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Sample records for lesioned mammalian central

  1. Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous tissue

    SciTech Connect

    Kalderon, N.; Alfieri, A.A.; Fuks, Z. )

    1990-12-01

    We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.

  2. IN VITRO MAMMALIAN MUTAGENESIS AS A MODEL FOR GENETIC LESIONS IN HUMAN CANCER

    EPA Science Inventory

    Recently, in vitro mammalian cell assays of mutagenesis have been criticized as being poorly predictive of long-term in vivo rodent assays of carcinogenicity. Yet in vitro as says using mammalian cells might be expected to register types of genetic lesions thought to be important...

  3. Optical Detection of Preneoplastic Lesions of the Central Airways

    PubMed Central

    van der Leest, C.; Amelink, A.; van Klaveren, R. J.; Hoogsteden, H. C.; Sterenborg, H. J. C. M.; Aerts, J. G. J. V.

    2012-01-01

    Current routine diagnosis of premalignant lesions of the central airways is hampered due to a limited sensitivity (white light bronchoscopy) and resolution (computer tomography (CT), positron emission tomography (PET)) of currently used techniques. To improve the detection of these subtle mucosal abnormalities, novel optical imaging bronchoscopic techniques have been developed over the past decade. In this review we highlight the technological developments in the field of endoscopic imaging, and describe their advantages and disadvantages in clinical use. PMID:22550600

  4. Central changes in primary afferent fibers following peripheral nerve lesions.

    PubMed

    Coggeshall, R E; Lekan, H A; Doubell, T P; Allchorne, A; Woolf, C J

    1997-04-01

    Cutting or crushing rat sciatic nerve does not significantly reduce the number of central myelinated sensory axons in the dorsal roots entering the fourth and fifth lumbar segments even over very extended periods of time. Unmyelinated axons were reduced by approximately 50%, but only long after sciatic nerve lesions (four to eight months), and reinnervation of the peripheral target did not rescue these axons. This indicates that a peripheral nerve lesion sets up a slowly developing but major shift towards large afferent fiber domination of primary afferent input into the spinal cord. In addition, since myelinated axons are never lost, this is good evidence that the cells that give rise to these fibers are also not lost. If this is the case, this would indicate that adult primary sensory neurons with myelinated axons do not depend on peripheral target innervation for survival. PMID:9130791

  5. Development-Inspired Reprogramming of the Mammalian Central Nervous System

    PubMed Central

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-01

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the exciting demonstration that the identity of differentiated cells is not irreversibly determined but can be changed back to a pluripotent state under appropriate instructive signals. The principle that differentiated cells can revert to an embryonic state and even be converted directly from one cell-type into another not only turns fundamental principles of development on their head but also has profound implications for regenerative medicine. Replacement of diseased tissue with newly reprogrammed cells and modeling of human disease are concrete opportunities. Here, we focus on the central nervous system to consider whether and how reprogramming of cell identity may impact regeneration and modeling of a system historically considered immutable and hardwired. PMID:24482482

  6. N-NITROSODIETHYLAMINE-INDUCED HEPATOCARCINOGENESIS IN ESTUARINE SHEEPSHEAD MINNOW ('CYPRINODON VARIEGATUS'): NEOPLASMS AND RELATED LESIONS COMPARED WITH MAMMALIAN LESIONS

    EPA Science Inventory

    Groups of estuarine sheepshead minnows (Cyprinodon variegatus) were exposed to 50-60 mg/l N-nitrosodiethylamine (DENA) for five to six weeks. Exposure was stopped and the fish were then transferred to clean, flowing seawater. Induced liver lesions were studied in periodic samples...

  7. Efficient and Reliable Production of Vectors for the Study of the Repair, Mutagenesis, and Phenotypic Consequences of Defined DNA Damage Lesions in Mammalian Cells

    PubMed Central

    Petrova, Lucy; Gran, Christine; Bjoras, Magnar; Doetsch, Paul W.

    2016-01-01

    Mammalian cells are constantly and unavoidably exposed to DNA damage from endogenous and exogenous sources, frequently to the detriment of genomic integrity and biological function. Cells acquire a large number of chemically diverse lesions per day, and each can have a different genetic fate and biological consequences. However, our knowledge of how and when specific lesions are repaired or how they may compromise the fidelity of DNA replication or transcription and lead to deleterious biological endpoints in mammalian cells is limited. Studying individual lesions requires technically challenging approaches for the targeted introduction of defined lesions into relevant DNA sequences of interest. Here, we present a systematic analysis of factors influencing yield and an improved, efficient and reliable protocol for the production of mammalian expression phagemid vectors containing defined DNA base modifications in any sequence position of either complementary DNA strand. We applied our improved protocol to study the transcriptional mutagenesis-mediated phenotypic consequences of the common oxidative lesion 5-hydroxyuracil, placed in the G12 mutational hotspot of the KRAS oncogene. 5-OHU induced sustained oncogenic signaling in Neil1-/-Neil2-/- mouse cells. The resulting advance in technology will have broad applicability for investigation of single lesion DNA repair, mutagenesis, and DNA damage responses in mammalian cells. PMID:27362559

  8. ssiRNA Induced Gene Silencing is Transmitted Between Cells From the Mammalian Central Nervous System

    PubMed Central

    Zhao, Tian-Yong; Zou, Shi-Ping; Alimova, Yelena V.; Wang, Guoying; Hauser, Kurt F.; Ghandour, M. Said; Knapp, Pamela E.

    2014-01-01

    Although siRNA induced gene silencing can be transmitted between cells in plants and in C. elegans, this phenomenon has been barely studied in mammalian cells. Both immortalized oligodendrocytes and SNB-19 glioblastoma cells were transfected with siRNA constructs for PTEN (phosphatase and tensin homolog deleted on chromosome 10) or Akt (Akt/protein kinase B). Co-cultures were established between silenced cells and non-silenced cells which were hygromycin resistant and/or expressed green fluorescent protein (GFP). After fluorescence sorting or hygromycin selection to remove the silenced cells, the expression of PTEN or Akt genes in the originally unsilenced cells was in all cases significantly decreased. Importantly, silencing did not occur in transwell culture studies, suggesting that transmission of the silencing signal requires a close association between cells. These results provide the first direct demonstration that an siRNA induced silencing signal can be transmitted between mammalian central nervous system (CNS) cells. PMID:16923165

  9. Spatial and temporal vision of macaques after central retinal lesions

    SciTech Connect

    Merigan, W.H.; Pasternak, T.; Zehl, D.

    1981-07-01

    Spatial contrast and temporal modulation sensitivity of two macaque monkeys were measured at three luminance levels before and after binocular laser coagulation of the fovea. The radius of the lesions ranged from 1.6 to 2.2 degree from the center of the fovea. After placement of the lesions, the visibility of high spatial frequencies was greatly reduced, although sensitivity at middle and low spatial frequencies was unaffected. No loss of spatial resolution was found at the lowest luminance tested. When temporal modulation sensitivity was tested with 4 deg targets, foveal lesions had no effect at any temporal frequency or luminance. However, with a 0.57 degree target, sensitivity to lower temporal frequencies was impaired. Thus visual loss after destruction of the fovea is limited to high luminance, small targets, and the resolution of fine detail.

  10. Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system

    PubMed Central

    Randall, Andrew D; Kurihara, Mai; Brandon, Nicholas J; Brown, Jon T

    2014-01-01

    The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular-level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS. PMID:24712987

  11. Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system.

    PubMed

    Randall, Andrew D; Kurihara, Mai; Brandon, Nicholas J; Brown, Jon T

    2014-04-01

    The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular-level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS. PMID:24712987

  12. Surgical Management of Mandibular Central Incisors with Dumbbell Shaped Periapical Lesion: A Case Report

    PubMed Central

    Venigalla, Bhuvan Shome; Patil, Jayaprakash D.; Jayaprakash, Thumu; Chaitanya, C. H. Krishna; Kalluru, Rama S.

    2014-01-01

    Dental traumatic injuries may affect the teeth and alveolar bone directly or indirectly. Pulpal necrosis and chronic and apical periodontitis with cystic changes are the most common sequelae of the dental traumatic injuries, if the teeth are not treated immediately. This case report focuses on the conventional and surgical management of mandibular central incisors. A twenty-four-year-old male patient presented with pain in the mandibular central incisors. Radiographic examination revealed mandibular central incisors with dumbbell shaped periapical lesion. After root canal treatment, parendodontic surgery was performed for mandibular central incisors. After one-year recall examination, the teeth were asymptomatic and periapical lesion had healed. PMID:25105031

  13. The Intrinsic Electrophysiological Properties of Mammalian Neurons: Insights into Central Nervous System Function

    NASA Astrophysics Data System (ADS)

    Llinas, Rodolfo R.

    1988-12-01

    This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhytmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input.

  14. Holocene mammalian change in the central Columbia Basin of eastern Washington state, USA

    NASA Astrophysics Data System (ADS)

    Lyman, R. Lee

    2016-08-01

    Predictions of changes in the Holocene mammalian fauna of the central Columbia Basin in eastern Washington (USA) based on environmental changes are largely met. Taxonomic richness is greatest during periods of cool-moist climate. Rates of input of faunal remains to the paleozoological record may suggest greater mammalian biomass during periods of greater moisture but are difficult to interpret without data on sampling intensity in the form of volume of sediment excavated. Abundances of leporids and grazing ungulates fluctuate in concert with abundance of grass. Several biogeographic records are tantalizing but require additional study and data before being accepted as valid. Records of red fox (Vulpes vulpes) indicate this species was present in the central basin during the Holocene contrary to historic records and recent suggestions modern foxes there are escapees from fur farms. Bison (Bison bison) and bighorn sheep (Ovis canadensis) underwent diminution of body size during the Holocene. Modern efforts to conserve the Columbia Basin ecosystem are advised to consider the Holocene record as indicative of what may happen to that ecosystem in the future.

  15. [Image-guided stereotaxic biopsy of central nervous system lesions].

    PubMed

    Nasser, J A; Confort, C I; Ferraz, A; Esperança, J C; Duarte, F

    1998-06-01

    In a series of 44 image guided stereotactic biopsy from August 1995 until March 1997, findings were as follows (frequency order). Tumors, glioblastoma was the most frequent. Primary lymphoma and other conditions associated to AIDS. Metastasis, three cases, Vasculites, two cases, Arachnoid cyst, Creutzfeldt-Jakob, cortical degeneration, inespecific calcification (one case each). The age varied from 1 to 83 years. Forty one lesions were supratentorial, two infratentorial, and one was outside the brain (dura and skull) and we used stereotaxy to localize it. There was no mortality and morbidity was 2.3%. The literature is reviewed. We conclude that this procedure is safe and highly diagnostic. PMID:9698729

  16. Imaging single synaptic vesicles in Mammalian central synapses with quantum dots.

    PubMed

    Zhang, Qi

    2013-01-01

    This protocol describes a sensitive and rigorous method to monitor the movement and turnover of single synaptic vesicles in live presynaptic terminals of mammalian central nervous system. This technique makes use of Photoluminescent semiconductor nanocrystals, quantum dots (Qdots), by their nanometer size, superior photoproperties, and pH-sensitivity. In comparison with previous fluorescent probes like styryl dyes and pH-sensitive fluorescent proteins, Qdots offer strict loading ratio, multi-modality detection, single vesicle precision, and most importantly distinctive signals for different modes of vesicle fusion. Qdots are spectrally compatible with existing fluorescent probes for synaptic vesicles and thus allow multichannel -imaging. With easy modification, this technique can be applied to other types of synapses and cells. PMID:23494380

  17. Animal Models for Investigating the Central Control of the Mammalian Diving Response

    PubMed Central

    McCulloch, Paul Frederick

    2012-01-01

    Pioneering studies by Per Scholander indicated that the diving response consists of reflexly induced apnea, bradycardia and an alteration of blood flow that maintains perfusion of the heart and brain. More recently field physiological studies have shown that many marine animals can adjust cardiorespiratory aspects of their diving response depending upon the behavioral situation. This could suggest that the very labile heart rate during diving is under direct cortical control. However, the final control of autonomic nervous system functioning resides within the brainstem and not the cortex. Many physiologists regard the brain as a “black box” where important neuronal functioning occurs, but the complexity of such functioning leaves systematic investigation a daunting task. As a consequence the central control of the diving response has been under-investigated. Thus, to further advance the field of diving physiology by understanding its central neuronal control, it would be first necessary to understand the reflex circuitry that exists within the brainstem of diving animals. To do this will require an appropriate animal model. In this review, two animals, the muskrat and rat, will be offered as animal models to investigate the central aspects of the diving response. Firstly, although these rodents are not marine animals, natural histories indicate that both animals can and do exploit aquatic environments. Secondly, physiological recordings during natural and simulated diving indicate that both animals possess the same basic physiological responses to underwater submersion that occur in marine animals. Thirdly, the size and ease of housing of both animals makes them attractive laboratory research animals. Finally, the enormous amount of scientific literature regarding rodent brainstem autonomic control mechanisms, and the availability of brain atlases, makes these animals ideal choices to study the central control of the mammalian diving response. PMID:22661956

  18. Animal models for investigating the central control of the Mammalian diving response.

    PubMed

    McCulloch, Paul Frederick

    2012-01-01

    Pioneering studies by Per Scholander indicated that the diving response consists of reflexly induced apnea, bradycardia and an alteration of blood flow that maintains perfusion of the heart and brain. More recently field physiological studies have shown that many marine animals can adjust cardiorespiratory aspects of their diving response depending upon the behavioral situation. This could suggest that the very labile heart rate during diving is under direct cortical control. However, the final control of autonomic nervous system functioning resides within the brainstem and not the cortex. Many physiologists regard the brain as a "black box" where important neuronal functioning occurs, but the complexity of such functioning leaves systematic investigation a daunting task. As a consequence the central control of the diving response has been under-investigated. Thus, to further advance the field of diving physiology by understanding its central neuronal control, it would be first necessary to understand the reflex circuitry that exists within the brainstem of diving animals. To do this will require an appropriate animal model. In this review, two animals, the muskrat and rat, will be offered as animal models to investigate the central aspects of the diving response. Firstly, although these rodents are not marine animals, natural histories indicate that both animals can and do exploit aquatic environments. Secondly, physiological recordings during natural and simulated diving indicate that both animals possess the same basic physiological responses to underwater submersion that occur in marine animals. Thirdly, the size and ease of housing of both animals makes them attractive laboratory research animals. Finally, the enormous amount of scientific literature regarding rodent brainstem autonomic control mechanisms, and the availability of brain atlases, makes these animals ideal choices to study the central control of the mammalian diving response. PMID:22661956

  19. Human neural progenitor cells in central nervous system lesions.

    PubMed

    Åkesson, Elisabet; Sundström, Erik

    2016-02-01

    Various immature cells can be isolated from human embryonic and fetal central nervous system (CNS) residual tissue and potentially be used in cell therapy for a number of neurological diseases and CNS insults. Transplantation of neural stem and progenitor cells is essential for replacing lost cells, particularly in the CNS with very limited endogenous regenerative capacity. However, while dopamine released from transplanted cells can substitute the lost dopamine neurons in the experimental models of Parkinson's disease, stem and progenitor cells primarily have a neuroprotective effect, probably through the release of trophic factors. Understanding the therapeutic effects of transplanted cells is crucial to determine the design of clinical trials. During the last few years, a number of clinical trials for CNS diseases and insults such as amyotrophic lateral sclerosis (ALS), stroke, and spinal cord trauma using neural progenitor cells have been initiated. Data from these early studies will provide vital information on the safety of transplanting these cells, which still is a major concern. That the beneficial results observed in experimental models also can be repeated in the clinical setting is highly hoped for. PMID:26803559

  20. 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

  1. Sodium currents activate without a Hodgkin-and-Huxley-type delay in central mammalian neurons.

    PubMed

    Baranauskas, Gytis; Martina, Marco

    2006-01-11

    Hodgkin and Huxley established that sodium currents in the squid giant axons activate after a delay, which is explained by the model of a channel with three identical independent gates that all have to open before the channel can pass current (the HH model). It is assumed that this model can adequately describe the sodium current activation time course in all mammalian central neurons, although there is no experimental evidence to support such a conjecture. We performed high temporal resolution studies of sodium currents gating in three types of central neurons. The results show that, within the tested voltage range from -55 to -35 mV, in all of these neurons, the activation time course of the current could be fit, after a brief delay, with a monoexponential function. The duration of delay from the start of the voltage command to the start of the extrapolated monoexponential fit was much smaller than predicted by the HH model. For example, in prefrontal cortex pyramidal neurons, at -46 mV and 12 degrees C, the observed average delay was 140 micros versus the 740 micros predicted by the two-gate HH model and the 1180 micros predicted by the three-gate HH model. These results can be explained by a model with two closed states and one open state. In this model, the transition between two closed states is approximately five times faster than the transition between the second closed state and the open state. This model captures all major properties of the sodium current activation. In addition, the proposed model reproduces the observed action potential shape more accurately than the traditional HH model. PMID:16407565

  2. Gross and histopathological findings in unusual lesions caused by Streptococcus suis in pigs. II. Central nervous system lesions.

    PubMed Central

    Sanford, S E

    1987-01-01

    Subacute meningoencephalitis or meningoencephalomyelitis caused by Streptococcus suis was diagnosed in 53 pigs over a four-year period. Affected pigs averaging 11 weeks of age with a range from five days to 26 weeks, had been treated with antibiotics and had partially recovered. Hyperemia of meningeal vessels and modest increase in cerebrospinal fluid were the most common gross central nervous system lesions. Histologically, fibrin, edema and a mixture of inflammatory cells were present in meninges and choroid plexus. Linear and perivascular infiltrates of neutrophils and mononuclear inflammatory cells invaded the brain and spinal cord and similar infiltrates were in lumina of ventricles and the spinal canal. Inflammatory cells also invaded the superficial layers of the brain directly from the overlying meninges. Bilateral subacute optic perineuritis and Gasserian ganglioneuritis also occurred. Segmental cortical necrosis of cerebellar folia characterized by degeneration, necrosis, neuronophagia and drop out of groups of Purkinje cells was a distinct lesion seen in 27 of the 53 pigs. Mild spongiosis of white matter in the cerebellum and brain stem accompanied these changes. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:3453269

  3. Neurophysiological markers of plastic brain reorganization following central and peripheral lesions.

    PubMed

    Ferreri, Florinda; Guerra, Andrea; Rossini, Paolo Maria

    2014-12-01

    There is increasing evidence supporting the concept that adult brain has the remarkable ability to plastically reorganize itself. Brain plasticity involves distinct functional and structural components and plays a crucial role in reorganizing central nervous system's networks after central and peripheral lesions in order to partly or totally restore lost and/or compromised functions. This plastic rearrangement occurs in fact not only after a central nervous system injury but also following a peripheral lesion. Interestingly, the existence of a certain type of maladaptive plasticity was clearly recognized in the last decade, which gives reason for example to poor out- come performances or aberrant phenomena. In this review we analyze stroke and amputees studies, as illustrative conditions of central and peripheral nervous system damage, and discuss the adaptive as well maladaptive plastic brain changes following these lesions. The emerging possibility, through neuro-imaging and neurophysiological advanced techniques, to clarify some crucial issues underlying brain plasticity will give the chance to modulate these mechanisms in a highly personalized therapy. This approach may have a tremendous impact in a variety of neuropsychiatric disorders opening a new era of restorative medicine. PMID:25987182

  4. Lesions of the central nucleus of the amygdala decrease taste threshold for sodium chloride in rats.

    PubMed

    Li, Jinrong; Yan, Jianqun; Chen, Ke; Lu, Bo; Wang, Qian; Yan, Wei; Zhao, Xiaolin

    2012-10-01

    Previous studies reported that NaCl intake was down-regulated in rats with bilateral lesions of the central nucleus of the amygdala (CeA). In line with the evidence from anatomical and physiological studies, such an inhibition could be the result of altered taste threshold for NaCl, one of the important factors in assessing taste functions. To assess the effect of CeA on the taste threshold for NaCl, a conditioned taste aversion (CTA) to a suprathreshold concentration of NaCl (0.1M) in rats with bilateral lesions of CeA or sham lesions was first established. And then, two-bottle choice tests between water and a series of concentrations of NaCl were conducted. The taste threshold for NaCl is defined as the lowest concentration at which there is a reliable difference scores between conditioned and control subjects. Rats with CeA lesions acquired a taste aversion for 0.1M NaCl when it was paired with LiCl and still retained the aversion after the two-bottle choice test. The results of the two-bottle choice test showed that the taste threshold for NaCl was 0.0006M in rats with CeA lesions, whereas in rats with sham lesions the threshold was 0.005M, which was identical to that of normal rats. The conditioned results confirm the claim that CeA is not essential in the profile of conditioned taste aversion. Our findings demonstrate that lesions of the CeA increased the sensitivity to NaCl taste in rats, indicating that the CeA may be involved in encoding the intensity of salty gustation elicited by NaCl. PMID:22796484

  5. Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system.

    PubMed Central

    Luneau, C J; Williams, J B; Marshall, J; Levitan, E S; Oliva, C; Smith, J S; Antanavage, J; Folander, K; Stein, R B; Swanson, R

    1991-01-01

    In an attempt to define the molecular basis of the functional diversity of K+ channels, we have isolated overlapping rat brain cDNAs that encoded a neuronal delayed rectifier K+ channel, K,4, that is structurally related to the Drosophila Shaw protein. Unlike previously characterized mammalian K+ channel genes, which each contain a single protein-coding exon, K,4 arises from alternative exon usage at a locus that also encodes another mammalian Shaw homolog, NGK2. Thus, the enormous diversity of K+ channels in mammals can be generated not just through gene duplication and divergence but also through alternative splicing of RNA. Images PMID:2023941

  6. 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. PMID:20709072

  7. 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.

  8. [Direct assay of radiation-induced DNA base lesions to mammalian cells]. Final progress report, September 1, 1991--November 1, 1993

    SciTech Connect

    Not Available

    1993-12-31

    We have successfully developed the GC/MS technique so that an assessment of base damage in mammalian cells can be accomplished. The technique now has a sensitivity that will allow one to perform research in the low dose region suitable for hazards evaluation. The research on the hydrated DNA molecule has been seminal in generating a better understanding of the mechanisms by which low LET radiation induces DNA damage in mammalian cells. Also reported here are (1) the methodology for hydrating and irradiating DNA has been developed, (2) the procedures for identifying and quantitating radiation-induced DNA damage by HPLC and GC/MS have been mastered, (3) an hypotheses that radiation-induced damage in closely associated water molecules can result in DNA damage which is indistinguishable from that caused by direct ionization of the DNA has been generated and supported by experimental data, and (4) mathematical expressions that relate DNA lesion formation to the important parameters in the above hypotheses have been constructed so that the predictions of the hypotheses can now be tested.

  9. 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. PMID:26679618

  10. Lentiviral vectors as tools to understand central nervous system biology in mammalian model organisms

    PubMed Central

    Parr-Brownlie, Louise C.; Bosch-Bouju, Clémentine; Schoderboeck, Lucia; Sizemore, Rachel J.; Abraham, Wickliffe C.; Hughes, Stephanie M.

    2015-01-01

    Lentiviruses have been extensively used as gene delivery vectors since the mid-1990s. Usually derived from the human immunodeficiency virus genome, they mediate efficient gene transfer to non-dividing cells, including neurons and glia in the adult mammalian brain. In addition, integration of the recombinant lentiviral construct into the host genome provides permanent expression, including the progeny of dividing neural precursors. In this review, we describe targeted vectors with modified envelope glycoproteins and expression of transgenes under the regulation of cell-selective and inducible promoters. This technology has broad utility to address fundamental questions in neuroscience and we outline how this has been used in rodents and primates. Combining viral tract tracing with immunohistochemistry and confocal or electron microscopy, lentiviral vectors provide a tool to selectively label and trace specific neuronal populations at gross or ultrastructural levels. Additionally, new generation optogenetic technologies can be readily utilized to analyze neuronal circuit and gene functions in the mature mammalian brain. Examples of these applications, limitations of current systems and prospects for future developments to enhance neuroscience knowledge will be reviewed. Finally, we will discuss how these vectors may be translated from gene therapy trials into the clinical setting. PMID:26041987

  11. Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous system neurons

    PubMed Central

    Chen, Meifan; Geoffroy, Cédric G.; Wong, Hetty N.; Tress, Oliver; Nguyen, Mallorie T.; Holzman, Lawrence B.; Jin, Yishi; Zheng, Binhai

    2016-01-01

    Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage kinase family with high sequence identity to Dual Leucine Zipper Kinase (DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to injury, the role of LZK in mammalian neurons is poorly understood. By gain- and loss-of-function analyses in neuronal cultures, we identify LZK as a novel positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity positively regulating LZK protein levels. Neuronal maturation or activity deprivation activates the LZK-MKK4-JNK pathway. LZK and DLK share commonalities in signaling, regulation, and effects on axon extension. Furthermore, LZK-dependent regulation of DLK protein expression and the lack of additive effects on axon growth upon co-manipulation suggest complex functional interaction and cross-regulation between these two kinases. Together, our data support the possibility for two structurally related MAP3Ks to work in concert to mediate axonal responses to external insult or injury in mammalian CNS neurons. PMID:27511108

  12. Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous system neurons.

    PubMed

    Chen, Meifan; Geoffroy, Cédric G; Wong, Hetty N; Tress, Oliver; Nguyen, Mallorie T; Holzman, Lawrence B; Jin, Yishi; Zheng, Binhai

    2016-01-01

    Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage kinase family with high sequence identity to Dual Leucine Zipper Kinase (DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to injury, the role of LZK in mammalian neurons is poorly understood. By gain- and loss-of-function analyses in neuronal cultures, we identify LZK as a novel positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity positively regulating LZK protein levels. Neuronal maturation or activity deprivation activates the LZK-MKK4-JNK pathway. LZK and DLK share commonalities in signaling, regulation, and effects on axon extension. Furthermore, LZK-dependent regulation of DLK protein expression and the lack of additive effects on axon growth upon co-manipulation suggest complex functional interaction and cross-regulation between these two kinases. Together, our data support the possibility for two structurally related MAP3Ks to work in concert to mediate axonal responses to external insult or injury in mammalian CNS neurons. PMID:27511108

  13. Expression of Fos during sham sucrose intake in rats with central gustatory lesions

    PubMed Central

    Mungarndee, Suriyaphun S.; Lundy, Robert F.; Norgren, Ralph

    2008-01-01

    For humans and rodents, ingesting sucrose is rewarding. This experiment tested the prediction that the neural activity produced by sapid sucrose reaches reward systems via projections from the pons through the limbic system. Gastric cannulas drained ingested fluid before absorption. For 10 days, the rats alternated an hour of this sham ingestion between sucrose and water. On the final test day, half of them sham drank water and the other half 0.6 M sucrose. Thirty minutes later, the rats were killed and their brains immunohistochemically stained for Fos. The groups consisted of controls and rats with excitotoxic lesions in the gustatory thalamus (TTA), the medial (gustatory) parabrachial nucleus (PBN), or the lateral (visceral afferent) parabrachial nucleus. In controls, compared with water, sham ingesting sucrose produced significantly more Fos-positive neurons in the nucleus of the solitary tract, PBN, TTA, and gustatory cortex (GC). In the ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the stria terminalis, central nucleus of amygdala, and the shell of nucleus accumbens. Thalamic lesions blocked the sucrose effect in GC but not in the ventral forebrain. After lateral PBN lesions, the Fos distributions produced by distilled H2O or sucrose intake did not differ from controls. Bilateral medial PBN damage, however, eliminated the sucrose-induced Fos increase not only in the TTA and GC but also in the ventral forebrain. Thus ventral forebrain areas associated with affective responses appear to be activated directly by PBN gustatory neurons rather than via the thalamocortical taste system. PMID:18635449

  14. Expression of Fos during sham sucrose intake in rats with central gustatory lesions.

    PubMed

    Mungarndee, Suriyaphun S; Lundy, Robert F; Norgren, Ralph

    2008-09-01

    For humans and rodents, ingesting sucrose is rewarding. This experiment tested the prediction that the neural activity produced by sapid sucrose reaches reward systems via projections from the pons through the limbic system. Gastric cannulas drained ingested fluid before absorption. For 10 days, the rats alternated an hour of this sham ingestion between sucrose and water. On the final test day, half of them sham drank water and the other half 0.6 M sucrose. Thirty minutes later, the rats were killed and their brains immunohistochemically stained for Fos. The groups consisted of controls and rats with excitotoxic lesions in the gustatory thalamus (TTA), the medial (gustatory) parabrachial nucleus (PBN), or the lateral (visceral afferent) parabrachial nucleus. In controls, compared with water, sham ingesting sucrose produced significantly more Fos-positive neurons in the nucleus of the solitary tract, PBN, TTA, and gustatory cortex (GC). In the ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the stria terminalis, central nucleus of amygdala, and the shell of nucleus accumbens. Thalamic lesions blocked the sucrose effect in GC but not in the ventral forebrain. After lateral PBN lesions, the Fos distributions produced by distilled H(2)O or sucrose intake did not differ from controls. Bilateral medial PBN damage, however, eliminated the sucrose-induced Fos increase not only in the TTA and GC but also in the ventral forebrain. Thus ventral forebrain areas associated with affective responses appear to be activated directly by PBN gustatory neurons rather than via the thalamocortical taste system. PMID:18635449

  15. Non-invasive neuromuscular electrical stimulation in patients with central nervous system lesions: an educational review.

    PubMed

    Schuhfried, Othmar; Crevenna, Richard; Fialka-Moser, Veronika; Paternostro-Sluga, Tatjana

    2012-02-01

    The aim of this educational review is to provide an overview of the clinical application of transcutaneous electrical stimulation of the extremities in patients with upper motor neurone lesions. In general two methods of electrical stimulation can be distinguished: (i) therapeutic electrical stimulation, and (ii) functional electrical stimulation. Therapeutic electrical stimulation improves neuromuscular functional condition by strengthening muscles, increasing motor control, reducing spasticity, decreasing pain and increasing range of motion. Transcutaneous electrical stimulation may be used for neuromuscular electrical stimulation inducing repetitive muscle contraction, electromyography-triggered neuromuscular electrical stimulation, position-triggered electrical stimulation and subsensory or sensory transcutaneous electric stimulation. Functional electrical stimulation provokes muscle contraction and thereby produces a functionally useful movement during stimulation. In patients with spinal cord injuries or stroke, electrical upper limb neuroprostheses are applied to enhance upper limb and hand function, and electrical lower limb neuroprostheses are applied for restoration of standing and walking. For example, a dropped foot stimulator is used to trigger ankle dorsiflexion to restore gait function. A review of the literature and clinical experience of the use of therapeutic electrical stimulation as well as of functional electrical stimulation in combination with botulinum toxin, exercise therapy and/or splinting are presented. Although the evidence is limited we conclude that neuromuscular electrical stimulation in patients with central nervous system lesions can be an effective modality to improve function, and that combination with other treatments has an additive therapeutic effect. PMID:22334346

  16. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    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.

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

    PubMed

    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 Ca(2+) signalling across a large field of view. The developed system opens up a host of novel applications for the neuroscience community. PMID:27215692

  19. 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

  20. 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

  1. The mammalian tachykinin ligand-receptor system: an emerging target for central neurological disorders

    PubMed Central

    Pantaleo, Nick; Chadwick, Wayne; Park, Sung-Soo; Wang, Liyun; Zhou, Yu; Martin, Bronwen; Maudsley, Stuart

    2010-01-01

    Our understanding of the complex signaling neurophysiology of the central nervous system has facilitated the exploration of potential novel receptor-ligand system targets for disorders of this most complex organ. In recent years, many relatively neglected receptor-ligand systems have been re-evaluated with respect to their ability to potently modulate discrete tracts in the central nervous system. One such system is the tachykinin (previously neurokinin) system. The multiple heptahelical G protein-coupled receptors and neuropeptide ligands that comprise this system may be significantly involved in more central nervous systems actions than previously thought, including sleep disorders, amyotrophic lateral sclerosis, Alzheimer’s and Machado-Joseph disease. The development of our understanding of the role of the tachykinin receptor-ligand system in higher order central functions is likely to allow the creation of more specific and selective tachykinin-related neurotherapeutics. PMID:20632965

  2. Quantitative autoradiographic characterization of GA-BA sub B receptors in mammalian central nervous system

    SciTech Connect

    Chu, D.Chin-Mei.

    1989-01-01

    The inhibitory effects of the amino acid neurotransmitter {gamma}-aminobutyric acid (GABA) within the nervous system appear to be mediated through two distinct classes of receptors: GABA{sub A} and GABA{sub B} receptors. A quantitative autoradiographic method with {sup 3}H-GABA was developed to examine the hypotheses that GABA{sub A} and GABA{sub B} sites have distinct anatomical distributions, pharmacologic properties, and synaptic localizations within the rodent nervous system. The method was also applied to a comparative study of these receptors in postmortem human brain from individuals afflicted with Alzheimer's disease and those without neurologic disease. The results indicated that GABA{sub B} receptors occur in fewer numbers and have a lower affinity for GABA than GABA{sub A} receptors in both rodent and human brain. Within rodent brain, the distribution of these two receptor populations were clearly distinct. GABA{sub B} receptors were enriched in the medial habenula, interpeduncular nucleus, cerebellar molecular layer and olfactory glomerular layer. After selective lesions of postsynaptic neurons of the corticostriatal and perforant pathway, both GABA{sub B} and GABA{sub A} receptors were significantly decreased in number. Lesions of the presynaptic limbs of the perforant but not the corticostriatal pathway resulted in upregulation of both GABA receptors in the area of innervation. GABA{sub B} receptors were also upregulated in CA3 dendritic regions after destruction of dentate granule neurons.

  3. 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).

  4. Mammalian Axoneme Central Pair Complex Proteins: Broader Roles Revealed by Gene Knockout Phenotypes

    PubMed Central

    Teves, Maria E.; Nagarkatti-Gude, David R.; Zhang, Zhibing; Strauss, Jerome F.

    2016-01-01

    The axoneme genes, their encoded proteins, their functions and the structures they form are largely conserved across species. Much of our knowledge of the function and structure of axoneme proteins in cilia and flagella is derived from studies on model organisms like the green algae, Chlamydomonas reinhardtii. The core structure of cilia and flagella is the axoneme, which in most motile cilia and flagella contains a 9 + 2 configuration of microtubules. The two central microtubules are the scaffold of the central pair complex (CPC). Mutations that disrupt CPC genes in Chlamydomonas and other model organisms result in defects in assembly, stability and function of the axoneme, leading to flagellar motility defects. However, targeted mutations generated in mice in the orthologous CPC genes have revealed significant differences in phenotypes of mutants compared to Chlamydomonas. Here we review observations that support the concept of cell-type specific roles for the CPC genes in mice, and an expanded repertoire of functions for the products of these genes in cilia, including non-motile cilia, and other microtubule-associated cellular functions. PMID:26785425

  5. Central perception of position sense involves a distributed neural network - Evidence from lesion-behavior analyses.

    PubMed

    Findlater, Sonja E; Desai, Jamsheed A; Semrau, Jennifer A; Kenzie, Jeffrey M; Rorden, Chris; Herter, Troy M; Scott, Stephen H; Dukelow, Sean P

    2016-06-01

    It is well established that proprioceptive inputs from the periphery are important for the constant update of arm position for perception and guiding motor action. The degree to which we are consciously aware of the position of our limb depends on the task. Our understanding of the central processing of position sense is rather limited, largely based on findings in animals and individual human case studies. The present study used statistical lesion-behavior analysis and an arm position matching task to investigate position sense in a large sample of subjects after acute stroke. We excluded subjects who performed abnormally on clinical testing or a robotic visually guided reaching task with their matching arm in order to minimize the potential confound of ipsilesional impairment. Our findings revealed that a number of regions are important for processing position sense and include the posterior parietal cortex, the transverse temporal gyrus, and the arcuate fasciculus. Further, our results revealed that position sense has dissociable components - spatial variability, perceived workspace area, and perceived workspace location. Each component is associated with unique neuroanatomical correlates. These findings extend the current understanding of the neural processing of position sense and identify some brain areas that are not classically associated with proprioception. PMID:27085894

  6. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

    PubMed Central

    Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

  7. Amino acids as central synaptic transmitters or modulators in mammalian thermoregulation

    SciTech Connect

    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 intracerebroventricular 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.

  8. Regeneration strategies after the adult mammalian central nervous system injury—biomaterials

    PubMed Central

    Gao, Yudan; Yang, Zhaoyang; Li, Xiaoguang

    2016-01-01

    The central nervous system (CNS) has very restricted intrinsic regeneration ability under the injury or disease condition. Innovative repair strategies, therefore, are urgently needed to facilitate tissue regeneration and functional recovery. The published tissue repair/regeneration strategies, such as cell and/or drug delivery, has been demonstrated to have some therapeutic effects on experimental animal models, but can hardly find clinical applications due to such methods as the extremely low survival rate of transplanted cells, difficulty in integrating with the host or restriction of blood–brain barriers to administration patterns. Using biomaterials can not only increase the survival rate of grafts and their integration with the host in the injured CNS area, but also sustainably deliver bioproducts to the local injured area, thus improving the microenvironment in that area. This review mainly introduces the advances of various strategies concerning facilitating CNS regeneration. PMID:27047678

  9. NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation

    SciTech Connect

    Richards, T.

    1984-09-01

    NMR imaging, NMR spectroscopic, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the central nervous system after helium beam in vivo irradiation of the rodent brain. The spectroscopic observations reported in this dissertation were made possible by development of methods for measuring the NMR parameters of the rodent brain in vivo and in vitro. The methods include (1) depth selective spectroscopy using an optimization of rf pulse energy based on a priori knowledge of N-acetyl aspartate and lipid spectra of the normal brain, (2) phase-encoded proton spectroscopy of the living rodent using a surface coil, and (3) dual aqueous and organic tissue extraction technique for spectroscopy. Radiation induced increases were observed in lipid and p-choline peaks of the proton spectrum, in vivo. Proton NMR spectroscopy measurements on brain extracts (aqueous and organic solvents) were made to observe chemical changes that could not be seen in vivo. Radiation-induced changes were observed in lactate, GABA, glutamate, and p-choline peak areas of the aqueous fraction spectra. In the organic fraction, decreases were observed in peak area ratios of the terminal-methyl peaks, the N-methyl groups of choline, and at a peak at 2.84 ppM (phosphatidyl ethanolamine and phosphatidyl serine resonances) relative to TMS. With histology and Evans blue injections, blood-brain barrier alternations were seen as early as 4 days after irradiation. 83 references, 53 figures.

  10. 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

  11. Role of microglia and astrocyte in central pain syndrome following electrolytic lesion at the spinothalamic tract in rats.

    PubMed

    Naseri, Kobra; Saghaei, Elham; Abbaszadeh, Fatemeh; Afhami, Mina; Haeri, Ali; Rahimi, Farzaneh; Jorjani, Masoumeh

    2013-03-01

    Central pain syndrome (CPS) is a debilitating state and one of the consequences of spinal cord injury in patients. Many pathophysiological aspects of CPS are not well documented. Spinal glia activation has been identified as a key factor in the sensory component of chronic pain. In this study, the role of glial subtypes in the process of CPS induced by unilateral electrolytic lesion of spinothalamic tract (STT) is investigated. Male rats received a laminectomy at T8-T9 and then unilateral electrolytic lesion centered on the STT. Thermal and mechanical thresholds as well as locomotor function were measured on days 0, 3, 7, 14, 21, and 28 post-injuries by tail flick, von Frey filament, and open field tests, respectively. To investigate the spinal glial activation following denervation in STT-lesioned groups, Iba1 and GFAP were detected by immunohistochemistry and Western blotting at the same time points. Data showed that STT lesion significantly decreased thermal pain at day 3 in comparison with sham groups. Significant bilateral allodynia appeared in hind paws at day 14 after spinal cord injury and continued to day 28 (P < 0.05). Additionally, electrolytic spinal lesion attenuated locomotor function of injured animals after 7 days (P < 0.05). In both histological assessments and Western blotting, Iba1 increased at days 3 and 7 while increased GFAP occurred from day 14 to 28 after lesion. It appears that microglial activation is important in the early stages of pain development and astrocytic activation occurs later. These events may lead to behavioral outcomes especially central neuropathic pain. PMID:22722907

  12. Arteriovenous Malformations and Other Vascular Lesions of the Central Nervous System

    MedlinePlus

    ... major blood vessel involved, this lesion is located deep inside the brain. It is frequently associated with ... AVMs also can form from blood vessels located deep inside the interior of the cerebrum (the main ...

  13. Exploring the Altered Dynamics of Mammalian Central Carbon Metabolic Pathway in Cancer Cells: A Classical Control Theoretic Approach

    PubMed Central

    Paul, Debjyoti; Dasgupta, Abhijit; De, Rajat K.

    2015-01-01

    Background In contrast with normal cells, most of the cancer cells depend on aerobic glycolysis for energy production in the form of adenosine triphosphate (ATP) bypassing mitochondrial oxidative phosphorylation. Moreover, compared to normal cells, cancer cells exhibit higher consumption of glucose with higher production of lactate. Again, higher rate of glycolysis provides the necessary glycolytic intermediary precursors for DNA, protein and lipid synthesis to maintain high active proliferation of the tumor cells. In this scenario, classical control theory based approach may be useful to explore the altered dynamics of the cancer cells. Since the dynamics of the cancer cells is different from that of the normal cells, understanding their dynamics may lead to development of novel therapeutic strategies. Method We have developed a model based on the state space equations of classical control theory along with an order reduction technique to mimic the actual dynamic behavior of mammalian central carbon metabolic (CCM) pathway in normal cells. Here, we have modified Michaelis Menten kinetic equation to incorporate feedback mechanism along with perturbations and cross talks associated with a metabolic pathway. Furthermore, we have perturbed the proposed model to reduce the mitochondrial oxidative phosphorylation. Thereafter, we have connected proportional-integral (PI) controller(s) with the model for tuning it to behave like the CCM pathway of a cancer cell. This methodology allows one to track the altered dynamics mediated by different enzymes. Results and Discussions The proposed model successfully mimics all the probable dynamics of the CCM pathway in normal cells. Moreover, experimental results demonstrate that in cancer cells, a coordination among enzymes catalyzing pentose phosphate pathway and intermediate glycolytic enzymes along with switching of pyruvate kinase (M2 isoform) plays an important role to maintain their altered dynamics. PMID:26367460

  14. Analogs of 2-amino-4-phosphonobutanoic acid (APB) as antagonists of excitatory neurotransmission in the mammalian central nervous system

    SciTech Connect

    Crooks, S.L.

    1986-01-01

    The status of L-glutamate as an excitatory neurotransmitter in the mammalian central nervous system awaits elucidation due to the lack of potent and specific antagonists. The glutamate analog L-2-amino-4-phosphonobutanoic acid (L-APB) is a moderately potent antagonist of excitatory neurotransmission in the rate hippocampus (IC/sub 50/) = 2.5 ..mu..M), and this compound invites development of potentially more potent analogs. The directions of exploration in this research include: (1) modification of the dianionic capability on the side chain of APB; (2) variation of the spatial relationships between the charged groups on APB; (3) substitution of methyl groups for hydrogens at the N-, 2-, 3-, and 4-positions of APB in order to probe the steric tolerance of the APB recognition site; and (4) restriction of the conformations available to APB by including its structure in cyclic analogs. The biological activity of the analogs was measured electrophysiologically in the rat hippocampal slice. The ability of the APB analogs to displace DL-(/sup 3/H)-APB from a rat brain synaptosomal membrane preparation was also measured. The dianionic capability of the phosphonate moiety was not crucial for antagonist activity but appeared to contribute greatly to potency. An ..cap alpha..-relationship of the amino group to the carboxylate moiety appeared to be crucial for activity. The cyclic analogs were weaker than APB, although cyclopentyl analogs of APB did retain useful activity. The differences in potency noted for the APB analogs in these two assays suggested that the APB recognition sites in these two systems were not identical.

  15. 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

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

    PubMed

    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

  17. Role of the lesion scar in the response to damage and repair of the central nervous system.

    PubMed

    Kawano, Hitoshi; Kimura-Kuroda, Junko; Komuta, Yukari; Yoshioka, Nozomu; Li, Hong Peng; Kawamura, Koki; Li, Ying; Raisman, Geoffrey

    2012-07-01

    Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation. PMID:22362507

  18. Disruption of neuroendocrine stress responses to acute ferret odor by medial, but not central amygdala lesions in rats

    PubMed Central

    Masini, Cher V.; Sasse, Sarah K.; Garcia, Robert J.; Nyhuis, Tara J.; Day, Heidi E.W.; Campeau, Serge

    2009-01-01

    Investigations of the neural pathways associated with responses to predators have implicated the medial amygdala (MeA) as an important region involved in defensive behaviors. To our knowledge, however, the involvement of the MeA in neuroendocrine responses to predator odor exposure has not been investigated. Therefore, the present study examined the effects of MeA disruption in rats exposed to ferret or control odor on hypothalamo-pituitary-adrenocortical (HPA) axis activation. Bilateral lesions of the MeA were made in Sprague- Dawley rats with the neurotoxin ibotenic acid (10 µg/µl; 0.3 µl /side). As a control for regional specificity, additional groups of rats were given lesions in the central amygdala (CeA). One week after recovery, the rats were exposed to ferret or strawberry control towels in small cages to examine HPA axis responses as determined by plasma corticosterone and adrenocorticotropin hormone (ACTH) levels. Rats with complete bilateral MeA but not CeA lesions displayed significantly less corticosterone and ACTH release compared to sham-operated control rats only in the ferret odor conditions. These results suggest that the MeA is an important structure involved in the HPA axis responses to predator odors, in support of previous studies investigating behavioral responses under similar conditions. PMID:19615352

  19. Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.

    PubMed

    Pochiro, Joseph M; Lindquist, Derick H

    2016-06-01

    In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding. PMID:26486933

  20. Central Neurogenic Hyperventilation Related to Post-Hypoxic Thalamic Lesion in a Child

    PubMed Central

    Gençpinar, Pinar; Karaali, Kamil; Haspolat, Şenay; Dursun, Oğuz

    2016-01-01

    Central neurogenic hyperventilation (CNH) is a rare clinical condition, whose mechanism is still unclear. Here, we report a 3-year-old male patient, who had bilateral thalamic, putaminal and globus pallideal infarction resulted in CNH without brainstem involvement. This case may illustrate a possible role for the thalamus in regulating ventilation. PMID:27127601

  1. Bilateral central pain sensitization in rats following a unilateral thalamic lesion may be treated with high doses of ketamine

    PubMed Central

    2013-01-01

    Background Central post-stroke pain is a neuropathic pain condition caused by a vascular lesion, of either ischemic or hemorrhagic origin, in the central nervous system and more precisely involving the spinothalamocortical pathway responsible for the transmission of painful sensations. Few animal models have been developed to study this problem. The objectives of this study were to evaluate different modalities of pain in a central neuropathic pain rat model and to assess the effects of ketamine administered at different doses. Animals were evaluated on the rotarod, Hargreaves, Von Frey and acetone tests. A very small hemorrhage was created by injecting a collagenase solution in the right ventral posterolateral thalamic nucleus. Following the establishment of the neuropathy, ketamine was evaluated as a therapeutic drug for this condition. Results Histopathological observations showed a well localized lesion with neuronal necrosis and astrocytosis following the collagenase injection that was localized within the VPL. No significant change in motor coordination was observed following surgery in either the saline or collagensae groups. In the collagenase group, a significant decrease in mechanical allodynia threshold was observed. A sporadic and transient cold allodynia was also noted. No thermal hyperalgesia was seen following the collagenase injection. Ketamine was then tested as a potential therapeutic drug. A significant decrease in motor coordination was seen only following the administration of 25 mg/kg of ketamine in both groups. An alleviation of mechanical allodynia was achieved only with the high ketamine dose. The minimal effective ketamine serum concentration (150 ng/mL) was only achieved in animals that received 25 mg/kg. Conclusions An intrathalamic hemorrhage induced a bilateral mechanical allodynia in rats. Cold hyperalgesia was observed in 60% of these animals. Mechanical allodynia was alleviated with high doses of ketamine which corresponded

  2. Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System.

    PubMed

    Geoffroy, Cédric G; Hilton, Brett J; Tetzlaff, Wolfram; Zheng, Binhai

    2016-04-12

    How aging impacts axon regeneration after CNS injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced decline in neuron-intrinsic growth state, as assessed by mTOR activity, neuronal soma size, and axonal growth proximal to a spinal cord injury. However, axonal regeneration distal to injury is greatly diminished, accompanied by increased expression of astroglial and inflammatory markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent decline in axon regeneration, as revealed when neuron-intrinsic growth state is elevated. These results have important implications for developing strategies to promote axonal repair after CNS injuries or diseases, which increasingly affect middle-aged to aging populations. PMID:27050519

  3. [New approaches in the study of neuroplasticity process in patients with central nervous system lesion].

    PubMed

    Chernikova, L A; Kremneva, E I; Cherviakov, A V; Saenko, I V; Konovalov, R N; Piramidov, M A; Kozlovskaia, I B

    2013-01-01

    Methods which on one hand can ensure the patient's mobility and on other hand activate afferents inputs are the main in rehabilitation treatment. Recent studies has shown that plasticity is structural base of recovery after central nervous system injury. Reorganization of cortical areas and increase of preserved structures functional effectiveness (intensification afferent input) are an anatomical basis of plasticity. However, sensory correction methods, without accounting of functional condition of patients, can lead to the formation of pathological symptoms: spasticity, hyperreflexia, etc. So the main aim is to study adequate management of the neuroplasticity process. This problem cannot be solving without modern methods of neuroimaging and brain mapping. The new approach for study cortical mechanisms of neuroplasticity, responsible for locomotion, was developed in the present study. This approach is complex use of functional magnetic resonance imaging (fMRI) and navigation transcranial magnetic stimulation (nTMS). It was showed that vast fMRI activation area in the first and the second sensorimotor area emerges with passive sensorimotor paradigm using that imitate backing load during walking. The mechanical stimulator footsteps backing zones "Corvit" uses for create this paradigm, nTMS examination, which used after fMRI, help localize the motor representation of muscles which control locomotion more accurately. We guess that new approach can be used for neuroplasticity process study and assessment of neuroplasticity changes during rehabilitation for restore and correct the walking. PMID:23885553

  4. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

    PubMed Central

    Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  5. Errors, limitations, and pitfalls in the diagnosis of central and peripheral nervous system lesions in intraoperative cytology and frozen sections

    PubMed Central

    Chand, Priyanka; Amit, Sonal; Gupta, Raghvendra; Agarwal, Asha

    2016-01-01

    Context: Intraoperative cytology and frozen section play an important role in the diagnosis of neurosurgical specimens. There are limitations in both these procedures but understanding the errors and pitfalls may help in increasing the diagnostic yield. Aims: To find the diagnostic accuracy of intraoperative cytology and frozen section for central and peripheral nervous system (PNS) lesions and analyze the errors, pitfalls, and limitations in these procedures. Settings and Design: Eighty cases were included in this prospective study in a span of 1.5 years. Materials and Methods: The crush preparations and the frozen sections were stained with hematoxylin and eosin method. The diagnosis of crush smears and the frozen sections were compared with the diagnosis in the paraffin section, which was considered as the gold standard. Statistical Analyses Used: Diagnostic accuracy, sensitivity, and specificity. Results: The diagnostic accuracy of crush smears was 91.25% with a sensitivity of 95.5% and specificity of 100%. In the frozen sections, the overall diagnostic accuracy was 95%, sensitivity was 96.8%, and specificity was 100%. The categories of pitfalls noted in this study were categorization of spindle cell lesions, differentiation of oligodendroglioma from astrocytoma in frozen sections, differentiation of coagulative tumor necrosis of glioblastoma multiforme (GBM) from the caseous necrosis of tuberculosis, grading of gliomas in frozen section, and differentiation of the normal granular cells of the cerebellum from the lymphocytes in cytological smears. Conclusions: Crush smear and frozen section are complimentary procedures. When both are used together, the diagnostic yield is substantially increased. PMID:27279685

  6. DO SYMPATHETIC NEURONS COORDINATE CELLULAR DEVELOPMENT IN THE HEART AND KIDNEY? EFFECTS OF NEONATAL CENTRAL AND PERIPHERAL CATECHOLMINERGIC LESIONS ON CARDIAC AND RENAL NUCLEIC ACIDS AND PROTEINS

    EPA Science Inventory

    Sympathetic nerve activity has been hypothesized to set the timing of cellular maturational events in target tissues. n the current study, this hypothesis was tested by lesioning catecholamine pathways in the periphery and central nervous system through the use of subcutaneous or...

  7. [Study of efficiency of ceraxon in the treatment of lag psychomotor development of children with hypoxic-ischemic lesions of central nervous system].

    PubMed

    Rubtsova, Ie I; Klimova, T M; Hechko, Kh A

    2014-01-01

    The study involved 76 children aged 0-2, who suffered perinatal hypoxic-ischemic central nervous system lesion. Psychomotor development of children has been studied, and the results that demonstrate the effectiveness of incorporating ceraxon in the complex therapy of hypoxic-ischemic encephalopathy, have been obtained. PMID:25796838

  8. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    PubMed Central

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics. PMID:21921682

  9. 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. PMID:9676975

  10. Southern Hemisphere humpback whales wintering off Central America: insights from water temperature into the longest mammalian migration.

    PubMed

    Rasmussen, Kristin; Palacios, Daniel M; Calambokidis, John; Saborío, Marco T; Dalla Rosa, Luciano; Secchi, Eduardo R; Steiger, Gretchen H; Allen, Judith M; Stone, Gregory S

    2007-06-22

    We report on a wintering area off the Pacific coast of Central America for humpback whales (Megaptera novaeangliae) migrating from feeding areas off Antarctica. We document seven individuals, including a mother/calf pair, that made this migration (approx. 8300km), the longest movement undertaken by any mammal. Whales were observed as far north as 11 degrees N off Costa Rica, in an area also used by a boreal population during the opposite winter season, resulting in unique spatial overlap between Northern and Southern Hemisphere populations. The occurrence of such a northerly wintering area is coincident with the development of an equatorial tongue of cold water in the eastern South Pacific, a pattern that is repeated in the eastern South Atlantic. A survey of location and water temperature at the wintering areas worldwide indicates that they are found in warm waters (21.1-28.3 degrees C), irrespective of latitude. We contend that while availability of suitable reproductive habitat in the wintering areas is important at the fine scale, water temperature influences whale distribution at the basin scale. Calf development in warm water may lead to larger adult size and increased reproductive success, a strategy that supports the energy conservation hypothesis as a reason for migration. PMID:17412669

  11. Non-human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient-responsive pathway

    PubMed Central

    Nijland, Mark J; Schlabritz-Loutsevitch, Natalia E; Hubbard, Gene B; Nathanielsz, Peter W; Cox, Laura A

    2007-01-01

    Developmental programming is defined as the process by which gene–environment interaction in the developing organism leads to permanent changes in phenotype and function. Numerous reports of maternal nutrient restriction during pregnancy demonstrate altered renal development. Typically this alteration manifests as a reduction in the total number of glomeruli in the mature kidney of the offspring, and suggests that predisposition to develop chronic renal disease may include an in utero origin. In a previous study, we defined the transcriptome in the kidney from fetuses of control (CON, fed ad libitum) and nutrient-restricted (NR, fed 70% of CON starting at 0.16 gestation (G)) pregnancies at half-way through gestation (0.5G), and established transcriptome and morphological changes in NR kidneys compared to CON. One goal of the present study was to use transcriptome data from fetal kidneys of CON and NR mothers at 0.5G with histological data to identify the molecular mechanisms that may regulate renal development. A second goal was to identify mechanisms by which NR elicits its affect on fetal baboon kidney. We have used an end-of-pathway gene expression analysis to prioritize and identify key pathways regulating the 0.5G kidney phenotype in response NR. From these data we have determined that the mammalian target of rapamycin (mTOR) signalling pathway is central to this phenotype. PMID:17185341

  12. A fuzzy logic controller based approach to model the switching mechanism of the mammalian central carbon metabolic pathway in normal and cancer cells.

    PubMed

    Dasgupta, Abhijit; Paul, Debjyoti; De, Rajat K

    2016-07-19

    Dynamics of large nonlinear complex systems, like metabolic networks, depend on several parameters. A metabolic pathway may switch to another pathway in accordance with the current state of parameters in both normal and cancer cells. Here, most of the parameter values are unknown to us. A fuzzy logic controller (FLC) has been developed here for the purpose of modeling metabolic networks by approximating the reasons for the behaviour of a system and applying expert knowledge to track switching between metabolic pathways. The simulation results can track the switching between glycolysis and gluconeogenesis, as well as glycolysis and pentose phosphate pathways (PPP) in normal cells. Unlike normal cells, pyruvate kinase (M2 isoform) (PKM2) switches alternatively between its two oligomeric forms, i.e. an active tetramer and a relatively low activity dimer, in cancer cells. Besides, there is a coordination among PKM2 switching and enzymes catalyzing PPP. These phenomena help cancer cells to maintain their high energy demand and macromolecular synthesis. However, the reduction of initial adenosine triphosphate (ATP) to a very low concentration, decreasing initial glucose uptake, destroying coordination between glycolysis and PPP, and replacement of PKM2 by its relatively inactive oligomeric form (dimer) or inhibition of the translation of PKM2 may destabilize the mutated control mechanism of the mammalian central carbon metabolic (CCM) pathway in cancer cells. The performance of the model is compared appropriately with some existing ones. PMID:27225801

  13. Stress decreases, while central nucleus amygdala lesions increase, IL-8 and MIP-1alpha gene expression during tissue healing in non-human primates.

    PubMed

    Kalin, Ned H; Shelton, Steven E; Engeland, Christopher G; Haraldsson, H Magnus; Marucha, Phillip T

    2006-11-01

    Stress impairs healing and in part this effect is thought to be mediated by glucocorticoids. However, the brain systems that underlie the effects of stress on healing remain to be determined. Since the central nucleus of the amygdala (CeA) plays a role in mediating an individual's behavioral and physiological reactivity to stress, we investigated, in rhesus monkeys, whether selective lesions of the CeA altered the gene expression of chemokines (IL-8 and MIP-1alpha) that are associated with early dermal healing. We used rhesus monkeys because they provide an excellent animal model to investigate brain mechanisms relevant to human stress, anxiety, and psychopathology. Hypothalamic-pituitary-adrenal (HPA) activity was assessed in the monkeys prior to the wound healing experiment demonstrating that the CeA lesions reduce HPA activity. In the healing experiment, stress decreased IL-8 and MIP-1alpha gene expression in both CeA lesioned and non-lesioned animals. Conversely, the CeA lesions increased the tissue expression of IL-8 and MIP-1alpha mRNA prior to and after stress exposure. These results demonstrate that in primates the CeA is a key brain region involved in the regulation of processes associated with wound healing. Because of brain and behavioral similarities between rhesus monkeys and humans, these results are particularly relevant to understanding brain mechanisms that influence healing in humans. PMID:16574374

  14. Effects of central nervous system lesions on the expression of galanin: a comparative in situ hybridization and immunohistochemical study.

    PubMed Central

    Cortés, R; Villar, M J; Verhofstad, A; Hökfelt, T

    1990-01-01

    We have used in situ hybridization and immunohistochemistry to study the expression of galanin mRNA and galanin-like immunoreactivity after decortication and lesions of the ventral hippocampus. After decortication the levels of both galanin mRNA and galanin-like immunoreactivity were increased in the dorsal raphe nucleus. In addition, in decorticated rats, but not in controls, galanin mRNA could be seen in dorsal and ventral nuclei of the thalamus and in the remaining parts of the cortex. Increases in galanin mRNA and galanin-like immunoreactivity were also observed in the septum-vertical diagonal band after electrocoagulation lesions of the ventral hippocampus. In contrast, no changes were found after ibotenic acid lesions of the same hippocampal area. These results suggest that increases in the expression of galanin occur in certain neuron populations after direct lesion of their axons and/or terminal fields. Images PMID:1699231

  15. Assessment of oral mucosal lesions among psychiatric inmates residing in central jail, Bhopal, Madhya Pradesh, India: A cross-sectional survey

    PubMed Central

    Arjun, Torwane Nilesh; Sudhir, Hongal; Sahu, R. N.; Saxena, Vrinda; Saxena, Eshani; Jain, Shubham

    2014-01-01

    Aim: The aim of the current cross-sectional study was to assess oral mucosal lesions among psychiatric jail patients residing in central jail, Bhopal, Madhya Pradesh, India. Materials and Methods: The study subjects consisted of prediagnosed psychiatric patients residing in central jail, Bhopal. A matched control consisting of cross section of the population, that is, jail inmates residing in the same central jail locality was also examined to compare the psychiatric subjects. The WHO oral health assessment proforma, 1997 along with 18-item questionnaire was used for the oral health examination. Results: A total number of subjects examined were 244, which comprised of 122 psychiatric inmates and 122 nonpsychiatric inmates. Among all psychiatric inmates, about 57.4% of inmates had a diagnosis of depression, 14.8% had psychotic disorders (like schizophrenia), and 12.3% had anxiety disorder. A total of 77% study inmates, which comprised of 87.7% psychiatrics and 66.4% nonpsychiatrics had a habit of tobacco consumption (smokeless or smoking). Overall prevalence of oral mucosal lesions among the inmates was 85 (34.8%), which comprised of 39.3% psychiatric inmates and 30.3% nonpsychiatric inmates. Conclusion: The information presented in this study adds to our understanding of the common oral mucosal lesions occurring in a psychiatric inmate population. Leukoplakia and oral submucous fibrosis were the most common types of oral mucosal lesions found. Efforts to increase patient awareness of the oral effects of tobacco use and to eliminate the habit are needed to improve oral and general health of the prison population. PMID:25316937

  16. 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

  17. 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. PMID:8823386

  18. Mammalian pheromones.

    PubMed

    Liberles, Stephen D

    2014-01-01

    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

  19. 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

  20. 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

  1. Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion.

    PubMed Central

    Liedtke, W.; Edelmann, W.; Chiu, F. C.; Kucherlapati, R.; Raine, C. S.

    1998-01-01

    Insights into the role of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), have only recently emerged with reports on subtle abnormalities in GFAP-deficient mice, including the documentation of defective long-term maintenance of central nervous system myelination. Here, we extend these observations by examining the astroglial response in GFAP-/- mice with autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Clinically, the monophasic disease was more severe in GFAP-/- mice than in wild-type littermates despite increased remyelination in the former. More in keeping with the clinical course was the observation of an infiltrative EAE lesion in GFAP-/- mice. GFAP-/- astrocytes had a reduced cytoarchitectural stability as evidenced by less abundant and irregularly spaced hemidesmosomes. The blunt GFAP-/- astrocyte processes possessed intermediate filaments consisting mainly of vimentin, though to a lesser degree than in the wild-type. In contrast, in wild-type littermates, GFAP was most abundant and nestin occurred at lower levels. Taken together, the present study introduces the novel concepts that GFAP plays an important role in the control of clinical disease associated with formation of a clearly defined edge to the EAE lesion and that GFAP is operative in the regulation of the intermediate filament components in reactive fibrillary astrogliosis. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:9422542

  2. Rib lesions in skeletons from early neolithic sites in Central Germany: on the trail of tuberculosis at the onset of agriculture.

    PubMed

    Nicklisch, Nicole; Maixner, Frank; Ganslmeier, Robert; Friederich, Susanne; Dresely, Veit; Meller, Harald; Zink, Albert; Alt, Kurt W

    2012-11-01

    As an infectious disease, tuberculosis (TB) is one of the major causes of death worldwide. Paleopathological and paleomicrobiological studies indicate a long standing association of the causative agent Mycobacterium tuberculosis and its human host. Since the occurrence and the epidemic spread of this pathogen seem to be closely linked to social and biological factors, it is of particular interest to understand better the role of TB during periods of social and nutritional change such as the Neolithic. In this study, 118 individuals from three sites in Saxony-Anhalt (Germany) dating to the Linear Pottery Culture (5400-4800 BC) were examined macroscopically to identify TB related bone lesions. In two individuals, Pott's disease was detected. In addition, periosteal reactions of varying degrees and frequency were observed mainly along the neck of the ribs in 6.5% (2/31) of subadults and 35.1% (20/57) of adults, with one site standing out markedly. Rib lesions, however, are not specific indicators of TB as they can also be caused by other diseases; so additional investigations were undertaken using histology and micro-CT scans to say more about the disease process. Supplementary molecular analyses indicate the presence of pathogens belonging to the Mycobacterium tuberculosis complex in individuals of all sites. Furthermore, we discuss the occurrence and spread of TB during the Neolithic with regard to nutritional aspects and possible risks of infection. The data presented provide important insights into the health status of Early Neolithic populations in Central Germany. PMID:23042554

  3. Lesions of the central nervous system induced by intracerebral inoculation of BALB/c mice with rabies virus (CVS-11).

    PubMed

    Kojima, Daisuke; Park, Chun-Ho; Tsujikawa, Shintarou; Kohara, Keiko; Hatai, Hitoshi; Oyamada, Toshifumi; Noguchi, Akira; Inoue, Satoshi

    2010-08-01

    BALB/c mice were inoculated intracerebrally with fixed rabies virus (CVS-11) and pathomorphological changes in the central nervous system were studied. Infected mice showed ruffled hair, hunchback, anorexia, emaciation and ataxia at 5 days postinoculation (DPI), but paralysis did not occur. Viral antigens were first detected in the pyramidal cells of the cerebral cortex and hippocampus at 3 DPI, and these cells exhibited apoptosis at 5 DPI. Microglial cells and astroglial cells significantly increased in the areas of the nerve cells which showed apoptosis. However, spinal neurons and spinal dorsal root ganglion cells did not exhibit apoptosis despite virus infection. These observations indicate that different mechanism which causes apoptosis exists among the neurons of the brain and spinal cord, and glial cells play an important role in pathogenesis of the experimental rabies. PMID:20339258

  4. Mammalian sleep

    NASA Astrophysics Data System (ADS)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  5. Mammalian aromatases.

    PubMed

    Conley, A; Hinshelwood, M

    2001-05-01

    Aromatase is the enzyme complex that catalyses the synthesis of oestrogens from androgens, and therefore it has unique potential to influence the physiological balance between the sex steroid hormones. Both aromatase cytochrome P450 (P450arom) and NADPH-cytochrome P450 reductase (reductase), the two essential components of the enzyme complex, are highly conserved among mammals and vertebrates. Aromatase expression occurs in the gonads and brain, and is essential for reproductive development and fertility. Of interest are the complex mechanisms involving alternative promoter utilization that have evolved to control tissue-specific expression in these tissues. In addition, in a number of species, including humans, expression of aromatase has a broader tissue distribution, including placenta, adipose and bone. The relevance of oestrogen synthesis and possibly androgen metabolism in these peripheral sites of expression is now becoming clear from studies in P450arom knockout (ArKO) mice and from genetic defects recognized recently in both men and women. Important species differences in the physiological roles of aromatase expression are also likely to emerge, despite the highly conserved nature of the enzyme system. The identification of functionally distinct, tissue-specific isozymes of P450arom in at least one mammal, pigs, and several species of fish indicates that there are additional subtle, but physiologically significant, species-specific roles for aromatase. Comparative studies of mammalian and other vertebrate aromatases will expand understanding of the role played by this ancient enzyme system in the evolution of reproduction and the adaptive influence of oestrogen synthesis on general health and well being. PMID:11427156

  6. Identification of PGAM5 as a Mammalian Protein Histidine Phosphatase that Plays a Central Role to Negatively Regulate CD4(+) T Cells.

    PubMed

    Panda, Saswati; Srivastava, Shekhar; Li, Zhai; Vaeth, Martin; Fuhs, Stephen R; Hunter, Tony; Skolnik, Edward Y

    2016-08-01

    Whereas phosphorylation of serine, threonine, and tyrosine is exceedingly well characterized, the role of histidine phosphorylation in mammalian signaling is largely unexplored. Here we show that phosphoglycerate mutase family 5 (PGAM5) functions as a phosphohistidine phosphatase that specifically associates with and dephosphorylates the catalytic histidine on nucleoside diphosphate kinase B (NDPK-B). By dephosphorylating NDPK-B, PGAM5 negatively regulates CD4(+) T cells by inhibiting NDPK-B-mediated histidine phosphorylation and activation of the K(+) channel KCa3.1, which is required for TCR-stimulated Ca(2+) influx and cytokine production. Using recently developed monoclonal antibodies that specifically recognize phosphorylation of nitrogens at the N1 (1-pHis) or N3 (3-pHis) positions of the imidazole ring, we detect for the first time phosphoisoform-specific regulation of histidine-phosphorylated proteins in vivo, and we link these modifications to TCR signaling. These results represent an important step forward in studying the role of histidine phosphorylation in mammalian biology and disease. PMID:27453048

  7. Mammalian phospholipase C.

    PubMed

    Kadamur, Ganesh; Ross, Elliott M

    2013-01-01

    Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale. PMID:23140367

  8. Cellular and Molecular Characterization of Multipolar Map5-Expressing Cells: A Subset of Newly Generated, Stage-Specific Parenchymal Cells in the Mammalian Central Nervous System

    PubMed Central

    Crociara, Paola; Parolisi, Roberta; Conte, Daniele; Fumagalli, Marta; Bonfanti, Luca

    2013-01-01

    Although extremely interesting in adult neuro-glio-genesis and promising as an endogenous source for repair, parenchymal progenitors remain largely obscure in their identity and physiology, due to a scarce availability of stage-specific markers. What appears difficult is the distinction between real cell populations and various differentiation stages of the same population. Here we focused on a subset of multipolar, polydendrocyte-like cells (mMap5 cells) expressing the microtubule associated protein 5 (Map5), which is known to be present in most neurons. We characterized the morphology, phenotype, regional distribution, proliferative dynamics, and stage-specific marker expression of these cells in the rabbit and mouse CNS, also assessing their existence in other mammalian species. mMap5 cells were never found to co-express the Ng2 antigen. They appear to be a population of glial cells sharing features but also differences with Ng2+progenitor cells. We show that mMap5 cells are newly generated, postmitotic parenchymal elements of the oligodendroglial lineage, thus being a stage-specific population of polydendrocytes. Finally, we report that the number of mMap5 cells, although reduced within the brain of adult/old animals, can increase in neurodegenerative and traumatic conditions. PMID:23667595

  9. Tuning and playing a motor rhythm: how metabotropic glutamate receptors orchestrate generation of motor patterns in the mammalian central nervous system.

    PubMed

    Nistri, Andrea; Ostroumov, Konstantin; Sharifullina, Elina; Taccola, Giuliano

    2006-04-15

    Repeated motor activities like locomotion, mastication and respiration need rhythmic discharges of functionally connected neurons termed central pattern generators (CPGs) that cyclically activate motoneurons even in the absence of descending commands from higher centres. For motor pattern generation, CPGs require integration of multiple processes including activation of ion channels and transmitter receptors at strategic locations within motor networks. One emerging mechanism is activation of glutamate metabotropic receptors (mGluRs) belonging to group I, while group II and III mGluRs appear to play an inhibitory function on sensory inputs. Group I mGluRs generate neuronal membrane depolarization with input resistance increase and rapid fluctuations in intracellular Ca(2+), leading to enhanced excitability and rhythmicity. While synchronicity is probably due to modulation of inhibitory synaptic transmission, these oscillations occurring in coincidence with strong afferent stimuli or application of excitatory agents can trigger locomotor-like patterns. Hence, mGluR-sensitive spinal oscillators play a role in accessory networks for locomotor CPG activation. In brainstem networks supplying tongue muscle motoneurons, group I receptors facilitate excitatory synaptic inputs and evoke synchronous oscillations which stabilize motoneuron firing at regular, low frequency necessary for rhythmic tongue contractions. In this case, synchronicity depends on the strong electrical coupling amongst motoneurons rather than inhibitory transmission, while cyclic activation of K(ATP) conductances sets its periodicity. Activation of mGluRs is therefore a powerful strategy to trigger and recruit patterned discharges of motoneurons. PMID:16469790

  10. Assessment of Crop Damage by Protected Wild Mammalian Herbivores on the Western Boundary of Tadoba-Andhari Tiger Reserve (TATR), Central India

    PubMed Central

    Bayani, Abhijeet; Tiwade, Dilip; Dongre, Ashok; Dongre, Aravind P.; Phatak, Rasika; Watve, Milind

    2016-01-01

    Crop raiding by wild herbivores close to an area of protected wildlife is a serious problem that can potentially undermine conservation efforts. Since there is orders of magnitude difference between farmers’ perception of damage and the compensation given by the government, an objective and realistic estimate of damage was found essential. We employed four different approaches to estimate the extent of and patterns in crop damage by wild herbivores along the western boundary of Tadoba-Andhari Tiger Reserve in the state of Maharashtra, central India. These approaches highlight different aspects of the problem but converge on an estimated damage of over 50% for the fields adjacent to the forest, gradually reducing in intensity with distance. We found that the visual damage assessment method currently employed by the government for paying compensation to farmers was uncorrelated to and grossly underestimated actual damage. The findings necessitate a radical rethinking of policies to assess, mitigate as well as compensate for crop damage caused by protected wildlife species. PMID:27093293

  11. Assessment of Crop Damage by Protected Wild Mammalian Herbivores on the Western Boundary of Tadoba-Andhari Tiger Reserve (TATR), Central India.

    PubMed

    Bayani, Abhijeet; Tiwade, Dilip; Dongre, Ashok; Dongre, Aravind P; Phatak, Rasika; Watve, Milind

    2016-01-01

    Crop raiding by wild herbivores close to an area of protected wildlife is a serious problem that can potentially undermine conservation efforts. Since there is orders of magnitude difference between farmers' perception of damage and the compensation given by the government, an objective and realistic estimate of damage was found essential. We employed four different approaches to estimate the extent of and patterns in crop damage by wild herbivores along the western boundary of Tadoba-Andhari Tiger Reserve in the state of Maharashtra, central India. These approaches highlight different aspects of the problem but converge on an estimated damage of over 50% for the fields adjacent to the forest, gradually reducing in intensity with distance. We found that the visual damage assessment method currently employed by the government for paying compensation to farmers was uncorrelated to and grossly underestimated actual damage. The findings necessitate a radical rethinking of policies to assess, mitigate as well as compensate for crop damage caused by protected wildlife species. PMID:27093293

  12. Mast cells in mammalian brain.

    PubMed

    Dropp, J J

    1976-01-01

    Mast cells, which had until recently been believed to be not present in the mammalian brain, were studied in the brains of 29 mammalian species. Although there was considerable intraspecific and interspecific variation, mast cells were most numerous within the leptomeninges (especially in those overlying the cerebrum and the dorsal thalamus - most rodents, most carnivores, chimpanzees, squirrel monkeys and elephant), the cerebral cortex (most rodents, tiger, fox, chimpanzee, tarsier, and elephant) and in many nuclei of the dorsal thalamus (most rodents, tiger, lion, and fox). In some mammals, mast cells were also numerous in the stroma of the telencephalic choroid plexuses (chimpanzee, squirrel monkey), the putamen and the claustrum (chimpanzee), the subfornical organ (pack rat, tiger, chimpanzee), the olfactory peduncles (hooded rat, albino rat), the stroma of the diencephalic choroid plexus (lion, chimpanzee, squirrel monkey), the pineal organ (chimpanzee, squirrel monkey), some nuclei of the hypothalamus (tiger), the infundibulum (hooded rat, tiger, fox) the area postrema (pack rat, chinchilla, lion, spider monkey, chimpanzee, fox) and some nuclei and tracts of the metencephalon and the myelencephalon (tiger). Neither the sex of the animal nor electrolytic lesions made in the brains of some of the animals at various times prior to sacrifice appeared to effect the number and the distribution of mast cells. Age-related changes in mast cell number and distribution were detected in the albino rat. PMID:961335

  13. Rare Form of Erdheim-Chester Disease Presenting with Isolated Central Skeletal Lesions Treated with a Combination of Alfa-Interferon and Zoledronic Acid

    PubMed Central

    Bulycheva, E. N.; Baykov, V. V.; Zaraĭskiĭ, M. I.; Salogub, G. N.

    2015-01-01

    Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis, which manifests under an extensive variety of clinical symptoms. This creates a challenge for the physician, who is required to recognize and diagnose the disease in the early stages. Despite this considerable challenge, in the last decade there has been a dramatic increase in ECD diagnoses, in most part due to an increasing awareness of this rare disorder. Involvement of the axial skeleton is exclusively uncommon with no official recommendations for the treatment of the bone lesions. Here, we present a case report of a young male patient with isolated lesions of the spine, ribs, and pelvis, who was successfully treated with a combination therapy of alfa-interferon and zoledronic acid. PMID:25949835

  14. Vascular Lesions.

    PubMed

    Jahnke, Marla N

    2016-08-01

    Vascular lesions in childhood are comprised of vascular tumors and vascular malformations. Vascular tumors encompass neoplasms of the vascular system, of which infantile hemangiomas (IHs) are the most common. Vascular malformations, on the other hand, consist of lesions due to anomalous development of the vascular system, including the capillary, venous, arterial, and lymphatic systems. Capillary malformations represent the most frequent type of vascular malformation. IHs and vascular malformations tend to follow relatively predictable growth patterns in that IHs grow then involute during early childhood, whereas vascular malformations tend to exhibit little change. Both vascular tumors and vascular malformations can demonstrate a wide range of severity and potential associated complications necessitating specialist intervention when appropriate. Evaluation and treatment of the most common types of vascular lesions are discussed in this article. [Pediatr Ann. 2016;45(8):e299-e305.]. PMID:27517358

  15. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) has differential efficacy for causing central noradrenergic lesions in two different rat strains: comparison between Long-Evans and Sprague-Dawley rats.

    PubMed

    Schuerger, R J; Balaban, C D

    1995-05-01

    We tested the hypothesis that Long-Evans (LE) and Sprague-Dawley (SD) rat strains were equally sensitive to the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) with respect to central lesions of locus coeruleus (LC) terminals as measured by immunohistochemical localization of dopamine-beta-hydroxylase (D beta H). Analysis of D beta H immunoreactivity was made by both qualitative and quantitative methods. Intraperitoneal injections of 50 mg/kg DSP-4 caused a dramatic reduction of noradrenergic terminals in the neocortex, hippocampus and cerebellum of SD, but not LE rats as compared to saline-injected controls. This finding indicates that LE rats are less sensitive than SD rats to the neurotoxic effects of DSP-4 in the central nervous system. PMID:7475238

  16. [Foot lesions].

    PubMed

    Stelzner, C; Schellong, S; Wollina, U; Machetanz, J; Unger, L

    2013-11-01

    The foot is the target organ of a variety of internal diseases. Of upmost importance is the diabetic foot syndrome (DFS). Its complex pathophysiology is driven by the diabetic neuropathy, a vastly worsening effect is contributed by infection and ischemia. Seemingly localised lesions have the potential for phlegmone and septicaemia if not diagnosed and drained early. The acral lesions of peripheral artery occlusive disease (PAOD) have unique features as well. However, their life-threatening potential is lower than that of DFS even if the limb is critical. Notably, isolated foot lesions with a mere venous cause may arise from insufficient perforator veins; the accompanying areas of haemosiderosis will lead the diagnostic path. Cholesterol embolization (blue toe syndrome, trash foot) elicits a unique clinical picture and will become more frequent with increasing numbers of catheter-based procedures. Finally, descriptions are given of podagra and of foot mycosis as disease entities not linked to perfusion. The present review focuses on the depiction of disease and its diagnosis, leaving therapeutic considerations untouched. PMID:24114468

  17. Mammalian cardiolipin biosynthesis.

    PubMed

    Mejia, Edgard M; Nguyen, Hieu; Hatch, Grant M

    2014-04-01

    Cardiolipin is a major phospholipid in mitochondria and is involved in the generation of cellular energy in the form of ATP. In mammalian and eukaryotic cells it is synthesized via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol phosphate pathway. This brief review will describe some of the more recent studies on mammalian cardiolipin biosynthesis and provide an overview of regulation of cardiolipin biosynthesis. In addition, the important role that this key phospholipid plays in disease processes including heart failure, diabetes, thyroid hormone disease and the genetic disease Barth Syndrome will be discussed. PMID:24144810

  18. Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening program in Central Italy.

    PubMed

    Visioli, Carmen Beatriz; Crocetti, Emanuele; Zappa, Marco; Iossa, Anna; Andersson, Karin Louise; Bulgaresi, Paolo; Alfieri, Antonia; Amunni, Gianni

    2015-06-01

    Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35% (1st round) to 20% (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC. PMID:24917238

  19. Central diabetes insipidus in an HHV6 encephalitis patient with a posterior pituitary lesion that developed after tandem cord blood transplantation.

    PubMed

    Kawamoto, Shinichiro; Hatanaka, Kazuo; Imakita, Masami; Tamaki, Toshiharu

    2013-01-01

    A 60-year-old myelodysplastic syndrome patient underwent tandem cord blood transplantation. The primary cord blood graft was rejected, and human herpesvirus 6 (HHV6) encephalitis developed after engraftment of secondary cord blood. Polyuria and adipsic hypernatremia were observed during treatment of the encephalitis. The patient died of bacteremia caused by methicillin-resistant Streptococcus epidermis. HHV6 infection in the posterior pituitary was confirmed on autopsy, as was infection of the hippocampus, but not of the hypothalamus. This is the first case report of central diabetes insipidus caused by an HHV6 posterior pituitary infection demonstrated on a pathological examination. PMID:23676599

  20. 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

  1. Pox-like lesions and haemorrhagic fever in two concurrent cases in the Central African Republic: case investigation and management in difficult circumstances

    PubMed Central

    Froeschl, Guenter; Kayembe, Pitchou Kasongo

    2015-01-01

    Cases of monkeypox in humans are frequently reported from the Democratic Republic of Congo. The few reports from the Central African Republic have been limited to cases in the far South closely bordering the Congos. Team members of an international medical organisation have suspected clinically two human cases of MPX, associated with clinical signs of coagulopathy and haemorrhage in the North of the country. Key findings were history of a squirrel, fever and vesicular dermal eruptions. Subsequently patients developed profuse epistaxis and hematemesis, associated with clinical signs of shock. Both patients were isolated and treated symptomatically. Samples were sent to a regional reference laboratory, who initially issued a confirmation of the suspected diagnosis of MPX in both cases. The result was later revised, and additional analyses of samples could not confirm the diagnosis. PMID:26664524

  2. Mammalian Septins Nomenclature

    PubMed Central

    Macara, Ian G.; Baldarelli, Richard; Field, Christine M.; Glotzer, Michael; Hayashi, Yasuhide; Hsu, Shu-Chan; Kennedy, Mary B.; Kinoshita, Makoto; Longtine, Mark; Low, Claudia; Maltais, Lois J.; McKenzie, Louise; Mitchison, Timothy J.; Nishikawa, Toru; Noda, Makoto; Petty, Elizabeth M.; Peifer, Mark; Pringle, John R.; Robinson, Phillip J.; Roth, Dagmar; Russell, S.E. Hilary; Stuhlmann, Heidi; Tanaka, Manami; Tanaka, Tomoo; Trimble, William S.; Ware, Jerry; Zeleznik-Le, Nancy J.; Zieger, Barbara

    2002-01-01

    There are 10 known mammalian septin genes, some of which produce multiple splice variants. The current nomenclature for the genes and gene products is very confusing, with several different names having been given to the same gene product and distinct names given to splice variants of the same gene. Moreover, some names are based on those of yeast or Drosophila septins that are not the closest homologues. Therefore, we suggest that the mammalian septin field adopt a common nomenclature system, based on that adopted by the Mouse Genomic Nomenclature Committee and accepted by the Human Genome Organization Gene Nomenclature Committee. The human and mouse septin genes will be named SEPT1–SEPT10 and Sept1–Sept10, respectively. Splice variants will be designated by an underscore followed by a lowercase “v” and a number, e.g., SEPT4_v1. PMID:12475938

  3. Mammalian sweet taste receptors.

    PubMed

    Nelson, G; Hoon, M A; Chandrashekar, J; Zhang, Y; Ryba, N J; Zuker, C S

    2001-08-10

    The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery. PMID:11509186

  4. 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

  5. Efficient secretion of biologically active Chondroitinase ABC from mammalian cells in the absence of an N-terminal signal peptide.

    PubMed

    Klüppel, Michael

    2011-05-01

    Proteoglycans carrying chondroitin sulfate side chains have been shown to fulfill important biological functions in development, disease, and signaling. One area of considerable interest is the functional importance of chondroitin sulfates as inhibitors of the regeneration of axonal projections in the mammalian central nervous system. In animal models of spinal cord injury, injections of the enzyme Chondroitinase ABC from the bacterium Proteus vulgaris into the lesion site leads to degradation of chondroitin sulfates, and promotes axonal regeneration and significant functional recovery. Here, a mammalian expression system of an epitope-tagged Chondroitinase ABC protein is described. It is demonstrated that the addition of a eukaryotic secretion signal sequence to the N-terminus of the bacterial Chondroitinase ABC sequence allowed secretion, but interfered with function of the secreted enzyme. In contrast, expression of the Chondroitinase ABC gene without N-terminal eukaryotic secretion sequence or bacterial hydrophobic leader sequence led to efficient secretion of a biologically active Chondroitinase ABC protein from both immortalized and primary cells. Moreover, the C-terminal epitope tag could be utilized to follow expression of this protein. This novel Chondroitinase ABC gene is a valuable tool for a better understanding of the in vivo roles of chondroitin sulfates in mammalian development and disease, as well as in gene therapy approaches, including the treatment of spinal chord injuries. PMID:21213020

  6. Hearing disorders in brainstem lesions.

    PubMed

    Celesia, Gastone G

    2015-01-01

    Auditory processing can be disrupted by brainstem lesions. It is estimated that approximately 57% of brainstem lesions are associated with auditory disorders. However diseases of the brainstem usually involve many structures, producing a plethora of other neurologic deficits, often relegating "auditory symptoms in the background." Lesions below or within the cochlear nuclei result in ipsilateral auditory-processing abnormalities detected in routine testing; disorders rostral to the cochlear nuclei may result in bilateral abnormalities or may be silent. Lesions in the superior olivary complex and trapezoid body show a mixture of ipsilateral, contralateral, and bilateral abnormalities, whereas lesions of the lateral lemniscus, inferior colliculus, and medial geniculate body do not affect peripheral auditory processing and result in predominantly subtle contralateral abnormalities that may be missed by routine auditory testing. In these cases psychophysical methods developed for the evaluation of central auditory function should be employed (e.g., dichotic listening, interaural time perception, sound localization). The extensive connections of the auditory brainstem nuclei not only are responsible for binaural interaction but also assure redundancy in the system. This redundancy may explain why small brainstem lesions are sometimes clinically silent. Any disorder of the brainstem (e.g., neoplasms, vascular disorders, infections, trauma, demyelinating disorders, neurodegenerative diseases, malformations) that involves the auditory pathways and/or centers may produce hearing abnormalities. PMID:25726288

  7. Mammalian Endogenous Retroviruses.

    PubMed

    Mager, Dixie L; Stoye, Jonathan P

    2015-02-01

    Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles. PMID:26104559

  8. Mammalian Kidney Development: Principles, Progress, and Projections

    PubMed Central

    Little, Melissa H.; McMahon, Andrew P.

    2012-01-01

    The mammalian kidney is a vital organ with considerable cellular complexity and functional diversity. Kidney development is notable for requiring distinct but coincident tubulogenic processes involving reciprocal inductive signals between mesenchymal and epithelial progenitor compartments. Key molecular pathways mediating these interactions have been identified. Further, advances in the analysis of gene expression and gene activity, coupled with a detailed knowledge of cell origins, are enhancing our understanding of kidney morphogenesis and unraveling the normal processes of postnatal repair and identifying disease-causing mechanisms. This article focuses on recent insights into central regulatory processes governing organ assembly and renal disease, and predicts future directions for the field. PMID:22550230

  9. The mammalian blastocyst.

    PubMed

    Frankenberg, Stephen R; de Barros, Flavia R O; Rossant, Janet; Renfree, Marilyn B

    2016-01-01

    The blastocyst is a mammalian invention that carries the embryo from cleavage to gastrulation. For such a simple structure, it exhibits remarkable diversity in its mode of formation, morphology, longevity, and intimacy with the uterine endometrium. This review explores this diversity in the light of the evolution of viviparity, comparing the three main groups of mammals: monotremes, marsupials, and eutherians. The principal drivers in blastocyst evolution were loss of yolk coupled with evolution of the placenta. An important outcome of blastocyst development is differentiation of two extraembryonic lineages (trophoblast and hypoblast) that contribute to the placenta. While in many species trophoblast segregation is often coupled with blastocyst formation, in marsupials and at least some Afrotherians, these events do not coincide. Thus, many questions regarding the conservation of molecular mechanisms controlling these events are of great interest but currently unresolved. For further resources related to this article, please visit the WIREs website. PMID:26799266

  10. Oral Lesions and Lymphoproliferative Disorders

    PubMed Central

    Castellarin, P.; Pozzato, G.; Tirelli, G.; Di Lenarda, R.; Biasotto, M.

    2010-01-01

    Lymphoproliferative disorders are heterogeneous malignancy characterized by the expansion of a lymphoid clone more or less differentiated. At the level of the oral cavity, the lymphoproliferative disorder can occur in various ways, most commonly as lymphoid lesions with extranodal externalization, but sometimes, oral lesions may represent a localization of a disease spread. With regard to the primary localizations of lymphoproliferative disorders, a careful examination of the head and neck, oral, and oropharyngeal area is necessary in order to identify suspicious lesions, and their early detection results in a better prognosis for the patient. Numerous complications have been described and frequently found at oral level, due to pathology or different therapeutic strategies. These complications require precise diagnosis and measures to oral health care. In all this, oral pathologists, as well as dental practitioners, have a central role in the treatment and long-term monitoring of these patients. PMID:20871659

  11. Factors Influencing the Central Nervous System Distribution of a Novel Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GSK2126458: Implications for Overcoming Resistance with Combination Therapy for Melanoma Brain Metastases.

    PubMed

    Vaidhyanathan, Shruthi; Wilken-Resman, Brynna; Ma, Daniel J; Parrish, Karen E; Mittapalli, Rajendar K; Carlson, Brett L; Sarkaria, Jann N; Elmquist, William F

    2016-02-01

    Small molecule inhibitors targeting the mitogen-activated protein kinase pathway (Braf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) have had success in extending survival for patients with metastatic melanoma. Unfortunately, resistance may occur via cross-activation of alternate signaling pathways. One approach to overcome resistance is to simultaneously target the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway. Recent reports have shown that GSK2126458 [2,4-difluoro-N-(2-methoxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl) benzenesulfonamide], a dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor, can overcome acquired resistance to Braf and mitogen-activated protein kinase kinase inhibitors in vitro. These resistance mechanisms may be especially important in melanoma brain metastases because of limited drug delivery across the blood-brain barrier. The purpose of this study was to investigate factors that influence the brain distribution of GSK2126458 and to examine the efficacy of GSK2126458 in a novel patient-derived melanoma xenograft (PDX) model. Both in vitro and in vivo studies indicate that GSK2126458 is a substrate for P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp), two dominant active efflux transporters in the blood-brain barrier. The steady-state brain distribution of GSK2126458 was 8-fold higher in the P-gp/Bcrp knockout mice compared with the wild type. We also observed that when simultaneously infused to steady state, GSK212658, dabrafenib, and trametinib, a rational combination to overcome mitogen-activated protein kinase inhibitor resistance, all had limited brain distribution. Coadministration of elacridar, a P-gp/Bcrp inhibitor, increased the brain distribution of GSK2126458 by approximately 7-fold in wild-type mice. In the PDX model, GSK2126458 showed efficacy in flank tumors but was ineffective in intracranial melanoma. These results show that

  12. Mammalian Wax Biosynthesis

    PubMed Central

    Cheng, Jeffrey B.; Russell, David W.

    2009-01-01

    Wax monoesters are synthesized by the esterification of fatty alcohols and fatty acids. A mammalian enzyme that catalyzes this reaction has not been isolated. We used expression cloning to identify cDNAs encoding a wax synthase in the mouse preputial gland. The wax synthase gene is located on the X chromosome and encodes a member of the acyltransferase family of enzymes that synthesize neutral lipids. Expression of wax synthase in cultured cells led to the formation of wax monoesters from straight chain saturated, unsaturated, and polyunsaturated fatty alcohols and acids. Polyisoprenols also were incorporated into wax monoesters by the enzyme. The wax synthase had little or no ability to synthesize cholesteryl esters, diacylglycerols, or triacylglycerols, whereas other acyltransferases, including the acyl-CoA:monoacylglycerol acyltransferase 1 and 2 enzymes and the acyl-CoA:diacylglycerol acyltransferase 1 and 2 enzymes, exhibited modest wax monoester synthesis activities. Confocal light microscopy indicated that the wax synthase was localized in membranes of the endoplasmic reticulum. Wax synthase mRNA was abundant in tissues rich in sebaceous glands such as the preputial gland and eyelid and was present at lower levels in other tissues. Coexpression of cDNAs specifying fatty acyl-CoA reductase 1 and wax synthase led to the synthesis of wax monoesters. The data suggest that wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes. PMID:15220349

  13. Structure of mammalian metallothionein

    SciTech Connect

    Kaegi, J.H.R.; Vasak, M.; Lerch, K.; Gilg, D.E.O.; Hunziker, P.; Bernhard, W.R.; Good, M.

    1984-03-01

    All mammalian metallothioneins characterized contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for seven metal-binding sites. Native metallothioneins are usually heterogeneous in metal composition, with Zn, Cd, and Cu occurring in varying proportions. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, Co, Hg, Pb, Bi, have now been prepared by in vitro reconstitution from the metal-free apoprotein. By spectroscopic analysis of such derivatives it was established that all cysteine residues participate in metal binding, that each metal ion is bound to four thiolate ligands, and that the symmetry of each complex is close to that of a tetrahedron. To satisfy the requirements of the overall Me/sub 7/(Cys/sup -/)/sub 20/ stoichiometry, the complexes must be combined to form metal-thiolate cluster structures. The actual spatial organization of the clusters and the polypeptide chain remains to be established. An attractive possibility is the arrangement of the tetrahedral metal-thiolates in adamantane-like structures surrounded by properly folded segments of the chain providing the ligands. /sup 1/H-NMR data and infrared absorption measurements are consistent with a tightly folded structure rich in ..beta..-type conformation. 79 references, 11 figures, 4 tables.

  14. 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

  15. Mammalian Sirtuins and Energy Metabolism

    PubMed Central

    Li, Xiaoling; Kazgan, Nevzat

    2011-01-01

    Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes. PMID:21614150

  16. 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

  17. 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. PMID:26990983

  18. 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. PMID:16350345

  19. Mammalian DNA Repair. Final Report

    SciTech Connect

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  20. Mammalian Interphase Cdks

    PubMed Central

    2012-01-01

    Cyclin-dependent kinases (Cdks) drive cell cycle progression in all eukaryotes. Yeasts have a single major Cdk that mediates distinct cell cycle transitions via association with different cyclins. The closest homolog in mammals, Cdk1, drives mitosis. Mammals have additional Cdks—Cdk2, Cdk4, and Cdk6—that represent the major Cdks activated during interphase (iCdks). A large body of evidence has accrued that suggests that activation of iCdks dictates progression though interphase. In apparent contradiction, deficiency in each individual iCdk, respectively, in knockout mice proved to be compatible with live birth and in some instances fertility. Moreover, murine embryos could be derived with Cdk1 as the only functional Cdk. Thus, none of the iCdks is strictly essential for mammalian cell cycle progression, raising the possibility that Cdk1 is the dominant regulator in interphase. However, an absence of iCdks has been accompanied by major shifts in cyclin association to Cdk1, suggesting gain in function. After considerable tweaking, a chemical genetic approach has recently been able to examine the impact of acute inhibition of Cdk2 activity without marked distortion of cyclin/Cdk complex formation. The results suggest that, when expressed at its normal levels, Cdk2 performs essential roles in driving human cells into S phase and maintaining genomic stability. These new findings appear to have restored order to the cell cycle field, bringing it full circle to the view that iCdks indeed play important roles. They also underscore the caveat in knockdown and knockout approaches that protein underexpression can significantly perturb a protein interaction network. We discuss the implications of the new synthesis for future cell cycle studies and anti–Cdk-based therapy of cancer and other diseases. PMID:23634250

  1. Isotope Labeling in Mammalian Cells

    PubMed Central

    Dutta, Arpana; Saxena, Krishna; Klein-Seetharaman, Judith

    2011-01-01

    Isotope labeling of proteins represents an important and often required tool for the application of nuclear magnetic resonance (NMR) spectroscopy to investigate the structure and dynamics of proteins. Mammalian expression systems have conventionally been considered to be too weak and inefficient for protein expression. However, recent advances have significantly improved the expression levels of these systems. Here, we provide an overview of some of the recent developments in expression strategies for mammalian expression systems in view of NMR investigations. PMID:22167668

  2. DNA repair and radiation sensitivity in mammalian cells

    SciTech Connect

    Chen, D.J.C.; Stackhouse, M. ); Chen, D.S. . Dept. of Radiation Oncology)

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  3. DNA repair and radiation sensitivity in mammalian cells

    SciTech Connect

    Chen, D.J.C.; Stackhouse, M.; Chen, D.S.

    1993-02-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  4. 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.

  5. Base excision repair intermediates are mutagenic in mammalian cells

    PubMed Central

    Simonelli, Valeria; Narciso, Laura; Dogliotti, Eugenia; Fortini, Paola

    2005-01-01

    Base excision repair (BER) is the main pathway for repair of DNA damage in mammalian cells. This pathway leads to the formation of DNA repair intermediates which, if still unsolved, cause cell lethality and mutagenesis. To characterize mutations induced by BER intermediates in mammalian cells, an SV-40 derived shuttle vector was constructed carrying a site-specific lesion within the recognition sequence of a restriction endonuclease. The mutation spectra of abasic (AP) sites, 5′-deoxyribose-5-phosphate (5′dRp) and 3′-[2,3-didehydro-2,3-dideoxy-ribose] (3′ddR5p) single-strand breaks (ssb) in mammalian cells was analysed by RFLP/PCR and mutation frequency was estimated by quantitative PCR. Point mutations were the predominant events occurring at all BER intermediates. The AP site-induced mutation spectrum supports evidence for the ‘A-rule’ and is also consistent with the use of the 5′ neighbouring base to instruct nucleotide incorporation (5′-rule). Preferential adenine insertion was also observed after in vivo replication of 5′dRp or 3′ddR5p ssb. We provide original evidence that not only the abasic site but also its derivatives ‘faceless’ BER intermediates are mutagenic, with a similar mutation frequency, in mammalian cells. Our findings support the hypothesis that unattended BER intermediates could be a constant threat for genome integrity as well as a spontaneous source of mutations. PMID:16077026

  6. Focusing on RISC assembly in mammalian cells

    SciTech Connect

    Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; 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.

  7. DIFFERENTIAL RECOVERY OF 'TK' AND 'HGPRT' INDUCED MUTANTS IN MAMMALIAN CELLS

    EPA Science Inventory

    Human genetic disease is known to result from both point mutations and chromosomal aberrations. It is therefore critical that short-term in vitro mammalian tests be evaluated as to their capabilities for detecting both types of lesions. Research to date indicates that L5178Y/TK p...

  8. Sirtuins: Guardians of Mammalian Healthspan

    PubMed Central

    Giblin, William; Skinner, Mary E.; Lombard, David B.

    2014-01-01

    The first link between sirtuins and longevity was made 15 years ago in yeast. These initial studies sparked efforts by many laboratories working in diverse model organisms to elucidate the relationships between sirtuins, lifespan, and age-associated dysfunction. Here we discuss the current understanding of how sirtuins relate to aging. We focus primarily on mammalian sirtuins SIRT1, SIRT3, and SIRT6, the three sirtuins for which the most relevant data are available. Strikingly, a large body of evidence now indicates that these and other mammalian sirtuins suppress a variety of age-related pathologies and promote healthspan. Moreover, increased expression of SIRT1 or SIRT6 extends mouse lifespan. Overall, these data point to important roles for sirtuins in promoting mammalian health, and perhaps in modulating the aging process. PMID:24877878

  9. Electroporation into Cultured Mammalian Embryos

    NASA Astrophysics Data System (ADS)

    Nomura, Tadashi; Takahashi, Masanori; Osumi, Noriko

    Over the last century, mammalian embryos have been used extensively as a common animal model to investigate fundamental questions in the field of developmental biology. More recently, the establishment of transgenic and gene-targeting systems in laboratory mice has enabled researchers to unveil the genetic mechanisms under lying complex developmental processes (Mak, 2007). However, our understanding of cell—cell interactions and their molecular basis in the early stages of mammalian embryogenesis is still very fragmentary. One of the major problems is the difficulty of precise manipulation and limited accessibility to mammalian embryos via uterus wall. Unfortunately, existing tissue and organotypic culture systems per se do not fully recapitulate three-dimensional, dynamic processes of organogenesis observed in vivo. Although transgenic animal technology and virus-mediated gene delivery are useful to manipulate gene expression, these techniques take much time and financial costs, which limit their use.

  10. Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells.

    PubMed

    Izhar, Lior; Ziv, Omer; Cohen, Isadora S; Geacintov, Nicholas E; Livneh, Zvi

    2013-04-16

    DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis. PMID:23530190

  11. Ghost cell lesions

    PubMed Central

    Rajesh, E.; Jimson, Sudha; Masthan, K. M. K.; Balachander, N.

    2015-01-01

    Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms. PMID:26015694

  12. [Surprising white lesions].

    PubMed

    Nolte, J W; van der Waal, I

    2011-09-01

    A 46-year-old man appeared with white lesions of the oral cavity. A previously taken biopsy revealed no classifying diagnosis and treatment with mouth rinse produced no improvement. A new biopsy was taken, on which the pathologist performed additional tests. This resulted in the diagnosis 'syphilis'. The patient was treated with benzylpenicillin and the oral white lesions disappeared. Although nowadays syphilis is rare, special attention is required when noticing these kinds of lesions of the oral cavity. PMID:21957637

  13. DNA repair in mammalian embryos.

    PubMed

    Jaroudi, Souraya; SenGupta, Sioban

    2007-01-01

    Mammalian cells have developed complex mechanisms to identify DNA damage and activate the required response to maintain genome integrity. Those mechanisms include DNA damage detection, DNA repair, cell cycle arrest and apoptosis which operate together to protect the conceptus from DNA damage originating either in parental gametes or in the embryo's somatic cells. DNA repair in the newly fertilized preimplantation embryo is believed to rely entirely on the oocyte's machinery (mRNAs and proteins deposited and stored prior to ovulation). DNA repair genes have been shown to be expressed in the early stages of mammalian development. The survival of the embryo necessitates that the oocyte be sufficiently equipped with maternal stored products and that embryonic gene expression commences at the correct time. A Medline based literature search was performed using the keywords 'DNA repair' and 'embryo development' or 'gametogenesis' (publication dates between 1995 and 2006). Mammalian studies which investigated gene expression were selected. Further articles were acquired from the citations in the articles obtained from the preliminary Medline search. This paper reviews mammalian DNA repair from gametogenesis to preimplantation embryos to late gestational stages. PMID:17141556

  14. Efficacy and Safety of Mammalian Target of Rapamycin Inhibitors in Vascular Anomalies: A Systematic Review.

    PubMed

    Nadal, Marion; Giraudeau, Bruno; Tavernier, Elsa; Jonville-Bera, Annie-Pierre; Lorette, Gerárd; Maruani, Annabel

    2016-05-01

    Mammalian target of rapamycin (mTOR) inhibitors are a promising new treatment in vascular anomalies, but no published randomized controlled trials are available. The aim of this systematic review of all reported cases was to assess the efficacy and safety of mTOR inhibitors in all vascular anomalies, except cancers, in children and adults. In November 2014 MEDLINE, CENTRAL, LILACS and EMBASE were searched for studies of mTOR inhibitors in any vascular condition, except for malignant lesions, in humans. Fourteen publications and 9 posters, with data on 25 and 59 patients, respectively, all < 18 years old were included. Of these patients, 35.7% (n = 30) had vascular tumours, and 64.3% (n = 54) had malformations. Sirolimus was the most frequent mTOR inhibitor used (98.8%, n = 83). It was efficient in all cases, at a median time of 2 weeks (95% confidence interval 1-10 weeks). Sirolimus was well tolerated, the main side-effect being mouth sores, which led to treatment withdrawal in one case. The dosage of sirolimus was heterogeneous, the most common being 1.6 mg/m2/day. PMID:26607948

  15. Molecular mechanisms of DNA damage recognition for mammalian nucleotide excision repair.

    PubMed

    Sugasawa, Kaoru

    2016-08-01

    For faithful DNA repair, it is crucial for cells to locate lesions precisely within the vast genome. In the mammalian global genomic nucleotide excision repair (NER) pathway, this difficult task is accomplished through multiple steps, in which the xeroderma pigmentosum group C (XPC) protein complex plays a central role. XPC senses the presence of oscillating 'normal' bases in the DNA duplex, and its binding properties contribute to the extremely broad substrate specificity of NER. Unlike XPC, which acts as a versatile sensor of DNA helical distortion, the UV-damaged DNA-binding protein (UV-DDB) is more specialized, recognizing UV-induced photolesions and facilitating recruitment of XPC. Recent single-molecule analyses and structural studies have advanced our understanding of how UV-DDB finds its targets, particularly in the context of chromatin. After XPC binds DNA, it is necessary to verify the presence of damage in order to avoid potentially deleterious incisions at damage-free sites. Accumulating evidence suggests that XPA and the helicase activity of transcription factor IIH (TFIIH) cooperate to verify abnormalities in DNA chemistry. This chapter reviews recent findings about the mechanisms underlying the efficiency, versatility, and accuracy of NER. PMID:27264556

  16. Preinvasive lesions

    Cancer.gov

    This definition is for allocation of lesions with preinvasive/borderline properties. It is currently aimed at newly identified neoplasms, which may be similar to those described in humans. In mouse pathology, many adenomas may be preinvasive/borderline lesions. However, their inclusion in the preinvasive category can be justified only upon development of better diagnostic criteria.

  17. Noninfectious penile lesions.

    PubMed

    Teichman, Joel M H; Sea, Jason; Thompson, Ian M; Elston, Dirk M

    2010-01-15

    Family physicians commonly diagnose and manage penile cutaneous lesions. Noninfectious lesions may be classified as inflammatory and papulosquamous (e.g., psoriasis, lichen sclerosus, angiokeratomas, lichen nitidus, lichen planus), or as neoplastic (e.g., carcinoma in situ, invasive squamous cell carcinoma). The clinical presentation and appearance of the lesions guide the diagnosis. Psoriasis presents as red or salmon-colored plaques with overlying scales, often with systemic lesions. Lichen sclerosus presents as a phimotic, hypopigmented prepuce or glans penis with a cellophane-like texture. Angiokeratomas are typically asymptomatic, well-circumscribed, red or blue papules, whereas lichen nitidus usually produces asymptomatic pinhead-sized, hypopigmented papules. The lesions of lichen planus are pruritic, violaceous, polygonal papules that are typically systemic. Carcinoma in situ should be suspected if the patient has velvety red or keratotic plaques of the glans penis or prepuce, whereas invasive squamous cell carcinoma presents as a painless lump, ulcer, or fungating irregular mass. Some benign lesions, such as psoriasis and lichen planus, can mimic carcinoma in situ or squamous cell carcinoma. Biopsy is indicated if the diagnosis is in doubt or neoplasm cannot be excluded. The management of benign penile lesions usually involves observation or topical corticosteroids; however, neoplastic lesions generally require surgery. PMID:20082512

  18. Imaging Pediatric Vascular Lesions.

    PubMed

    Nguyen, Tuyet A; Krakowski, Andrew C; Naheedy, John H; Kruk, Peter G; Friedlander, Sheila Fallon

    2015-12-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  19. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  20. Extragastric Dieulafoy's lesion

    PubMed Central

    Gauci, James; Galea, Samuel; Galea, Joseph; Schembri, Mark

    2014-01-01

    A 74-year-old man on warfarin for aortic valve replacement presented with recurrent episodes of melaena. An initial oesophagogastroduodenoscopy (OGD) was normal, as were red cell scanning and colonoscopy. It was a third OGD that revealed the cause of the melaena—a vascular lesion in the duodenum, at the junction between D1 and D2. An extragastric Dieulafoy's lesion was diagnosed, and the lesion was injected with epinephrine and tattooed. Over the following months, episodes of bleeding recurred despite further attempts at injection. Percutaneous radiologically assisted embolisation of the gastroduodenal artery, and eventually duodenotomy and oversuturing of the lesion were performed to no avail. The patient has undergone over 10 endoscopies, and has received over 70 units of packed red cells to date, since his initial presentation 6 years ago. Attempts to stop the bleeding permanently have been difficult, highlighting the complexity of managing such a lesion. PMID:25216921

  1. 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.

  2. 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

  3. An overview of mammalian pluripotency.

    PubMed

    Wu, Jun; Yamauchi, Takayoshi; Izpisua Belmonte, Juan Carlos

    2016-05-15

    Mammalian pluripotency is the ability to give rise to all somatic cells as well as the germ cells of an adult mammal. It is a unique feature of embryonic epiblast cells, existing only transiently, as cells pass through early developmental stages. By contrast, pluripotency can be captured and stabilized indefinitely in cell culture and can also be reactivated in differentiated cells via nuclear reprogramming. Pluripotent stem cells (PSCs) are the in vitro carriers of pluripotency and they can inhabit discrete pluripotent states depending on the stage at which they were derived and their culture conditions. Here, and in the accompanying poster, we provide a summary of mammalian pluripotency both in vivo and in vitro, and highlight recent and future applications of PSCs for basic and translational research. PMID:27190034

  4. DNA INTERSTRAND CROSSLINK REPAIR IN MAMMALIAN CELLS: STEP BY STEP

    PubMed Central

    Muniandy, Parameswary; Liu, Jia; Majumdar, Alokes; Liu, Su-ting; Seidman, Michael M.

    2009-01-01

    Interstrand DNA crosslinks (ICLs) are formed by natural products of metabolism and by chemotherapeutic reagents. Work in E. coli identified a two cycle repair scheme involving incisions on one strand on either side of the ICL (unhooking) producing a gapped intermediate with the incised oligonucleotide attached to the intact strand. The gap is filled by recombinational repair or lesion bypass synthesis. The remaining monoadduct is then removed by Nucleotide Excision Repair (NER). Despite considerable effort, our understanding of each step in mammalian cells is still quite limited. In part this reflects the variety of crosslinking compounds, each with distinct structural features, used by different investigators. Also, multiple repair pathways are involved, variably operative during the cell cycle. G1 phase repair requires functions from NER, although the mechanism of recognition has not been determined. Repair can be initiated by encounters with the transcriptional apparatus, or a replication fork. In the case of the latter, the reconstruction of a replication fork, stalled or broken by collision with an ICL, adds to the complexity of the repair process. The enzymology of unhooking, the identity of the lesion bypass polymerases required to fill the first repair gap, and the functions involved in the second repair cycle are all subjects of active inquiry. Here we will review current understanding of each step in ICL repair in mammalian cells. PMID:20039786

  5. Olfactory sensitivity in mammalian species.

    PubMed

    Wackermannová, M; Pinc, L; Jebavý, L

    2016-07-18

    Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described. PMID:27070753

  6. Sensory Feedback Control of Mammalian Vocalizations

    PubMed Central

    Smotherman, Michael S.

    2007-01-01

    Somatosensory and auditory feedback mechanisms are dynamic components of the vocal motor pattern generator in mammals. This review explores how sensory cues arising from central auditory and somatosensory pathways actively guide the production of both simple sounds and complex phrases in mammals. While human speech is a uniquely sophisticated example of mammalian vocal behavior, other mammals can serve as examples of how sensory feedback guides complex vocal patterns. Echolocating bats in particular are unique in their absolute dependence on voice control for survival: these animals must constantly adjust the acoustic and temporal patterns of their orientation sounds to efficiently navigate and forage for insects at high speeds under the cover of darkness. Many species of bats also utter a broad repertoire of communication sounds. The functional neuroanatomy of the bat vocal motor pathway is basically identical to other mammals, but the acute significance of sensory feedback in echolocation has made this a profitable model system for studying general principles of sensorimotor integration with regard to vocalizing. Bats and humans are similar in that they both maintain precise control of many different voice parameters, both exhibit a similar suite of responses to altered auditory feedback, and for both the efficacy of sensory feedback depends upon behavioral context. By comparing similarities and differences in the ways sensory feedback influences voice in humans and bats, we may shed light on the basic architecture of the mammalian vocal motor system and perhaps be able to better distinguish those features of human vocal control that evolved uniquely in support of speech and language. PMID:17449116

  7. Sensory feedback control of mammalian vocalizations.

    PubMed

    Smotherman, Michael S

    2007-09-01

    Somatosensory and auditory feedback mechanisms are dynamic components of the vocal motor pattern generator in mammals. This review explores how sensory cues arising from central auditory and somatosensory pathways actively guide the production of both simple sounds and complex phrases in mammals. While human speech is a uniquely sophisticated example of mammalian vocal behavior, other mammals can serve as examples of how sensory feedback guides complex vocal patterns. Echolocating bats in particular are unique in their absolute dependence on voice control for survival: these animals must constantly adjust the acoustic and temporal patterns of their orientation sounds to efficiently navigate and forage for insects at high speeds under the cover of darkness. Many species of bats also utter a broad repertoire of communication sounds. The functional neuroanatomy of the bat vocal motor pathway is basically identical to other mammals, but the acute significance of sensory feedback in echolocation has made this a profitable model system for studying general principles of sensorimotor integration with regard to vocalizing. Bats and humans are similar in that they both maintain precise control of many different voice parameters, both exhibit a similar suite of responses to altered auditory feedback, and for both the efficacy of sensory feedback depends upon behavioral context. By comparing similarities and differences in the ways sensory feedback influences voice in humans and bats, we may shed light on the basic architecture of the mammalian vocal motor system and perhaps be able to better distinguish those features of human vocal control that evolved uniquely in support of speech and language. PMID:17449116

  8. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  9. Oral Lesions in Neonates.

    PubMed

    Patil, Shankargouda; Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  10. Retinal lesions in septicemia.

    PubMed

    Neudorfer, M; Barnea, Y; Geyer, O; Siegman-Igra, Y

    1993-12-15

    We explored the association between septicemia and specific retinal lesions in a prospective controlled study. Hemorrhages, cotton-wool spots, or Roth's spots were found in 24 of 101 septicemic patients (24%), compared to four of 99 age- and gender-matched control patients (4%) (P = .0002). There was no significant association between types of organisms or focus of infection and the presence of specific lesions. Histologic examination of affected eyes disclosed cytoid bodies in the nerve fiber layer without inflammation. A definite association between septicemia and retinal lesions was found and indicates the need for routine ophthalmoscopy in septicemic patients. PMID:8250076

  11. Talar Dome Lesion

    MedlinePlus

    ... be helpful in reducing the pain and inflammation. Physical therapy . Range-of-motion and strengthening exercises are beneficial once the lesion is adequately healed. Physical therapy may also include techniques to reduce pain and ...

  12. Hypervascular liver lesions.

    PubMed

    Kamaya, Aya; Maturen, Katherine E; Tye, Grace A; Liu, Yueyi I; Parti, Naveen N; Desser, Terry S

    2009-10-01

    Hypervascular hepatocellular lesions include both benign and malignant etiologies. In the benign category, focal nodular hyperplasia and adenoma are typically hypervascular. In addition, some regenerative nodules in cirrhosis may be hypervascular. Malignant hypervascular primary hepatocellular lesions include hepatocellular carcinoma, fibrolamellar carcinoma, and peripheral cholangiocarcinoma. Vascular liver lesions often appear hypervascular because they tend to follow the enhancement of the blood pool; these include hemangiomas, arteriovenous malformations, angiosarcomas, and peliosis. While most gastrointestinal malignancies that metastasize to the liver will appear hypovascular on arterial and portal-venous phase imaging, certain cancers such as metastatic neuroendocrine tumors (including pancreatic neuroendocrine tumors, carcinoid, and gastrointestinal stromal tumors) tend to produce hypervascular metastases due to the greater recruitment of arterial blood supply. Finally, rare hepatic lesions such as glomus tumor and inflammatory pseudotumor may have a hypervascular appearance. PMID:19842564

  13. 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

  14. Evaluation of Parotid Lesions.

    PubMed

    Kuan, Edward C; Mallen-St Clair, Jon; St John, Maie A

    2016-04-01

    The differential diagnosis of a parotid lesion is broad, and the otolaryngologist must consider inflammatory, neoplastic, autoimmune, traumatic, infectious, or congenital causes. A comprehensive history and physical examination, in conjunction with judicious use of radiographic imaging (MRI, computed tomography, ultrasonography, nuclear medicine studies), laboratory studies, and pathologic analysis (fine-needle aspiration, core biopsy, incisional biopsy), facilitates making an accurate diagnosis. This article reviews the key history and physical elements and adjunctive diagnostic tools available for working up parotid lesions. PMID:26902978

  15. Multiple Osteolytic Lesions

    PubMed Central

    Vinayachandran, Divya; Sankarapandian, Sathasivasubramanian

    2013-01-01

    Several systemic diseases initially present with various oral manifestations. Investigation of these oral symptoms may at times lead to the diagnosis of grave underlying life-threatening conditions. We present one such case, where the patient manifested with gross enlargement of the mandible, along with lesions in the lower limbs. These lesions were the initial manifestation and on further investigations the patient was diagnosed with multiple myeloma. PMID:24516769

  16. Petrous Apex Lesions

    PubMed Central

    Amedee, Ronald G.; Gianoli, Gerard J.; Mann, Wolf J.

    1994-01-01

    The purpose of this article is to detail our experience in treating 69 patients over the past 6 years with pathologic processes involving the petrous apex. These included 25 (36%) primary petrous apex lesions, 40 (58%) lesions that involved the petrous apex by direct invasion from an adjacent region, and four (6%) lesions that were the result of metastatic spread from a distant site. Although lesions of the petrous apex are uncommon, they may present significant morbidity to the patient. The symptoms elicited by these lesions are usually vague and nonlocalizing in the early stages but may progress to include multiple cranial neuropathies. Successful results are contingent on early diagnosis, which requires a high index of suspicion and use of appropriate imaging modalities. Thorough preoperative assessment with use of computed tomography, magnetic resonance imaging, and carotid arteriography is essential to plan the surgical approach. We present this collection of patients in order to aid in the further preoperative characterization of the differences in primary and secondary lesions of the petrous apex. PMID:17170919

  17. Colorectal Subepithelial Lesions

    PubMed Central

    2015-01-01

    Most of subepithelial lesion (SEL) being identified was accidentally discovered as small bulging lesion covered with normal mucosa from endoscopic screening. The type of treatment and prognosis vary depending on the type of tumor, it would be crucial to perform an accurate differential diagnosis. Since the differentiation of SEL relied on the indirect findings observed from the mucosal surface using an endoscopy only in the past, it was able to confirm the presence of lesion only but difficult to identify complex detailed nature of the lesion. However, after the endoscopic ultrasonography (EUS) was introduced, it became possible to identify extrinsic compression, and size of intramural tumors, internal properties and contour so that it gets possible to have differential diagnosis of lesions and prediction on the lesion whether it is malignant or benign. In addition, the use of EUS-guided fine needle aspiration and EUS-guided core biopsy made it possible to make histological differential diagnosis. This study intended to investigate endoscopic and EUS findings, histological diagnosis, treatment regimen and impression of colorectal SELs. PMID:26240803

  18. How difficult is inference of mammalian causal gene regulatory networks?

    PubMed

    Djordjevic, Djordje; Yang, Andrian; Zadoorian, Armella; Rungrugeecharoen, Kevin; Ho, Joshua W K

    2014-01-01

    Gene regulatory networks (GRNs) play a central role in systems biology, especially in the study of mammalian organ development. One key question remains largely unanswered: Is it possible to infer mammalian causal GRNs using observable gene co-expression patterns alone? We assembled two mouse GRN datasets (embryonic tooth and heart) and matching microarray gene expression profiles to systematically investigate the difficulties of mammalian causal GRN inference. The GRNs were assembled based on > 2,000 pieces of experimental genetic perturbation evidence from manually reading > 150 primary research articles. Each piece of perturbation evidence records the qualitative change of the expression of one gene following knock-down or over-expression of another gene. Our data have thorough annotation of tissue types and embryonic stages, as well as the type of regulation (activation, inhibition and no effect), which uniquely allows us to estimate both sensitivity and specificity of the inference of tissue specific causal GRN edges. Using these unprecedented datasets, we found that gene co-expression does not reliably distinguish true positive from false positive interactions, making inference of GRN in mammalian development very difficult. Nonetheless, if we have expression profiling data from genetic or molecular perturbation experiments, such as gene knock-out or signalling stimulation, it is possible to use the set of differentially expressed genes to recover causal regulatory relationships with good sensitivity and specificity. Our result supports the importance of using perturbation experimental data in causal network reconstruction. Furthermore, we showed that causal gene regulatory relationship can be highly cell type or developmental stage specific, suggesting the importance of employing expression profiles from homogeneous cell populations. This study provides essential datasets and empirical evidence to guide the development of new GRN inference methods for

  19. Evolutionary paths to mammalian cochleae.

    PubMed

    Manley, Geoffrey A

    2012-12-01

    Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in paleontological techniques, especially the use of micro-CT scans, now provide important new insights that are here reviewed. True mammals arose more than 200 million years (Ma) ago. Of these, three lineages survived into recent geological times. These animals uniquely developed three middle ear ossicles, but these ossicles were not initially freely suspended as in modern mammals. The earliest mammalian cochleae were only about 2 mm long and contained a lagena macula. In the multituberculate and monotreme mammalian lineages, the cochlea remained relatively short and did not coil, even in modern representatives. In the lineage leading to modern therians (placental and marsupial mammals), cochlear coiling did develop, but only after a period of at least 60 Ma. Even Late Jurassic mammals show only a 270 ° cochlear coil and a cochlear canal length of merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not realized until the early Cretaceous (~125 Ma). At that time, therian mammals arose and possessed a fully coiled cochlea. The evolution of modern features of the middle ear and cochlea in the many later lineages of therians was, however, a mosaic and different features arose at different times. In parallel with cochlear structural evolution, prestins in therian mammals evolved into effective components of a new motor system. Ultrasonic hearing developed quite late-the earliest bat cochleae (~60 Ma) did not show features characteristic of those of modern bats that are sensitive to high ultrasonic frequencies. PMID:22983571

  20. Meniscal Ramp Lesions

    PubMed Central

    Chahla, Jorge; Dean, Chase S.; Moatshe, Gilbert; Mitchell, Justin J.; Cram, Tyler R.; Yacuzzi, Carlos; LaPrade, Robert F.

    2016-01-01

    Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, and consequently, ramp lesions often go undiagnosed. Therefore, to rule out a ramp lesion, an arthroscopic evaluation with probing of the posterior horn of the medial meniscus should be performed. Several treatment options have been reported, including nonsurgical management, inside-out meniscal repair, or all-inside meniscal repair. In cases of isolated ramp lesions, a standard meniscal repair rehabilitation protocol should be followed. However, when a concomitant ACL reconstruction (ACLR) is performed, the rehabilitation should follow the designated ACLR postoperative protocol. The purpose of this article was to review the current literature regarding meniscal ramp lesions and summarize the pertinent anatomy, biomechanics, diagnostic strategies, recommended treatment options, and postoperative protocol. PMID:27504467

  1. DNA modifications in the mammalian brain

    PubMed Central

    Shin, Jaehoon; Ming, Guo-li; Song, Hongjun

    2014-01-01

    DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function. PMID:25135973

  2. Ion channels, phosphorylation and mammalian sperm capacitation

    PubMed Central

    Visconti, Pablo E; Krapf, Dario; de la Vega-Beltrán, José Luis; Acevedo, Juan José; Darszon, Alberto

    2011-01-01

    Sexually reproducing animals require an orchestrated communication between spermatozoa and the egg to generate a new individual. Capacitation, a maturational complex phenomenon that occurs in the female reproductive tract, renders spermatozoa capable of binding and fusing with the oocyte, and it is a requirement for mammalian fertilization. Capacitation encompasses plasma membrane reorganization, ion permeability regulation, cholesterol loss and changes in the phosphorylation state of many proteins. Novel tools to study sperm ion channels, image intracellular ionic changes and proteins with better spatial and temporal resolution, are unraveling how modifications in sperm ion transport and phosphorylation states lead to capacitation. Recent evidence indicates that two parallel pathways regulate phosphorylation events leading to capacitation, one of them requiring activation of protein kinase A and the second one involving inactivation of ser/thr phosphatases. This review examines the involvement of ion transporters and phosphorylation signaling processes needed for spermatozoa to achieve capacitation. Understanding the molecular mechanisms leading to fertilization is central for societies to deal with rising male infertility rates, to develop safe male gamete-based contraceptives and to preserve biodiversity through better assisted fertilization strategies. PMID:21540868

  3. Ontogenetic development of the mammalian circadian system.

    PubMed

    Weinert, Dietmar

    2005-01-01

    This review summarizes the current knowledge about the ontogenetic development of the circadian system in mammals. The developmental changes of overt rhythms are discussed, although the main focus of the review is the underlying neuronal and molecular mechanisms. In addition, the review describes ontogenetic development, not only as a process of morpho-functional maturation. The need of repeated adaptations and readaptations due to changing developmental stage and environmental conditions is also considered. The review analyzes mainly rodent data, obtained from the literature and from the author's own studies. Results from other species, including humans, are presented to demonstrate common features and species-dependent differences. The review first describes the development of the suprachiasmatic nuclei as the central pacemaker system and shows that intrinsic circadian rhythms are already generated in the mammalian fetus. As in adult organisms, the period length is different from 24 h and needs continuous correction by environmental periodicities, or zeitgebers. The investigation of the ontogenetic development of the mechanisms of entrainment reveals that, at prenatal and early postnatal stages, non-photic cues deriving from the mother are effective. Light-dark entrainment develops later. At a certain age, both photic and non-photic zeitgebers may act in parallel, even though the respective time information is 12 h out of phase. That leads to a temporary internal desynchronization. Because rhythmic information needs to be transferred to effector organs, the corresponding neural and humoral signalling pathways are also briefly described. Finally, to be able to transform a rhythmic signal into an overt rhythm, the corresponding effector organs must be functionally mature. As many of these organs are able to generate their own intrinsic rhythms, another aspect of the review is dedicated to the development of peripheral oscillators and mechanisms of their entrainment

  4. The Physiologic Impact of Unilateral Recurrent Laryngeal Nerve (RLN) Lesion on Infant Oropharyngeal and Esophageal Performance.

    PubMed

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

    2015-12-01

    Recurrent laryngeal nerve (RLN) injury in neonates, a complication of patent ductus arteriosus corrective surgery, leads to aspiration and swallowing complications. Severity of symptoms and prognosis for recovery are variable. We transected the RLN unilaterally in an infant mammalian animal model to characterize the degree and variability of dysphagia in a controlled experimental setting. We tested the hypotheses that (1) both airway protection and esophageal function would be compromised by lesion, (2) given our design, variability between multiple post-lesion trials would be minimal, and (3) variability among individuals would be minimal. Individuals' swallowing performance was assessed pre- and post-lesion using high speed VFSS. Aspiration was assessed using the Infant Mammalian Penetration-Aspiration Scale (IMPAS). Esophageal function was assessed using two measures devised for this study. Our results indicate that RLN lesion leads to increased frequency of aspiration, and increased esophageal dysfunction, with significant variation in these basic patterns at all levels. On average, aspiration worsened with time post-lesion. Within a single feeding sequence, the distribution of unsafe swallows varied. Individuals changed post-lesion either by increasing average IMPAS score, or by increasing variation in IMPAS score. Unilateral RLN transection resulted in dysphagia with both compromised airway protection and esophageal function. Despite consistent, experimentally controlled injury, significant variation in response to lesion remained. Aspiration following RLN lesion was due to more than unilateral vocal fold paralysis. We suggest that neurological variation underlies this pattern. PMID:26285799

  5. Genital lesions following bestiality.

    PubMed

    Mittal, A; Shenoi, S D; Kumar, K B; Sharma, P V

    2000-01-01

    A 48-year-old man presented with painful genital lesions with history of bestiality and abnor-mal sexual behaviour. Examination revealed multiple irregular tender ulcers and erosions, with phimosis and left sided tender inguinal adenopathy. VDRL, TPHA, HIV-ELISA were negative. He was treated with ciprofloxacin 500mg b.d. along with saline compresses with complete resolution. PMID:20877040

  6. Producing Newborn Synchronous Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  7. Body Size in Mammalian Paleobiology

    NASA Astrophysics Data System (ADS)

    Damuth, John; MacFadden, Bruce J.

    1990-11-01

    This valuable collection of essays presents and evaluates techniques of body-mass estimation and reviews current and potential applications of body-size estimates in paleobiology. Papers discuss explicitly the errors and biases of various regression techniques and predictor variables, and the identification of functionally similar groups of species for improving the accuracy of estimates. At the same time other chapters review and discuss the physiological, ecological, and behavioral correlates of body size in extant mammals; the significance of body-mass distributions in mammalian faunas; and the ecology and evolution of body size in particular paleofaunas. Coverage is particularly detailed for carnivores, primates, and ungulates, but information is also presented on marsupials, rodents, and proboscideans.

  8. Determinants of Mammalian Nucleolar Architecture

    PubMed Central

    Farley, Katherine I.; Surovtseva, Yulia; Merkel, Janie; Baserga, Susan J.

    2015-01-01

    The nucleolus is responsible for the production of ribosomes, essential machines which synthesize all proteins needed by the cell. The structure of human nucleoli is highly dynamic and is directly related to its functions in ribosome biogenesis. Despite the importance of this organelle, the intricate relationship between nucleolar structure and function remains largely unexplored. How do cells control nucleolar formation and function? What are the minimal requirements for making a functional nucleolus? Here we review what is currently known regarding mammalian nucleolar formation at nucleolar organizer regions (NORs), which can be studied by observing the dissolution and reformation of the nucleolus during each cell division. Additionally, the nucleolus can be examined by analyzing how alterations in nucleolar function manifest in differences in nucleolar architecture. Furthermore, changes in nucleolar structure and function are correlated with cancer, highlighting the importance of studying the determinants of nucleolar formation. PMID:25670395

  9. Development of the Mammalian Kidney.

    PubMed

    McMahon, Andrew P

    2016-01-01

    The basic unit of kidney function is the nephron. In the mouse, around 14,000 nephrons form in a 10-day period extending into early neonatal life, while the human fetus forms the adult complement of nephrons in a 32-week period completed prior to birth. This review discusses our current understanding of mammalian nephrogenesis: the contributing cell types and the regulatory processes at play. A conceptual developmental framework has emerged for the mouse kidney. This framework is now guiding studies of human kidney development enabled in part by in vitro systems of pluripotent stem cell-seeded nephrogenesis. A near future goal will be to translate our developmental knowledge-base to the productive engineering of new kidney structures for regenerative medicine. PMID:26969971

  10. Central odontogenic fibroma

    PubMed Central

    Venugopal, Sanjay; Radhakrishna, Satish; Raj, Akshatha; Sawhney, Anshul

    2014-01-01

    Central odontogenic fibroma (COF), which has been categorized under the subheading of odontogenic tumors of ectomesenchyme, is such an uncommon neoplasm that much of its nature is left uncharted. COF is a rare tumor that accounts for 0.1% of all odontogenic tumors. Clinically, the lesion grows slowly and leads to cortical expansion. Radiologically, the lesion may be unilocular or multilocular. In some cases, it may be associated with root resorption or displacement. Histopathologically, the lesion is characterized by mature collagen fibers and numerous fibroblasts. A case of COF of the mandible in a male patient aged 49 years is described in this report. The patient showed no symptoms, no history of swelling discomfort or pain, and was unaware of the presence of the lesion. Orthopantomogram (OPG) showed generalized bone loss along with a unilocular radiolucent area, with a clear sclerotic lining and angular bone loss. Surgical enucleation of the lesion along with placement of osseo-graft, which is a bioresorbable demineralized bone matrix (DMBM), and platelet-rich fibrin was carried out in the defect site. Following surgery, patient was recalled for revaluation of the lesion; the surgical site showed good healing and an increase in bone height was seen. PMID:24872637

  11. Recent advances in mammalian protein production

    PubMed Central

    Bandaranayake, Ashok D.; Almo, Steven C.

    2014-01-01

    Mammalian protein production platforms have had a profound impact in many areas of basic and applied research, and an increasing number of blockbuster drugs are recombinant mammalian proteins. With global sales of these drugs exceeding US$120 billion per year, both industry and academic research groups continue to develop cost effective methods for producing mammalian proteins to support preclinical and clinical evaluations of potential therapeutics. While a wide range of platforms have been successfully exploited for laboratory use, the bulk of recent biologics have been produced in mammalian cell lines due to the requirement for post translational modification and the biosynthetic complexity of the target proteins. In this review we highlight the range of mammalian expression platforms available for recombinant protein production, as well as advances in technologies for the rapid and efficient selection of highly productive clones. PMID:24316512

  12. 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

  13. Demyelinative chiamal lesions.

    PubMed

    Spector, R H; Glaser, J S; Schatz, N J

    1980-12-01

    To clarify the clinical syndrome of demyelinative chiasmal involvement, six case histories were analyzed and the literature was reviewed. This entitity is characterized by especial predilection for women in the third to fifth decades; visual deficites of a chiasmal pattern that may be modest to marked, with a generallly good prognosis for functional recovery; and other signs and symptoms, not necessarily severe, of scattered lesions of the neuraxis. Neuroradiological studies, especially laminography of the sellar area and computerized tomography, must be employed to rule out a suprasellar mass lesion. The efficacy of systemic corticosteroid therapy is moot, but it seems reasonable to use such agents during acute stages, especially where vision is severely reduced on both sides. PMID:7447764

  14. Novel lesion detection aids.

    PubMed

    Neuhaus, K W; Longbottom, C; Ellwood, R; Lussi, A

    2009-01-01

    Several non-invasive and novel aids for the detection of (and in some cases monitoring of) caries lesions have been introduced in the field of 'caries diagnostics' over the last 15 years. This chapter focusses on those available to dentists at the time of writing; continuing research is bound to lead to further developments in the coming years. Laser fluorescence is based on measurements of back-scattered fluorescence of a 655-nm light source. It enhances occlusal and (potentially) approximal lesion detection and enables semi-quantitative caries monitoring. Systematic reviews have identified false-positive results as a limitation. Quantitative light-induced fluorescence is another sensitive method to quantitatively detect and measure mineral loss both in enamel and some dentine lesions; again, the trade-offs with lower specificity when compared with clinical visual detection must be considered. Subtraction radiography is based on the principle of digitally superimposing two radiographs with exactly the same projection geometry. This method is applicable for approximal surfaces and occlusal caries involving dentine but is not yet widely available. Electrical caries measurements gather either site-specific or surface-specific information of teeth and tooth structure. Fixed-frequency devices perform best for occlusal dentine caries but the method has also shown promise for lesions in enamel and other tooth surfaces with multi-frequency approaches. All methods require further research and further validation in well-designed clinical trials. In the future, they could have useful applications in clinical practice as part of a personalized, comprehensive caries management system. PMID:19494675

  15. Mammalian reproduction: an ecological perspective.

    PubMed

    Bronson, F H

    1985-02-01

    The objectives of this paper are to organize our concepts about the environmental regulation of reproduction in mammals and to delineate important gaps in our knowledge of this subject. The environmental factors of major importance for mammalian reproduction are food availability, ambient temperature, rainfall, the day/night cycle and a variety of social cues. The synthesis offered here uses as its core the bioenergetic control of reproduction. Thus, for example, annual patterns of breeding are viewed as reflecting primarily the caloric costs of the female's reproductive effort as they relate to the energetic costs and gains associated with her foraging effort. Body size of the female is an important consideration since it is correlated with both potential fat reserves and life span. Variation in nutrient availability may or may not be an important consideration. The evolutionary forces that have shaped the breeding success of males usually are fundamentally different from those acting on females and, by implication, the environmental controls governing reproduction probably also often differ either qualitatively or quantitatively in the two sexes. Mammals often live in habitats where energetic and nutrient challenges vary seasonally, even in the tropics. When seasonal breeding is required, a mammal may use a predictor such as photoperiod or a secondary plant compound to prepare metabolically for reproduction. A reasonable argument can be made, however, that opportunistic breeding, unenforced by a predictor, may be the most prevalent strategy extant among today's mammals. Social cues can have potent modulating actions. They can act either via discrete neural and endocrine pathways to alter specific processes such as ovulation, or they can induce nonspecific emotional states that secondarily affect reproduction. Many major gaps remain in our knowledge about the environmental regulation of mammalian reproduction. For one, we have a paucity of information about the

  16. Medication Management of Jaw Lesions for Dental Patients.

    PubMed

    Ogle, Orrett E; Santosh, Arvind Babu Rajendra

    2016-04-01

    Most pathologic lesions of the jaws or of oral mucosa are treated successfully by surgical interventions. For treatment of the central giant cell lesion, aneurysmal bone cysts, histiocytosis of the mandible, hemangioma, odontogenic keratocyst, Paget disease, oral submucous fibrosis, and oral lichen planus, medical management consisting of intralesional injections, sclerosing agents, and systemic bisphosphonates is as successful as surgical procedures with fewer complications. Pharmacology of agents used and protocols are presented. PMID:27040297

  17. Mammalian Carboxylesterase 5: Comparative Biochemistry and Genomics

    PubMed Central

    Holmes, Roger S; Cox, Laura A; VandeBerg, John L

    2008-01-01

    Carboxylesterase 5 (CES5) (also called cauxin or CES7) is one of at least five mammalian CES gene families encoding enzymes of broad substrate specificity and catalysing hydrolytic and transesterification reactions. In silico methods were used to predict the amino acid sequences, secondary structures and gene locations for CES5 genes and gene products. Amino acid sequence alignments of mammalian CES5 enzymes enabled identification of key CES sequences previously reported for human CES1, as well as other sequences that are specific to the CES5 gene family, which were consistent with being monomeric in subunit structure and available for secretion into body fluids. Predicted secondary structures for mammalian CES5 demonstrated significant conservation with human CES1 as well as distinctive mammalian CES5 like structures. Mammalian CES5 genes are located in tandem with the CES1 gene(s), are transcribed on the reverse strand and contained 13 exons. CES5 has been previously reported in high concentrations in the urine (cauxin) of adult male cats, and within a protein complex of mammalian male epididymal fluids. Roles for CES5 may include regulating urinary levels of male cat pheromones; catalysing lipid transfer reactions within mammalian male reproductive fluids; and protecting neural tissue from drugs and xenobiotics. PMID:19727319

  18. 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. PMID:22319549

  19. [Color Doppler sonography of focal abdominal lesions].

    PubMed

    Licanin, Zoran; Lincender, Lidija; Djurović, V; Salihefendić, Nizama; Smajlović, Fahrudin

    2004-01-01

    Color Doppler sonography (CDS--spectral, color and power), harmonic imaging techniques (THI, PHI), possibility of 3D analysis of picture, usage of contrast agents, have raised the values of ultrasound as a diagnostic method to a very high level. THI--non-linear gray scale modality, is based on the processing of higher reflected frequencies, that has improved a picture resolution, which is presented with less artifacts and limiting effects of obesity and gases. Ultrasound contrast agents improve analysis of micro and macro circulation of the examined area, and with the assessment of velocity of supply in ROI (wash in), distribution and time of signal weakening (wash out), are significantly increasing diagnostic value of ultrasound. Besides the anatomical and topographic presentation of examined region (color, power), Color Doppler sonography gives us haemodynamic-functional information on vascularisation of that region, as well as on pathologic vascularisation if present. Avascular aspect of a focal pathologic lesion corresponds to a cyst or haematoma, while coloration and positive spectral curve discover that anechogenic lesions actually represents aneurysms, pseudoaneurysms or AVF. In local inflammatory lesion, abscess in an acute phase, CDS shows first increased, and then decreased central perfusion, while in a chronic phase, a pericapsular vascularisation is present. Contribution of CDS in differentiation of hepatic tumors (hemangioma, HCC and metastasis) is very significant. Central color dots along the peripheral blood vessels and the blush phenomenon are characteristics of capillary hemangioma, peritumoral vascular ring "basket" of HCC, and "detour" sign of metastasis. The central artery, RI from 0.45 to 0.60 and radial spreading characterize FNH. Hepatic adenoma is characterized by an intratumoral vein, and rarely by a vascular hallo. Further on, blood velocity in tumor defined by Color Doppler, distinguishes malignant from benign lesion, where 40 cm/s is a

  20. Improving diagnosis of atraumatic splenic lesions, part I: nonneoplastic lesions.

    PubMed

    Ricci, Zina J; Oh, Sarah K; Chernyak, Victoria; Flusberg, Milana; Rozenblit, Alla M; Kaul, Bindu; Stein, Marjorie W; Mazzariol, Fernanda S

    2016-01-01

    Focal atraumatic splenic lesions often pose a diagnostic challenge on cross-sectional imaging. They can be categorized based on etiology as nonneoplastic (reviewed in Part I), benign neoplastic, and malignant neoplastic lesions. Lesions can also be characterized based on prevalence as common, uncommon, and rare. Familiarity with pertinent clinical parameters, etiology, pathology, prevalence, and ancillary features such as splenomegaly, concomitant hepatic involvement, and extrasplenic findings, in addition to knowledge of imaging spectra of these lesions, can improve diagnostic confidence. Since the nonneoplastic lesions are usually easily recognized, it is critical that the radiologist identifies them avoiding unnecessary work up. PMID:27317223

  1. Fate Mapping Mammalian Corneal Epithelia.

    PubMed

    Richardson, Alexander; Wakefield, Denis; Di Girolamo, Nick

    2016-04-01

    The anterior aspect of the cornea consists of a stratified squamous epithelium, thought to be maintained by a rare population of stem cells (SCs) that reside in the limbal transition zone. Although migration of cells that replenish the corneal epithelium has been studied for over a century, the process is still poorly understood and not well characterized. Numerous techniques have been employed to examine corneal epithelial dynamics, including visualization by light microscopy, the incorporation of vital dyes and DNA labels, and transplantation of genetically marked cells that have acted as cell and lineage beacons. Modern-day lineage tracing utilizes molecular methods to determine the fate of a specific cell and its progeny over time. Classically employed in developmental biology, lineage tracing has been used more recently to track the progeny of adult SCs in a number of organs to pin-point their location and understand their movement and influence on tissue regeneration. This review highlights key discoveries that have led researchers to develop cutting-edge genetic tools to effectively and more accurately monitor turnover and displacement of cells within the mammalian corneal epithelium. Collating information on the basic biology of SCs will have clinical ramifications in furthering our knowledge of the processes that govern their role in homeostasis, wound-healing, transplantation, and how we can improve current unsatisfactory SC-based therapies for patients suffering blinding corneal disease. PMID:26774909

  2. Possible mechanisms of mammalian immunocontraception.

    PubMed

    Barber, M R; Fayrer-Hosken, R A

    2000-03-01

    Ecological and conservation programs in ecosystems around the world have experienced varied success in population management. One of the greatest problems is that human expansion has led to the shrinking of wildlife habitat and, as a result, the overpopulation of many different species has occurred. The pressures exerted by the increased number of animals has caused environmental damage. The humane and practical control of these populations has solicited the scientific community to arrive at a safe, effective, and cost-efficient means of population control. Immunocontraception using zona pellucida antigens, specifically porcine zona pellucida (pZP), has become one of the most promising population control tools in the world today, with notable successes in horses and elephants. A conundrum has risen where pZP, a single vaccine, successfully induces an immunocontraceptive effect in multiple species of mammals. This review describes the most current data pertaining to the mammalian zona pellucida and immunocontraception, and from these studies, we suggest several potential mechanisms of immunocontraception. PMID:10706942

  3. Mammalian cell cultivation in space

    NASA Astrophysics Data System (ADS)

    Gmünder, Felix K.; Suter, Robert N.; Kiess, M.; Urfer, R.; Nordau, C.-G.; Cogoli, A.

    Equipment used in space for the cultivation of mammalian cells does not meet the usual standard of earth bound bioreactors. Thus, the development of a space worthy bioreactor is mandatory for two reasons: First, to investigate the effect on single cells of the space environment in general and microgravity conditions in particular, and second, to provide researchers on long term missions and the Space Station with cell material. However, expertise for this venture is not at hand. A small and simple device for animal cell culture experiments aboard Spacelab (Dynamic Cell Culture System; DCCS) was developed. It provides 2 cell culture chambers, one is operated as a batch system, the other one as a perfusion system. The cell chambers have a volume of 200 μl. Medium exchange is achieved with an automatic osmotic pump. The system is neither mechanically stirred nor equipped with sensors. Oxygen for cell growth is provided by a gas chamber that is adjacent to the cell chambers. The oxygen gradient produced by the growing cells serves to maintain the oxygen influx by diffusion. Hamster kidney cells growing on microcarriers were used to test the biological performance of the DCCS. On ground tests suggest that this system is feasible.

  4. Mammalian mitochondrial beta-oxidation.

    PubMed Central

    Eaton, S; Bartlett, K; Pourfarzam, M

    1996-01-01

    The enzymic stages of mammalian mitochondrial beta-oxidation were elucidated some 30-40 years ago. However, the discovery of a membrane-associated multifunctional enzyme of beta-oxidation, a membrane-associated acyl-CoA dehydrogenase and characterization of the carnitine palmitoyl transferase system at the protein and at the genetic level has demonstrated that the enzymes of the system itself are incompletely understood. Deficiencies of many of the enzymes have been recognized as important causes of disease. In addition, the study of these disorders has led to a greater understanding of the molecular mechanism of beta-oxidation and the import, processing and assembly of the beta-oxidation enzymes within the mitochondrion. The tissue-specific regulation, intramitochondrial control and supramolecular organization of the pathway is becoming better understood as sensitive analytical and molecular techniques are applied. This review aims to cover enzymological and organizational aspects of mitochondrial beta-oxidation together with the biochemical aspects of inherited disorders of beta-oxidation and the intrinsic control of beta-oxidation. PMID:8973539

  5. Cell death in mammalian development.

    PubMed

    Penaloza, C; Orlanski, S; Ye, Y; Entezari-Zaher, T; Javdan, M; Zakeri, Z

    2008-01-01

    During embryogenesis there is an exquisite orchestration of cellular division, movement, differentiation, and death. Cell death is one of the most important aspects of organization of the developing embryo, as alteration in timing, level, or pattern of cell death can lead to developmental anomalies. Cell death shapes the embryo and defines the eventual functions of the organs. Cells die using different paths; understanding which path a dying cell takes helps us define the signals that regulate the fate of the cell. Our understanding of cell death in development stems from a number of observations indicating genetic regulation of the death process. With today's increased knowledge of the pathways of cell death and the identification of the genes whose products regulate the pathways we know that, although elimination of some of these gene products has no developmental phenotype, alteration of several others has profound effects. In this review we discuss the types and distributions of cell death seen in developing mammalian embryos as well as the gene products that may regulate the process. PMID:18220829

  6. Ghrelin Receptors in Non-Mammalian Vertebrates

    PubMed Central

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2012-01-01

    The growth hormone secretagogue-receptor (GHS-R) was discovered in humans and pigs in 1996. The endogenous ligand, ghrelin, was discovered 3 years later, in 1999, and our understanding of the physiological significance of the ghrelin system in vertebrates has grown steadily since then. Although the ghrelin system in non-mammalian vertebrates is a subject of great interest, protein sequence data for the receptor in non-mammalian vertebrates has been limited until recently, and related biological information has not been well organized. In this review, we summarize current information related to the ghrelin receptor in non-mammalian vertebrates. PMID:23882259

  7. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    PubMed

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis. PMID:26847090

  8. Skin lesion of blastomycosis

    MedlinePlus

    ... in: Africa Canada Central and southeastern United States India Israel Saudi Arabia A person gets infected by ... This infection is treated with antifungal drugs such as amphotericin B, ... (directly in the vein) drugs are used, depending on the ...

  9. Cystic Lesions of the Mediastinum.

    PubMed

    Vargas, Daniel; Suby-Long, Thomas; Restrepo, Carlos S

    2016-06-01

    Cystic lesions are commonly seen in the mediastinum, and they may arise from virtually any organ. The vast majority of these lesions are benign and result in no symptoms. When large, cysts may produce symptoms related to compression of adjacent structures. The most common mediastinal cysts are pericardial and foregut duplication cysts. Both computed tomography and magnetic resonance are routinely used to evaluate these lesions. Although computed tomography offers superior spatial resolution, magnetic resonance is useful in differentiating cysts that contain proteinaceous material from solid lesions. Occasionally, cysts arise from solid lesions, such as thymoma or teratoma. Although cysts are alike in appearance, location helps narrowing the differential diagnoses. PMID:27261346

  10. 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

  11. 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

  12. Mammalian Response to Cenozoic Climatic Change

    NASA Astrophysics Data System (ADS)

    Blois, Jessica L.; Hadly, Elizabeth A.

    2009-05-01

    Multiple episodes of rapid and gradual climatic changes influenced the evolution and ecology of mammalian species and communities throughout the Cenozoic. Climatic change influenced the abundance, genetic diversity, morphology, and geographic ranges of individual species. Within communities these responses interacted to catalyze immigration, speciation, and extinction. Combined they affected long-term patterns of community stability, functional turnover, biotic turnover, and diversity. Although the relative influence of climate on particular evolutionary processes is oft debated, an understanding of processes at the root of biotic change yields important insights into the complexity of mammalian response. Ultimately, all responses trace to events experienced by populations. However, many such processes emerge as patterns above the species level, where shared life history traits and evolutionary history allow us to generalize about mammalian response to climatic change. These generalizations provide the greatest power to understand and predict mammalian responses to current and future global change.

  13. Bats and Rodents Shape Mammalian Retroviral Phylogeny

    PubMed Central

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-01-01

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general. PMID:26548564

  14. Bats and Rodents Shape Mammalian Retroviral Phylogeny.

    PubMed

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-01-01

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general. PMID:26548564

  15. Mammalian synthetic biology: emerging medical applications.

    PubMed

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

    2015-05-01

    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

  16. [Multifocal Vitelliform Retinal Lesion].

    PubMed

    Streicher, T; Špirková, J; Ilavská, M

    2015-06-01

    The authors present retrospective follow up of patient with bilateral multifocal vitelliform retinal lesion during the 18 years period. At this time, spontaneous improvement of objective picture on retina and subjective visual troubles was observed. It is probable, that this case is a part of the same symptom complex as a variant of Best´s hereditary disease. This conclusion was based on initial stadium of phenotypical expressivity and additional evaluations. The course and outcomes of visual functions were different. The hereditary transmission was not confirmed. PMID:26201364

  17. Structural brain lesions in inflammatory bowel disease

    PubMed Central

    Dolapcioglu, Can; Dolapcioglu, Hatice

    2015-01-01

    Central nervous system (CNS) complications or manifestations of inflammatory bowel disease deserve particular attention because symptomatic conditions can require early diagnosis and treatment, whereas unexplained manifestations might be linked with pathogenic mechanisms. This review focuses on both symptomatic and asymptomatic brain lesions detectable on imaging studies, as well as their frequency and potential mechanisms. A direct causal relationship between inflammatory bowel disease (IBD) and asymptomatic structural brain changes has not been demonstrated, but several possible explanations, including vasculitis, thromboembolism and malnutrition, have been proposed. IBD is associated with a tendency for thromboembolisms; therefore, cerebrovascular thromboembolism represents the most frequent and grave CNS complication. Vasculitis, demyelinating conditions and CNS infections are among the other CNS manifestations of the disease. Biological agents also represent a risk factor, particularly for demyelination. Identification of the nature and potential mechanisms of brain lesions detectable on imaging studies would shed further light on the disease process and could improve patient care through early diagnosis and treatment. PMID:26600970

  18. Reverse genetics for mammalian reovirus.

    PubMed

    Boehme, Karl W; Ikizler, Miné; Kobayashi, Takeshi; Dermody, Terence S

    2011-10-01

    Mammalian orthoreoviruses (reoviruses) are highly tractable models for studies of viral replication and pathogenesis. The versatility of reovirus as an experimental model has been enhanced by development of a plasmid-based reverse genetics system. Infectious reovirus can be recovered from cells transfected with plasmids encoding cDNAs of each reovirus gene segment using a strategy that does not require helper virus and is independent of selection. In this system, transcription of each gene segment is driven by bacteriophage T7 RNA polymerase, which can be supplied transiently by recombinant vaccinia virus (rDIs-T7pol) or by cells that constitutively express the enzyme. Reverse genetics systems have been developed for two prototype reovirus strains, type 1 Lang (T1L) and type 3 Dearing (T3D). Each reovirus cDNA was encoded on an independent plasmid for the first-generation rescue system. The efficiency of virus recovery was enhanced in a second-generation system by combining the cDNAs for multiple reovirus gene segments onto single plasmids to reduce the number of plasmids from 10 to 4. The reduction in plasmid number and the use of baby hamster kidney cells that express T7 RNA polymerase increased the efficiency of viral rescue, reduced the incubation time required to recover infectious virus, and eliminated potential biosafety concerns associated with the use of recombinant vaccinia virus. Reovirus reverse genetics has been used to introduce mutations into viral capsid and nonstructural components to study viral protein-structure activity relationships and can be exploited to engineer recombinant reoviruses for vaccine and oncolytic applications. PMID:21798351

  19. Hacking the genetic code of mammalian cells.

    PubMed

    Schwarzer, Dirk

    2009-07-01

    A genetic shuttle: The highlighted article, which was recently published by Schultz, Geierstanger and co-workers, describes a straightforward scheme for enlarging the genetic code of mammalian cells. An orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for a new amino acid can be evolved in E. coli and subsequently transferred into mammalian cells. The feasibility of this approach was demonstrated by adding a photocaged lysine derivative to the genetic repertoire of a human cell line. PMID:19533721

  20. 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.

  1. Mammalian phylogeny reveals recent diversification rate shifts.

    PubMed

    Stadler, Tanja

    2011-04-12

    Phylogenetic trees of present-day species allow investigation of the rate of evolution that led to the present-day diversity. A recent analysis of the mammalian phylogeny challenged the view of explosive mammalian evolution after the Cretaceous-Tertiary (K/T) boundary (65 Mya). However, due to lack of appropriate methods, the diversification (speciation minus extinction) rates in the more recent past of mammalian evolution could not be determined. In this paper, I provide a method that reveals that the tempo of mammalian evolution did not change until ∼ 33 Mya. This constant period was followed by a peak of diversification rates between 33 and 30 Mya. Thereafter, diversification rates remained high and constant until 8.55 Mya. Diversification rates declined significantly at 8.55 and 3.35 Mya. Investigation of mammalian subgroups (marsupials, placentals, and the six largest placental subgroups) reveals that the diversification rate peak at 33-30 Mya is mainly driven by rodents, cetartiodactyla, and marsupials. The recent diversification rate decrease is significant for all analyzed subgroups but eulipotyphla, cetartiodactyla, and primates. My likelihood approach is not limited to mammalian evolution. It provides a robust framework to infer diversification rate changes and mass extinction events in phylogenies, reconstructed from, e.g., present-day species or virus data. In particular, the method is very robust toward noise and uncertainty in the phylogeny and can account for incomplete taxon sampling. PMID:21444816

  2. Brain-derived neurotrophic factor induces post-lesion transcommissural growth of olivary axons that develop normal climbing fibers on mature Purkinje cells.

    PubMed

    Dixon, Kirsty J; Sherrard, Rachel M

    2006-11-01

    In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, post-lesion plasticity may generate alternate paths providing models to investigate factors that promote reinnervation to appropriate targets. Following unilateral transection of the neonatal rat olivocerebellar pathway, axons from the remaining inferior olive reinnervate the denervated hemicerebellum and develop climbing fiber arbors on Purkinje cells. However, the capacity to recreate this accurate target reinnervation in a mature system remains unknown. In rats lesioned on day 15 (P15) or 30 and treated with intracerebellar injection of brain-derived neurotrophic factor (BDNF) or vehicle 24 h later, the morphology and organisation of transcommissural olivocerebellar reinnervation was examined using neuronal tracing and immunohistochemistry. In all animals BDNF, but not vehicle, induced transcommissural olivocerebellar axonal growth into the denervated hemicerebellum. The distribution of reinnervating climbing fibers was not confined to the injection sites but extended throughout the denervated hemivermis and, less densely, up to 3.5 mm into the hemisphere. Transcommissural olivocerebellar axons were organised into parasagittal microzones that were almost symmetrical to those in the right hemicerebellum. Reinnervating climbing fiber arbors were predominantly normal, but in the P30-lesioned group 10% were either branched within the molecular layer forming a smaller secondary arbor or were less branched, and in the P15 lesion group the reinnervating arbors extended their terminals almost to the pial surface and were larger than control arbors (P < 0.02). These results show that BDNF can induce transcommissural olivocerebellar reinnervation, which resembles developmental neuroplasticity to promote appropriate target reinnervation in a mature environment. PMID:16790241

  3. 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

  4. 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

  5. Andersson lesion in ankylosing spondylitis.

    PubMed

    Dhakad, Urmila; Das, Siddharth K

    2013-01-01

    A middle-aged male patient developed acute back pain and a lumbar vertebral lesion following trivial physical trauma. The lesion was considered as tuberculous on vertebral x-rays and MRI. After biopsy of the lesion and spinal fixation, the patient was kept on empirical antituberculous treatment (ATT) to which he did not respond. On re-evaluation he was diagnosed to have an Andersson lesion in ankylosing spondylitis (AS). ATT was stopped and he was successfully managed by rest, steroids, methotrexate and sulfasalazine. A careful look at the patient's plain x-ray spine and awareness about the lesion can avoid misdiagnosis of this characteristic vertebral lesion found in AS. PMID:23559648

  6. Direct assay of radiation-induced DNA base lesions in mammalian cells

    SciTech Connect

    Not Available

    1992-01-01

    Adenine (Ade), 2'-deoxyadenosine (dAdo), 5'-deoxyadenosine monophosphate (dAUT), single stranded poly adenylic acid [poly (dA)], double stranded deoxyadenylic-thymidylic acid [ds poly (dA-T)] and salmon testis DNA were irradiated with 500 Gy under oxic and anoxic conditions. The major damage products were analyzed by BPLC with optical detection and quantitated in terms of the percentage of the adenosine in each model compound found as a specific damage product. Outside of the Ade free base, 8-OH-dAdo was the major oxic damage product from each model compound. The type and quantity of the major damage products depended on the sequence and conformation of the model compounds under anoxic conditions. When dAdo and dAMP were irradiated under anoxic conditions, the major damage product was either the R or S isomer of 8,5'cdAdo and little Ade or [alpha]-dAdo was observed. However, when poly(dA), poly(dA-dT), and salmon testis DNA were [gamma]-irradiated under nitrogen, the major deoxyadenosine damage product was identified as the [alpha]-anomer of deoxyadenosine. No [alpha]-deoxyadenosine was detected after irradiation under oxic conditions. The presence of nucleotides with the [alpha]-configuration at the anomeric carbon atom in the DNA chain may have a significant effect on its tertiary structure and possibly modify its biological activity.

  7. 'Flight of colours' in lesions of the visual system.

    PubMed

    Feldman, M; Todman, L; Bender, M B

    1974-11-01

    A bright pocket flashlight was directed into one eye for 10 seconds; the subject then closed the eyelids and reported the sequence of after-image colours observed. Lesions of the visual system which compromised bilateral central colour vision also reduced or abolished the `flight of colours'. This simple bedside test of each eye independently is of value in detecting mild defects of central vision. PMID:4457619

  8. Focal lesions in normal liver.

    PubMed

    Semelka, Richard C; Martin, Diego R; Balci, N Cem

    2005-10-01

    A variety of lesions occur in the normal liver. This review will describe the most common benign, malignant, and infectious lesions. Illustration will be made of the magnetic resonance imaging (MRI) appearance of the most common of these. Due to the high accuracy for liver lesion detection and characterization, and the intrinsic safety of the modality, MR should be considered the primary imaging tool to investigate liver diseases. PMID:16174062

  9. Pigmented Lesion of Buccal Mucosa

    PubMed Central

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  10. Stress-induced cervical lesions.

    PubMed

    Braem, M; Lambrechts, P; Vanherle, G

    1992-05-01

    The increasing occurrence of dental lesions at the cervical surfaces requires more knowledge of the causes of the process. Acidic and abrasive mechanisms have clearly been documented as causes but the stress theory by Lee and Eakle is still controversial. This report describes several incidences of possible stress-induced lesions according to the characteristics described by Lee and Eakle. The occurrences of subgingival lesions lend credence to the stress-induction theory by exclusion of other superimposing etiologic factors. With the current concepts, a perceptive approach to the treatment of cervical lesions can be executed. PMID:1527763

  11. Pigmented lesion of buccal mucosa.

    PubMed

    Bajpai, Manas; Kumar, Malay; Kumar, Manish; Agarwal, Deshant

    2014-01-01

    Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestation of systemic illness and malignant neoplasm. Diagnosis of such lesions requires a proper case history, extraoral and intraoral examination, and, in some cases, biopsy, aspiration cytology, and laboratory investigations. Here we present a case of purple lesion on the buccal mucosa of a 34-year-old male patient which was provisionally diagnosed as mucocele but on the basis of histopathological picture it was finally diagnosed as angiofibroma, and we also discuss the clinical and histopathological differential diagnosis. PMID:25161669

  12. 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.

  13. A Comparative Study of Mammalian Diversification Pattern

    PubMed Central

    Yu, Wenhua; Xu, Junxiao; Wu, Yi; Yang, Guang

    2012-01-01

    Although mammals have long been regarded as a successful radiation, the diversification pattern among the clades is still poorly known. Higher-level phylogenies are conflicting and comprehensive comparative analyses are still lacking. Using a recently published supermatrix encompassing nearly all extant mammalian families and a novel comparative likelihood approach (MEDUSA), the diversification pattern of mammalian groups was examined. Both order- and family-level phylogenetic analyses revealed the rapid radiation of Boreoeutheria and Euaustralidelphia in the early mammalian history. The observation of a diversification burst within Boreoeutheria at approximately 100 My supports the Long Fuse model in elucidating placental diversification progress, and the rapid radiation of Euaustralidelphia suggests an important role of biogeographic dispersal events in triggering early Australian marsupial rapid radiation. Diversification analyses based on family-level diversity tree revealed seven additional clades with exceptional diversification rate shifts, six of which represent accelerations in net diversification rate as compared to the background pattern. The shifts gave origin to the clades Muridae+Cricetidae, Bovidae+Moschidae+Cervidae, Simiiformes, Echimyidae, Odontoceti (excluding Physeteridae+Kogiidae+Platanistidae), Macropodidae, and Vespertilionidae. Moderate to high extinction rates from background and boreoeutherian diversification patterns indicate the important role of turnovers in shaping the heterogeneous taxonomic richness observed among extant mammalian groups. Furthermore, the present results emphasize the key role of extinction on erasing unusual diversification signals, and suggest that further studies are needed to clarify the historical radiation of some mammalian groups for which MEDUSA did not detect exceptional diversification rates. PMID:22457604

  14. 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.

  15. 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.

  16. Electric fences to reduce mammalian predation on waterfowl nests

    USGS Publications Warehouse

    Lokemoen, J.T.; Doty, H.A.; Sharp, D.E.; Neaville, J.E.

    1982-01-01

    We evaluated electric fences as predator barriers to reduce high losses of waterfowl nests to mammalian predation at Waterfowl Production Areas (WPAs). The work was done in 1978-81 on 3 paired sites in central North Dakota and western Minnesota. Resident mammalian predators were trapped from inside the exclosures. All 3 fences operated during the study period with few major maintenance problems. Nest success in the exclosures was 65% in North Dakota and 55% in Minnesota vs. 45 and 12% in the respective controls. Cover inside the electric fence produced 7.8 more young/ha than cover in control plots in North Dakota during the 3 years. Cover inside the 2 electric fences in Minnesota yielded 9.5 and 4.3 more young/ha than cover in control plots during the 3 years. Using construction costs only we estimated that each additional duckling produced in cover protected by electric fencing cost $0.65 in North Dakota and $0.87 in Minnesota.

  17. Undetectable histone O-GlcNAcylation in mammalian cells.

    PubMed

    Gagnon, Jessica; Daou, Salima; Zamorano, Natalia; Iannantuono, Nicholas V G; Hammond-Martel, Ian; Mashtalir, Nazar; Bonneil, Eric; Wurtele, Hugo; Thibault, Pierre; Affar, El Bachir

    2015-01-01

    O-GlcNAcylation is a posttranslational modification catalyzed by the O-Linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and reversed by O-GlcNAcase (OGA). Numerous transcriptional regulators, including chromatin modifying enzymes, transcription factors, and co-factors, are targeted by O-GlcNAcylation, indicating that this modification is central for chromatin-associated processes. Recently, OGT-mediated O-GlcNAcylation was reported to be a novel histone modification, suggesting a potential role in directly coordinating chromatin structure and function. In contrast, using multiple biochemical approaches, we report here that histone O-GlcNAcylation is undetectable in mammalian cells. Conversely, O-GlcNAcylation of the transcription regulators Host Cell Factor-1 (HCF-1) and Ten-Eleven Translocation protein 2 (TET2) could be readily observed. Our study raises questions on the occurrence and abundance of O-GlcNAcylation as a histone modification in mammalian cells and reveals technical complications regarding the detection of genuine protein O-GlcNAcylation. Therefore, the identification of the specific contexts in which histone O-GlcNAcylation might occur is still to be established. PMID:26075789

  18. RNAi pathway participates in chromosome segregation in mammalian cells

    PubMed Central

    Huang, Chuan; Wang, Xiaolin; Liu, Xu; Cao, Shuhuan; Shan, Ge

    2015-01-01

    The RNAi machinery is a mighty regulator in a myriad of life events. Despite lines of evidence that small RNAs and components of the RNAi pathway may be associated with structure and behavior of mitotic chromosomes in diverse organisms, a direct role of the RNAi pathway in mammalian mitotic chromosome segregation remains elusive. Here we report that Dicer and AGO2, two central components of the mammalian RNAi pathway, participate in the chromosome segregation. Knockdown of Dicer or AGO2 results in a higher incidence of chromosome lagging, and this effect is independent from microRNAs as examined with DGCR8 knockout cells. Further investigation has revealed that α-satellite RNA, a noncoding RNA derived from centromeric repeat region, is managed by AGO2 under the guidance of endogenous small interference RNAs (ASAT siRNAs) generated by Dicer. Furthermore, the slicer activity of AGO2 is essential for the chromosome segregation. Level and distribution of chromosome-associated α-satellite RNA have crucial regulatory effect on the localization of centromeric proteins such as centromere protein C1 (CENPC1). With these results, we also provide a paradigm in which the RNAi pathway participates in vital cellular events through the maintenance of level and distribution of noncoding RNAs in cells.

  19. Biochemistry of growth inhibition by ammonium ions in mammalian cells

    SciTech Connect

    Ryll, T.; Valley, U.; Wagner, R. . Cell Culture Techniques Dept.)

    1994-06-20

    The intracellular pool of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine has been shown to act as a central target during the inhibitory action of ammonium ions in vitro cultivated mammalian cell cultures. This pool has been demonstrated to be elevated at the end of a batch cultivation and very quickly as a response to exogenously applied ammonium chloride by using four different cell lines (hybridoma, BHK, CHO, and Ltk-929). The amount of enlarged UDP aminohexoses is correlated to the inhibitor concentration and additionally dependent on the cell line. The formation of the UDP sugars is associated with a transient reduction of the UTP pool. Moreover, the quick formation of UDP-GNAC is strictly dependent on the presence of, glucose and ammonium. Both metabolites act as biochemical precursors. Additionally, the formation of UDP-GNAc after ammonium application has been shown to increase with an elevated cultivation pH and to be independent of the inhibition of transcription and translation processes. The intracellular amount of UDP-GNAc correlates with the level of growth inhibition in mammalian cell lines.

  20. 5-Hydroxymethylcytosine – the elusive epigenetic mark in mammalian DNA

    PubMed Central

    Kriukienė, Edita; Liutkevičiūtė, Zita

    2012-01-01

    Over the past decade, epigenetic phenomena claimed a central role in cell regulatory processes and proved important factors for understanding complex human diseases. One of the best understood epigenetic mechanisms is DNA methylation. In the mammalian genome, cytosines (C) were long known to exist in two functional states: unmethylated or methylated at the 5-position of the pyrimidine ring (5mC). Recent studies of genomic DNA from the human and mouse brain, neurons and from mouse embryonic stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethyl-cytosine (hmC) by the action of 2-oxoglutarate- and Fe(II)-dependent oxygenases of the TET family. These findings provided important clues in a long elusive mechanism of active DNA demethylation and bolstered a fresh wave of studies in the area of epigenetic regulation in mammals. This 15 review is dedicated to critical assessment of the most popular techniques with respect to their suitability for analysis of hmC in mammalian genomes. It also discusses the most recent data on biochemical and chemical aspects of the formation and further conversion of this nucleobase in DNA and its possible biological roles in cell differentiation, embryogenesis and brain function. PMID:22842880

  1. Capacitation-Associated Glycocomponents of Mammalian Sperm.

    PubMed

    Liu, Min

    2016-05-01

    Mammalian fertilization is a series of events that are mostly carbohydrate mediated. The male gamete glycocomponents are extensively synthesized and modified during sperm development and sperm transport in the reproductive tracts. Freshly ejaculated mammalian sperm are required to undergo capacitation, which takes place in the female reproductive system, in order to become fully fertilizable. Several lines of evidence reveal changes in glycosylated sperm constituents during capacitation. Although the contributions of these molecular changes to capacitation are not completely understood, the presence, rearrangement, and/or modification of these sperm glycocomponents have been demonstrated to be important for fertilization. The following review summarizes mammalian sperm glycoconstituents, with emphasis on their molecular changes during capacitation. PMID:26363036

  2. 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

  3. Toward predictive models of mammalian cells.

    PubMed

    Ma'ayan, Avi; Blitzer, Robert D; Iyengar, Ravi

    2005-01-01

    Progress in experimental and theoretical biology is likely to provide us with the opportunity to assemble detailed predictive models of mammalian cells. Using a functional format to describe the organization of mammalian cells, we describe current approaches for developing qualitative and quantitative models using data from a variety of experimental sources. Recent developments and applications of graph theory to biological networks are reviewed. The use of these qualitative models to identify the topology of regulatory motifs and functional modules is discussed. Cellular homeostasis and plasticity are interpreted within the framework of balance between regulatory motifs and interactions between modules. From this analysis we identify the need for detailed quantitative models on the basis of the representation of the chemistry underlying the cellular process. The use of deterministic, stochastic, and hybrid models to represent cellular processes is reviewed, and an initial integrated approach for the development of large-scale predictive models of a mammalian cell is presented. PMID:15869393

  4. 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.

  5. 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.

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

    PubMed

    Pavelková Řičánková, Věra; 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

  7. 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

  8. [Brain temperature in patients with central nervous system lesions].

    PubMed

    Mariak, Z; Lysoń, T; Piekarski, P; Lewko, J; Jadeszko, M; Szydlik, P

    2000-01-01

    The knowledge of human brain temperature is still very limited. In this report we investigated the relationship between brain and trunk temperature in neurosurgical patients during normothermia and fever. Another problem addressed was that of possible gradients of temperature within the brain. We carried out direct recordings of temperature in 63 operated, neurosurgical patients with a variety of intracranial pathologies. Flexible, teflon-coated thermocouples were placed intracranially during neurosurgical procedures. Oesophageal, rectal and tympanic temperatures were also monitored. An error of up to 1.3 degrees C is to be expected in single cases if brain temperature is deduced from the rectal or oesophageal temperature. Mean differences between brain temperature and core body temperature measured in the rectum or in the oesophagus, were between 0 to 0.3 degree C. Tympanic temperature (Tty) improved the approximation of brain temperature (Tbr) to within the mean difference between Tbr-Tty close to 0 degree C. Nevertheless Tty also differed from Tbr by as much as 1 degree C in single cases. Brain temperature was the highest body temperature measured, either in normothermia or in fever. Temperature gradients were proved to exist between the warmer brain interior and cooler surface, with maximal differences in temperature reaching 0.6 degree C. This temperature gradient tended to increase along with the rise in intracranial pressure and deterioration of the level of consciousness. Our results suggest that conclusions regarding brain temperature drawn on the basis of other core temperatures, may lead to significant errors, and intracranial temperature measurement is desirable in neurosurgical intensive care. Temperature gradients within the brain may exacerbate its biochemical injury during ischaemia and fever--a combination seen frequently in neurosurgical patients. This may be particularly so, since brain temperature in fever is the highest body temperature in a high proportion of these patients. PMID:10979544

  9. Fortuitously discovered liver lesions

    PubMed Central

    Dietrich, Christoph F; Sharma, Malay; Gibson, Robert N; Schreiber-Dietrich, Dagmar; Jenssen, Christian

    2013-01-01

    The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrast-enhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as image-guided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g., in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible. PMID:23745019

  10. 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.

  11. Epigenetic Regulation of Mammalian Stem Cells

    PubMed Central

    Li, Xuekun

    2008-01-01

    Two critical properties of stem cells are self-renewal and multipotency. The maintenance of their “stemness” state and commitment to differentiation are therefore tightly controlled by intricate molecular networks. Epigenetic mechanisms, including DNA methylation, chromatin remodeling and the noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. Recent studies have shown that epigenetic regulators are key players in stem cell biology and their dysfunction can result in human diseases such as cancer and neurodevelopmental disorders. Here, we review the recent evidences that advance our knowledge in epigenetic regulations of mammalian stem cells, with focus on embryonic stem cells and neural stem cells. PMID:18393635

  12. Detection of apoptosis in mammalian development.

    PubMed

    Lin, Lin; Penaloza, Carlos; Ye, Yixia; Lockshin, Richard A; Zakeri, Zahra

    2009-01-01

    Mammalian development is dependent on an intricate orchestration of cell proliferation and death. Deregulation in the levels, localization, and type of cell death can lead to disease and even death of the developing embryo. The mechanisms involved in such deregulation are many; alterations and or manipulations of these can aid in the detection, prevention and possible treatments of any effects this de-regulation may have. Here we describe how cell death can be detected during mammalian development, using diverse staining and microscopy methods, while taking advantage of the advancements in cell death mechanisms, derived from biochemical and teratological studies in the field. PMID:19609762

  13. Cystic lesions of the pancreas

    PubMed Central

    Hruban, Ralph H.; Fukushima, Noriyoshi

    2008-01-01

    Summary In contrast to the relatively uniform pathology and the unyielding dismal outcome associated with infiltrating ductal adenocarcinoma of the pancreas, cystic lesions have a broad spectrum of gross and microscopic pathologies, and a range of clinical outcomes. The common cystic lesions of the pancreas are reviewed with emphasis on practical tips for distinguishing between the main entities. PMID:20953247

  14. Hamartomatous tongue lesions in children.

    PubMed

    Kreiger, Portia A; Ernst, Linda M; Elden, Lisa M; Kazahaya, Ken; Alawi, Faizan; Russo, Pierre A

    2007-08-01

    The incidence and spectrum of tongue lesions in children, in particular tongue hamartomas, is relatively unknown. We report a retrospective review of all tongue lesions seen at a major tertiary care children's hospital over an 18-year period with an emphasis on describing tongue hamartomas. A total of 135 tongue lesions were identified. Vascular/lymphatic lesions (36/135) were the most common followed by mucus extravasation phenomenon (22/135). Interestingly, hamartomatous lesions (18/135) were the third most common lesion category identified. Lingual hamartomas were predominantly submucosal in location and were classified histologically by tissue composition as follows: neurovascular (2/18), smooth muscle predominant (5/18), fat predominant (1/18), and smooth muscle and fat containing (10/18). All 5 smooth muscle predominant hamartomas also contained vasculature, and 1 case additionally contained salivary gland tissue. The single fat predominant hamartoma additionally contained vessels and salivary gland. The final 10 hamartomas contained varying amounts of both smooth muscle and fat, and also admixed combinations of vessels, nerves, and salivary glands. Two of these 10 cases additionally contained foci of choristomatous elements, including cutaneous adnexal structures and cartilage. Most patients with hamartomatous lesions were young, 2 years or less. Eight cases were congenital in origin. Females outnumbered males by 2:1. The majority of lesions (16/18) were dorsal in location, and 4 patients had a syndromic association, all oral-facial-digital syndrome. PMID:17667541

  15. Nonsurgical management of periapical lesions

    PubMed Central

    Fernandes, Marina; de Ataide, Ida

    2010-01-01

    Periapical lesions develop as sequelae to pulp disease. They often occur without any episode of acute pain and are discovered on routine radiographic examination. The incidence of cysts within periapical lesions varies between 6 and 55%. The occurrence of periapical granulomas ranges between 9.3 and 87.1%, and of abscesses between 28.7 and 70.07%. It is accepted that all inflammatory periapical lesions should be initially treated with conservative nonsurgical procedures. Studies have reported a success rate of up to 85% after endodontic treatment of teeth with periapical lesions. A review of literature was performed by using electronic and hand searching methods for the nonsurgical management of periapical lesions. Various methods can be used in the nonsurgical management of periapical lesions: the conservative root canal treatment, decompression technique, active nonsurgical decompression technique, aspiration-irrigation technique, method using calcium hydroxide, Lesion Sterilization and Repair Therapy, and the Apexum procedure. Monitoring the healing of periapical lesions is essential through periodic follow-up examinations. PMID:21217952

  16. The DeMSTification of mammalian Ste20 kinases.

    PubMed

    Radu, Maria; Chernoff, Jonathan

    2009-05-26

    When first reported in 1995, the mammalian Ste20-like kinases (Mst) 1 and 2 were so named both for their similarity to the yeast kinase Ste20 and for the fact that their function was, to us, a deep mystery. While much remains to be explained about the regulation and role of these kinases, the veil has been at least partly raised on the Msts, revealing unexpected modes of activation and function. Work in model organisms suggests a central growth-suppressive role for Mst orthologs, with intriguing possible links to other established tumor suppressors. This minireview underlines our current understanding of how Mst1 and Mst2 are regulated, and how activation of these proteins influences cell survival and proliferation. PMID:19467213

  17. The management of lesions of the jaws with liquid nitrogen cryotherapy.

    PubMed

    Pogrel, M A

    1995-12-01

    The mandible and maxilla suffer from a number of lesions that, though benign, have a high recurrence rate (10 percent to 80 percent) after simple enucleation. These include the ameloblastoma, keratocyst, odontogenic myxoma, central giant cell granuloma and ossifying fibroma. The appropriate treatment of these lesions is controversial, eliciting accusations of both undertreatment and overtreatment. Liquid nitrogen cryotherapy may be a valuable treatment modality to prevent recurrences of these lesions without causing cosmetic deformity. PMID:9052029

  18. Central pain: "new" syndromes and their evaluation.

    PubMed

    Berić, A

    1993-10-01

    Central pain syndrome is defined as pain associated with a lesion of the central nervous system. It has a low incidence but is frequently intractable and does not have effective treatment. The cause of central pain is speculative; however, the single common sensory abnormality in patients with central pain is interruption of spinothalamocortical nociceptive pathways. It appears that severe central nervous system lesions, with total destruction of ascending sensory systems, do not lead to a central pain syndrome; and that setting of mild, moderate, or severe disruption of the anterolateral ascending system with partial or complete preservation of the dorsal column/medial lemniscus functions is most frequently associated with central pain syndrome. Furthermore, even during remission, dysesthesias and pain could be triggered by additional afferent input to the large fiber/dorsal column/medial lemniscus system and, once established, they may not be abolished by additional deafferentation. PMID:8413354

  19. Radioguided occult lesion localization (ROLL) of the nonpalpable breast lesions.

    PubMed

    Zgajnar, J; Hocevar, M; Frkovic-Grazio, S; Hertl, K; Schweiger, E; Besic, N

    2004-01-01

    Standard localization techniques of the nonpalpable breast lesions (guide wire, carbon, skin marking) have several disadvantages. Radioguided occult lesion localization (ROLL) was recently proposed as a better alternative resulting in wider surgical margins and lower average specimen weight. The aim of our study was to compare ROLL to our previously published series of the standard guidewire localization, performed at the Institute of Oncology Ljubljana. ROLL was performed in 110 nonpalpable breast lesions. Human serum albumin macroaggregats, marked with 1.8-5.5 MBq 99mTc was injected in the nonpalpable lesion. During surgery the radioactive breast tissue was excised using hand held gamma probe. Nonpalpable breast lesions were excised in all 110 patients. The definitive histology revealed 32 invasive carcinomas, 19 DCIS, 5 LCIS in and 54 benign breast lesions. Mean specimen weight was 40 g which is less in comparison to 53 g of the guidewire series (p=0.002). Surgical margins were clear in 36/51 (70%) invasive breast cancer or DCIS patients and close or involved in 15/51 (30%) patients. Compared to the guidewire series, where 41/92 (44%) margins were clear and 51/92 (56%) were close or involved, the difference was statistically significant (p=0.005). ROLL proved to be superior to guidewire localization in our series, allowing excision of the nonpalpable breast lesion with wider surgical margins despite lower average specimen weight. PMID:15640944

  20. Dentition and lesion history.

    PubMed

    Eggertsson, H; Ferreira-Zandona, A

    2009-01-01

    Dental caries is a process that typically keeps recurring throughout life, and the consequences are too often seen as irreversible damage to the dentition. At various stages of life, different parts of the dentition are affected, and the effects continue to be seen in the dentition long after the events took place. They bear witness to previous occurrences of this process throughout the lifetime of an individual. This chapter reviews the linkage between the caries process and the dental caries lesion history of the human dentition. The prevalence and distribution of the caries burden are very variable and closely tied to cultural aspects. In the primary dentition, income and education have been found to be inversely associated with: (1) any early childhood caries and (2) the maxillary incisor caries pattern. A positive association between these caries patterns and minority ethnicity/race status was also identified. These patterns are different from those of the permanent dentition. Well-documented changes in caries prevalence have been observed throughout history, most closely tied to availability and amount of refined sugar consumed. Changes in caries rates are also well documented in the 20th century, mainly with the advent of fluoride in several forms, first as a steep decline and recently as being relatively unchanged. It is likely that there will be dramatic changes in the rates and distribution of dental caries in the future, due to changes in behavioural factors and therapeutic measures. The description drawn is based on the dental caries pattern experienced in modern western societies. PMID:19494678

  1. Spectrum of prostatic lesions

    PubMed Central

    2013-01-01

    Background Prostate gland of male reproductive system is about the size of walnut and surrounds the urethra. Most frequently encountered diseases affecting prostate are Prostatitis, Benign prostatic hyperplasia and Prostatic cancer .Our objective of study was to evaluate the spectrum and correlation of prostatic lesions with presenting complaints of patient. Methods It was a cross-sectional study conducted in Pathology Department of Dow Medical College, Dow University of Health Sciences during the period of 1st January 2010 to December 2012. Pathology department of Dow Medical College collected specimens from both Civil Hospital and Lyari General Hospital Karachi, Pakistan. Specimens were taken through transurethral resection of prostate (TURP), simple prostatectomy and radical prostatectomy. A questionnaire was made and information including name, age, ward name of hospital, laboratory number, clinical diagnosis and symptoms were noted in it. Data was entered and analyzed through SPSS 19. Result During the targeted months, 48 prostatic specimens were received with a mean age of 65.7 + -7.6 years. Common presenting complains were urinary retention in 23(47.9%) patients, followed by dribbling in 12(25%). Out of 48 patients, 42 have Benign Prostatic Hyperplasia and 6 have Prostatic Adenocarcinoma. Both Benign Prostatic Hyperplasia and Prostatic Adenocarcinoma were more prevalent in the age group of 60-70 years. Conclusion Frequency of prostatic cancer is on the rise and measures should be taken for its early detection. Screening protocols and awareness programs need to be introduced. Screening programs should be focused on level of androgens and molecular pathogenesis. PMID:24063260

  2. The cytogenetics of mammalian autosomal rearrangements

    SciTech Connect

    Daniel, A.

    1988-01-01

    Combining data from animal and clinical studies with classical cytogenetic observations, the volume provides information on various aspects of mammalian autosomal rearrangements. Topics range from the reproductive consequences to carriers of autosomal rearrangements to the application of structural rearrangements and DNA probes to gene mapping. In addition, the book presents an overview of new perspectives and future directions for research.

  3. Mammalian PGRPs also mind the fort.

    PubMed

    Rubino, Stephen; Lee, Jooeun; Girardin, Stephen E

    2010-08-19

    Peptidoglycan recognition proteins (PGRPs or Pglyrps) regulate antibacterial responses in Drosophila, yet their functions in humans remain unclear. In this issue of Cell Host & Microbe, Saha and colleagues report that mammalian PGRPs can prevent aberrant interferon-gamma--induced inflammatory damage in vivo by modulating the composition of the intestinal bacterial flora. PMID:20709290

  4. Architecture of mammalian respiratory complex I

    PubMed Central

    Hirst, Judy

    2014-01-01

    Complex I (NADH:ubiquinone oxidoreductase) is essential for oxidative phosphorylation in mammalian mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the energy-transducing inner membrane, providing electrons for respiration and driving ATP synthesis. Mammalian complex I contains 44 different nuclear- and mitochondrial-encoded subunits, with a combined mass of 1 MDa. The fourteen conserved ‘core’ subunits have been structurally defined in the minimal, bacterial complex, but the structures and arrangement of the 30 ‘supernumerary’ subunits are unknown. Here, we describe a 5 Å resolution structure of complex I from Bos taurus heart mitochondria, a close relative of the human enzyme, determined by single-particle electron cryo-microscopy. We present the structures of the mammalian core subunits that contain eight iron-sulphur clusters and 60 transmembrane helices, identify 18 supernumerary transmembrane helices, and assign and model 14 supernumerary subunits. Thus, we significantly advance knowledge of the structure of mammalian complex I and the architecture of its supernumerary ensemble around the core domains. Our structure provides insights into the roles of the supernumerary subunits in regulation, assembly and homeostasis, and a basis for understanding the effects of mutations that cause a diverse range of human diseases. PMID:25209663

  5. 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

  6. A promoter-level mammalian expression atlas

    PubMed Central

    2015-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. PMID:24670764

  7. Isolation of genomic DNA from mammalian cells.

    PubMed

    Koh, Cheryl M

    2013-01-01

    The isolation of genomic DNA from mammalian cells is a routine molecular biology laboratory technique with numerous downstream applications. The isolated DNA can be used as a template for PCR, cloning, and genotyping and to generate genomic DNA libraries. It can also be used for sequencing to detect mutations and other alterations, and for DNA methylation analyses. PMID:24011044

  8. [Placental developmental defects in cloned mammalian animals].

    PubMed

    Ao, Zheng; Liu, Dewu; Cai, Gengyuan; Wu, Zhenfang; Li, Zicong

    2016-05-01

    The cloning technique, also called somatic cell nuclear transfer (SCNT), has been successfully established and gradually applied to various mammalian species. However, the developmental rate of SCNT mammalian embryos is very low, usually at 1% to 5%, which limits the application of SCNT. Placental developmental defects are considered as the main cause of SCNT embryo development inhibition. Almost all of SCNT-derived mammalian placentas exhibit various abnormalities, such as placental hyperplasia, vascular defects and umbilical cord malformation. Mechanistically, these abnormalities result from failure of establishment of correct epigenetic modification in the trophectoderm genome, which leads to erroneous expression of important genes for placenta development-related, particularly imprinted genes. Consequently, aberrant imprinted gene expression gives rise to placental morphologic abnormalities and functional defects, therefore decreases developmental competence of cloned embryos. Currently, although numerous methods that can improve the developmental ability of SCNT-derived embryos have been reported, most of them are unable to substantially enhance the success rate of SCNT due to failure to eliminate the placental development defects. In this review, we summarize placental abnormalities and imprinted gene expression in mammalian cloning, and propose directions for the future research aiming to improve the cloning efficiency. PMID:27232488

  9. MAMMALIAN CELL MUTAGENESIS, BANBURY CONFERENCE (JOURNAL VERSION)

    EPA Science Inventory

    A conference on mammalian cell mutagenesis was held at the Banbury Center, Cold Spring Harbor, NY, USA, March 22-25, 1987. The objective of the conference was to provide a forum for discussions concerning the genetic, biochemical, and molecular basis of induced mutations in stand...

  10. Structure of mammalian respiratory complex I.

    PubMed

    Zhu, Jiapeng; Vinothkumar, Kutti R; Hirst, Judy

    2016-08-18

    Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane. Mammalian complex I (ref. 1) contains 45 subunits, comprising 14 core subunits that house the catalytic machinery (and are conserved from bacteria to humans) and a mammalian-specific cohort of 31 supernumerary subunits. Knowledge of the structures and functions of the supernumerary subunits is fragmentary. Here we describe a 4.2-Å resolution single-particle electron cryomicroscopy structure of complex I from Bos taurus. We have located and modelled all 45 subunits, including the 31 supernumerary subunits, to provide the entire structure of the mammalian complex. Computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally dynamic regions and match biochemical descriptions of the 'active-to-de-active' enzyme transition that occurs during hypoxia. Our structures therefore provide a foundation for understanding complex I assembly and the effects of mutations that cause clinically relevant complex I dysfunctions, give insights into the structural and functional roles of the supernumerary subunits and reveal new information on the mechanism and regulation of catalysis. PMID:27509854

  11. 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.

  12. 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.

  13. Cold shock response in mammalian cells.

    PubMed

    Fujita, J

    1999-11-01

    Compared to bacteria and plants, the cold shock response has attracted little attention in mammals except in some areas such as adaptive thermogenesis, cold tolerance, storage of cells and organs, and recently, treatment of brain damage and protein production. At the cellular level, some responses of mammalian cells are similar to microorganisms; cold stress changes the lipid composition of cellular membranes, and suppresses the rate of protein synthesis and cell proliferation. Although previous studies have mostly dealt with temperatures below 20 degrees C, mild hypothermia (32 degrees C) can change the cell's response to subsequent stresses as exemplified by APG-1, a member of the HSP110 family. Furthermore, 32 degrees C induces expression of CIRP (cold-inducible RNA-binding protein), the first cold shock protein identified in mammalian cells, without recovery at 37 degrees C. Remniscent of HSP, CIRP is also expressed at 37 degrees C and developmentary regulated, possibly working as an RNA chaperone. Mammalian cells are metabolically active at 32 degrees C, and cells may survive and respond to stresses with different strategies from those at 37 degrees C. Cellular and molecular biology of mammalian cells at 32 degrees C is a new area expected to have considerable implications for medical sciences and possibly biotechnology. PMID:10943555

  14. AMMONIA REMOVAL FROM MAMMALIAN CELL CULTURE MEDIUM

    EPA Science Inventory

    Metabolites such as ammonia and lactic formed during mammalian cell culture can frequently be toxic to the cells themselves beyond a threshold concentration of the metabolites. ell culture conducted in the presence of such accumulated metabolites is therefore limited in productiv...

  15. Medical and experimental mammalian genetics: A perspective

    SciTech Connect

    McKusick, V.A.; Roderick, T.H.; Mori, J.; Paul, N.W.

    1987-01-01

    This book contains 14 papers. Some of the titles are: Structure and Organization of Mammalian Chromosomes: Normal and Abnormal; Globin Gene Structure and the Nature of Mutation; Retroviral DNA Content of the Mouse Genome; Maternal Genes: Mitochondrial Diseases; Human Evolution; and Prospects for Gene Replacement Therapy.

  16. Ticks Take Cues from Mammalian Interferon.

    PubMed

    de Silva, Aravinda M

    2016-07-13

    Interferons are considered a first line of immune defense restricted to vertebrates. In this issue of Cell Host & Microbe, Smith et al. (2016) demonstrate that mammalian interferon γ activates an antimicrobial response within ticks feeding on blood. The study suggests that arthropods have a parallel interferon-like defense system. PMID:27414493

  17. Genomics in mammalian cell culture bioprocessing

    PubMed Central

    Wuest, Diane M.; Harcum, Sarah W.; Lee, Kelvin H.

    2013-01-01

    Explicitly identifying the genome of a host organism including sequencing, mapping, and annotating its genetic code has become a priority in the field of biotechnology with aims at improving the efficiency and understanding of cell culture bioprocessing. Recombinant protein therapeutics, primarily produced in mammalian cells, constitute a $108 billion global market. The most common mammalian cell line used in biologic production processes is the Chinese hamster ovary (CHO) cell line, and although great improvements have been made in titer production over the past 25 years, the underlying molecular and physiological factors are not well understood. Confident understanding of CHO bioprocessing elements (e.g. cell line selection, protein production, and reproducibility of process performance and product specifications) would significantly improve with a well understood genome. This review describes mammalian cell culture use in bioprocessing, the importance of obtaining CHO cell line genetic sequences, and the current status of sequencing efforts. Furthermore, transcriptomic techniques and gene expression tools are presented, and case studies exploring genomic techniques and applications aimed to improve mammalian bioprocess performance are reviewed. Finally, future implications of genomic advances are surmised. PMID:22079893

  18. 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.

  19. Molecular targets to promote central nervous system regeneration.

    PubMed

    Ferraro, Gino B; Alabed, Yazan Z; Fournier, Alyson E

    2004-01-01

    Trauma in the adult mammalian central nervous system (CNS) results in devastating clinical consequences due to the failure of injured axons to spontaneously regenerate. This regenerative failure can be attributed to both a lack of positive cues and to the presence of inhibitory cues that actively prevent regeneration. Substantial progress has been made in elucidating the molecular identity of negative cues present at the CNS injury site following injury. In the past several years, multiple myelin-associated inhibitors including Nogo, Myelin-associated glycoprotein and Oligodendrocyte-myelin glycoprotein have been characterized. Furthermore a neuronal receptor complex and several intracellular substrates leading to outgrowth inhibition have been identified. Rapid progress has also been made in identifying the role of neurotrophins and other positive cues in promoting axonal regrowth. The most recent advances in our understanding of positive stimuli for axon regeneration come from transplantation studies at the CNS lesion site. A number of artificial substrates, tissues, and cells including fetal cells, neural stem cells, Schwann cells and olfactory-ensheathing cells have been tested in animal models of CNS injury. Based on our expanded knowledge of inhibitory influences and on the positive characteristics of various transplants, a number of interventions have been tested to promote recovery in models of CNS trauma. These advances represent the first steps in developing a viable therapy to promote axon regeneration following CNS trauma. PMID:16181067

  20. 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

  1. No Carious Cervical Lesions: Abfraction

    PubMed Central

    Shetty, Sumanth M; Shetty, Rashmi G; Mattigatti, Sudha; Managoli, Noopur A; Rairam, Surabhi G; Patil, Ashwini M

    2013-01-01

    Abfraction or Theory of Abfraction is a theory explaining the non-carious cervical lesions (NCCL). It suggests that they are caused by flexural forces, usually from cyclic loading; the enamel, especially at the cementoenamel junction (CEJ), undergoes this pattern of destruction by separating the enamel rods. Clinical aspect importance of these ineart lesions are at most important to be detected for early intervention and treatment modalities as options during the progression of the disease. How to cite this article: Shetty SM, Shetty RG, Mattigatti S, Managoli NA, Rairam SG, Patil AM. No Carious Cervical Lesions: Abfraction. J Int Oral Health 2013; 5(5):142-5. PMID:24324319

  2. Nerve lesioning with direct current

    NASA Astrophysics Data System (ADS)

    Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

    2011-02-01

    Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

  3. Enhanced Neurite Growth from Mammalian Neurons in Three-Dimensional Salmon Fibrin Gels

    PubMed Central

    Ju, Yo-El; Janmey, Paul A.; McCormick, Margaret; Sawyer, Evelyn S.; Flanagan, Lisa A.

    2007-01-01

    Three-dimensional fibrin matrices have been used as cellular substrates in vitro and as bridging materials for central nervous system repair. Cells can be embedded within fibrin gels since the polymerization process is non-toxic, making fibrin an attractive scaffold for transplanted cells. Most studies have utilized fibrin prepared from human or bovine blood proteins. However, fish fibrin may be well suited for neuronal growth since fish undergo remarkable central nervous system regeneration and molecules implicated in this process are present in fibrin. We assessed the growth of mammalian central nervous system neurons in bovine, human, and salmon fibrin and found that salmon fibrin gels encouraged the greatest degree of neurite (dendrite and axon) growth and were the most resistant to degradation by cellular proteases. The neurite growth-promoting effect was not due to the thrombin used to polymerize the gels or to any copurifying plasminogen. Co-purified fibronectin partially accounted for the effect on neurites, and blockade of fibrinogen/fibrin-binding integrins markedly decreased neurite growth. Anion exchange chromatography revealed different elution profiles for salmon and mammalian fibrinogens. These data demonstrate that salmon fibrin encourages the growth of neurites from mammalian neurons and suggest that salmon fibrin may be a beneficial scaffold for neuronal regrowth after CNS injury. PMID:17258313

  4. 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

  5. The effect of ascetic acid on mammalian cells

    SciTech Connect

    Mariana, Oana C; Trujillo, Antoinette; Sanders, Claire K; Burnett, Kassidy S; Freyer, James P; Mourant, Judith R

    2010-01-01

    Effects of the contrast agent, acetic acid, on mammalian cells are studied using light scattering measurements, viability and fluorescence pH assays. Results depend on whether cells are in PBS or are live and metabolizing. Acetic acid is a contrast agent used to aid the detection of cancerous and precancerous lesions of the uterine cervix. Typically 3% or 5% acetic acid is applied to the swface of the cervix and areas of the tissue that turn 'acetowhite' are considered more likely to be precancerous. The mechanism of action of acetic acid has never been understood in detail, although there are several hypotheses. One is that a decrease in pH causes cytokeratins in epithelial cells to polymerize. We will present data demonstrating that this is not the sole mechanism of acetowhitening. Another hypothesis is that a decrease in pH in the nucleus causes deacetylation of the histones which in turn results in a dense chromatin structure. Relevant to this hypothesis we have measured the internal pH of cells. Additional goals of this work are to understand what physical changes result in acetowhitening, to understand why there is variation in how cells respond to acetic acid, and to investigate how acetowhitening affects the light scatter properties measured by a fiber-optic probe we have developed for cervical cancer diagnostics.

  6. MRI of Focal Liver Lesions.

    PubMed

    Albiin, Nils

    2012-05-01

    Magnetic resonance imaging, MRI has more advantages than ultrasound, computed tomography, CT, positron emission tomography, PET, or any other imaging modality in diagnosing focal hepatic masses. With a combination of basic T1 and T2 weighted sequences, diffusion weighted imaging, DWI, and hepatobiliary gadolinium contrast agents, that is gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB), most liver lesions can be adequately diagnosed. Benign lesions, as cyst, hemangioma, focal nodular hyperplasia, FNH or adenoma, can be distinguished from malignant lesions. In a non-cirrhotic liver, the most common malignant lesions are metastases which may be hypovascular or hypervascular. In the cirrhotic liver hepatocellular carcinoma, HCC, is of considerable importance. Besides, intrahepatic cholangiocarcinoma and other less common malignancies has to be assessed. In this review, the techniques and typical MRI features are presented as well as the new algorithm issued by American Association for the Study of the Liver Diseases (AASLD). PMID:23049491

  7. Electrocautery for Precancerous Anal Lesions

    Cancer.gov

    Results from a randomized clinical trial conducted in Amsterdam suggest that electrocautery is better than topical imiquimod or fluorouracil at treating potentially precancerous anal lesions in HIV-positive men who have sex with men.

  8. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers. PMID:27390104

  9. NON-MAMMALIAN ESTROGENICITY SCREEN: RAINBOW TROUT ESTROGEN RECEPTOR BINDING

    EPA Science Inventory

    The U.S. EPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. Current assays for measuring endocrine activity are primarily mammalian-based. The appropriateness of extrapolating mammalian results to non-mammalian species is uncert...

  10. Benign Pediatric Salivary Gland Lesions.

    PubMed

    Carlson, Eric R; Ord, Robert A

    2016-02-01

    Salivary gland lesions are rare in pediatric patients. In addition, the types of salivary gland tumors are different in their distribution in specific sites in the major and minor salivary glands in children compared with adults. This article reviews benign neoplastic and nonneoplastic salivary gland disorders in pediatric patients to help clinicians to develop an orderly differential diagnosis that will lead to expedient treatment of pediatric patients with salivary gland lesions. PMID:26614702

  11. Pineal lesions: a multidisciplinary challenge.

    PubMed

    Westphal, Manfred; Emami, Pedram

    2015-01-01

    The pineal region is a complex anatomical compartment, harbouring the pineal gland surrounded by the quadrigeminal plate and the confluents of the internal cerebral veins to form the vein of Galen. The complexity of lesions in that region, however, goes far beyond the pineal parenchyma proper. Originating in the pineal gland, there are not only benign cysts but also numerous different tumour types. In addition, lesions such as tectal gliomas, tentorial meningiomas and choroid plexus papillomas arise from the surrounding structures, occupying that regions. Furthermore, the area has an affinity for metastatic lesions. Vascular lesions complete the spectrum mainly as small tectal arteriovenous malformations or cavernous haemangiomas.Taken together, there is a wide spectrum of lesions, many unique to that region, which call for a multidisciplinary approach. The limited access and anatomical complexity have generated a spectrum of anatomical approaches and raised the interest for neuroendoscopic approaches. Equally complex is the spectrum of treatment modalities such as microsurgery as the main option but stereotactic radiosurgery as an alternative or adjuvant to surgery for selected cases, radiation as for germinoma (see below) and or combinatorial chemotherapy, which may need to precede any other ablative technique as constituents.In this context, we review the current literature and our own series to obtain a snapshot sentiment of how to approach pineal lesions, how to interrelate alternative/competing concepts and review the recent technological advances. PMID:25411146

  12. Unusual lesions of the mediastinum

    PubMed Central

    Shamsuddin, Fatima; Khadilkar, Urmila N; Saha, Debarshi

    2015-01-01

    Objectives: To study unusual lesions in the mediastinum, which do not originate from the thymus, lymph nodes, neural tissues or germ cells, and tissues that normally engender pathologic lesions in the mediastinum. Materials and Methods: Of the 65 cases seen, 12 unusual lesion were encountered in a 5½ year period from 2006 to 2011. Results: Two cases of nodular colloid goiter and one each of the mediastinal cyst, undifferentiated carcinoma, and Langerhans cell histiocytosis (LCH) affected the anterosuperior mediastinum. In the middle mediastinum, one case each of the mesothelioma, malignant gastrointestinal stromal tumor (GIST), squamous cell carcinoma (SCC), solitary fibrous tumor (SFT), and pleomorphic sarcoma (PS) was seen. One case of meningeal melanocytoma (Mme) and primary pleural liposarcoma (PL) involved the posterior mediastinum. Persistent disease was seen in LCH after 2 years. Of all the cases with malignant lesions, only the patient with SCC was alive after 1 year. Conclusion: The cases of primary and SCC, LCH, melanocytoma, liposarcoma and PS, and GIST are unexpected and very rarely have paradigms in the mediastinum. Radiologic impression and knowledge of the compartment where these lesions arose from hardly assisted in arriving at a definitive opinion as the lesions were not typical of this location. A high index of suspicion and the immunohistochemical profile facilitated the final diagnosis. PMID:26664161

  13. Simulation of spiculated breast lesions

    NASA Astrophysics Data System (ADS)

    Elangovan, Premkumar; Alrehily, Faisal; Pinto, R. Ferrari; Rashidnasab, Alaleh; Dance, David R.; Young, Kenneth C.; Wells, Kevin

    2016-03-01

    Virtual clinical trials are a promising new approach increasingly used for the evaluation and comparison of breast imaging modalities. A key component in such an assessment paradigm is the use of simulated pathology, in particular, simulation of lesions. Breast mass lesions can be generally classified into two categories based on their appearance; nonspiculated masses and spiculated masses. In our previous work, we have successfully simulated non-spiculated masses using a fractal growth process known as diffusion limited aggregation. In this new work, we have extended the DLA model to simulate spiculated lesions by using features extracted from patient DBT images containing spiculated lesions. The features extracted included spicule length, width, curvature and distribution. This information was used to simulate realistic looking spicules which were attached to the surface of a DLA mass to produce a spiculated mass. A batch of simulated spiculated masses was inserted into normal patient images and presented to an experienced radiologist for review. The study yielded promising results with the radiologist rating 60% of simulated lesions in 2D and 50% of simulated lesions in DBT as realistic.

  14. DNA lesions: A thermodynamic perspective

    SciTech Connect

    Plum, G.E.; Breslauer, K.J.

    1994-12-31

    The studies described in this paper are part of an overall program project entitled {open_quotes}The Chemistry and Biology of Exocyclic DNA Adducts and Oxidative DNA Damage.{close_quotes}. Initially, all the project leaders discuss and agree on biologically interesting lesions to target for study. Then begins the process of developing the chemistry required to synthesize modified nucleosides that either correspond to or model the damage sites of interest. Such modified nucleotides then are incorporated into oligonucleotides that are hybridized to their complements, thereby forming lesion-containing duplex structures. In any given duplex, the identity of the lesion-opposing nucleoside on the complementary strand is systematically altered, thereby allowing us to evaluate the impact on duplex properties of the identity of the base opposite the lesion. For comparative purposes, the undamaged parent Watson-Crick duplex also is synthesized. Such families of DNA duplexes are then sent for independent physiochemical characterizations. Armed with an extensive body of biophysical data, one then searches for correlations between the physiochemical influences of the lesions on duplex properties and the biological consequences of each lesion. At this stage, our approach is highly empirical. Ultimately, we hope that our studies will reveal correlations between physiochemical properties and biological consequences such that we will develop predictive powers and gain insight into the mechanisms of recognition, repair, and mutagenesis.

  15. The Africa Madagascar connection and mammalian migrations

    NASA Astrophysics Data System (ADS)

    Rabinowitz, Philip D.; Woods, Stephen

    2006-03-01

    Madagascar separated from Africa in the Middle-Late Jurassic and has been in its present position relative to Africa since the Early Cretaceous (˜120-130 my). Several Early Eocene to Late Oligocene (˜50-26 my) terrestrial mammalian groups are observed on Madagascar that have a similar ancestral lineage to those found in Africa. These mammalian groups means of transport across the Mozambique Channel from Africa to Madagascar was either by traversing on exposed land masses across a land bridge or by swimming/rafting, since (1) Madagascar has been separated from mainland Africa for at least 70 my before their arrival, and (2) it is unlikely that similar ancestral lineage's evolved simultaneously in separated regions. No evidence has been found for a land bridge across the Mozambique Channel. The mammals thus either swam or have been swept away on vegetation mats from rivers flowing out of Mozambique or Tanzania.

  16. Mammalian Sperm Motility: Observation and Theory

    NASA Astrophysics Data System (ADS)

    Gaffney, E. A.; Gadêlha, H.; Smith, D. J.; Blake, J. R.; Kirkman-Brown, J. C.

    2011-01-01

    Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics.

  17. Mammalian hairs in Early Cretaceous amber

    NASA Astrophysics Data System (ADS)

    Vullo, Romain; Girard, Vincent; Azar, Dany; Néraudeau, Didier

    2010-07-01

    Two mammalian hairs have been found in association with an empty puparium in a ˜100-million-year-old amber (Early Cretaceous) from France. Although hair is known to be an ancestral, ubiquitous feature in the crown Mammalia, the structure of Mesozoic hair has never been described. In contrast to fur and hair of some Jurassic and Cretaceous mammals preserved as carbonized filaments, the exceptional preservation of the fossils described here allows for the study of the cuticular structure. Results show the oldest direct evidence of hair with a modern scale pattern. This discovery implies that the morphology of hair cuticula may have remained unchanged throughout most of mammalian evolution. The association of these hairs with a possible fly puparium provides paleoecological information and indicates peculiar taphonomic conditions.

  18. Mammalian Sirtuins: Biological Insights and Disease Relevance

    PubMed Central

    Haigis, Marcia C.; Sinclair, David A.

    2010-01-01

    Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years. PMID:20078221

  19. 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

  20. Freezing mammalian cells for production of biopharmaceuticals.

    PubMed

    Seth, Gargi

    2012-03-01

    Cryopreservation techniques utilize very low temperatures to preserve the structure and function of living cells. Various strategies have been developed for freezing mammalian cells of biological and medical significance. This paper highlights the importance and application of cryopreservation for recombinant mammalian cells used in the biopharmaceutical industry to produce high-value protein therapeutics. It is a primer that aims to give insight into the basic principles of cell freezing for the benefit of biopharmaceutical researchers with limited or no prior experience in cryobiology. For the more familiar researchers, key cell banking parameters such as the cell density and hold conditions have been reviewed to possibly help optimize their specific cell freezing protocols. It is important to understand the mechanisms underlying the freezing of complex and sensitive cellular entities as we implement best practices around the techniques and strategies used for cryopreservation. PMID:22226818

  1. Structure and function of mammalian aldehyde oxidases.

    PubMed

    Terao, Mineko; Romão, Maria João; Leimkühler, Silke; Bolis, Marco; Fratelli, Maddalena; Coelho, Catarina; Santos-Silva, Teresa; Garattini, Enrico

    2016-04-01

    Mammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX. PMID:26920149

  2. 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

  3. Glia in mammalian development and disease.

    PubMed

    Zuchero, J Bradley; Barres, Ben A

    2015-11-15

    Glia account for more than half of the cells in the mammalian nervous system, and the past few decades have witnessed a flood of studies that detail novel functions for glia in nervous system development, plasticity and disease. Here, and in the accompanying poster, we review the origins of glia and discuss their diverse roles during development, in the adult nervous system and in the context of disease. PMID:26577203

  4. Mammalian cells contain a second nucleocytoplasmic hexosaminidase.

    PubMed

    Gutternigg, Martin; Rendić, Dubravko; Voglauer, Regina; Iskratsch, Thomas; Wilson, Iain B H

    2009-04-01

    Some thirty years ago, work on mammalian tissues suggested the presence of two cytosolic hexosaminidases in mammalian cells; one of these has been more recently characterized in a recombinant form and has an important role in cellular function due to its ability to cleave beta-N-acetylglucosamine residues from a variety of nuclear and cytoplasmic proteins. However, the molecular nature of the second cytosolic hexosaminidase, named hexosaminidase D, has remained obscure. In the present study, we molecularly characterize for the first time the human and murine recombinant forms of enzymes, encoded by HEXDC genes, which appear to correspond to hexosaminidase D in terms of substrate specificity, pH dependency and temperature stability. Furthermore, a Myc-tagged form of this novel hexosaminidase displays a nucleocytoplasmic localization. Transcripts of the corresponding gene are expressed in a number of murine tissues. On the basis of its sequence, this enzyme represents, along with the lysosomal hexosaminidase subunits encoded by the HEXA and HEXB genes, the third class 20 glycosidase to be identified from mammalian sources. PMID:19040401

  5. [Telomere Recombination in Normal Mammalian Cells].

    PubMed

    Zhdanova, N S; Rubtsov, N B

    2016-01-01

    Two mechanisms of telomere length maintenance are known to date. The first includes the use of a special enzymatic telomerase complex to solve the problems that arise during the replication of linear DNA in a normal diploid and part of tumor cells. Alternative lengthening of telomeres (ALT), which is based on the homologous recombination of telomere DNA, represents the second mechanism. Until recently, ALT was assumed to be expressed only in 15-20% of tumors lacking active telomerase and, together with telomerase reactivation represented one of two possibilities to overcome the replicative senescence observed in somatic mammalian cells due to aging or during cell culturing in vitro. Previously described sporadic cases of combinations of the two mechanisms of telomere length maintenance in several cell lines in vitro were attributed to the experimental design rather than to a real biological phenomenon, since active cellular division without active telomerase was considered to be the "gold standard" of ALT. The present review describes the morphological and functional reorganizations of mammalian telomeres observed with ALT activation, as well as recently observed,and well-documented cases of combinations between ALT-like and telomerase-dependent mechanisms in mammalian cells. The possible role of telomere recombination in telomerase-dependent cells is discussed. PMID:27183789

  6. Aneuploidy in mammalian somatic cells in vivo.

    PubMed

    Cimino, M C; Tice, R R; Liang, J C

    1986-01-01

    Aneuploidy is an important potential source of human disease and of reproductive failure. Nevertheless, the ability of chemical agents to induce aneuploidy has been investigated only sporadically in intact (whole-animal) mammalian systems. A search of the available literature from the EMCT Aneuploidy File (for years 1970-1983) provided 112 papers that dealt with aneuploidy in mammalian somatic cells in vivo. 59 of these papers did not meet minimal criteria for analysis and were rejected from subsequent review. Of the remaining 53 papers that dealt with aneuploidy induction by chemical agents in mammalian somatic cells in vivo, only 3 (6%) contained data that were considered to be supported conclusively by adequate study designs, execution, and reporting. These 3 papers dealt with 2 chemicals, one of which, mercury, was negative for aneuploidy induction in humans, and the other, pyrimethamine, was positive in an experimental rodent study. The majority of papers (94%) were considered inconclusive for a variety of reasons. The most common reasons for calling a study inconclusive were (a) combining data on hyperploidy with those on hypoploidy and/or polyploidy, (b) an inadequate or unspecified number of animals and/or cells per animal scored per treatment group, and (c) poor data presentation such that animal-to-animal variability could not be assessed. Suggestions for protocol development are made, and the future directions of research into aneuploidy induction are discussed. PMID:3941670

  7. 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.

  8. How to Build Transcriptional Network Models of Mammalian Pattern Formation

    PubMed Central

    Kioussi, Chrissa; Gross, Michael K.

    2008-01-01

    Background Genetic regulatory networks of sequence specific transcription factors underlie pattern formation in multicellular organisms. Deciphering and representing the mammalian networks is a central problem in development, neurobiology, and regenerative medicine. Transcriptional networks specify intermingled embryonic cell populations during pattern formation in the vertebrate neural tube. Each embryonic population gives rise to a distinct type of adult neuron. The homeodomain transcription factor Lbx1 is expressed in five such populations and loss of Lbx1 leads to distinct respecifications in each of the five populations. Methodology/Principal Findings We have purified normal and respecified pools of these five populations from embryos bearing one or two copies of the null Lbx1GFP allele, respectively. Microarrays were used to show that expression levels of 8% of all transcription factor genes were altered in the respecified pool. These transcription factor genes constitute 20–30% of the active nodes of the transcriptional network that governs neural tube patterning. Half of the 141 regulated nodes were located in the top 150 clusters of ultraconserved non-coding regions. Generally, Lbx1 repressed genes that have expression patterns outside of the Lbx1-expressing domain and activated genes that have expression patterns inside the Lbx1-expressing domain. Conclusions/Significance Constraining epistasis analysis of Lbx1 to only those cells that normally express Lbx1 allowed unprecedented sensitivity in identifying Lbx1 network interactions and allowed the interactions to be assigned to a specific set of cell populations. We call this method ANCEA, or active node constrained epistasis analysis, and think that it will be generally useful in discovering and assigning network interactions to specific populations. We discuss how ANCEA, coupled with population partitioning analysis, can greatly facilitate the systematic dissection of transcriptional networks that

  9. [Placenta and preeclampsia: relationships between anatomical lesions and clinical symptoms].

    PubMed

    Marcorelles, P

    2010-03-01

    The histopathological examination of the placenta is part of the investigational workout since it is a convenient method of examining the central organ involved in the disease process. Characteristic lesions are the vascular placental lesions, and even though their discovery is neither necessary nor specific, they become all the more suggestive of the disease as they are found to be numerous. These vascular lesions are characterized by a microscopic involvement of the basal layer also termed atherosis, associated with uteroplacental artery displasia and its consequences: Infarction, retroplacental haematoma plus all other microscopic injuries of the placenta. These are mainly found in the severe forms of the disease and are usually associated with a placental underdevelopment and IUGR. PMID:20338716

  10. 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

  11. Central myofibroma of the maxilla

    PubMed Central

    Kaur, Paramjeet; Chowalta, Rajat; Lata, Jeevan

    2016-01-01

    Myofibroma is a rare benign localized or generalized proliferation of myofibroblastic tissue occurring mostly in infants or children. In the oral region, most lesions occur in the mandible, lip, buccal mucosa, and tongue; however, the lesions arising in the maxilla are very rare. Myofibroma has an aggressive clinical presentation and is often treated aggressively because of an inappropriate diagnosis. A unique feature of central myofibroma of the jaws is the potential for teeth and other odontogenic structures to be involved by tumor. We report a case of myofibroma arising in the left side of the maxilla of a 12-year-old girl and describe the differential diagnosis from other spindle cell lesions of neural and smooth muscle origin. We treated the case using surgical excision under general anesthesia. Immunohistochemical staining was done for establishing the diagnosis since histopathological diagnosis with conventional staining could not distinguish myofibroma from spindle cell tumors. PMID:27041905

  12. [Focal liver lesion, incidental finding].

    PubMed

    Dietrich, C F; Jenssen, C

    2012-10-01

    The differential diagnosis of incidentally found Focal Liver Lesions (FLL) is complex. Screening procedures so far are only defined for patients with liver cirrhosis. Characterization of a FLL begins as soon as it is detected. Taking patients history and thorough clinical examination are essential. An imaging procedure that is used to detect liver masses should also allow the examiner to determine whether the lesion is benign or malignant. Conventional B-mode US and colour Doppler imaging are effective at detecting and characterizing typical liver cysts and calcifications. Laboratory data, computed tomography, magnetic resonance imaging and imaging guided liver biopsy are complementary methods.Contrast Enhanced Ultrasound (CEUS) is a well established diagnostic imaging technique for a variety of indications and applications. One of the most important applications is in the liver where it is frequently a first-line technique for the detection and diagnosis (characterization) of focal liver lesions (FLL). In this setting the accurate differentiation of benign from malignant lesions is critical to ensure the patient undergoes the appropriate therapeutic option. This has been documented in recently published guidelines, in particular in terms of the enhancement patterns of the most common FLL hemangioma, focal nodular hyperplasia hepatocellular adenoma and their differentiation from malignant lesions. In this article the role of CEUS in the characterization of incidentally found FLL is described. PMID:23033169

  13. Skin lesions in returning travellers.

    PubMed

    Korzeniewski, Krzysztof; Juszczak, Dariusz; Jerzemowski, Janusz

    2015-01-01

    Skin lesions, apart from diarrhoeas, fever of unknown origin, and respiratory tract infections belong to the most frequent medical problems in travellers returned from tropical and subtropical destinations, accounting more than 10% of reported cases. Most dermatoses have their clinical onset during travel, although some of them can occur after return. Travel-related dermatological problems can have a wide spectrum of clinical picture, from macular, popular or nodular rash, linear and migratory lesions, to plaques, vesicles, bullae, erosions or ulcers. Skin conditions in returning travellers may be of infectious and non-infectious aetiologies. Infectious lesions may be originally tropical (e.g. dengue, chikungunya, schistosomiasis, leishmaniasis, myiasis, tungiasis, loiasis), although the majority are cosmopolitan (arthropod bites, sunburns, allergic rashes). The evaluation of skin lesions depends on many factors, including immune status of patients, use of medicines, exposure on health hazards (fauna, flora, risky behaviours), as well as the time, duration and location of travel. As the number of travellers to tropical and subtropical destinations has been continuously rising, the number of skin illnesses has also been increasing. This means that specialists in travel medicine need to extend their knowledge of epidemiology, clinical features and diagnosis of travel-related health problems including skin lesions in returning travellers. PMID:26394319

  14. Loss of CLPP alleviates mitochondrial cardiomyopathy without affecting the mammalian UPRmt.

    PubMed

    Seiferling, Dominic; Szczepanowska, Karolina; Becker, Christina; Senft, Katharina; Hermans, Steffen; Maiti, Priyanka; König, Tim; Kukat, Alexandra; Trifunovic, Aleksandra

    2016-07-01

    The mitochondrial matrix protease CLPP plays a central role in the activation of the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans Far less is known about mammalian UPR(mt) signaling, although similar roles were assumed for central players, including CLPP To better understand the mammalian UPR(mt) signaling, we deleted CLPP in hearts of DARS2-deficient animals that show robust induction of UPR(mt) due to strong dysregulation of mitochondrial translation. Remarkably, our results clearly show that mammalian CLPP is neither required for, nor it regulates the UPR(mt) in mammals. Surprisingly, we demonstrate that a strong mitochondrial cardiomyopathy and diminished respiration due to DARS2 deficiency can be alleviated by the loss of CLPP, leading to an increased de novo synthesis of individual OXPHOS subunits. These results question our current understanding of the UPR(mt) signaling in mammals, while introducing CLPP as a possible novel target for therapeutic intervention in mitochondrial diseases. PMID:27154400

  15. Brain lesions and eating disorders

    PubMed Central

    Uher, R; Treasure, J

    2005-01-01

    Objective: To evaluate the relation between lesions of various brain structures and the development of eating disorders and thus inform the neurobiological research on the aetiology of these mental illnesses. Method: We systematically reviewed 54 previously published case reports of eating disorders with brain damage. Lesion location, presence of typical psychopathology, and evidence suggestive of causal association were recorded. Results: Although simple changes in appetite and eating behaviour occur with hypothalamic and brain stem lesions, more complex syndromes, including characteristic psychopathology of eating disorders, are associated with right frontal and temporal lobe damage. Conclusions: These findings challenge the traditional view that eating disorders are linked to hypothalamic disturbance and suggest a major role of frontotemporal circuits with right hemispheric predominance in the pathogenesis. PMID:15897510

  16. 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

  17. Renal lesions of nondomestic felids.

    PubMed

    Newkirk, K M; Newman, S J; White, L A; Rohrbach, B W; Ramsay, E C

    2011-05-01

    To comprehensively evaluate the occurrence of renal lesions in a variety of nondomestic felids, necropsy cases from 1978 to 2008 were reviewed from a municipal zoo and a large cat sanctuary for those in which the kidneys were examined histologically. Seventy exotic felids were identified (25 tigers, 18 lions, 6 cougars, 5 leopards, 3 snow leopards, 3 clouded leopards, 3 Canadian lynx, 2 ocelots, 2 bobcats, 2 cheetahs, 1 jaguar), and their histologic renal lesions were evaluated and compared. The most common lesion was tubulointerstitial nephritis (TIN); 36 of 70 (51%) cats were affected to some degree. Lymphocytic interstitial nephritis was the most common lesion in the tigers (9 of 25, 36%) and was rarely seen in other species. Although the renal pelvis was not available for all cats, 28 of 47 (60%) had some degree of lymphocytic pyelitis. There was no significant association between the presence of pyelitis and that of TIN. Only 1 cat had pyelonephritis. Renal papillary necrosis was present in 13 of 70 (19%) cats and was significantly associated with historical nonsteroidal anti-inflammatory drug treatment (odds ratio, 7.1; 95% confidence interval, 1.9 to 26.8). Only 1 cat (lion) had amyloid accumulation, and it was restricted to the corticomedullary junction. Primary glomerular lesions were absent in all cats. Intraepithelial pigment was identified in many of the cats but was not correlated with severity of TIN. Despite several previous reports describing primary glomerular disease or renal amyloidosis in exotic felids, these lesions were rare to absent in this population. PMID:20876911

  18. Can Small Lesions Induce Language Reorganization as Large Lesions Do?

    ERIC Educational Resources Information Center

    Maestu, Fernando; Saldana, Cristobal; Amo, Carlos; Gonzalez-Hidalgo, Mercedes; Fernandez, Alberto; Fernandez, Santiago; Mata, Pedro; Papanicolaou, Andrew; Ortiz, Tomas

    2004-01-01

    Shift of the cortical mechanisms of language from the usually dominant left to the non-dominant right hemisphere has been demonstrated in the presence of large brain lesions. Here, we report a similar phenomenon in a patient with a cavernoma over the anterolateral superior temporal gyrus associated with epilepsy. Language mapping was performed by…

  19. Lesion detectability in digital radiography

    NASA Astrophysics Data System (ADS)

    Gagne, Robert M.; Boswell, Jonathan S.; Myers, Kyle J.; Peter, Guillaume

    2001-06-01

    The usefulness of Fourier-based measures of imaging performance has come into question for the evaluation of digital imaging systems. Figures of merit such as detective quantum efficiency are relevant for linear, shift-invariant systems with stationary noise. However, no digital imaging system is shift invariant, and realistic images do not satisfy the stationarity condition. Our methods for task- based evaluation of imaging systems, based on lesion detectability, do not require such assumptions. We have computed the performance of Hotelling and nonprewhitening matched-filter observers for the task of lesion detection in digital radiography.

  20. Cutaneous lesions of the nose

    PubMed Central

    2010-01-01

    Skin diseases on the nose are seen in a variety of medical disciplines. Dermatologists, otorhinolaryngologists, general practitioners and general plastic and dermatologic surgeons are regularly consulted regarding cutaneous lesions on the nose. This article is the second part of a review series dealing with cutaneous lesions on the head and face, which are frequently seen in daily practice by a dermatologic surgeon. In this review, we focus on those skin diseases on the nose where surgery or laser therapy is considered a possible treatment option or that can be surgically evaluated. PMID:20525327

  1. BLACK LESIONS OF THE SKIN

    PubMed Central

    Becker, S. William

    1958-01-01

    Benign melanocytic lesions include lentigo, ephelid (freckle), pigmented nevus, sacral spot, blue nevus, and combined nevus and blue nevus. Malignant melanocytic lesions are melanomas, which arise from melanocytes at the epidermodermal junction, or, rarely, from blue nevi. They usually originate in brown plaques known as lentigo maligna, in pigmented nevi, or in normal skin. Melanoma is diagnosed clinically in less than 50 per cent of instances. Biopsy is therefore of great importance, since practically all melanoma can be cured by adequate early resection. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8. PMID:13511215

  2. Apraxia in deep cerebral lesions.

    PubMed Central

    Agostoni, E; Coletti, A; Orlando, G; Tredici, G

    1983-01-01

    In a series of 50 patients with cerebrovascular lesions (demonstrated with CT scan), seven patients had lesions located in the basal ganglia and/or thalamus. All these seven patients were apractic. Ideomotor apraxia was present in all patients; five also had constructional apraxia, and one had bucco-facial apraxia. None of the patients had utilisation apraxia. These observations indicated that apraxia is not only a "high cerebral (cortical) function", but may depend also on the integrity of subcortical circuits and structures. PMID:6619888

  3. Localized lesions in secondary syphilis.

    PubMed

    Dar, Nasser Rashid; Raza, Naeem

    2008-05-01

    The clinical manifestations of secondary syphilis are variable and can mimic many skin diseases, mostly being generalized and symmetrical in distribution. Localized lesions of secondary syphilis are rarely seen in dermatology clinics. We report an unusual presentation wherein a patient had localized lesions over face and soles only. There is a need for increased awareness on the part of physicians to recognize new patterns of syphilitic infection, together with a willingness to consider the diagnosis of syphilis in patients with unusual clinical features. PMID:18541087

  4. Significance of retinal laser lesion location and subretinal hemorrhage in bridging choroidal neovascular complexes

    NASA Astrophysics Data System (ADS)

    Schuschereba, Steven T.; Clarkson, Donna R.; Valo, Lynn M.; Brown, Jeremiah, Jr.; Stuck, Bruce E.

    2003-06-01

    Purpose: To determine funduscopic criteria that will help predict when bridging choroidal neovascular (CNV) complexes will develop after laser retinal trauma and to define early preventive treatment targets. Methods: Ten rhesus monkeys were used and retinal lesions were produced by Nd:YAG exposures (20ns, 1-2mJ, 1064nm, min. spot size) simulating human accidental laser trauma to the central fundus. Funduscopy and fluorescein/ICG angiography were conducted at day 1, 4, and 14, and at 2 and 4 months, and animals terminated for histologic evaluation. Predisposition for bridging fibrovascular complexes was evaluated for single lesions, two small lesions showing coalescing hemorrhages, and multiple lesions involved with large field subretinal and vitreous hemorrhages. Results: Elevated CNVs were present in all single lesions with confined subretinal hemorrhages. All lesion sets that showed initial and small coalescing subretinal hemorrhages formed bridging CNV scars. No bridging CNVs occurred in lesion sets involving a vitreous hemorrhage adjacent to a confined, but small subretinal hemorrhage. In large field subretinal hemorrhages involving multiple laser lesions, complex CNV formation occurred. Extensive secondary photoreceptor losses occurred in confined hemorrhage and CNV zones. Conclusion: Trauma presenting with evidence of coalescing and confined subretinal hemorrhages between two adjacent lesions has a high chance of forming choroidal neovascular bridge complexes between the involved lesions. CNV formation may be related to the long residence time, break down products, and clearance processes of extravasated blood. Removal of trapped blood and curtailing angiogenesis and cellular proliferation may be helpful treatment strategies.

  5. 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.

  6. Endothelial Cell Integrin Laminin Receptor Expression in Multiple Sclerosis Lesions

    PubMed Central

    Sobel, Raymond A.; Hinojoza, Julian R.; Maeda, Atsuko; Chen, Michael

    1998-01-01

    Laminin, a major glycoprotein component of vessel basement membranes, is recognized by β1- and β3-integrins expressed on endothelial cells. To determine how endothelial cell integrins might function in multiple sclerosis (MS) lesions, integrin laminin receptors and laminin were analyzed in central nervous system samples from MS patients and controls by immunohistochemistry. In active MS lesions, endothelial cell VLA-6 and β1 subunits were decreased compared to controls whereas αv subunit and VLA-1 were increased. In chronic inactive lesions β1, VLA-6 and αv were the same as controls but VLA-1 remained increased. α3 subunit was constant in all samples. By immunoelectron microscopy VLA-1, VLA-6, β1, and laminin were distributed throughout endothelial cells; αv was adjacent to and on luminal surfaces; αv and VLA-1 were on intercellular junctions. These results indicate distinct regulation and functions of these integrins in different lesion stages. In active lesions decreased endothelial cell β1/VLA-6 could result in their detachment from laminin thereby facilitating leukocyte transvascular migration and blood-brain barrier breakdown. αv and VLA-1 on intercellular junctions may participate in re-establishing vessel integrity after leukocyte migration. Luminal surface αv also likely binds intraluminal ligands and cells. In chronic inactive plaques persistently elevated endothelial cell VLA-1 correlates with longstanding endothelial cell and blood-brain barrier dysfunction. PMID:9708801

  7. [Auditory hallucinations in lesions of the brain stem].

    PubMed

    Cambier, J; Decroix, J P; Masson, C

    1987-01-01

    Since the publication by Jean Lhermitte in 1922 of his paper on hallucinosis, the peduncular type has been described as a purely visual phenomenon. However, limited brain stem lesions can give rise to analogous manifestations in the auditory field. Five cases of auditory hallucinosis are reviewed, the first four resulting from a lesion of tegmentum of pons responsible for contralateral hemi-anesthesia and homolateral facial palsy with paralysis of laterality. Central type hypoacusis and a severe disorder of localization of sounds revealed a lesion of trapezoid body. The fifth case resulted from a peduncular lesion in region supplied by superior cerebellar artery, the auditory deficit being related to a lesion of inferior corpus quadrigeminum. In one patient, the auditory hallucinosis was followed by a period of visual hallucinations and oneiric delusions. Both auditory and visual hallucinosis can be related to hypnagogic hallucinations. Dream mechanisms (the geniculo-occipital spikes system) escape from normal inhibitory control exerted by the raphe nuclei. Auditory deafferentation could predispose to auditory hallucinosis. PMID:3629075

  8. Prevalence of oral soft tissue lesions in Vidisha

    PubMed Central

    2010-01-01

    Background The purpose of this study was to determine the prevalence of oral soft tissue lesions in patients and to assess their clinicopathological attributes. 3030 subjects belonging to a semi-urban district of Vidisha in Central India were screened. Patients were examined with an overhead examination light and those who were identified with a questionable lesion underwent further investigations. Statistical analysis was done using the SPSS software. Findings 8.4 percent of the population studied had one or more oral lesions, associated with prosthetic use, trauma and tobacco consumption. With reference to the habit of tobacco use, 635(21%) were smokers, 1272(42%) tobacco chewers, 341(11%) smokers and chewers, while 1464(48%) neither smoked nor chewed. 256 patients were found to have significant mucosal lesions. Of these, 216 cases agreed to undergo scalpel biopsy confirmation. 88 had leukoplakia, 21 had oral submucous fibrosis, 9 showed smoker's melanosis, 6 patients had lichen planus, 17 had dysplasia, 2 patients had squamous cell carcinoma while there was 1 patient each with lichenoid reaction, angina bullosa hemorrhagica, allergic stomatitis and nutritional stomatitis. Conclusions The findings in this population reveal a high prevalence of oral soft tissue lesions and a rampant misuse of variety of addictive substances in the community. Close follow up and systematic evaluation is required in this population. There is an urgent need for awareness programs involving the community health workers, dentists and allied medical professionals. PMID:20181008

  9. Neonatal Amygdala Lesions Alter Responsiveness to Objects in Juvenile Macaques

    PubMed Central

    Bliss-Moreau, Eliza; Toscano, Jessica E.; Bauman, Melissa; Mason, William A.; Amaral, David G.

    2013-01-01

    The amygdala is widely recognized to play a central role in emotional processing. In nonhuman primates, the amygdala appears to be critical for generating appropriate behavioral responses in emotionally salient contexts. One common finding is that macaque monkeys that receive amygdala lesions as adults are behaviorally uninhibited in the presence of potentially dangerous objects. While control animals avoid these objects, amygdala-lesioned animals readily interact with them. Despite a large literature documenting the role of the amygdala in emotional processing in adult rhesus macaques, little research has assessed the role of the amygdala across the macaque neurodevelopmental trajectory. We assessed the behavioral responses of three-year-old (juvenile) rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at two weeks of age. Animals were presented with salient objects known to produce robust fear-related responses in macaques (e.g., snakes and reptile-like objects), mammal-like objects that included animal-like features (e.g., eyes and mouths) but not reptile-like features (e.g., scales), and non-animal objects. The visual complexity of objects was scaled to vary the objects' salience. In contrast to control and hippocampus-lesioned animals, amygdale-lesioned animals were uninhibited in the presence of potentially dangerous objects. They readily retrieved food rewards placed near these objects and physically explored the objects. Furthermore, while control and hippocampus-lesioned animals differentiated between levels of object complexity, amygdala-lesioned animals did not. Taken together, these findings suggest that early damage to the amygdala, like damage during adulthood, permanently compromises emotional processing. PMID:21215794

  10. Steroid hydroxylations: A paradigm for cytochrome P450 catalyzed mammalian monooxygenation reactions

    SciTech Connect

    Estabrook, Ronald W. . E-mail: Ronald.estabrook@utsouthwestern.edu

    2005-12-09

    The present article reviews the history of research on the hydroxylation of steroid hormones as catalyzed by enzymes present in mammalian tissues. The report describes how studies of steroid hormone synthesis have played a central role in the discovery of the monooxygenase functions of the cytochrome P450s. Studies of steroid hydroxylation reactions can be credited with showing that: (a) the adrenal mitochondrial enzyme catalyzing the 11{beta}-hydroxylation of deoxycorticosterone was the first mammalian enzyme shown by O{sup 18} studies to be an oxygenase; (b) the adrenal microsomal enzyme catalyzing the 21-hydroxylation of steroids was the first mammalian enzyme to show experimentally the proposed 1:1:1 stoichiometry (substrate:oxygen:reduced pyridine nucleotide) of a monooxygenase reaction; (c) application of the photochemical action spectrum technique for reversal of carbon monoxide inhibition of the 21-hydroxylation of 17{alpha}-OH progesterone was the first demonstration that cytochrome P450 was an oxygenase; (d) spectrophotometric studies of the binding of 17{alpha}-OH progesterone to bovine adrenal microsomal P450 revealed the first step in the cyclic reaction scheme of P450, as it catalyzes the 'activation' of oxygen in a monooxygenase reaction; (e) purified adrenodoxin was shown to function as an electron transport component of the adrenal mitochondrial monooxygenase system required for the activity of the 11{beta}-hydroxylase reaction. Adrenodoxin was the first iron-sulfur protein isolated and purified from mammalian tissues and the first soluble protein identified as a reductase of a P450; (f) fractionation of adrenal mitochondrial P450 and incubation with adrenodoxin and a cytosolic (flavoprotein) fraction were the first demonstration of the reconstitution of a mammalian P450 monooxygenase reaction.

  11. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis.

    PubMed

    Li, Xue; Oghi, Kenneth A; Zhang, Jie; Krones, Anna; Bush, Kevin T; Glass, Christopher K; Nigam, Sanjay K; Aggarwal, Aneel K; Maas, Richard; Rose, David W; Rosenfeld, Michael G

    2003-11-20

    The precise mechanistic relationship between gene activation and repression events is a central question in mammalian organogenesis, as exemplified by the evolutionarily conserved sine oculis (Six), eyes absent (Eya) and dachshund (Dach) network of genetically interacting proteins. Here, we report that Six1 is required for the development of murine kidney, muscle and inner ear, and that it exhibits synergistic genetic interactions with Eya factors. We demonstrate that the Eya family has a protein phosphatase function, and that its enzymatic activity is required for regulating genes encoding growth control and signalling molecules, modulating precursor cell proliferation. The phosphatase function of Eya switches the function of Six1-Dach from repression to activation, causing transcriptional activation through recruitment of co-activators. The gene-specific recruitment of a co-activator with intrinsic phosphatase activity provides a molecular mechanism for activation of specific gene targets, including those regulating precursor cell proliferation and survival in mammalian organogenesis. PMID:14628042

  12. 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

  13. Evolution and functions of Oct4 homologs in non-mammalian vertebrates.

    PubMed

    Onichtchouk, Daria

    2016-06-01

    PouV class transcription factor Oct4/Pou5f1 is a central regulator of indefinite pluripotency in mammalian embryonic stem cells (ESCs) but also participates in cell lineage specification in mouse embryos and in differentiating cell cultures. The molecular basis for this versatility, which is shared between Oct4 and its non-mammalian homologs Pou5f1 and Pou5f3, is not yet completely understood. Here, I review the current understanding of the evolution of PouV class transcription factors and discuss equivalent and diverse roles of Oct4 homologs in pluripotency, differentiation, and cell behavior in different vertebrate embryos. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin. PMID:27058398

  14. Central hypoventilation and brainstem dysgenesis.

    PubMed

    Armangue, Thais; Macaya, Alfons; Vazquez, Elida; Jurado, Maria José; Roig-Quilis, Manuel

    2012-04-01

    We report on a newborn with congenital hypotonia, unilateral facial palsy, sucking and swallowing difficulties, velopalatine incoordination, and unilateral impairment of the auditory brainstem responses, attributable to brainstem dysgenesis. On follow-up, the child manifested developmental delay and central hypoventilation syndrome during sleep. The ventilation abnormality during sleep with insensitivity to hypercapnia, associated with unilateral facial paralysis, indicates a pontine lesion, including the parafacial respiratory group. PMID:22490775

  15. 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.

  16. Flow cytometric sexing of mammalian sperm.

    PubMed

    Garner, Duane L

    2006-03-15

    This review reexamines parameters needed for optimization of flow cytometric sexing mammalian sperm and updates the current status of sperm sexing for various species where this technology is currently being applied. Differences in DNA content have provided both a method to differentiate between these sex-determining gametes and a method to sort them that can be used for predetermining sex in mammals. Although the DNA content of all cells for each mammalian species is highly conserved, slight but measurable DNA content differences of sperm occur within species even among cattle breeds due to different sizes of Y-chromosomes. Most mammals produce flattened, oval-headed sperm that can be oriented within a sorter using hydrodynamic forces. Multiplying the percentage the difference in DNA content of the X- or Y-chromosome bearing sperm times the area of the flat profile of the sperm head gives a simple sorting index that suggests that bull and boar sperm are well suited for separation in a flow sorter. Successful sperm sexing of various species must take into account the relative susceptibilities of gametes to the stresses that occur during sexing. Sorting conditions must be optimized for each species to achieve acceptable sperm sexing efficiency, usually at 90% accuracy. In the commercial application of sperm sexing to cattle, fertility of sex-sorted bull sperm at 2 x 10(6)/dose remains at 70-80% of unsexed sperm at normal doses of 10 to 20 x 10(6) sperm. DNA content measurements have been used to identify the sex-chromosome bearing sperm populations with good accuracy in semen from at least 23 mammalian species, and normal-appearing offspring have been produced from sexed sperm of at least seven species. PMID:16242764

  17. Structure of transcribing mammalian RNA polymerase II.

    PubMed

    Bernecky, Carrie; Herzog, Franz; Baumeister, Wolfgang; Plitzko, Jürgen M; Cramer, Patrick

    2016-01-28

    RNA polymerase (Pol) II produces messenger RNA during transcription of protein-coding genes in all eukaryotic cells. The Pol II structure is known at high resolution from X-ray crystallography for two yeast species. Structural studies of mammalian Pol II, however, remain limited to low-resolution electron microscopy analysis of human Pol II and its complexes with various proteins. Here we report the 3.4 Å resolution cryo-electron microscopy structure of mammalian Pol II in the form of a transcribing complex comprising DNA template and RNA transcript. We use bovine Pol II, which is identical to the human enzyme except for seven amino-acid residues. The obtained atomic model closely resembles its yeast counterpart, but also reveals unknown features. Binding of nucleic acids to the polymerase involves 'induced fit' of the mobile Pol II clamp and active centre region. DNA downstream of the transcription bubble contacts a conserved 'TPSA motif' in the jaw domain of the Pol II subunit RPB5, an interaction that is apparently already established during transcription initiation. Upstream DNA emanates from the active centre cleft at an angle of approximately 105° with respect to downstream DNA. This position of upstream DNA allows for binding of the general transcription elongation factor DSIF (SPT4-SPT5) that we localize over the active centre cleft in a conserved position on the clamp domain of Pol II. Our results define the structure of mammalian Pol II in its functional state, indicate that previous crystallographic analysis of yeast Pol II is relevant for understanding gene transcription in all eukaryotes, and provide a starting point for a mechanistic analysis of human transcription. PMID:26789250

  18. 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

  19. Stochastic resonance in mammalian neuronal networks

    SciTech Connect

    Gluckman, B.J.; So, P.; Netoff, T.I.; Spano, M.L.; Schiff, S.J. |

    1998-09-01

    We present stochastic resonance observed in the dynamics of neuronal networks from mammalian brain. Both sinusoidal signals and random noise were superimposed into an applied electric field. As the amplitude of the noise component was increased, an optimization (increase then decrease) in the signal-to-noise ratio of the network response to the sinusoidal signal was observed. The relationship between the measures used to characterize the dynamics is discussed. Finally, a computational model of these neuronal networks that includes the neuronal interactions with the electric field is presented to illustrate the physics behind the essential features of the experiment. {copyright} {ital 1998 American Institute of Physics.}

  20. Site of Mammalian Sperm Acrosome Reaction.

    PubMed

    Hirohashi, Noritaka

    2016-01-01

    Until recently, no special attention has been paid to the question of the site of mammalian sperm acrosome reaction (AR) in the female reproductive tract. Because AR is an essential process that enables the spermatozoon to fertilize, it is generally believed that it occurs at a specific step during sperm-egg interaction. It is generally thought that "the site of action coincides with the site of commitment." Thus, understanding the roles of AR and acrosomal substances is needed to gain insight into the site of the sperm commitment to undergo AR. PMID:27194354

  1. Mammalian cell culture capacity for biopharmaceutical manufacturing.

    PubMed

    Ecker, Dawn M; Ransohoff, Thomas C

    2014-01-01

    : With worldwide sales of biopharmaceuticals increasing each year and continuing growth on the horizon, the manufacture of mammalian biopharmaceuticals has become a major global enterprise. We describe the current and future industry wide supply of manufacturing capacity with regard to capacity type, distribution, and geographic location. Bioreactor capacity and the use of single-use products for biomanufacturing are also profiled. An analysis of the use of this capacity is performed, including a discussion of current trends that will influence capacity growth, availability, and utilization in the coming years. PMID:23748352

  2. Mammalian Developmental Genetics in the Twentieth Century

    PubMed Central

    Artzt, Karen

    2012-01-01

    This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas. PMID:23212897

  3. Apoptotic processes during mammalian preimplantation development.

    PubMed

    Fabian, Dusan; Koppel, Juraj; Maddox-Hyttel, Poul

    2005-07-15

    The paper provides a review of the current state of knowledge on apoptosis during normal preimplantation development based on the literature and on the authors' own findings. Information is focused on the occurrence and the characteristics of spontaneous apoptotic processes. Reports concerning the chronology and the incidence of programmed cell death in mouse, cow, pig and human embryos in early preimplantation stages up to the blastocyst stage are summarized. In addition, specific attributes of the apoptotic process in mammalian preimplantation development are provided, including the description of both morphological and biochemical features of cell death. PMID:15955348

  4. Tension tests on mammalian collagen fibrils.

    PubMed

    Liu, Yehe; Ballarini, Roberto; Eppell, Steven J

    2016-02-01

    A brief overview of isolated collagen fibril mechanics testing is followed by presentation of the first results testing fibrils isolated from load-bearing mammalian tendons using a microelectromechanical systems platform. The in vitro modulus (326 ± 112 MPa) and fracture stress (71 ± 23 MPa) are shown to be lower than previously measured on fibrils extracted from sea cucumber dermis and tested with the same technique. Scanning electron microscope images show the fibrils can fail with a mechanism that involves circumferential rupture, whereas the core of the fibril stays at least partially intact. PMID:26855757

  5. Light-sheet imaging of mammalian development.

    PubMed

    de Medeiros, Gustavo; Balázs, Bálint; Hufnagel, Lars

    2016-07-01

    Tackling modern cell and developmental biology questions requires fast 3D imaging with sub-cellular resolution over extended periods of time. Fluorescence microscopy has emerged as a powerful tool to image biological samples with high spatial and temporal resolution with molecular specificity. In particular, the highly efficient illumination and detection scheme of light-sheet fluorescence microscopy is starting to revolutionize the way we can monitor cellular and developmental processes in vivo. Here we summarize the state-of-the art of light-sheet imaging with a focus on mammalian development - from instrumentation, mounting and sample handling to data processing. PMID:27288888

  6. Mammalian Gravity Receptors: Structure and Metabolism

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1985-01-01

    Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

  7. Derivation of the mammalian skull vault

    PubMed Central

    MORRISS-KAY, GILLIAN M.

    2001-01-01

    This review describes the evolutionary history of the mammalian skull vault as a basis for understanding its complex structure. Current information on the developmental tissue origins of the skull vault bones (mesoderm and neural crest) is assessed for mammals and other tetrapods. This information is discussed in the context of evolutionary changes in the proportions of the skull vault bones at the sarcopterygian-tetrapod transition. The dual tissue origin of the skull vault is considered in relation to the molecular mechanisms underlying osteogenic cell proliferation and differentiation in the sutural growth centres and in the proportionate contributions of different sutures to skull growth. PMID:11523816

  8. Cystic Lesions in Autoimmune Pancreatitis.

    PubMed

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases. PMID:26675058

  9. Neuromuscular lesions in restrained rabbits.

    PubMed

    Mendlowski, B

    1975-01-01

    Ten of 16 rabbits restrained 6 h daily for 35 days developed focal to diffuse degeneration of the sciatic nerves. Very small necrotic areas also were found in the skeletal muscles of seven of 16 rabbits, but the muscle lesions did not correlate with the nerve changes. PMID:180647

  10. Cystic lesions of the pancreas

    PubMed Central

    Karoumpalis, Ioannis; Christodoulou, Dimitrios K.

    2016-01-01

    Different types of benign or malignant cystic lesions can be observed in the pancreas. Pancreatic cystic lesions are classified under pathology terms into simple retention cysts, pseudocysts and cystic neoplasms. Mucinous cystic neoplasm is a frequent type of cystic neoplasm and has a malignant potential. Serous cystadenoma follows in frequency and is usually benign. Intraductal papillary mucinous neoplasms are the most commonly resected cystic pancreatic neoplasms characterized by dilated segments of the main pancreatic duct and/or side branches, the wall of which is covered by mucus secreting cells. These neoplasms can occupy the pancreatic head or any part of the organ. Solid pseudopapillary tumor is rare, has a low tendency for malignancy, and is usually located in the pancreatic body or tail. Endoscopic ultrasound with the use of fine-needle aspiration and cytology permits discrimination of those lesions. In this review, the main characteristics of those lesions are presented, as well as recommendations regarding their follow up and management according to recent guidelines. PMID:27065727

  11. Cystic lesions of the pancreas.

    PubMed

    Karoumpalis, Ioannis; Christodoulou, Dimitrios K

    2016-01-01

    Different types of benign or malignant cystic lesions can be observed in the pancreas. Pancreatic cystic lesions are classified under pathology terms into simple retention cysts, pseudocysts and cystic neoplasms. Mucinous cystic neoplasm is a frequent type of cystic neoplasm and has a malignant potential. Serous cystadenoma follows in frequency and is usually benign. Intraductal papillary mucinous neoplasms are the most commonly resected cystic pancreatic neoplasms characterized by dilated segments of the main pancreatic duct and/or side branches, the wall of which is covered by mucus secreting cells. These neoplasms can occupy the pancreatic head or any part of the organ. Solid pseudopapillary tumor is rare, has a low tendency for malignancy, and is usually located in the pancreatic body or tail. Endoscopic ultrasound with the use of fine-needle aspiration and cytology permits discrimination of those lesions. In this review, the main characteristics of those lesions are presented, as well as recommendations regarding their follow up and management according to recent guidelines. PMID:27065727

  12. Odontogenic lesions in pediatric patients.

    PubMed

    Fang, Qi-Gen; Shi, Shuang; Sun, Chang-Fu

    2014-05-01

    The purpose was to evaluate our 20-year experience of pediatric odontogenic lesions. Pediatric patients with a diagnosis of odontogenic lesion were identified. Three hundred ten patients were odontogenic; dentigerous cyst was seen in 62.0% of the cases. Most (70.2%) of them occurred in mixed dentition period, and it had a male preponderance. Odontogenic keratocystic tumor occurred in the permanent dentition period. It had an equal site distribution. Odontoma was seen in 20.0% of the cases. Its site of predilection was the mandible. Ameloblastoma was the most common odontogenic tumor. Most of the cases occurred in the permanent dentition period. It affected the male and female equally. Calcifying epithelioma odontogenic tumor was seen in 11.8% of the cases. All the lesions occurred in the primary dentition period. It had no sex or site preponderance. Myxoma was seen in 3.6% of the cases. It was most common in the permanent dentition period, and it was more frequent in the male. Iliac crest bone graft was successfully performed in 28 patients, postoperative infection occurred in 2 patients, and no donor-site dysfunctions were reported. The observed differences in lesion type and distribution in this study compared with previous researches may be attributable to genetic and geographic variation in the populations studied. Iliac crest bone graft was suggested for pediatric mandible reconstruction. PMID:24785745

  13. Molecular imaging of cerebrovascular lesions.

    PubMed

    Chalouhi, Nohra; Jabbour, Pascal; Magnotta, Vincent; Hasan, David

    2014-04-01

    Inflammation is a key component in the pathogenesis of cerebrovascular lesions. Two agents have emerged as promising possibilities for imaging cerebrovascular lesions. These agents are ferumoxytol and myeloperoxidase (MPO)-specific paramagnetic magnetic resonance (MR) contrast agent. Ferumoxytol is an iron oxide nanoparticle coated by a carbohydrate shell that is used in MRI studies as an inflammatory marker as it is cleared by macrophages. Ferumoxytol-enhanced MRI allows noninvasive assessment of the inflammatory status of cerebral aneurysms and arteriovenous malformations and, possibly, may differentiate "unstable" lesions that require early intervention from "stable" lesions that can be safely observed. Several pilot studies have also suggested that MPO-specific paramagnetic MR contrast agent, di-5-hydroxytryptamide of gadopentetate dimeglumine, may allow imaging of inflammation in the wall of saccular aneurysms in animal models. However, studies in human subjects have yet to be performed. In this paper, we review current data regarding ferumoxytol-enhanced MRI and MPO-specific paramagnetic MR contrast agent and discuss current and future applications. PMID:24323714

  14. SLAP lesions: a treatment algorithm.

    PubMed

    Brockmeyer, Matthias; Tompkins, Marc; Kohn, Dieter M; Lorbach, Olaf

    2016-02-01

    Tears of the superior labrum involving the biceps anchor are a common entity, especially in athletes, and may highly impair shoulder function. If conservative treatment fails, successful arthroscopic repair of symptomatic SLAP lesions has been described in the literature particularly for young athletes. However, the results in throwing athletes are less successful with a significant amount of patients who will not regain their pre-injury level of performance. The clinical results of SLAP repairs in middle-aged and older patients are mixed, with worse results and higher revision rates as compared to younger patients. In this population, tenotomy or tenodesis of the biceps tendon is a viable alternative to SLAP repairs in order to improve clinical outcomes. The present article introduces a treatment algorithm for SLAP lesions based upon the recent literature as well as the authors' clinical experience. The type of lesion, age of patient, concomitant lesions, and functional requirements, as well as sport activity level of the patient, need to be considered. Moreover, normal variations and degenerative changes in the SLAP complex have to be distinguished from "true" SLAP lesions in order to improve results and avoid overtreatment. The suggestion for a treatment algorithm includes: type I: conservative treatment or arthroscopic debridement, type II: SLAP repair or biceps tenotomy/tenodesis, type III: resection of the instable bucket-handle tear, type IV: SLAP repair (biceps tenotomy/tenodesis if >50 % of biceps tendon is affected), type V: Bankart repair and SLAP repair, type VI: resection of the flap and SLAP repair, and type VII: refixation of the anterosuperior labrum and SLAP repair. PMID:26818554

  15. Central line infections - hospitals

    MedlinePlus

    ... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

  16. Mammalian Rest/Activity Patterns Explained by Physiologically Based Modeling

    PubMed Central

    Phillips, A. J. K.; Fulcher, B. D.; Robinson, P. A.; Klerman, E. B.

    2013-01-01

    Circadian rhythms are fundamental to life. In mammals, these rhythms are generated by pacemaker neurons in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is remarkably consistent in structure and function between species, yet mammalian rest/activity patterns are extremely diverse, including diurnal, nocturnal, and crepuscular behaviors. Two mechanisms have been proposed to account for this diversity: (i) modulation of SCN output by downstream nuclei, and (ii) direct effects of light on activity. These two mechanisms are difficult to disentangle experimentally and their respective roles remain unknown. To address this, we developed a computational model to simulate the two mechanisms and their influence on temporal niche. In our model, SCN output is relayed via the subparaventricular zone (SPZ) to the dorsomedial hypothalamus (DMH), and thence to ventrolateral preoptic nuclei (VLPO) and lateral hypothalamus (LHA). Using this model, we generated rich phenotypes that closely resemble experimental data. Modulation of SCN output at the SPZ was found to generate a full spectrum of diurnal-to-nocturnal phenotypes. Intriguingly, we also uncovered a novel mechanism for crepuscular behavior: if DMH/VLPO and DMH/LHA projections act cooperatively, daily activity is unimodal, but if they act competitively, activity can become bimodal. In addition, we successfully reproduced diurnal/nocturnal switching in the rodent Octodon degu using coordinated inversions in both masking and circadian modulation. Finally, the model correctly predicted the SCN lesion phenotype in squirrel monkeys: loss of circadian rhythmicity and emergence of ∼4-h sleep/wake cycles. In capturing these diverse phenotypes, the model provides a powerful new framework for understanding rest/activity patterns and relating them to underlying physiology. Given the ubiquitous effects of temporal organization on all aspects of animal behavior and physiology, this study sheds light on the physiological

  17. 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.

  18. Pleistocene paleoenvironmental reconstructions and mammalian evolution in South-East Asia: focus on fossil faunas from Thailand

    NASA Astrophysics Data System (ADS)

    Tougard, C.; Montuire, S.

    2006-01-01

    Mammalian faunal studies have provided various clues for a better reconstruction of hominid Quaternary paleoenvironments. In this work, two methods were used: (1) the cenogram method, based on a graphical representation of the mammalian community structure, and (2) the species richness of murine rodents to estimate climatic parameters. These methods were applied to Middle and Late Pleistocene mammalian faunas of South-East Asia, from South China to Indonesia. Special emphasis was laid on a fauna from north-east Thailand dated back to approximately 170,000 years (i.e. a glacial period). This Thai fauna seems characteristic of a slightly open forested environment intermediate between those of present-day central Myanmar and the northern part of South China. In the Thai fauna, the occurrence of both cool-loving mammalian taxa, currently living further north, and species of larger body size than their living counterparts, indicates cooler and probably drier climatic conditions than present-day climates in Thailand. These results are quite consistent with Middle Pleistocene palynological records from South China and eastern Java. From other less well-documented Pleistocene faunas, taken into account in this work, humid climatic conditions of interglacial periods were revealed from large mammalian taxa.

  19. Redox regulation of mammalian sperm capacitation

    PubMed Central

    O’Flaherty, Cristian

    2015-01-01

    Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility. PMID:25926608

  20. The Mammalian Ovary from Genesis to Revelation

    PubMed Central

    Edson, Mark A.; Nagaraja, Ankur K.; Matzuk, Martin M.

    2009-01-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago. PMID:19776209

  1. Production of small RNAs by mammalian Dicer.

    PubMed

    Svobodova, Eliska; Kubikova, Jana; Svoboda, Petr

    2016-06-01

    MicroRNA (miRNA) and RNA interference (RNAi) pathways employ RNase III Dicer for the biogenesis of small RNAs guiding post-transcriptional repression. Requirements for Dicer activity differ in the two pathways. The biogenesis of miRNAs requires a single Dicer cleavage of a short hairpin precursor to produce a small RNA with a precisely defined sequence, while small RNAs in RNAi come from a processive cleavage of a long double-stranded RNA (dsRNA) into a pool of small RNAs with different sequences. While Dicer is generally conserved among eukaryotes, its substrate recognition, cleavage, and biological roles differ. In Metazoa, a single Dicer can function as a universal factor for RNAi and miRNA pathways or as a factor adapted specifically for one of the pathways. In this review, we focus on the structure, function, and evolution of mammalian Dicer. We discuss key structural features of Dicer and other factors defining Dicer substrate repertoire and biological functions in mammals in comparison with invertebrate models. The key for adaptation of Dicer for miRNA or RNAi pathways is the N-terminal helicase, a dynamically evolving Dicer domain. Its functionality differs between mammals and invertebrates: the mammalian Dicer is well adapted to produce miRNAs while its ability to support RNAi is limited. PMID:27048428

  2. Ballistic transfection of mammalian cells in vivo

    SciTech Connect

    Kolesnikov, V.A.; Zelenin, A.V.; Zelenina, I.A.

    1995-11-01

    The method of ballistic transfection initially proposed for genetic transformation of plants was used for animal cells in vitro and in situ. The method consists in bombarding the transfected cells with microparticles of heavy metals carrying foreign DNA. Penetrating the cell nucleus, the microparticles transport the introduced gene. Successful genetic transformation of the cultured mouse cells and fish embryos was realized, and this allowed the study of mammalian cells in situ. The performed studies allowed us to demonstrate expression of the reporter genes of chloramphenicol acetyltransferase, galactosidase, and neomycin phosphotransferase in the mouse liver, mammary gland and kidney explants, in the liver and cross-striated muscle of mouse and rat in situ, and in developing mouse embryos at the stages of two-cell embryo, morula, and blastocyst. All these genes were introduced by ballistic transfection. In the liver and cross-striated muscle the transgene activity was detected within two to three months after transfection. Thus, the ballistic introduction of the foreign genes in the cells in situ was demonstrated, and this opens possibilities for the use of this method in gene therapy. Methodical aspects of the bombarding and transfection are considered in detail, and the published data on transfection and genetic transformation of mammalian cells are discussed. 41 refs., 13 figs., 1 tab.

  3. An Adaptive Threshold in Mammalian Neocortical Evolution

    PubMed Central

    Kalinka, Alex T.; Tomancak, Pavel; Huttner, Wieland B.

    2014-01-01

    Expansion of the neocortex is a hallmark of human evolution. However, determining which adaptive mechanisms facilitated its expansion remains an open question. Here we show, using the gyrencephaly index (GI) and other physiological and life-history data for 102 mammalian species, that gyrencephaly is an ancestral mammalian trait. We find that variation in GI does not evolve linearly across species, but that mammals constitute two principal groups above and below a GI threshold value of 1.5, approximately equal to 109 neurons, which may be characterized by distinct constellations of physiological and life-history traits. By integrating data on neurogenic period, neuroepithelial founder pool size, cell-cycle length, progenitor-type abundances, and cortical neuron number into discrete mathematical models, we identify symmetric proliferative divisions of basal progenitors in the subventricular zone of the developing neocortex as evolutionarily necessary for generating a 14-fold increase in daily prenatal neuron production, traversal of the GI threshold, and thus establishment of two principal groups. We conclude that, despite considerable neuroanatomical differences, changes in the length of the neurogenic period alone, rather than any novel neurogenic progenitor lineage, are sufficient to explain differences in neuron number and neocortical size between species within the same principal group. PMID:25405475

  4. 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

  5. Catabolic flexibility of mammalian-associated lactobacilli

    PubMed Central

    2013-01-01

    Metabolic flexibility may be generally defined as “the capacity for the organism to adapt fuel oxidation to fuel availability”. The metabolic diversification strategies used by individual bacteria vary greatly from the use of novel or acquired enzymes to the use of plasmid-localised genes and transporters. In this review, we describe the ability of lactobacilli to utilise a variety of carbon sources from their current or new environments in order to grow and survive. The genus Lactobacillus now includes more than 150 species, many with adaptive capabilities, broad metabolic capacity and species/strain variance. They are therefore, an informative example of a cell factory capable of adapting to new niches with differing nutritional landscapes. Indeed, lactobacilli naturally colonise and grow in a wide variety of environmental niches which include the roots and foliage of plants, silage, various fermented foods and beverages, the human vagina and the mammalian gastrointestinal tract (GIT; including the mouth, stomach, small intestine and large intestine). Here we primarily describe the metabolic flexibility of some lactobacilli isolated from the mammalian gastrointestinal tract, and we also describe some of the food-associated species with a proven ability to adapt to the GIT. As examples this review concentrates on the following species - Lb. plantarum, Lb. acidophilus, Lb. ruminis, Lb. salivarius, Lb. reuteri and Lb. sakei, to highlight the diversity and inter-relationships between the catabolic nature of species within the genus. PMID:23680304

  6. Catabolic flexibility of mammalian-associated lactobacilli.

    PubMed

    O'Donnell, Michelle M; O'Toole, Paul W; Ross, Reynolds Paul

    2013-01-01

    Metabolic flexibility may be generally defined as "the capacity for the organism to adapt fuel oxidation to fuel availability". The metabolic diversification strategies used by individual bacteria vary greatly from the use of novel or acquired enzymes to the use of plasmid-localised genes and transporters. In this review, we describe the ability of lactobacilli to utilise a variety of carbon sources from their current or new environments in order to grow and survive. The genus Lactobacillus now includes more than 150 species, many with adaptive capabilities, broad metabolic capacity and species/strain variance. They are therefore, an informative example of a cell factory capable of adapting to new niches with differing nutritional landscapes. Indeed, lactobacilli naturally colonise and grow in a wide variety of environmental niches which include the roots and foliage of plants, silage, various fermented foods and beverages, the human vagina and the mammalian gastrointestinal tract (GIT; including the mouth, stomach, small intestine and large intestine). Here we primarily describe the metabolic flexibility of some lactobacilli isolated from the mammalian gastrointestinal tract, and we also describe some of the food-associated species with a proven ability to adapt to the GIT. As examples this review concentrates on the following species - Lb. plantarum, Lb. acidophilus, Lb. ruminis, Lb. salivarius, Lb. reuteri and Lb. sakei, to highlight the diversity and inter-relationships between the catabolic nature of species within the genus. PMID:23680304

  7. Ecological adaptation determines functional mammalian olfactory subgenomes

    PubMed Central

    Hayden, Sara; Bekaert, Michaël; Crider, Tess A.; Mariani, Stefano; Murphy, William J.; Teeling, Emma C.

    2010-01-01

    The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes. Although these genes are well annotated in the finished human and mouse genomes, we still do not understand which receptors bind specific odorants or how they fully function. Previous comparative studies have been taxonomically limited and mostly focused on the percentage of OR pseudogenes within species. No study has investigated the adaptive changes of functional OR gene families across phylogenetically and ecologically diverse mammals. To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families and thus the odorants they bind, we compared the functional OR gene repertoires from 50 mammalian genomes. We amplified more than 2000 OR genes in aquatic, semi-aquatic, and flying mammals and coupled these data with 48,000 OR genes from mostly terrestrial mammals, extracted from genomic projects. Phylogenomic, Bayesian assignment, and principle component analyses partitioned species by ecotype (aquatic, semi-aquatic, terrestrial, flying) rather than phylogenetic relatedness, and identified OR families important for each habitat. Functional OR gene repertoires were reduced independently in the multiple origins of aquatic mammals and were significantly divergent in bats. We reject recent neutralist views of olfactory subgenome evolution and correlate specific OR gene families with physiological requirements, a preliminary step toward unraveling the relationship between specific odors and respective OR gene families. PMID:19952139

  8. 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. PMID:10791785

  9. CONDITIONING LESIONS BEFORE OR AFTER SPINAL CORD INJURY RECRUIT BROAD GENETIC MECHANISMS THAT SUSTAIN AXONAL REGENERATION: SUPERIORITY TO CAMP-MEDIATED EFFECTS

    PubMed Central

    Blesch, Armin; Lu, Paul; Tsukada, Shingo; Alto, Laura Taylor; Roet, Kasper; Coppola, Giovanni; Geschwind, Dan; Tuszynski, Mark H.

    2012-01-01

    Previous studies indicate that peripheral nerve conditioning lesions significantly enhance central axonal regeneration via modulation of cAMP-mediated mechanisms. To gain insight into the nature and temporal dependence of neural mechanisms underlying conditioning lesion effects on central axonal regeneration, we compared the efficacy of peripheral sciatic nerve crush lesions to cAMP elevations (in lumbar dorsal root ganglia) on central sensory axonal regeneration when administered either before or after cervical spinal cord lesions. We found significantly greater effects of conditioning lesions compared to cAMP elevations on central axonal regeneration when combined with cellular grafts at the lesion site and viral neurotrophin delivery; further, these effects persisted whether conditioning lesions were applied prior to or shortly after spinal cord injury. Indeed, conditioning lesions recruited extensively greater sets of genetic mechanisms of possible relevance to axonal regeneration compared to cAMP administration, and sustained these changes for significantly greater time periods through the post-lesion period. We conclude that cAMP-mediated mechanisms account for only a portion of the potency of conditioning lesions on central axonal regeneration, and that recruitment of broader genetic mechanisms can extend the effect and duration of cellular events that support axonal growth. PMID:22227059

  10. Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with Mammalian target of rapamycin inhibitors.

    PubMed

    Prato, Giulia; Mancardi, Maria Margherita; Baglietto, Maria Giuseppina; Janis, Sara; Vercellino, Nadia; Rossi, Andrea; Consales, Alessandro; Raso, Alessandro; Garrè, Maria Luisa

    2014-09-01

    Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy. PMID:24056156

  11. Granuloma faciale with extrafacial lesions.

    PubMed

    Rossiello, Luigi; Palla, Marco; Aiello, Francesco Saviero; Baroni, Adone; Satriano, Rocco Alfredo

    2007-01-01

    A 35-year-old man presented with a 7-year history of gradually enlarging plaques on his face and trunk. The first lesions had developed on both sides of the forehead and the left cheekbone (Figure 1). Four years later similar lesions appeared on his neck and back. He presented a histologic report of a biopsy specimen from a facial plaque performed 5 years earlier that was diagnostic for granuloma faciale. He had different treatments such as topical steroids and cryotherapy without improvement. The appearance of new lesions on his trunk and the gradual enlarging of the old lesions convinced the patient to seek further treatment. Physical examination revealed dusky, violaceous plaques and papules, 0.5 to 2 cm, well-circumscribed, slightly elevated, and located on the face and trunk, with mild pruritus (Figure 1 and Figure 2). Laboratory investigations, including complete blood cell count, VDRL test, antinuclear antibody test, biochemical parameters, and chest x-ray, did not reveal any abnormalities. A skin biopsy taken from the upper part of the back showed similar features to the facial lesion, detected 5 years before, revealing a dense, polymorphous infiltrate involving mid and deep dermis and displaying a diffuse and perivascular pattern (Figure 3A). A narrow grenz zone of normal collagen was consistently observed between dermal infiltrate and epidermis as well as around the pilosebaceous follicles (Figure 3A). The infiltrate mainly consisted of eosinophils and lymphocytes, but neutrophils (often displaying leukocytoclasis), macrophages, and plasma cells were also present (Figures 3B, 3C). Some mast cells were also identified by staining with toluidine blue (Figure 3D). Perivascular infiltrates were often seen, sometimes penetrating vessel walls and in association with leukocytoclasis. Hyalinization of vessel walls, extravasation of red blood cells around capillaries, and nuclear dust were also noted. The epidermis did not show any remarkable change except for

  12. Mottled Mice and Non-Mammalian Models of Menkes Disease

    PubMed Central

    Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł; Grzmil, Paweł; Starzyński, Rafał; Pierzchała, Olga; Møller, Lisbeth Birk

    2015-01-01

    Menkes disease is a multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene and characterized by progressive neurodegeneration and severe connective tissue defects. The ATP7A protein is a copper (Cu)-transporting ATPase expressed in all tissues and plays a critical role in the maintenance of copper homeostasis in cells of the whole body. ATP7A participates in copper absorption in the small intestine and in copper transport to the central nervous system (CNS) across the blood-brain-barrier (BBB) and blood–cerebrospinal fluid barrier (BCSFB). Cu is essential for synaptogenesis and axonal development. In cells, ATP7A participates in the incorporation of copper into Cu-dependent enzymes during the course of its maturation in the secretory pathway. There is a high degree of homology (>80%) between the human ATP7A and murine Atp7a genes. Mice with mutations in the Atp7a gene, called mottled mutants, are well-established and excellent models of Menkes disease. Mottled mutants closely recapitulate the Menkes phenotype and are invaluable for studying Cu-metabolism. They provide useful models for exploring and testing new forms of therapy in Menkes disease. Recently, non-mammalian models of Menkes disease, Drosophila melanogaster and Danio rerio mutants were used in experiments which would be technically difficult to carry out in mammals. PMID:26732058

  13. Understanding global patterns of mammalian functional and phylogenetic diversity

    PubMed Central

    Safi, Kamran; Cianciaruso, Marcus V.; Loyola, Rafael D.; Brito, Daniel; Armour-Marshall, Katrina; Diniz-Filho, José Alexandre F.

    2011-01-01

    Documenting and exploring the patterns of diversity of life on Earth has always been a central theme in biology. Species richness despite being the most commonly used measure of diversity in macroecological studies suffers from not considering the evolutionary and ecological differences among species. Phylogenetic diversity (PD) and functional diversity (FD) have been proposed as alternative measures to overcome this limitation. Although species richness, PD and FD are closely related, their relationships have never been investigated on a global scale. Comparing PD and FD with species richness corroborated the general assumptions of surrogacy of the different diversity measures. However, the analysis of the residual variance suggested that the mismatches between the diversity measures are influenced by environmental conditions. PD increased relative to species richness with increasing mean annual temperature, whereas FD decreased with decreasing seasonality relative to PD. We also show that the tropical areas are characterized by a FD deficit, a phenomenon, that suggests that in tropical areas more species can be packed into the ecological space. We discuss potential mechanisms that could have resulted in the gradient of spatial mismatch observed in the different biodiversity measures and draw parallels to local scale studies. We conclude that the use of multiple diversity measures on a global scale can help to elucidate the relative importance of historical and ecological processes shaping the present gradients in mammalian diversity. PMID:21807734

  14. Mammalian cadherins DCHS1-FAT4 affect functional cerebral architecture.

    PubMed

    Beste, Christian; Ocklenburg, Sebastian; von der Hagen, Maja; Di Donato, Nataliya

    2016-06-01

    Cortical development is a complex process where a multitude of factors, including cadherins, plays an important role and where disruptions are known to have far reaching effects in neural development and cortical patterning. Cadherins play a central role in structural left-right differentiation during brain and body development, but their effect on a functional level remains elusive. We addressed this question by examining functional cerebral asymmetries in a patient with Van Maldergem Syndrome (VMS) (MIM#601390), which is caused by mutations in DCHS1-FAT4 cadherins, using a dichotic listening task. Using neurophysiological (EEG) data, we show that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. Basic perceptual processing of biaurally presented auditory stimuli was unaffected. This suggests that the strength and emergence of functional cerebral asymmetries is a direct function of proliferation and differentiation of neuronal stem cells. Moreover, these results support the recent assumption that the molecular mechanisms establishing early left-right differentiation are an important factor in the ontogenesis of functional lateralization. PMID:25930014

  15. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    PubMed

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-10-01

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization. PMID:26384869

  16. Microbial community profiling shows dysbiosis in the lesional skin of Vitiligo subjects.

    PubMed

    Ganju, Parul; Nagpal, Sunil; Mohammed, M H; Nishal Kumar, P; Pandey, Rajesh; Natarajan, Vivek T; Mande, Sharmila S; Gokhale, Rajesh S

    2016-01-01

    Healthy human skin harbours a diverse array of microbes that comprise the skin microbiome. Commensal bacteria constitute an important component of resident microbiome and are intricately linked to skin health. Recent studies describe an association between altered skin microbial community and epidemiology of diseases, like psoriasis, atopic dermatitis etc. In this study, we compare the differences in bacterial community of lesional and non-lesional skin of vitiligo subjects. Our study reveals dysbiosis in the diversity of microbial community structure in lesional skin of vitiligo subjects. Although individual specific signature is dominant over the vitiligo-specific microbiota, a clear decrease in taxonomic richness and evenness can be noted in lesional patches. Investigation of community specific correlation networks reveals distinctive pattern of interactions between resident bacterial populations of the two sites (lesional and non-lesional). While Actinobacterial species constitute the central regulatory nodes (w.r.t. degree of interaction) in non-lesional skin, species belonging to Firmicutes dominate on lesional sites. We propose that the changes in taxonomic characteristics of vitiligo lesions, as revealed by our study, could play a crucial role in altering the maintenance and severity of disease. Future studies would elucidate mechanistic relevance of these microbial dynamics that can provide new avenues for therapeutic interventions. PMID:26758568

  17. Microbial community profiling shows dysbiosis in the lesional skin of Vitiligo subjects

    PubMed Central

    Ganju, Parul; Nagpal, Sunil; Mohammed, MH; Nishal Kumar, P; Pandey, Rajesh; Natarajan, Vivek T; Mande, Sharmila S.; Gokhale, Rajesh S.

    2016-01-01

    Healthy human skin harbours a diverse array of microbes that comprise the skin microbiome. Commensal bacteria constitute an important component of resident microbiome and are intricately linked to skin health. Recent studies describe an association between altered skin microbial community and epidemiology of diseases, like psoriasis, atopic dermatitis etc. In this study, we compare the differences in bacterial community of lesional and non-lesional skin of vitiligo subjects. Our study reveals dysbiosis in the diversity of microbial community structure in lesional skin of vitiligo subjects. Although individual specific signature is dominant over the vitiligo-specific microbiota, a clear decrease in taxonomic richness and evenness can be noted in lesional patches. Investigation of community specific correlation networks reveals distinctive pattern of interactions between resident bacterial populations of the two sites (lesional and non-lesional). While Actinobacterial species constitute the central regulatory nodes (w.r.t. degree of interaction) in non-lesional skin, species belonging to Firmicutes dominate on lesional sites. We propose that the changes in taxonomic characteristics of vitiligo lesions, as revealed by our study, could play a crucial role in altering the maintenance and severity of disease. Future studies would elucidate mechanistic relevance of these microbial dynamics that can provide new avenues for therapeutic interventions. PMID:26758568

  18. 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. PMID:27002924

  19. Brain lesions affect penile reflexes.

    PubMed

    Monaghan, E P; Arjomand, J; Breedlove, S M

    1993-03-01

    Electrolytic lesions of several potential brain afferents to the spinal nucleus of the bulbocavernosus (SNB) affect the display of penile reflexes. Ablation of the median and pontine raphe areas significantly potentiates the expression of cups and flips. Animals with a bilateral lesion of the paraventricular nucleus of the hypothalamus have a shorter latency to the first erection but otherwise display normal reflex behavior. Although bilateral destruction of the lateral vestibular nucleus (LVN) completely eliminated penile reflex activity, it also caused significant motor impairment thus clouding conclusions concerning the normal role of the LVN in penile reflex behavior. These and other results support the hypothesis that these brain regions which project to the SNB region normally modulate spinal reflex behavior of the rat penis. PMID:8440513

  20. Cytologic diagnosis of pulmonary lesions.

    PubMed

    Rossi, Esther Diana; Mulè, Antonino; Maggiore, Claudia; Miraglia, Antonella; Lauriola, Libero; Vecchio, Fabio Maria; Fadda, Guido

    2004-01-01

    The major types of cytologic preparations used in most laboratories to detect the lesions of the lower respiratory tract (LRT) are examined. These methods include sputum, bronchial washing, bronchial brushing, bronchoalveolar lavage (BAL) and fine-needle aspiration biopsy (FNAB). Sputum represents the simplest and most cost-effective sampling method even though fiberoptic bronchoscopy and radiologic guided FNAB are superseding it as the first diagnostic choice in most cases. There are advantages and disadvantages associated with each technique:bronchial brushing and FNABs tend to preserve both the cellular details and their architectural arrangement whereas sputum and bronchial washing often cause a variable degree of cellular degeneration and fragmentation. As a result, most pulmonary lesions may be detected and correctly diagnosed if multiple techniques are used to acquire diagnostic material. CT-guided FNAB represents the most effective method to achieve a correct diagnosis in pulmonary tumors. PMID:15852720

  1. Are parenchymal AVMs congenital lesions?

    PubMed

    Morales-Valero, Saul F; Bortolotti, Carlo; Sturiale, Carmelo; Sturiale, Carmelo L; Lanzino, Giuseppe

    2014-09-01

    A long-held dogma in neurosurgery is that parenchymal arteriovenous malformations (AVMs) are congenital. However, there is no strong evidence supporting this theory. An increasing number of documented cases of de novo formation of parenchymal AVMs cast doubt on their congenital nature and suggest that indeed the majority of these lesions may form after birth. Further evidence suggesting the postnatal development of parenchymal AVMs comes from the exceedingly rare diagnosis of these lesions in utero despite the widespread availability of high-resolution imaging modalities such as ultrasound and fetal MRI. The exact mechanism of AVM formation has yet to be elucidated, but most likely involves genetic susceptibility and environmental triggering factors. In this review, the authors report 2 cases of de novo AVM formation and analyze the evidence suggesting that they represent an acquired condition. PMID:25175439

  2. Damage and repair of irradiated mammalian brain

    SciTech Connect

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K.; Stanford Univ., CA . Medical Center; Brookside Hospital, San Pablo, CA )

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

  3. Genome size evolution: sizing mammalian genomes.

    PubMed

    Redi, C A; Capanna, E

    2012-01-01

    The study of genome size (GS) and its variation is so fascinating to the scientific community because it constitutes the link between the present-day analytical and molecular studies of the genome and the old trunk of the holistic and synthetic view of the genome. The GS of several taxa vary over a broad range and do not correlate with the complexity of the organisms (the C-value paradox). However, the biology of transposable elements has let us reach a satisfactory view of the molecular mechanisms that give rise to GS variation and novelties, providing a less perplexing view of the significance of the GS (C-enigma). The knowledge of the composition and structure of a genome is a pre-requisite for trying to understand the evolution of the main genome signature: its size. The radiation of mammals provides an approximately 180-million-year test case for theories of how GS evolves. It has been found from data-mining GS databases that GS is a useful cyto-taxonomical instrument at the level of orders/superorders, providing genomic signatures characterizing Monotremata, Marsupialia, Afrotheria, Xenarthra, Laurasiatheria, and Euarchontoglires. A hypothetical ancestral mammalian-like GS of 2.9-3.7 pg has been suggested. This value appears compatible with the average values calculated for the high systematic levels of the extant Monotremata (∼2.97 pg) and Marsupialia (∼4.07 pg), suggesting invasion of mobile DNA elements concurrently with the separation of the older clades of Afrotheria (∼5.5 pg) and Xenarthra (∼4.5 pg) with larger GS, leaving the Euarchontoglires (∼3.4 pg) and Laurasiatheria (∼2.8 pg) genomes with fewer transposable elements. However, the paucity of GS data (546 mammalian species sized from 5,488 living species) for species, genera, and families calls for caution. Considering that mammalian species may be vanished even before they are known, GS data are sorely needed to phenotype the effects brought about by their variation and to validate any

  4. Lymphoproliferative lesions of the skin

    PubMed Central

    Cerroni, L

    2006-01-01

    Diagnosis and differential diagnosis of cutaneous lymphoproliferative disorders is one of the most difficult areas in dermatopathology, and biopsies are often taken to rule out a cutaneous lymphoma in patients with “unclear” or “therapy‐resistant” skin lesions. Histopathological features alone often enable a given case to be classified to a diagnostic group (eg, epidermotropic lymphomas), but seldom allow a definitive diagnosis to be made. Performing several biopsies from morphologically different lesions is suggested, especially in patients with suspicion of mycosis fungoides. Immunohistochemistry is often crucial for proper classification of the cases, but in some instances is not helpful (eg, early lesions of mycosis fungoides). Although molecular techniques provide new, powerful tools for diagnosing cutaneous lymphoproliferative disorders, results of molecular methods should always be interpreted with the clinicopathological features, keeping in mind the possibility of false positivity and false negativity. In many cases, a definitive diagnosis can be made only on careful correlation of the clinical with the histopathological, immunophenotypical and molecular features. PMID:16873563

  5. Imaging of skull base lesions.

    PubMed

    Kelly, Hillary R; Curtin, Hugh D

    2016-01-01

    Skull base imaging requires a thorough knowledge of the complex anatomy of this region, including the numerous fissures and foramina and the major neurovascular structures that traverse them. Computed tomography (CT) and magnetic resonance imaging (MRI) play complementary roles in imaging of the skull base. MR is the preferred modality for evaluation of the soft tissues, the cranial nerves, and the medullary spaces of bone, while CT is preferred for demonstrating thin cortical bone structure. The anatomic location and origin of a lesion as well as the specific CT and MR findings can often narrow the differential diagnosis to a short list of possibilities. However, the primary role of the imaging specialist in evaluating the skull base is usually to define the extent of the lesion and determine its relationship to vital neurovascular structures. Technologic advances in imaging and radiation therapy, as well as surgical technique, have allowed for more aggressive approaches and improved outcomes, further emphasizing the importance of precise preoperative mapping of skull base lesions via imaging. Tumors arising from and affecting the cranial nerves at the skull base are considered here. PMID:27432686

  6. Eye lesions in pet birds.

    PubMed

    Tsai, S S; Park, J H; Hirai, K; Itakura, C

    1993-03-01

    Amongst eye lesions in birds that died in quarantine, cataracts were the most common disorders (37/241, 15.4%), being prevalent in the annular pads of cockatiels (Nymphicus hollandicus), Amazon parrots (Amazona aestiva aestiva) and budgerigars (Melopsittacus undulatus). The incidence in male birds was more than twice that in females. Deposition of crystals, mostly in the cornea, was the second most frequent lesion (21/293, 8.7%), mainly found in cockatiels, parakeets (Psittacula krameri manillensis), Amazon parrots (Amazona aestiva aestiva), budgerigars and finches (Poephila gouldiae gouldiae). These corneal crystals were negative to PAS and Kossa's stains. Six parakeets (Psittacula krameri manillensis) had calcium salts deposited in the inner plexiform layer of the retina and occasionally in the iris and ciliary body. Neither inflammation nor neo-vascularization was observed when cataracts, corneal crystalline deposition, and retinal and ciliary calcification were present. Intranuclear inclusion bodies typical for papovavirus infection were found in the eyelids of six budgerigars (2.5%). Similar inclusions were simultaneously found in the pars ciliaris retinae (4, 1.7%), inner plexiform of retina (1, 0.4%) and anterior epithelium of the cornea (1, 0.4%). Other lesions such as candidial endophthalmitis, conjunctival cryptosporidiosis, corneal dystrophy, keratitis, corneal perforation and iridocyclitis, were occasional findings. PMID:18671000

  7. [Infected lesions of diabetic foot].

    PubMed

    Vitale, Mario; Zeppa, Pio; Esposito, Isabella; Esposito, Silvano

    2012-01-01

    The diabetic foot lesions are the result of a complex set of factors including peripheral neuropathy, trauma, joint deformities and perfusion abnormalities. The foot becomes vulnerable and insensitive to minor injuries caused by excessive pressure, mechanically or minimum thermal insults that can determine the primum movens of a foot ulcer. Due to the trauma, the subcutaneous tissues are exposed to bacterial colonization. Therefore, the wound can develop an infection. So, the first step in the treatment of the lesion is the evaluation of tissue damage, in order to guide therapy and prognosis. Wagner's classification, used by over 25 years, is still one of the best known systems of lesion classification; however, it is giving way to the most recent Texas's classification. However, in both systems infection have a minority role. Therefore, the Infectious Diseases Society of America has developed a classification system that divides infections in mild, moderate and severe. The purpose of this classification is to recognize the severe patients because they require immediate hospitalization, parenteral antibiotic therapy and specific instrumental examinations. PMID:22982693

  8. Automatic segmentation of psoriasis lesions

    NASA Astrophysics Data System (ADS)

    Ning, Yang; Shi, Chenbo; Wang, Li; Shu, Chang

    2014-10-01

    The automatic segmentation of psoriatic lesions is widely researched these years. It is an important step in Computer-aid methods of calculating PASI for estimation of lesions. Currently those algorithms can only handle single erythema or only deal with scaling segmentation. In practice, scaling and erythema are often mixed together. In order to get the segmentation of lesions area - this paper proposes an algorithm based on Random forests with color and texture features. The algorithm has three steps. The first step, the polarized light is applied based on the skin's Tyndall-effect in the imaging to eliminate the reflection and Lab color space are used for fitting the human perception. The second step, sliding window and its sub windows are used to get textural feature and color feature. In this step, a feature of image roughness has been defined, so that scaling can be easily separated from normal skin. In the end, Random forests will be used to ensure the generalization ability of the algorithm. This algorithm can give reliable segmentation results even the image has different lighting conditions, skin types. In the data set offered by Union Hospital, more than 90% images can be segmented accurately.

  9. 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.

  10. Diving into the Ice Bucket Challenge: Intraparenchymal Hemorrhage and the Mammalian Diving Reflex.

    PubMed

    McKee, Kathleen; Nelson, Sarah; Batra, Ayush; Klein, Joshua P; Henderson, Galen V

    2015-07-01

    Triggered by facial exposure to cold water and apnea, the mammalian diving reflex consists of bradycardia and peripheral arteriolar vasoconstriction leading to an increase in central arterial pressure. It has been previously associated with ischemic stroke but not definitively with intracerebral hemorrhage. We present a case of intracerebral hemorrhage occurring in a woman with poorly controlled hypertension following her participation in the amyotrophic lateral sclerosis fund-raising "Ice Bucket Challenge," in which ice-cold water was poured on her head. We suspect that facial exposure to ice-cold water triggered the diving reflex, causing a hypertensive surge and ultimately the intracerebral hemorrhage. PMID:26288676

  11. Systematic Review of Central Post Stroke Pain: What Is Happening in the Central Nervous System?

    PubMed

    Akyuz, Gulseren; Kuru, Pinar

    2016-08-01

    Central poststroke pain (CPSP) is one of the most common central neuropathic pain syndromes seen after stroke. It is mainly related with vascular damage at certain brain territory and pain related to corresponding body areas. In the past, it was described as one of the definitive symptoms of thalamic lesion. However, recent findings suggest that it is not only seen after thalamic lesions but also seen after vascular lesions in any part of the central nervous system. Although there are certain hypotheses to explain physiopathologic mechanisms of CPSP, further evidence is needed. The majority of the cases are intractable and unresponsive to analgesic treatment. Electrical stimulation such as deep brain stimulation and repetitive transcranial magnetic stimulation seems to be effective in certain cases. In this systematic review, recent advancements related to CPSP mechanisms have been evaluated. Further investigations are needed in order to reveal the mystery of the pathophysiologic mechanisms of CPSP. PMID:27175563

  12. Chemical analysis of individual mammalian cells

    SciTech Connect

    Tan, W.; Yeung, E.S.

    1994-12-31

    The extremely small size of mammalian cells creates an unusual challenge for the analytical chemist, both in terms of separation and detection. Under a microscope, it is possible to confirm the injection of individual cells such as erythrocyte into capillaries with 10-{mu}m i.d. by hydrostatic pressure. The ionic contents can then be separated by capillary electrophoresis after the cell lyses. Enzymes at the zeptomole level can be monitored by on-column fluorescence enzyme assay. On-column particle-counting immunoassay can be applied to a broad range of analytes (antigens), also at the zeptomole level. The authors report here the simultaneous determination of the amounts of glucose-6-phosphate dehydrogenase (G6PDH) and their activities in individual erythrocytes by using a combination of the two detection schemes. Insights into the degradation of proteins as a function of cell age can be derived.

  13. Crystal structure of mammalian acid sphingomyelinase.

    PubMed

    Gorelik, Alexei; Illes, Katalin; Heinz, Leonhard X; Superti-Furga, Giulio; Nagar, Bhushan

    2016-01-01

    Acid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann-Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site. Strikingly, the membrane interacting saposin domain assumes either a closed globular conformation independent from the catalytic domain, or an open conformation, which establishes an interface with the catalytic domain essential for activity. Structural mapping of Niemann-Pick mutations reveals that most of them likely destabilize the protein's fold. This study sheds light on the molecular mechanism of ASMase function, and provides a platform for the rational development of ASMase inhibitors and therapeutic use of recombinant ASMase. PMID:27435900

  14. Crystal structure of mammalian acid sphingomyelinase

    PubMed Central

    Gorelik, Alexei; Illes, Katalin; Heinz, Leonhard X.; Superti-Furga, Giulio; Nagar, Bhushan

    2016-01-01

    Acid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann–Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site. Strikingly, the membrane interacting saposin domain assumes either a closed globular conformation independent from the catalytic domain, or an open conformation, which establishes an interface with the catalytic domain essential for activity. Structural mapping of Niemann–Pick mutations reveals that most of them likely destabilize the protein's fold. This study sheds light on the molecular mechanism of ASMase function, and provides a platform for the rational development of ASMase inhibitors and therapeutic use of recombinant ASMase. PMID:27435900

  15. Hysteresis in a synthetic mammalian gene network.

    PubMed

    Kramer, Beat P; Fussenegger, Martin

    2005-07-01

    Bistable and hysteretic switches, enabling cells to adopt multiple internal expression states in response to a single external input signal, have a pivotal impact on biological systems, ranging from cell-fate decisions to cell-cycle control. We have designed a synthetic hysteretic mammalian transcription network. A positive feedback loop, consisting of a transgene and transactivator (TA) cotranscribed by TA's cognate promoter, is repressed by constitutive expression of a macrolide-dependent transcriptional silencer, whose activity is modulated by the macrolide antibiotic erythromycin. The antibiotic concentration, at which a quasi-discontinuous switch of transgene expression occurs, depends on the history of the synthetic transcription circuitry. If the network components are imbalanced, a graded rather than a quasi-discontinuous signal integration takes place. These findings are consistent with a mathematical model. Synthetic gene networks, which are able to emulate natural gene expression behavior, may foster progress in future gene therapy and tissue engineering initiatives. PMID:15972812

  16. Nomenclature for mammalian soluble glutathione transferases.

    PubMed

    Mannervik, Bengt; Board, Philip G; Hayes, John D; Listowsky, Irving; Pearson, William R

    2005-01-01

    The nomenclature for human soluble glutathione transferases (GSTs) is extended to include new members of the GST superfamily that have been discovered, sequenced, and shown to be expressed. The GST nomenclature is based on primary structure similarities and the division of GSTs into classes of more closely related sequences. The classes are designated by the names of the Greek letters: Alpha, Mu, Pi, etc., abbreviated in Roman capitals: A, M, P, and so on. (The Greek characters should not be used.) Class members are distinguished by Arabic numerals and the native dimeric protein structures are named according to their subunit composition (e.g., GST A1-2 is the enzyme composed of subunits 1 and 2 in the Alpha class). Soluble GSTs from other mammalian species can be classified in the same manner as the human enzymes, and this chapter presents the application of the nomenclature to the rat and mouse GSTs. PMID:16399376

  17. Trapping mammalian protein complexes in viral particles

    PubMed Central

    Eyckerman, Sven; Titeca, Kevin; Van Quickelberghe, Emmy; Cloots, Eva; Verhee, Annick; Samyn, Noortje; De Ceuninck, Leentje; Timmerman, Evy; De Sutter, Delphine; Lievens, Sam; Van Calenbergh, Serge; Gevaert, Kris; Tavernier, Jan

    2016-01-01

    Cell lysis is an inevitable step in classical mass spectrometry–based strategies to analyse protein complexes. Complementary lysis conditions, in situ cross-linking strategies and proximal labelling techniques are currently used to reduce lysis effects on the protein complex. We have developed Virotrap, a viral particle sorting approach that obviates the need for cell homogenization and preserves the protein complexes during purification. By fusing a bait protein to the HIV-1 GAG protein, we show that interaction partners become trapped within virus-like particles (VLPs) that bud from mammalian cells. Using an efficient VLP enrichment protocol, Virotrap allows the detection of known binary interactions and MS-based identification of novel protein partners as well. In addition, we show the identification of stimulus-dependent interactions and demonstrate trapping of protein partners for small molecules. Virotrap constitutes an elegant complementary approach to the arsenal of methods to study protein complexes. PMID:27122307

  18. Fundamentals of Expression in Mammalian Cells.

    PubMed

    Dyson, Michael R

    2016-01-01

    Expression of proteins in mammalian cells is a key technology important for many functional studies on human and higher eukaryotic genes. Studies include the mapping of protein interactions, solving protein structure by crystallization and X-ray diffraction or solution phase NMR and the generation of antibodies to enable a range of studies to be performed including protein detection in vivo. In addition the production of therapeutic proteins and antibodies, now a multi billion dollar industry, has driven major advances in cell line engineering for the production of grams per liter of active proteins and antibodies. Here the key factors that need to be considered for successful expression in HEK293 and CHO cells are reviewed including host cells, expression vector design, transient transfection methods, stable cell line generation and cultivation conditions. PMID:27165328

  19. Mammalian telomeres and their partnership with lamins

    PubMed Central

    Burla, Romina; La Torre, Mattia; Saggio, Isabella

    2016-01-01

    ABSTRACT Chromosome ends are complex structures, which require a panel of factors for their elongation, replication, and protection. We describe here the mechanics of mammalian telomeres, dynamics and maintainance in relation to lamins. Multiple biochemical connections, including association of telomeres to the nuclear envelope and matrix, of telomeric proteins to lamins, and of lamin-associated proteins to chromosome ends, underline the interplay between lamins and telomeres. Paths toward senescence, such as defective telomere replication, altered heterochromatin organization, and impaired DNA repair, are common to lamins' and telomeres' dysfunction. The convergence of phenotypes can be interpreted through a model of dynamic, lamin-controlled functional platforms dedicated to the function of telomeres as fragile sites. The features of telomeropathies and laminopathies, and of animal models underline further overlapping aspects, including the alteration of stem cell compartments. We expect that future studies of basic biology and on aging will benefit from the analysis of this telomere-lamina interplay. PMID:27116558

  20. Global Epigenomic Reconfiguration During Mammalian Brain Development

    PubMed Central

    Nery, Joseph R.; Urich, Mark; Puddifoot, Clare A.; Johnson, Nicholas D.; Lucero, Jacinta; Huang, Yun; Dwork, Andrew J.; Schultz, Matthew D.; Yu, Miao; Tonti-Filippini, Julian; Heyn, Holger; Hu, Shijun; Wu, Joseph C.; Rao, Anjana; Esteller, Manel; He, Chuan; Haghighi, Fatemeh G.; Sejnowski, Terrence J.; Behrens, M. Margarita; Ecker, Joseph R.

    2013-01-01

    DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity. PMID:23828890

  1. New consensus nomenclature for mammalian keratins

    PubMed Central

    Schweizer, Jürgen; Bowden, Paul E.; Coulombe, Pierre A.; Langbein, Lutz; Lane, E. Birgitte; Magin, Thomas M.; Maltais, Lois; Omary, M. Bishr; Parry, David A.D.; Rogers, Michael A.; Wright, Mathew W.

    2006-01-01

    Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human keratins, it offers the flexibility needed to incorporate additional keratins from other mammalian species. PMID:16831889

  2. Cenozoic climate change influences mammalian evolutionary dynamics

    PubMed Central

    Figueirido, Borja; Janis, Christine M.; Pérez-Claros, Juan A.; De Renzi, Miquel; Palmqvist, Paul

    2012-01-01

    Global climate change is having profound impacts on the natural world. However, climate influence on faunal dynamics at macroevolutionary scales remains poorly understood. In this paper we investigate the influence of climate over deep time on the diversity patterns of Cenozoic North American mammals. We use factor analysis to identify temporally correlated assemblages of taxa, or major evolutionary faunas that we can then study in relation to climatic change over the past 65 million years. These taxa can be grouped into six consecutive faunal associations that show some correspondence with the qualitative mammalian chronofaunas of previous workers. We also show that the diversity pattern of most of these chronofaunas can be correlated with the stacked deep-sea benthic foraminiferal oxygen isotope (δ18O) curve, which strongly suggests climatic forcing of faunal dynamics over a large macroevolutionary timescale. This study demonstrates the profound influence of climate on the diversity patterns of North American terrestrial mammals over the Cenozoic. PMID:22203974

  3. Ocular lesions in the Earth Day, 1970, histoplasmosis epidemic.

    PubMed

    Davidorf, F H; Anderson, J D

    1975-01-01

    The relationship between systemic histoplasmosis and this particular clinical picutre of a central choroiditis with peripheral atrophic lesions in the fundus was postulated by Woods in 1960 [19]. Since that time there have been many studies attempting to substantiate his hyptthesis [1, 3-5, 7-18]. In a large study performed in Walkersville, Maryland, which is an area endemic for histoplasmosis [14], the prevalence of the characteristic peripheral histoplasmic lesion in the fundus was 27 per 1000 population. The prevalence was 44 per 1000 population with positive histoplasmosis skin tests. In a similar study done in sothern Ohio, the prevalence of peripheral fundus lesions was 1.6 percent of 1417 patients examined [1]. Several generalizations can be made from the information obtained in studying the students involved in the Willis flu, and these can be compared with information from the control students from Bellingham. First, the acute infection at Willis School did not cause significant ocular abnormalities. This finding is supported by the fact that no significant differences occurred in the fundus lesions seen in the control group of students who lived in the same geographic area but were not clinically ill from histoplasmosis. Our evidence shows that the eyegrounds of the individuals living in this area were different from those of the students who lived outside the central Ohio area. How do we account for the similarity of ocular lesions in the affected students and the Delaware control group? Perhaps by the age of 11 or 12, a person living in the histoplasmosis belt will have already been exposed to histoplasmosis, resulting in the characteristic scars that are seen. If, in fact, histoplasmosis is the etiological agent in the patients who are diagnosed as having presumed ocular histoplasmosis, difficulty arises in understanding why those individuals involved in the epidemic did not have more scars than the control group. Perhaps the numbers of patients

  4. Voltage-gated sodium channels in the mammalian heart

    PubMed Central

    Zimmer, Thomas; Haufe, Volker; Blechschmidt, Steve

    2014-01-01

    Mammalian species express nine functional voltage-gated Na+ channels. Three of them, the cardiac-specific isoform Nav1.5 and the neuronal isoforms Nav1.8 and Nav1.9, are relatively resistant to the neurotoxin tetrodotoxin (TTX; IC50 ≥ 1 μM). The other six isoforms are highly sensitive to TTX with IC50 values in the nanomolar range. These isoforms are expressed in the central nervous system (Nav1.1, Nav1.2, Nav1.3, Nav1.6), in the skeletal muscle (Nav1.4), and in the peripheral nervous system (Nav1.6, Nav1.7). The isoform Nav1.5, encoded by the SCN5A gene, is responsible for the upstroke of the action potential in the heart. Mutations in SCN5A are associated with a variety of life-threatening arrhythmias, like long QT syndrome type 3 (LQT3), Brugada syndrome (BrS) or cardiac conduction disease (CCD). Previous immunohistochemical and electrophysiological assays demonstrated the cardiac expression of neuronal and skeletal muscle Na+ channels in the heart of various mammals, which led to far-reaching speculations on their function. However, when comparing the Na+ channel mRNA patterns in the heart of various mammalian species, only minute quantities of transcripts for TTX-sensitive Na+ channels were detectable in whole pig and human hearts, suggesting that these channels are not involved in cardiac excitation phenomena in higher mammals. This conclusion is strongly supported by the fact that mutations in TTX-sensitive Na+ channels were associated with epilepsy or skeletal muscle diseases, rather than with a pathological cardiac phenotype. Moreover, previous data from TTX-intoxicated animals and from cases of human tetrodotoxication showed that low TTX dosages caused at most little alterations of both the cardiac output and the electrocardiogram. Recently, genome-wide association studies identified SCN10A, the gene encoding Nav1.8, as a determinant of cardiac conduction parameters, and mutations in SCN10A have been associated with BrS. These novel findings opened a

  5. [Vesiculobullous lesions of the oral mucosa].

    PubMed

    Spijkervet, F K; Vissink, A; Raghoebar, G M; van der Waal, I

    2001-06-01

    In general practice, the dentist can be confronted with a vesiculobullous lesion of the oral mucosa. In many cases the lesion can be classified as recurrent herpes labialis, but many other causes can induce a vesiculobullous lesion of the oral mucosa and perioral skin as well. This article gives an overview of the various vesiculous and bullous lesions of the oral mucous membranes. Special attention is given to the possible causes and their treatment. PMID:11441714

  6. [Imaging spinal cord cystic lesions in adults].

    PubMed

    Kremer, S; Bierry, G; Abu Eid, M; Bogorin, A; Koob, M; Zöllner, G; Dietemann, J L

    2007-05-01

    Intrarachidian cystic lesions are frequent, with highly varied causes. They can be classified according to their location into intramedullary cystic lesions and extramedullary cystic lesions. In these two categories, they can then be regrouped according to the tissue from which they develop. MRI is the first-choice examination for the study of the intracanal contents and the differential diagnosis between the various lesions. PMID:17541357

  7. Signal transduction in mammalian oocytes during fertilization.

    PubMed

    Machaty, Zoltan

    2016-01-01

    Mammalian embryo development begins when the fertilizing sperm triggers a series of elevations in the oocyte's intracellular free Ca(2+) concentration. The elevations are the result of repeated release and re-uptake of Ca(2+) stored in the smooth endoplasmic reticulum. Ca(2+) release is primarily mediated by the phosphoinositide signaling system of the oocyte. The system is stimulated when the sperm causes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG); IP3 then binds its receptor on the surface of the endoplasmic reticulum that induces Ca(2+) release. The manner in which the sperm generates IP3, the Ca(2+) mobilizing second messenger, has been the subject of extensive research for a long time. The sperm factor hypothesis has eventually gained general acceptance, according to which it is a molecule from the sperm that diffuses into the ooplasm and stimulates the phosphoinositide cascade. Much evidence now indicates that the sperm-derived factor is phospholipase C-zeta (PLCζ) that cleaves PIP2 and generates IP3, eventually leading to oocyte activation. A recent addition to the candidate sperm factor list is the post-acrosomal sheath WW domain-binding protein (PAWP), whose role at fertilization is currently under debate. Ca(2+) influx across the plasma membrane is also important as, in the absence of extracellular Ca(2+), the oscillations run down prematurely. In pig oocytes, the influx that sustains the oscillations seems to be regulated by the filling status of the stores, whereas in the mouse other mechanisms might be involved. This work summarizes the current understanding of Ca(2+) signaling in mammalian oocytes. PMID:26453398

  8. Roles for learning in mammalian chemosensory responses.

    PubMed

    Griffiths, Philip R; Brennan, Peter A

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". A rich variety of chemosignals have been identified that influence mammalian behaviour, including peptides, proteins and volatiles. Many of these elicit innate effects acting either as pheromones within species or allelochemicals between species. However, even innate pheromonal responses in mammals are not as hard-wired as the original definition of the term would suggest. Many, if not most mammalian pheromonal responses are only elicited in certain behavioural or physiological contexts. Furthermore, certain pheromones are themselves rewarding and act as unconditioned stimuli to link non-pheromonal stimuli to the pheromonal response, via associative learning. The medial amygdala, has emerged as a potential site for this convergence by which learned chemosensory input is able to gain control over innately-driven output circuits. The medial amygdala is also an important site for associating social chemosensory information that enables recognition of conspecifics and heterospecifics by association of their complex chemosensory signatures both within and across olfactory chemosensory systems. Learning can also influence pheromonal responses more directly to adapt them to changing physiological and behavioural context. Neuromodulators such as noradrenaline and oxytocin can plasticise neural circuits to gate transmission of chemosensory information. More recent evidence points to a role for neurogenesis in this adaptation, both at the peripheral level of the sensory neurons and via the incorporation of new neurons into existing olfactory bulb circuits. The emerging picture is of integrated and flexible responses to chemosignals that adapt them to the environmental and physiological context in which they occur. PMID:25200200

  9. Engineered Trehalose Permeable to Mammalian Cells

    PubMed Central

    Abazari, Alireza; Meimetis, Labros G.; Budin, Ghyslain; Bale, Shyam Sundhar; Weissleder, Ralph; Toner, Mehmet

    2015-01-01

    Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre) demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre) and trehalose tetraacetate (4-O-Ac-Tre). Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants) reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies. PMID:26115179

  10. Mechanoaccumulative Elements of the Mammalian Actin Cytoskeleton.

    PubMed

    Schiffhauer, Eric S; Luo, Tianzhi; Mohan, Krithika; Srivastava, Vasudha; Qian, Xuyu; Griffis, Eric R; Iglesias, Pablo A; Robinson, Douglas N

    2016-06-01

    To change shape, divide, form junctions, and migrate, cells reorganize their cytoskeletons in response to changing mechanical environments [1-4]. Actin cytoskeletal elements, including myosin II motors and actin crosslinkers, structurally remodel and activate signaling pathways in response to imposed stresses [5-9]. Recent studies demonstrate the importance of force-dependent structural rearrangement of α-catenin in adherens junctions [10] and vinculin's molecular clutch mechanism in focal adhesions [11]. However, the complete landscape of cytoskeletal mechanoresponsive proteins and the mechanisms by which these elements sense and respond to force remain to be elucidated. To find mechanosensitive elements in mammalian cells, we examined protein relocalization in response to controlled external stresses applied to individual cells. Here, we show that non-muscle myosin II, α-actinin, and filamin accumulate to mechanically stressed regions in cells from diverse lineages. Using reaction-diffusion models for force-sensitive binding, we successfully predicted which mammalian α-actinin and filamin paralogs would be mechanoaccumulative. Furthermore, a "Goldilocks zone" must exist for each protein where the actin-binding affinity must be optimal for accumulation. In addition, we leveraged genetic mutants to gain a molecular understanding of the mechanisms of α-actinin and filamin catch-bonding behavior. Two distinct modes of mechanoaccumulation can be observed: a fast, diffusion-based accumulation and a slower, myosin II-dependent cortical flow phase that acts on proteins with specific binding lifetimes. Finally, we uncovered cell-type- and cell-cycle-stage-specific control of the mechanosensation of myosin IIB, but not myosin IIA or IIC. Overall, these mechanoaccumulative mechanisms drive the cell's response to physical perturbation during proper tissue development and disease. PMID:27185555

  11. 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. PMID:24999056

  12. Modification of N-glycosylation sites allows secretion of bacterial chondroitinase ABC from mammalian cells

    PubMed Central

    Muir, Elizabeth M.; Fyfe, Ian; Gardiner, Sonya; Li, Li; Warren, Philippa; Fawcett, James W.; Keynes, Roger J.; Rogers, John H.

    2010-01-01

    Although many eukaryotic proteins have been secreted by transfected bacterial cells, little is known about how a bacterial protein is treated as it passes through the secretory pathway when expressed in a eukaryotic cell. The eukaryotic N-glycosylation system could interfere with folding and secretion of prokaryotic proteins whose sequence has not been adapted for glycosylation in structurally appropriate locations. Here we show that such interference does indeed occur for chondroitinase ABC from the bacterium Proteus vulgaris, and can be overcome by eliminating potential N-glycosylation sites. Chondroitinase ABC was heavily glycosylated when expressed in mammalian cells or in a mammalian translation system, and this process prevented secretion of functional enzyme. Directed mutagenesis of selected N-glycosylation sites allowed efficient secretion of active chondroitinase. As these proteoglycans are known to inhibit regeneration of axons in the mammalian central nervous system, the modified chondroitinase gene is a potential tool for gene therapy to promote neural regeneration, ultimately in human spinal cord injury. PMID:19900493

  13. MAMMALIAN CELL GENE MUTATION ASSAYS WORKING GROUP REPORT

    EPA Science Inventory

    Mammalian cell gene mutation assays have been used for many years and the diversity of the available systems attests to the varied methods found to grow mammalian dells and detect mutations. s part of the International Workshop on Standardization of Genotoxicity Test Procedures, ...

  14. An Analytical Study of Mammalian Bite Wounds Requiring Inpatient Management

    PubMed Central

    Lee, Young-Geun; Kim, Woo-Kyung

    2013-01-01

    Background Mammalian bite injuries create a public health problem because of their frequency, potential severity, and increasing number. Some researchers have performed fragmentary analyses of bite wounds caused by certain mammalian species. However, little practical information is available concerning serious mammalian bite wounds that require hospitalization and intensive wound management. Therefore, the purpose of this study was to perform a general review of serious mammalian bite wounds. Methods We performed a retrospective review of the medical charts of 68 patients who were referred to our plastic surgery department for the treatment of bite wounds between January 2003 and October 2012. The cases were analyzed according to the species, patient demographics, environmental factors, injury characteristics, and clinical course. Results Among the 68 cases of mammalian bite injury, 58 (85%) were caused by dogs, 8 by humans, and 2 by cats. Most of those bitten by a human and both of those bitten by cats were male. Only one-third of all the patients were children or adolescents. The most frequent site of injury was the face, with 40 cases, followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with secondary intention healing. Sixty-one patients underwent delayed procedures, including delayed direct closure, skin graft, composite graft, and local flap. Conclusions Based on overall findings from our review of the 68 cases of mammalian bites, we suggest practical guidelines for the management of mammalian bite injuries, which could be useful in the treatment of serious mammalian bite wounds. PMID:24286042

  15. 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…

  16. Chemical sensing in mammalian host-bacterial commensal associations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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....

  17. Reduced Anterior Cruciate Ligament Vascularization Is Associated With Chondral Knee Lesions.

    PubMed

    Hetsroni, Iftach; Manor, Amir; Finsterbush, Alex; Lowe, Joseph; Mann, Gideon; Palmanovich, Ezequiel

    2016-07-01

    This study tested the association between periligamentous vascularization of the anterior cruciate ligament (ACL) and the presence of chondral knee lesions via retrospective analysis of prospectively collected data from 702 consecutive knee arthroscopic procedures. In each case, the ACL periligamentous envelope was documented as follows: (1) vascular, where the ACL was covered with blood vessels along its entire length; (2) centrally avascular, where the central third of the ACL was not covered but peripheral vascularized coverage was present; and (3) avascular, where there was no blood vessel coverage of the ACL. Inclusion criteria for the study were as follows: (1) age older than 18 years and (2) normal knee ligament laxity. Univariate analysis and multiple logistic regression were used to test the association between chondral lesions and each of the variables: sex, age, meniscus tear, decreased ACL vascularity, and concomitant chondral lesion in another knee compartment. The cohort included 516 knees. In the univariate analysis, all variables were associated with a chondral lesion, but only older age and decreased ACL vascularity were associated with chondral lesions in each knee compartment. In the regression model, only decreased ACL vascularity was associated with chondral lesions in each knee compartment. For avascular knees, the odds ratio was 2.84 for medial femoral condyle lesions (95% confidence interval, 1.73-4.68; P=.000), 2.44 for lateral femoral condyle lesions (95% confidence interval, 1.19-5.03; P=.015), and 2.48 for patellofemoral lesions (95% confidence interval, 1.55-3.97; P=.000). The findings showed that decreased ACL periligamentous vascularization is associated with chondral lesions of the femoral condyles in knees with preserved ACL laxity. [Orthopedics. 2016; 39(4):e737-e743.]. PMID:27111071

  18. Brain lesion induced by 1319nm laser radiation

    NASA Astrophysics Data System (ADS)

    Yang, Zaifu; Chen, Hongxia; Wang, Jiarui; Chen, Peng; Ma, Ping; Qian, Huanwen

    2010-11-01

    The laser-tissue interaction has not been well defined at the 1319 nm wavelength for brain exposure. The goal of this research effort was to identify the behavioral and histological changes of brain lesion induced by 1319 nm laser. The experiment was performed on China Kunming mice. Unilateral brain lesions were created with a continuous-wave Nd:YAG laser (1319nm). The brain lesions were identified through behavioral observation and histological haematoxylin and eosin (H&E) staining method. The behavior change was observed for a radiant exposure range of 97~773 J/cm2. The histology of the recovery process was identified for radiant exposure of 580 J/cm2. Subjects were sacrificed 1 hour, 1 week, 2 weeks, 3 months, 7 months and 13 months after laser irradiation. Results showed that after laser exposure, behavioral deficits, including kyphosis, tail entasia, or whole body paralysis could be noted right after the animals recovered from anesthesia while gradually disappeared within several days and never recurred again. Histologically, the laser lesion showed a typical architecture dependent on the interval following laser treatment. The central zone of coagulation necrosis is not apparent right after exposure but becomes obvious within several days. The nerotic tissue though may persist for a long time, will finally be completely resorbed. No carbonization granules formed under our exposure condition.

  19. Cutaneous Leishmaniasis: An Overlooked Etiology of Midfacial Destructive Lesions

    PubMed Central

    Alam, Elie; Abbas, Ossama

    2016-01-01

    Background Midline destructive lesions of the face (MDL) have a wide range of etiologies. Cutaneous Leishmaniasis (CL) is rarely reported as a possible cause. Methods Fifteen patients with solitary nasal lesions caused by CL were studied. The clinical data, biopsies/scrapings and PCR were collected/performed. Ridley’s Pattern (RP) and Parasitic Index (PI) were documented. Results Patients’ age ranged from 1 to 60 years including 7 males and 8 females. The duration of the observed lesions ranged from 1 to 18 months. Clinically, the lesions showed 6 patterns varying from dermal erythematous papulonodular with no epidermal changes to destructive erythematous plaque with massive central hemorrhagic crust. The clinical impression ranged from neoplastic to inflammatory processes. RP varied among the cases [RP 3 (n = 6), RP 4 (n = 3), RP 5 (n = 6)]. All cases show low PI [PI 0 (n = 7), PI 1 (n = 6), PI 2 (n = 1), and PI 3 (n = 1)]. Higher PI was noted in the pediatric group [average age 24 years for PI 0–1 vs. 6.5 years for PI 2–3]. Molecular speciation showed Leishmania tropica (n = 13) and Leishmania major (n = 2). All the patients received Meglumine Antimoniate (Glucantine) injections and had initial cure defined as complete scarring and disappearance of inflammatory signs within 3 months. Conclusion Leishmaniasis may cause MDL especially in endemic areas. PCR is instrumental in confirming the diagnosis. MDL caused by CL showed wide spectrum of clinical and microscopic presentation. PMID:26862748

  20. [Histopathology of central nervous system cavernomas].

    PubMed

    Mosnier, J-F; Brunon, J; Nuti, C

    2007-06-01

    Central nervous system cavernomas are vascular malformations, which occur in two circumstances: sporadic forms and familial autosomal dominant forms. The lesion consists of enlarged, closely packed vessels without interposition of brain parenchyma, surrounded by hemosiderin and gliosis, calcified in few cases. In 80% of sporadic forms the lesion is unique, multiple lesions are rare (median: 4). In familial forms the lesions are always multiple. Cavernomas are often associated with other vascular malformations, especially with venous developmental anomalies. The size of cavernomas is variable from 1 mm to several centimeters. About 70% of cases are supratentorial and 30% in the posterior fossa, particularly in the brain stem. Macroscopic and histopathological findings are typical and the diagnostic is generally easy. PMID:17498756

  1. USE OF NON-MAMMALIAN ALTERNATIVE MODELS FOR NEUROTOXICOLOGICAL STUDY

    PubMed Central

    Peterson, Randall T.; Nass, Richard; Boyd, Windy A.; Freedman, Jonathan H.; Dong, Ke; Narahashi, Toshio

    2009-01-01

    The field of neurotoxicology needs to satisfy two opposing demands: the testing of a growing list of chemicals, and resource limitations and ethical concerns associated with testing using traditional mammalian species. National and international government agencies have defined a need to reduce, refine or replace mammalian species in toxicological testing with alternative testing methods and non-mammalian models. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expense and using fewer mammals. Recent advances in genetic technologies and the strong conservation between human and non-mammalian genomes allows for the dissection of the molecular pathways involved in neurotoxicological responses and neurological diseases using genetically tractable organisms. In this review, applications of four non-mammalian species, Zebrafish, cockroach, Drosophila, and Caenorhabditis elegans, in the investigation of neurotoxicology and neurological diseases are presented. PMID:18538410

  2. ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines

    SciTech Connect

    Zask, Arie; Verheijen, Jeroen C.; Curran, Kevin; Kaplan, Joshua; Richard, David J.; Nowak, Pawel; Malwitz, David J.; Brooijmans, Natasja; Bard, Joel; Svenson, Kristine; Lucas, Judy; Toral-Barza, Lourdes; Zhang, Wei-Guo; Hollander, Irwin; Gibbons, James J.; Abraham, Robert T.; Ayral-Kaloustian, Semiramis; Mansour, Tarek S.; Yu, Ker

    2009-09-18

    The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.

  3. Towards regenerating the mammalian heart: challenges in evaluating experimentally induced adult mammalian cardiomyocyte proliferation.

    PubMed

    Zebrowski, David C; Becker, Robert; Engel, Felix B

    2016-05-01

    In recent years, there has been a dramatic increase in research aimed at regenerating the mammalian heart by promoting endogenous cardiomyocyte proliferation. Despite many encouraging successes, it remains unclear if we are any closer to achieving levels of mammalian cardiomyocyte proliferation for regeneration as seen during zebrafish regeneration. Furthermore, current cardiac regenerative approaches do not clarify whether the induced cardiomyocyte proliferation is an epiphenomena or responsible for the observed improvement in cardiac function. Moreover, due to the lack of standardized protocols to determine cardiomyocyte proliferation in vivo, it remains unclear if one mammalian regenerative factor is more effective than another. Here, we discuss current methods to identify and evaluate factors for the induction of cardiomyocyte proliferation and challenges therein. Addressing challenges in evaluating adult cardiomyocyte proliferation will assist in determining 1) which regenerative factors should be pursued in large animal studies; 2) if a particular level of cell cycle regulation presents a better therapeutic target than another (e.g., mitogenic receptors vs. cyclins); and 3) which combinatorial approaches offer the greatest likelihood of success. As more and more regenerative studies come to pass, progress will require a system that not only can evaluate efficacy in an objective manner but can also consolidate observations in a meaningful way. PMID:26921436

  4. Overview of Glutamatergic Dysregulation in Central Pathologies

    PubMed Central

    Miladinovic, Tanya; Nashed, Mina G.; Singh, Gurmit

    2015-01-01

    As the major excitatory neurotransmitter in the mammalian central nervous system, glutamate plays a key role in many central pathologies, including gliomas, psychiatric, neurodevelopmental, and neurodegenerative disorders. Post-mortem and serological studies have implicated glutamatergic dysregulation in these pathologies, and pharmacological modulation of glutamate receptors and transporters has provided further validation for the involvement of glutamate. Furthermore, efforts from genetic, in vitro, and animal studies are actively elucidating the specific glutamatergic mechanisms that contribute to the aetiology of central pathologies. However, details regarding specific mechanisms remain sparse and progress in effectively modulating glutamate to alleviate symptoms or inhibit disease states has been relatively slow. In this report, we review what is currently known about glutamate signalling in central pathologies. We also discuss glutamate’s mediating role in comorbidities, specifically cancer-induced bone pain and depression. PMID:26569330

  5. 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

  6. 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

    2011-01-01

    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

  7. Skin lesions: mirror images of oral lesion infections.

    PubMed

    Phanuphak, N

    2006-01-01

    Skin lesions can be the presenting signs for HIV disease and are among the most prevalent manifestations throughout the course of HIV disease. Correlation of skin diseases and HIV disease staging has long been recognized and used to guide medical management in resource-limited settings. The purpose of this paper is to give a review of common skin infections presented in HIV-infected patients. Common skin infections presenting in HIV-infected patients include viral, fungal, mycobacterial, and bacterial infections, along with skin infestation. Key diagnostic points correlate with certain HIV disease staging for many skin diseases. These can help facilitate appropriate diagnosis and referral by health care personnel when treating HIV-infected patients who have skin lesions. Knowledge of common skin manifestations found in HIV-infected patients is essential for all health care personnel who work in the HIV field. Most skin infections presenting in HIV-infected patients can be treated effectively if the correct diagnosis and appropriate referral are made promptly. PMID:16672553

  8. Hyperspectral imaging of melanocytic lesions.

    PubMed

    Gaudi, Sudeep; Meyer, Rebecca; Ranka, Jayshree; Granahan, James C; Israel, Steven A; Yachik, Theodore R; Jukic, Drazen M

    2014-02-01

    Hyperspectral imaging (HSI) allows the identification of objects through the analysis of their unique spectral signatures. Although first developed many years ago for use in terrestrial remote sensing, this technology has more recently been studied for application in the medical field. With preliminary data favoring a role for HSI in distinguishing normal and lesional skin tissues, we sought to investigate the potential use of HSI as a diagnostic aid in the classification of atypical Spitzoid neoplasms, a group of lesions that often leave dermatopathologists bewildered. One hundred and two hematoxylin and eosin-stained tissue samples were divided into 1 of 4 diagnostic categories (Spitz nevus, Spitz nevus with unusual features, atypical Spitzoid neoplasm, and Spitzoid malignant melanoma) and 1 of 2 control groups (benign melanocytic nevus and malignant melanoma). A region of interest was selected from the dermal component of each sample, thereby maximizing the examination of melanocytes. Tissue samples were examined at ×400 magnification using a spectroscopy system interfaced with a light microscope. The absorbance patterns of wavelengths from 385 to 880 nm were measured and then analyzed within and among groups. All tissue groups demonstrated 3 common absorbance spectra at 496, 533, and 838 nm. Each sample group contained at least one absorption point that was unique to that group. The Spitzoid malignant melanoma category had the highest number of total and unique absorption points for any sample group. The data were then clustered into 12 representative spectral classes. Although each of the sample groups contained all 12 spectral vectors, they did so in differing proportions. These preliminary results reveal differences in the spectral signatures of the Spitzoid lesions examined in this study. Further investigation into a role for HSI in classifying atypical Spitzoid neoplasms is encouraged. PMID:24247577

  9. Central nervous system regeneration: from leech to opossum.

    PubMed

    Mladinic, M; Muller, K J; Nicholls, J G

    2009-06-15

    A major problem of neurobiology concerns the failure of injured mammalian spinal cord to repair itself. This review summarizes work done on two preparations in which regeneration can occur: the central nervous system of an invertebrate, the leech, and the spinal cord of an immature mammal, the opossum. The aim is to understand cellular and molecular mechanisms that promote and prevent regeneration. In the leech, an individual axon regrows successfully to re-establish connections with its synaptic target, while avoiding other neurons. Functions that were lost are thereby restored. Moreover, pairs of identified neurons become re-connected with appropriate synapses in culture. It has been shown that microglial cells and nitric oxide play key roles in leech CNS regeneration. In the opossum, the neonatal brain and spinal cord are so tiny that they survive well in culture. Fibres grow across spinal cord lesions in neonatal animals and in vitro, but axon regeneration stops abruptly between postnatal days 9 and 12. A comprehensive search has been made in spinal cords that can and cannot regenerate to identify genes and establish their locations. At 9 days, growth-promoting genes, their receptors and key transcription molecules are up-regulated. By contrast at 12 days, growth-inhibitory molecules associated with myelin are prominent. The complete sequence of the opossum genome and new methods for transfecting genes offer ways to determine which molecules promote and which inhibit spinal cord regeneration. These results lead to questions about how basic research on mechanisms of regeneration could be 'translated' into effective therapies for patients with spinal cord injuries. PMID:19525562

  10. Multiple lesion track structure model

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.

    1992-01-01

    A multilesion cell kinetic model is derived, and radiation kinetic coefficients are related to the Katz track structure model. The repair-related coefficients are determined from the delayed plating experiments of Yang et al. for the C3H10T1/2 cell system. The model agrees well with the x ray and heavy ion experiments of Yang et al. for the immediate plating, delaying plating, and fractionated exposure protocols employed by Yang. A study is made of the effects of target fragments in energetic proton exposures and of the repair-deficient target-fragment-induced lesions.

  11. Pancreatic Lesion: Malignancy or Abscess?

    PubMed

    Shulik, Oleg; Cavanagh, Yana; Grossman, Matthew

    2016-01-01

    BACKGROUND Pancreatic abscesses are rare. They may be seen in patients with pancreatic inflammation or pancreatitis. Patients with pancreatic abscesses may have abdominal pain, fever, chills, and nausea/vomiting or an inability to eat. Presentation with alternate symptomatology is extremely unusual. CASE REPORT A 67-year-old Asian male presented with painless, afebrile obstructive jaundice and a CA 19-9 of 1732 IU. He was found to have a 3.1×2.4 cm low-density lesion in the head of the pancreas and the right lobe of the liver, suggesting malignancy. Surgical management was considered, however additional diagnostic workup, including an endoscopic retrograde cholangiopancreatography (ERCP), was performed to complete staging of the presumed mass. A smooth, 3-cm-long, tapering stricture was found it the common bile duct. It was stented from the common hepatic duct to the duodenum. Subsequent endoscopic ultrasound (EUS) evaluation of the pancreatic head lesion revealed a drainable fluid collection that was aspirated and found to contain pyogenic material on pathology. The patient's symptoms resolved, and he was subsequently managed conservatively. A repeat ERCP confirmed complete resolution of the previously visualized cystic lesion. Interestingly, laboratory values showed concomitant normalization of CA 19-9 to 40 IU. CONCLUSIONS EUS-guided biopsy is not widely regarded as a required step before surgery, in the management of patients with pancreatic masses. It is generally reserved for determination of resectability or staging, and only utilized when clinically indicated. However, this practice may be associated with an inherently significant risk of misdiagnosis and subsequent unnecessary surgery, as illustrated by this case. Malignancy was initially suspected in our patient and surgical resection was recommended. Endoscopic measures were only pursued to complete staging. We propose that EUS-guided biopsy may be a crucial diagnostic step in the management algorithm

  12. Pancreatic Lesion: Malignancy or Abscess?

    PubMed Central

    Shulik, Oleg; Cavanagh, Yana; Grossman, Matthew

    2016-01-01

    Patient: Male, 67 Final Diagnosis: Pancreatic abscess Symptoms: Jaundice • fatigue • anorexia • subjective weight loss Medication: — Clinical Procedure: Therapeutic endoscopic ultrasound guided fine needle aspiration • biliary stenting • endoscopic cholangiopancreatography Specialty: Gastroenterology and Hepatology Objective: Rare coexistance of disease or pathology Background: Pancreatic abscesses are rare. They may be seen in patients with pancreatic inflammation or pancreatitis. Patients with pancreatic abscesses may have abdominal pain, fever, chills, and nausea/vomiting or an inability to eat. Presentation with alternate symptomatology is extremely unusual. Case Report: A 67-year-old Asian male presented with painless, afebrile obstructive jaundice and a CA 19-9 of 1732 IU. He was found to have a 3.1×2.4 cm low-density lesion in the head of the pancreas and the right lobe of the liver, suggesting malignancy. Surgical management was considered, however additional diagnostic workup, including an endoscopic retrograde cholangiopancreatography (ERCP), was performed to complete staging of the presumed mass. A smooth, 3-cm-long, tapering stricture was found it the common bile duct. It was stented from the common hepatic duct to the duodenum. Subsequent endoscopic ultrasound (EUS) evaluation of the pancreatic head lesion revealed a drainable fluid collection that was aspirated and found to contain pyogenic material on pathology. The patient’s symptoms resolved, and he was subsequently managed conservatively. A repeat ERCP confirmed complete resolution of the previously visualized cystic lesion. Interestingly, laboratory values showed concomitant normalization of CA 19-9 to 40 IU. Conclusions: EUS-guided biopsy is not widely regarded as a required step before surgery, in the management of patients with pancreatic masses. It is generally reserved for determination of resectability or staging, and only utilized when clinically indicated. However, this

  13. Computer-aided tracking of MS lesions

    NASA Astrophysics Data System (ADS)

    Sturm, Deborah; Gurwitz Kletenik, Devorah; Koshy, Philip

    2011-03-01

    Multiple Sclerosis (MS) lesions are known to change over time. The location, size and shape characteristics of lesions are often used to diagnose and to track disease progression. We have improved our lesion-browsing tool that allows users to automatically locate successive significant lesions in a MRI stack. In addition, an automatic alignment feature was implemented to facilitate comparisons across stacks. A lesion stack is formed that can be browsed independently or in tandem with the image windows. Lesions of interest can then be measured, rendered and rotated. Multiple windows allow the viewer to compare the size and shape of lesions from the MRI images of the same patient taken at different time intervals.

  14. Association of immunophilins with mammalian TRPC channels.

    PubMed

    Sinkins, William G; Goel, Monu; Estacion, Mark; Schilling, William P

    2004-08-13

    Drosophila photoreceptor channels TRP and TRPL are held in a large signalplex by the scaffolding protein, INAD. Immunophilin FKBP59, another member of the signalplex, binds to both INAD and TRPL. Mutation P702Q or P709Q in the highly conserved TRPL sequence (701)LPPPFNVLP(709), eliminates TRPL interaction with FKBP59. The first leucylprolyl (LP) dipeptide in this region is conserved in mammalian TRPC channel proteins. However, the second LP is changed to isoleucylprolyl (IP) in TRPC1, -C4, and -C5, and valylprolyl (VP) in TRPC3, -C6, and -C7. The purpose of the present study was to determine if mammalian FKBP12 or FKBP52 interact with TRPC channel proteins. Using TRPC-specific antibodies, immunoprecipitations from Sf9 cells individually co-expressing each of the TRPC proteins along with the immunophilins showed that TRPC3, -C6, and -C7 interact with FKBP12, whereas TRPC1, -C4, and -C5 interact with FKBP52. The binding of FKBP12 and FKBP52 was specific and could be displaced by the immunosuppressant drug FK506, at concentrations of 0.5 and 10 microm, respectively. To evaluate TRPC-immunophilin interactions in vivo, immunoprecipitations were performed using membrane lysates of rat cerebral cortex. FKBP12 co-immunoprecipitated with TRPC3, -C6, and -C7 from rat brain, whereas FKBP52 was found to associate with TRPC1, -C4, and -C5. The association of immunophilins with the TRPC channels in rat brain lysates could be displaced by FK506. Receptor-mediated activation of TRPC6, stably expressed in HEK cells, was significantly inhibited by FK506, which also disrupted interaction between TRPC6 and the endogenous immunophilin found in HEK cells. Pro to Gln mutations in the first LP dipeptide in the putative FKBP binding domain eliminated FKBP12 and FKBP52 interaction with TRPC3 and -C6, and TRPC1 and -C4, respectively. However, mutual swap of VP and IP in TRPC3 and TRPC5 did not alter the association or the selectivity of the channels for their respective immunophilin binding

  15. Mammalian ion-coupled solute transporters.

    PubMed Central

    Hediger, M A; Kanai, Y; You, G; Nussberger, S

    1995-01-01

    Active transport of solutes into and out of cells proceeds via specialized transporters that utilize diverse energy-coupling mechanisms. Ion-coupled transporters link uphill solute transport to downhill electrochemical ion gradients. In mammals, these transporters are coupled to the co-transport of H+, Na+, Cl- and/or to the countertransport of K+ or OH-. By contrast, ATP-dependent transporters are directly energized by the hydrolysis of ATP. The development of expression cloning approaches to select cDNA clones solely based on their capacity to induce transport function in Xenopus oocytes has led to the cloning of several ion-coupled transporter cDNAs and revealed new insights into structural designs, energy-coupling mechanisms and physiological relevance of the transporter proteins. Different types of mammalian ion-coupled transporters are illustrated by discussing transporters isolated in our own laboratory such as the Na+/glucose co-transporters SGLT1 and SGLT2, the H(+)-coupled oligopeptide transporters PepT1 and PepT2, and the Na(+)- and K(+)-dependent neuronal and epithelial high affinity glutamate transporter EAAC1. Most mammalian ion-coupled organic solute transporters studied so far can be grouped into the following transporter families: (1) the predominantly Na(+)-coupled transporter family which includes the Na+/glucose co-transporters SGLT1, SGLT2, SGLT3 (SAAT-pSGLT2) and the inositol transporter SMIT, (2) the Na(+)- and Cl(-)-coupled transporter family which includes the neurotransmitter transporters of gamma-amino-butyric acid (GABA), serotonin, dopamine, norepinephrine, glycine and proline as well as transporters of beta-amino acids, (3) the Na(+)- and K(+)-dependent glutamate/neurotransmitter family which includes the high affinity glutamate transporters EAAC1, GLT-1, GLAST, EAAT4 and the neutral amino acid transporters ASCT1 and SATT1 reminiscent of system ASC and (4) the H(+)-coupled oligopeptide transporter family which includes the intestinal H

  16. Absence of post-lesion reactive gliosis in elasmobranchs and turtles and its bearing on the evolution of astroglia.

    PubMed

    Kálmán, M; Somiya, Hiro; Lazarevic, Lidia; Milosevic, Ivan; Ari, Csilla; Majorossy, K

    2013-09-01

    In the mature mammalian and avian central nervous systems, neuronal destructions are followed by reactive gliosis, but data on other vertebrates are rather controversial. Mammals and birds belong to different amniote groups (Synapsida and Diapsida, respectively), but exhibit common general features in their glial architecture, mainly the predominance of astrocytes. Two vertebrate groups seem to be in special positions of glial evolution: turtles (Testudiniformes) and skates and rays (Batoidea). The purely ependymoglial system of turtles seems to be the simplest one among the extant amniotes. In skates and rays, true astrocytes are preponderant glial elements, in contrast to the other "anamniotes" (and even to reptiles). We investigated stab wounds by the immunohistochemical detection of GFAP in turtles (Trachemys-formerly Pseudemys-scripta elegans), a skate (Raja clavata) and rays (Dasyatis akajei and Torpedo marmorata). Sharks (Scyliorhinus canicula) as ependymoglia-predominated chondrichthyans, and-for positive controls-rats were also studied. In the elasmobranchs, other astroglial markers: glutamine synthetase and S100 protein were also applied. Neither turtles nor elasmobranchs presented considerable astroglial reactions. Critically surveying the former reports on different vertebrates, these results complete the picture that typical post-lesion reactive gliosis is confined to mammals and birds. Analysis of the astroglial systems from phylogenetic perspective suggests that the capability of forming glial demarcation and scar formation evolved independently in mammals and birds. Predominance of astrocytes is a necessary condition but not sufficient for reactive gliosis. The intense glial reactivity of mammals and birds may be attributed to their complex cerebralization. PMID:23640845

  17. 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

    2016-01-01

    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. PMID:27613398

  18. [Arthroscopic management of recent or chronic lesions of triangular fibrocartilage complex of the wrist].

    PubMed

    Fontès, D

    2006-11-01

    Lesions of the triangular fibrocartilage complex of the wrist (TFCC) have perfectly been dismembered by Andrew Palmer and have largely benefited from progress of arthroscopy of the wrist. One distinguishes thus traumatic lesions (class 1) individualized according to their localization, central (1-A), ulnar (1-B), radial (1-D) or distal (1-C). Central lesions are classically associated to a positive ulnar variance. The clinical symptomatology evokes a meniscal like syndrome of the wrist. In case of failure of the medical treatment, it will be necessary to propose a surgical procedure guided by histopathology of the triangular complex. Thus, ulnar peripheral richly vascularized lesions (1-B) could therefore potentially heal and will have to benefit by an attempt of surgical reattachment (arthroscopic technique of Whipple, Poehling or other techniques) or by an osteosynthesis in case of fracture on the basis on the ulnar styloid process. Central fibrocartilage lesions (1-A) or radial avulsions (1-D) are less vascularized and have therefore little probability to heal; they will benefit then ideally from the endoscopic debridement of unstable flaps of the central portion of TFCC. No immobilization is required and rehabilitation is immediately undertaken. Less frequent class 1-C lesions justify in our practice a simple arthroscopic regularization, alone complete ruptures could have necessitate a direct suture. Class 2 degenerative lesions are graduated (A to E) according to evolution of the chondromalacia of the ulnar head and carpal bone, perforation of the central disc and lunotriquetral ligament degeneration. They are usually associated with a constitutional or an acquired ulnar plus variance syndrome, for example after a distal radius fracture malunion. The clinical symptomatology needs to differentiate them from the simple frequent physiological perforations after the age of 50 years. Arthroscopy will allow to regularize unstable non-vascularized lesions and to

  19. [Arthroscopic management of recent or chronic lesions of Triangular Fibrocartilage Complex of the wrist.

    PubMed

    Fontès, D

    2006-11-01

    Lesions of the triangular fibrocartilage complex of the wrist (TFCC) have perfectly been dismembered by Andrew Palmer and have largely benefited from progress of arthroscopy of the wrist. One distinguishes thus traumatic lesions (class 1) individualized according to their localization, central (1-A), ulnar (1-B), radial (1-D) or distal (1-C). Central lesions are classically associated to a positive ulnar variance. The clinical symptomatology evokes a meniscal like syndrome of the wrist. In case of failure of the medical treatment, it will be necessary to propose a surgical procedure guided by histopathology of the triangular complex. Thus, ulnar peripheral richly vascularized lesions (1-B) could therefore potentially heal and will have to benefit by an attempt of surgical reattachment (arthroscopic technique of Whipple, Poehling or other techniques) or by an osteosynthesis in case of fracture on the basis on the ulnar styloid process. Central fibrocartilage lesions (1-A) or radial avulsions (1-D) are less vascularized and have therefore little probability to heal; they will benefit then ideally from the endoscopic debridement of unstable flaps of the central portion of TFCC. No immobilization is required and rehabilitation is immediately undertaken. Less frequent class 1-C lesions justify in our practice a simple arthroscopic regularization, alone complete ruptures could have necessitate a direct suture. Class 2 degenerative lesions are graduated (A to E) according to evolution of the chondromalacia of the ulnar head and carpal bone, perforation of the central disc and lunotriquetral ligament degeneration. They are usually associated with a constitutional or an acquired ulnar plus variance syndrome, for example after a distal radius fracture malunion. The clinical symptomatology needs to differentiate them from the simple frequent physiological perforations after the age of 50 years. Arthroscopy will allow to regularize unstable non-vascularized lesions and to

  20. Central Italy

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Clouds and haze cover most of the Italian peninsula in this view of central Italy (41.5N, 14.0E) but the Bay of Naples region with Mt. Vesuvius and the island of Capri are clear. The Adriatic Sea in the background separates Italy from the cloud covered Balkans of eastern Europe and the Tyrrhenian Sea in the foreground lies between the Italian mainland and the off scene islands of Corsica and Sardinia. Several aircraft contrails can also be seen.

  1. Maintenance and Expression of Mammalian Mitochondrial DNA.

    PubMed

    Gustafsson, Claes M; Falkenberg, Maria; Larsson, Nils-Göran

    2016-06-01

    Mammalian mitochondrial DNA (mtDNA) encodes 13 proteins that are essential for the function of the oxidative phosphorylation system, which is composed of four respiratory-chain complexes and adenosine triphosphate (ATP) synthase. Remarkably, the maintenance and expression of mtDNA depend on the mitochondrial import of hundreds of nuclear-encoded proteins that control genome maintenance, replication, transcription, RNA maturation, and mitochondrial translation. The importance of this complex regulatory system is underscored by the identification of numerous mutations of nuclear genes that impair mtDNA maintenance and expression at different levels, causing human mitochondrial diseases with pleiotropic clinical manifestations. The basic scientific understanding of the mechanisms controlling mtDNA function has progressed considerably during the past few years, thanks to advances in biochemistry, genetics, and structural biology. The challenges for the future will be to understand how mtDNA maintenance and expression are regulated and to what extent direct intramitochondrial cross talk between different processes, such as transcription and translation, is important. PMID:27023847

  2. Sources of Error in Mammalian Genetic Screens

    PubMed Central

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z.; Elledge, Stephen J.

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc. This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  3. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  4. From Immunity and Vaccines to Mammalian Regeneration

    PubMed Central

    Heber-Katz, Ellen

    2015-01-01

    Our current understanding of major histocompatibility complex (MHC)-mediated antigen presentation in self and nonself immune recognition was derived from immunological studies of autoimmunity and virus-host interactions, respectively. The trimolecular complex of the MHC molecule, antigen, and T-cell receptor accounts for the phenomena of immunodominance and MHC degeneracy in both types of responses and constrains vaccine development. Out of such considerations, we developed a simple peptide vaccine construct that obviates immunodominance, resulting in a broadly protective T-cell response in the absence of antibody. In the course of autoimmunity studies, we identified the MRL mouse strain as a mammalian model of amphibian-like regeneration. A significant level of DNA damage in the cells from this mouse pointed to the role of the cell cycle checkpoint gene CDKN1a, or p21cip1/waf1. The MRL mouse has highly reduced levels of this molecule, and a genetic knockout of this single gene in otherwise nonregenerating strains led to an MRL-type regenerative response, indicating that the ability to regenerate has not been lost during evolution. PMID:26116734

  5. Mammalian meiotic silencing exhibits sexually dimorphic features.

    PubMed

    Cloutier, J M; Mahadevaiah, S K; ElInati, E; Tóth, A; Turner, James

    2016-06-01

    During mammalian meiotic prophase I, surveillance mechanisms exist to ensure that germ cells with defective synapsis or recombination are eliminated, thereby preventing the generation of aneuploid gametes and embryos. Meiosis in females is more error-prone than in males, and this is in part because the prophase I surveillance mechanisms are less efficient in females. A mechanistic understanding of this sexual dimorphism is currently lacking. In both sexes, asynapsed chromosomes are transcriptionally inactivated by ATR-dependent phosphorylation of histone H2AFX. This process, termed meiotic silencing, has been proposed to perform an important prophase I surveillance role. While the transcriptional effects of meiotic silencing at individual genes are well described in the male germ line, analogous studies in the female germ line have not been performed. Here we apply single- and multigene RNA fluorescence in situ hybridization (RNA FISH) to oocytes from chromosomally abnormal mouse models to uncover potential sex differences in the silencing response. Notably, we find that meiotic silencing in females is less efficient than in males. Within individual oocytes, genes located on the same asynapsed chromosome are silenced to differing extents, thereby generating mosaicism in gene expression profiles across oocyte populations. Analysis of sex-reversed XY female mice reveals that the sexual dimorphism in silencing is determined by gonadal sex rather than sex chromosome constitution. We propose that sex differences in meiotic silencing impact on the sexually dimorphic prophase I response to asynapsis. PMID:26712235

  6. ORC proteins in the mammalian zygote.

    PubMed

    Ortega, Michael A; Nguyen, Hieu; Ward, W Steven

    2016-01-01

    The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA synthesis. These proteins have complex mechanisms of assembly into the ORC complex and unexpected localizations in the mitotic chromosomes, cytoplasm, and nuclear structures. The mammalian zygote is a potentially important model that may contribute to our understanding of the mechanisms and features influencing origin establishment and in the identification of other functions of the ORC proteins. Together with expected localizations to the chromatin during G1, we found an unexpected distribution in the cytoplasm that appeared to accumulate ORC proteins suggesting potential roles for ORC subunits in mitosis and chromatin segregation. ORC1, 2, 3, and 5 all localize to the area between the separating maternal chromosomes shortly after fertilization. ORC4 forms a cage around the set of chromosomes that will be extruded during polar body formation before it binds to the chromatin shortly before zygotic DNA replication. These data suggest that the ORC proteins may also play roles in preparing the cell for DNA replication in addition to their direct role in establishing functional replication origins. PMID:26453397

  7. Mammalian cells defective in DNA mismatch correction

    SciTech Connect

    Branch, P.; Aquilina, G.; Hess, P.

    1994-12-31

    Mammalian cells counteract the cytotoxicity of methylating agents, including some used in antitumor chemotherapy, by removing the methylated base, O{sup 6}-methylguanine (O{sup 6}-meG) from their DNA. This removal is normally effected by a specific DNA repair enzyme (O{sup 6}-meG-DNA methyltransferase) that is expressed constitutively. In addition, an alternative type of resistance to methylating agents can be acquired after exposure of cells to the drug. This acquired resistance is highly specific for O{sup 6}-meG and is unusual in that alkylation of DNA is normal and there is no increase in the rate of repair of O{sup 6}-meG or any other damaged base. Instead, the cell is able to tolerate the presence of the usually cytotoxic O{sup 6}-meG and to replicate its DNA normally. The ambiguity of base pairing by O{sup 6}-meG and the observation that tolerant cells are also cross-resistant to the structurally similar 6-thioguanine in DNA has led to the suggestion that the cytotoxicity of O{sup 6}-meG (and 6-thioguanine) arises from ineffective attempts at DNA mismatch correction. This model postulates that tolerance arises as a consequence of loss of this important pathway.

  8. RNAi microarray analysis in cultured mammalian cells.

    PubMed

    Mousses, Spyro; Caplen, Natasha J; Cornelison, Robert; Weaver, Don; Basik, Mark; Hautaniemi, Sampsa; Elkahloun, Abdel G; Lotufo, Roberto A; Choudary, Ashish; Dougherty, Edward R; Suh, Ed; Kallioniemi, Olli

    2003-10-01

    RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) is a powerful new tool for analyzing gene knockdown phenotypes in living mammalian cells. To facilitate large-scale, high-throughput functional genomics studies using RNAi, we have developed a microarray-based technology for highly parallel analysis. Specifically, siRNAs in a transfection matrix were first arrayed on glass slides, overlaid with a monolayer of adherent cells, incubated to allow reverse transfection, and assessed for the effects of gene silencing by digital image analysis at a single cell level. Validation experiments with HeLa cells stably expressing GFP showed spatially confined, sequence-specific, time- and dose-dependent inhibition of green fluorescence for those cells growing directly on microspots containing siRNA targeting the GFP sequence. Microarray-based siRNA transfections analyzed with a custom-made quantitative image analysis system produced results that were identical to those from traditional well-based transfection, quantified by flow cytometry. Finally, to integrate experimental details, image analysis, data display, and data archiving, we developed a prototype information management system for high-throughput cell-based analyses. In summary, this RNAi microarray platform, together with ongoing efforts to develop large-scale human siRNA libraries, should facilitate genomic-scale cell-based analyses of gene function. PMID:14525932

  9. Sources of Error in Mammalian Genetic Screens.

    PubMed

    Sack, Laura Magill; Davoli, Teresa; Xu, Qikai; Li, Mamie Z; Elledge, Stephen J

    2016-01-01

    Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs), from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias. PMID:27402361

  10. The First Mammalian Aldehyde Oxidase Crystal Structure

    PubMed Central

    Coelho, Catarina; Mahro, Martin; Trincão, José; Carvalho, Alexandra T. P.; Ramos, Maria João; Terao, Mineko; Garattini, Enrico; Leimkühler, Silke; Romão, Maria João

    2012-01-01

    Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 Å. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity. PMID:23019336

  11. Cell fate regulation in early mammalian development

    NASA Astrophysics Data System (ADS)

    Oron, Efrat; Ivanova, Natalia

    2012-08-01

    Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

  12. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  13. Evidence for compartmentalization of mammalian carotenoid metabolism

    PubMed Central

    Palczewski, Grzegorz; Amengual, Jaume; Hoppel, Charles L.; von Lintig, Johannes

    2014-01-01

    The critical role of retinoids (vitamin A and its derivatives) for vision, reproduction, and survival has been well established. Vitamin A is produced from dietary carotenoids such as β-carotene by centric cleavage via the enzyme BCO1. The biochemical and molecular identification of a second structurally related β-carotene metabolizing enzyme, BCO2, has led to a prolonged debate about its relevance in vitamin A biology. While BCO1 cleaves provitamin A carotenoids, BCO2 is more promiscuous and also metabolizes nonprovitamin A carotenoids such as zeaxanthin into long-chain apo-carotenoids. Herein we demonstrate, in cell lines, that human BCO2 is associated with the inner mitochondrial membrane. Different human BCO2 isoforms possess cleavable N-terminal leader sequences critical for mitochondrial import. Subfractionation of murine hepatic mitochondria confirmed the localization of BCO2 to the inner mitochondrial membrane. Studies in BCO2-knockout mice revealed that zeaxanthin accumulates in the inner mitochondrial membrane; in contrast, β-carotene is retained predominantly in the cytoplasm. Thus, we provide evidence for a compartmentalization of carotenoid metabolism that prevents competition between BCO1 and BCO2 for the provitamin and the production of noncanonical β-carotene metabolites.—Palczewski, G., Amengual, J., Hoppel, C. L., von Lintig, J. Evidence for compartmentalization of mammalian carotenoid metabolism. PMID:25002123

  14. Mammalian oocyte growth and development in vitro.

    PubMed

    Eppig, J J; O'Brien, M; Wigglesworth, K

    1996-06-01

    This paper is a review of the current status of technology for mammalian oocyte growth and development in vitro. It compares and contrasts the characteristics of the various culture systems that have been devised for the culture of either isolated preantral follicles or the oocyte-granulosa cell complexes form preantral follicles. The advantages and disadvantages of these various systems are discussed. Endpoints for the evaluation of oocyte development in vitro, including oocyte maturation and embryogenesis, are described. Considerations for the improvement of the culture systems are also presented. These include discussions of the possible effects of apoptosis and inappropriate differentiation of oocyte-associated granulosa cells on oocyte development. Finally, the potential applications of the technology for oocyte growth and development in vitro are discussed. For example, studies of oocyte development in vitro could help to identify specific molecules produced during oocyte development that are essential for normal early embryogenesis and perhaps recognize defects leading to infertility or abnormalities in embryonic development. Moreover, the culture systems may provide the methods necessary to enlarge the populations of valuable agricultural, pharmaceutical product-producing, and endangered animals, and to rescue the oocytes of women about to undergo clinical procedures that place oocytes at risk. PMID:9115726

  15. Presence of thiamine pyrophosphate in mammalian peroxisomes

    PubMed Central

    Fraccascia, Patrizia; Sniekers, Mieke; Casteels, Minne; Van Veldhoven, Paul P

    2007-01-01

    Background Thiamine pyrophosphate (TPP) is a cofactor for 2-hydroxyacyl-CoA lyase 1 (HACL1), a peroxisomal enzyme essential for the α-oxidation of phytanic acid and 2-hydroxy straight chain fatty acids. So far, HACL1 is the only known peroxisomal TPP-dependent enzyme in mammals. Little is known about the transport of metabolites and cofactors across the peroxisomal membrane and no peroxisomal thiamine or TPP carrier has been identified in mammals yet. This study was undertaken to get a better insight into these issues and to shed light on the role of TPP in peroxisomal metabolism. Results Because of the crucial role of the cofactor TPP, we reanalyzed its subcellular localization in rat liver. In addition to the known mitochondrial and cytosolic pools, we demonstrated, for the first time, that peroxisomes contain TPP (177 ± 2 pmol/mg protein). Subsequently, we verified whether TPP could be synthesized from its precursor thiamine, in situ, by a peroxisomal thiamine pyrophosphokinase (TPK). However, TPK activity was exclusively recovered in the cytosol. Conclusion Our results clearly indicate that mammalian peroxisomes do contain TPP but that no pyrophosphorylation of thiamine occurs in these organelles, implying that thiamine must enter the peroxisome already pyrophosphorylated. Consequently, TPP entry may depend on a specific transport system or, in a bound form, on HACL1 translocation. PMID:17596263

  16. Hibernation and daily torpor minimize mammalian extinctions

    NASA Astrophysics Data System (ADS)

    Geiser, Fritz; Turbill, Christopher

    2009-10-01

    Small mammals appear to be less vulnerable to extinction than large species, but the underlying reasons are poorly understood. Here, we provide evidence that almost all (93.5%) of 61 recently extinct mammal species were homeothermic, maintaining a constant high body temperature and thus energy expenditure, which demands a high intake of food, long foraging times, and thus exposure to predators. In contrast, only 6.5% of extinct mammals were likely heterothermic and employed multi-day torpor (hibernation) or daily torpor, even though torpor is widespread within more than half of all mammalian orders. Torpor is characterized by substantial reductions of body temperature and energy expenditure and enhances survival during adverse conditions by minimizing food and water requirements, and consequently reduces foraging requirements and exposure to predators. Moreover, because life span is generally longer in heterothermic mammals than in related homeotherms, heterotherms can employ a ‘sit-and-wait’ strategy to withstand adverse periods and then repopulate when circumstances improve. Thus, torpor is a crucial but hitherto unappreciated attribute of small mammals for avoiding extinction. Many opportunistic heterothermic species, because of their plastic energetic requirements, may also stand a better chance of future survival than homeothermic species in the face of greater climatic extremes and changes in environmental conditions caused by global warming.

  17. Apoptosis in mammalian oocytes: a review.

    PubMed

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K

    2015-08-01

    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals. PMID:25958165

  18. Repair of radiation damage in mammalian cells

    SciTech Connect

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  19. Angiogenesis is inhibitory for mammalian digit regeneration

    PubMed Central

    Yu, Ling; Yan, Mingquan; Simkin, Jennifer; Ketcham, Paulina D.; Leininger, Eric; Han, Manjong

    2014-01-01

    Abstract The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration.

  20. The Nucleosome Map of the Mammalian Liver

    PubMed Central

    Li, Zhaoyu; Schug, Jonathan; Tuteja, Geetu; White, Peter; Kaestner, Klaus H.

    2011-01-01

    Mammalian genomes contain billions of basepairs of DNA that must be highly compacted as chromatin to fit into the nano-scale of the nucleus, but yet be accessible to allow for transcription to occur. Binding to nucleosomal DNA is critical for ‘pioneer’ transcription factors such as the winged helix transcription factors Foxa1 and Foxa2 to regulate chromatin structure and gene activation. Here we report the genome-wide map of nucleosome positions in the mouse liver, with emphasis on transcriptional start sites, CpG islands, Foxa2 binding sites, and their correlation with gene expression. Despite the heterogeneity of liver tissue, we could clearly discern the nucleosome pattern of the predominant liver cell, the hepatocyte. By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP (also known as Crebbp), and p300 (Ep300) in Foxa1/2-deficient livers we find, surprisingly, that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1/2. PMID:21623366

  1. Functions of miRNAs during Mammalian Heart Development

    PubMed Central

    Yan, Shun; Jiao, Kai

    2016-01-01

    MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest cells. Recent data have identified various miRNAs as critical regulators of the proper differentiation, proliferation, and survival of these cell types. In this review, we briefly introduce the contemporary understanding of mammalian cardiac development. We also focus on recent developments in the field of cardiac miRNAs and their functions during the development of different cell types. PMID:27213371

  2. Fishing for mammalian paradigms in the teleost immune system

    PubMed Central

    Sunyer, J Oriol

    2013-01-01

    Recent years have witnessed a renaissance in the study of fish immune systems. Such studies have greatly expanded the knowledge of the evolution and diversification of vertebrate immune systems. Several findings in those studies have overturned old paradigms about the immune system and led to the discovery of novel aspects of mammalian immunity. Here I focus on how findings pertaining to immunity in teleost (bony) fish have led to major new insights about mammalian B cell function in innate and adaptive immunity. Additionally, I illustrate how the discovery of the most ancient mucosal immunoglobulin described thus far will help resolve unsettled paradigms of mammalian mucosal immunity. PMID:23507645

  3. Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice.

    PubMed

    Peterson, Douglas E; O'Shaughnessy, Joyce A; Rugo, Hope S; Elad, Sharon; Schubert, Mark M; Viet, Chi T; Campbell-Baird, Cynthia; Hronek, Jan; Seery, Virginia; Divers, Josephine; Glaspy, John; Schmidt, Brian L; Meiller, Timothy F

    2016-08-01

    In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop. PMID:27334013

  4. Training rats to voluntarily dive underwater: investigations of the mammalian diving response.

    PubMed

    McCulloch, Paul F

    2014-01-01

    Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the

  5. Dental infection simulating skin lesion.

    PubMed

    Abuabara, Allan; Schramm, Celso Alfredo; Zielak, João César; Baratto-Filho, Flares

    2012-01-01

    Orocutaneous fistulas or cutaneous sinus, a tract of dental origin, is an uncommon but well-documented condition that usually requires emergency treatment. Such condition may be misdiagnosed by physicians and dentists and may sometimes be confused with bone and skin tumor, osteomyelitis, congenital fistula, salivary gland fistula, pyogenic granuloma, infected cyst, deep mycotic infection, and other pathologies. A case of facial sinus tract that was initially misdiagnosed by a physician as a nonodontogenic lesion is presented. Nonsurgical endodontic therapy was the treatment of choice for this case. Facial cutaneous sinus tracts must be considered of dental origin. Early diagnosis and prompt treatment minimize patient discomfort and esthetic problems, reducing the possibility of further complications such as sepsis and osteomyelitis. PMID:22892779

  6. Trigeminal Neuralgia and Radiofrequency Lesioning

    PubMed Central

    Eugene, Andy R.

    2016-01-01

    Trigeminal Neuralgia is a disorder that is characterized with electrical-type shocking pain in the face and jaw. This pain may either present as sharp unbearable pain unilateral or bilaterally. There is no definite etiology for this condition. There are various treatment methods that are currently being used to relieve the pain. One of the pharmacological treatments is Carbamazepine and the most prevalent surgical treatments include Gamma Knife Surgery (GKS), Microvascular Decompression (MVD) and Radiofrequency Lesioning (RFL). Although, MVD is the most used surgical method it is not an option for all the patients due to the intensity of the procedure. RFL is used when MVD is not suitable. In this paper we present the various options in the treatment of Trigeminal Neuralgia. PMID:26770820

  7. Mammalian Transcription-Coupled Excision Repair

    PubMed Central

    Vermeulen, Wim; Fousteri, Maria

    2013-01-01

    Transcriptional arrest caused by DNA damage is detrimental for cells and organisms as it impinges on gene expression and thereby on cell growth and survival. To alleviate transcriptional arrest, cells trigger a transcription-dependent genome surveillance pathway, termed transcription-coupled nucleotide excision repair (TC-NER) that ensures rapid removal of such transcription-impeding DNA lesions and prevents persistent stalling of transcription. Defective TC-NER is causatively linked to Cockayne syndrome, a rare severe genetic disorder with multisystem abnormalities that results in patients’ death in early adulthood. Here we review recent data on how damage-arrested transcription is actively coupled to TC-NER in mammals and discuss new emerging models concerning the role of TC-NER-specific factors in this process. PMID:23906714

  8. Cutaneous lesions in new born.

    PubMed

    Sachdeva, Meenakshi; Kaur, Surjeet; Nagpal, Madhu; Dewan, S P

    2002-01-01

    Five hundred unselected newborn babies delivered in the Department of Obstetrics and Gynaecology, Unit II of SGBT Hospital attached to Government Medical College, Amritsar during April 2000 to October 2000 were examined for cutaneous lesions daily for the first five days after birth. Different cutaneous lesions were seen in 474(94.8%) newborns. The physiological skin changes observed in order of frequency were Epstein pearls in 305(61%), Mongolian spot in 301(60.2%), superficial cutaneous desquamation in 200(40%), icterus in 128(25.6%), milia in 119(23.8%), sebaceous gland hyperplasia in 107(21.4%), occipital alopecia in 94(18.8%), lanugo in 72(14.4%), peripheral cyanosis in 47(9.4%), breast hypertrophy in 29(5.8%) and miniature puberty in 28(5.6%) newborns. Of the transient non-infective skin diseases, erythema toxicum neonatorum was observed most commonly in 105(21%), followed by miliaria rubra in 103(20.6%) and acne neonatorum in 27(5.4%) newborns. The naevi and other developmental defects in the descending order were salmon patch in 69(13.8%), congenital melanocytic noevi in 10(2%), accessory tragi in 3(0.6%), spina bifida in 2(0.4%), hydrocephalus in 1(0.2%) and poliosis in 1(0.2%) newborns. Cradle cap was the only dermatitis observed in 50(10%) newborns. One (0.2%) case each of Harlequin ichthyosis and labial cyst was seen. PMID:17656992

  9. Longitudinal Study of New Eye Lesions in Children with Toxoplasmosis Who Were Not Treated During the First Year of Life

    PubMed Central

    PHAN, LAURA; KASZA, KRISTEN; JALBRZIKOWSKI, JESSICA; NOBLE, A. GWENDOLYN; LATKANY, PAUL; KUO, ANNIE; MIELER, WILLIAM; MEYERS, SANFORD; RABIAH, PETER; BOYER, KENNETH; SWISHER, CHARLES; METS, MARILYN; ROIZEN, NANCY; CEZAR, SIMONE; SAUTTER, MARI; REMINGTON, JACK; MEIER, PAUL; MCLEOD, RIMA

    2009-01-01

    PURPOSE To determine the incidence of new chorioretinal lesions in children with toxoplasmosis diagnosed after, and therefore not treated during, their first year. DESIGN Prospective longitudinal cohort study. METHODS Thirty-eight children were evaluated in Chicago between 1981 and 2005 for new chorioretinal lesions. Thirty-eight children and mothers had serum IgG antibody to Toxoplasma gondii. RESULTS Twenty-eight of 38 children had one of the following: diagnosis with serum antibody to T. gondii indicative of chronic infection at age 24 months, central nervous system calcifications, hydrocephalus, illness compatible with congenital toxoplasmosis perinatally but not diagnosed at that time. Twenty-five returned for follow-up during 1981 to 2005. Their mean (range) age at last exam was 10.9 ± 5.7 (range, 3.5 to 27.2) years and mean follow-up was 5.7 ± 2.9 years. Eighteen (72%) children developed at least one new lesion. Thirteen (52%) had new central lesions, 11 (44%) had new peripheral lesions, and six (24%) had both. Thirteen (52%) had new lesions diagnosed at age ≥ 10 years. New lesions were found at more than one visit in four (22%), and bilateral new lesions developed in seven (39%) of 18 children who developed new lesions. Of 10 additional children with eye findings and serologic tests indicative of chronic infection, six returned for follow-up, four (67%) developing new lesions at ≥ 10 years of age. CONCLUSIONS More than 70% developed new chorioretinal lesions. New lesions were commonly diagnosed after the first decade of life. PMID:18619570

  10. [Vascular lesions of the small intestine].

    PubMed

    Yano, Tomonori; Yamamoto, Hironori

    2008-07-01

    Small-intestinal vascular lesions accounted for the bleeding source in a large percentage of the patients with mid-GI-bleeding. The progress of enteroscopy has been changing the diagnostic and therapeutic algorithm for them. There are 3 pathological conditions of vascular lesions. Angioectasia is characterized by venous/capillary lesions, Dieulafoy' s lesion is characterized by arterial lesions, and AVM is a condition in which arteries and veins are directly connected without capillary beds. We classified vascular lesions with consideration of the presence or absence of pulsatility. The presence or absence of arterial components provides important information in understanding the pathological conditions. This classification will be useful for selecting hemostatic procedure and outcome studies. PMID:18616125

  11. Malignancy and the benign lymphoepithelial lesion.

    PubMed

    Batsakis, J G; Bernacki, E G; Rice, D H; Stebler, M E

    1975-02-01

    The benign lymphoepithelial lesion of salivary glands is now considered the histological hallmark of a variety of clinical and pathological disorders affecting salivary tissues. Malignancy arising in the lesion is uncommon, but may take origin in either the epithelial or lymphoreticular components. Lymphomas and pseudolymphomas associated with salivary gland lymphoepithelial lesions have been predominately extra-salivary and strongly correlated with Sjögren's syndrome. Epithelial malignancy has not been associated with autoimmunity and with few exceptions has been of the anaplastic type. This report presents two patients with intra-salivary lymphomas arising in a benign lymphoepithelial lesion of salivary glands and a patient with anaplastic carcinoma arising in the epithelial islands of the lesion. The fourth patient manifested pseudolymphomatous lymphoreticular hyperplasia in lung and submandibular gland and illustrates the possible multiple organ involvement that may occur in patients with benign lymphoepithelial lesion, even without clinical evidence of concommitant autoimmune disorders. PMID:1172885

  12. Calcified Cystic Lesion of the Pancreas.

    PubMed

    Li, Tao; Chen, Zhi-Qiang; Meng, Zhi-Xin; Hong, Jian-Guo; Zhi, Xu-Ting

    2016-06-01

    Pancreatic cystic lesion is a relatively uncommon condition with an estimated prevalence of 2 % in the general population. In the past two decades, there has been a dramatic increase in the prevalence of pancreatic cystic lesions because of the widespread use of high-resolution imaging, as well as the aging of the population. Pancreatic cystic lesions cover a wide spectrum of pathology and can range from obviously benign to borderline malignant potential lesions to overt malignancy. Though the presence of mural nodules, septa-like structures, or calcification on imaging examination contributes to the differential diagnosis, preoperatively determining the biological nature of these cystic lesions is sometimes challenging. In this paper, we report a rare case of pancreatic cystic lesion with an egg-shell like calcification. Complete resection was performed and histological examination confirmed the diagnosis of calcified pancreatic pseudocyst. PMID:26992398

  13. Activation of Mammalian target of rapamycin in canine mammary carcinomas: an immunohistochemical study.

    PubMed

    Delgado, L; Gärtner, F; Dias Pereira, P

    2015-01-01

    Mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cell growth, proliferation and survival. Activation of mTOR has been reported in various tumour types, including human breast cancer; however, the expression of mTOR in canine mammary tumours has not been examined. In the present study, expression of the activated form of mTOR (phospho-mTOR [p-mTOR]) was examined immunohistochemically in five normal canine mammary glands, 45 canine mammary carcinomas and their corresponding metastatic lesions (n = 15). Phospho-mTOR was not expressed in normal canine mammary tissue, but cytoplasmic labelling was observed in 78% of canine mammary carcinomas. Two carcinomas had both cytoplasmic and nuclear labelling. No significant relationship was found between p-mTOR cytoplasmic expression and histological type or grading of carcinomas, degree of tubular formation, anisokaryosis, mitotic activity or lymph node metastasis. In all except one case, the expression pattern of p-mTOR in lymph node metastases was similar or decreased when compared with the primary lesion. The findings suggest that p-mTOR is involved in mammary carcinogenesis in dogs. However, p-mTOR cytoplasmic expression does not appear to be a prognostic indicator in canine mammary carcinomas, which may be related to its subcellular location in the neoplastic cells. Canine mammary tumours may provide a model for the development of innovative medical strategies involving mTOR inhibitors in human breast cancer. PMID:25670666

  14. The influence of concentration of DNA on the radiosensitivity of mammalian cells

    SciTech Connect

    Hawkins, Roland B. . E-mail: rhawkins@ochsner.org

    2005-10-01

    Purpose: To develop relations that explicitly show the dependence of the linear-quadratic survival parameters {alpha} and {beta} on the nuclear volume, average DNA concentration, and degree to which the chromatin is condensed in zones of the nucleus. Methods and Materials: The microdosimetric-kinetic model of mammalian cell killing is used. Results: The relations indicate an increased tendency for lethal lesions to form by pairwise combination of potentially lethal lesions in regions of relatively greater local DNA concentration. In particular, the value of {beta} is proportional to the average nuclear concentration of DNA and to a parameter that reflects the condensation of DNA into a relatively concentrated phase, such as occurs in mitotic chromosomes and heterochromatin. These relations indicate local DNA concentration in the nucleus is a significant determinant of three magnitude of {beta}. Because {alpha} is composed of a term that is proportional to {beta}, it is also affected by DNA concentration, generally to equal or less degree. Conclusion: It may be possible to establish a correlation between nuclear size and morphology, as determined from microscope slides prepared from biopsy specimens, with radiation sensitivity and the {alpha}/{beta} ratio that could be useful in radiation treatment planning.

  15. The Trypanosoma cruzi Diamine Transporter Is Essential for Robust Infection of Mammalian Cells

    PubMed Central

    Hasne, Marie-Pierre; Soysa, Radika; Ullman, Buddy

    2016-01-01

    Trypanosoma cruzi is incapable of synthesizing putrescine or cadaverine de novo, and, therefore, salvage of polyamines from the host milieu is an obligatory nutritional function for the parasite. A high-affinity diamine transporter (TcPOT1) from T. cruzi has been identified previously that recognizes both putrescine and cadaverine as ligands. In order to assess the functional role of TcPOT1 in intact parasites, a Δtcpot1 null mutant was constructed by targeted gene replacement and characterized. The Δtcpot1 mutant lacked high-affinity putrescine-cadaverine transport capability but retained the capacity to transport diamines via a non-saturable, low-affinity mechanism. Transport of spermidine and arginine was not impacted by the Δtcpot1 lesion. The Δtcpot1 cell line exhibited a significant but not total defect in its ability to subsist in Vero cells, although initial infection rates were not affected by the lesion. These findings reveal that TcPOT1 is the sole high-affinity diamine permease in T. cruzi, that genetic obliteration of TcPOT1 impairs the ability of the parasite to maintain a robust infection in mammalian cells, and that a secondary low-affinity uptake mechanism for this key parasite nutrient is operative but insufficient for optimal infection. PMID:27050410

  16. Neuroanatomy: connectome connects fly and mammalian brain networks.

    PubMed

    Kaiser, Marcus

    2015-05-18

    A recent study shows that brain connectivity in Drosophila melanogaster follows a small-world, modular and rich-club organisation that facilitates information processing. This organisation shows a striking similarity with the mammalian brain. PMID:25989081

  17. GENE EXPRESSION IN PRE-IMPLANTATION MAMMALIAN EMBRYOS

    EPA Science Inventory

    The pre-implantation mammalian embryo is initially under the control of maternal informational macromolecules that are accumulated during oogenesis. ubsequently, the genetic program of development becomes dependent upon new transcription derived from activation of the embryonic g...

  18. Profiling Signaling Peptides in Single Mammalian Cells Using Mass Spectrometry

    PubMed Central

    Rubakhin, Stanislav S.; Churchill, James D.; Greenough, William T.; Sweedler, Jonathan V.

    2008-01-01

    The peptide content of individual mammalian cells is profiled using matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry. Both enzymatic and non-enzymatic procedures, including a glycerol cell stabilization method, are reported for the isolation of individual mammalian cells in a manner compatible with MALDI MS measurements. Guided microdeposition of MALDI matrix allows samples to be created with suitable analyte-to-matrix ratios. More than fifteen peptides are observed in individual rat intermediate pituitary cells. The combination of accurate mass data, expected cleavages by proteolytic enzymes, and post-source decay sequencing allows identification of fourteen of these peptides as pro-opiomelanocortin prohormone-derived molecules. These protocols permit the classification of individual mammalian cells by peptide profile, the elucidation of cell-specific prohormone processing, and the discovery of new signaling peptides on a cell-to-cell basis in a wide variety of mammalian cell types. PMID:17037931

  19. Genome exposure and regulation in mammalian cells.

    PubMed

    Puck, T T; Webb, P; Johnson, R

    1998-09-01

    A method of measurement of exposed DNA (i.e. hypersensitive to DNase I hydrolysis) as opposed to sequestered (hydrolysis resistant) DNA in isolated nuclei of mammalian cells is described. While cell cultures exhibit some differences in behavior from day to day, the general pattern of exposed and sequestered DNA is satisfactorily reproducible and agrees with results previously obtained by other methods. The general pattern of DNA hydrolysis exhibited by all cells tested consists of a curve which at first rises sharply with increasing DNase I, and then becomes almost horizontal, indicating that roughly about half of the nuclear DNA is highly sequestered. In 4 cases where transformed cells (Raszip6, CHO, HL60 and PC12) were compared, each with its more normal homolog (3T3, and the reverse transformed versions of CHO, HL60 and PC12, achieved by dibutyryl cyclic AMP [DBcAMP], retinoic acid, and nerve growth factor [NGF] respectively), the transformed form displayed less genome exposure than the nontransformed form at every DNase I dose tested. When Ca++ was excluded from the hydrolysis medium in both the Raszip6-3T3 and the CHO-DBcAMP systems, the normal cell forms lost their increased exposure reverting to that of the transformed forms. Therefore Ca++ appears necessary for maintenance of the DNA in the more highly exposed state characteristic of the nontransformed phenotype. LiCl increases the DNA exposure of all transformed cells tested. Dextran sulfate and heparin each can increase the DNA exposure of several different cancers. Colcemid prevents the increase of exposure of CHO by DBcAMP but it must be administered before or simultaneously with the latter compound. Measurements on mouse biopsies reveal large differences in exposure in different normal tissues. Thus, the exposure from adult liver cells was greater than that of adult brain, but both fetal liver and fetal brain had significantly greater exposure than their adult counterparts. Exposure in normal human

  20. Magnetic resonance imaging in central pontine myelinolysis.

    PubMed Central

    Thompson, P D; Miller, D; Gledhill, R F; Rossor, M N

    1989-01-01

    Magnetic resonance imaging (MRI) was performed in two patients in whom a clinical diagnosis of central pontine myelinolysis (CPM) had been made. MRI showed lesions in the pons in both cases about 2 years after the illness, at a time when the spastic quadriparesis and pseudobulbar palsy had recovered. The persisting abnormal signals in CPM are likely to be due to fibrillary gliosis. Persistence of lesions on MRI means that the diagnosis of CPM may be electively, after the acute illness has resolved. Images PMID:2732743

  1. Cell lineage in mammalian craniofacial mesenchyme.

    PubMed

    Yoshida, Toshiyuki; Vivatbutsiri, Philaiporn; Morriss-Kay, Gillian; Saga, Yumiko; Iseki, Sachiko

    2008-01-01

    We have analysed the contributions of neural crest and mesoderm to mammalian craniofacial mesenchyme and its derivatives by cell lineage tracing experiments in mouse embryos, using the permanent genetic markers Wnt1-cre for neural crest and Mesp1-cre for mesoderm, combined with the Rosa26 reporter. At the end of neural crest cell migration (E9.5) the two patterns are reciprocal, with a mutual boundary just posterior to the eye. Mesodermal cells expressing endothelial markers (angioblasts) are found not to respect this boundary; they are associated with the migrating neural crest from the 5-somite stage, and by E9.5 they form a pre-endothelial meshwork throughout the cranial mesenchyme. Mesodermal cells of the myogenic lineage also migrate with neural crest cells, as the branchial arches form. By E17.5 the neural crest-mesoderm boundary in the subectodermal mesenchyme becomes out of register with that of the underlying skeletogenic layer, which is between the frontal and parietal bones. At E13.5 the primordia of these bones lie basolateral to the brain, extending towards the vertex of the skull during the following 4-5 days. We used DiI labelling of the bone primordia in ex-utero E13.5 embryos to distinguish between two possibilities for the origin of the frontal and parietal bones: (1) recruitment from adjacent connective tissue or (2) proliferation of the original primordia. The results clearly demonstrated that the bone primordia extend vertically by intrinsic growth, without detectable recruitment of adjacent mesenchymal cells. PMID:18617001

  2. Evolution of the mammalian dentate gyrus.

    PubMed

    Hevner, Robert F

    2016-02-15

    The dentate gyrus (DG), a part of the hippocampal formation, has important functions in learning, memory, and adult neurogenesis. Compared with homologous areas in sauropsids (birds and reptiles), the mammalian DG is larger and exhibits qualitatively different phenotypes: 1) folded (C- or V-shaped) granule neuron layer, concave toward the hilus and delimited by a hippocampal fissure; 2) nonperiventricular adult neurogenesis; and 3) prolonged ontogeny, involving extensive abventricular (basal) migration and proliferation of neural stem and progenitor cells (NSPCs). Although gaps remain, available data indicate that these DG traits are present in all orders of mammals, including monotremes and marsupials. The exception is Cetacea (whales, dolphins, and porpoises), in which DG size, convolution, and adult neurogenesis have undergone evolutionary regression. Parsimony suggests that increased growth and convolution of the DG arose in stem mammals concurrently with nonperiventricular adult hippocampal neurogenesis and basal migration of NSPCs during development. These traits could all result from an evolutionary change that enhanced radial migration of NSPCs out of the periventricular zones, possibly by epithelial-mesenchymal transition, to colonize and maintain nonperiventricular proliferative niches. In turn, increased NSPC migration and clonal expansion might be a consequence of growth in the cortical hem (medial patterning center), which produces morphogens such as Wnt3a, generates Cajal-Retzius neurons, and is regulated by Lhx2. Finally, correlations between DG convolution and neocortical gyrification (or capacity for gyrification) suggest that enhanced abventricular migration and proliferation of NSPCs played a transformative role in growth and folding of neocortex as well as archicortex. PMID:26179319

  3. Assays for mammalian tyrosinase: a comparative study

    SciTech Connect

    Jara, J.R.; Solano, F.; Lozano, J.A.

    1988-01-01

    This work describes a comparative study of the tyrosinase activity determined using three methods which are the most extensively employed; two radiometric assays using L-tyrosine as substrate (tyrosine hydroxylase and melanin formation activities) and one spectrophotometric assay using L-dopa (dopa oxidase activity). The three methods were simultaneously employed to measure the activities of the soluble, melanosomal, and microsomal tyrosinase isozymes from Harding-Passey mouse melanoma through their purification processes. The aim of this study was to find any correlation among the tyrosinase activities measured by the three different assays and to determine whether that correlation varied with the isozyme and its degree of purification. The results show that mammalian tyrosinase has a greater turnover number for L-dopa than for L-tyrosine. Thus, enzyme activity, expressed as mumol of substrate transformed per min, is higher in assays using L-dopa as substrate than those using L-tyrosine. Moreover, the percentage of hydroxylated L-tyrosine that is converted into melanin is low and is affected by several factors, apparently decreasing the tyrosinase activity measured by the melanin formation assay. Bearing these considerations in mind, average interassay factors are proposed. Their values are 10 to transform melanin formation into tyrosine hydroxylase activity, 100 to transform tyrosine hydroxylase into dopa oxidase activity, and 1,000 to transform melanin formation into dopa oxidase activity. Variations in these values due to the presence in the tyrosinase preparations of either inhibitors or regulatory factors in melanogenesis independent of tyrosinase are also discussed.

  4. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    PubMed

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR. PMID:26895065

  5. 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.

  6. 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.

  7. Flexible 5-Guanidino-4-nitroimidazole DNA Lesions: Structures and Thermodynamics †

    PubMed Central

    Jia, Lei; Shafirovich, Vladimir; Shapiro, Robert; Geacintov, Nicholas E.; Broyde, Suse

    2008-01-01

    5-Guanidino-4-nitroimidazole (NI), derived from guanine oxidation by reactive oxygen and nitrogen species, contains an unusual flexible ring opened structure, with nitro and guanidino groups which possess multiple hydrogen bonding capabilities. In vitro primer extension experiments with bacterial and mammalian polymerases show that NI incorporates C as well as A and G opposite the lesion, depending on the polymerase. In order to elucidate structural and thermodynamic properties of the mutagenic NI lesion, we have investigated the structure of the modified base itself and the NI-containing nucleoside with high level quantum mechanical calculations, and have employed molecular modeling and molecular dynamics simulations in solution for the lesion in B-DNA duplexes with four partner bases opposite the NI. Our results show that the NI adopts a planar structure at the damaged-base level. However, in the nucleoside and in DNA duplexes, steric hindrance between the guanidino group and its linked sugar causes NI to be non-planar. The NI lesion can adopt both syn and anti conformations on the DNA duplex level, with the guanidino group positioned in the DNA major and minor grooves, respectively; the specific preference depends on the partner base. Based on hydrogen bonding and stacking interactions, groove dimensions, and bending, we find that the least distorted NI modified duplex contains partner C, consistent with incorporation of C opposite NI. However, hydrogen bonding interactions between NI with partner G or A are also found, which would be compatible with the observed mismatches. PMID:16716075

  8. [Tumor-like lesions of bone].

    PubMed

    Erlemann, R; Jundt, G

    2016-06-01

    Historically, tumor-like lesions of bone were defined as non-neoplastic bone lesions. Today, however, some of them are considered real neoplasms. They are among the most frequent bone lesions. They usually grow slowly, but occasionally they grow rapidly. Many of them can be diagnosed by plain films alone; in others, CT and MRI yield additional features for a correct diagnosis. Some lesions do not need treatment; others should be resected, and some may even recur. Non-ossifying fibroma, juvenile and aneurysmal bone cysts, fibrous and osteofibrous dysplasia and eosinophilic granuloma are presented. PMID:27216410

  9. Mammalian Tribbles Homologs at the Crossroads of Endoplasmic Reticulum Stress and Mammalian Target of Rapamycin Pathways

    PubMed Central

    Cunard, Robyn

    2013-01-01

    In 2000, investigators discovered Tribbles, a Drosophila protein that coordinates morphogenesis by inhibiting mitosis. Further work has delineated Xenopus (Xtrb2), Nematode (Nipi-3), and mammalian homologs of Drosophila tribbles, which include TRB1, TRB2, and TRB3. The sequences of tribbles homologs are highly conserved, and despite their protein kinase structure, to date they have not been shown to have kinase activity. TRB family members play a role in the differentiation of macrophages, lymphocytes, muscle cells, adipocytes, and osteoblasts. TRB isoforms also coordinate a number of critical cellular processes including glucose and lipid metabolism, inflammation, cellular stress, survival, apoptosis, and tumorigenesis. TRB family members modulate multiple complex signaling networks including mitogen activated protein kinase cascades, protein kinase B/AKT signaling, mammalian target of rapamycin, and inflammatory pathways. The following review will discuss metazoan homologs of Drosophila tribbles, their structure, expression patterns, and functions. In particular, we will focus on TRB3 function in the kidney in podocytes. This review will also discuss the key signaling pathways with which tribbles proteins interact and provide a rationale for developing novel therapeutics that exploit these interactions to provide better treatment options for both acute and chronic kidney disease. PMID:24490110

  10. 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

  11. Incorporation of mammalian actin into microfilaments in plant cell nucleus

    PubMed Central

    Paves, Heiti; Truve, Erkki

    2004-01-01

    Background Actin is an ancient molecule that shows more than 90% amino acid homology between mammalian and plant actins. The regions of the actin molecule that are involved in F-actin assembly are largely conserved, and it is likely that mammalian actin is able to incorporate into microfilaments in plant cells but there is no experimental evidence until now. Results Visualization of microfilaments in onion bulb scale epidermis cells by different techniques revealed that rhodamine-phalloidin stained F-actin besides cytoplasm also in the nuclei whereas GFP-mouse talin hybrid protein did not enter the nuclei. Microinjection of fluorescently labeled actin was applied to study the presence of nuclear microfilaments in plant cells. Ratio imaging of injected fluorescent rabbit skeletal muscle actin and phalloidin staining of the microinjected cells showed that mammalian actin was able to incorporate into plant F-actin. The incorporation occurred preferentially in the nucleus and in the perinuclear region of plant cells whereas part of plant microfilaments, mostly in the periphery of cytoplasm, did not incorporate mammalian actin. Conclusions Microinjected mammalian actin is able to enter plant cell's nucleus, whereas incorporation of mammalian actin into plant F-actin occurs preferentially in the nucleus and perinuclear area. PMID:15102327

  12. 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.

  13. a Computational Model for Lesion Dynamics in Multiple Sclerosis of the Brain

    NASA Astrophysics Data System (ADS)

    Mohan, T. R. Krishna; Sen, Surajit; Ramanathan, Murali

    Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) that is characterized by lesions with inflammatory cells, axons with the insulating myelin sheath damaged, and axonal loss. The causes of MS are not known and there is as yet no cure. The purpose of this research was to evaluate a physically motivated network model for lesion formation in the brain. The parsimonious network model contained two elements: (i) a spatially spreading pathological process causing cell damage and death leading to neuro-degeneration and, (ii) generation of alarm signals by the damaged cells that lead to activation of programmed death of cells surrounding the lesions in an attempt to contain the spatial spread of the pathologic process. Simulation results with a range of network geometries indicated that the model was capable of describing lesion progression and arrest. The modeling results also demonstrated dynamical complexity with sensitivity to initial conditions.

  14. 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

  15. 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

    2013-01-01

    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

  16. Neurological lesions in chickens experimentally infected with virulent Newcastle disease virus isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Distribution, character, and severity of lesions were evaluated in tissues from the central nervous system of chickens inoculated with 10 different Newcastle disease virus (NDV) isolates: CA 1083, Korea 97-147, Australia (all velogenic viscerotropic); Texas GB and Turkey North Dakota (both velogenic...

  17. Central Endoscopy Reading in Inflammatory Bowel Diseases.

    PubMed

    Panés, Julián; Feagan, Brian G; Hussain, Fez; Levesque, Barrett G; Travis, Simon P

    2016-09-01

    Endoscopic assessment of the presence and severity of endoscopic lesions has become an essential part of clinical trials in ulcerative colitis and Crohn's disease, for both patient eligibility and outcome measures. Variability in lesion interpretation between and within observers and the potential bias of local investigators in patient assessment have long been recognized. This variability can be reduced, although not completely removed, by independent evaluation of the examinations by experienced off-site (central) readers, properly trained in regard to lesion definition and identification, that should be removed from direct patient contact and blinded to any other clinical or study data. Adding endoscopic demonstration of active disease to eligibility criteria has the potential to reduce placebo response rates, whereas in outcome assessment it has the potential to provide a more precise estimation of the treatment effect, increasing the efficiency of the study. Central endoscopy reading is still at the beginning of its development, and the paradigms of central reading need refinement in terms of the number of readers, the process by which a final score is assigned, the selection and sequence of central readers, and the endoscopic indices of choice. PMID:27604978

  18. Central auditory testing and dyslexia.

    PubMed

    Welsh, L W; Welsh, J J; Healy, M P

    1980-06-01

    A group of dyslexic pupils with normal end organ function was studied by a central auditory battery to determine whether a hearing disability existed. The clinical features of dyslexia are presented with emphasis on the psychological developmental and functional disorders associated with this reading problem. The central battery of Willeford was selected as the test medium and the results of the 77 dyslexic students were compared to the normative data. The model proposed by Sparks, et al., is accepted as the mechanism for dichotic audition. Reference is made to the organic basis of reading disorders from lesion in the calcarine area to the angular gyrus. The competing sentence test, binaural fusion, rapidly alternating speech perception, and filtered speech are described in detail and are organic foundation for the study. The authors indentified a high rate of failure in this investigation. Over 50% of the dyslexic students failed two of the four tests, and each of the 77 failed at least one component. The most sensitive tests were binaural fusion and filtered speech with less variation from the norm in the remaining two components. The effect of maturation in central audition was measured in each of the four tests. The data suggest: 1. the scores are lower in the early ages in each test; 2. that rapidly alternating speech and competing sentences approach the normal range albeit somewhat delayed; and 3. that binaural fusion and filtered speech improve in score somewhat but rather moderately and never approach the normal range. Based upon the central auditory data and in conjunction with the anatomical pathways of vision, the authors suggest the site of lesion to be in the temporo-parietal cortex and the association fibers. PMID:7382713

  19. Computational Modeling of Mammalian Signaling Networks

    PubMed Central

    Hughey, Jacob J; Lee, Timothy K; Covert, Markus W

    2011-01-01

    One of the most exciting developments in signal transduction research has been the proliferation of studies in which a biological discovery was initiated by computational modeling. Here we review the major efforts that enable such studies. First, we describe the experimental technologies that are generally used to identify the molecular components and interactions in, and dynamic behavior exhibited by, a network of interest. Next, we review the mathematical approaches that are used to model signaling network behavior. Finally, we focus on three specific instances of “model-driven discovery”: cases in which computational modeling of a signaling network has led to new insights which have been verified experimentally. Signal transduction networks are the bridge between the extraordinarily complex extracellular environment and a carefully orchestrated cellular response. These networks are largely composed of proteins which can interact, move to specific cellular locations, or be modified or degraded. The integration of these events often leads to the activation or inactivation of transcription factors, which then induce or repress the expression of thousands of genes. Because of this critical role in translating environmental cues to cellular behaviors, malfunctioning signaling networks can lead to a variety of pathologies. One example is cancer, in which many of the key genes found to be involved in cancer onset and development are components of signaling pathways [1, 2]. A detailed understanding of the cellular signaling networks underlying such diseases would likely be extremely useful in developing new treatments. However, the complexity of signaling networks is such that their integrated functions cannot be determined without computational simulation. In recent years, mathematical modeling of signal transduction has led to some exciting new findings and biological discoveries. Here, we review the work that has enabled computational modeling of mammalian

  20. Precancerous lesions of oral mucosa

    PubMed Central

    Yardimci, Gurkan; Kutlubay, Zekayi; Engin, Burhan; Tuzun, Yalcin

    2014-01-01

    Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaque-like, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary. The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used. PMID:25516862

  1. Focal liver lesions found incidentally

    PubMed Central

    Algarni, Abdullah A; Alshuhri, Abdullah H; Alonazi, Majed M; Mourad, Moustafa Mabrouk; Bramhall, Simon R

    2016-01-01

    Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision. PMID:27028805

  2. Evaluation of hepatic cystic lesions.

    PubMed

    Lantinga, Marten A; Gevers, Tom J G; Drenth, Joost P H

    2013-06-21

    Hepatic cysts are increasingly found as a mere coincidence on abdominal imaging techniques, such as ultrasonography (USG), computed tomography (CT) and magnetic resonance imaging (MRI). These cysts often present a diagnostic challenge. Therefore, we performed a review of the recent literature and developed an evidence-based diagnostic algorithm to guide clinicians in characterising these lesions. Simple cysts are the most common cystic liver disease, and diagnosis is based on typical USG characteristics. Serodiagnostic tests and microbubble contrast-enhanced ultrasound (CEUS) are invaluable in differentiating complicated cysts, echinococcosis and cystadenoma/cystadenocarcinoma when USG, CT and MRI show ambiguous findings. Therefore, serodiagnostic tests and CEUS reduce the need for invasive procedures. Polycystic liver disease (PLD) is arbitrarily defined as the presence of > 20 liver cysts and can present as two distinct genetic disorders: autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (PCLD). Although genetic testing for ADPKD and PCLD is possible, it is rarely performed because it does not affect the therapeutic management of PLD. USG screening of the liver and both kidneys combined with extensive family history taking are the cornerstone of diagnostic decision making in PLD. In conclusion, an amalgamation of these recent advances results in a diagnostic algorithm that facilitates evidence-based clinical decision making. PMID:23801855

  3. [Mandibular lesions in multiple myeloma].

    PubMed

    Scutellari, P N; Orzincolo, C

    1992-03-01

    A review was made of 237 cases of multiple myeloma seen at the Institute of Radiology and Hematology of the Ferrara University from 1984 through 1990. The results showed skeletal involvement of the mandible to be present in 25 patients (10.54%). The diagnosis of multiple myeloma was based on the following criteria: 1) increased number of abnormal, atypical or immature plasma cells in the bone marrow; 2) the presence of a monoclonal protein in the serum or urine; 3) bone lesions consistent with those of myeloma. Symptoms include pain and swelling of the oral cavity, tooth mobility and loss, numbness along the inferior dental nerve, and paresthesia of the lower lip. The typical radiographic appearance is a well-defined "punched-out" lytic defect, solitary or multiple; sometimes, the defect enlarges and appears "bubbly" or septated. Permeative lytic areas, with blurred outlines, are a rare pattern, which is radiologically indistinguishable from skeletal metastases. The involvement of the oral cavity and jaw in multiple myeloma has been often reported in literature: nevertheless, if radiographs of the jaws had been systematically taken in all the cases, its incidence would probably have been much higher than previously suspected. PMID:1579669

  4. Cathepsin Protease Inhibition Reduces Endometriosis Lesion Establishment.

    PubMed

    Porter, Kristi M; Wieser, Friedrich A; Wilder, Catera L; Sidell, Neil; Platt, Manu O

    2016-05-01

    Endometriosis is a gynecologic disease characterized by the ectopic presence of endometrial tissue on organs within the peritoneal cavity, causing debilitating abdominal pain and infertility. Current treatments alleviate moderate pain symptoms associated with the disorder but exhibit limited ability to prevent new or recurring lesion establishment and growth. Retrograde menstruation has been implicated for introducing endometrial tissue into the peritoneal cavity, but molecular mechanisms underlying attachment and invasion are not fully understood. We hypothesize that cysteine cathepsins, a group of powerful extracellular matrix proteases, facilitate endometrial tissue invasion and endometriosis lesion establishment in the peritoneal wall and inhibiting this activity would decrease endometriosis lesion implantation. To test this, we used an immunocompetent endometriosis mouse model and found that endometriotic lesions exhibited a greater than 5-fold increase in active cathepsins compared to tissue from peritoneal wall or eutopic endometrium, with cathepsins L and K specifically implicated. Human endometriosis lesions also exhibited greater cathepsin activity than adjacent peritoneum tissue, supporting the mouse results. Finally, we tested the hypothesis that inhibiting cathepsin activity could block endometriosis lesion attachment and implantation in vivo. Intraperitoneal injection of the broad cysteine cathepsin inhibitor, E-64, significantly reduced the number of attached endometriosis lesions in our murine model compared to vehicle-treated controls demonstrating that cathepsin proteases contribute to endometriosis lesion establishment, and their inhibition may provide a novel, nonhormonal therapy for endometriosis. PMID:26482207

  5. Sentinel lesions of primary CNS lymphoma.

    PubMed Central

    Alderson, L; Fetell, M R; Sisti, M; Hochberg, F; Cohen, M; Louis, D N

    1996-01-01

    Some patients ultimately diagnosed with primary CNS lymphoma (PCNSL) have transient symptomatic contrast enhancing lesions. These "sentinel lesions" of PCNSL recede spontaneously or with corticosteroid treatment and present an important diagnostic dilemma because they show variable, but non-diagnostic histopathological features. Four previously healthy, immunocompetent patients aged 49 to 58 years had contrast enhancing intraparenchymal brain lesions. Before biopsy, three of the four were treated with corticosteroids. Initial biopsies showed demyelination with axonal sparing in two, non-specific inflammation in one, and normal brain in one. Infiltrating lymphocytes predominantly expressed T cell markers with rare B cells. All four patients recovered within two to four weeks after the initial biopsy and imaging studies showed resolution of the lesions. The CSF was normal in three of the four patients tested; oligoclonal bands were absent in both of the two tested. After seven to 11 months, each patient developed new symptomatic lesions in a different region of the brain, biopsy of which showed a B cell PCNSL. The mechanism of spontaneous involution of sentinel lesions is not understood, but may represent host immunity against the tumour. Sentinel lesions of PCNSL should be considered in patients with contrast enhancing focal parenchymal lesions that show non-specific or demyelinative histopathological changes. Close clinical and radiographic follow up is essential if PCNSL is to be diagnosed early in such patients. Images PMID:8558135

  6. Quantitative Analysis of Vascular Heterogeneity in Breast Lesions Using Contrast-Enhanced 3-D Harmonic and Subharmonic Ultrasound Imaging

    PubMed Central

    Sridharan, Anush; Eisenbrey, John R.; Machado, Priscilla; Ojeda-Fournier, Haydee; Wilkes, Annina; Sevrukov, Alexander; Mattrey, Robert F.; Wallace, Kirk; Chalek, Carl L.; Thomenius, Kai E.; Forsberg, Flemming

    2015-01-01

    Ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using contrast-enhanced 3-D harmonic (HI) and subharmonic (SHI) ultrasound imaging was investigated in a clinical population. Patients (n = 134) identified with breast lesions on mammography were scanned using power Doppler imaging, contrast-enhanced 3-D HI, and 3-D SHI on a modified Logiq 9 scanner (GE Healthcare). A region of interest corresponding to ultrasound contrast agent flow was identified in 4D View (GE Medical Systems) and mapped to raw slice data to generate a map of time-intensity curves for the lesion volume. Time points corresponding to baseline, peak intensity, and washout of ultrasound contrast agent were identified and used to generate and compare vascular heterogeneity plots for malignant and benign lesions. Vascularity was observed with power Doppler imaging in 84 lesions (63 benign and 21 malignant). The 3-D HI showed flow in 8 lesions (5 benign and 3 malignant), whereas 3-D SHI visualized flow in 68 lesions (49 benign and 19 malignant). Analysis of vascular heterogeneity in the 3-D SHI volumes found benign lesions having a significant difference in vascularity between central and peripheral sections (1.71 ± 0.96 vs. 1.13 ± 0.79 dB, p < 0.001, respectively), whereas malignant lesions showed no difference (1.66 ± 1.39 vs. 1.24 ± 1.14 dB, p = 0.24), indicative of more vascular coverage. These preliminary results suggest quantitative evaluation of vascular heterogeneity in breast lesions using contrast-enhanced 3-D SHI is feasible and able to detect variations in vascularity between central and peripheral sections for benign and malignant lesions. PMID:25935933

  7. Molecular aging of the mammalian vestibular system.

    PubMed

    Brosel, Sonja; Laub, Christoph; Averdam, Anne; Bender, Andreas; Elstner, Matthias

    2016-03-01

    Dizziness and imbalance frequently affect the elderly and contribute to falls and frailty. In many geriatric patients, clinical testing uncovers a dysfunction of the vestibular system, but no specific etiology can be identified. Neuropathological studies have demonstrated age-related degeneration of peripheral and central vestibular neurons, but the molecular mechanisms are poorly understood. In contrast, recent studies into age-related hearing loss strongly implicate mitochondrial dysfunction, oxidative stress and apoptotic cell death of cochlear hair cells. While some data suggest that analogous biological pathomechanisms may underlie vestibular dysfunction, actual proof is missing. In this review, we summarize the available data on the molecular causes of vestibular dysfunction. PMID:26739358

  8. Intraorbital Cystic Lesions: An Imaging Spectrum.

    PubMed

    Pahwa, Shivani; Sharma, Sanjay; Das, Chandan J; Dhamija, Ekta; Agrawal, Saurabh

    2015-01-01

    Presence of a cyst or a cystic component in an intraorbital mass often narrows the list of differential diagnoses to specific entities. Such a lesion in the orbit may arise from structures within the orbit, globe, and lacrimal system or from neighboring paranasal sinuses or meninges. Common congenital and developmental lesions encountered within the orbit include dermoids and epidermoids, and infrequently coloboma. Parasitic cysts (cysticercus), orbital abscess, mucocele, and vascular lesions are the most common acquired pathologies giving rise to fluid-containing lesions within the orbit. The role of a radiologist is crucial in expediting the diagnosis of orbital lesions with the help of characteristic imaging features on ultrasound, computed tomography, or magnetic resonance imaging. It also helps in identifying complications in others where formulation of an early and effective management strategy is vital for preserving vision. PMID:25908230

  9. Radiological evaluation of post-tracheostomy lesions

    PubMed Central

    Macmillan, Alexander S.; James, A. Everette; Stitik, Frederick P.; Grillo, Hermes C.

    1971-01-01

    Post-tracheostomy lesions are becoming more commonplace and surgical techniques for definitive repair of these abnormalities are being developed. These lesions, in general, occur at two sites, the proximal lesions at the tracheostomy incision and the distal lesions 1·5 to 2·5 cm inferior in the area of the tracheostomy balloon cuff. Granuloma formation, stenosis, tracheomalacia, and perforation of the tracheal wall have been encountered in our experience. Clinical symptoms depend upon the type and location of the lesion as well as on the patient's awareness and physical activity. Radiological evaluation offers an accurate method to depict the anatomical and physiological alterations. This radiological assessment should begin with routine postero-anterior and lateral chest radiographs followed by fluoroscopy. Laminograms and special oblique views are often helpful. Contrast tracheograms using powdered tantalum allow good mucosal detail as well as excellent delineation of structural and physiological abnormalities. Images PMID:5144647

  10. Molecular identification of ancient and modern mammalian magnesium transporters.

    PubMed

    Quamme, Gary A

    2010-03-01

    A large number of mammalian Mg(2+) transporters have been hypothesized on the basis of physiological data, but few have been investigated at the molecular level. The recent identification of a number of novel proteins that mediate Mg(2+) transport has enhanced our understanding of how Mg(2+) is translocated across mammalian membranes. Some of these transporters have some similarity to those found in prokaryocytes and yeast cells. Human Mrs2, a mitochondrial Mg(2+) channel, shares many of the properties of the bacterial CorA and yeast Alr1 proteins. The SLC41 family of mammalian Mg(2+) transporters has a similarity with some regions of the bacterial MgtE transporters. The mammalian ancient conserved domain protein (ACDP) Mg(2+) transporters are found in prokaryotes, suggesting an ancient origin. However, other newly identified mammalian transporters, including TRPM6/7, MagT, NIPA, MMgT, and HIP14 families, are not represented in prokaryotic genomes, suggesting more recent development. MagT, NIPA, MMgT, and HIP14 transporters were identified by differential gene expression using microarray analysis. These proteins, which are found in many different tissues and subcellular organelles, demonstrate a diversity of structural properties and biophysical functions. The mammalian Mg(2+) transporters have no obvious amino acid similarities, indicating that there are many ways to transport Mg(2+) across membranes. Most of these proteins transport a number of divalent cations across membranes. Only MagT1 and NIPA2 are selective for Mg(2+). Many of the identified mammalian Mg(2+) transporters are associated with a number of congenital disorders encompassing a wide range of tissues, including intestine, kidney, brain, nervous system, and skin. It is anticipated that future research will identify other novel Mg(2+) transporters and reveal other diseases. PMID:19940067

  11. Mammalian lipocalin allergens--insights into their enigmatic allergenicity.

    PubMed

    Virtanen, T; Kinnunen, T; Rytkönen-Nissinen, M

    2012-04-01

    Most of the important mammal-derived respiratory allergens, as well as a milk allergen and a few insect allergens, belong to the lipocalin protein family. As mammalian lipocalin allergens are found in dander, saliva and urine, they disperse effectively and are widely present in the indoor environments. Initially, lipocalins were characterized as transport proteins for small, principally hydrophobic molecules, but now they are known to be involved in many other biological functions. Although the amino acid identity between lipocalins is generally at the level of 20-30%, it can be considerably higher. Lipocalin allergens do not exhibit any known physicochemical, functional or structural property that would account for their allergenicity, that is, the capacity to induce T-helper type 2 immunity against them. A distinctive feature of mammalian lipocalin allergens is their poor capacity to stimulate the cellular arm of the human or murine immune system. Nevertheless, they induce IgE production in a large proportion of atopic individuals exposed to the allergen source. The poor capacity of mammalian lipocalin allergens to stimulate the cellular immune system does not appear to result from the function of regulatory T cells. Instead, the T cell epitopes of mammalian lipocalin allergens are few and those examined have proved to be suboptimal. Moreover, the frequency of mammalian lipocalin allergen-specific CD4(+) T cells is very low in the peripheral blood. Importantly, recent research suggests that the lipocalin allergen-specific T cell repertoires differ considerably between allergic and healthy subjects. These observations are compatible with our hypothesis that the way CD4(+) T-helper cells recognize the epitopes of mammalian lipocalin allergens may be implicated in their allergenicity. Indeed, as several lipocalins exhibit homologies of 40-60% over species, mammalian lipocalin allergens may be immunologically at the borderline of self and non-self, which would not

  12. Vascularisation of the central nervous system

    PubMed Central

    Tata, Mathew; Ruhrberg, Christiana; Fantin, Alessandro

    2015-01-01

    The developing central nervous system (CNS) is vascularised through the angiogenic invasion of blood vessels from a perineural vascular plexus, followed by continued sprouting and remodelling until a hierarchical vascular network is formed. Remarkably, vascularisation occurs without perturbing the intricate architecture of the neurogenic niches or the emerging neural networks. We discuss the mouse hindbrain, forebrain and retina as widely used models to study developmental angiogenesis in the mammalian CNS and provide an overview of key cellular and molecular mechanisms regulating the vascularisation of these organs. PMID:26222953

  13. Gephyrin: a central GABAergic synapse organizer.

    PubMed

    Choii, Gayoung; Ko, Jaewon

    2015-01-01

    Gephyrin is a central element that anchors, clusters and stabilizes glycine and γ-aminobutyric acid type A receptors at inhibitory synapses of the mammalian brain. It self-assembles into a hexagonal lattice and interacts with various inhibitory synaptic proteins. Intriguingly, the clustering of gephyrin, which is regulated by multiple posttranslational modifications, is critical for inhibitory synapse formation and function. In this review, we summarize the basic properties of gephyrin and describe recent findings regarding its roles in inhibitory synapse formation, function and plasticity. We will also discuss the implications for the pathophysiology of brain disorders and raise the remaining open questions in this field. PMID:25882190

  14. Massively parallel cis-regulatory analysis in the mammalian central nervous system

    PubMed Central

    Shen, Susan Q.; Myers, Connie A.; Hughes, Andrew E.O.; Byrne, Leah C.; Flannery, John G.; Corbo, Joseph C.

    2016-01-01

    Cis-regulatory elements (CREs, e.g., promoters and enhancers) regulate gene expression, and variants within CREs can modulate disease risk. Next-generation sequencing has enabled the rapid generation of genomic data that predict the locations of CREs, but a bottleneck lies in functionally interpreting these data. To address this issue, massively parallel reporter assays (MPRAs) have emerged, in which barcoded reporter libraries are introduced into cells, and the resulting barcoded transcripts are quantified by next-generation sequencing. Thus far, MPRAs have been largely restricted to assaying short CREs in a limited repertoire of cultured cell types. Here, we present two advances that extend the biological relevance and applicability of MPRAs. First, we adapt exome capture technology to instead capture candidate CREs, thereby tiling across the targeted regions and markedly increasing the length of CREs that can be readily assayed. Second, we package the library into adeno-associated virus (AAV), thereby allowing delivery to target organs in vivo. As a proof of concept, we introduce a capture library of about 46,000 constructs, corresponding to roughly 3500 DNase I hypersensitive (DHS) sites, into the mouse retina by ex vivo plasmid electroporation and into the mouse cerebral cortex by in vivo AAV injection. We demonstrate tissue-specific cis-regulatory activity of DHSs and provide examples of high-resolution truncation mutation analysis for multiplex parsing of CREs. Our approach should enable massively parallel functional analysis of a wide range of CREs in any organ or species that can be infected by AAV, such as nonhuman primates and human stem cell–derived organoids. PMID:26576614

  15. Synaptic inhibition and γ-aminobutyric acid in the mammalian central nervous system

    PubMed Central

    OBATA, Kunihiko

    2013-01-01

    Signal transmission through synapses connecting two neurons is mediated by release of neurotransmitter from the presynaptic axon terminals and activation of its receptor at the postsynaptic neurons. γ-Aminobutyric acid (GABA), non-protein amino acid formed by decarboxylation of glutamic acid, is a principal neurotransmitter at inhibitory synapses of vertebrate and invertebrate nervous system. On one hand glutamic acid serves as a principal excitatory neurotransmitter. This article reviews GABA researches on; (1) synaptic inhibition by membrane hyperpolarization, (2) exclusive localization in inhibitory neurons, (3) release from inhibitory neurons, (4) excitatory action at developmental stage, (5) phenotype of GABA-deficient mouse produced by gene-targeting, (6) developmental adjustment of neural network and (7) neurological/psychiatric disorder. In the end, GABA functions in simple nervous system and plants, and non-amino acid neurotransmitters were supplemented. PMID:23574805

  16. 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. PMID:25595250

  17. Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy.

    PubMed

    Woolf, C J; Shortland, P; Reynolds, M; Ridings, J; Doubell, T; Coggeshall, R E

    1995-09-11

    We have investigated the time course and extent to which peripheral nerve lesions cause a morphological reorganization of the central terminals of choleragenoid-horseradish peroxidase (B-HRP)-labelled primary afferent fibers in the mammalian dorsal horn. Choleragenoid-horseradish peroxidase is retrogradely transported by myelinated (A) sensory axons to laminae I, III, IV and V of the normal dorsal horn of the spinal cord, leaving lamina II unlabelled. We previously showed that peripheral axotomy results in the sprouting of numerous B-HRP-labelled large myelinated sensory axons into lamina II. We show here that this spread of B-HRP-labelled axons into lamina II is detectable at 1 week, maximal by 2 weeks and persists for over 6 months postlesion. By 9 months, however, B-HRP fibers no longer appear in lamina II. The sprouting into lamina II occurs whether regeneration is allowed (crush) or prevented (section with ligation), and does not reverse at times when peripheral fibers reinnervate the periphery. We also show that 15 times more synaptic terminals in lamina II are labelled by B-HRP 2 weeks after axotomy than in the normal. We interpret this as indicating that the sprouting fibers are making synaptic contacts with postsynaptic targets. This implies that A-fiber terminal reorganization is a prominent and long-lasting but not permanent feature of peripheral axotomy. We also provide evidence that this sprouting is the consequence of a combination of an atrophic loss of central synaptic terminals and the conditioning of the sensory neurons by peripheral axotomy. The sprouting of large sensory fibers into the spinal territory where postsynaptic targets usually receive only small afferent fiber input may bear on the intractable touch-evoked pain that can follow nerve injury. PMID:7499558

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

    PubMed Central

    Li, Ping; Noegel, Angelika A.

    2015-01-01

    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 linker of nucleoskeleton and cytoskeleton (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. PMID:26476453

  19. Mammalian CNS barosensitivity: studied by brain-stem auditory-evoked potential in mice.

    PubMed

    Chen, Ruiyong; Xiao, Weibing; Li, Jun; He, Jia; Chen, Haiting

    2012-01-01

    High pressure nervous syndrome (HPNS) is an instinctive response of mammalian high-class nervous functions to increased hydrostatic pressure. Electrophysiological activity of mammalian central nervous system (CNS), including brainstem auditory-evoked potential (BAEP), has characteristic changes under pressure. Here we recorded BAEP of 63 mice exposed to 0-4.0 MPa. The results showed that interpeak latencies between wave I and wave IV (IPL1-4) and their changes under pressures (deltaIPL1-4) responded to increasing pressure in a biphase pattern, shortened under pressure from 0 to 0.7MPa, then prolonged later. There were significantly negative correlations between base IPL1-4s and deltaIPL1-4s (p < 0.01). Individual IPL1-4s were supposed to respond to increasing pressure in a relative steady pattern in accordance with its base IPL1-4s. Those with shorter-base IPL1-4 presented direct increases in IPL1-4. However, those with longer-base IPL1-4 had a decreased IPL1-4 under small to moderate pressure then rebounded later. Our results suggested that mammalian CNS functions were susceptible to small to moderate pressure, as well as a higher pressure than 1.0MPa. Mice, as a statistical mass, had an "optimum" pressure about 0.7MPa, rather than atmospheric pressure, referred as shortest IPL1-4s. An individual's response to high pressure might be relied on his base biological condition. Our results highlighted a new approach to investigate a practical strategy to medical selecting barotolerant candidates for deep divers. Diversity of individual susceptibility to hydrostatic pressure was under discussed. Underlying mechanisms of the "optimum" pressure for CNS function and its significance to neurophysiology remain open to further exploration. PMID:22400446

  20. Selection for intrabody solubility in mammalian cells using GFP fusions.

    PubMed

    Guglielmi, Laurence; Denis, Vincent; Vezzio-Vié, Nadia; Bec, Nicole; Dariavach, Piona; Larroque, Christian; Martineau, Pierre

    2011-12-01

    Single-chain antibody fragments (scFv) expressed in the cytoplasm of mammalian cells, also called intrabodies, have many applications in functional proteomics. These applications are, however, limited by the aggregation-prone behaviour of many intrabodies. We show here that two scFv with highly homologous sequences and comparable soluble expression levels in Escherichia coli cytoplasm have different behaviours in mammalian cells. When over-expressed, one of the scFv aggregates in the cytoplasm whereas the second one is soluble and active. When expressed at low levels, using a retroviral vector, as a fusion with the green fluorescent protein (GFP) the former does not form aggregates and is degraded, resulting in weakly fluorescent cells, whereas the latter is expressed as a soluble protein, resulting in strongly fluorescent cells. These data suggest that the GFP signal can be used to evaluate the soluble expression of intrabodies in mammalian cells. When applied to a subset of an E.coli-optimised intrabody library, we showed that the population of GFP+ cells contains indeed soluble mammalian intrabodies. Altogether, our data demonstrate that the requirements for soluble intrabody expression are different in E.coli and mammalian cells, and that intrabody libraries can be directly optimised in human cells using a simple GFP-based assay. PMID:21997307