicircular canals via vestibular nuclei and the thalamus to the parieto-insular vestibular cortex regularly cause deviations of perceived verticality in the frontal roll plane. These tilts are ipsilateral in peripheral and in ponto-medullary lesions and contralateral in ponto-mesencephalic lesions. Unilateral lesions of the vestibular thalamus or cortex cause smaller tilts of the perceived vertical, which may be either ipsilateral or contralateral. Using a neural network model, we previously explained why unilateral vestibular midbrain lesions rarely manifest with rotational vertigo. We here extend this approach, focussing on the direction-specific deviations of perceived verticality in the roll plane caused by acute unilateral vestibular lesions from the labyrinth to the cortex. Traditionally, the effect of unilateral peripheral lesions on perceived verticality has been attributed to a lesion-based bias of the otolith system. We here suggest, on the basis of a comparison of model simulations with patient data, that perceived visual tilt after peripheral lesions is caused by the effect of a torsional semicircular canal bias on the central gravity estimator. We further argue that the change of gravity coding from a peripheral/brainstem vectorial representation in otolith coordinates to a distributed population coding at thalamic and cortical levels can explain why unilateral thalamic and cortical lesions have a variable effect on perceived verticality. Finally, we propose how the population-coding network for gravity direction might implement the elements required for the well-known perceptual underestimation of the subjective visual vertical in tilted body positions.

Tumor-induced Osteomalacia in a 3-Year-Old With Unresectable Central Giant Cell Lesions.

PubMed

Crossen, Stephanie S; Zambrano, Eduardo; Newman, Beverley; Bernstein, Jonathan A; Messner, Anna H; Bachrach, Laura K; Twist, Clare J

2017-01-01

Tumor-induced osteomalacia (TIO) is a rare cause of hypophosphatemia involving overproduction of fibroblast growth factor 23. TIO has been described largely in adults with small mesenchymal tumors. We report a case of TIO in a child who presented with knee pain and radiographic findings concerning for rickets, and was found to have maxillomandibular giant cell lesions. The patient was treated with oral phosphorus and calcitriol, surgical debulking, and intralesional corticosteroids, which resulted in tumor regression and normalization of serum fibroblast growth factor 23 and phosphorus. This case illustrates the occurrence of this rare paraneoplastic syndrome in children and adds to our knowledge about clinical manifestations and pathologic findings associated with pediatric TIO.

A dual host vector for Fab phage display and expression of native IgG in mammalian cells.

PubMed

Tesar, Devin; Hötzel, Isidro

2013-10-01

A significant bottleneck in antibody discovery by phage display is the transfer of immunoglobulin variable regions from phage clones to vectors that express immunoglobulin G (IgG) in mammalian cells for screening. Here, we describe a novel phagemid vector for Fab phage display that allows expression of native IgG in mammalian cells without sub-cloning. The vector uses an optimized mammalian signal sequence that drives robust expression of Fab fragments fused to an M13 phage coat protein in Escherichia coli and IgG expression in mammalian cells. To allow the expression of Fab fragments fused to a phage coat protein in E.coli and full-length IgG in mammalian cells from the same vector without sub-cloning, the sequence encoding the phage coat protein was embedded in an optimized synthetic intron within the immunoglobulin heavy chain gene. This intron is removed from transcripts in mammalian cells by RNA splicing. Using this vector, we constructed a synthetic Fab phage display library with diversity in the heavy chain only and selected for clones binding different antigens. Co-transfection of mammalian cells with DNA from individual phage clones and a plasmid expressing the invariant light chain resulted in the expression of native IgG that was used to assay affinity, ligand blocking activity and specificity.

Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin.

PubMed

Ogrodnik, Mikołaj; Salmonowicz, Hanna; Brown, Rachel; Turkowska, Joanna; Średniawa, Władysław; Pattabiraman, Sundararaghavan; Amen, Triana; Abraham, Ayelet-chen; Eichler, Noam; Lyakhovetsky, Roman; Kaganovich, Daniel

2014-06-03

Aging is associated with the accumulation of several types of damage: in particular, damage to the proteome. Recent work points to a conserved replicative rejuvenation mechanism that works by preventing the inheritance of damaged and misfolded proteins by specific cells during division. Asymmetric inheritance of misfolded and aggregated proteins has been shown in bacteria and yeast, but relatively little evidence exists for a similar mechanism in mammalian cells. Here, we demonstrate, using long-term 4D imaging, that the vimentin intermediate filament establishes mitotic polarity in mammalian cell lines and mediates the asymmetric partitioning of damaged proteins. We show that mammalian JUNQ inclusion bodies containing soluble misfolded proteins are inherited asymmetrically, similarly to JUNQ quality-control inclusions observed in yeast. Mammalian IPOD-like inclusion bodies, meanwhile, are not always inherited by the same cell as the JUNQ. Our study suggests that the mammalian cytoskeleton and intermediate filaments provide the physical scaffold for asymmetric inheritance of dynamic quality-control JUNQ inclusions. Mammalian IPOD inclusions containing amyloidogenic proteins are not partitioned as effectively during mitosis as their counterparts in yeast. These findings provide a valuable mechanistic basis for studying the process of asymmetric inheritance in mammalian cells, including cells potentially undergoing polar divisions, such as differentiating stem cells and cancer cells.

Is the morphology and activity of the occlusal carious lesion related to the lesion progression stage?

PubMed

Neves, Aline Almeida; Vargas, Daniel Otero Amaral; Santos, Thais Maria Pires; Lopes, Ricardo Tadeu; Sousa, Frederico Barbosa

2016-12-01

To investigate the relationship between degree of dentin demineralization with both lesion activity and morphology of the occlusal carious cavity. Occlusal sites (n=138) were identified by visual examination (Nyvad's scores 0-6) in 67 extracted teeth which were scanned in a high energy micro-CT. After 3D reconstruction, each stack was resliced in the mesio-distal direction and tooth mineral density (MD) was measured along a path from enamel to the deepest part of dentin in the slice showing the most severe carious involvement. Each site was classified in "open" or "closed" (if cavitated) depending on the morphology of the surrounding enamel walls as measured using micro-CT and as active or inactive in enamel or dentin by a clinical scoring system. Lesions showing dentin cavitation presented higher demineralization degree compared to non-cavitated, or enamel cavitated lesions. Inactive lesions presented lower demineralization degree compared to active lesions, although with a low effect size. According to the morphological aspect of the carious cavity, open enamel lesions showed lower dentin demineralization degree than closed lesion environments. Active lesions showed higher dentin demineralization degree than inactive ones, while lesions showing closed cavitation resulted in higher dentin demineralization degree only for enamel lesions. Including those parameters in treatment decisions may help to improve prognosis and increase effectiveness of the caries diagnostic systems in the clinical setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Amygdala central nucleus interacts with dorsolateral striatum to regulate the acquisition of habits

PubMed Central

Lingawi, Nura W.; Balleine, Bernard W.

2012-01-01

The role of the amygdala central nucleus (CeN) in habit learning was assessed in two experiments. First we examined the effects of bilateral lesions of the anterior CeN on an overtraining-induced lever press habit evaluated using an outcome devaluation protocol. Overtraining generated habitual performance and rendered sham lesioned rats insensitive to outcome devaluation, an effect that was also found in rats given control lesions of the posterior CeN. In contrast, rats with lesions of the anterior CeN did not show normal habit acquisition and their performance remained goal-directed and sensitive to outcome devaluation. Nevertheless, lesions of either the posterior or the anterior CeN abolished the general excitatory influence of a Pavlovian CS on instrumental performance. Next we assessed the functional interaction between the CeN and dorsolateral striatum (DLS), a region previously implicated in the acquisition of habits, using asymmetrical lesions to disconnect these structures. Rats were given a unilateral lesion of anterior CeN and a unilateral lesion of the DLS, made either ipsilateral (control) or contralateral (disconnection) to the CeN lesion, and given overtraining followed by outcome devaluation. Although the ipsilateral lesioned rats were insensitive to devaluation, the contralateral CeN-DLS lesion impaired habit acquisition rendering performance sensitive to the devaluation treatment. These results are the first to implicate the CeN and its connection with a circuit involving DLS in habit learning. They imply that, in instrumental conditioning, regions of amygdala parse the instrumental outcome into the reward and reinforcement signals mediating goal-directed and habitual actions, respectively. PMID:22262905

Imaging modalities for characterising focal pancreatic lesions.

PubMed

Best, Lawrence Mj; Rawji, Vishal; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-17

Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions. To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions. We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively. Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical

Constitutive Expression of Mammalian Nitric Oxide Synthase in Tobacco Plants Triggers Disease Resistance to Pathogens

PubMed Central

Chun, Hyun Jin; Park, Hyeong Cheol; Koo, Sung Cheol; Lee, Ju Huck; Park, Chan Young; Choi, Man Soo; Kang, Chang Ho; Baek, Dongwon; Cheong, Yong Hwa; Yun, Dae-Jin; Chung, Woo Sik; Cho, Moo Je; Kim, Min Chul

2012-01-01

Nitric oxide (NO) is known for its role in the activation of plant defense responses. To examine the involvement and mode of action of NO in plant defense responses, we introduced calmodulin-dependent mammalian neuronal nitric oxide synthase (nNOS), which controls the CaMV35S promoter, into wild-type and NahG tobacco plants. Constitutive expression of nNOS led to NO production and triggered spontaneous induction of leaf lesions. Transgenic plants accumulated high amounts of H2O2, with catalase activity lower than that in the wild type. nNOS transgenic plants contained high levels of salicylic acid (SA), and they induced an array of SA-, jasmonic acid (JA)-, and/or ethylene (ET)-related genes. Consequently, NahG co-expression blocked the induction of systemic acquired resistance (SAR)-associated genes in transgenic plants, implying SA is involved in NO-mediated induction of SAR genes. The transgenic plants exhibited enhanced resistance to a spectrum of pathogens, including bacteria, fungi, and viruses. Our results suggest a highly ranked regulatory role for NO in SA-, JA-, and/or ET-dependent pathways that lead to disease resistance. PMID:23124383

Imaging inflammatory acne: lesion detection and tracking

NASA Astrophysics Data System (ADS)

Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos

2010-02-01

It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

Molecular Markers for Interspecies Transmission of Avian Influenza Viruses in Mammalian Hosts

PubMed Central

Lee, Taehyung

2017-01-01

In the last decade, a wide range of avian influenza viruses (AIVs) have infected various mammalian hosts and continuously threaten both human and animal health. It is a result of overcoming the inter-species barrier which is mostly associated with gene reassortment and accumulation of mutations in their gene segments. Several recent studies have shed insights into the phenotypic and genetic changes that are involved in the interspecies transmission of AIVs. These studies have a major focus on transmission from avian to mammalian species due to the high zoonotic potential of the viruses. As more mammalian species have been infected with these viruses, there is higher risk of genetic evolution of these viruses that may lead to the next human pandemic which represents and raises public health concern. Thus, understanding the mechanism of interspecies transmission and molecular determinants through which the emerging AIVs can acquire the ability to transmit to humans and other mammals is an important key in evaluating the potential risk caused by AIVs among humans. Here, we summarize previous and recent studies on molecular markers that are specifically involved in the transmission of avian-derived influenza viruses to various mammalian hosts including humans, pigs, horses, dogs, and marine mammals. PMID:29236050

A p53-dependent response limits the viability of mammalian haploid cells

PubMed Central

Olbrich, Teresa; Mayor-Ruiz, Cristina; Vega-Sendino, Maria; Gomez, Carmen; Ortega, Sagrario; Ruiz, Sergio; Fernandez-Capetillo, Oscar

2017-01-01

The recent development of haploid cell lines has facilitated forward genetic screenings in mammalian cells. These lines include near-haploid human cell lines isolated from a patient with chronic myelogenous leukemia (KBM7 and HAP1), as well as haploid embryonic stem cells derived from several organisms. In all cases, haploidy was shown to be an unstable state, so that cultures of mammalian haploid cells rapidly become enriched in diploids. Here we show that the observed diploidization is due to a proliferative disadvantage of haploid cells compared with diploid cells. Accordingly, single-cell–sorted haploid mammalian cells maintain the haploid state for prolonged periods, owing to the absence of competing diploids. Although the duration of interphase is similar in haploid and diploid cells, haploid cells spend longer in mitosis, indicative of problems in chromosome segregation. In agreement with this, a substantial proportion of the haploids die at or shortly after the last mitosis through activation of a p53-dependent cytotoxic response. Finally, we show that p53 deletion stabilizes haploidy in human HAP1 cells and haploid mouse embryonic stem cells. We propose that, similar to aneuploidy or tetraploidy, haploidy triggers a p53-dependent response that limits the fitness of mammalian cells. PMID:28808015

Feedback repression is required for mammalian circadian clock function.

PubMed

Sato, Trey K; Yamada, Rikuhiro G; Ukai, Hideki; Baggs, Julie E; Miraglia, Loren J; Kobayashi, Tetsuya J; Welsh, David K; Kay, Steve A; Ueda, Hiroki R; Hogenesch, John B

2006-03-01

Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive. Here, we developed a molecular genetic screen in mammalian cells to identify mutants of the circadian transcriptional activators CLOCK and BMAL1, which were uncoupled from CRYPTOCHROME (CRY)-mediated transcriptional repression. Notably, mutations in the PER-ARNT-SIM domain of CLOCK and the C terminus of BMAL1 resulted in synergistic insensitivity through reduced physical interactions with CRY. Coexpression of these mutant proteins in cultured fibroblasts caused arrhythmic phenotypes in population and single-cell assays. These data demonstrate that CRY-mediated repression of the CLOCK/BMAL1 complex activity is required for maintenance of circadian rhythmicity and provide formal proof that transcriptional feedback is required for mammalian clock function.

Live-cell imaging of mammalian RNAs with Spinach2.

PubMed

Strack, Rita L; Jaffrey, Samie R

2015-01-01

The ability to monitor RNAs of interest in living cells is crucial to understanding the function, dynamics, and regulation of this important class of molecules. In recent years, numerous strategies have been developed with the goal of imaging individual RNAs of interest in living cells, each with their own advantages and limitations. This chapter provides an overview of current methods of live-cell RNA imaging, including a detailed discussion of genetically encoded strategies for labeling RNAs in mammalian cells. This chapter then focuses on the development and use of "RNA mimics of GFP" or Spinach technology for tagging mammalian RNAs and includes a detailed protocol for imaging 5S and CGG60 RNA with the recently described Spinach2 tag. © 2015 Elsevier Inc. All rights reserved.

Leadership in Mammalian Societies: Emergence, Distribution, Power, and Payoff.

PubMed

Smith, Jennifer E; Gavrilets, Sergey; Mulder, Monique Borgerhoff; Hooper, Paul L; Mouden, Claire El; Nettle, Daniel; Hauert, Christoph; Hill, Kim; Perry, Susan; Pusey, Anne E; van Vugt, Mark; Smith, Eric Alden

2016-01-01

Leadership is an active area of research in both the biological and social sciences. This review provides a transdisciplinary synthesis of biological and social-science views of leadership from an evolutionary perspective, and examines patterns of leadership in a set of small-scale human and non-human mammalian societies. We review empirical and theoretical work on leadership in four domains: movement, food acquisition, within-group conflict mediation, and between-group interactions. We categorize patterns of variation in leadership in five dimensions: distribution (across individuals), emergence (achieved versus inherited), power, relative payoff to leadership, and generality (across domains). We find that human leadership exhibits commonalities with and differences from the broader mammalian pattern, raising interesting theoretical and empirical issues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of amygdala lesions on overexpectation phenomena in food cup approach and autoshaping procedures.

PubMed

Holland, Peter C

2016-08-01

Prediction error (PE) plays a critical role in most modern theories of associative learning, by determining the effectiveness of conditioned stimuli (CS) or unconditioned stimuli (US). Here, we examined the effects of lesions of central (CeA) or basolateral (BLA) amygdala on performance in overexpectation tasks. In 2 experiments, after 2 CSs were separately paired with the US, they were combined and followed by the same US. In a subsequent test, we observed losses in strength of both CSs, as expected if the negative PE generated on reinforced compound trials encouraged inhibitory learning. CeA lesions, known to interfere with PE-induced enhancements in CS effectiveness, reduced those losses, suggesting that normally the negative PE also enhances cue associability in this task. BLA lesions had no effect. When a novel cue accompanied the reinforced compound, it acquired net conditioned inhibition, despite its consistent pairings with the US, consonant with US effectiveness models. That acquisition was unaffected by either CeA or BLA lesions, suggesting different rules for assignment of credit of changes in cue strength and cue associability. Finally, we examined a puzzling autoshaping phenomenon previously attributed to overexpectation effects. When a previously food-paired auditory cue was combined with the insertion of a lever and paired with the same food US, the auditory cue not only failed to block conditioning to the lever, but also lost strength, as in an overexpectation experiment. This effect was abolished by BLA lesions but unaffected by CeA lesions, suggesting it was unrelated to other overexpectation effects. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Immediate and long-term changes of fundus autofluorescence in continuous wave laser lesions of the retina.

PubMed

Framme, Carsten; Roider, Johann

2004-01-01

To determine whether fundus autofluorescence imaging is able to show changes in retinal pigment epithelium (RPE) fluorescence after thermal laser photocoagulation. In vivo imaging of fundus autofluorescence was performed with a scanning laser ophthalmoscope. A laser with a wavelength of 488 nm was used for excitation of the tissue and autofluorescence was detected above 500 nm using a barrier filter. One hundred eight eyes of 87 patients who had had previous laser treatment were monitored. The appearance and size of the laser lesions were documented and correlated to the time of treatment. Immediate changes were observed prospectively in 13 eyes; long-term follow-up was studied retrospectively in 95 eyes. In all patients but one, autofluorescence was decreased in the area of laser lesions 1 hour after laser treatment. After 1 month, previously decreased autofluorescence in all lesions changed to significantly increased autofluorescence, which was stable up to 6 months after treatment. Mixed forms were present approximately 6 to 12 months after treatment, showing a central island of increased autofluorescence surrounded by a ring of decreased autofluorescence. After 1 to 2 years, lesions again changed to complete dark spots, enlarging later on. RPE destruction and subsequent proliferation after continuous wave laser photocoagulation can be visualized noninvasively by autofluorescence imaging. Immediate decreased autofluorescence may indicate acute damage of the RPE, subsequent increased autofluorescence seems to indicate proliferative behavior of the RPE, and final dark spots can indicate RPE atrophy secondary to a denaturation of neurosensory retinal tissue. Thus, autofluorescence can be used in the long-term monitoring of RPE changes after laser treatment. The enlargement of the laser atrophy zone demonstrates the potential risk of visual loss after central laser photocoagulation even years after treatment.

Right medial thalamic lesion causes isolated retrograde amnesia.

PubMed

Miller, L A; Caine, D; Harding, A; Thompson, E J; Large, M; Watson, J D

2001-01-01

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

Pre-existing central nervous system lesions negate cytokine requirements for regional experimental autoimmune encephalomyelitis development.

PubMed

Li, Xin; Lees, Jason R

2013-03-01

In region-specific forms of experimental autoimmune encephalomyelitis (EAE), lesion initiation is regulated by T-cell-produced interferon-γ (IFN-γ) resulting in spinal cord disease in the presence of IFN-γ and cerebellar disease in the absence of IFN-γ. Although this role for IFN-γ in regional disease initiation is well defined, little is known about the consequences of previous tissue inflammation on subsequent regional disease, information vital to the development of therapeutics in established disease states. This study addressed the hypothesis that previous establishment of regional EAE would determine subsequent tissue localization of new T-cell invasion and associated symptoms regardless of the presence or absence of IFN-γ production. Serial transfer of optimal or suboptimal doses of encephalitogenic IFN-γ-sufficient or -deficient T-cell lines was used to examine the development of new clinical responses associated with the spinal cord and cerebellum at various times after EAE initiation. Previous inflammation within either cerebellum or spinal cord allowed subsequent T-cell driven inflammation within that tissue regardless of IFN-γ presence. Further, T-cell IFN-γ production after initial lesion formation exacerbated disease within the cerebellum, suggesting that IFN-γ plays different roles at different stages of cerebellar disease. For the spinal cord, IFN-γ-deficient cells (that are ordinarily cerebellum disease initiators) were capable of driving new spinal-cord-associated clinical symptoms more than 60 days after the initial acute EAE resolution. These data suggest that previous inflammation modulates the molecular requirements for new neuroinflammation development. © 2012 Blackwell Publishing Ltd.

Dysregulation of Mammalian Target of Rapamycin Signaling in Mouse Models of Autism.

PubMed

Huber, Kimberly M; Klann, Eric; Costa-Mattioli, Mauro; Zukin, R Suzanne

2015-10-14

The mammalian target of rapamycin (mTOR) is a central regulator of a diverse array of cellular processes, including cell growth, proliferation, autophagy, translation, and actin polymerization. Components of the mTOR cascade are present at synapses and influence synaptic plasticity and spine morphogenesis. A prevailing view is that the study of mTOR and its role in autism spectrum disorders (ASDs) will elucidate the molecular mechanisms by which mTOR regulates neuronal function under physiological and pathological conditions. Although many ASDs arise as a result of mutations in genes with multiple molecular functions, they appear to converge on common biological pathways that give rise to autism-relevant behaviors. Dysregulation of mTOR signaling has been identified as a phenotypic feature common to fragile X syndrome, tuberous sclerosis complex 1 and 2, neurofibromatosis 1, phosphatase and tensin homolog, and potentially Rett syndrome. Below are a summary of topics covered in a symposium that presents dysregulation of mTOR as a unifying theme in a subset of ASDs. Copyright © 2015 the authors 0270-6474/15/3513836-07$15.00/0.

Robotic multi-well planar patch-clamp for native and primary mammalian cells

PubMed Central

Milligan, Carol J; Li, Jing; Sukumar, Piruthivi; Majeed, Yasser; Dallas, Mark L; English, Anne; Emery, Paul; Porter, Karen E; Smith, Andrew M; McFadzean, Ian; Beccano-Kelly, Dayne; Bahnasi, Yahya; Cheong, Alex; Naylor, Jacqueline; Zeng, Fanning; Liu, Xing; Gamper, Nikita; Jiang, Lin-Hua; Pearson, Hugh A; Peers, Chris; Robertson, Brian; Beech, David J

2009-01-01

Multi-well robotic planar patch-clamp has become common in drug development and safety programmes because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. It has not, however, been adopted significantly in other important areas of ion channel research, where conventional patch-clamp remains the favoured method. Here we show the wider potential of the multi-well approach with the capability for efficient intracellular solution exchange, describing protocols and success rates for recording from a range of native and primary mammalian cells derived from blood vessels, arthritic joints, and the immune and central nervous systems. The protocol involves preparing a suspension of single cells to be dispensed robotically into 4-8 microfluidic chambers each containing a glass chip with a small aperture. Under automated control, giga-seals and whole-cell access are achieved followed by pre-programmed routines of voltage paradigms and fast extracellular or intracellular solution exchange. Recording from 48 chambers usually takes 1-6 hr depending on the experimental design and yields 16-33 cell recordings. PMID:19197268

Engineering Escherichia coli into a protein delivery system for mammalian cells.

PubMed

Reeves, Analise Z; Spears, William E; Du, Juan; Tan, Kah Yong; Wagers, Amy J; Lesser, Cammie F

2015-05-15

Many Gram-negative pathogens encode type 3 secretion systems, sophisticated nanomachines that deliver proteins directly into the cytoplasm of mammalian cells. These systems present attractive opportunities for therapeutic protein delivery applications; however, their utility has been limited by their inherent pathogenicity. Here, we report the reengineering of a laboratory strain of Escherichia coli with a tunable type 3 secretion system that can efficiently deliver heterologous proteins into mammalian cells, thereby circumventing the need for virulence attenuation. We first introduced a 31 kB region of Shigella flexneri DNA that encodes all of the information needed to form the secretion nanomachine onto a plasmid that can be directly propagated within E. coli or integrated into the E. coli chromosome. To provide flexible control over type 3 secretion and protein delivery, we generated plasmids expressing master regulators of the type 3 system from either constitutive or inducible promoters. We then constructed a Gateway-compatible plasmid library of type 3 secretion sequences to enable rapid screening and identification of sequences that do not perturb function when fused to heterologous protein substrates and optimized their delivery into mammalian cells. Combining these elements, we found that coordinated expression of the type 3 secretion system and modified target protein substrates produces a nonpathogenic strain that expresses, secretes, and delivers heterologous proteins into mammalian cells. This reengineered system thus provides a highly flexible protein delivery platform with potential for future therapeutic applications.

Fossilized Mammalian Erythrocytes Associated With a Tick Reveal Ancient Piroplasms.

PubMed

Poinar, George

2017-07-01

Ticks transmit a variety of pathogenic organisms to vertebrates, especially mammals. The fossil record of such associations is extremely rare. An engorged nymphal tick of the genus Ambylomma in Dominican amber was surrounded by erythrocytes from its mammalian host. Some of the exposed erythrocytes contained developmental stages of a hemoprotozoan resembling members of the Order Piroplasmida. The fossil piroplasm is described, its stages compared with those of extant piroplasms, and reasons provided why the mammalian host could have been a primate. The parasites were also found in the gut epithelial cells and body cavity of the fossil tick. Aside from providing the first fossil mammalian red blood cells and the first fossil intraerythrocytic hemoparasites, the present discovery shows that tick-piroplasm associations were already well established in the Tertiary. This discovery provides a timescale that can be used in future studies on the evolution of the Piroplasmida. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com Version of Record, first published online March 20, 2017 with fixed content and layout in compliance with Art. 8.1.3.2 ICZN.

TOXIC TRACE METALS IN MAMMALIAN HAIR AND NAILS

EPA Science Inventory

Data have been compiled from the available world literature on the accumulation and bioconcentration of selected toxic trace metals in human hair and nails and other mammalian hair, fur, nails, claws, and hoofs. The toxic trace metals and metalloids include antimony, arsenic, bor...

Fate and Metabolism of PBDEs in Mammalian Systems

USDA-ARS?s Scientific Manuscript database

Polybrominated diphenyl ethers (PBDEs) belong to an emerging class of persistent organic pollutants (POPs). Although the toxicology of PBDEs is not well developed, they are persistent and bioaccumulative, and therefore, of growing environmental concern. The metabolism of PBDEs in mammalian systems h...

Central nervous system lesions: correlation of intraoperative and final diagnoses, six year experience at a referral centre in a developing country, Pakistan.

PubMed

Ud Din, Nasir; Memon, Aisha; Idress, Romana; Ahmad, Zubair; Hasan, Sheema

2011-01-01

Intraoperative consultation of CNS lesions provides accurate diagnosis to neurosurgeons. Some lesions, however, may cause diagnostic difficulty. In this study accuracy of intraoperative consultations of CNS lesions and discrepancies in diagnosis and deferrals were analysed. All CNS cases from May 1, 2004 to September 20, 2010 in which intraoperative frozen section had been performed, and which were reported in the Section of Histopathology, Aga Khan University Hospital, Karachi Pakistan were retrieved. The diagnoses given on FS were compared with the final diagnosis given on permanent sections (and additional material if received), as indicated in the frozen section and final pathology report. During the study period, 171 CNS cases were received for intraoperative consultation. In all cases, cryostat sections (FS) plus cytology smears were prepared. The ages of the patients ranged from 03 to 77 years. 106 were males and 65 were females. Out of these 171 cases, 160 cases (94.1 %) were concordant, 10 cases (5.8 %) were discrepant, and one case was deferred until permanent sections. The diagnostic accuracy of frozen section was 88.9%. The sensitivity and specificity were 94.8% and 87.5% respectively. The positive predictive value was 98.6% and negative predictive value was 63.6%. All our cases in which intraoperative consultation was requested were sent for primary diagnosis. Adequacy per se was not a criterion for sending cases for intraoperative consultation. Our results show a reasonably high percentage of accuracy in the intraoperative diagnosis of CNS lesions. However, there are limitations and some lesions pose a diagnostic challenge. There is a need to improve our own diagnostic skills and establish better communication with neurosurgeons.

Central diabetes insipidus in children with acute brain insult.

PubMed

Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

2011-12-01

Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

Mammalian meat allergy following a tick bite: a case report.

PubMed

Jackson, W Landon

2018-02-01

The alpha-gal allergy is an emerging IgE-mediated reaction against the galactose-alpha-1,3-galactose carbohydrate found in mammalian meats. Patients with this condition will develop anaphylactic symptoms 3-6 h after the ingestion of mammalian meat food products such as beef, pork or lamb. The prevalence of this allergy is drastically increasing and severe reactions including anaphylactic shock have been reported, yet many patients experience symptoms for years before a diagnosis is made. We describe the presentation, diagnosis and management of a patient with the alpha-gal allergy in attempt to improve early recognition and management of patients with this condition.

Mammalian meat allergy following a tick bite: a case report

PubMed Central

2018-01-01

Abstract The alpha-gal allergy is an emerging IgE-mediated reaction against the galactose-alpha-1,3-galactose carbohydrate found in mammalian meats. Patients with this condition will develop anaphylactic symptoms 3–6 h after the ingestion of mammalian meat food products such as beef, pork or lamb. The prevalence of this allergy is drastically increasing and severe reactions including anaphylactic shock have been reported, yet many patients experience symptoms for years before a diagnosis is made. We describe the presentation, diagnosis and management of a patient with the alpha-gal allergy in attempt to improve early recognition and management of patients with this condition. PMID:29492269

Regulation of mammalian cell differentiation by long non-coding RNAs

PubMed Central

Hu, Wenqian; Alvarez-Dominguez, Juan R; Lodish, Harvey F

2012-01-01

Differentiation of specialized cell types from stem and progenitor cells is tightly regulated at several levels, both during development and during somatic tissue homeostasis. Many long non-coding RNAs have been recognized as an additional layer of regulation in the specification of cellular identities; these non-coding species can modulate gene-expression programmes in various biological contexts through diverse mechanisms at the transcriptional, translational or messenger RNA stability levels. Here, we summarize findings that implicate long non-coding RNAs in the control of mammalian cell differentiation. We focus on several representative differentiation systems and discuss how specific long non-coding RNAs contribute to the regulation of mammalian development. PMID:23070366