Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons.

PubMed

Locati, Mauro D; Pagano, Johanna F B; Ensink, Wim A; van Olst, Marina; van Leeuwen, Selina; Nehrdich, Ulrike; Zhu, Kongju; Spaink, Herman P; Girard, Geneviève; Rauwerda, Han; Jonker, Martijs J; Dekker, Rob J; Breit, Timo M

2017-04-01

5S rRNA is a ribosomal core component, transcribed from many gene copies organized in genomic repeats. Some eukaryotic species have two 5S rRNA types defined by their predominant expression in oogenesis or adult tissue. Our next-generation sequencing study on zebrafish egg, embryo, and adult tissue identified maternal-type 5S rRNA that is exclusively accumulated during oogenesis, replaced throughout the embryogenesis by a somatic-type, and thus virtually absent in adult somatic tissue. The maternal-type 5S rDNA contains several thousands of gene copies on chromosome 4 in tandem repeats with small intergenic regions, whereas the somatic-type is present in only 12 gene copies on chromosome 18 with large intergenic regions. The nine-nucleotide variation between the two 5S rRNA types likely affects TFIII binding and riboprotein L5 binding, probably leading to storage of maternal-type rRNA. Remarkably, these sequence differences are located exactly at the sequence-specific target site for genome integration by the 5S rRNA-specific Mutsu retrotransposon family. Thus, we could define maternal- and somatic-type MutsuDr subfamilies. Furthermore, we identified four additional maternal-type and two new somatic-type MutsuDr subfamilies, each with their own target sequence. This target-site specificity, frequently intact maternal-type retrotransposon elements, plus specific presence of Mutsu retrotransposon RNA and piRNA in egg and adult tissue, suggest an involvement of retrotransposons in achieving the differential copy number of the two types of 5S rDNA loci. © 2017 Locati et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

PubMed Central

Castori, Marco

2012-01-01

Ehlers-Danlos syndrome, hypermobility type, constituting a phenotypic continuum with or, perhaps, corresponding to the joint hypermobility syndrome (JHS/EDS-HT), is likely the most common, though the least recognized, heritable connective tissue disorder. Known for decades as a hereditary condition with predominant rheumatologic manifestations, it is now emerging as a multisystemic disorder with widespread manifestations. Nevertheless, the practitioners' awareness of this condition is generally poor and most patients await years or, perhaps, decades before reaching the correct diagnosis. Among the various sites of disease manifestations, skin and mucosae represent a neglected organ where the dermatologist can easily spot diagnostic clues, which consistently integrate joint hypermobility and other orthopedic/neurologic manifestations at physical examination. In this paper, actual knowledge on JHS/EDS-HT is summarized in various sections. Particular attention has been posed on overlooked manifestations, including cutaneous, mucosal, and oropharyngeal features, and early diagnosis techniques, as a major point of interest for the practicing dermatologist. Actual research progresses on JH/EDS-HT envisage an unexpected link between heritable dysfunctions of the connective tissue and a wide range of functional somatic syndromes, most of them commonly diagnosed in the office of various specialists, comprising dermatologists. PMID:23227356

Somatic mutations contribute to genotypic diversity in sterile and fertile populations of the threatened shrub, Grevillea rhizomatosa (Proteaceae).

PubMed

Gross, C L; Nelson, Penelope A; Haddadchi, Azadeh; Fatemi, Mohammad

2012-02-01

Grevillea rhizomatosa is a spreading shrub which exhibits multiple breeding strategies within a narrow area in the fire-prone heathlands of eastern Australia. Reproductive strategies include self-compatibility, self-incompatibility and clonality (with and without sterility). The close proximity of contrasting breeding systems provides an opportunity to explore the evolution of sterility and to compare and contrast the origins of genotypic diversity (recombinant or somatic) against degrees of sexual expression. ISSR markers for 120 band positions (putative loci) were used to compare genetic diversity among five populations at a macro-scale of 5 m between samples (n = 244 shrubs), and at a micro-scale of nearest neighbours for all plants in five 25-m(2) quadrats with contrasting fertilities (n = 162 shrubs). Nearest-neighbour sampling included several clusters of connected ramets. Matrix incompatibility (MIC) analyses were used to evaluate the relative contribution of recombination and somatic mutation to genotype diversity. High levels of genotypic diversity were found in all populations regardless of fertilities (fertile populations, G/N ≥ 0·94; sterile populations, G/N ≥ 0·97) and most sterile populations had a unique genetic profile. Somatic mutations were detected along connected ramets in ten out of 42 ramet clusters. MIC analyses showed that somatic mutations have contributed to diversity in all populations and particularly so in sterile populations. Somatic mutations contribute significantly to gene diversity in sterile populations of Grevillea rhizomatosa, the accumulation of which is the likely cause of male and female sterility. High levels of genetic diversity therefore may not always be synonymous with sexual fitness and genetic health. We hypothesize that frequent fires drive selection for clonal reproduction, at the cost of flowering such that sexual functions are not maintained through selection, and the build-up of somatic mutations in meristems results in high genotype diversity at the cost of pollen and ovule fertilities.

Proteogenomics connects somatic mutations to signalling in breast cancer.

PubMed

Mertins, Philipp; Mani, D R; Ruggles, Kelly V; Gillette, Michael A; Clauser, Karl R; Wang, Pei; Wang, Xianlong; Qiao, Jana W; Cao, Song; Petralia, Francesca; Kawaler, Emily; Mundt, Filip; Krug, Karsten; Tu, Zhidong; Lei, Jonathan T; Gatza, Michael L; Wilkerson, Matthew; Perou, Charles M; Yellapantula, Venkata; Huang, Kuan-lin; Lin, Chenwei; McLellan, Michael D; Yan, Ping; Davies, Sherri R; Townsend, R Reid; Skates, Steven J; Wang, Jing; Zhang, Bing; Kinsinger, Christopher R; Mesri, Mehdi; Rodriguez, Henry; Ding, Li; Paulovich, Amanda G; Fenyö, David; Ellis, Matthew J; Carr, Steven A

2016-06-02

Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.

Residues in the analyst of the patient's symbiotic connection at a somatic level: unrepresented states in the patient and analyst.

PubMed

Godsil, Geraldine

2018-02-01

This paper discusses the residues of a somatic countertransference that revealed its meaning several years after apparently successful analytic work had ended. Psychoanalytic and Jungian analytic ideas on primitive communication, dissociation and enactment are explored in the working through of a shared respiratory symptom between patient and analyst. Growth in the analyst was necessary so that the patient's communication at a somatic level could be understood. Bleger's concept that both the patient's and analyst's body are part of the setting was central in the working through. © 2018, The Society of Analytical Psychology.

[Functional somatization: a conceptual review].

PubMed

Fabião, Cristina; Fleming, Manuela; Barbosa, António

2011-01-01

The authors have brought together and analised texts about the history of the concept of hysteria. In these texts hysteria is fundamentally considered a disease of organic origin (of the womb), and, in the Middle Age, evidence of demonic possession. From the XVII century onwards, apart from the etiopathogenic concepts, also taken into consideration are aspects connected to the differential diagnosis with other similar entities and the therapy used each period. Even, in subsequent centuries, authors such as Syndenham, who consider hysteria to be a multidimensional entity, are rare. Empiricism has contributed to discoveries in biology and physiology, both general and of the nervous system itself, and given birth to the formulation of the Spinal Irritation Theory and Reflex Theory. These theories have led to strictly organic treatment of hysteria, in the same way that hysterectomies were performed to alleviate somatic symptoms connected to this disease. The introduction of hypnosis in medical practice, with Charcot in X1X century, allowed for the element of suggestion to be observed ( a non organic element) which accompanies the symptoms of hysteria. Two of his disciples, Janet and Freud, would define and isolate psychic mechanisms in the symptoms of hysteria: Dissociation of the consciousness (Janet) and Conversion (Freud). The last one developed a therapeutic method of a psychological nature for hysteria. The therapeutic implications and the pertinence of the distinction between unspecific somatization or functional (of somatic origin) somatization and somatization linked to disassociation mechanisms and conversion (psychic origin) are discussed as well as the evolution of international classification systems of somatization and the questions posed by the algorithms chosen for the cataloguing of symptoms. A revision of the relevant empirical studies about the association of somatization with depressive and anxiety disorders, within the general population, is made. The characteristics that permeate the clinical descriptions of somatoform disorders (whose validity criteria remain weak) and are not integrated within the diagnostic criteria for somatoform disorders are considered. We draw conclusions about the difficulties and consequences of the changes that some authors advocate in relation to the new classification system for somatoform syndromes.

A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland.

PubMed

Sands, Dorota; Umławska, Wioleta; Zielińska, Anna

2015-03-16

Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = -0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = -0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = -0.75 and Z-score = -0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters.

Serotypes and DNA fingerprint profiles of Pasteurella multocida isolated from raptors

USGS Publications Warehouse

Wilson, M.A.; Duncan, R.M.; Nordholm, G.E.; Berlowski, B.M.

1995-01-01

Pasteurella multocida isolates from 21 raptors were examined by DNA fingerprint profile and serotyping methods. Isolates were obtained from noncaptive birds of prey found in 11 states from November 28, 1979, through February 10, 1993. Nine isolates were from bald eagles, and the remaining isolates were from hawks, falcons, and owls. Seven isolates were members of capsule group A, and 14 were nonencapsulated. One isolate was identified as somatic type 3, and another was type 3,4,7; both had unique HhaI DNA fingerprint profiles. Nineteen isolates expressed somatic type 1 antigen; HhaI profiles of all type 1 isolates were identical to each other and to the HhaI profile of the reference somatic type 1, strain X-73. The 19 type 1 isolates were differentiated by sequential digestion of DNA with HpaII; four HpaII fingerprint profiles were obtained. The HpaII profile of one isolate was identical to the HpaII profile of strain X-73. Incidence of P. multocida somatic type 1 in raptors suggests that this type may be prevalent in other wildlife or wildlife environments.

Inducing somatic meiosis-like reduction at high frequency by caffeine in root-tip cells of Vicia faba.

PubMed

Chen, Y; Zhang, L; Zhou, Y; Geng, Y; Chen, Z

2000-07-20

Germinated seeds of Vicia faba were treated in caffeine solutions of different concentration for different durations to establish the inducing system of somatic meiosis-like reduction. The highest frequency of somatic meiosis-like reduction could reach up to 54.0% by treating the root tips in 70 mmol/l caffeine solution for 2 h and restoring for 24 h. Two types of somatic meiosis-like reduction were observed. One was reductional grouping, in which the chromosomes in a cell usually separated into two groups, and the role of spindle fibers did not show. The other type was somatic meiosis, which was analogous to meiosis presenting in gametogenesis, and chromosome pairing and chiasmata were visualized.

Gender-Associated Mitochondrial DNA Heteroplasmy in Somatic Tissues of the Endangered Freshwater Mussel Unio crassus (Bivalvia: Unionidae): Implications for Sex Identification and Phylogeographical Studies.

PubMed

Mioduchowska, Monika; Kaczmarczyk, Agnieszka; Zając, Katarzyna; Zając, Tadeusz; Sell, Jerzy

2016-11-01

Some bivalve species possess two independent mitochondrial DNA lineages: maternally (F-type) and paternally (M-type) inherited. This phenomenon is called doubly uniparental inheritance. It is generally agreed that F-type mtDNA is typically present in female somatic and gonadal tissues as well as in male somatic tissues, whereas the M-type mtDNA occurs only in male germ line and gonadal tissue. In the present study, the mtDNA heteroplasmy (for both F and M genomes) in male somatic tissues of Unio crassus (Philipsson, 1788), species threatened with extinction, has been confirmed. Taking advantage from the presence of Mcox1 marker only in male somatic tissues, we developed a new method of sex identification in this endangered species, using nondestructive tissue sampling. Probability of correct sex identification was estimated at 97.5%. The present study is the first report on gender-associated mitochondrial DNA heteroplasmy in male somatic tissues of thick-shelled river mussel and first approach to U. crassus sex identification at molecular level. Our study also confirmed the utility of paternally inherited Mcox1 gene fragment as a complementary molecular tool for resolving phylogeographical relationships among populations of thick-shelled river mussel. © 2017 Wiley Periodicals, Inc.

Somatic embryogenesis from flower explants of cocoa (Theobroma cacao L.).

PubMed

Silva, J J; Debergh, P

2001-01-01

Two types of flower explants, staminoides and petals, were used for in vitro induction of somatic embryos in cocoa. After 14 days in culture, we observed globular structures and callus formation on both types of explants. However, the better results were obtained on staminoides: 98.3% formed callus and 86.2% somatic embryos on Murashige and Skoog (1962) medium supplemented with sucrose, coconut water, 2,4-D, kinetin and agar.

Pasteurella multocida isolated from wild birds of North America: a serotype and DNA fingerprint study of isolates from 1978 to 1993

USGS Publications Warehouse

Wilson, M.A.; Duncan, R.M.; Nordholm, G.E.; Berlowski, B.M.

1995-01-01

Serotype and DNA fingerprint methods were used to study Pasteurella multocida isolated from 320 wild birds of North America. Isolates were collected during 1978-93. The HhaI profiles of 314 isolates matched the HhaI profile of somatic reference type 1, strain X-73; somatic type 1 antigen was expressed by 310 isolates, and the serotype of four isolates was undetected. Differentiation of the 314 isolates was observed by digestion of DNA with HpaII. None of the HpaII profiles matched the HpaII profile of X-73 (designated HhaI 001/HpaII 001). Three HpaII profiles were recognized among the somatic type 1 isolates: HpaII 002 (n = 18), HpaII 003 (n = 122), and HpaII 004 (n = 174). Profile HpaII 002 was found among isolates collected during 1979-83. Profile HpaII 003 was identified from isolates collected during 1979-89, with the exception of two isolates in 1992. The HpaII 004 profile was identified from isolates collected during 1983-93. Of the six remaining isolates, four expressed somatic type 4 and had HhaI profiles identical to the somatic type 4 reference strain P-1662 profile (designated HhaI 004); these isolates were differentiated by digestion of DNA with HpaII. One isolate was identified as serotype F:11, and another was serotype A:3,4. In the present study, 314 of 316 (99.4%) isolates from wild birds in the Central, Mississippi, and Pacific flyways during 1978-93, were P. multocida somatic type 1.

The Mind/Body Connection and the Practice of Classical Ballet

ERIC Educational Resources Information Center

Dixon, Emma

2005-01-01

This paper examines two very different approaches to dance training, ballet technique and the somatic discipline of Topf technique ("TT"). It explores and evaluates the application of TT to ballet training. Initially, what is meant by the term "mind/body connection" is discussed, and then the paper examines, in a theoretical and a practical sense,…

A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland

PubMed Central

Sands, Dorota; Zielińska, Anna

2015-01-01

Introduction Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. Material and methods The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. Results The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = –0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = –0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = –0.75 and Z-score = –0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. Conclusions The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters. PMID:25861303

Loss of CMD2‐mediated resistance to cassava mosaic disease in plants regenerated through somatic embryogenesis

PubMed Central

Chauhan, Raj Deepika; Wagaba, Henry; Moll, Theodore; Alicai, Titus; Miano, Douglas; Carrington, James C.; Taylor, Nigel J.

2016-01-01

Summary Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are the two most important viral diseases affecting cassava production in Africa. Three sources of resistance are employed to combat CMD: polygenic recessive resistance, termed CMD1, the dominant monogenic type, named CMD2, and the recently characterized CMD3. The farmer‐preferred cultivar TME 204 carries inherent resistance to CMD mediated by CMD2, but is highly susceptible to CBSD. Selected plants of TME 204 produced for RNA interference (RNAi)‐mediated resistance to CBSD were regenerated via somatic embryogenesis and tested in confined field trials in East Africa. Although micropropagated, wild‐type TME 204 plants exhibited the expected levels of resistance, all plants regenerated via somatic embryogenesis were found to be highly susceptible to CMD. Glasshouse studies using infectious clones of East African cassava mosaic virus conclusively demonstrated that the process of somatic embryogenesis used to regenerate cassava caused the resulting plants to become susceptible to CMD. This phenomenon could be replicated in the two additional CMD2‐type varieties TME 3 and TME 7, but the CMD1‐type cultivar TMS 30572 and the CMD3‐type cultivar TMS 98/0505 maintained resistance to CMD after passage through somatic embryogenesis. Data are presented to define the specific tissue culture step at which the loss of CMD resistance occurs and to show that the loss of CMD2‐mediated resistance is maintained across vegetative generations. These findings reveal new aspects of the widely used technique of somatic embryogenesis, and the stability of field‐level resistance in CMD2‐type cultivars presently grown by farmers in East Africa, where CMD pressure is high. PMID:26662210

Survival of prototype strains of somatic coliphage families in environmental waters and when exposed to UV low-pressure monochromatic radiation or heat.

PubMed

Lee, Hee Suk; Sobsey, Mark D

2011-06-01

The potential use of specific somatic coliphage taxonomic groups as viral indicators based on their persistence and prevalence in water was investigated. Representative type strains of the 4 major somatic coliphage taxonomic groups were seeded into reagent water and an ambient surface water source of drinking water and the survival of the added phages was measured over 90 days at temperatures of 23-25 and 4 °C. Microviridae (type strain PhiX174), Siphoviridae (type strain Lambda), and Myoviridae (type strain T4) viruses were the most persistent in water at the temperatures tested. The Microviridae (type strain PhiX174) and the Siphoviridae (type strain Lambda) were the most resistant viruses to UV radiation and the Myoviridae (type strain T4) and the Microviridae (type strain PhiX174) were the most resistant viruses to heat. Based on their greater persistence in water over time and their relative resistance to heat and/or UV radiation, the Myoviridae (type strain T4), the Microviridae (type strain PhiX174), and the Siphoviridae (type strain Lambda) were the preferred candidate somatic coliphages as fecal indicator viruses in water, with the Microviridae (type strain PhiX174) the most resistant to these conditions overall. Copyright © 2011 Elsevier Ltd. All rights reserved.

Traditional Chinese medicinal herbal tea consumption, self-reported somatization, and alexithymia.

PubMed

Chio, Pit Hoi; Zaroff, Charles M

2015-06-01

Somatic presentations of distress are common cross-culturally, although perhaps more so in Asian cultures. Somatic presentations of distress may be associated with alexithymia, a difficulty in experiencing and expressing emotions. Although the constructs of somatization and alexithymia have been examined in depth both within and across cultures, there is minimal information on culture-specific behaviors utilized to cope with stress in individuals who tend to somaticize distress or are alexithymic. The current report investigates the association between somatization and alexithymia, and a culture-specific behavior of traditional Chinese medicinal herbal tea consumption, in a nonclinical, young adult sample. A sample of 222 undergraduate university students of Chinese ethnicity completed self-report measures of somatization and the related construct of somatosensory amplification, alexithymia, and attitude toward the consumption of herbal tea possessing traditional Chinese medicinal value. After controlling for gender, alexithymia was significantly correlated with somatization (r[220] = 0.29, P < 0.05) and somatosensory amplification (r[220] = 0.19, P < 0.05). Attitudes toward herbal tea consumption were significantly correlated with somatosensory amplification (r[220] = 0.16, P < 0.05). The connection between alexithymia and somatization was confirmed in the current report in a nonclinical sample. A culture-specific behavior (consumption of traditional Chinese medicinal herbal tea) was significantly associated with somatosensory amplification. Potential etiologies and implications of the current findings are discussed. © 2014 Wiley Publishing Asia Pty Ltd.

Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence Detection and Activity Propagation

PubMed Central

Chua, Yansong; Morrison, Abigail

2016-01-01

The role of dendritic spiking mechanisms in neural processing is so far poorly understood. To investigate the role of calcium spikes in the functional properties of the single neuron and recurrent networks, we investigated a three compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in the distal compartment. By performing single neuron simulations with noisy synaptic input and occasional large coincident input at either just the distal compartment or at both somatic and distal compartments, we show that the presence of calcium spikes confers a substantial advantage for coincidence detection in the former case and a lesser advantage in the latter. We further show that the experimentally observed critical frequency phenomenon, in which action potentials triggered by stimuli near the soma above a certain frequency trigger a calcium spike at distal dendrites, leading to further somatic depolarization, is not exhibited by a neuron receiving realistically noisy synaptic input, and so is unlikely to be a necessary component of coincidence detection. We next investigate the effect of calcium spikes in propagation of spiking activities in a feed-forward network (FFN) embedded in a balanced recurrent network. The excitatory neurons in the network are again connected to either just the distal, or both somatic and distal compartments. With purely distal connectivity, activity propagation is stable and distinguishable for a large range of recurrent synaptic strengths if the feed-forward connections are sufficiently strong, but propagation does not occur in the absence of calcium spikes. When connections are made to both the somatic and the distal compartments, activity propagation is achieved for neurons with active calcium dynamics at a much smaller number of neurons per pool, compared to a network of passive neurons, but quickly becomes unstable as the strength of recurrent synapses increases. Activity propagation at higher scaling factors can be stabilized by increasing network inhibition or introducing short term depression in the excitatory synapses, but the signal to noise ratio remains low. Our results demonstrate that the interaction of synchrony with dendritic spiking mechanisms can have profound consequences for the dynamics on the single neuron and network level. PMID:27499740

Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence Detection and Activity Propagation.

PubMed

Chua, Yansong; Morrison, Abigail

2016-01-01

The role of dendritic spiking mechanisms in neural processing is so far poorly understood. To investigate the role of calcium spikes in the functional properties of the single neuron and recurrent networks, we investigated a three compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in the distal compartment. By performing single neuron simulations with noisy synaptic input and occasional large coincident input at either just the distal compartment or at both somatic and distal compartments, we show that the presence of calcium spikes confers a substantial advantage for coincidence detection in the former case and a lesser advantage in the latter. We further show that the experimentally observed critical frequency phenomenon, in which action potentials triggered by stimuli near the soma above a certain frequency trigger a calcium spike at distal dendrites, leading to further somatic depolarization, is not exhibited by a neuron receiving realistically noisy synaptic input, and so is unlikely to be a necessary component of coincidence detection. We next investigate the effect of calcium spikes in propagation of spiking activities in a feed-forward network (FFN) embedded in a balanced recurrent network. The excitatory neurons in the network are again connected to either just the distal, or both somatic and distal compartments. With purely distal connectivity, activity propagation is stable and distinguishable for a large range of recurrent synaptic strengths if the feed-forward connections are sufficiently strong, but propagation does not occur in the absence of calcium spikes. When connections are made to both the somatic and the distal compartments, activity propagation is achieved for neurons with active calcium dynamics at a much smaller number of neurons per pool, compared to a network of passive neurons, but quickly becomes unstable as the strength of recurrent synapses increases. Activity propagation at higher scaling factors can be stabilized by increasing network inhibition or introducing short term depression in the excitatory synapses, but the signal to noise ratio remains low. Our results demonstrate that the interaction of synchrony with dendritic spiking mechanisms can have profound consequences for the dynamics on the single neuron and network level.

Differences in Cell Division Rates Drive the Evolution of Terminal Differentiation in Microbes

PubMed Central

Matias Rodrigues, João F.; Rankin, Daniel J.; Rossetti, Valentina; Wagner, Andreas; Bagheri, Homayoun C.

2012-01-01

Multicellular differentiated organisms are composed of cells that begin by developing from a single pluripotent germ cell. In many organisms, a proportion of cells differentiate into specialized somatic cells. Whether these cells lose their pluripotency or are able to reverse their differentiated state has important consequences. Reversibly differentiated cells can potentially regenerate parts of an organism and allow reproduction through fragmentation. In many organisms, however, somatic differentiation is terminal, thereby restricting the developmental paths to reproduction. The reason why terminal differentiation is a common developmental strategy remains unexplored. To understand the conditions that affect the evolution of terminal versus reversible differentiation, we developed a computational model inspired by differentiating cyanobacteria. We simulated the evolution of a population of two cell types –nitrogen fixing or photosynthetic– that exchange resources. The traits that control differentiation rates between cell types are allowed to evolve in the model. Although the topology of cell interactions and differentiation costs play a role in the evolution of terminal and reversible differentiation, the most important factor is the difference in division rates between cell types. Faster dividing cells always evolve to become the germ line. Our results explain why most multicellular differentiated cyanobacteria have terminally differentiated cells, while some have reversibly differentiated cells. We further observed that symbioses involving two cooperating lineages can evolve under conditions where aggregate size, connectivity, and differentiation costs are high. This may explain why plants engage in symbiotic interactions with diazotrophic bacteria. PMID:22511858

Is chronic pain associated with somatization/hypochondriasis? An evidence-based structured review.

PubMed

Fishbain, David A; Lewis, John E; Gao, Jinrun; Cole, Brandly; Steele Rosomoff, R

2009-01-01

This is an evidence-based structured review. The objectives of this review were to answer the following questions: (1) Are somatization/hypochondriasis associated with chronic pain? (2) Is the degree of somatization/hypochondriasis related to pain levels? (3) Does pain treatment improve somatization/hypochondriasis? (4) Are some pain diagnoses differentially associated with somatization/hypochondriasis? Fifty-seven studies which fulfilled inclusion criteria and had high quality scores were sorted by the above-mentioned objectives. Agency for health care policy and research guidelines were utilized to type and characterize the strength/consistency of the study evidence within each objective. Somatization and hypochondriasis were both consistently associated with chronic pain (consistency ratings B and A, respectively). Study evidence indicated a correlation between pain intensity and presence of somatization and hypochondriasis (consistency rating A and B, respectively). Pain treatment improved somatization and hypochondriasis (consistency rating B and A, respectively). Some chronic pain diagnostic groups somatized more (consistency rating B). Somatization is commonly associated with chronic pain and may relate to pain levels.

Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

PubMed Central

Hamada, Mustafa S.; Goethals, Sarah; de Vries, Sharon I.; Brette, Romain

2016-01-01

In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies. PMID:27930291

Negative Social Contextual Stressors and Somatic Symptoms Among Young Black Males: An Exploratory Study

PubMed Central

Scott, Lionel D.; McCoy, Henrika

2016-01-01

This study examines whether negative social contextual stressors were associated with somatic symptoms among young Black males (N = 74) after accounting for background and psychological characteristics. Using Cunningham and Spencer’s Black Male Experiences Measure, negative social contextual stressors connoted those experiences connected to the personal attributes, devaluation, and negative imagery of young Black males, such as being followed when entering a store or police or security guards asking them what they are doing when hanging out (e.g., in the park or playground or on the street corner). Results showed that such stressors made a unique and significant contribution to the experience of somatic symptoms. Future research directions and implications for addressing the larger societal perceptions of young Black males are discussed. PMID:27134517

Negative Social Contextual Stressors and Somatic Symptoms Among Young Black Males: An Exploratory Study.

PubMed

Scott, Lionel D; McCoy, Henrika

This study examines whether negative social contextual stressors were associated with somatic symptoms among young Black males ( N = 74) after accounting for background and psychological characteristics. Using Cunningham and Spencer's Black Male Experiences Measure, negative social contextual stressors connoted those experiences connected to the personal attributes, devaluation, and negative imagery of young Black males, such as being followed when entering a store or police or security guards asking them what they are doing when hanging out (e.g., in the park or playground or on the street corner). Results showed that such stressors made a unique and significant contribution to the experience of somatic symptoms. Future research directions and implications for addressing the larger societal perceptions of young Black males are discussed.

Bidirectional Causal Connectivity in the Cortico-Limbic-Cerebellar Circuit Related to Structural Alterations in First-Episode, Drug-Naive Somatization Disorder

PubMed Central

Li, Ranran; Liu, Feng; Su, Qinji; Zhang, Zhikun; Zhao, Jin; Wang, Ying; Wu, Renrong; Zhao, Jingping; Guo, Wenbin

2018-01-01

Background: Anatomical and functional deficits in the cortico-limbic-cerebellar circuit are involved in the neurobiology of somatization disorder (SD). The present study was performed to examine causal connectivity of the cortico-limbic-cerebellar circuit related to structural deficits in first-episode, drug-naive patients with SD at rest. Methods: A total of 25 first-episode, drug-naive patients with SD and 28 healthy controls underwent structural and resting-state functional magnetic resonance imaging. Voxel-based morphometry and Granger causality analysis (GCA) were used to analyze the data. Results: Results showed that patients with SD exhibited decreased gray matter volume (GMV) in the right cerebellum Crus I, and increased GMV in the left anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left angular gyrus. Causal connectivity of the cortico-limbic-cerebellar circuit was partly affected by structural alterations in the patients. Patients with SD showed bidirectional cortico-limbic connectivity abnormalities and bidirectional cortico-cerebellar and limbic-cerebellar connectivity abnormalities. The mean GMV of the right MFG was negatively correlated with the scores of the somatization subscale of the symptom checklist-90 and persistent error response of the Wisconsin Card Sorting Test (WCST) in the patients. A negative correlation was observed between increased driving connectivity from the right MFG to the right fusiform gyrus/cerebellum IV, V and the scores of the Eysenck Personality Questionnaire extraversion subscale. The mean GMV of the left ACC was negatively correlated with the WCST number of errors and persistent error response. Negative correlation was found between the causal effect from the left ACC to the right middle temporal gyrus and the scores of WCST number of categories achieved. Conclusions: Our findings show the partial effects of structural alterations on the cortico-limbic-cerebellar circuit in first-episode, drug-naive patients with SD. Correlations are observed between anatomical alterations or causal effects and clinical variables in patients with SD, and bear clinical significance. The present study emphasizes the importance of the cortico-limbic-cerebellar circuit in the neurobiology of SD. PMID:29755373

The chloroplast and mitochondrial DNA type are correlated with the nuclear composition of somatic hybrid calli of Solanum tuberosum and Nicotiana plumbaginifolia.

PubMed

Wolters, A M; Koornneef, M; Gilissen, L J

1993-09-01

This paper describes the analysis of chloroplast (cp) DNA and mitochondrial (mt) DNA in 21 somatic hybrid calli of Solanum tuberosum and Nicotiana plumbaginifolia by means of Southern-blot hybridization. Each of these calli contained only one type of cpDNA; 14 had the N. plumbaginifolia (Np) type and seven the S. tuberosum (St) type. N. plumbaginifolia cpDNA was present in hybrids previously shown to contain predominantly N. plumbaginifolia chromosomes whereas hybrids in which S. tuberosum chromosomes predominated possessed cpDNA from potato. We have analyzed the mtDNA of these 21 somatic hybrid calli using four restriction enzyme/probe combinations. Most fusion products had only, or mostly, mtDNA fragments from the parent that predominated in the nucleus. The hybrids containing mtDNA fragments from only one parent (and new fragments) also possessed chloroplasts from the same species. The results suggest the existence of a strong nucleo-cytoplasmic incongruity which affects the genome composition of somatic hybrids between distantly related species.

Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials.

PubMed

Myoga, Michael H; Beierlein, Michael; Regehr, Wade G

2009-06-17

Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from postnatal day 17 (P17)-P19 rats, which had dendrites that averaged 60 microm in length, and in short SC dendrites from P30-P33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons, in which dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-P19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity.

The relationship between nature relatedness and anxiety.

PubMed

Martyn, Patricia; Brymer, Eric

2016-07-01

This study investigated the relationship between anxiety and feelings of being connected to nature. Two standardised self-report scales, the Nature Relatedness Scale and the State Trait Inventory for Cognitive and Somatic Anxiety, were used in tandem with a qualitative question. Quantitative results indicated that connection to nature was significantly related to lower levels of overall, state cognitive and trait cognitive anxiety. Qualitative results revealed seven themes: relaxation, time out, enjoyment, connection, expanse, sensory engagement and a healthy perspective. Taken together, these results suggest that opportunities that enhance experiences of being connected to nature may reduce unhelpful anxiety. © The Author(s) 2014.

Mass production of somatic embryos expressing Escherichia coli heat-labile enterotoxin B subunit in Siberian ginseng.

PubMed

Kang, Tae-Jin; Lee, Won-Seok; Choi, Eun-Gyung; Kim, Jae-Whune; Kim, Bang-Geul; Yang, Moon-Sik

2006-01-24

The B subunit of Escherichia coli heat-labile toxin (LTB) is a potent mucosal immunogen and immunoadjuvant for co-administered antigens. In order to produce large scale of LTB for the development of edible vaccine, we used transgenic somatic embryos of Siberian ginseng, which is known as medicinal plant. When transgenic somatic embryos were cultured in 130L air-lift type bioreactor, they were developed to mature somatic embryos through somatic embryogenesis and contained approximately 0.36% LTB of the total soluble protein. Enzyme-linked immunosorbent assay indicated that the somatic embryo-synthesized LTB protein bound specifically to GM1-ganglioside, suggesting the LTB subunits formed active pentamers. Therefore, the use of the bioreactor system for expression of LTB proteins in somatic embryos allows for continuous mass production in a short-term period.

Protocols for Callus and Somatic Embryo Initiation for Hibiscus sabdariffa L. (Malvaceae): Influence of Explant Type, Sugar, and Plant Growth Regulators

USDA-ARS?s Scientific Manuscript database

A significant work on callus induction and somatic embryogenesis was realized for Hibiscus sabdariffa. Two genotypes (Hibiscus sabdariffa and Hibiscus sabdariffa var. altissima) two sugars (sucrose and glucose) and three concentrations (1 %, 2%, 3%) of each sugar, 3 explant types (root, hypocotyl, c...

Somatic embryogenesis in forestry: A practical approach to cloning the best trees

Treesearch

Alex M. Diner

1999-01-01

Trees as well as humans have two basic cell types based on genetic content: somatic cells and gametic or reproductive cells. Somatic cells, such as skin cells or the sapwood cells in a tree, have at least twice (2n) the base set of chromosomes. The reproductive cells (gametic cells) have a single (n) set of chromosomes.

Flow cytometric and morphological analyses of Pinus pinaster somatic embryogenesis.

PubMed

Marum, Liliana; Loureiro, João; Rodriguez, Eleazar; Santos, Conceição; Oliveira, M Margarida; Miguel, Célia

2009-09-25

An approach combining morphological profiling and flow cytometric analysis was used to assess genetic stability during the several steps of somatic embryogenesis in Pinus pinaster. Embryogenic cell lines of P. pinaster were established from immature zygotic embryos excised from seeds obtained from open-pollinated trees. During the maturation stage, phenotype of somatic embryos was characterized as being either normal or abnormal. Based upon the prevalent morphological traits, different types of abnormal embryos underwent further classification and quantification. Nuclear DNA content of maritime pine using the zygotic embryos was estimated to be 57.04 pg/2C, using propidium iodide flow cytometry. According to the same methodology, no significant differences (P< or =0.01) in DNA ploidy were detected among the most frequently observed abnormal phenotypes, embryogenic cell lines, zygotic and normal somatic embryos, and somatic embryogenesis-derived plantlets. Although the differences in DNA ploidy level do not exclude the occurrence of a low level of aneuploidy, the results obtained point to the absence of major changes in ploidy level during the somatic embryogenesis process of this economically important species. Therefore, our primary goal of true-to-typeness was assured at this level.

Somatic tinnitus prevalence and treatment with tinnitus retraining therapy.

PubMed

Ostermann, K; Lurquin, P; Horoi, M; Cotton, P; Hervé, V; Thill, M P

2016-01-01

Somatic tinnitus originates from increased activity of the dorsal cochlear nucleus, a cross-point between the somatic and auditory systems. Its activity can be modified by auditory stimulation or somatic system manipulation. Thus, sound enrichment and white noise stimulation might decrease tinnitus and associated somatic symptoms. The present uncontrolled study sought to determine somatic tinnitus prevalence among tinnitus sufferers, and to investigate whether sound therapy with counselling (tinnitus retraining therapy; TRT) may decrease tinnitus-associated somatic symptoms. To determine somatic tinnitus prevalence, 70 patients following the TRT protocol completed the Jastreboff Structured Interview (JSI) with additional questions regarding the presence and type of somatic symptoms. Among 21 somatic tinnitus patients, we further investigated the effects of TRT on tinnitus-associated facial dysesthesia. Before and after three months of TRT, tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI), and facial dysesthesia was assessed with an extended JSI-based questionnaire. Among the evaluated tinnitus patients, 56% presented somatic tinnitus-including 51% with facial dysesthesia, 36% who could modulate tinnitus by head and neck movements, and 13% with both conditions. Self-evaluation indicated that TRT significantly improved tinnitus and facial dysesthesia in 76% of patients. Three months of TRT led to a 50% decrease in mean THI and JSI scores regarding facial dysesthesia. Somatic tinnitus is a frequent and underestimated condition. We suggest an extension of the JSI, including specific questions regarding somatic tinnitus. TRT significantly improved tinnitus and accompanying facial dysesthesia, and could be a useful somatic tinnitus treatment.

An experiential mind-body approach to the management of medically unexplained symptoms.

PubMed

Bakal, D; Steiert, M; Coll, P; Schaefer, J

2006-01-01

This article outlines an experiential mind-body framework for understanding and treating patients with medically unexplained symptoms. The model relies on somatic awareness, a normal part of consciousness, to resolve the mind-body dualism inherent in conventional multidisciplinary approaches. Somatic awareness represents a guiding healing heuristic which allows for a linear treatment application of the biopsychosocial model. The heuristic acknowledges the validity of the patient's physical symptoms and identifies psychological and social factors needed for the healing process. Somatic awareness is used to direct changes in coping styles, illness beliefs, medication dependence and personal dynamics that are necessary to achieve symptom control. The mind-body concept is consistent with and supported by neurobiological models which draw on central nervous system mechanisms to explain medically unexplained symptoms. The concept is also supported by a recent hypothesis concerning the role peripheral connective tissue may play in influencing illness and well-being. Finally, somatic awareness is described as having potential to enhance understanding and conscious use of inner healing mechanisms at the basis of the placebo effect.

Bloom syndrome: a mendelian prototype of somatic mutational disease.

PubMed

German, J

1993-11-01

Spontaneous mutations in human somatic cells occur far more often than normal in individuals with Bloom syndrome. The basis for understanding these mutations and their developmental consequences emerges from examination of BS at the molecular, cellular, and clinical levels. The major clinical feature of BS, proportional dwarfism, as well as its major clinical complication, an exceptionally early emergence of neoplasia of the types and sites that affect the general population, are attributable to the excessive occurrence of mutations in somatic cells. Here, the following aspects of BS are discussed: (i) the BS phenotype; (ii) neoplasia in BS, including the means--the Bloom's Syndrome Registry--by which the significant risk for diverse sites and types of cancer in these patients was revealed; (iii) the biological basis for the cancer proneness of BS; and, finally, (iv) the significance for both basic human biology and clinical medicine of BS as the prototype of somatic mutational disease.

A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma.

PubMed

Ozawa, Michael G; Bhaduri, Aparna; Chisholm, Karen M; Baker, Steven A; Ma, Lisa; Zehnder, James L; Luna-Fineman, Sandra; Link, Michael P; Merker, Jason D; Arber, Daniel A; Ohgami, Robert S

2016-10-01

Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p.Lys66Arg in the transcription factor interferon regulatory factor 8 (IRF8) in 3 of 6 cases (50%) of pediatric-type follicular lymphoma. This specific point mutation was not detected in pediatric marginal zone lymphoma or in adult-type follicular lymphoma. Additional somatic point mutations in pediatric-type follicular lymphoma were observed in genes involved in transcription, intracellular signaling, and cell proliferation. In pediatric marginal zone lymphoma, no recurrent mutation was identified; however, somatic point mutations were observed in genes involved in cellular adhesion, cytokine regulatory elements, and cellular proliferation. A somatic variant in AMOTL1, a recurrently mutated gene in splenic marginal zone lymphoma, was also identified in a case of pediatric marginal zone lymphoma. The overall non-synonymous mutational burden was low in both pediatric-type follicular lymphoma and pediatric marginal zone lymphoma (4.6 mutations per exome). Altogether, these findings support a distinctive genetic basis for pediatric-type follicular lymphoma and pediatric marginal zone lymphoma when compared with adult subtypes and to one another. Moreover, identification of a recurrent point mutation in IRF8 provides insight into a potential driver mutation in the pathogenesis of pediatric-type follicular lymphoma with implications for novel diagnostic or therapeutic strategies.

A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma

PubMed Central

Ozawa, Michael G; Bhaduri, Aparna; Chisholm, Karen M; Baker, Steven A; Ma, Lisa; Zehnder, James L; Luna-Fineman, Sandra; Link, Michael P; Merker, Jason D; Arber, Daniel A; Ohgami, Robert S

2016-01-01

Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p.Lys66Arg in the transcription factor interferon regulatory factor 8 (IRF8) in 3 of 6 cases (50%) of pediatric-type follicular lymphoma. This specific point mutation was not detected in pediatric marginal zone lymphoma or in adult-type follicular lymphoma. Additional somatic point mutations in pediatric-type follicular lymphoma were observed in genes involved in transcription, intracellular signaling, and cell proliferation. In pediatric marginal zone lymphoma, no recurrent mutation was identified; however, somatic point mutations were observed in genes involved in cellular adhesion, cytokine regulatory elements, and cellular proliferation. A somatic variant in AMOTL1, a recurrently mutated gene in splenic marginal zone lymphoma, was also identified in a case of pediatric marginal zone lymphoma. The overall non-synonymous mutational burden was low in both pediatric-type follicular lymphoma and pediatric marginal zone lymphoma (4.6 mutations per exome). Altogether, these findings support a distinctive genetic basis for pediatric-type follicular lymphoma and pediatric marginal zone lymphoma when compared with adult subtypes and to one another. Moreover, identification of a recurrent point mutation in IRF8 provides insight into a potential driver mutation in the pathogenesis of pediatric-type follicular lymphoma with implications for novel diagnostic or therapeutic strategies. PMID:27338637

Analysis of cytoplasmic genomes in somatic hybrids between navel orange (Citrus sinensis Osb.) and 'Murcott' tangor.

PubMed

Kobayashi, S; Ohgawara, T; Fujiwara, K; Oiyama, I

1991-07-01

Somatic hybrid plants were produced by protoplast fusion of navel orange and 'Murcott' tangor. Hybridity of the plants was confirmed by the restriction endonuclease analysis of nuclear ribosomal DNA. All of the plants (16 clones) were normal, uniform, and had the amphidiploid chromosome number of 36 (2n=2x=18 for each parent). The cpDNA analysis showed that each of the 16 somatic hybrids contained either one parental chloroplast genome or the other. In all cases, the mitochondrial genomes of the regenerated somatic hybrids were of the navel orange type.

Effect of presynaptic membrane potential on electrical vs. chemical synaptic transmission

PubMed Central

Evans, Colin G.; Ludwar, Bjoern Ch.; Kang, Timothy

2011-01-01

The growing realization that electrical coupling is present in the mammalian brain has sparked renewed interest in determining its functional significance and contrasting it with chemical transmission. One question of interest is whether the two types of transmission can be selectively regulated, e.g., if a cell makes both types of connections can electrical transmission occur in the absence of chemical transmission? We explore this issue in an experimentally advantageous preparation. B21, the neuron we study, is an Aplysia sensory neuron involved in feeding that makes electrical and chemical connections with other identified cells. Previously we demonstrated that chemical synaptic transmission is membrane potential dependent. It occurs when B21 is centrally depolarized prior to and during peripheral activation, but does not occur if B21 is peripherally activated at its resting membrane potential. In this article we study effects of membrane potential on electrical transmission. We demonstrate that maximal potentiation occurs in different voltage ranges for the two types of transmission, with potentiation of electrical transmission occurring at more hyperpolarized potentials (i.e., requiring less central depolarization). Furthermore, we describe a physiologically relevant type of stimulus that induces both spiking and an envelope of depolarization in the somatic region of B21. This depolarization does not induce functional chemical synaptic transmission but is comparable to the depolarization needed to maximally potentiate electrical transmission. In this study we therefore characterize a situation in which electrical and chemical transmission can be selectively controlled by membrane potential. PMID:21593394

DeepGene: an advanced cancer type classifier based on deep learning and somatic point mutations.

PubMed

Yuan, Yuchen; Shi, Yi; Li, Changyang; Kim, Jinman; Cai, Weidong; Han, Zeguang; Feng, David Dagan

2016-12-23

With the developments of DNA sequencing technology, large amounts of sequencing data have become available in recent years and provide unprecedented opportunities for advanced association studies between somatic point mutations and cancer types/subtypes, which may contribute to more accurate somatic point mutation based cancer classification (SMCC). However in existing SMCC methods, issues like high data sparsity, small volume of sample size, and the application of simple linear classifiers, are major obstacles in improving the classification performance. To address the obstacles in existing SMCC studies, we propose DeepGene, an advanced deep neural network (DNN) based classifier, that consists of three steps: firstly, the clustered gene filtering (CGF) concentrates the gene data by mutation occurrence frequency, filtering out the majority of irrelevant genes; secondly, the indexed sparsity reduction (ISR) converts the gene data into indexes of its non-zero elements, thereby significantly suppressing the impact of data sparsity; finally, the data after CGF and ISR is fed into a DNN classifier, which extracts high-level features for accurate classification. Experimental results on our curated TCGA-DeepGene dataset, which is a reformulated subset of the TCGA dataset containing 12 selected types of cancer, show that CGF, ISR and DNN all contribute in improving the overall classification performance. We further compare DeepGene with three widely adopted classifiers and demonstrate that DeepGene has at least 24% performance improvement in terms of testing accuracy. Based on deep learning and somatic point mutation data, we devise DeepGene, an advanced cancer type classifier, which addresses the obstacles in existing SMCC studies. Experiments indicate that DeepGene outperforms three widely adopted existing classifiers, which is mainly attributed to its deep learning module that is able to extract the high level features between combinatorial somatic point mutations and cancer types.

Do early changes in the HAM-D-17 anxiety/somatization factor items affect treatment outcome among depressed outpatients? Comparison of two controlled trials of St John’s Wort (Hypericum Perforatum) versus an SSRI

PubMed Central

Bitran, Stella; Farabaugh, Amy H; Ameral, Victoria E; LaRocca, Rachel A; Clain, Alisabet J; Fava, Maurizio; Mischoulon, David

2011-01-01

Objective To assess whether early changes in HAM-D-17 anxiety/somatization items predict remission in two controlled studies of hypericum perforatum (St. John’s wort) versus an SSRI for major depressive disorder (MDD). Methods The Hypericum Depression Trial Study Group (NIMH) study randomized 340 subjects to hypericum, sertraline, or placebo for 8 weeks. The MGH study randomized 135 subjects to hypericum, fluoxetine, or placebo for 12 weeks. We examined whether remission was associated with early changes in anxiety/somatization symptoms. Results In the NIMH study, significant associations were observed between remission and early improvement in the anxiety-psychic item (sertraline arm), somatic-gastrointestinal item (hypericum arm), and somatic symptoms-general (placebo arm). None of the three treatment arms of the MGH study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety-psychic (SSRI arm), somatic-gastrointestinal and hypochondriasis (hypericum arm), and anxiety-psychic and somatic symptoms-general (placebo arm). In the entire sample, remission was associated with improvement in the anxiety-psychic, somatic-gastrointestinal, and somatic symptoms-general items. Conclusions The number and type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the HAM-D-17 anxiety/somatization items may help predict remission of MDD. PMID:21278577

Ehlers-Danlos syndrome in a young woman with anorexia nervosa and complex somatic symptoms.

PubMed

Lee, Michelle; Strand, Mattias

2018-03-01

The Ehler-Danlos syndromes (EDS) are a group of clinically heterogeneous connective tissue disorders characterized by joint hypermobility, hyperextensibility of the skin, and a general connective tissue fragility that can induce symptoms from multiple organ systems. We present a case of comorbid anorexia nervosa and EDS in a 23-year old woman with a multitude of somatic symptoms that were initially attributed to the eating disorder but that were likely caused by the underlying EDS. Various EDS symptoms, such as gastrointestinal complaints, smell and taste abnormalities, and altered somatosensory awareness may resemble or mask an underlying eating disorder, and vice versa. Because of the large clinical heterogeneity, correctly identifying symptoms of EDS presents a challenge for clinicians, who should be aware of this group of underdiagnosed and potentially serious syndromes. The Beighton Hypermobility Score is an easily applicable screening instrument in assessing potential EDS in patients with joint hypermobility. © 2017 Wiley Periodicals, Inc.

Identification and characterization of bZIP-type transcription factors involved in carrot (Daucus carota L.) somatic embryogenesis.

PubMed

Guan, Yucheng; Ren, Haibo; Xie, He; Ma, Zeyang; Chen, Fan

2009-10-01

Seed dormancy is an important adaptive trait that enables seeds of many species to remain quiescent until conditions become favorable for germination. Abscisic acid (ABA) plays an important role in these developmental processes. Like dormancy and germination, the elongation of carrot somatic embryo radicles is retarded by sucrose concentrations at or above 6%, and normal growth resumes at sucrose concentrations below 3%. Using a yeast one-hybrid screening system, we isolated two bZIP-type transcription factors, CAREB1 and CAREB2, from a cDNA library prepared from carrot somatic embryos cultured in a high-sucrose medium. Both CAREB1 and CAREB2 were localized to the nucleus, and specifically bound to the ABA response element (ABRE) in the Dc3 promoter. Expression of CAREB2 was induced in seedlings by drought and exogenous ABA application; whereas expression of CAREB1 increased during late embryogenesis, and reduced dramatically when somatic embryos were treated with fluridone, an inhibitor of ABA synthesis. Overexpression of CAREB1 caused somatic embryos to develop slowly when cultured in low-sucrose medium, and retarded the elongation of the radicles. These results indicate that CAREB1 and CAREB2 have similar DNA-binding activities, but play different roles during carrot development. Our results indicate that CAREB1 functions as an important trans-acting factor in the ABA signal transduction pathway during carrot somatic embryogenesis.

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types.

PubMed

Cheng, Feixiong; Liu, Chuang; Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-09-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics.

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

PubMed Central

Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-01-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

Totipotency, Pluripotency and Nuclear Reprogramming

NASA Astrophysics Data System (ADS)

Mitalipov, Shoukhrat; Wolf, Don

Mammalian development commences with the totipotent zygote which is capable of developing into all the specialized cells that make up the adult animal. As development unfolds, cells of the early embryo proliferate and differentiate into the first two lineages, the pluripotent inner cell mass and the trophectoderm. Pluripotent cells can be isolated, adapted and propagated indefinitely in vitro in an undifferentiated state as embryonic stem cells (ESCs). ESCs retain their ability to differentiate into cells representing the three major germ layers: endoderm, mesoderm or ectoderm or any of the 200+ cell types present in the adult body. Since many human diseases result from defects in a single cell type, pluripotent human ESCs represent an unlimited source of any cell or tissue type for replacement therapy thus providing a possible cure for many devastating conditions. Pluripotent cells resembling ESCs can also be derived experimentally by the nuclear reprogramming of somatic cells. Reprogrammed somatic cells may have an even more important role in cell replacement therapies since the patient's own somatic cells can be used for reprogramming thereby eliminating immune based rejection of transplanted cells. In this review, we summarize two major approaches to reprogramming: (1) somatic cell nuclear transfer and (2) direct reprogramming using genetic manipulations.

[Influence of genotype, explant type and component of culture medium on in vitro callus induction and shoot organogenesis of tomato (Solanum lycopersicum L.)].

PubMed

Khaliluev, M R; Bogoutdinova, L R; Baranova, G B; Baranova, E N; Kharchenko, P N; Dolgov, S V

2014-01-01

The influence of explant type as well as of the type of growth regulators and concentration on callus induction processes and somatic organogenesis of shoots was studied in vitro on four tomato genotypes of Russian breeding. Cytological study of callus tissue was conducted. It was established that tomato varieties possess a substantially greater ability to indirect shoot organogenesis compared with the F1 hybrid. The highest frequency of somatic organogenesis of shoots, as well as their number per explant, was observed for most of the genotypes studied during the cultivation of cotyledons on Murashige-Skoog culture medium containing 2 mg/l of zeatin in combination with 0.1 mg/l of 3-indoleacetic acid. An effective protocol of indirect somatic organogenesis of shoots from different explants of tomato varieties with a frequency of more than 80% was developed.

Alexithymia and Somatization in Depressed Patients: The Role of the Type of Somatic Symptom Attribution

PubMed Central

TAYCAN, Okan; ÖZDEMİR, Armağan; ERDOĞAN TAYCAN, Serap

2017-01-01

Introduction This study aimed to establish the association between alexithymia and various factors, mainly somatization, and to determine the predictors of alexithymia in depressed patients. Methods A total of 90 patients with major depressive disorder who met The Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnostic criteria were administered the Toronto Alexithymia Scale (TAS), Beck Depression Inventory, Symptom Checklist-90 (SCL-90), Somatosensory Amplification Scale, and Symptom Interpretation Questionnaire. The patients were classified into two groups as alexithymic and non-alexithymic with respect to the TAS cut-off points (≥59=alexithymic). Predictors of alexithymia were tested by multiple linear regression analysis. Results Of all patients, 36 (40%) were in the alexithymic group. The percentage of women, depression severity, level of general psychopathology and distress, and somatic symptom reporting (SCL-90), as well as the tendency to somatosensory amplification and three forms of somatic symptom attributions, were significantly higher in alexithymic patients than in non-alexithymic patients. Furthermore, age, depression severity, somatic symptom reporting, and the tendency to attribute physical symptoms to somatic causes were predictors of alexithymia. Conclusion The results indicated an intimate association between alexithymia and somatization in depressed patients. Therefore, when evaluating depressed patients with alexithymia, their tendency for somatization should be considered, and alexithymic individuals should be assessed with particular attention, considering that somatization can mask the underlying depressive condition. PMID:28680305

DNA polymerase η mutational signatures are found in a variety of different types of cancer.

PubMed

Rogozin, Igor B; Goncearenco, Alexander; Lada, Artem G; De, Subhajyoti; Yurchenko, Vyacheslav; Nudelman, German; Panchenko, Anna R; Cooper, David N; Pavlov, Youri I

2018-01-01

DNA polymerase (pol) η is a specialized error-prone polymerase with at least two quite different and contrasting cellular roles: to mitigate the genetic consequences of solar UV irradiation, and promote somatic hypermutation in the variable regions of immunoglobulin genes. Misregulation and mistargeting of pol η can compromise genome integrity. We explored whether the mutational signature of pol η could be found in datasets of human somatic mutations derived from normal and cancer cells. A substantial excess of single and tandem somatic mutations within known pol η mutable motifs was noted in skin cancer as well as in many other types of human cancer, suggesting that somatic mutations in A:T bases generated by DNA polymerase η are a common feature of tumorigenesis. Another peculiarity of pol ηmutational signatures, mutations in YCG motifs, led us to speculate that error-prone DNA synthesis opposite methylated CpG dinucleotides by misregulated pol η in tumors might constitute an additional mechanism of cytosine demethylation in this hypermutable dinucleotide.

Trauma exposure and the mediating role of posttraumatic stress on somatic symptoms in civilian war victims.

PubMed

Morina, Naser; Schnyder, Ulrich; Klaghofer, Richard; Müller, Julia; Martin-Soelch, Chantal

2018-04-10

It has been well documented that the exposure to war has a negative effect on the psychological health of civilian. However, little is known on the impact of war exposure on the physical health of the civilian population. In addition, the link between trauma exposure and somatic symptoms remain poorly understood. This cross-sectional study examined levels of somatic symptoms in the aftermath of war, and the mediating role of posttraumatic stress symptoms in the relationship between trauma exposure and somatic symptoms. Civilian war survivors (N = 142) from Kosovo were assessed for potentially traumatic events, posttraumatic stress symptoms, and somatic symptoms. Data were analyzed using mediation analyses. Posttraumatic stress disorder (PTSD) symptoms were categorized based on King's four factor model (Psychol Assessment. 10: 90-96, 1998). Participants reported on average more than 5 types of traumatic exposure. The cut-off indicative for PTSD was exceeded by 26.1% of participants. Symptom levels of PTSD were associated with somatic symptoms. The relationship between trauma exposure and somatic symptoms was partly mediated by the active avoidance and hyperarousal symptom clusters of PTSD. Active avoidance and hyperarousal symptoms seem to play a key role in traumatized people suffering from somatic symptoms.

Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among depressed outpatients? Comparison of two controlled trials of St John's wort (Hypericum perforatum) versus a SSRI.

PubMed

Bitran, Stella; Farabaugh, Amy H; Ameral, Victoria E; LaRocca, Rachel A; Clain, Alisabet J; Fava, Maurizio; Mischoulon, David

2011-07-01

To assess whether early changes in Hamilton Depression Rating Scale-17 anxiety/somatization items predict remission in two controlled studies of Hypericum perforatum (St John's wort) versus selective serotonin reuptake inhibitors for major depressive disorder. The Hypericum Depression Trial Study Group (National Institute of Mental Health) randomized 340 patients to Hypericum, sertraline, or placebo for 8 weeks, whereas the Massachusetts General Hospital study randomized 135 patients to Hypericum, fluoxetine, or placebo for 12 weeks. The investigators examined whether remission was associated with early changes in anxiety/somatization symptoms. In the National Institute of Mental Health study, significant associations were observed between remission and early improvement in the anxiety (psychic) item (sertraline arm), somatic (gastrointestinal item; Hypericum arm), and somatic (general) symptoms (placebo arm). None of the three treatment arms of the Massachusetts General Hospital study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety (psychic; selective serotonin reuptake inhibitors arm), somatic (gastrointestinal), and hypochondriasis (Hypericum arm), and anxiety (psychic) and somatic (general) symptoms (placebo arm). In the entire sample, remission was associated with the improvement in the anxiety (psychic), somatic (gastrointestinal), and somatic (general) items. The number and the type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the Hamilton Depression Rating Scale-17 anxiety/somatization items may help to predict remission of major depressive disorder.

The impact of somatic symptoms on the course of major depressive disorder.

PubMed

Bekhuis, Ella; Boschloo, Lynn; Rosmalen, Judith G M; de Boer, Marrit K; Schoevers, Robert A

2016-11-15

Somatic symptoms have been suggested to negatively affect the course of major depressive disorder (MDD). Mechanisms behind this association, however, remain elusive. This study examines the impact of somatic symptoms on MDD prognosis and aims to determine whether this effect can be explained by psychiatric characteristics, somatic diseases, lifestyle factors, and disability. In 463 MDD patients (mean age=44.9 years, 69.8% female) from the Netherlands Study of Depression and Anxiety (NESDA), we examined whether the type and number of somatic symptom clusters predicted the two-year persistence of MDD. Diagnoses of MDD were established with the Composite International Diagnostic Interview (CIDI) and somatic symptom clusters were assessed with the Four-Dimensional Symptom Questionnaire (4DSQ) somatization scale. Psychiatric characteristics, somatic diseases, lifestyle factors, and disability were taken into account as factors potentially underlying the association. The cardiopulmonary, gastrointestinal, and general cluster significantly predicted the two-year persistence of MDD, but only when two or more of these clusters were present (OR=2.32, 95% CI=1.51-3.57, p=<0.001). Although the association was partly explained by MDD severity, the presence of multiple somatic symptom clusters remained a significant predictor after considering all potentially underlying factors (OR=1.69, 95%CI=1.07-2.68, p=0.03). Somatic symptoms are predictors of a worse prognosis of MDD independent of psychiatric characteristics, somatic diseases, lifestyle factors, and disability. These results stress the importance of considering somatic symptoms in the diagnostic and treatment trajectory of patients with MDD. Future research should focus on identifying treatment modalities targeting depressive as well as somatic symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer.

PubMed

van Haaften, Gijs; Dalgliesh, Gillian L; Davies, Helen; Chen, Lina; Bignell, Graham; Greenman, Chris; Edkins, Sarah; Hardy, Claire; O'Meara, Sarah; Teague, Jon; Butler, Adam; Hinton, Jonathan; Latimer, Calli; Andrews, Jenny; Barthorpe, Syd; Beare, Dave; Buck, Gemma; Campbell, Peter J; Cole, Jennifer; Forbes, Simon; Jia, Mingming; Jones, David; Kok, Chai Yin; Leroy, Catherine; Lin, Meng-Lay; McBride, David J; Maddison, Mark; Maquire, Simon; McLay, Kirsten; Menzies, Andrew; Mironenko, Tatiana; Mulderrig, Lee; Mudie, Laura; Pleasance, Erin; Shepherd, Rebecca; Smith, Raffaella; Stebbings, Lucy; Stephens, Philip; Tang, Gurpreet; Tarpey, Patrick S; Turner, Rachel; Turrell, Kelly; Varian, Jennifer; West, Sofie; Widaa, Sara; Wray, Paul; Collins, V Peter; Ichimura, Koichi; Law, Simon; Wong, John; Yuen, Siu Tsan; Leung, Suet Yi; Tonon, Giovanni; DePinho, Ronald A; Tai, Yu-Tzu; Anderson, Kenneth C; Kahnoski, Richard J; Massie, Aaron; Khoo, Sok Kean; Teh, Bin Tean; Stratton, Michael R; Futreal, P Andrew

2009-05-01

Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase gene UTX, pointing to histone H3 lysine methylation deregulation in multiple tumor types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene.

Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer

PubMed Central

van Haaften, Gijs; Dalgliesh, Gillian L; Davies, Helen; Chen, Lina; Bignell, Graham; Greenman, Chris; Edkins, Sarah; Hardy, Claire; O’Meara, Sarah; Teague, Jon; Butler, Adam; Hinton, Jonathan; Latimer, Calli; Andrews, Jenny; Barthorpe, Syd; Beare, Dave; Buck, Gemma; Campbell, Peter J; Cole, Jennifer; Dunmore, Rebecca; Forbes, Simon; Jia, Mingming; Jones, David; Kok, Chai Yin; Leroy, Catherine; Lin, Meng-Lay; McBride, David J; Maddison, Mark; Maquire, Simon; McLay, Kirsten; Menzies, Andrew; Mironenko, Tatiana; Lee, Mulderrig; Mudie, Laura; Pleasance, Erin; Shepherd, Rebecca; Smith, Raffaella; Stebbings, Lucy; Stephens, Philip; Tang, Gurpreet; Tarpey, Patrick S; Turner, Rachel; Turrell, Kelly; Varian, Jennifer; West, Sofie; Widaa, Sara; Wray, Paul; Collins, V Peter; Ichimura, Koichi; Law, Simon; Wong, John; Yuen, Siu Tsan; Leung, Suet Yi; Tonon, Giovanni; DePinho, Ronald A; Tai, Yu-Tzu; Anderson, Kenneth C; Kahnoski, Richard J.; Massie, Aaron; Khoo, Sok Kean; Teh, Bin Tean; Stratton, Michael R; Futreal, P Andrew

2010-01-01

Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase, UTX, pointing to histone H3 lysine methylation deregulation in multiple tumour types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene. PMID:19330029

Network diffusion-based analysis of high-throughput data for the detection of differentially enriched modules

PubMed Central

Bersanelli, Matteo; Mosca, Ettore; Remondini, Daniel; Castellani, Gastone; Milanesi, Luciano

2016-01-01

A relation exists between network proximity of molecular entities in interaction networks, functional similarity and association with diseases. The identification of network regions associated with biological functions and pathologies is a major goal in systems biology. We describe a network diffusion-based pipeline for the interpretation of different types of omics in the context of molecular interaction networks. We introduce the network smoothing index, a network-based quantity that allows to jointly quantify the amount of omics information in genes and in their network neighbourhood, using network diffusion to define network proximity. The approach is applicable to both descriptive and inferential statistics calculated on omics data. We also show that network resampling, applied to gene lists ranked by quantities derived from the network smoothing index, indicates the presence of significantly connected genes. As a proof of principle, we identified gene modules enriched in somatic mutations and transcriptional variations observed in samples of prostate adenocarcinoma (PRAD). In line with the local hypothesis, network smoothing index and network resampling underlined the existence of a connected component of genes harbouring molecular alterations in PRAD. PMID:27731320

[Parietal Cortices and Body Information].

PubMed

Naito, Eiichi; Amemiya, Kaoru; Morita, Tomoyo

2016-11-01

Proprioceptive signals originating from skeletal muscles and joints contribute to the formation of both the human body schema and the body image. In this chapter, we introduce various types of bodily illusions that are elicited by proprioceptive inputs, and we discuss distinct functions implemented by different parietal cortices. First, we illustrate the primary importance of the motor network in the processing of proprioceptive (kinesthetic) signals originating from muscle spindles. Next, we argue that the right inferior parietal cortex, in concert with the inferior frontal cortex (both regions connected by the inferior branch of the superior longitudinal fasciculus-SLF III), may be involved in the conscious experience of body image. Further, we hypothesize other functions of distinct parietal regions: the association between internal hand motor representation with external object representation in the left inferior parietal cortex, visuo-kinesthetic processing in the bilateral posterior parietal cortices, and the integration of somatic signals from different body parts in the higher-order somatosensory parietal cortices. Our results indicate that a distinct parietal region, in concert with its anatomically and functionally connected frontal regions, probably plays specialized roles in the processing of body-related information.

Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes

PubMed Central

2011-01-01

Background During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. Methods A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Results Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. Conclusions The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study. Please see Commentary: http://www.biomedcentral.com/1741-7015/9/13/abstract. PMID:21291537

Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes.

PubMed

Ross, Kenneth Andrew

2011-02-03

During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study.

["Burnout"--is it a disease or rather a consequence of (work-) stress?].

PubMed

Koehler, U; Koehler, Y L

2014-08-01

Burnout is a work related health impairment comprising three dimensions: emotional exhaustion, depersonalisation and reduced personal accomplishment. Not least because of the highly frequented term "burnout" within the German speaking area, there is a rising interest in the connection of work related stress and psychological and somatic complaints. Burnout is not a disease in the proper sense but a physiological construct. Coherence between work related stress and the development of psychological and somatic diseases has been proven by many studies. However burnout requires a differential diagnostic categorisation. Therapeutic procedures and prevention measures should be initiated based on the forms and categorisation of work related stress. © Georg Thieme Verlag KG Stuttgart · New York.

RNA splicing and its connection with other regulatory layers in somatic cell reprogramming.

PubMed

Zavolan, Mihaela; Kanitz, Alexander

2018-06-01

Understanding how cell identity is established and maintained is one of the most exciting challenges of molecular biology today. Recent work has added a conserved layer of RNA splicing and other post-transcriptional regulatory processes to the transcriptional and epigenetic networks already known to cooperate in the establishment and maintenance of cell identity. Here we summarize these findings, highlighting specifically the multitude of splicing factors that can modulate the efficiency of somatic cell reprogramming. Distinct patterns of gene expression dynamics of these factors during reprogramming suggest that further improvements in efficiency could be obtained through optimal timing of overexpression or knockdown of individual regulators. Copyright © 2017 Elsevier Ltd. All rights reserved.

Surgical anatomy of the retroperitoneal spaces, Part V: Surgical applications and complications.

PubMed

Mirilas, Petros; Skandalakis, John E

2010-04-01

Knowledge of the surgical anatomy of the retroperitoneum is crucial for surgery of the retroperitoneal organs. Surgery is essential for treatment of retroperitoneal pathologies. The list of these diseases is extensive and comprises acute and chronic inflammatory processes (abscess, injury, hematoma, idiopathic fibrosis), metastatic neoplasms, and primary neoplasms from fibroadipose tissue, connective tissue, smooth and striated muscle, vascular tissue, somatic and sympathetic nervous tissue, extraadrenal chromaffin tissue, and lymphatic tissue. The retroperitoneum can be approached and explored by several routes, including the transperitoneal route and the extraperitoneal route. The retroperitoneal approach to the iliac fossa is used for ectopic renal transplantation. Safe and reliable primary retroperitoneal access can be performed for laparoscopic exploration. The anatomic complications of retroperitoneal surgery are the complications of the organs located in several compartments of the retroperitoneal space. Complications may arise from incisions to the somatic wall, somatic nerves, blood and lymphatic vessels, lymph nodes, visceral autonomous plexuses, and neighboring splanchna.

Bridging the divide

PubMed Central

McLean, Peter F; Cooley, Lynn

2014-01-01

Ring canals are made from arrested cleavage furrows, and provide direct cytoplasmic connections among sibling cells. They are well documented for their participation in Drosophila oogenesis, but little is known about their role in several somatic tissues in which they are also found. Using a variety of genetic tools in live and fixed tissue, we recently demonstrated that rapid intercellular exchange occurs through somatic ring canals by diffusion, and presented evidence that ring canals permit equilibration of protein among transcriptionally mosaic cells. We also used a novel combination of markers to evaluate the extent of protein movement within and across mitotic clones in follicle cells and imaginal discs, providing evidence of robust movement of GFP between the 2 sides of mitotic clones and frequently into non-recombined cells. These data suggest that, depending on the experimental setup and proteins of interest, inter-clonal diffusion of protein may alter the interpretation of clonal data in follicle cells. Here, we discuss these results and provide additional insight into the impact of ring canals in Drosophila somatic tissues. PMID:24406334

Stereotype threat and lift effects in motor task performance: the mediating role of somatic and cognitive anxiety.

PubMed

Laurin, Raphael

2013-01-01

The aim of this investigation was to replicate the stereotype threat and lift effects in a motor task in a neutral sex-typed activity, using somatic and cognitive anxiety as key mediators of these phenomena. It was hypothesized that an ingroup/outgroup social categorization based on gender would have distinctive effects for female and male participants. A total of 161 French physical education students were randomly assigned to three threat conditions--no threat, female threat, and male threat--thus leading to a 3 x 2 (threat by gender) design. The analyses revealed a stereotype lift effect on the performances for both male and female participants, as well as a stereotype threat effect only for female participants. They also indicated that somatic anxiety had a mediating effect on the performance of female participants targeted by a negative stereotype, but that it had a facilitating effect on their performance. The stereotype threat and lift effects on motor tasks were replicated in a neutral sex-typed activity and somatic anxiety seems to have a facilitating mediating effect of the relationships between the gender-conditions (control or female threat) interaction and free-throw performance. The model used to distinguish somatic and cognitive anxiety appeared to be a relevant means of explaining the stereotype threat and lift mechanisms.

The visceromotor and somatic afferent nerves of the penis.

PubMed

Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

2015-05-01

Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients.

PubMed

Morales, Fernando; Vásquez, Melissa; Santamaría, Carolina; Cuenca, Patricia; Corrales, Eyleen; Monckton, Darren G

2016-04-01

Somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 is age-dependent, tissue-specific and expansion-biased, contributing toward the tissue-specificity and progressive nature of the symptoms. Previously, using regression modelling of repeat instability we showed that variation in the rate of somatic expansion in blood DNA contributes toward variation in age of onset, directly implicating somatic expansion in the disease pathway. Here, we confirm these results using a larger more genetically homogenous Costa Rican DM1 cohort (p<0.001). Interestingly, we also provide evidence that supports subtle sex-dependent differences in repeat length-dependent age at onset and somatic mutational dynamics. Previously, we demonstrated that variation in the rate of somatic expansion was a heritable quantitative trait. Given the important role that DNA mismatch repair genes play in mediating expansions in mouse models, we tested for modifier gene effects with 13 DNA mismatch gene polymorphisms (one each in MSH2, PMS2, MSH6 and MLH1; and nine in MSH3). After correcting for allele length and age effects, we identified three polymorphisms in MSH3 that were associated with variation in somatic instability: Rs26279 (p=0.003); Rs1677658 (p=0.009); and Rs10168 (p=0.031). However, only the association with Rs26279 remained significant after multiple testing correction. Although we revealed a statistically significant association between Rs26279 and somatic instability, we did not detect an association with the age at onset. Individuals with the A/A genotype for Rs26279 tended to show a greater propensity to expand the CTG repeat than other genotypes. Interestingly, this SNP results in an amino acid change in the critical ATPase domain of MSH3 and is potentially functionally dimorphic. These data suggest that MSH3 is a key player in generating somatic variation in DM1 patients and further highlight MSH3 as a potential therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

Water relations in culture media influence maturation of avocado somatic embryos.

PubMed

Márquez-Martín, Belén; Sesmero, Rafael; Quesada, Miguel A; Pliego-Alfaro, Fernando; Sánchez-Romero, Carolina

2011-11-15

Application of transformation and other biotechnological tools in avocado (Persea americana Mill.) is hampered by difficulties in obtaining mature somatic embryos capable of germination at an acceptable rate. In this work, we evaluated the effect of different compounds affecting medium water relations on maturation of avocado somatic embryos. Culture media were characterized with respect to gel strength, water potential and osmotic potential. Improved production of mature somatic embryos was achieved with gelling agent concentrations higher than those considered standard. The osmotic agents such as sorbitol and PEG did not have positive effects on embryo maturation. The number of w-o mature somatic embryos per culture was positively correlated with medium gel strength. Gel strength was significantly affected by gelling agent type as well as by gelling agent and PEG concentration. Medium water potential was influenced by sorbitol concentration; incorporation of PEG to a culture medium did not affect medium water potential. The highest maturation results were achieved on a medium gelled with 10 gl(-1) agar. Moreover, these somatic embryos had improved germination rates. These results corroborate the role of water restriction as a key factor controlling maturation of somatic embryos. Copyright © 2011 Elsevier GmbH. All rights reserved.

Attribution of somatic symptoms in hypochondriasis.

PubMed

Neng, Julia M B; Weck, Florian

2015-01-01

The misinterpretation of bodily symptoms as an indicator of a serious illness is a key feature of the criteria and the cognitive-behavioural models of hypochondriasis. Previous research suggests that individuals suffering from health anxiety endorse attributions of physical disease, whereas persons with elevated general anxiety have the tendency to attribute psychological causes to their symptoms. However, whether a somatic attribution style is specific to patients with hypochondriasis, as opposed to those with anxiety disorders, has not yet been investigated and is therefore part of the present study. Fifty patients with hypochondriasis, 50 patients with a primary anxiety disorder and 50 healthy participants were presented with nine common bodily sensations and had to spontaneously attribute possible causes to the symptoms. Patients with hypochondriasis differed from patients with anxiety disorders and healthy controls in giving significantly fewer normalizing explanations, but attributing more often in terms of moderate or serious diseases. Patients with anxiety disorders also made significantly fewer normalizing attributions and more somatic attributions to a severe illness than healthy controls. There were no differences between the groups in the frequency of psychological attributions and somatic attributions concerning mild diseases. The present study demonstrates that hypochondriasis is associated with a disorder-specific attribution style connecting somatic symptoms primarily with moderate and serious diseases. By contrast, normalizing attributions are largely omitted from consideration by patients with hypochondriasis. The findings conform with the cognitive conception of hypochondriasis and support the strategy of modifying symptom attributions, as practiced in cognitive-behavioural therapy. Copyright © 2013 John Wiley & Sons, Ltd.

The Relationship between the Physical Activity Environment, Nature Relatedness, Anxiety, and the Psychological Well-being Benefits of Regular Exercisers

PubMed Central

Lawton, Emma; Brymer, Eric; Clough, Peter; Denovan, Andrew

2017-01-01

Research from a variety of scientific fields suggests that physical activity in nature and feelings of connection to nature enhance psychological health and well-being. This study investigated the psychological health and well-being impact of the physical activity environment for those already undertaking the recommended weekly amount of physical activity. This topic is important for the design of health and well-being environments and interventions involving physical activity. Participants (N = 262) aged 18–71 years (M = 34.5, SD = 13.1) who met the UK physical activity guidelines completed the Nature Relatedness Scale, the trait section of the State Trait Inventory for Cognitive and Somatic Anxiety and the Psychological Well-Being Scale. Analysis via Multivariate ANOVA indicated that participants who engaged in outdoor physical activity reported significantly lower somatic anxiety levels and higher Nature Relatedness experience (NRexp). Significant results were not evident for wellbeing. Hierarchical regressions revealed that the psychological well-being facet of autonomy, NRexp, and outdoor physical activity predicted lower somatic anxiety, whereas indoor physical activity predicted higher somatic anxiety. Results indicate that somatic anxiety is lower for outdoor physical activity participation, and that outdoor activity, in conjunction with autonomy and NRexp, predicts lower anxiety levels. The findings extend previous work by demonstrating the impact of the physical activity environment on anxiety levels, as well as the contribution of outdoor physical activity and well-being facets to the previously established Nature Relatedness-anxiety relationship. PMID:28694788

The Relationship between the Physical Activity Environment, Nature Relatedness, Anxiety, and the Psychological Well-being Benefits of Regular Exercisers.

PubMed

Lawton, Emma; Brymer, Eric; Clough, Peter; Denovan, Andrew

2017-01-01

Research from a variety of scientific fields suggests that physical activity in nature and feelings of connection to nature enhance psychological health and well-being. This study investigated the psychological health and well-being impact of the physical activity environment for those already undertaking the recommended weekly amount of physical activity. This topic is important for the design of health and well-being environments and interventions involving physical activity. Participants ( N = 262) aged 18-71 years ( M = 34.5, SD = 13.1) who met the UK physical activity guidelines completed the Nature Relatedness Scale, the trait section of the State Trait Inventory for Cognitive and Somatic Anxiety and the Psychological Well-Being Scale. Analysis via Multivariate ANOVA indicated that participants who engaged in outdoor physical activity reported significantly lower somatic anxiety levels and higher Nature Relatedness experience (NRexp). Significant results were not evident for wellbeing. Hierarchical regressions revealed that the psychological well-being facet of autonomy, NRexp, and outdoor physical activity predicted lower somatic anxiety, whereas indoor physical activity predicted higher somatic anxiety. Results indicate that somatic anxiety is lower for outdoor physical activity participation, and that outdoor activity, in conjunction with autonomy and NRexp, predicts lower anxiety levels. The findings extend previous work by demonstrating the impact of the physical activity environment on anxiety levels, as well as the contribution of outdoor physical activity and well-being facets to the previously established Nature Relatedness-anxiety relationship.

Part Two: What Therapists Need to Know

ERIC Educational Resources Information Center

Purinton, Matthew C. P.

2011-01-01

When dealing with families that have been somatically fixated, it is important to initially focus on the symptoms, while not getting dragged into the way that the symptoms have become a centrally organizing event for the family. This allows the clinician to connect with the family around the physical symptoms, which they have become hypervigilant…

Somaesthetic Training, Aesthetics, Ethics, and the Politics of Difference in Richard Shusterman's "Body Consciousness"

ERIC Educational Resources Information Center

Powell, Kimberly

2010-01-01

In this essay, the author first addresses the theme of disciplined somatic training and its relationship to self-awareness and transformation. Her attention is focused specifically on the chapter on Ludwig Wittgenstein, in which Richard Shusterman presents and then elaborates upon the philosopher's connections between conscious bodily feelings and…

Embodying analysis: the body and the therapeutic process.

PubMed

Martini, Salvatore

2016-02-01

This paper considers the transfer of somatic effects from patient to analyst, which gives rise to embodied countertransference, functioning as an organ of primitive communication. By means of processes of projective identification, the analyst experiences somatic disturbances within himself or herself that are connected to the split-off complexes of the analysand. The analysty's own attempt at mind-body integration ushers the patient towards a progressive understanding and acceptance of his or her inner suffering. Such experiences of psychic contagion between patient and analyst are related to Jung's 'psychology of the transference' and the idea of the 'subtle body' as an unconscious shared area. The re-attribution of meaning to pre-verbal psychic experiences within the 'embodied reverie' of the analyst enables the analytic dyad to reach the archetypal energies and structuring power of the collective unconscious. A detailed case example is presented of how the emergence of the vitalizing connection between the psyche and the soma, severed through traumatic early relations with parents or carers, allows the instinctual impulse of the Self to manifest, thereby reactivating the process of individuation. © 2016, The Society of Analytical Psychology.

[Anthropometric indexes of the state of nutrition and eating habits, and recreational physical activity of working physically men aged 20-60 of urban population].

PubMed

Gacek, Maria; Chrzanowska, Maria

2011-01-01

The aim of this studies was the comparison of somatic indexes and eating habits of working physically men who prefer different ways (active vs. passive) of spending their free time. The studies has been carried out on a group of 1271 people who work in HTS (steelworks) in Nowa Huta (one of Cracow's districts), including 523 men aged 20-40 (181 active and 342 non-active) and 748 men aged 40-60 (194 active and 554 non-active). Men referred to as active declared active spending of their free time and taking up recreational physical activity at lest twice a week. The presented research has not revealed statistically important differentiation of somatic parameters depending on preferred way of spending free time, or a connection between the physical activity level during free time and some eating habits indicating more rational choices, connected with the control of energy value of the diet, larger consumption of vegetables and fruit and smaller consumption of sweet products, and less frequently appearance of 'canine appetite' in the case of active men.

Psychosocial Risk Factors for Upper Respiratory Infections: Assessment of Upper Respiratory Illness during Basic Training

DTIC Science & Technology

1988-05-23

association was low enough to ensure that the URI composite was not merely an index of somatic stress reactions or hypochondriasis . The eight-item...report somatic symptoms in response to stress. Adjusted URI Severity also is consistent with the clinical practice of ruling out other possible types

Long-Term Follow-Up of Individuals Undergoing Sex-Reassignment Surgery: Somatic Morbidity and Cause of Death.

PubMed

Simonsen, Rikke Kildevæld; Hald, Gert Martin; Kristensen, Ellids; Giraldi, Annamaria

2016-03-01

Studies of mortality and somatic well-being after sex-reassignment surgery (SRS) of transsexual individuals are equivocal. Accordingly, the present study investigated mortality and somatic morbidity using a sample of transsexual individuals who comprised 98% (n = 104) of all surgically reassigned transsexual individuals in Denmark. To investigate somatic morbidity before and after SRS and cause of death and its relation to somatic morbidity after SRS in Danish individuals who underwent SRS from 1978 through 2010. Somatic morbidity and mortality in 104 sex-reassigned individuals were identified retrospectively by data from the Danish National Health Register and the Cause of Death Register. Somatic morbidity and cause of death. Overall, 19.2% of the sample were registered with somatic morbidity before SRS and 23.1% after SRS (P = not significant). In total, 8.6% had somatic morbidity before and after SRS. The most common diagnostic category was cardiovascular disease, affecting 18 individuals, 9 before and 14 after SRS, and 5 of those 14 who were affected after SRS had cardiovascular disease before and after SRS. Ten individuals died after SRS at an average age of 53.5 ± 7.9 years (male to female) and 53.5 ± 7.3 years (female to male). Of 98% of all Danish transsexuals who officially underwent SRS from 1978 through 2010, one in three had somatic morbidity and approximately 1 in 10 had died. No significant differences in somatic morbidity or mortality were found between male-to-female and female-to-male individuals. Despite the young average age at death and the relatively larger number of individuals with somatic morbidity, the present study design does not allow for determination of casual relations between, for example, specific types of hormonal or surgical treatment received and somatic morbidity and mortality. Copyright © 2016. Published by Elsevier Inc.

Differential associations of specific depressive and anxiety disorders with somatic symptoms.

PubMed

Bekhuis, Ella; Boschloo, Lynn; Rosmalen, Judith G M; Schoevers, Robert A

2015-02-01

Previous studies have shown that depressive and anxiety disorders are strongly related to somatic symptoms, but much is unclear about the specificity of this association. This study examines the associations of specific depressive and anxiety disorders with somatic symptoms, and whether these associations are independent of comorbid depressive and anxiety disorders. Cross-sectional data were derived from The Netherlands Study of Depression and Anxiety (NESDA). A total of 2008 persons (mean age: 41.6 years, 64.9% women) were included, consisting of 1367 patients with a past-month DSM-diagnosis (established with the Composite International Diagnostic Interview [CIDI]) of depressive disorder (major depressive disorder, dysthymic disorder) and/or anxiety disorder (generalized anxiety disorder, social phobia, panic disorder, agoraphobia), and 641 controls. Somatic symptoms were assessed with the somatization scale of the Four-Dimensional Symptom Questionnaire (4DSQ), and included cardiopulmonary, musculoskeletal, gastrointestinal, and general symptoms. Analyses were adjusted for covariates such as chronic somatic diseases, sociodemographics, and lifestyle factors. All clusters of somatic symptoms were more prevalent in patients with depressive and/or anxiety disorders than in controls (all p<.001). Multivariable logistic regression analyses showed that all types of depressive and anxiety disorders were independently related to somatic symptoms, except for dysthymic disorder. Major depressive disorder showed the strongest associations. Associations remained similar after adjustment for covariates. This study demonstrated that depressive and anxiety disorders show strong and partly differential associations with somatic symptoms. Future research should investigate whether an adequate consideration and treatment of somatic symptoms in depressed and/or anxious patients improve treatment outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Borderline Personality in the Medical Setting

PubMed Central

Sansone, Lori A.

2015-01-01

Objective: Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings—namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. Data Sources: We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet’s syndrome, somatic preoccupation, somatic. Study Selection: Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. Results: According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Conclusions: Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation. PMID:26644960

Somatic embryogenesis, scanning electron microscopy, histology and biochemical analysis at different developing stages of embryogenesis in six date palm (Phoenix dactylifera L.) cultivars.

PubMed

Aslam, Junaid; Khan, Saeed Ahmad; Cheruth, Abdul Jaleel; Mujib, Abdul; Sharma, Maheshwar Pershad; Srivastava, Prem Shanker

2011-10-01

An efficient somatic embryogenesis system has been established in six date palm (Phoenix dactylifera L.) cultivars (Barhee, Zardai, Khalasah, Muzati, Shishi and Zart). Somatic embryogenesis (SE) was growth regulators and cultivars dependent. Friable embryogenic callus was induced from excised shoot tips on MS medium supplemented with various auxins particularly 2,4-dichlorophenoxyacetic acid (2,4-D, 1.5 mg 1(-l)). Suspension culture increased embryogenesis potentiality. Only a-naphthaleneacetic acid (NAA, 0.5 mg 1(-1)) produced somatic embryos in culture. Somatic embryos germinated and converted into plantlets in N(6)-benzyladenine (BAP, 0.75 mg 1(-l)) added medium following a treatment with thidiazuron (TDZ, 1.0 mg 1(-l)) for maturation. Scanning electron microscopy showed early stages of somatic embryo particularly, globular types, and was in masses. Different developing stages of embryogenesis (heart, torpedo and cotyledonary) were observed under histological preparation of embryogenic callus. Biochemical screening at various stages of somatic embryogenesis (embryogenic callus, somatic embryos, matured, germinated embryos and converted plantlets) of date palm cultivars has been conducted and discussed in detail. The result discussed in this paper indicates that somatic embryos were produced in numbers and converted plantlets can be used as a good source of alternative propagation. Genetic modification to the embryo precursor cell may improve the fruit quality and yield further.

Somatic embryogenesis, scanning electron microscopy, histology and biochemical analysis at different developing stages of embryogenesis in six date palm (Phoenix dactylifera L.) cultivars

PubMed Central

Aslam, Junaid; Khan, Saeed Ahmad; Cheruth, Abdul Jaleel; Mujib, Abdul; Sharma, Maheshwar Pershad; Srivastava, Prem Shanker

2011-01-01

An efficient somatic embryogenesis system has been established in six date palm (Phoenix dactylifera L.) cultivars (Barhee, Zardai, Khalasah, Muzati, Shishi and Zart). Somatic embryogenesis (SE) was growth regulators and cultivars dependent. Friable embryogenic callus was induced from excised shoot tips on MS medium supplemented with various auxins particularly 2,4-dichlorophenoxyacetic acid (2,4-D, 1.5 mg 1−l). Suspension culture increased embryogenesis potentiality. Only a-naphthaleneacetic acid (NAA, 0.5 mg 1−1) produced somatic embryos in culture. Somatic embryos germinated and converted into plantlets in N6-benzyladenine (BAP, 0.75 mg 1−l) added medium following a treatment with thidiazuron (TDZ, 1.0 mg 1−l) for maturation. Scanning electron microscopy showed early stages of somatic embryo particularly, globular types, and was in masses. Different developing stages of embryogenesis (heart, torpedo and cotyledonary) were observed under histological preparation of embryogenic callus. Biochemical screening at various stages of somatic embryogenesis (embryogenic callus, somatic embryos, matured, germinated embryos and converted plantlets) of date palm cultivars has been conducted and discussed in detail. The result discussed in this paper indicates that somatic embryos were produced in numbers and converted plantlets can be used as a good source of alternative propagation. Genetic modification to the embryo precursor cell may improve the fruit quality and yield further. PMID:23961149

Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer.

PubMed

Shinmura, Kazuya; Kato, Hisami; Kawanishi, Yuichi; Igarashi, Hisaki; Goto, Masanori; Tao, Hong; Inoue, Yusuke; Nakamura, Satoki; Misawa, Kiyoshi; Mineta, Hiroyuki; Sugimura, Haruhiko

2016-01-01

The effects of abnormalities in the DNA glycosylases NEIL1, NEIL2, and NEIL3 on human cancer have not been fully elucidated. In this paper, we found that the median somatic total mutation loads and the median somatic single nucleotide mutation loads exhibited significant inverse correlations with the median NEIL1 and NEIL2 expression levels and a significant positive correlation with the median NEIL3 expression level using data for 13 cancer types from the Cancer Genome Atlas (TCGA) database. A subset of the cancer types exhibited reduced NEIL1 and NEIL2 expressions and elevated NEIL3 expression, and such abnormal expressions of NEIL1, NEIL2, and NEIL3 were also significantly associated with the mutation loads in cancer. As a mechanism underlying the reduced expression of NEIL1 in cancer, the epigenetic silencing of NEIL1 through promoter hypermethylation was found. Finally, we investigated the reason why an elevated NEIL3 expression level was associated with an increased number of somatic mutations in cancer and found that NEIL3 expression was positively correlated with the expression of APOBEC3B, a potent inducer of mutations, in diverse cancers. These results suggested that the abnormal expressions of NEIL1, NEIL2, and NEIL3 are involved in cancer through their association with the somatic mutation load.

An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types

PubMed Central

Park, Sunho; Kim, Seung-Jun; Yu, Donghyeon; Peña-Llopis, Samuel; Gao, Jianjiong; Park, Jin Suk; Chen, Beibei; Norris, Jessie; Wang, Xinlei; Chen, Min; Kim, Minsoo; Yong, Jeongsik; Wardak, Zabi; Choe, Kevin; Story, Michael; Starr, Timothy; Cheong, Jae-Ho; Hwang, Tae Hyun

2016-01-01

Motivation: Identification of altered pathways that are clinically relevant across human cancers is a key challenge in cancer genomics. Precise identification and understanding of these altered pathways may provide novel insights into patient stratification, therapeutic strategies and the development of new drugs. However, a challenge remains in accurately identifying pathways altered by somatic mutations across human cancers, due to the diverse mutation spectrum. We developed an innovative approach to integrate somatic mutation data with gene networks and pathways, in order to identify pathways altered by somatic mutations across cancers. Results: We applied our approach to The Cancer Genome Atlas (TCGA) dataset of somatic mutations in 4790 cancer patients with 19 different types of tumors. Our analysis identified cancer-type-specific altered pathways enriched with known cancer-relevant genes and targets of currently available drugs. To investigate the clinical significance of these altered pathways, we performed consensus clustering for patient stratification using member genes in the altered pathways coupled with gene expression datasets from 4870 patients from TCGA, and multiple independent cohorts confirmed that the altered pathways could be used to stratify patients into subgroups with significantly different clinical outcomes. Of particular significance, certain patient subpopulations with poor prognosis were identified because they had specific altered pathways for which there are available targeted therapies. These findings could be used to tailor and intensify therapy in these patients, for whom current therapy is suboptimal. Availability and implementation: The code is available at: http://www.taehyunlab.org. Contact: jhcheong@yuhs.ac or taehyun.hwang@utsouthwestern.edu or taehyun.cs@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26635139

Connecting with Frequent Adolescent Visitors to the School Nurse through the Use of Intentional Interviewing

ERIC Educational Resources Information Center

Pavletic, Adria C.

2011-01-01

Nurses as accessible, helping adults within schools have daily opportunities to reach adolescents with unmet mental health needs. Understanding the relationship between frequent clinic visits or somatic complaints as a sign of underlying problems, which may be organic or psychoemotional in origin, requires the unique skill set of the school nurse.…

Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas.

PubMed

Furukawa, Toru; Sakamoto, Hitomi; Takeuchi, Shoko; Ameri, Mitra; Kuboki, Yuko; Yamamoto, Toshiyuki; Hatori, Takashi; Yamamoto, Masakazu; Sugiyama, Masanori; Ohike, Nobuyuki; Yamaguchi, Hiroshi; Shimizu, Michio; Shibata, Noriyuki; Shimizu, Kyoko; Shiratori, Keiko

2015-03-06

Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we identified recurrent mutations of BRCA2 and FAT genes. BRCA2 showed somatic or germline premature termination mutations, with loss of the wild-type allele in 3 of 7 tumors. FAT1, FAT3, and FAT4 showed somatic or germline missense mutations in 4 of 7 tumors. The germline FAT mutations were with loss of the wild-type allele. Loss of BRCA2 expression was observed in 5 of 11 tumors. One patient with a BRCA2-mutated tumor experienced complete remission of liver metastasis following cisplatinum chemotherapy. In conclusion, acinar cell carcinomas show a distinct mutation pattern and often harbor somatic or germline mutations of BRCA2 and FAT genes. This result may warrant assessment of BRCA2 abrogation in patients with the carcinoma to determine their sensitivity to chemotherapy.

Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

PubMed Central

Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry

2015-01-01

The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca2+-activated K+ channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. SIGNIFICANCE STATEMENT Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main compartments: dendritic, somatic, and axonal. How the neurons receive information, process it, and pass on new information depends upon how these three compartments operate. While it has long been assumed that axons are simply for conducting information from the cell body to the synapses, here we demonstrate that the axons of different types of interneurons, the inhibitory cells, possess differing electrophysiological properties. This result implies that differing types of interneurons perform different tasks in the cortex, not only through their anatomical connections, but also through how their axons operate. PMID:26609152

EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation

PubMed Central

Béguelin, Wendy; Popovic, Relja; Teater, Matt; Jiang, Yanwen; Bunting, Karen L.; Rosen, Monica; Shen, Hao; Yang, Shao Ning; Wang, Ling; Ezponda, Teresa; Martinez-Garcia, Eva; Zhang, Haikuo; Zhang, Yupeng; Verma, Sharad K.; McCabe, Michael T.; Ott, Heidi M.; Van Aller, Glenn S.; Kruger, Ryan G.; Liu, Yan; McHugh, Charles F.; Scott, David W.; Chung, Young Rock; Kelleher, Neil; Shaknovich, Rita; Creasy, Caretha L.; Gascoyne, Randy D.; Wong, Kwok-Kin; Cerchietti, Leandro C.; Levine, Ross L.; Abdel-Wahab, Omar; Licht, Jonathan D.; Elemento, Olivier; Melnick, Ari M.

2013-01-01

The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B-cells and targeted by somatic mutations in B-cell lymphomas. Here we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions in mice. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B-cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets in B-cells, and in human B-cell lymphomas. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GCB-type DLBCLs are mostly addicted to EZH2, regardless of mutation status, but not the more differentiated ABC-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting. PMID:23680150

Intraspecific competition and density dependence of food consumption and growth in Arctic charr.

PubMed

Amundsen, Per-Arne; Knudsen, Rune; Klemetsen, Anders

2007-01-01

1. Intraspecific competition for restricted food resources is considered to play a fundamental part in density dependence of somatic growth and other population characteristics, but studies simultaneously addressing the interrelationships between population density, food acquisition and somatic growth have been missing. 2. We explored the food consumption and individual growth rates of Arctic charr Salvelinus alpinus in a long-term survey following a large-scale density manipulation experiment in a subarctic lake. 3. Prior to the initiation of the experiment, the population density was high and the somatic growth rates low, revealing a severely overcrowded and stunted fish population. 4. During the 6-year period of stock depletion the population density of Arctic charr was reduced with about 75%, resulting in an almost twofold increase in food consumption rates and enhanced individual growth rates of the fish. 5. Over the decade following the density manipulation experiment, the population density gradually rose to intermediate levels, accompanied by corresponding reductions in food consumption and somatic growth rates. 6. The study revealed negative relationships with population density for both food consumption and individual growth rates, reflecting a strong positive correlation between quantitative food intake and somatic growth rates. 7. Both the growth and consumption rate relationships with population density were well described by negative power curves, suggesting that large density perturbations are necessary to induce improved feeding conditions and growth rates in stunted fish populations. 8. The findings demonstrate that quantitative food consumption represents the connective link between population density and individual growth rates, apparently being highly influenced by intraspecific competition for limited resources.

Pre-screening method for somatic cell contamination in human sperm epigenetic studies.

PubMed

Jenkins, Timothy G; Liu, Lihua; Aston, Kenneth I; Carrell, Douglas T

2018-04-01

Sperm epigenetic profiles are frequently studied and are of great interest in many fields. One major technical concern when assessing these marks is the potential for somatic cell contamination. Because somatic cells have dramatically different epigenetic signatures, even small levels of contamination can result in significant problems in analysis and interpretation of data. In this study we evaluate an assay, which we designed to offer a reliable 'pre-screen' for somatic cell contamination that directly assesses the DNA being used in the study to determine tissue purity. In brief, we designed an inexpensive and simple assay that utilizes the strong differential methylation between sperm and somatic cells at four genomic loci to assess the general purity of samples prior to performing expensive and time intensive assays. The assay is able to reliably detect contamination qualitatively by running the sample on an agarose gel, or quantitatively with the use of a bioanalyzer. With this technique we have found that we can detect potentially contaminating signals in samples of many different types, including those from patients with poor sperm phenotypes (oligozoospermia, asthenozoospermia, and teratozoospermia). We also have found that the use of multiple sites to determine potential contamination is key, as some conditions (asthenozoospermia specifically) appear at one site to reflect a somatic-like profile, while at all other sites it appears to have very typical sperm DNA methylation signatures. Taken together, the use of the assay described herein was effective at identifying contamination and could be implemented in many labs to quickly and inexpensively pre-screen samples prior to performing far more expensive and labor intensive procedures. Additionally, the principles applied to the development of this assay could be easily adapted for the development of other assays to pre-screen different tissue/cell types or model organisms.

Metamorphosis of mesothelial cells with active horizontal motility in tissue culture.

PubMed

Nagai, Hirotaka; Chew, Shan Hwu; Okazaki, Yasumasa; Funahashi, Satomi; Namba, Takashi; Kato, Takuya; Enomoto, Atsushi; Jiang, Li; Akatsuka, Shinya; Toyokuni, Shinya

2013-01-01

Mesothelial cells, which have diverse roles in physiology and pathology, constitute the mesothelium along with connective tissue and the basement membrane; the mesothelium serves to shield the somatic cavities. After mesothelial injury, mesothelial cells undergo tissue recovery. However, the mechanism of mesothelial regeneration remains poorly understood. In this study, we used confocal time-lapse microscopy to demonstrate that transformed mesothelial cells (MeT5A) and mouse peritoneal mesothelial cells can randomly migrate between cells in cell culture and in ex vivo tissue culture, respectively. Moreover, peritoneal mesothelial cells changed their morphology from a flattened shape to a cuboidal one prior to the migration. Conversely, MDCKII epithelial cells forming tight cell-cell contacts with one another do not alter the arrangement of adjacent cells during movement. Our evidence complements the current hypotheses of mesothelial regeneration and suggests that certain types of differentiated mesothelial cells undergo morphological changes before initiating migration to repair injured sites.

Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs

PubMed Central

2013-01-01

Background The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations – changes specific to a tumor and not within an individual’s germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific. Results We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity. Conclusion We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic. PMID:23642077

Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs.

PubMed

Christoforides, Alexis; Carpten, John D; Weiss, Glen J; Demeure, Michael J; Von Hoff, Daniel D; Craig, David W

2013-05-04

The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations--changes specific to a tumor and not within an individual's germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific. We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity. We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic.

Religious coping and cognitive symptoms of depression in elderly medical patients.

PubMed

Koenig, H G; Cohen, H J; Blazer, D G; Kudler, H S; Krishnan, K R; Sibert, T E

1995-01-01

The investigators examined associations between depressive symptom type and religious coping in 832 consecutively admitted older medical inpatients. Cognitive symptoms of depression, but not somatic symptoms, were related to religious coping. Boredom, loss of interest, social withdrawal, feeling downhearted and blue, restlessness, feeling like a failure, feeling hopeless, or feeling that other people were better off were all significantly less common among religious copers. Difficulty initiating new activities was the only somatic symptom related to this coping behavior. Religious coping, a strategy heavily dependent on cognitive processes, is associated with fewer cognitive but not somatic symptoms of depression in medically ill older patients

Uncoupling the Trade-Off between Somatic Proteostasis and Reproduction in Caenorhabditis elegans Models of Polyglutamine Diseases

PubMed Central

Shemesh, Netta; Shai, Nadav; Meshnik, Lana; Katalan, Rotem; Ben-Zvi, Anat

2017-01-01

Caenorhabditis elegans somatic protein homeostasis (proteostasis) is actively remodeled at the onset of reproduction. This proteostatic collapse is regulated cell-nonautonomously by signals from the reproductive system that transmit the commitment to reproduction to somatic cells. Here, we asked whether the link between the reproductive system and somatic proteostasis could be uncoupled by activating downstream effectors in the gonadal longevity cascade. Specifically, we examined whether over-expression of lipl-4 (lipl-4(oe)), a target gene of the gonadal longevity pathway, or increase in arachidonic acid (AA) levels, associated with lipl-4(oe), modulated proteostasis and reproduction. We found that lipl-4(oe) rescued somatic proteostasis and postponed the onset of aggregation and toxicity in C. elegans models of polyglutamine (polyQ) diseases. However, lipl-4(oe) also disrupted fatty acid transport into developing oocytes and reduced reproductive success. In contrast, diet supplementation of AA recapitulated lipl-4(oe)-mediated proteostasis enhancement in wild type animals but did not affect the reproductive system. Thus, the gonadal longevity pathway mediates a trade-off between somatic maintenance and reproduction, in part by regulating the expression of genes, such as lipl-4, with inverse effects on somatic maintenance and reproduction. We propose that AA could uncouple such germline to soma crosstalk, with beneficial implications protein misfolding diseases. PMID:28503130

E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer.

PubMed

Lopes-Ramos, Camila M; Barros, Bruna P; Koyama, Fernanda C; Carpinetti, Paola A; Pezuk, Julia; Doimo, Nayara T S; Habr-Gama, Angelita; Perez, Rodrigo O; Parmigiani, Raphael B

2017-01-01

Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.

Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

PubMed Central

Streeter, Kristi A.; Sunshine, Michael D.; Patel, Shreya; Gonzalez-Rothi, Elisa J.; Reier, Paul J.

2017-01-01

Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most midcervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multielectrode array was used to record C4/5 spinal discharge before [baseline (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O2, H1–H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared with BL (19%; p < 0.0001). Another subset had a similar response following each episode (40%) compared with BL (19%; p < 0.0001). In the latter group, connectivity remained elevated 15 min post-AIH (30%; p = 0.0002). Inhibitory C-IN connectivity increased during H1–H3 (4.5%; p = 0.0160), but was reduced 15 min post-AIH (0.5%; p = 0.0439). Spike-triggered averaging indicated that a subset of C-INs is synaptically coupled to phrenic motoneurons and excitatory inputs to these “pre-phrenic” cells increased during AIH. We conclude that AIH alters connectivity of the midcervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network. SIGNIFICANCE STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH. PMID:28751456

A Simple Model-Based Approach to Inferring and Visualizing Cancer Mutation Signatures

PubMed Central

Shiraishi, Yuichi; Tremmel, Georg; Miyano, Satoru; Stephens, Matthew

2015-01-01

Recent advances in sequencing technologies have enabled the production of massive amounts of data on somatic mutations from cancer genomes. These data have led to the detection of characteristic patterns of somatic mutations or “mutation signatures” at an unprecedented resolution, with the potential for new insights into the causes and mechanisms of tumorigenesis. Here we present new methods for modelling, identifying and visualizing such mutation signatures. Our methods greatly simplify mutation signature models compared with existing approaches, reducing the number of parameters by orders of magnitude even while increasing the contextual factors (e.g. the number of flanking bases) that are accounted for. This improves both sensitivity and robustness of inferred signatures. We also provide a new intuitive way to visualize the signatures, analogous to the use of sequence logos to visualize transcription factor binding sites. We illustrate our new method on somatic mutation data from urothelial carcinoma of the upper urinary tract, and a larger dataset from 30 diverse cancer types. The results illustrate several important features of our methods, including the ability of our new visualization tool to clearly highlight the key features of each signature, the improved robustness of signature inferences from small sample sizes, and more detailed inference of signature characteristics such as strand biases and sequence context effects at the base two positions 5′ to the mutated site. The overall framework of our work is based on probabilistic models that are closely connected with “mixed-membership models” which are widely used in population genetic admixture analysis, and in machine learning for document clustering. We argue that recognizing these relationships should help improve understanding of mutation signature extraction problems, and suggests ways to further improve the statistical methods. Our methods are implemented in an R package pmsignature (https://github.com/friend1ws/pmsignature) and a web application available at https://friend1ws.shinyapps.io/pmsignature_shiny/. PMID:26630308

Embodied niche construction in the hominin lineage: semiotic structure and sustained attention in human embodied cognition

PubMed Central

Stutz, Aaron J.

2014-01-01

Human evolution unfolded through a rather distinctive, dynamically constructed ecological niche. The human niche is not only generally terrestrial in habitat, while being flexibly and extensively heterotrophic in food-web connections. It is also defined by semiotically structured and structuring embodied cognitive interfaces, connecting the individual organism with the wider environment. The embodied dimensions of niche-population co-evolution have long involved semiotic system construction, which I hypothesize to be an evolutionarily primitive aspect of learning and higher-level cognitive integration and attention in the great apes and humans alike. A clearly pre-linguistic form of semiotic cognitive structuration is suggested to involve recursively learned and constructed object icons. Higher-level cognitive iconic representation of visually, auditorily, or haptically perceived extrasomatic objects would be learned and evoked through indexical connections to proprioceptive and affective somatic states. Thus, private cognitive signs would be defined, not only by their learned and perceived extrasomatic referents, but also by their associations to iconically represented somatic states. This evolutionary modification of animal associative learning is suggested to be adaptive in ecological niches occupied by long-lived, large-bodied ape species, facilitating memory construction and recall in highly varied foraging and social contexts, while sustaining selective attention during goal-directed behavioral sequences. The embodied niche construction (ENC) hypothesis of human evolution posits that in the early hominin lineage, natural selection further modified the ancestral ape semiotic adaptations, favoring the recursive structuration of concise iconic narratives of embodied interaction with the environment. PMID:25136323

Embodied niche construction in the hominin lineage: semiotic structure and sustained attention in human embodied cognition.

PubMed

Stutz, Aaron J

2014-01-01

Human evolution unfolded through a rather distinctive, dynamically constructed ecological niche. The human niche is not only generally terrestrial in habitat, while being flexibly and extensively heterotrophic in food-web connections. It is also defined by semiotically structured and structuring embodied cognitive interfaces, connecting the individual organism with the wider environment. The embodied dimensions of niche-population co-evolution have long involved semiotic system construction, which I hypothesize to be an evolutionarily primitive aspect of learning and higher-level cognitive integration and attention in the great apes and humans alike. A clearly pre-linguistic form of semiotic cognitive structuration is suggested to involve recursively learned and constructed object icons. Higher-level cognitive iconic representation of visually, auditorily, or haptically perceived extrasomatic objects would be learned and evoked through indexical connections to proprioceptive and affective somatic states. Thus, private cognitive signs would be defined, not only by their learned and perceived extrasomatic referents, but also by their associations to iconically represented somatic states. This evolutionary modification of animal associative learning is suggested to be adaptive in ecological niches occupied by long-lived, large-bodied ape species, facilitating memory construction and recall in highly varied foraging and social contexts, while sustaining selective attention during goal-directed behavioral sequences. The embodied niche construction (ENC) hypothesis of human evolution posits that in the early hominin lineage, natural selection further modified the ancestral ape semiotic adaptations, favoring the recursive structuration of concise iconic narratives of embodied interaction with the environment.

Micropropagation of Iris sp.

PubMed

Jevremović, Slađana; Jeknić, Zoran; Subotić, Angelina

2013-01-01

Irises are perennial plants widely used as ornamental garden plants or cut flowers. Some species accumulate secondary metabolites, making them highly valuable to the pharmaceutical and perfume industries. Micropropagation of irises has successfully been accomplished by culturing zygotic embryos, different flower parts, and leaf base tissues as starting explants. Plantlets are regenerated via somatic embryogenesis, organogenesis, or both processes at the same time depending on media composition and plant species. A large number of uniform plants are produced by somatic embryogenesis, however, some species have decreased morphogenetic potential overtime. Shoot cultures obtained by organogenesis can be multiplied for many years. Somatic embryogenic tissue can be reestablished from leaf bases of in vitro-grown shoots. The highest number of plants can be obtained by cell suspension cultures. This chapter describes effective in vitro plant regeneration protocols for Iris species from different types of explants by somatic embryogenesis and/or organogenesis suitable for the mass propagation of ornamental and pharmaceutical irises.

The reporting of specific physical symptoms for mental distress in general practice.

PubMed

de Waal, Margot W M; Arnold, Ingrid A; Spinhoven, Philip; Eekhof, Just A H; van Hemert, Albert M

2005-08-01

Do patients report specific physical symptoms in the presence of mental distress, taking into account the presence of somatic disease? Cross-sectional data were collected from 1458 participants in eight general practices in The Netherlands. Electronic patient records provided information on somatic disease. Questionnaires included the Hospital Anxiety and Depression Scale (HADS) to measure mental distress and the Physical Symptom Checklist (PSC). Patients reporting mental distress reported all types of physical symptoms more often than did patients without mental distress. Multivariate analyses in women, corrected for the presence of somatic disease, did not substantially change the univariate pattern. Odds ratios were particularly high (>6) for feeling tired or having low energy, fatigue without exertion and forgetfulness. It is the level of mental distress rather than gender or somatic disease that accounts for the reporting of any physical symptom. Fatigue might be an exception, but here, the classification as "physical" rather then "mental" is somewhat ambiguous.

Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

PubMed

Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

2017-09-01

The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

Abnormalities in human pluripotent cells due to reprogramming mechanisms

PubMed Central

Ma, Hong; Morey, Robert; O’Neil, Ryan C.; He, Yupeng; Daughtry, Brittany; Schultz, Matthew D.; Hariharan, Manoj; Nery, Joseph R.; Castanon, Rosa; Sabatini, Karen; Thiagarajan, Rathi D.; Tachibana, Masahito; Kang, Eunju; Tippner-Hedges, Rebecca; Ahmed, Riffat; Gutierrez, Nuria Marti; Van Dyken, Crystal; Polat, Alim; Sugawara, Atsushi; Sparman, Michelle; Gokhale, Sumita; Amato, Paula; Wolf, Don P.; Ecker, Joseph R.; Laurent, Louise C.; Mitalipov, Shoukhrat

2016-01-01

Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the ‘gold standard’, they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies. PMID:25008523

Chemical compound-based direct reprogramming for future clinical applications

PubMed Central

Takeda, Yukimasa; Harada, Yoshinori; Yoshikawa, Toshikazu; Dai, Ping

2018-01-01

Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state. Because the strategy also depends on forced expression of exogenous lineage-specific transcription factors, the direct reprogramming in a chemical compound-based manner is an ideal approach to further reduce the risk for tumorigenesis. So far, a number of reported research efforts have revealed that combinations of chemical compounds and cell-type specific medium transdifferentiate somatic cells into desired cell types including neuronal cells, glial cells, neural stem cells, brown adipocytes, cardiomyocytes, somatic progenitor cells, and pluripotent stem cells. These desired cells rapidly converted from patient-derived autologous fibroblasts can be applied for their own transplantation therapy to avoid immune rejection. However, complete chemical compound-induced conversions remain challenging particularly in adult human-derived fibroblasts compared with mouse embryonic fibroblasts (MEFs). This review summarizes up-to-date progress in each specific cell type and discusses prospects for future clinical application toward cell transplantation therapy. PMID:29739872

A wider view on gastric erosion: detailed evaluation of complex somatic and behavioral changes in rats treated with indomethacin at gastric ulcerogenic dose.

PubMed

Filaretova, L P; Bagaeva, T R; Morozova, O Y; Zelena, D

2014-10-01

Gastric erosion is widespread side effect of nonsteroidal anti-inflammatory drugs. To examine the complexity of the brain-gut axis regulation, indomethacin-induced gastric erosion formation was studied in connection with somatic and behavioral changes. During a constant telemetric recording of heart rate, body temperature, and locomotion of male rats we examined the effects of 24 h fasting, indomethacin (35 mg/kg s.c.) injection, and refeeding at 4 h. Behavior was analyzed on elevated plus maze (EPM) at 24 h and somatic changes at 72 h. Gastric erosion developed 4 h after indomethacin injection, healed 72 h later contrasted by large injury in the small intestine. As classical signs of chronic stress, body and thymus weight were reduced while adrenal weight was enhanced 72 h after indomethacin injection. Fasting by itself changed all telemetrically recorded parameters with most prominent decrease in heart rate. Indomethacin induced similar diminishing effects with earliest and strongest temperature decrease. As a sign of more anxious phenotype locomotion reducing effect of indomethacin injection was detected on EPM. The EPM-induced temperature elevation was missing in indomethacin-treated animals. Fasting by itself induce somatic changes, which can make the animals more vulnerable to ulcerogenic stimuli. Development of indomethacin-induced gastrointestinal lesions happened in parallel with disturbances of heart rate, core body temperature, and chronic stress-like somatic changes as well as anxiety-like behavior. We have to be more aware of the existence of the brain-gut axis and should study changes in the whole body rather than focusing on a specific organ. elevated plus maze.

Finnish Sixth Graders as Victims of Adult, Peer, and Co-Occurring Adult and Peer Violence: Depression, Somatization, and Violent Ideation in Relation to Victimization

ERIC Educational Resources Information Center

Uusitalo-Malmivaara, Lotta

2013-01-01

This study examined the experiences of peer and adult victimization of 737 12-year-old Finnish students. Of the respondents, 28.4% had experienced peer or adult, or both kinds of violence. Peer violence was the most common type of violence, while adult violence was rare. The associations between victimization and depression, somatization and…

Analyzing Somatic Genome Rearrangements in Human Cancers by Using Whole-Exome Sequencing | Office of Cancer Genomics

Cancer.gov

Although exome sequencing data are generated primarily to detect single-nucleotide variants and indels, they can also be used to identify a subset of genomic rearrangements whose breakpoints are located in or near exons. Using >4,600 tumor and normal pairs across 15 cancer types, we identified over 9,000 high confidence somatic rearrangements, including a large number of gene fusions.

Brooke-Spiegler syndrome: report of 10 patients from 8 families with novel germline mutations: evidence of diverse somatic mutations in the same patient regardless of tumor type.

PubMed

Sima, Radek; Vanecek, Tomas; Kacerovska, Denisa; Trubac, Pavel; Cribier, Bernard; Rutten, Arno; Vazmitel, Marina; Spagnolo, Dominic V; Litvik, Radek; Vantuchova, Yvetta; Weyers, Wolfgang; Pearce, Robert L; Pearn, John; Michal, Michal; Kazakov, Dmitry V

2010-06-01

Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms including spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma (cribriform trichoblastoma). BSS patients have various mutations in the CYLD gene, a tumor suppressor gene located on chromosome 16q. Our search of the literature revealed 51 germline CYLD mutations reported to date. Somatic CYLD mutations have rarely been investigated. We studied 10 patients from 8 families with BSS. Analysis of germline mutations of the CYLD gene was performed using either peripheral blood or nontumorous tissue. In addition, 19 formalin-fixed paraffin-embedded tumor samples were analyzed for somatic mutations, including loss of heterozygosity studies. A total of 38 tumors were available for histopathologic review. We have identified 8 novel germline mutations, all of which consisted of substitutions, deletions, and insertions/duplications and all except one led to premature stop codons. The substitution mutation in a single case was also predicted to disrupt protein function and seems causally implicated in tumor formation. We demonstrate for the first time that somatic events, loss of heterozygosity, or sequence mutations may differ among multiple neoplasms even of the same histologic type, occurring in the same patient.

Tumorigenicity assessment of human cell-processed therapeutic products.

PubMed

Yasuda, Satoshi; Sato, Yoji

2015-09-01

Human pluripotent stem cells (hPSCs) are expected to be sources of various cell types used for cell therapy, although hPSCs are intrinsically tumorigenic and form teratomas in immunodeficient animals after transplant. Despite the urgent need, no detailed guideline for the assessment of tumorigenicity of human cell-processed therapeutic products (hCTPs) has been issued. Here we describe our consideration on tumorigenicity and related tests of hCTPs. The purposes of those tests for hPSC-based products are classified into three categories: 1) quality control of raw materials; 2) quality control of intermediate/final products; and 3) safety assessment of final products. Appropriate types of tests need to be selected, taking the purpose(s) into consideration. In contrast, human somatic (and somatic stem) cells are believed to have little tumorigenicity. Therefore, GMP-compliant quality control is essential to avoid contamination of somatic cell-derived products with tumorigenic cells. Compared with in vivo tumorigenicity tests, in vitro cell proliferation assays may be more useful and reasonable for detecting immortalized cells that have a growth advantage in somatic cell-based products. The results obtained from tumorigenicity and related tests for hCTPs should meet the criteria for decisions on product development, manufacturing processes, and clinical applications. Copyright © 2015.

Simultaneous detection of somatic and F-specific coliphages in different settings by Escherichia coli strain CB390.

PubMed

Agulló-Barceló, Miriam; Galofré, Belén; Sala, Lluís; García-Aljaro, Cristina; Lucena, Francisco; Jofre, Juan

2016-09-01

Bacteriophages are increasingly being used as water quality indicators. Two groups of phages infecting Escherichia coli, somatic and F-specific coliphages, are being considered as indicators of fecal and viral contamination for several types of water around the world. However, some uncertainties remain regarding which coliphages to assess. Recently, E. coli strain CB390 has been reported to be suitable for simultaneous detection of both groups, which seems to be more informative than determining only one of the groups. Here, a significant number of samples from different settings, mostly those where F-specific phages have been reported to outnumber somatic coliphages, are analyzed for somatic coliphages, F-specific RNA phages by standardized methods and coliphages detected by host strain CB390. The results presented here confirm that the numbers of phages counted using CB390 are equivalent to the sum of the somatic and F-specific coliphages counted independently in all settings. Hence the usefulness of this strain for simultaneous detection of somatic and F-specific coliphages is confirmed. Also, sets of data on the presence of coliphages in reclaimed and groundwater are reported. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Three forms of somatization presenting in primary care settings in Spain.

PubMed

García-Campayo, J; Lobo, A; Pérez-Echeverría, M J; Campos, R

1998-09-01

The objective of this paper is to study the prevalence and clinical characteristics of functional, hypochondriacal, and presenting somatization (FSTS, HSTS, and PSTS, respectively) defined by standardized criteria, as well as the validity of their distinction in primary care in Spain. A two-stage epidemiological study of a representative sample (N = 1559) of primary care patients was carried out. In the first phase, the validated Spanish versions of General Health Questionnaire, Mini-Mental State Examination, and CAGE were used. In the second phase, the Standardized Polyvalent Psychiatric Interview, an interview for the multiaxial assessment of medical patients, was employed. The prevalence of any form of somatization in Spain was 21.3% (FSTS: 16.2%, PSTS: 9.4%, HSTS: 6.7%). Overlap of any of the three clinical forms was very frequent (42.7%). FSTS patients tended to be more chronic and showed higher scores in fatigue but lower scores in both depression and anxiety. Chronicity was frequent among somatizers, particularly in those who fulfilled more than one kind of somatization. Differences in diagnostic distribution among the three groups were also observed. In conclusion, this is the first study giving support to the validity of the distinction among three types of somatization in Spain, but overlap was more frequent than reported in North American studies.

Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.

PubMed

Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R; Greenleaf, William J; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H

2015-07-01

Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors. Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote lineage differentiation. Here we test this method using genetic lineage tracing for expression of endogenous Nanog and Oct4 and for X chromosome reactivation, as these events mark acquisition of pluripotency. We show that the vast majority of reprogrammed cardiomyocytes or neural stem cells obtained from mouse fibroblasts by OSKM-induced 'transdifferentiation' pass through a transient pluripotent state, and that their derivation is molecularly coupled to iPSC formation mechanisms. Our findings underscore the importance of defining trajectories during cell reprogramming by various methods.

Transient Acquisition of Pluripotency During Somatic Cell Transdifferentiation with iPSC Reprogramming Factors

PubMed Central

Maza, Itay; Caspi, Inbal; Zviran, Asaf; Chomsky, Elad; Rais, Yoach; Viukov, Sergey; Geula, Shay; Buenrostro, Jason D.; Weinberger, Leehee; Krupalnik, Vladislav; Hanna, Suhair; Zerbib, Mirie; Dutton, James R.; Greenleaf, William J.; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H.

2015-01-01

Somatic cells can be transdifferentiated to other cell types without passing through a pluripotent state by ectopic expression of appropriate transcription factors1,2. Recent reports have proposed an alternative transdifferentiation method in which fibroblasts are directly converted to various mature somatic cell types by brief expression of the induced pluripotent stem cell (iPSC) reprogramming factors Oct4, Sox2, Klf4 and c-Myc (OSKM) followed by cell expansion in media that promote lineage differentiation3–6. Here we test this method using genetic lineage tracing for expression of endogenous Nanog and Oct4 and for X chromosome reactivation, as these events mark acquisition of pluripotency. We show that the vast majority of reprogrammed cardiomyocytes or neural stem cells obtained from mouse fibroblasts by OSKM-induced transdifferentiation pass through a transient pluripotent state, and that their derivation is molecularly coupled to iPSC formation mechanisms. Our findings underscore the importance of defining trajectories during cell reprogramming by different methods. PMID:26098448

Changes in oil content of transgenic soybeans expressing the yeast SLC1 gene.

PubMed

Rao, Suryadevara S; Hildebrand, David

2009-10-01

The wild type (Wt) and mutant form of yeast (sphingolipid compensation) genes, SLC1 and SLC1-1, have been shown to have lysophosphatidic acid acyltransferase (LPAT) activities (Nageic et al. in J Biol Chem 269:22156-22163, 1993). Expression of these LPAT genes was reported to increase oil content in transgenic Arabidopsis and Brassica napus. It is of interest to determine if the TAG content increase would also be seen in soybeans. Therefore, the wild type SLC1 was expressed in soybean somatic embryos under the control of seed specific phaseolin promoter. Some transgenic somatic embryos and in both T2 and T3 transgenic seeds showed higher oil contents. Compared to controls, the average increase in triglyceride values went up by 1.5% in transgenic somatic embryos. A maximum of 3.2% increase in seed oil content was observed in a T3 line. Expression of the yeast Wt LPAT gene did not alter the fatty acid composition of the seed oil.

Emerging patterns of somatic mutations in cancer

PubMed Central

Watson, Ian R.; Takahashi, Koichi; Futreal, P. Andrew; Chin, Lynda

2014-01-01

The advance in technological tools for massively parallel, high-throughput sequencing of DNA has enabled the comprehensive characterization of somatic mutations in large number of tumor samples. Here, we review recent cancer genomic studies that have assembled emerging views of the landscapes of somatic mutations through deep sequencing analyses of the coding exomes and whole genomes in various cancer types. We discuss the comparative genomics of different cancers, including mutation rates, spectrums, and roles of environmental insults that influence these processes. We highlight the developing statistical approaches used to identify significantly mutated genes, and discuss the emerging biological and clinical insights from such analyses as well as the challenges ahead translating these genomic data into clinical impacts. PMID:24022702

Piwi Is Required in Multiple Cell Types to Control Germline Stem Cell Lineage Development in the Drosophila Ovary

PubMed Central

Ma, Xing; Wang, Su; Do, Trieu; Song, Xiaoqing; Inaba, Mayu; Nishimoto, Yoshiya; Liu, Lu-ping; Gao, Yuan; Mao, Ying; Li, Hui; McDowell, William; Park, Jungeun; Malanowski, Kate; Peak, Allison; Perera, Anoja; Li, Hua; Gaudenz, Karin; Haug, Jeff; Yamashita, Yukiko; Lin, Haifan; Ni, Jian-quan; Xie, Ting

2014-01-01

The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary. PMID:24658126

The subcellular distribution of T-type Ca2+ channels in interneurons of the lateral geniculate nucleus.

PubMed

Allken, Vaneeda; Chepkoech, Joy-Loi; Einevoll, Gaute T; Halnes, Geir

2014-01-01

Inhibitory interneurons (INs) in the lateral geniculate nucleus (LGN) provide both axonal and dendritic GABA output to thalamocortical relay cells (TCs). Distal parts of the IN dendrites often enter into complex arrangements known as triadic synapses, where the IN dendrite plays a dual role as postsynaptic to retinal input and presynaptic to TC dendrites. Dendritic GABA release can be triggered by retinal input, in a highly localized process that is functionally isolated from the soma, but can also be triggered by somatically elicited Ca(2+)-spikes and possibly by backpropagating action potentials. Ca(2+)-spikes in INs are predominantly mediated by T-type Ca(2+)-channels (T-channels). Due to the complex nature of the dendritic signalling, the function of the IN is likely to depend critically on how T-channels are distributed over the somatodendritic membrane (T-distribution). To study the relationship between the T-distribution and several IN response properties, we here run a series of simulations where we vary the T-distribution in a multicompartmental IN model with a realistic morphology. We find that the somatic response to somatic current injection is facilitated by a high T-channel density in the soma-region. Conversely, a high T-channel density in the distal dendritic region is found to facilitate dendritic signalling in both the outward direction (increases the response in distal dendrites to somatic input) and the inward direction (the soma responds stronger to distal synaptic input). The real T-distribution is likely to reflect a compromise between several neural functions, involving somatic response patterns and dendritic signalling.

The Subcellular Distribution of T-Type Ca2+ Channels in Interneurons of the Lateral Geniculate Nucleus

PubMed Central

Allken, Vaneeda; Chepkoech, Joy-Loi; Einevoll, Gaute T.; Halnes, Geir

2014-01-01

Inhibitory interneurons (INs) in the lateral geniculate nucleus (LGN) provide both axonal and dendritic GABA output to thalamocortical relay cells (TCs). Distal parts of the IN dendrites often enter into complex arrangements known as triadic synapses, where the IN dendrite plays a dual role as postsynaptic to retinal input and presynaptic to TC dendrites. Dendritic GABA release can be triggered by retinal input, in a highly localized process that is functionally isolated from the soma, but can also be triggered by somatically elicited Ca2+-spikes and possibly by backpropagating action potentials. Ca2+-spikes in INs are predominantly mediated by T-type Ca2+-channels (T-channels). Due to the complex nature of the dendritic signalling, the function of the IN is likely to depend critically on how T-channels are distributed over the somatodendritic membrane (T-distribution). To study the relationship between the T-distribution and several IN response properties, we here run a series of simulations where we vary the T-distribution in a multicompartmental IN model with a realistic morphology. We find that the somatic response to somatic current injection is facilitated by a high T-channel density in the soma-region. Conversely, a high T-channel density in the distal dendritic region is found to facilitate dendritic signalling in both the outward direction (increases the response in distal dendrites to somatic input) and the inward direction (the soma responds stronger to distal synaptic input). The real T-distribution is likely to reflect a compromise between several neural functions, involving somatic response patterns and dendritic signalling. PMID:25268996

Differential nuclear remodeling of mammalian somatic cells by Xenopus laevis oocyte and egg cytoplasm

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

Alberio, Ramiro; Johnson, Andrew D.; Stick, Reimer

2005-07-01

The mechanisms governing nuclear reprogramming have not been fully elucidated yet; however, recent studies show a universally conserved ability of both oocyte and egg components to reprogram gene expression in somatic cells. The activation of genes associated with pluripotency by oocyte/egg components may require the remodeling of nuclear structures, such that they can acquire the features of early embryos and pluripotent cells. Here, we report on the remodeling of the nuclear lamina of mammalian cells by Xenopus oocyte and egg extracts. Lamin A/C is removed from somatic cells incubated in oocyte and egg extracts in an active process that requiresmore » permeable nuclear pores. Removal of lamin A/C is specific, since B-type lamins are not changed, and it is not dependent on the incorporation Xenopus egg specific lamin III. Moreover, transcriptional activity is differentially regulated in somatic cells incubated in the extracts. Pol I and II transcriptions are maintained in cells in oocyte extracts; however, both activities are abolished in egg extracts. Our study shows that components of oocyte and egg extracts can modify the nuclear lamina of somatic cells and that this nuclear remodeling induces a structural change in the nucleus which may have implications for transcriptional activity. These experiments suggest that modifications in the nuclear lamina structure by the removal of somatic proteins and the incorporation of oocyte/egg components may contribute to the reprogramming of somatic cell nuclei and may define a characteristic configuration of pluripotent cells.« less

Genetics of the connective tissue proteins: Assignment of the gene for human type I procollagen to chromosome 17 by analysis of cell hybrids and microcell hybrids*

PubMed Central

Raj, Cholappadi V. Sundar; Church, Robert L.; Klobutcher, Lawrence A.; Ruddle, Frank H.

1977-01-01

Somatic cell hybrids between mouse and human cell lines have been used to identify the specific chromosome that governs the synthesis of type I procollagen. Fourteen hybrid clones and subclones were derived independently from crosses between mouse parents [LM (thymidine kinase-negative) or A9 (hypoxanthine phosphoribosyltransferase-negative)] and human cells (human diploid lung fibroblasts WI-38 or diploid skin fibroblasts GM5, GM17, and GM9). The cultures were labeled with [3H]proline in modified Eagle's medium without serum. Radioactive procollagens were purified from the medium by the method of Church et al. [(1974) J. Mol. Biol. 86, 785-799]. DEAE-cellulose chromatography was used to separate collagen and type I and type III procollagen. Human type I procollagen was assayed by double immunodiffusion analysis with type I procollagen antibodies prepared by immunizing rabbits with purified human type I procollagen. These analyses combined with karyology and isozyme analyses of each hybrid line have produced evidence for the assignment of the gene for human type I procollagen to chromosome 17. A human microcell-mouse hybrid cell line containing only human chromosome 17 was positive for human type I procollagen, lending further support to the assignment of the human type I procollagen gene to chromosome 17. Finally, by using a hybrid line containing only the long arm of human chromosome 17 translocated onto a mouse chromosome, the type I procollagen gene can be assigned more specifically to the long arm of chromosome 17. Images PMID:412188

Assignment of electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) to human chromosome 4q33 by fluorescence in situ hybridization and somatic cell hybridization.

PubMed

Spector, E B; Seltzer, W K; Goodman, S I

1999-08-01

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a nuclear-encoded protein located in the inner mitochondrial membrane. Inherited defects of ETF-QO cause glutaric acidemia type II. We here describe the localization of the ETF-QO gene to human chromosome 4q33 by somatic cell hybridization and fluorescence in situ hybridization. Copyright 1999 Academic Press.

Role of Somatic Testicular Cells during Mouse Spermatogenesis in Three-Dimensional Collagen Gel Culture System

PubMed Central

Khajavi, Noushafarin; Akbari, Mohammad; Abolhassani, Farid; Dehpour, Ahmad Reza; Koruji, Morteza; Habibi Roudkenar, Mehryar

2014-01-01

Objective Spermatogonial stem cells (SSCs) are the only cell type that can restore fertility to an infertile recipient following transplantation. Much effort has been made to develop a protocol for differentiating isolated SSCs in vitro. Recently, three-dimensional (3D) culture system has been introduced as an appropriate microenvironment for clonal expansion and differentiation of SSCs. This system provides structural support and multiple options for several manipulation such as addition of different cells. Somatic cells have a critical role in stimulating spermatogenesis. They provide complex cell to cell interaction, transport proteins and produce enzymes and regulatory factors. This study aimed to optimize the culture condition by adding somatic testicular cells to the collagen gel culture system in order to induce spermatogenesis progression. Materials and Methods In this experimental study, the disassociation of SSCs was performed by using a two-step enzymatic digestion of type I collagenase, hyaluronidase and DNase. Somatic testicular cells including Sertoli cells and peritubular cells were obtained after the second digestion. SSCs were isolated by Magnetic Activated Cell Sorting (MACS) using GDNF family receptor alpha-1 (Gfrα-1) antibody. Two experimental designs were investigated. 1. Gfrα-1 positive SSCs were cultured in a collagen solution. 2. Somatic testicular cells were added to the Gfrα-1 positive SSCs in a collagen solution. Spermatogenesis progression was determined after three weeks by staining of synaptonemal complex protein 3 (SCP3)-positive cells. Semi-quantitative Reverse Transcription PCR was undertaken for SCP3 as a meiotic marker and, Crem and Thyroid transcription factor-1 (TTF1) as post meiotic markers. For statistical analysis student t test was performed. Results Testicular supporter cells increased the expression of meiotic and post meiotic markers and had a positive effect on extensive colony formation. Conclusion Collagen gel culture system supported by somatic testicular cells provides a microenvironment that mimics seminiferous epithelium and induces spermatogenesis in vitro. PMID:24518977

Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments

PubMed Central

Goodell, Margaret A.; Nguyen, Hoang; Shroyer, Noah

2017-01-01

Somatic stem cells replenish many tissues throughout life to repair damage and to maintain tissue homeostasis. Stem cell function is frequently described as following a hierarchical model in which a single master cell undergoes self-renewal and differentiation into multiple cell types and is responsible for most regenerative activity. However, recent data from studies on blood, skin and intestinal epithelium all point to the concomitant action of multiple types of stem cells with distinct everyday roles. Under stress conditions such as acute injury, the surprising developmental flexibility of these stem cells enables them to adapt to diverse roles and to acquire different regeneration capabilities. This paradigm shift raises many new questions about the developmental origins, inter-relationships and molecular regulation of these multiple stem cell types. PMID:25907613

Human Connections and Their Roles in the Occupational Well-being of Healthcare Professionals: A Study on Loneliness and Empathy

PubMed Central

Soler-Gonzalez, Jorge; San-Martín, Montserrat; Delgado-Bolton, Roberto; Vivanco, Luis

2017-01-01

Human connections are key to the promotion of health and prevention of illness; moreover, illness can cause deterioration of human connections. Healthcare professional–patient relationships are key to ensuring the preservation of adequate human connections. It is important for healthcare professionals to develop their ability to foster satisfactory human connections because: (i) they represent social support for patients; and (ii) they prevent work-related stress. In this study we assessed the relationship between absence (loneliness) and presence (empathy) of human connections with the occupational well-being of healthcare professionals. The Scale of Collateral Effects, which measures somatization, exhaustion, and work alienation; the Jefferson Scale of Empathy; and the Social and Emotional Loneliness Scale for Adults, were mailed to 628 healthcare professionals working in Spanish public healthcare institutions. The following explanatory variables were used to evaluate work well-being: (a) empathy, as a professional competence; (b) loneliness, age, and family burden, as psychological indicators; and (c) professional experience, work dedication, and salary, as work indicators. Comparison, correlation, and regression analyses were performed to measure the relationships among these variables and occupational well-being. Of 628 surveys mailed, 433 (69% response rate) were returned fully completed. Adequate reliability was confirmed for all instruments. The entire sample was divided into four groups, based on the combined variable, “occupation by sex.” Comparative analyses demonstrated differences among “occupation by sex” groups in collateral effects (p = 0.03) and empathy (p = 0.04), but not loneliness (p = 0.84). Inverse associations between empathy and collateral effects were confirmed for somatization (r = -0.16; p < 0.001), exhaustion (r = -0.14; p = 0.003), and work alienation (r = -0.16; p < 0.001). Furthermore, loneliness was positively associated with collateral effects (r = 0.22; p < 0.001). Neither family burden, nor work dedication to clinics or management activities were associated with the three collateral effects measured. These findings support an important role for empathy in the prevention of work stress in healthcare professionals. They also confirm that loneliness, as a multidimensional and domain specific experience, is detrimental to occupational well-being. PMID:28900410

Human Connections and Their Roles in the Occupational Well-being of Healthcare Professionals: A Study on Loneliness and Empathy.

PubMed

Soler-Gonzalez, Jorge; San-Martín, Montserrat; Delgado-Bolton, Roberto; Vivanco, Luis

2017-01-01

Human connections are key to the promotion of health and prevention of illness; moreover, illness can cause deterioration of human connections. Healthcare professional-patient relationships are key to ensuring the preservation of adequate human connections. It is important for healthcare professionals to develop their ability to foster satisfactory human connections because: (i) they represent social support for patients; and (ii) they prevent work-related stress. In this study we assessed the relationship between absence (loneliness) and presence (empathy) of human connections with the occupational well-being of healthcare professionals. The Scale of Collateral Effects, which measures somatization, exhaustion, and work alienation; the Jefferson Scale of Empathy; and the Social and Emotional Loneliness Scale for Adults, were mailed to 628 healthcare professionals working in Spanish public healthcare institutions. The following explanatory variables were used to evaluate work well-being: (a) empathy, as a professional competence; (b) loneliness, age, and family burden, as psychological indicators; and (c) professional experience, work dedication, and salary, as work indicators. Comparison, correlation, and regression analyses were performed to measure the relationships among these variables and occupational well-being. Of 628 surveys mailed, 433 (69% response rate) were returned fully completed. Adequate reliability was confirmed for all instruments. The entire sample was divided into four groups, based on the combined variable, "occupation by sex." Comparative analyses demonstrated differences among "occupation by sex" groups in collateral effects ( p = 0.03) and empathy ( p = 0.04), but not loneliness ( p = 0.84). Inverse associations between empathy and collateral effects were confirmed for somatization ( r = -0.16; p < 0.001), exhaustion ( r = -0.14; p = 0.003), and work alienation ( r = -0.16; p < 0.001). Furthermore, loneliness was positively associated with collateral effects ( r = 0.22; p < 0.001). Neither family burden, nor work dedication to clinics or management activities were associated with the three collateral effects measured. These findings support an important role for empathy in the prevention of work stress in healthcare professionals. They also confirm that loneliness, as a multidimensional and domain specific experience, is detrimental to occupational well-being.

Release of somatic embryogenic potential from excised zygotic embryos of carrot and maintenance of proembryonic cultures in hormone-free medium.

PubMed

Smith, D L; Krikorian, A D

1989-01-01

Excised zygotic embryos, mericarps ("seeds") and hypocotyls of seedlings of cultivated carrot Daucus carota cv. Scarlet Nantes were evaluated for their ability to generate somatic embryos on a semisolid hormone-free nutrient medium. Neither intact zygotic embryos nor hypocotyls ever produced somatic embryos. However, mericarps and broken zygotic embryos were excellent sources for somatic embryo production (response levels as high as 86%). Somatic embryo formation was highest from cotyledons, but was also observed on isolated hypocotyls and root tips of mature zygotic embryos. On media containing unreduced nitrogen, somatic embryo formation led to the generation of vigorous cultures comprised entirely of somatic embryos at various stages of development which in turn proliferated still other somatic embryos. However, a medium was devised which when 1-5 mM NH4+ was the sole nitrogen source, led only to a proliferation of globular proembryos. Sustained subculturing of these proembryos at 2-3 week intervals enabled establishment of highly uniform cultures in which no further development into more mature stages of embryonic development occurred. These have been maintained, without decline, as morphogenetically competent proembryonic globules for over ten months. A basal medium containing from 1-5 mM NH4+ as the sole nitrogen source appears not to be inductive to somatic proembryo formation. Instead, such a medium is best thought of as permissive to the expression of embryogenically determined cells within zygotic embryos. By excising and breaking or wounding zygotic embryos, constituent cells are probably released from positional or chemical restraints and thus are able to express their innate embryogenic potential. Once a proembryonic culture is established, this medium containing 1-5 mM NH4+ as the sole nitrogen source provides a nonpermissive environment to the development and growth of later embryonic stages, but it does allow the continued formation and multiplication of globular somatic proembryos. The sequence of events leading from excised broken zygotic embryos to the formation of somatic embryos and the maintenance of somatic proembryos are demonstrated by scanning electron microscopy and histological preparations. Germination levels from intact zygotic embryos on media with varying levels and ratios of unreduced vs. reduced inorganic nitrogen were determined as well and provided baseline or control data on the type of response obtained from nonwounded material.

Release of somatic embryogenic potential from excised zygotic embryos of carrot and maintenance of proembryonic cultures in hormone-free medium

NASA Technical Reports Server (NTRS)

Smith, D. L.; Krikorian, A. D.

1989-01-01

Excised zygotic embryos, mericarps ("seeds") and hypocotyls of seedlings of cultivated carrot Daucus carota cv. Scarlet Nantes were evaluated for their ability to generate somatic embryos on a semisolid hormone-free nutrient medium. Neither intact zygotic embryos nor hypocotyls ever produced somatic embryos. However, mericarps and broken zygotic embryos were excellent sources for somatic embryo production (response levels as high as 86%). Somatic embryo formation was highest from cotyledons, but was also observed on isolated hypocotyls and root tips of mature zygotic embryos. On media containing unreduced nitrogen, somatic embryo formation led to the generation of vigorous cultures comprised entirely of somatic embryos at various stages of development which in turn proliferated still other somatic embryos. However, a medium was devised which when 1-5 mM NH4+ was the sole nitrogen source, led only to a proliferation of globular proembryos. Sustained subculturing of these proembryos at 2-3 week intervals enabled establishment of highly uniform cultures in which no further development into more mature stages of embryonic development occurred. These have been maintained, without decline, as morphogenetically competent proembryonic globules for over ten months. A basal medium containing from 1-5 mM NH4+ as the sole nitrogen source appears not to be inductive to somatic proembryo formation. Instead, such a medium is best thought of as permissive to the expression of embryogenically determined cells within zygotic embryos. By excising and breaking or wounding zygotic embryos, constituent cells are probably released from positional or chemical restraints and thus are able to express their innate embryogenic potential. Once a proembryonic culture is established, this medium containing 1-5 mM NH4+ as the sole nitrogen source provides a nonpermissive environment to the development and growth of later embryonic stages, but it does allow the continued formation and multiplication of globular somatic proembryos. The sequence of events leading from excised broken zygotic embryos to the formation of somatic embryos and the maintenance of somatic proembryos are demonstrated by scanning electron microscopy and histological preparations. Germination levels from intact zygotic embryos on media with varying levels and ratios of unreduced vs. reduced inorganic nitrogen were determined as well and provided baseline or control data on the type of response obtained from nonwounded material.

Biomarkers for PTSD

DTIC Science & Technology

2010-07-01

connected disability (5). Development of biomarkers of PTSD is critical for DOD and VA as objective indicators of PTSD for use in post -deployment medical...2 C. W. Hoge, A. Terhakopian, C. A. Castro et al., Association of posttraumatic stress disorder with somatic symptoms, health care visits, and...seen at Department of Veterans Affairs facilities. Arch Intern Med 167, 476- 82 (2007). 5 P. B. Watson and B. Daniels, Follow up of post - traumatic

Solving medical mysteries: hidden stresses and unexplained symptoms.

PubMed

Clarke, David D

2016-09-01

Medically unexplained symptoms and chronic functional syndromes are common but few healthcare professionals have had formal training about their connection to psychosocial issues. A systematic approach to diagnosis and treatment based on experience with over 7000 of these patients is described. Outcomes improve with assessment for and treatment of current life stresses, the prolonged impact of adversity in childhood and somatic presentations of depression, post-traumatic stress, and anxiety disorders.

Establishment of a Somatic Cell Bank for Indian Buffalo Breeds and Assessing the Suitability of the Cryopreserved Cells for Somatic Cell Nuclear Transfer.

PubMed

Selokar, Naresh L; Sharma, Papori; Krishna, Ananth; Kumar, Deepak; Kumar, Dharmendra; Saini, Monika; Sharma, Arpna; Vijayalakshmy, Kennady; Yadav, Prem Singh

2018-06-01

Biobanks of cryopreserved gametes and embryos of domestic animals have been utilized to spread desired genotypes and to conserve the animal germplasm of endangered breeds. In principle, somatic cells can be used for the same purposes, and for reviving of animals, the somatic cells must be suitable for animal cloning techniques, such as somatic cell nuclear transfer. In the present study, we derived and cryopreserved somatic cells from three breeds of riverine and swamp-like type buffaloes and established a somatic cell bank. In total, 350 cryovials of 14 different individual animals (25 cryovials per animal) were cryopreserved and informative data such as breed value, origin, and others were documented. Immunostaining of the established cells against vimentin and cytokeratin suggested a commitment to the fibroblast lineage. In addition, microsatellite analysis was performed and documented for unambiguous parentage verification of clones in the future. Subsequently, the cryopreserved cells were tested for their suitability as nuclear donors (n = 7) using handmade cloning, and the reconstructed embryos were cultured in vitro. The cleavage rates (95.99% ± 2.17% vs. 82.18% ± 2.50%) and blastocyst rates (37.73% ± 1.54% vs. 24.31% ± 1.78%) were higher (p < 0.05) for riverine buffalo cells than that of swamp-like buffalo cells, whereas the total cell numbers of blastocysts (258.16 ± 36.25 vs. 198.16 ± 36.25, respectively) were similar. In conclusion, we demonstrated the feasibility of biobanking of buffalo somatic cells, and that the cryopreserved cells can be used to produce cloned embryos. This study encourages the development of somatic cell biobanks of domestic livestock, including endangered breeds of buffalo, to preserve valuable genotypes for future revitalization by animal cloning techniques.

Illness causal beliefs in Turkish immigrants

PubMed Central

Minas, Harry; Klimidis, Steven; Tuncer, Can

2007-01-01

Background People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia. Methods Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbourne. The socio-demographic characteristics of the sample were broadly similar to those of the Melbourne Turkish community. Five issues were examined: the structure of causal beliefs; the relative frequency of natural, supernatural and metaphysical beliefs; ascription of somatic, mental, or both somatic and mental conditions to the various causes; the correlations of belief types with socio-demographic, modernizing and acculturation variables; and the relationship between causal beliefs and current illness. Results Principal components analysis revealed two broad factors, accounting for 58 percent of the variation in scores on illness belief scales, distinctly interpretable as natural and supernatural beliefs. Second, beliefs in natural causes were more frequent than beliefs in supernatural causes. Third, some causal beliefs were commonly linked to both somatic and mental conditions while others were regarded as more specific to either somatic or mental disorders. Last, there was a range of correlations between endorsement of belief types and factors defining heterogeneity within the community, including with demographic factors, indicators of modernizing and acculturative processes, and the current presence of illness. Conclusion Results supported the classification of causal beliefs proposed by Murdock, Wilson & Frederick, with a division into natural and supernatural causes. While belief in natural causes is more common, belief in supernatural causes persists despite modernizing and acculturative influences. Different types of causal beliefs are held in relation to somatic or mental illness, and a variety of apparently logically incompatible beliefs may be concurrently held. Illness causal beliefs are dynamic and are related to demographic, modernizing, and acculturative factors, and to the current presence of illness. Any assumption of uniformity of illness causal beliefs within a community, even one that is relatively culturally homogeneous, is likely to be misleading. A better understanding of the diversity, and determinants, of illness causal beliefs can be of value in improving our understanding of illness experience, the clinical process, and in developing more effective health services and population health strategies. PMID:17645806

Illness causal beliefs in Turkish immigrants.

PubMed

Minas, Harry; Klimidis, Steven; Tuncer, Can

2007-07-24

People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia. Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbourne. The socio-demographic characteristics of the sample were broadly similar to those of the Melbourne Turkish community. Five issues were examined: the structure of causal beliefs; the relative frequency of natural, supernatural and metaphysical beliefs; ascription of somatic, mental, or both somatic and mental conditions to the various causes; the correlations of belief types with socio-demographic, modernizing and acculturation variables; and the relationship between causal beliefs and current illness. Principal components analysis revealed two broad factors, accounting for 58 percent of the variation in scores on illness belief scales, distinctly interpretable as natural and supernatural beliefs. Second, beliefs in natural causes were more frequent than beliefs in supernatural causes. Third, some causal beliefs were commonly linked to both somatic and mental conditions while others were regarded as more specific to either somatic or mental disorders. Last, there was a range of correlations between endorsement of belief types and factors defining heterogeneity within the community, including with demographic factors, indicators of modernizing and acculturative processes, and the current presence of illness. Results supported the classification of causal beliefs proposed by Murdock, Wilson & Frederick, with a division into natural and supernatural causes. While belief in natural causes is more common, belief in supernatural causes persists despite modernizing and acculturative influences. Different types of causal beliefs are held in relation to somatic or mental illness, and a variety of apparently logically incompatible beliefs may be concurrently held. Illness causal beliefs are dynamic and are related to demographic, modernizing, and acculturative factors, and to the current presence of illness. Any assumption of uniformity of illness causal beliefs within a community, even one that is relatively culturally homogeneous, is likely to be misleading. A better understanding of the diversity, and determinants, of illness causal beliefs can be of value in improving our understanding of illness experience, the clinical process, and in developing more effective health services and population health strategies.

Stable transformation via particle bombardment in two different soybean regeneration systems.

PubMed

Sato, S; Newell, C; Kolacz, K; Tredo, L; Finer, J; Hinchee, M

1993-05-01

The Biolistics(®) particle delivery system for the transformation of soybean (Glycine max L. Merr.) was evaluated in two different regeneration systems. The first system was multiple shoot proliferation from shoot tips obtained from immature zygotic embryos of the cultivar Williams 82, and the second was somatic embryogenesis from a long term proliferative suspension culture of the cultivar Fayette. Bombardment of shoot tips with tungsten particles, coated with precipitated DNA containing the gene for β-glucuronidase (GUS), produced GUS-positive sectors in 30% of the regenerated shoots. However, none of the regenerants which developed into plants continued to produce GUS positive tissue. Bombardment of embryogenic suspension cultures produced GUS positive globular somatic embryos which proliferated into GUS positive somatic embryos and plants. An average of 4 independent transgenic lines were generated per bombarded flask of an embryogenic suspension. Particle bombardment delivered particles into the first two cell layers of either shoot tips or somatic embryos. Histological analysis indicated that shoot organogenesis appeared to involve more than the first two superficial cell layers of a shoot tip, while somatic embryo proliferation occurred from the first cell layer of existing somatic embryos. The different transformation results obtained with these two systems appeared to be directly related to differences in the cell types which were responsible for regeneration and their accessibility to particle penetration.

Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers.

PubMed

Wood, Laura D; Calhoun, Eric S; Silliman, Natalie; Ptak, Janine; Szabo, Steve; Powell, Steve M; Riggins, Gregory J; Wang, Tian-Li; Yan, Hai; Gazdar, Adi; Kern, Scott E; Pennacchio, Len; Kinzler, Kenneth W; Vogelstein, Bert; Velculescu, Victor E

2006-10-01

Tyrosine kinases are major regulators of signal transduction cascades involved in cellular proliferation and have important roles in tumorigenesis. We have recently analyzed the tyrosine kinase gene family for alterations in human colorectal cancers and identified somatic mutations in seven members of this gene family. In this study we have used high-throughput sequencing approaches to further evaluate this subset of genes for genetic alterations in other human tumors. We identified somatic mutations in GUCY2F, EPHA3, and NTRK3 in breast, lung, and pancreatic cancers. Our results implicate these tyrosine kinase genes in the pathogenesis of other tumor types and suggest that they may be useful targets for diagnostic and therapeutic intervention in selected patients.

Somatic mosaicism in plants with special reference to somatic crossing over

PubMed Central

Vig, Baldev K.

1978-01-01

Plant systems in use for the detection of environmental mutagens appear capable of detecting all types of genetic effects which can be studied in animals. The study of somatic mosaicism, however, is better developed in plants than in higher animals. A case is presented here which shows the ability of plant systems in analyzing a host of genetic end points, including chromosome aberrations like deletions, somatic crossing over, numerical inequality, gene conversion, paramutations and point mutations. The systems in general use utilize certain varieties of Tradescantia, Glycine max, Nicotiana tabacum, Antirrhinum majus, Petunia hybrida, and Arabidopsis thaliana. Heterozygous plants or their homozygous counterparts with gene markers affecting chlorophyll development or anthocyanin in floral parts are exploited in these studies. Mutagens produce different frequencies of different types of spots typical of the mode of action of the agent. Analysis of these parameters may be used to predict, at least qualitatively, the kind of genetic damage that might be produced in man. Besides, one can test the validity of interpretation by traditional progeny tests of plants raised from tissue culture from sectors as in Nicotiana and/or by precursor analysis as done in Antirrhinum. The study of mosaicism in plants offers quite inexpensive, rapid, and reliable tests of mutagenicity at least as a preliminary eukaryotic test system. ImagesFIGURE 1.FIGURE 1.FIGURE 2.FIGURE 9. PMID:367771

Advances in computational approaches for prioritizing driver mutations and significantly mutated genes in cancer genomes.

PubMed

Cheng, Feixiong; Zhao, Junfei; Zhao, Zhongming

2016-07-01

Cancer is often driven by the accumulation of genetic alterations, including single nucleotide variants, small insertions or deletions, gene fusions, copy-number variations, and large chromosomal rearrangements. Recent advances in next-generation sequencing technologies have helped investigators generate massive amounts of cancer genomic data and catalog somatic mutations in both common and rare cancer types. So far, the somatic mutation landscapes and signatures of >10 major cancer types have been reported; however, pinpointing driver mutations and cancer genes from millions of available cancer somatic mutations remains a monumental challenge. To tackle this important task, many methods and computational tools have been developed during the past several years and, thus, a review of its advances is urgently needed. Here, we first summarize the main features of these methods and tools for whole-exome, whole-genome and whole-transcriptome sequencing data. Then, we discuss major challenges like tumor intra-heterogeneity, tumor sample saturation and functionality of synonymous mutations in cancer, all of which may result in false-positive discoveries. Finally, we highlight new directions in studying regulatory roles of noncoding somatic mutations and quantitatively measuring circulating tumor DNA in cancer. This review may help investigators find an appropriate tool for detecting potential driver or actionable mutations in rapidly emerging precision cancer medicine. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

PubMed

Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

2015-11-25

The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main compartments: dendritic, somatic, and axonal. How the neurons receive information, process it, and pass on new information depends upon how these three compartments operate. While it has long been assumed that axons are simply for conducting information from the cell body to the synapses, here we demonstrate that the axons of different types of interneurons, the inhibitory cells, possess differing electrophysiological properties. This result implies that differing types of interneurons perform different tasks in the cortex, not only through their anatomical connections, but also through how their axons operate. Copyright © 2015 the authors 0270-6474/15/3515555-13$15.00/0.

NetNorM: Capturing cancer-relevant information in somatic exome mutation data with gene networks for cancer stratification and prognosis.

PubMed

Le Morvan, Marine; Zinovyev, Andrei; Vert, Jean-Philippe

2017-06-01

Genome-wide somatic mutation profiles of tumours can now be assessed efficiently and promise to move precision medicine forward. Statistical analysis of mutation profiles is however challenging due to the low frequency of most mutations, the varying mutation rates across tumours, and the presence of a majority of passenger events that hide the contribution of driver events. Here we propose a method, NetNorM, to represent whole-exome somatic mutation data in a form that enhances cancer-relevant information using a gene network as background knowledge. We evaluate its relevance for two tasks: survival prediction and unsupervised patient stratification. Using data from 8 cancer types from The Cancer Genome Atlas (TCGA), we show that it improves over the raw binary mutation data and network diffusion for these two tasks. In doing so, we also provide a thorough assessment of somatic mutations prognostic power which has been overlooked by previous studies because of the sparse and binary nature of mutations.

Maturation of Shark Single-Domain (IgNAR) Antibodies: Evidence for Induced-Fit Binding

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

Stanfield, R.L.; Dooley, H.; Verdino, P.

2007-07-13

Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts withmore » antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.« less

Cloning mice and ES cells by nuclear transfer from somatic stem cells and fully differentiated cells.

PubMed

Wang, Zhongde

2011-01-01

Cloning animals by nuclear transfer (NT) has been successful in several mammalian species. In addition to cloning live animals (reproductive cloning), this technique has also been used in several species to establish cloned embryonic stem (ntES) cell lines from somatic cells. It is the latter application of this technique that has been heralded as being the potential means to produce isogenic embryonic stem cells from patients for cell therapy (therapeutic cloning). These two types of cloning differ only in the steps after cloned embryos are produced: for reproductive cloning the cloned embryos are transferred to surrogate mothers to allow them to develop to full term and for therapeutic cloning the cloned embryos are used to derive ntES cells. In this chapter, a detailed NT protocol in mouse by using somatic stem cells (neuron and skin stem cells) and fully differentiated somatic cells (cumulus cells and fibroblast cells) as nuclear donors is described.

Producing primate embryonic stem cells by somatic cell nuclear transfer.

PubMed

Byrne, J A; Pedersen, D A; Clepper, L L; Nelson, M; Sanger, W G; Gokhale, S; Wolf, D P; Mitalipov, S M

2007-11-22

Derivation of embryonic stem (ES) cells genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing concerns regarding rejection by the host immune system. However, the concept has only been achieved in the mouse, whereas inefficient reprogramming and poor embryonic development characterizes the results obtained in primates. Here, we used a modified SCNT approach to produce rhesus macaque blastocysts from adult skin fibroblasts, and successfully isolated two ES cell lines from these embryos. DNA analysis confirmed that nuclear DNA was identical to donor somatic cells and that mitochondrial DNA originated from oocytes. Both cell lines exhibited normal ES cell morphology, expressed key stem-cell markers, were transcriptionally similar to control ES cells and differentiated into multiple cell types in vitro and in vivo. Our results represent successful nuclear reprogramming of adult somatic cells into pluripotent ES cells and demonstrate proof-of-concept for therapeutic cloning in primates.

NetNorM: Capturing cancer-relevant information in somatic exome mutation data with gene networks for cancer stratification and prognosis

PubMed Central

2017-01-01

Genome-wide somatic mutation profiles of tumours can now be assessed efficiently and promise to move precision medicine forward. Statistical analysis of mutation profiles is however challenging due to the low frequency of most mutations, the varying mutation rates across tumours, and the presence of a majority of passenger events that hide the contribution of driver events. Here we propose a method, NetNorM, to represent whole-exome somatic mutation data in a form that enhances cancer-relevant information using a gene network as background knowledge. We evaluate its relevance for two tasks: survival prediction and unsupervised patient stratification. Using data from 8 cancer types from The Cancer Genome Atlas (TCGA), we show that it improves over the raw binary mutation data and network diffusion for these two tasks. In doing so, we also provide a thorough assessment of somatic mutations prognostic power which has been overlooked by previous studies because of the sparse and binary nature of mutations. PMID:28650955

[A new method for the classification of neonates based on maturity and somatic development].

PubMed

Berkö, P

1992-03-01

The author points out the sad fact that the methods of estimating classifying, comparative examining of the maturity, somatic development of newborns and the methods of marking off the retarded newborns used up to now are essentially centering round the birth-weight. He exposes the errors, deficiencies of these methods and confronts them with the possibilities of the NDN-system (newborn's somatic development and nutritional state) worked out earlier by him. He thinks the NDF-system to be able to express simultaneously and exactly the gestational age, weight- and length-development, state of being fed of the newborns and the relation to the populational average, the fact and type of retardation, as well. The informational means of NDF-system in NDF-index. The NDF-system makes it possible to break down the birth-weight centric view as it offers a more suitable and qualified method than used before to describe the maturity and somatic development and the classifying of the newborns on the basis of these.

Mated Progeny Production Is a Biomarker of Aging in Caenorhabditis elegans

PubMed Central

Pickett, Christopher L.; Dietrich, Nicholas; Chen, Junfang; Xiong, Chengjie; Kornfeld, Kerry

2013-01-01

The relationships between reproduction and aging are important for understanding the mechanisms of aging and evaluating evolutionary theories of aging. To investigate the effects of progeny production on reproductive and somatic aging, we conducted longitudinal studies of Caenorhabditis elegans hermaphrodites. For mated wild-type animals that were not sperm limited and survived past the end of the reproductive period, high levels of cross-progeny production were positively correlated with delayed reproductive and somatic aging. In this group of animals, individuals that generated more cross progeny also reproduced and lived longer than individuals that generated fewer cross progeny. These results indicate that progeny production does not accelerate reproductive or somatic aging. This longitudinal study demonstrated that cumulative cross progeny production through day four is an early-stage biomarker that is a positive predictor of longevity. Furthermore, in mated animals, high levels of early cross progeny production were positively correlated with high levels of late cross progeny production, indicating that early progeny production does not accelerate reproductive aging. The relationships between progeny production and aging were further evaluated by comparing self-fertile hermaphrodites that generated relatively few self progeny with mated hermaphrodites that generated many cross progeny. The timing of age-related somatic degeneration was similar in these groups, suggesting progeny production does not accelerate somatic aging. These studies rigorously define relationships between progeny production, reproductive aging, and somatic aging and identify new biomarkers of C. elegans aging. These results indicate that some mechanisms or pathways control age-related degeneration of both reproductive and somatic tissues in C. elegans. PMID:24142929

[Personality and somatic disorders].

PubMed

Darves-Bornoz, J-M

2018-06-08

In the title of this text, by somatic disorders we mean those physical illnesses clearly related to a non-psychiatric medical field, frequently termed psychosomatic illnesses and somatoform disorders. For forty years, a trend of thought has focused with pertinence on the psychological peculiarities in patients with severe somatic diseases. Moreover, causality was often supposed in the regularly mentioned association between personality features and somatoform disorders. However, the revival of the study of the earlier field of relationships between mind and body by Briquet, Charcot, Janet and Freud in his first period has led to the reassessment of the meaning of these observations. This reexamination is marked out by several assertions. Two of them work as preliminaries to argumentation: 1. existential wounds may produce long-lasting personality alterations; 2. existential wounds may produce somatoform disorders. These phenomena have been rediscovered over the last few years among assaulted subjects as well as war veterans in whom a frequent occurrence of somatizations has been, in addition, closely linked to the incidence of behavior or personality disorders. Two theses then emerge: 1. somatic diseases may produce long-lasting personality alterations; 2. until now no premorbid personality univocally predisposing to somatic diseases could be found. Indeed, during the 1980s a growing body of negative results coming from retrospective and prospective studies as well as anatomical comparisons have accumulated upon the potential role of certain personality factors in the incidence of somatic illnesses. This dialectic leads to the connection of two corollary assertions: 1. "pensée opératoire" and "alexithymia" in patients with somatic diseases may represent only an effect of the announcement or chronicity of the organic disease; 2. the old "dissociative hysteria" with somatic manifestations finds its substratum in existential wounds and not in pre-trauma personality. Indeed, on the one hand, recent publications do not allow the assertion to be confirmed that alexithymia and "pensée opératoire" predispose to somatizations. On the other hand, personality disorders in subjects with "dissociative hysteria" as well as their somatoform symptoms appear mainly as an effect of an existential wound and express in fact the Janetian concept of "a drop in Psychological Tension". Then, in spite of their differences, conversion and psychosomatic symptoms share the property of being a primitive response to existential wounds in which the subject cannot produce any appropriate psychic or behavioral response to his distress. Light is shed on these phenomena when put alongside the field of "fixed ideas" thought of by Pierre Janet as the recourse to archaic automatisms. Indeed, the experience which contradicts the vision of existence provokes an "unspeakable terror". It is mentally unrepresented or represented in too slight a way. In such cases, no previous personality prevails, but the resulting personality often appears modified, including when the breakdown of vision of the existence results from the diagnosis of an illness or its protracted course. Copyright © 2018 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Mosaic generalized neurofibromatosis 1: report of two cases.

PubMed

Hardin, Jori; Behm, Allan; Haber, Richard M

2014-01-01

We report two cases of mosaic generalized neurofibromatosis 1 (NF1) and review the history of the classification of segmental neurofibromatosis (SNF; Ricardi type NF-V). Somatic mutations giving rise to limited disease, such as segmental neurofibromatosis are manifestations of mosaicism. If the mutation occurs before tissue differentiation, the clinical phenotype will be generalized disease. Mutations that occur later in development give rise to disease that is confined to a single region. Segmental neurofibromatosis is caused by a somatic mutation of neurofibromatosis type 1, and should not be regarded as a distinct entity from neurofibromatosis 1. Cases previously referred to as unilateral or bilateral segmental neurofibromatosis are now best referred to as mosaic generalized or mosaic localized neurofibromatosis 1.

Actual neurosis as the underlying psychic structure of panic disorder, somatization, and somatoform disorder: an integration of Freudian and attachment perspectives.

PubMed

Verhaeghe, Paul; Vanheule, Stijn; De Rick, Ann

2007-10-01

Starting from a contemporary critique of the DSM-IV, this paper argues that the diagnostic categories of panic disorder somatization, and undifferentiated somatoform disorders can be understood as belonging to a common type of psychopathology--i.e., the Freudian actual neuroses. In addition to their strong clinical similarity, these disorders share an etiological similarity; and the authors propose a combination of Freud's focus on this type of patient's inability to represent an endogenous drive arousal with the post-Freudian focus on separation anxiety. An etiological hypothesis is put forward based on contemporary psychoanalytic attachment theory, highlighting mentalization. Concrete implications for a psychoanalytically based treatment are proposed.

Mice deficient in carbonic anhydrase type 8 exhibit motor dysfunctions and abnormal calcium dynamics in the somatic region of cerebellar granule cells.

PubMed

Lamont, Matthew G; Weber, John T

2015-06-01

The waddles (wdl) mouse is characterized by a namesake "side-to-side" waddling gait due to a homozygous mutation of the Car8 gene. This mutation results in non-functional copies of the protein carbonic anhydrase type 8. Rota-rod testing was conducted to characterize the wdl mutations' effect on motor output. Results indicated that younger homozygotes outperformed their older cohorts, an effect not seen in previous studies. Heterozygotes, which were thought to be free of motor impairment, displayed motor learning deficiencies when compared with wild type performance. Acute cerebellar slices were then utilized for fluorescent calcium imaging experiments, which revealed significant alterations in cerebellar granule cell somatic calcium signaling when exposed to glutamate. The contribution of GABAergic signaling to these alterations was also verified using bath application of bicuculline. Changes in somatic calcium signals were found to be applicable to an in vivo scenario by comparing group responses to electrical stimulation of afferent mossy fiber projections. Finally, intracellular calcium store function was also found to be altered by the wdl mutation when slices were treated with thapsigargin. These findings, taken together with previous work on the wdl mouse, indicate a widespread disruption in cerebellar circuitry hampering proper neuronal communication. Copyright © 2015 Elsevier B.V. All rights reserved.

Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci

PubMed Central

Philippe, Claude; Vargas-Landin, Dulce B; Doucet, Aurélien J; van Essen, Dominic; Vera-Otarola, Jorge; Kuciak, Monika; Corbin, Antoine; Nigumann, Pilvi; Cristofari, Gaël

2016-01-01

LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants. DOI: http://dx.doi.org/10.7554/eLife.13926.001 PMID:27016617

Disruption of the CRF(2) receptor pathway decreases the somatic expression of opiate withdrawal.

PubMed

Papaleo, Francesco; Ghozland, Sandy; Ingallinesi, Manuela; Roberts, Amanda J; Koob, George F; Contarino, Angelo

2008-11-01

Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF(1) and CRF(2). To investigate the role for the CRF(2) receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF(2) receptor (CRF(2)-/-). We employed a novel, clinically relevant mouse model of 'spontaneous' opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20-100 mg/kg, i.p.). We found that 8-128 h after the last opiate injection, CRF(2)-/- mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF(2)-/- mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF(2)-/- mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus-pituitary-adrenal axis in the CRF(2) receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF(2) receptor pathway in opiate withdrawal. The CRF(2) receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake.

Disruption of the CRF2 Receptor Pathway Decreases the Somatic Expression of Opiate Withdrawal

PubMed Central

Papaleo, Francesco; Ghozland, Sandy; Ingallinesi, Manuela; Roberts, Amanda J; Koob, George F; Contarino, Angelo

2009-01-01

Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF1 and CRF2. To investigate the role for the CRF2 receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF2 receptor (CRF2−/−). We employed a novel, clinically relevant mouse model of ‘spontaneous’ opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20–100 mg/kg, i.p.). We found that 8–128 h after the last opiate injection, CRF2−/− mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF2−/− mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF2−/− mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus–pituitary–adrenal axis in the CRF2 receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF2 receptor pathway in opiate withdrawal. The CRF2 receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake. PMID:18288089

Computational approaches to identify functional genetic variants in cancer genomes

PubMed Central

Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris; Ritchie, Graham R.S.; Creixell, Pau; Karchin, Rachel; Vazquez, Miguel; Fink, J. Lynn; Kassahn, Karin S.; Pearson, John V.; Bader, Gary; Boutros, Paul C.; Muthuswamy, Lakshmi; Ouellette, B.F. Francis; Reimand, Jüri; Linding, Rune; Shibata, Tatsuhiro; Valencia, Alfonso; Butler, Adam; Dronov, Serge; Flicek, Paul; Shannon, Nick B.; Carter, Hannah; Ding, Li; Sander, Chris; Stuart, Josh M.; Stein, Lincoln D.; Lopez-Bigas, Nuria

2014-01-01

The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor, but only a minority drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype. PMID:23900255

Somatic symptoms among US adolescent females: associations with sexual and physical violence exposure.

PubMed

Halpern, Carolyn Tucker; Tucker, Christine M; Bengtson, Angela; Kupper, Lawrence L; McLean, Samuel A; Martin, Sandra L

2013-12-01

The objective of this study is to examine the association between physical and sexual violence exposure and somatic symptoms among female adolescents. We studied a nationally representative sample of 8,531 females, aged 11-21 years, who participated in the 1994-1995 Wave I of the National Longitudinal Study of Adolescent Health (Add Health). Female adolescents were asked how often they had experienced 16 specific somatic symptoms during the past 12 months. Two summary categorical measures were constructed based on tertiles of the distributions for the entire female sample: (a) total number of different types of symptoms experienced, and (b) number of frequent (once a week or more often) different symptoms experienced. Groups were mutually exclusive. We examined associations between adolescents' violence exposure and somatic symptoms using multinomial logistic regression analyses. About 5 % of adolescent females reported both sexual and non-sexual violence, 3 % reported sexual violence only, 36 % reported non-sexual violence only, and 57 % reported no violence. Adolescents who experienced both sexual and non-sexual violence were the most likely to report many different symptoms and to experience very frequent or chronic symptoms. Likelihood of high symptomatology was next highest among adolescents who experienced sexual violence only, followed by females who experienced non-sexual violence only. Findings support an exposure-response association between violence exposure and somatic symptoms, suggesting that symptoms can be markers of victimization. Treating symptoms alone, without addressing the potential violence experienced, may not adequately improve adolescents' somatic complaints and well-being.

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

PubMed Central

Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

2014-01-01

Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

Truncation of LEAFY COTYLEDON1 Protein Is Required for Asexual Reproduction in Kalanchoë daigremontiana1[OPEN

PubMed Central

Garcês, Helena M.P.; Koenig, Daniel; Townsley, Brad T.; Kim, Minsung; Sinha, Neelima R.

2014-01-01

Kalanchoë daigremontiana reproduces asexually by generating numerous plantlets on its leaf margins. The formation of plantlets requires the somatic initiation of organogenic and embryogenic developmental programs in the leaves. However, unlike normal embryogenesis in seeds, leaf somatic embryogenesis bypasses seed dormancy to form viable plantlets. In Arabidopsis (Arabidopsis thaliana), seed dormancy and embryogenesis are initiated by the transcription factor LEAFY COTYLEDON1 (LEC1). The K. daigremontiana ortholog of LEC1 is expressed during leaf somatic embryo development. However, KdLEC1 encodes for a LEC1-type protein that has a unique B domain, with 11 unique amino acids and a premature stop codon. Moreover, the truncated KdLEC1 protein is not functional in Arabidopsis. Here, we show that K. daigremontiana transgenic plants expressing a functional, chimeric KdLEC1 gene under the control of Arabidopsis LEC1 promoter caused several developmental defects to leaf somatic embryos, including seed dormancy characteristics. The dormant plantlets also behaved as typical dormant seeds. Transgenic plantlets accumulated oil bodies and responded to the abscisic acid biosynthesis inhibitor fluridone, which broke somatic-embryo dormancy and promoted their normal development. Our results indicate that having a mutated form of LEC1 gene in K. daigremontiana is essential to bypass dormancy in the leaf embryos and generate viable plantlets, suggesting that the loss of a functional LEC1 promotes viviparous leaf somatic embryos and thus enhances vegetative propagation in K. daigremontiana. Mutations resulting in truncated LEC1 proteins may have been of a selective advantage in creating somatic propagules, because such mutations occurred independently in several Kalanchoë species, which form plantlets constitutively. PMID:24664206

Truncation of LEAFY COTYLEDON1 protein is required for asexual reproduction in Kalanchoë daigremontiana.

PubMed

Garcês, Helena M P; Koenig, Daniel; Townsley, Brad T; Kim, Minsung; Sinha, Neelima R

2014-05-01

Kalanchoë daigremontiana reproduces asexually by generating numerous plantlets on its leaf margins. The formation of plantlets requires the somatic initiation of organogenic and embryogenic developmental programs in the leaves. However, unlike normal embryogenesis in seeds, leaf somatic embryogenesis bypasses seed dormancy to form viable plantlets. In Arabidopsis (Arabidopsis thaliana), seed dormancy and embryogenesis are initiated by the transcription factor LEAFY COTYLEDON1 (LEC1). The K. daigremontiana ortholog of LEC1 is expressed during leaf somatic embryo development. However, KdLEC1 encodes for a LEC1-type protein that has a unique B domain, with 11 unique amino acids and a premature stop codon. Moreover, the truncated KdLEC1 protein is not functional in Arabidopsis. Here, we show that K. daigremontiana transgenic plants expressing a functional, chimeric KdLEC1 gene under the control of Arabidopsis LEC1 promoter caused several developmental defects to leaf somatic embryos, including seed dormancy characteristics. The dormant plantlets also behaved as typical dormant seeds. Transgenic plantlets accumulated oil bodies and responded to the abscisic acid biosynthesis inhibitor fluridone, which broke somatic-embryo dormancy and promoted their normal development. Our results indicate that having a mutated form of LEC1 gene in K. daigremontiana is essential to bypass dormancy in the leaf embryos and generate viable plantlets, suggesting that the loss of a functional LEC1 promotes viviparous leaf somatic embryos and thus enhances vegetative propagation in K. daigremontiana. Mutations resulting in truncated LEC1 proteins may have been of a selective advantage in creating somatic propagules, because such mutations occurred independently in several Kalanchoë species, which form plantlets constitutively.

High somatic distress with high long-term stability in selected patients with chronic depression: a 3-year follow-up of ratings with Karolinska Scales of Personality (KSP).

PubMed

Gardner, Ann; Hällström, Tore

2004-01-01

The main aim of the present study was to investigate mean levels and long-term stability of three scales from the Karolinska Scales of Personality (KSP), assessing somatic components of anxiety proneness in selected patients with chronic depressive symptoms. The KSP was filled in by 84 patients (26 men and 58 women) with a history of or ongoing major depression and audiological, or other comorbid somatic, symptoms. Mean scores for the Somatic Anxiety, Muscular Tension and Psychasthenia scales were above two standard deviations compared to a normative group sampled from the population. The KSP was filled in at follow-up by 65 patients. The mean interval between the ratings was 3.5 years. Comparisons between the ratings of the three scales revealed no significant mean score differences, and quite high individual stability. The mean scores were significantly increased in comparisons with depressed patients in primary care suggesting that these patients with chronic depression may comprise a depressive sub-type characterized by high "somatic distress". A putative origin for the high and stable scores in the presented sub-group of depressed patients, and the concept of "personality trait" in use even for pronounced symptoms, are discussed.

Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

PubMed Central

Vivekananda, Umesh; Novak, Pavel; Bello, Oscar D.; Korchev, Yuri E.; Krishnakumar, Shyam S.; Volynski, Kirill E.; Kullmann, Dimitri M.

2017-01-01

Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog–digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels. PMID:28193892

Induction of somatic embryogenesis in explants of shoot cultures established from adult Eucalyptus globulus and E. saligna × E. maidenii trees.

PubMed

Corredoira, E; Ballester, A; Ibarra, M; Vieitez, A M

2015-06-01

A reproducible procedure for induction of somatic embryogenesis (SE) from adult trees of Eucalyptus globulus Labill. and the hybrid E. saligna Smith × E. maidenii has been developed for the first time. Somatic embryos were obtained from both shoot apex and leaf explants of all three genotypes evaluated, although embryogenic frequencies were significantly influenced by the species/genotype, auxin and explant type. Picloram was more efficient for somatic embryo induction than naphthaleneacetic acid (NAA), with the highest frequency of induction being obtained in Murashige and Skoog medium containing 40 µM picloram and 40 mg l(-1) gum Arabic, in which 64% of the shoot apex explants and 68.8% of the leaf explants yielded somatic embryos. The embryogenic response of the hybrid was higher than that of the E. globulus, especially when NAA was used. The cultures initiated on picloram-containing medium consisted of nodular embryogenic structures surrounded by a mucilaginous coating layer that emerged from a watery callus developed from the initial explants. Cotyledonary somatic embryos were differentiated after subculture of these nodular embryogenic structures on a medium lacking plant growth regulators. Histological analysis confirmed the bipolar organization of the somatic embryos, with shoot and root meristems and closed procambial tissue that bifurcated into small cotyledons. The root pole was more differentiated than the shoot pole, which appeared to be formed by a few meristematic layers. Maintenance of the embryogenic lines by secondary SE was attained by subculturing individual cotyledonary embryos or small clusters of globular and torpedo embryos on medium with 16.11 µM NAA at 4- to 5-week intervals. Somatic embryos converted into plantlets after being transferred to liquid germination medium although plant regeneration remained poor. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Specific Phobia in Youth: Phenomenology and Psychological Characteristics

PubMed Central

Ollendick, Thomas H.; Raishevich, Natoshia; Davis, Thompson E.; Sirbu, Cristian; Öst, Lars-Göran

2012-01-01

Sociodemographic and psychological characteristics of 62 youth with animal and natural environment types of specific phobia were examined in a treatment-seeking sample. Differences due to age, sex, ethnicity, family structure, and family socioeconomic status were not found between youth with the two types of specific phobia. Moreover, differences were not obtained between the two groups in the clinical severity of their phobias, the perceived dangerousness of the feared outcomes associated with their phobias, the perceived levels of coping with their phobias, or overall fearfulness. However, differences between youth with the two types of specific phobias were found on somatic/anxious symptoms, depressive symptoms, and life satisfaction. In addition, differences were noted on withdrawn, somatic complaints, anxious/depressed symptoms, and social problems as reported by the mothers of these youngsters. Finally, differences in the percent of co-occurring anxiety disorders between youth with the two types of specific phobia were found. On all of the domains in which differences were found, youth with the natural environment type fared more poorly than those with the animal type. These findings converge with those obtained in treatment studies which indicate that youth with the natural environment type are more difficult to treat than youth with the animal type. PMID:20171334

Culture of East Indian sandalwood tree somatic embryos in air-lift bioreactors for production of santalols, phenolics and arabinogalactan proteins

PubMed Central

Misra, Biswapriya B.; Dey, Satyahari

2013-01-01

The East Indian sandalwood tree, Santalum album, yields one of the costliest heartwoods and precious essential oil. Unsurprisingly, this endangered forest species is severely affected due to unmet global demands, illegal trade and harvesting, overharvesting and an epidemic mycoplasmal spike disease. In vitro micropropagation endeavours have resulted in defined in vitro stages such as somatic embryos that are amenable to mass production in bioreactors. We report on somatic embryo production in a 10-L air-lift-type bioreactor, and compare the growth and biochemical parameters with those of a 2-L air-lift-type bioreactor. For the 10-L bioreactor with biomass (475.7 ± 18 g fresh weight; P < 0.01), concomitantly santalols (5.2 ± 0.15 mg L−1; P < 0.05), phenolics (31 ± 1.6 mg L−1) and arabinogalactan proteins (AGPs) (39 ± 3.1 mg L−1; P < 0.05) are produced in 28 days. In addition, we identified and quantified several santalols and phenolics by means of high-performance thin-layer chromatography and reverse-phase high-pressure liquid chromatography analyses, respectively. Results indicate that 10-L-capacity air-lift bioreactors are capable of supporting somatic embryo cultures, while the extracellular medium provides opportunities for production of industrial raw materials such as santalols, phenolics and AGPs. This will prove useful for further optimization and scale-up studies of plant-produced metabolites.

Somatic maturation and the relationship between bone mineral variables and types of sports among adolescents: cross-sectional study.

PubMed

Agostinete, Ricardo Ribeiro; Ito, Igor Hideki; Kemper, Han; Pastre, Carlos Marcelo; Rodrigues-Júnior, Mário Antônio; Luiz-de-Marco, Rafael; Fernandes, Rômulo Araújo

2017-01-01

Peak height velocity (PHV) is an important maturational event during adolescence that affects skeleton size. The objective here was to compare bone variables in adolescents who practiced different types of sports, and to identify whether differences in bone variables attributed to sports practice were dependent on somatic maturation status. Cross-sectional study, São Paulo State University (UNESP). The study was composed of 93 adolescents (12 to 16.5 years old), divided into three groups: no-sport group (n = 42), soccer/basketball group (n = 26) and swimming group (n = 25). Bone mineral density and content were measured using dual-energy x-ray absorptiometry and somatic maturation was estimated through using peak height velocity. Data on training load were provided by the coaches. Adolescents whose PHV occurred at an older age presented higher bone mineral density in their upper limbs (P = 0.018). After adjustments for confounders, such as somatic maturation, the swimmers presented lower values for bone mineral density in their lower limbs, spine and whole body. Only the bone mineral density in the upper limbs was similar between the groups. There was a negative relationship between whole-body bone mineral content and the weekly training hours (β: -1563.967; 95% confidence interval, CI: -2916.484 to -211.450). The differences in bone variables attributed to sport practice occurred independently of maturation, while high training load in situations of hypogravity seemed to be related to lower bone mass in swimmers.

Assessing the clinical utility of cancer genomic and proteomic data across tumor types.

PubMed

Yuan, Yuan; Van Allen, Eliezer M; Omberg, Larsson; Wagle, Nikhil; Amin-Mansour, Ali; Sokolov, Artem; Byers, Lauren A; Xu, Yanxun; Hess, Kenneth R; Diao, Lixia; Han, Leng; Huang, Xuelin; Lawrence, Michael S; Weinstein, John N; Stuart, Josh M; Mills, Gordon B; Garraway, Levi A; Margolin, Adam A; Getz, Gad; Liang, Han

2014-07-01

Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, microRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We find that incorporating molecular data with clinical variables yields statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2-23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data.

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome.

PubMed

Swanson, Larry W; Sporns, Olaf; Hahn, Joel D

2016-10-04

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure-function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network's modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system.

Reduction of bacteria and somatic coliphages in constructed wetlands for the treatment of combined sewer overflow (retention soil filters).

PubMed

Ruppelt, Jan P; Tondera, Katharina; Schreiber, Christiane; Kistemann, Thomas; Pinnekamp, Johannes

2018-05-01

Combined sewer overflows (CSOs) introduce numerous pathogens from fecal contamination, such as bacteria and viruses, into surface waters, thus endangering human health. In Germany, retention soil filters (RSFs) treat CSOs at sensitive discharge points and can contribute to reducing these hygienically relevant microorganisms. In this study, we evaluated the extent of how dry period, series connection and filter layer thickness influence the reduction efficiency of RSFs for Escherichia coli (E. coli), intestinal enterococci (I. E.) and somatic coliphages. To accomplish this, we had four pilot scale RSFs built on a test field at the wastewater treatment plant Aachen-Soers. While two filters were replicates, the other two filters were installed in a series connection. Moreover, one filter had a thinner filtration layer than the other three. Between April 2015 and December 2016, the RSFs were loaded in 37 trials with pre-conditioned CSO after dry periods ranging from 4 to 40 days. During 17 trials, samples for microbial analysis were taken and analyzed. The series connection of two filters showed that the removal increases when two systems with a filter layer of the same height are operated in series. Since the microorganisms are exposed twice to the environmental conditions on the filter surface and in the upper filter layers, there is a greater chance for abiotic adsorption increase. The same effect could be shown when filters with different depths were compared: the removal efficiency increases as filter thickness increases. This study provides new evidence that regardless of seasonal effects and dry period, RSFs can improve hygienic situation significantly. Copyright © 2018 Elsevier GmbH. All rights reserved.

Somatic Cell Nuclear Transfer in the Mouse

NASA Astrophysics Data System (ADS)

Kishigami, Satoshi; Wakayama, Teruhiko

Somatic cell nuclear transfer (SCNT) has become a unique and powerful tool for epigenetic reprogramming research and gene manipulation in animals since “Dolly,” the first animal cloned from an adult cell was reported in 1997. Although the success rates of somatic cloning have been inefficient and the mechanism of reprogramming is still largely unknown, this technique has been proven to work in more than 10 mammalian species. Among them, the mouse provides the best model for both basic and applied research of somatic cloning because of its abounding genetic resources, rapid sexual maturity and propagation, minimal requirements for housing, etc. This chapter describes a basic protocol for mouse cloning using cumulus cells, the most popular cell type for NT, in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. In particular, we focus on a new, more efficient mouse cloning protocol using trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which increases both in vitro and in vivo developmental rates from twofold to fivefold. This new method including TSA will be helpful to establish mouse cloning in many laboratories.

Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

PubMed

Werner, Benjamin; Sottoriva, Andrea

2018-06-01

The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.

Novel Somatic Mutation in LEMD3 Splice Site Results in Buschke-Ollendorff Syndrome with Polyostotic Melorheostosis and Osteopoikilosis.

PubMed

Gutierrez, Daniel; Cooper, Kevin D; Mitchell, Anna L; Cohn, Heather I

2015-01-01

Buschke-Ollendorff syndrome is a rare autosomal dominant disorder caused by loss of function in LEMD3, resulting in connective tissue nevi and varying bone dysplasia. Although typically benign, we describe a novel LEMD3 splice site mutation (IVS12 + 1delG) in a 13-year-old boy with Buschke-Ollendorff syndrome presenting with severe skeletal deformities, polyostotic melorheostosis, and osteopoikilosis. © 2015 Wiley Periodicals, Inc.

Efficient modification of the myostatin gene in porcine somatic cells and generation of knockout piglets.

PubMed

Rao, Shengbin; Fujimura, Tatsuya; Matsunari, Hitomi; Sakuma, Tetsushi; Nakano, Kazuaki; Watanabe, Masahito; Asano, Yoshinori; Kitagawa, Eri; Yamamoto, Takashi; Nagashima, Hiroshi

2016-01-01

Myostatin (MSTN) is a negative regulator of myogenesis, and disruption of its function causes increased muscle mass in various species. Here, we report the generation of MSTN-knockout (KO) pigs using genome editing technology combined with somatic-cell nuclear transfer (SCNT). Transcription activator-like effector nuclease (TALEN) with non-repeat-variable di-residue variations, called Platinum TALEN, was highly efficient in modifying genes in porcine somatic cells, which were then used for SCNT to create MSTN KO piglets. These piglets exhibited a double-muscled phenotype, possessing a higher body weight and longissimus muscle mass measuring 170% that of wild-type piglets, with double the number of muscle fibers. These results demonstrate that loss of MSTN increases muscle mass in pigs, which may help increase pork production for consumption in the future. © 2015 Wiley Periodicals, Inc.

Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer.

PubMed

Inoue, Kimiko; Kohda, Takashi; Sugimoto, Michihiko; Sado, Takashi; Ogonuki, Narumi; Matoba, Shogo; Shiura, Hirosuke; Ikeda, Rieko; Mochida, Keiji; Fujii, Takashi; Sawai, Ken; Otte, Arie P; Tian, X Cindy; Yang, Xiangzhong; Ishino, Fumitoshi; Abe, Kuniya; Ogura, Atsuo

2010-10-22

Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed normal global gene expression and resulted in about an eight- to ninefold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically down-regulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.

Parent-child Communication-centered Rehabilitative Approach for Pediatric Functional Somatic Symptoms.

PubMed

Gerner, Maya; Barak, Sharon; Landa, Jana; Eisenstein, Etzyona

2016-01-01

Functional somatic symptoms (FSS) are a type of somatization phenomenon. Integrative rehabilitation approaches are the preferred treatment for pediatric FSS. Parental roles in the treatment process have not been established. to present 1) a parent-focused treatment (PFT) for pediatric FSS and 2) the approach's preliminary results. The sample included 50 children with physical disabilities due to FSS. All children received PFT including physical and psychological therapy. A detailed description of the program's course and guiding principles is provided. FSS extinction and age-appropriate functioning. Post-program, 84% of participants did not exhibit FSS and 94% returned to age-appropriate functioning. At one-year follow-up, only 5% of participants experienced symptom recurrence. No associations were found between pre-admission symptoms and intervention duration. PFT is beneficial in treating pediatric FSS. Therefore, intensive parental involvement in rehabilitation may be cardinal.

Mammalian nuclear transplantation to Germinal Vesicle stage Xenopus oocytes – A method for quantitative transcriptional reprogramming

PubMed Central

Halley-Stott, R.P.; Pasque, V.; Astrand, C.; Miyamoto, K.; Simeoni, I.; Jullien, J.; Gurdon, J.B.

2010-01-01

Full-grown Xenopus oocytes in first meiotic prophase contain an immensely enlarged nucleus, the Germinal Vesicle (GV), that can be injected with several hundred somatic cell nuclei. When the nuclei of mammalian somatic cells or cultured cell lines are injected into a GV, a wide range of genes that are not transcribed in the donor cells, including pluripotency genes, start to be transcriptionally activated, and synthesize primary transcripts continuously for several days. Because of the large size and abundance of Xenopus laevis oocytes, this experimental system offers an opportunity to understand the mechanisms by which somatic cell nuclei can be reprogrammed to transcribe genes characteristic of oocytes and early embryos. The use of mammalian nuclei ensures that there is no background of endogenous maternal transcripts of the kind that are induced. The induced gene transcription takes place in the absence of cell division or DNA synthesis and does not require protein synthesis. Here we summarize new as well as established results that characterize this experimental system. In particular, we describe optimal conditions for transplanting somatic nuclei to oocytes and for the efficient activation of transcription by transplanted nuclei. We make a quantitative determination of transcript numbers for pluripotency and housekeeping genes, comparing cultured somatic cell nuclei with those of embryonic stem cells. Surprisingly we find that the transcriptional activation of somatic nuclei differs substantially from one donor cell-type to another and in respect of different pluripotency genes. We also determine the efficiency of an injected mRNA translation into protein. PMID:20123126

Innexin2 gap junctions in somatic support cells are required for cyst formation and for egg chamber formation in Drosophila.

PubMed

Mukai, Masanori; Kato, Hirotaka; Hira, Seiji; Nakamura, Katsuhiro; Kita, Hiroaki; Kobayashi, Satoru

2011-01-01

Germ cells require intimate associations with surrounding somatic cells during gametogenesis. During oogenesis, gap junctions mediate communication between germ cells and somatic support cells. However, the molecular mechanisms by which gap junctions regulate the developmental processes during oogenesis are poorly understood. We have identified a female sterile allele of innexin2 (inx2), which encodes a gap junction protein in Drosophila. In females bearing this inx2 allele, cyst formation and egg chamber formation are impaired. In wild-type germaria, Inx2 is strongly expressed in escort cells and follicle cells, both of which make close contact with germline cells. We show that inx2 function in germarial somatic cells is required for the survival of early germ cells and promotes cyst formation, probably downstream of EGFR pathway, and that inx2 function in follicle cells promotes egg chamber formation through the regulation of DE-cadherin and Bazooka (Baz) at the boundary between germ cells and follicle cells. Furthermore, genetic experiments demonstrate that inx2 interacts with the zero population growth (zpg) gene, which encodes a germline-specific gap junction protein. These results indicate a multifunctional role for Inx2 gap junctions in somatic support cells in the regulation of early germ cell survival, cyst formation and egg chamber formation. Inx2 gap junctions may mediate the transfer of nutrients and signal molecules between germ cells and somatic support cells, as well as play a role in the regulation of cell adhesion. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Widespread hyperalgesia in irritable bowel syndrome is dynamically maintained by tonic visceral impulse input and placebo/nocebo factors: Evidence from human psychophysics, animal models, and neuroimaging

PubMed Central

Price, Donald D.; Craggs, Jason G.; Zhou, QiQi; Verne, G. Nicholas; Perlstein, William M.; Robinson, Michael E.

2010-01-01

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that is often accompanied by both visceral and somatic hyperalgesia (enhanced pain from colorectal and somatic stimuli). Neural mechanisms of both types of hyperalgesia have been analyzed by neuroimaging studies of IBS patients and animal analog studies of “IBS-like” rats with delayed rectal and somatic hypersensitivity. Results from these studies suggest that pains associated with both visceral and widespread secondary cutaneous hyperalgesia are dynamically maintained by tonic impulse input from the non-inflamed colon and/or rectum and by brain-to-spinal cord facilitation. Enhanced visceral and somatic pains are accompanied by enhanced pain-related brain activity in IBS patients as compared to normal control subjects; placebos can normalize both their hyperalgesia and enhanced brain activity. That pain in IBS which is likely to be at least partly maintained by peripheral impulse input from the colon/rectum is supported by results showing that local rectal–colonic anesthesia normalizes visceral and somatic hyperalgesia in IBS patients and visceral and somatic hypersensitivity in “IBS-like” rats. Yet these forms of hyperalgesia are also highly modifiable by placebo and nocebo factors (e.g., expectations of relief or distress, respectively). Our working hypothesis is that synergistic interactions occur between placebo/nocebo factors and enhanced afferent processing so as to enhance, maintain, or reduce hyperalgesia in IBS. This explanatory model may be relevant to other persistent pain conditions. PMID:19375508

The path forward: 2015 International Children's Tumor Foundation conference on neurofibromatosis type 1, type 2, and schwannomatosis.

PubMed

Blakeley, Jaishri O; Bakker, Annette; Barker, Anne; Clapp, Wade; Ferner, Rosalie; Fisher, Michael J; Giovannini, Marco; Gutmann, David H; Karajannis, Matthias A; Kissil, Joseph L; Legius, Eric; Lloyd, Alison C; Packer, Roger J; Ramesh, Vijaya; Riccardi, Vincent M; Stevenson, David A; Ullrich, Nicole J; Upadhyaya, Meena; Stemmer-Rachamimov, Anat

2017-06-01

The Annual Children's Tumor Foundation International Neurofibromatosis Meeting is the premier venue for connecting discovery, translational and clinical scientists who are focused on neurofibromatosis types 1 and 2 (NF1 and NF2) and schwannomatosis (SWN). The meeting also features rare tumors such as glioma, meningioma, sarcoma, and neuroblastoma that occur both within these syndromes and spontaneously; associated with somatic mutations in NF1, NF2, and SWN. The meeting addresses both state of the field for current clinical care as well as emerging preclinical models fueling discovery of new therapeutic targets and discovery science initiatives investigating mechanisms of tumorigenesis. Importantly, this conference is a forum for presenting work in progress and bringing together all stakeholders in the scientific community. A highlight of the conference was the involvement of scientists from the pharmaceutical industry who presented growing efforts for rare disease therapeutic development in general and specifically, in pediatric patients with rare tumor syndromes. Another highlight was the focus on new investigators who presented new data about biomarker discovery, tumor pathogenesis, and diagnostic tools for NF1, NF2, and SWN. This report summarizes the themes of the meeting and a synthesis of the scientific discoveries presented at the conference in order to make the larger research community aware of progress in the neurofibromatoses. © 2017 Wiley Periodicals, Inc.

Roles of somatic A-type K(+) channels in the synaptic plasticity of hippocampal neurons.

PubMed

Yang, Yoon-Sil; Kim, Kyeong-Deok; Eun, Su-Yong; Jung, Sung-Cherl

2014-06-01

In the mammalian brain, information encoding and storage have been explained by revealing the cellular and molecular mechanisms of synaptic plasticity at various levels in the central nervous system, including the hippocampus and the cerebral cortices. The modulatory mechanisms of synaptic excitability that are correlated with neuronal tasks are fundamental factors for synaptic plasticity, and they are dependent on intracellular Ca(2+)-mediated signaling. In the present review, the A-type K(+) (IA) channel, one of the voltage-dependent cation channels, is considered as a key player in the modulation of Ca(2+) influx through synaptic NMDA receptors and their correlated signaling pathways. The cellular functions of IA channels indicate that they possibly play as integral parts of synaptic and somatic complexes, completing the initiation and stabilization of memory.

Bacteriophage ecology in a small community sewer system related to their indicative role in sewage pollution of drinking water.

PubMed

Gino, Efrat; Starosvetsky, Jeana; Armon, Robert

2007-10-01

In view of various studies looking for the merit of coliphages as indicators of water pollution with viruses originating from faecal material, a small agricultural community (population of approximately 1500 inhabitants of all ages, 2-3 km from Haifa) was selected in order to understand these bacteriophage ecology (F-RNA and somatic coliphages) in its sewer and oxidation pond system. Along the sewer lines, it was possible to isolate constantly both bacteriophage types (F-RNA and somatic coliphages) at 10(2)-10(4) plaque-forming units (pfu) ml(-1). The average numbers of somatic and F-RNA phages isolated from oxidation pond were 10(3)-10(4) pfu ml(-1); however, somatic coliphages were undetectable for several months (April-August). Significant high correlation (0.944 < R(2) < 0.99) was found between increased anionic detergent concentrations and F-RNA coliphage numbers. Infants less than 1 year old excreted both phage types and few only F-RNA coliphages (at high numbers > 10(5) pfu g(-1)) for up to 1 year. The excretion of F-RNA coliphages was highly linked to Escherichia coli F(+) harborage in the intestinal track as found in their faecal content. Finally, three bacterial hosts E. coli F(+), F(-) and CN(13) tested for survivability in sewage filtrate revealed that E. coli F(+) had the highest survivability under these conditions. Presence of somatic and F male-specific phages in sewer lines of a small community are influenced by several factors such as: anionic detergents, nutrients, temperature, source (mainly infants), shedding and survival capability of the host strain. Better understanding of coliphages ecology in sewer systems can enhance our evaluation of these proposed indicator/index microorganisms used in tracking environmental pollution of water, soil and crop contamination with faecal material containing enteric viruses.

Genotoxicity testing of different types of beverages in the Drosophila wing Somatic Mutation And Recombination Test.

PubMed

Graf, U; Moraga, A A; Castro, R; Díaz Carrillo, E

1994-05-01

Five wines and one brandy of Spanish origin as well as three herbal teas and ordinary black tea were tested for genotoxicity in the wing Somatic Mutation And Recombination Test (SMART) which makes use of the two recessive wing cell markers multiple wing hairs (mwh) and flare (flr3) on the left arm of chromosome 3 of Drosophila melanogaster. 3-day-old larvae trans-heterozygous for these two markers were fed the beverages at different concentrations and for different feeding periods using Drosophila instant medium. Somatic mutations or mitotic recombinations induced in the cells of the wing imaginal discs give rise to mutant single or twin spots on the wing blade of the emerging adult flies showing either the mwh phenotype or/and the flr phenotype. One of the red wines showed a clear genotoxic activity that was not due to its ethanol content. Two herbal teas (Urtica dioica, Achillea millefolium) and black tea (Camellia sinensis) proved to be weakly genotoxic as well. Furthermore, it was shown that quercetin and rutin, two flavonols present in beverages of plant origin, also exhibited weak genotoxic activity in the somatic cells of Drosophila. These results demonstrate that Drosophila in vivo somatic assays can detect the genotoxicity of complex mixtures such as beverages. In particular, it is possible to administer these test materials in the same form as that in which they are normally consumed.

Micropropagation of Codiaeum variegatum (L.) Blume and regeneration induction via adventitious buds and somatic embryogenesis.

PubMed

Radice, Silvia

2010-01-01

Codiaeum variegatum (L) Blume cv. "Corazon de oro" and cv. "Norma" are successfully micropropagated when culture are initiated with explants taken from newly sprouted shoots. The establishment and multiplication steps are possible when 1 mg/L BA or 1 mg/L IAA and 3 mg/L 2iP are added to MS medium, according to the cultivar respectively selected.Adventive organogenesis and somatic embryogenesis are induced from leaf explants taken from in vitro buds of croton. On leaf-sectioned of "Corazon de oro" cultured in vitro, 1 mg/L BA stimulates continuous somatic embryos development and induces some shoots too. Replacing BA with 1 mg/L TDZ induces up to 100% bud regeneration in the same explants. On the other hand, leaf-sectioned of C. variegatum cv. Norma does not start somatic embryo differentiation if 1 mg/L TDZ is not added to the MS basal medium. Incipient callus is observed after 30 days of culture, and then, subculture to MS with 1 mg/L BA allows the same process to show on the "Corazon de oro" cultivar. Somatic embryos show growth arrest that is partially overcome by transfer to hormone-free basal medium with activated charcoal. Root induction is possible on basal medium plus 1 mg/L IBA. Plantlets in the greenhouse have variegated leaves true-to-type.

Bovine somatic cell nuclear transfer.

PubMed

Ross, Pablo J; Cibelli, Jose B

2010-01-01

Somatic cell nuclear transfer (SCNT) is a technique by which the nucleus of a differentiated cell is introduced into an oocyte from which its genetic material has been removed by a process called enucleation. In mammals, the reconstructed embryo is artificially induced to initiate embryonic development (activation). The oocyte turns the somatic cell nucleus into an embryonic nucleus. This process is called nuclear reprogramming and involves an important change of cell fate, by which the somatic cell nucleus becomes capable of generating all the cell types required for the formation of a new individual, including extraembryonic tissues. Therefore, after transfer of a cloned embryo to a surrogate mother, an offspring genetically identical to the animal from which the somatic cells where isolated, is born. Cloning by nuclear transfer has potential applications in agriculture and biomedicine, but is limited by low efficiency. Cattle were the second mammalian species to be cloned after Dolly the sheep, and it is probably the most widely used species for SCNT experiments. This is, in part due to the high availability of bovine oocytes and the relatively higher efficiency levels usually obtained in cattle. Given the wide utilization of this species for cloning, several alternatives to this basic protocol can be found in the literature. Here we describe a basic protocol for bovine SCNT currently being used in our laboratory, which is amenable for the use of the nuclear transplantation technique for research or commercial purposes.

Effects of donor cell type and genotype on the efficiency of mouse somatic cell cloning.

PubMed

Inoue, Kimiko; Ogonuki, Narumi; Mochida, Keiji; Yamamoto, Yoshie; Takano, Kaoru; Kohda, Takashi; Ishino, Fumitoshi; Ogura, Atsuo

2003-10-01

Although it is widely assumed that the cell type and genotype of the donor cell affect the efficiency of somatic cell cloning, little systematic analysis has been done to verify this assumption. The present study was undertaken to examine whether donor cell type, donor genotype, or a combination thereof increased the efficiency of mouse cloning. Initially we assessed the developmental ability of embryos that were cloned from cumulus or immature Sertoli cells with six different genotypes (i.e., 2 x 6 factorial). Significantly better cleavage rates were obtained with cumulus cells than with Sertoli cells (P < 0.005, two-way ANOVA), which probably was due to the superior cell-cycle synchrony of cumulus cells at G0/G1. After embryo transfer, there was a significant effect of cell type on the birth rate, with Sertoli cells giving the better result (P < 0.005). Furthermore, there was a significant interaction (P < 0.05) between the cell type and genotype, which indicates that cloning efficiency is determined by a combination of these two factors. The highest mean birth rate (10.8 +/- 2.1%) was obtained with (B6 x 129)F1 Sertoli cells. In the second series of experiments, we examined whether the developmental ability of clones with the wild-type genotype (JF1) was improved when combined with the 129 genotype. Normal pups were cloned from cumulus and immature Sertoli cells of the (129 x JF1)F1 and (JF1 x 129)F1 genotypes, whereas no pups were born from cells with the (B6 x JF1)F1 genotype. The present study clearly demonstrates that the efficiency of somatic cell cloning, and in particular fetal survival after embryo transfer, may be improved significantly by choosing the appropriate combinations of cell type and genotype.

Climbing Mount Efficiency--small steps, not giant leaps towards higher cloning success in farm animals.

PubMed

Oback, Björn

2008-07-01

Despite more than a decade of research efforts, farm animal cloning by somatic cell nuclear transfer (SCNT) is still frustratingly inefficient. Inefficiency manifests itself at different levels, which are currently not well integrated. At the molecular level, it leads to widespread genetic, epigenetic and transcriptional aberrations in cloned embryos. At the organismal level, these genome-wide abnormalities compromise development of cloned foetuses and offspring. Specific molecular defects need to be causally linked to specific cloned phenotypes, in order to design specific treatments to correct them. Cloning efficiency depends on the ability of the nuclear donor cell to be fully reprogrammed into an embryonic state and the ability of the enucleated recipient cell to carry out the reprogramming reactions. It has been postulated that reprogrammability of the somatic donor cell epigenome is influenced by its differentiation status. However, direct comparisons between cells of divergent differentiation status within several somatic lineages have found no conclusive evidence for this. Choosing somatic stem cells as donors has not improved cloning efficiency, indicating that donor cell type may be less critical for cloning success. Different recipient cells, on the other hand, vary in their reprogramming ability. In bovine, using zygotes instead of oocytes has increased cloning success. Other improvements in livestock cloning efficiency include better coordinating donor cell type with cell cycle stage and aggregating cloned embryos. In the future, it will be important to demonstrate if these small increases at every step are cumulative, adding up to an integrated cloning protocol with greatly improved efficiency.

Germline Proliferation Is Regulated by Somatic Endocytic Genes via JNK and BMP Signaling in Drosophila.

PubMed

Tang, Yaning; Geng, Qing; Chen, Di; Zhao, Shaowei; Liu, Xian; Wang, Zhaohui

2017-05-01

Signals derived from the microenvironment contribute greatly to tumorigenesis . The underlying mechanism requires thorough investigation. Here, we use Drosophila testis as a model system to address this question, taking the advantage of the ease to distinguish germline and somatic cells and to track the cell numbers. In an EMS mutagenesis screen, we identified Rab5 , a key factor in endocytosis, for its nonautonomous role in germline proliferation. The disruption of Rab5 in somatic cyst cells, which escort the development of germline lineage, induced the overproliferation of underdifferentiated but genetically wild-type germ cells. We demonstrated that this nonautonomous effect was mediated by the transcriptional activation of Dpp [the fly homolog of bone morphogenetic protein (BMP)] by examining the Dpp-reporter expression and knocking down Dpp to block germline overgrowth. Consistently, the protein levels of Bam, the germline prodifferentiation factor normally accumulated in the absence of BMP/Dpp signaling, decreased in the overproliferating germ cells. Further, we discovered that the JNK signaling pathway operated between Rab5 and Dpp, because simultaneously inhibiting the JNK pathway and Rab5 in cyst cells prevented both dpp transcription and germline tumor growth. Additionally, we found that multiple endocytic genes, such as avl , TSG101 , Vps25 , or Cdc42 , were required in the somatic cyst cells to restrict germline amplification. These findings indicate that when the endocytic state of the surrounding cells is impaired, genetically wild-type germ cells overgrow. This nonautonomous model of tumorigenesis provides a simple system to dissect the relation between tumor and its niche. Copyright © 2017 by the Genetics Society of America.

Factors Associated with Suicidal Ideation and Quality of Life in Adolescents from Puerto Rico with Type 1 Diabetes.

PubMed

Guerrero-Ramírez, Grace; Cumba-Avilés, Eduardo

2018-03-01

People with type 1 diabetes (T1D) may experience significant changes in their daily routines due to this condition, which frequently results in depressive symptoms and the deterioration of their quality of life. We examined the factors associated with suicidal ideation (SI) and diabetes-related quality of life (DRQOL) in adolescents (aged 12 to 17) with T1D. The sample consisted of 51 youths (29 girls) recruited during a treatment study for depression. They completed the Diabetes Quality of Life for Youth questionnaire, the Suicidal Ideation Questionnaire Junior, and other measures that explore emotional, cognitive, somatic, behavioral, and relational aspects. Their caregivers completed the Barriers to Adherence Questionnaire and the Somatic Complaints subscale of the Child Behavior Checklist, among other measures. We used correlation and multiple linear regression analyses to identify the factors associated with the dependent variables. The variables associated with SI were depression, somatic complaints, perceived family emotional support, self care for diabetes, self-deprecation, helplessness, and hopelessness, among others. In a multiple regression analysis, the first 3 accounted for 46% of the variance. Those related to DRQOL included cognitive alterations, barriers to adherence, perceived family emotional support, self-efficacy for diabetes and for depression, helplessness, anxiety, and self-deprecation, among others. The first 4 accounted for 61% of the variance. Our findings highlight the impact of emotional, cognitive, somatic, behavioral, and relational aspects on the quality of mental health and the DRQOL of youth with T1D, as well as their pertinence for the development of psychosocial interventions for this population.

Neural pathways for colorectal control, relevance to spinal cord injury and treatment: a narrative review.

PubMed

Callaghan, Brid; Furness, John B; Pustovit, Ruslan V

2018-03-01

Narrative review. The purpose is to review the organisation of the nerve pathways that control defecation and to relate this knowledge to the deficits in colorectal function after SCI. A literature review was conducted to identify salient features of defecation control pathways and the functional consequences of damage to these pathways in SCI. The control pathways for defecation have separate pontine centres under cortical control that influence defecation. The pontine centres connect, separately, with autonomic preganglionic neurons of the spinal defecation centres and somatic motor neurons of Onuf's nucleus in the sacral spinal cord. Organised propulsive motor patterns can be generated by stimulation of the spinal defecation centres. Activation of the somatic neurons contracts the external sphincter. The analysis aids in interpreting the consequences of SCI and predicts therapeutic strategies. Analysis of the bowel control circuits identifies sites at which bowel function may be modulated after SCI. Colokinetic drugs that elicit propulsive contractions of the colorectum may provide valuable augmentation of non-pharmacological bowel management procedures.

Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

PubMed

Rudolph, Stephanie; Hull, Court; Regehr, Wade G

2015-11-25

Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The extent of inhibition depends on both spontaneous activity of GoCs and the excitatory synaptic input they receive. In this study, we find that different types of calcium channels are differentially distributed, with dendritic calcium channels being activated by somatic activity, boosting synaptic inputs and enabling bursting, and somatic calcium cannels promoting regular firing. We therefore challenge the current view that GoC dendrites are passive and identify the mechanisms that contribute to GoCs regulating the flow of sensory information in the cerebellar cortex. Copyright © 2015 the authors 0270-6474/15/3515492-13$15.00/0.

Donor cell differentiation, reprogramming, and cloning efficiency: elusive or illusive correlation?

PubMed

Oback, B; Wells, D N

2007-05-01

Compared to other assisted reproductive technologies, mammalian nuclear transfer (NT) cloning is inefficient in generating viable offspring. It has been postulated that nuclear reprogramming and cloning efficiency can be increased by choosing less differentiated cell types as nuclear donors. This hypothesis is mainly supported by comparative mouse cloning experiments using early blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic donor cells. We have re-evaluated these comparisons, taking into account different NT procedures, the use of donor cells from different genetic backgrounds, sex, cell cycle stages, and the lack of robust statistical significance when post-blastocyst development is compared. We argue that while the reprogrammability of early blastomeres appears to be much higher than that of somatic cells, it has so far not been conclusively determined whether differentiation status affects cloning efficiency within somatic donor cell lineages. Copyright (c) 2006 Wiley-Liss, Inc.

Clock-like mutational processes in human somatic cells

DOE PAGES

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; ...

2015-11-09

During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutationmore » rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This paper provides the first survey of clock-like mutational processes operating in human somatic cells.« less

Clock-like mutational processes in human somatic cells

PubMed Central

Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; Sale, Julian E.; Campbell, Peter J.; Nik-Zainal, Serena; Stratton, Michael R.

2016-01-01

During the course of a lifetime somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell’s genome. Some processes generate mutations throughout life at a constant rate in all individuals and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operative in human somatic cells. PMID:26551669

Somatic cell cloning: the ultimate form of nuclear reprogramming?

PubMed

Piedrahita, Jorge A; Mir, Bashir; Dindot, Scott; Walker, Shawn

2004-05-01

With the increasing difficulties associated with meeting the required needs for organs used in transplantation, alternative approaches need to be considered. These include the use of stem cells as potential sources of specialized cells, the ability to transdifferentiate cell types in culture, and the development of complete organs that can be used in humans. All of the above goals will require a complete understanding of the factors affecting cell differentiation and nuclear reprogramming. To make this a reality, however, techniques associated with cloning and genetic modifications in somatic cells need to be continued to be developed and optimized. This includes not only an enhancement of the rate of homologous recombination in somatic cells, but also a thorough understanding of the nuclear reprogramming process taking place during nuclear transfer. The understanding of this process is likely to have an effect beyond the area of nuclear transfer and assist with better methods for transdifferentiation of mammalian cells.

Different DNA methylation patterns detected by the Amplified Methylation Polymorphism Polymerase Chain Reaction (AMP PCR) technique among various cell types of bulls.

PubMed

Phutikanit, Nawapen; Suwimonteerabutr, Junpen; Harrison, Dion; D'Occhio, Michael; Carroll, Bernie; Techakumphu, Mongkol

2010-03-05

The purpose of this study was to apply an arbitrarily primed methylation sensitive polymerase chain reaction (PCR) assay called Amplified Methylation Polymorphism Polymerase Chain Reaction (AMP PCR) to investigate the methylation profiles of somatic and germ cells obtained from Holstein bulls. Genomic DNA was extracted from sperm, leukocytes and fibroblasts obtained from three bulls and digested with a methylation sensitive endonuclease (HpaII). The native genomic and enzyme treated DNA samples were used as templates in an arbitrarily primed-PCR assay with 30 sets of single short oligonucleotide primer. The PCR products were separated on silver stained denaturing polyacrylamide gels. Three types of PCR markers; digestion resistant-, digestion sensitive-, and digestion dependent markers, were analyzed based on the presence/absence polymorphism of the markers between the two templates. Approximately 1,000 PCR markers per sample were produced from 27 sets of primer and most of them (>90%) were digestion resistant markers. The highest percentage of digestion resistant markers was found in leukocytic DNA (94.8%) and the lowest in fibroblastic DNA (92.3%, P < or = 0.05). Spermatozoa contained a higher number of digestion sensitive markers when compared with the others (3.6% vs. 2.2% and 2.6% in leukocytes and fibroblasts respectively, P < or = 0.05). The powerfulness of the AMP PCR assay was the generation of methylation-associated markers without any prior knowledge of the genomic sequence. The data obtained from different primers provided an overview of genome wide DNA methylation content in different cell types. By using this technique, we found that DNA methylation profile is tissue-specific. Male germ cells were hypomethylated at the HpaII locations when compared with somatic cells, while the chromatin of the well-characterized somatic cells was heavily methylated when compared with that of the versatile somatic cells.

Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants with Single Ventricle

PubMed Central

Mital, Seema; Chung, Wendy K.; Colan, Steven D.; Sleeper, Lynn A.; Manlhiot, Cedric; Arrington, Cammon B.; Cnota, James F.; Graham, Eric M.; Mitchell, Michael E.; Goldmuntz, Elizabeth; Li, Jennifer S.; Levine, Jami C.; Lee, Teresa M.; Margossian, Renee; Hsu, Daphne T.

2011-01-01

Background We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function and response to enalapril in infants with single ventricle. Methods and Results Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with RAAS upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate (eGFR), and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high-risk), and those with <2 homozygous risk genotypes (low-risk) at two time points - before the superior-cavopulmonary-connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: 38 were high-risk, 116 were low-risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and eGFR increased after SCPC in the low-risk (p<0.05) but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline and height remained lower in the high-risk group at 14 months especially in those receiving enalapril (p<0.05). Conclusions RAAS-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. RAAS genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume unloading surgery. Follow-up is warranted to assess longterm impact. Clinical Trial Registration Clinical Trials.gov Identifier NCT00113087 PMID:21576655

Somatic Embryogenesis in Peach Palm Using the Thin Cell Layer Technique: Induction, Morpho-histological Aspects and AFLP Analysis of Somaclonal Variation

PubMed Central

Steinmacher, D. A.; Krohn, N. G.; Dantas, A. C. M.; Stefenon, V. M.; Clement, C. R.; Guerra, M. P.

2007-01-01

Background and Aims The thin cell layer (TCL) technique is based on the use of very small explants and has allowed enhanced in vitro morphogenesis in several plant species. The present study evaluated the TCL technique as a procedure for somatic embryo production and plantlet regeneration of peach palm. Methods TCL explants from different positions in the shoot apex and leaf sheath of peach palm were cultivated in MS culture medium supplemented with 0–600 µm Picloram in the presence of activated charcoal. The production of primary calli and embryogenic calli was evaluated in these different conditions. Histological and amplified fragment length polymorphism (AFLP) analyses were conducted to study in vitro morphogenetic responses and genetic stability, respectively, of the regenerated plantlets. Key Results Abundant primary callus induction was observed from TCLs of the shoot meristem in culture media supplemented with 150–600 µm Picloram (83–97 %, respectively). The production of embryogenic calli depends on Picloram concentration and explant position. The best response observed was 43 % embryogenic callus production from shoot meristem TCL on 300 µm Picloram. In maturation conditions, 34 ± 4 somatic embryos per embryogenic callus were obtained, and 45·0 ± 3·4 % of these fully developed somatic embryos were converted, resulting in plantlets ready for acclimatization, of which 80 % survived. Histological studies revealed that the first cellular division events occurred in cells adjacent to vascular tissue, resulting in primary calli, whose growth was ensured by a meristematic zone. A multicellular origin of the resulting somatic embryos arising from the meristematic zone is suggested. During maturation, histological analyses revealed bipolarization of the somatic embryos, as well as the development of new somatic embryos. AFLP analyses revealed that 92 % of the regenerated plantlets were true to type. The use of TCL explants considerably improves the number of calli and somatic embryos produced in comparison with previously described protocols for in vitro regeneration of peach palm. Conclusions The present study suggests that the TCL somatic embryogenesis protocol developed is feasible, although it still requires further optimization for in vitro multiplication of peach palm, especially the use of similar explants obtained from adult palm trees. PMID:17670751

Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome

PubMed Central

Swanson, Larry W.; Sporns, Olaf; Hahn, Joel D.

2016-01-01

The cerebral nuclei form the ventral division of the cerebral hemisphere and are thought to play an important role in neural systems controlling somatic movement and motivation. Network analysis was used to define global architectural features of intrinsic cerebral nuclei circuitry in one hemisphere (association connections) and between hemispheres (commissural connections). The analysis was based on more than 4,000 reports of histologically defined axonal connections involving all 45 gray matter regions of the rat cerebral nuclei and revealed the existence of four asymmetrically interconnected modules. The modules form four topographically distinct longitudinal columns that only partly correspond to previous interpretations of cerebral nuclei structure–function organization. The network of connections within and between modules in one hemisphere or the other is quite dense (about 40% of all possible connections), whereas the network of connections between hemispheres is weak and sparse (only about 5% of all possible connections). Particularly highly interconnected regions (rich club and hubs within it) form a topologically continuous band extending through two of the modules. Connection path lengths among numerous pairs of regions, and among some of the network’s modules, are relatively long, thus accounting for low global efficiency in network communication. These results provide a starting point for reexamining the connectional organization of the cerebral hemispheres as a whole (right and left cerebral cortex and cerebral nuclei together) and their relation to the rest of the nervous system. PMID:27647882

Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers

PubMed Central

Briggs, Sarah; Tomlinson, Ian

2013-01-01

Polymerases ϵ and δ are the main enzymes that replicate eukaryotic DNA. Accurate replication occurs through Watson–Crick base pairing and also through the action of the polymerases' exonuclease (proofreading) domains. We have recently shown that germline exonuclease domain mutations (EDMs) of POLE and POLD1 confer a high risk of multiple colorectal adenomas and carcinoma (CRC). POLD1 mutations also predispose to endometrial cancer (EC). These mutations are associated with high penetrance and dominant inheritance, although the phenotype can be variable. We have named the condition polymerase proofreading-associated polyposis (PPAP). Somatic POLE EDMs have also been found in sporadic CRCs and ECs, although very few somatic POLD1 EDMs have been detected. Both the germline and the somatic DNA polymerase EDMs cause an ‘ultramutated’, apparently microsatellite-stable, type of cancer, sometimes leading to over a million base substitutions per tumour. Here, we present the evidence for POLE and POLD1 as important contributors to the pathogenesis of CRC and EC, and highlight some of the key questions in this emerging field. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd PMID:23447401

Diagnostic criteria for psychosomatic research and somatic symptom disorders.

PubMed

Sirri, Laura; Fava, Giovanni A

2013-02-01

The Diagnostic Criteria for Psychosomatic Research (DCPR) were introduced in 1995 by an international group of investigators to expand the traditional domains of the disease model. The DCPR are a set of 12 'psychosomatic syndromes' which provide operational tools for psychosocial variables with prognostic and therapeutic implications in clinical settings. Eight syndromes concern the main manifestations of abnormal illness behaviour: somatization, hypochondriacal fears and beliefs, and illness denial. The other four syndromes (alexithymia, type A behaviour, demoralization and irritable mood) refer to the domain of psychological factors affecting medical conditions. This review describes the conceptual bases of the DCPR and the main findings concerning their application, with particular reference to the incremental information they added to the customary psychiatric classification. The DCPR were also compared with the provisional DSM-5 somatic symptom disorders. The DCPR were found to be more sensitive than DSM-IV in identifying subthreshold psychological distress and characterizing patients' psychological response to medical illness. DSM-5 somatic symptom disorders seem to neglect important clinical phenomena, such as illness denial, resulting in a narrow view of patients' functioning. The additional information provided by the DCPR may enhance the decision-making process.

Neurofibromin Deficiency-Associated Transcriptional Dysregulation Suggests a Novel Therapy for Tibial Pseudoarthrosis in NF1

PubMed Central

Paria, Nandina; Cho, Tae-Joon; Choi, In Ho; Kamiya, Nobuhiro; Kayembe, Kay; Mao, Rong; Margraf, Rebecca L.; Obermosser, Gerlinde; Oxendine, Ila; Sant, David W.; Song, Mi Hyun; Stevenson, David A.; Viskochil, David H.; Wise, Carol A.; Kim, Harry K.W.; Rios, Jonathan J

2014-01-01

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by mutations in NF1. Among the earliest manifestations is tibial pseudoarthrosis and persistent nonunion after fracture. To further understand the pathogenesis of pseudoarthrosis and the underlying bone remodeling defect, pseudoarthrosis tissue and cells cultured from surgically resected pseudoarthrosis tissue from NF1 individuals were analyzed using whole-exome and whole-transcriptome sequencing as well as genomewide microarray analysis. Genomewide analysis identified multiple genetic mechanisms resulting in somatic bi-allelic NF1 inactivation; no other genes with recurring somatic mutations were identified. Gene expression profiling identified dysregulated pathways associated with neurofibromin deficiency, including phosphoinosital-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. Unlike aggressive NF1-associated malignancies, tibial pseudoarthrosis tissue does not harbor a high frequency of somatic mutations in oncogenes or other tumor-suppressor genes, such as p53. However, gene expression profiling indicates pseudoarthrosis tissue has a tumor-promoting transcriptional pattern, despite lacking tumorigenic somatic mutations. Significant over-expression of specific cancer-associated genes in pseudoarthrosis highlights a potential for receptor tyrosine kinase inhibitors to target neurofibromin-deficient pseudoarthrosis and promote proper bone remodeling and fracture healing. PMID:24932921

Pyramidal tract stimulation restores normal corticospinal tract connections and visuomotor skill after early postnatal motor cortex activity blockade

PubMed Central

Salimi, I; Friel, KM; Martin, JH

2008-01-01

Motor development depends on forming specific connections between the corticospinal tract (CST) and the spinal cord. Blocking CST activity in kittens during the critical period for establishing connections with spinal motor circuits results in permanent impairments in connectivity and function. The changes in connections are consistent with the hypothesis that the inactive tract is less competitive in developing spinal connections than the active tract. In this study we tested the competition hypothesis by determining if activating CST axons, after prior silencing during the critical period, abrogated development of aberrant corticospinal connections and motor impairments. In kittens, we inactivated motor cortex by muscimol infusion between postnatal weeks 5-7. We next electrically stimulated CST axons in the medullary pyramid 2.5 hours daily, between weeks 7-10. In controls (n=3), CST terminations were densest within the contralateral deeper, premotor, spinal layers. After prior inactivation (n=3), CST terminations were densest within the dorsal, somatic sensory, layers. There were more ipsilateral terminations from the active tract. During visually guided locomotion, there was a movement endpoint impairment. Stimulation after inactivation (n=6) resulted in significantly fewer terminations in the sensory layers and more in the premotor layers, and fewer ipsilateral connections from active cortex. Chronic stimulation reduced the current threshold for evoking contralateral movements by pyramidal stimulation, suggesting strengthening of connections. Importantly, stimulation significantly improved stepping accuracy. These findings show the importance of activity-dependent processes in specifying CST connections. They also provide a strategy for harnessing activity to rescue CST axons at risk of developing aberrant connections after CNS injury. PMID:18632946

Stem Cells, Science, and Public Reasoning

ERIC Educational Resources Information Center

Hurlbut, J. Benjamin; Robert, Jason Scott

2012-01-01

These are interesting days in the scientific, social, and political debates about human embryonic stem cell research. Pluripotent stem cells--cells that can, in principle, give rise to the body's full range of cell types--were previously derivable only from human embryos that were destroyed in the process. Now, a variety of somatic cell types can…

Agrobacterium tumefaciens-mediated transformation for investigation of somatic recombination in the fungal pathogen Armillaria mellea.

PubMed

Baumgartner, Kendra; Fujiyoshi, Phillip; Foster, Gary D; Bailey, Andy M

2010-12-01

Armillaria root disease is one of the most damaging timber and fruit tree diseases in the world. Despite its economic importance, many basic questions about the biology of the causal fungi, Armillaria spp., are unanswered. For example, Armillaria undergoes matings between diploid and haploid mycelia, which can result in a recombinant diploid without meiosis. Evidence of such somatic recombination in natural populations suggests that this reproductive mode may affect the pathogen's ecology. Investigations of the mechanisms and adaptive consequences of somatic recombination are, however, hampered by the lack of a method to reliably synthesize somatic recombinants. Here we report the first genetic transformation system for the genus Armillaria. We transformed A. mellea with selective markers for use in diploid-haploid matings to reliably synthesize somatic recombinants. This was accomplished with Agrobacterium tumefaciens carrying pBGgHg, which carries the hygromycin phosphotransferase gene (hph). hph was integrated into transformants, as evidenced by serial transfer to selective media, PCR, reverse transcription-PCR (RT-PCR), and Southern hybridization. Nuclear and mitochondrial markers were developed to genotype synthesized mycelia. In matings between a wild-type diploid and hygromycin-resistant haploids (transgenic), we identified recombinant, hygromycin-resistant diploids and, additionally, hygromycin-resistant triploids, all with the mitochondrial haplotype of the haploid partner. Our approach created no mycelium in which the haploid nucleus was replaced by the diploid nucleus, the typical outcome of diploid-haploid matings in Armillaria. This genetic transformation system, in combination with new markers to track chromosomal and cytoplasmic inheritance in A. mellea, will advance research aimed at characterizing the significance of somatic recombination in the ecology of this important fungus.

Exome-wide Sequencing Shows Low Mutation Rates and Identifies Novel Mutated Genes in Seminomas.

PubMed

Cutcutache, Ioana; Suzuki, Yuka; Tan, Iain Beehuat; Ramgopal, Subhashini; Zhang, Shenli; Ramnarayanan, Kalpana; Gan, Anna; Lee, Heng Hong; Tay, Su Ting; Ooi, Aikseng; Ong, Choon Kiat; Bolthouse, Jonathan T; Lane, Brian R; Anema, John G; Kahnoski, Richard J; Tan, Patrick; Teh, Bin Tean; Rozen, Steven G

2015-07-01

Testicular germ cell tumors are the most common cancer diagnosed in young men, and seminomas are the most common type of these cancers. There have been no exome-wide examinations of genes mutated in seminomas or of overall rates of nonsilent somatic mutations in these tumors. The objective was to analyze somatic mutations in seminomas to determine which genes are affected and to determine rates of nonsilent mutations. Eight seminomas and matched normal samples were surgically obtained from eight patients. DNA was extracted from tissue samples and exome sequenced on massively parallel Illumina DNA sequencers. Single-nucleotide polymorphism chip-based copy number analysis was also performed to assess copy number alterations. The DNA sequencing read data were analyzed to detect somatic mutations including single-nucleotide substitutions and short insertions and deletions. The detected mutations were validated by independent sequencing and further checked for subclonality. The rate of nonsynonymous somatic mutations averaged 0.31 mutations/Mb. We detected nonsilent somatic mutations in 96 genes that were not previously known to be mutated in seminomas, of which some may be driver mutations. Many of the mutations appear to have been present in subclonal populations. In addition, two genes, KIT and KRAS, were affected in two tumors each with mutations that were previously observed in other cancers and are presumably oncogenic. Our study, the first report on exome sequencing of seminomas, detected somatic mutations in 96 new genes, several of which may be targetable drivers. Furthermore, our results show that seminoma mutation rates are five times higher than previously thought, but are nevertheless low compared to other common cancers. Similar low rates are seen in other cancers that also have excellent rates of remission achieved with chemotherapy. We examined the DNA sequences of seminomas, the most common type of testicular germ cell cancer. Our study identified 96 new genes in which mutations occurred during seminoma development, some of which might contribute to cancer development or progression. The study also showed that the rates of DNA mutations during seminoma development are higher than previously thought, but still lower than for other common solid-organ cancers. Such low rates are also observed among other cancers that, like seminomas, show excellent rates of disease remission after chemotherapy. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Characterization of a type-A response regulator differentially expressed during adventitious caulogenesis in Pinus pinaster.

PubMed

Alvarez, José M; Cortizo, Millán; Ordás, Ricardo J

2012-12-15

The molecular cloning and characterization of PipsRR1, a type-A response regulator in Pinus pinaster, is reported here. Type-A response regulators mediate downstream responses to cytokinin and act as negative feedback regulators of the signal transduction pathway. Some type-A response regulators in Arabidopsis have been related to de novo meristem formation. However, little information exists in Pinus spp. The PipsRR1 gene contains 5 exons, as do all type-A response regulators in Arabidopsis, and the deduced protein contains a receiver domain with the conserved DDK residues and a short C terminal extension. Expression analysis showed that the PipsRR1 gene is differentially expressed during the first phases of adventitious caulogenesis induced by benzyladenine in P. pinaster cotyledons, suggesting that PipsRR1 plays a role in caulogenesis in conifers. Additionally, a binary vector carrying the PipsRR1 promoter driving GFP:GUS expression was constructed to analyze the promoter activity in P. pinaster somatic embryos. The results of genetic transformation showed GUS activity during somatic embryo mass proliferation and embryo maturation. Copyright © 2012 Elsevier GmbH. All rights reserved.

Sexual Fate Change of XX Germ Cells Caused by the Deletion of SMAD4 and STRA8 Independent of Somatic Sex Reprogramming

PubMed Central

Wu, Quan; Fukuda, Kurumi; Kato, Yuzuru; Zhou, Zhi; Deng, Chu-Xia; Saga, Yumiko

2016-01-01

The differential programming of sperm and eggs in gonads is a fundamental topic in reproductive biology. Although the sexual fate of germ cells is believed to be determined by signaling factors from sexually differentiated somatic cells in fetal gonads, the molecular mechanism that determines germ cell fate is poorly understood. Herein, we show that mothers against decapentaplegic homolog 4 (SMAD4) in germ cells is required for female-type differentiation. Germ cells in Smad4-deficient ovaries respond to retinoic acid signaling but fail to undergo meiotic prophase I, which coincides with the weaker expression of genes required for follicular formation, indicating that SMAD4 signaling is essential for oocyte differentiation and meiotic progression. Intriguingly, germline-specific deletion of Smad4 in Stra8-null female germ cells resulted in the up-regulation of genes required for male gonocyte differentiation, including Nanos2 and PLZF, suggesting the initiation of male-type differentiation in ovaries. Moreover, our transcriptome analyses of mutant ovaries revealed that the sex change phenotype is achieved without global gene expression changes in somatic cells. Our results demonstrate that SMAD4 and STRA8 are essential factors that regulate the female fate of germ cells. PMID:27606421

Fibroblast growth factor receptors, developmental corruption and malignant disease.

PubMed

Kelleher, Fergal C; O'Sullivan, Hazel; Smyth, Elizabeth; McDermott, Ray; Viterbo, Antonella

2013-10-01

Fibroblast growth factors (FGF) are a family of ligands that bind to four different types of cell surface receptor entitled, FGFR1, FGFR2, FGFR3 and FGFR4. These receptors differ in their ligand binding affinity and tissue distribution. The prototypical receptor structure is that of an extracellular region comprising three immunoglobulin (Ig)-like domains, a hydrophobic transmembrane segment and a split intracellular tyrosine kinase domain. Alternative gene splicing affecting the extracellular third Ig loop also creates different receptor isoforms entitled FGFRIIIb and FGFRIIIc. Somatic fibroblast growth factor receptor (FGFR) mutations are implicated in different types of cancer and germline FGFR mutations occur in developmental syndromes particularly those in which craniosynostosis is a feature. The mutations found in both conditions are often identical. Many somatic FGFR mutations in cancer are gain-of-function mutations of established preclinical oncogenic potential. Gene amplification can also occur with 19-22% of squamous cell lung cancers for example having amplification of FGFR1. Ontologic comparators can be informative such as aberrant spermatogenesis being implicated in both spermatocytic seminomas and Apert syndrome. The former arises from somatic FGFR3 mutations and Apert syndrome arises from germline FGFR2 mutations. Finally, therapeutics directed at inhibiting the FGF/FGFR interaction are a promising subject for clinical trials.

Analytic validation and real-time clinical application of an amplicon-based targeted gene panel for advanced cancer

PubMed Central

Wing, Michele R.; Reeser, Julie W.; Smith, Amy M.; Reeder, Matthew; Martin, Dorrelyn; Jewell, Benjamin M.; Datta, Jharna; Miya, Jharna; Monk, J. Paul; Mortazavi, Amir; Otterson, Gregory A.; Goldberg, Richard M.; VanDeusen, Jeffrey B.; Cole, Sharon; Dittmar, Kristin; Jaiswal, Sunny; Kinzie, Matthew; Waikhom, Suraj; Freud, Aharon G.; Zhou, Xiao-Ping; Chen, Wei; Bhatt, Darshna; Roychowdhury, Sameek

2017-01-01

Multiplex somatic testing has emerged as a strategy to test patients with advanced cancer. We demonstrate our analytic validation approach for a gene hotspot panel and real-time prospective clinical application for any cancer type. The TruSight Tumor 26 assay amplifies 85 somatic hotspot regions across 26 genes. Using cell line and tumor mixes, we observed that 100% of the 14,715 targeted bases had at least 1000x raw coverage. We determined the sensitivity (100%, 95% CI: 96-100%), positive predictive value (100%, 95% CI: 96-100%), reproducibility (100% concordance), and limit of detection (3% variant allele frequency at 1000x read depth) of this assay to detect single nucleotide variants and small insertions and deletions. Next, we applied the assay prospectively in a clinical tumor sequencing study to evaluate 174 patients with metastatic or advanced cancer, including frozen tumors, formalin-fixed tumors, and enriched peripheral blood mononuclear cells in hematologic cancers. We reported one or more somatic mutations in 89 (53%) of the sequenced tumors (167 passing quality filters). Forty-three of these patients (26%) had mutations that would enable eligibility for targeted therapies. This study demonstrates the validity and feasibility of applying TruSight Tumor 26 for pan-cancer testing using multiple specimen types. PMID:29100271

Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

PubMed Central

Marcó, Sara; Pujol, Anna; Roca, Carles; Motas, Sandra; Ribera, Albert; Garcia, Miguel; Molas, Maria; Villacampa, Pilar; Melia, Cristian S.; Sánchez, Víctor; Sánchez, Xavier; Bertolin, Joan; Ruberte, Jesús; Haurigot, Virginia

2016-01-01

ABSTRACT Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches. PMID:27491071

Sexual Fate Change of XX Germ Cells Caused by the Deletion of SMAD4 and STRA8 Independent of Somatic Sex Reprogramming.

PubMed

Wu, Quan; Fukuda, Kurumi; Kato, Yuzuru; Zhou, Zhi; Deng, Chu-Xia; Saga, Yumiko

2016-09-01

The differential programming of sperm and eggs in gonads is a fundamental topic in reproductive biology. Although the sexual fate of germ cells is believed to be determined by signaling factors from sexually differentiated somatic cells in fetal gonads, the molecular mechanism that determines germ cell fate is poorly understood. Herein, we show that mothers against decapentaplegic homolog 4 (SMAD4) in germ cells is required for female-type differentiation. Germ cells in Smad4-deficient ovaries respond to retinoic acid signaling but fail to undergo meiotic prophase I, which coincides with the weaker expression of genes required for follicular formation, indicating that SMAD4 signaling is essential for oocyte differentiation and meiotic progression. Intriguingly, germline-specific deletion of Smad4 in Stra8-null female germ cells resulted in the up-regulation of genes required for male gonocyte differentiation, including Nanos2 and PLZF, suggesting the initiation of male-type differentiation in ovaries. Moreover, our transcriptome analyses of mutant ovaries revealed that the sex change phenotype is achieved without global gene expression changes in somatic cells. Our results demonstrate that SMAD4 and STRA8 are essential factors that regulate the female fate of germ cells.

Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins.

PubMed

van den Broek, Walther J A A; Nelen, Marcel R; Wansink, Derick G; Coerwinkel, Marga M; te Riele, Hein; Groenen, Patricia J T A; Wieringa, Bé

2002-01-15

The mechanism of expansion of the (CTG)n repeat in myotonic dystrophy (DM1) patients and the cause of its pathobiological effects are still largely unknown. Most likely, long repeats exert toxicity at the level of nuclear RNA transport or splicing. Here, we analyse cis- and trans-acting parameters that determine repeat behaviour in novel mouse models for DM1. Our mice carry 'humanized' myotonic dystrophy protein kinase (Dmpk) allele(s) with either a (CTG)84 or a (CTG)11 repeat, inserted at the correct position into the endogenous DM locus. Unlike in the human situation, the (CTG)84 repeat in the syntenic mouse environment was relatively stable during intergenerational segregation. However, somatic tissues showed substantial repeat expansions which were progressive upon aging and prominent in kidney, and in stomach and small intestine, where it was cell-type restricted. Other tissues examined showed only marginal size changes. The (CTG)11 allele was completely stable, as anticipated. Introducing the (CTG)84 allele into an Msh3-deficient background completely blocked the somatic repeat instability. In contrast, Msh6 deficiency resulted in a significant increase in the frequency of somatic expansions. Competition of Msh3 and Msh6 for binding to Msh2 in functional complexes with different DNA mismatch-recognition specificity may explain why the somatic (CTG)n expansion rate is differentially affected by ablation of Msh3 and Msh6.

Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation.

PubMed

Rivière, Guillaume; Lienhard, Daniel; Andrieu, Thomas; Vieau, Didier; Frey, Brigitte M; Frey, Felix J

2011-04-01

Somatic angiotensin-converting enzyme (sACE) is crucial in cardiovascular homeostasis and displays a tissue-specific profile. Epigenetic patterns modulate genes expression and their alterations were implied in pathologies including hypertension. However, the influence of DNA methylation and chromatin condensation state on the expression of sACE is unknown. We examined whether such epigenetic mechanisms could participate in the control of sACE expression in vitro and in vivo. We identified two CpG islands in the human ace-1 gene 3 kb proximal promoter region. Their methylation abolished the luciferase activity of ace-1 promoter/reporter constructs transfected into human liver (HepG2), colon (HT29), microvascular endothelial (HMEC-1) and lung (SUT) cell lines (p < 0.001). Bisulphite sequencing revealed a cell-type specific basal methylation pattern of the ace-1 gene -1,466/+25 region. As assessed by RT-qPCR, inhibition of DNA methylation by 5-aza-2'-deoxycytidine and/or of histone deacetylation by trichostatin A highly stimulated sACE mRNA expression cell-type specifically (p < 0.001 vs. vehicle treated cells). In the rat, in vivo 5-aza-cytidine injections demethylated the ace-1 promoter and increased sACE mRNA expression in the lungs and liver (p = 0.05), but not in the kidney. In conclusion, the expression level of somatic ACE is modulated by CpG-methylation and histone deacetylases inhibition. The basal methylation pattern of the promoter of the ace-1 gene is cell-type specific and correlates to sACE transcription. DNMT inhibition is associated with altered methylation of the ace-1 promoter and a cell-type and tissue-specific increase of sACE mRNA levels. This study indicates a strong influence of epigenetic mechanisms on sACE expression.

Recurrent gain-of-function USP8 mutations in Cushing's disease

PubMed Central

Ma, Zeng-Yi; Song, Zhi-Jian; Chen, Jian-Hua; Wang, Yong-Fei; Li, Shi-Qi; Zhou, Liang-Fu; Mao, Ying; Li, Yi-Ming; Hu, Rong-Gui; Zhang, Zhao-Yun; Ye, Hong-Ying; Shen, Ming; Shou, Xue-Fei; Li, Zhi-Qiang; Peng, Hong; Wang, Qing-Zhong; Zhou, Dai-Zhan; Qin, Xiao-Lan; Ji, Jue; Zheng, Jie; Chen, Hong; Wang, Yin; Geng, Dao-Ying; Tang, Wei-Jun; Fu, Chao-Wei; Shi, Zhi-Feng; Zhang, Yi-Chao; Ye, Zhao; He, Wen-Qiang; Zhang, Qi-Lin; Tang, Qi-Sheng; Xie, Rong; Shen, Jia-Wei; Wen, Zu-Jia; Zhou, Juan; Wang, Tao; Huang, Shan; Qiu, Hui-Jia; Qiao, Ni-Dan; Zhang, Yi; Pan, Li; Bao, Wei-Min; Liu, Ying-Chao; Huang, Chuan-Xin; Shi, Yong-Yong; Zhao, Yao

2015-01-01

Cushing's disease, also known as adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (PAs) that cause excess cortisol production, accounts for up to 85% of corticotrophin-dependent Cushing's syndrome cases. However, the genetic alterations in this disease are unclear. Here, we performed whole-exome sequencing of DNA derived from 12 ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs. We further evaluated somatic USP8 mutations in additional 258 PAs by Sanger sequencing. Targeted sequencing further identified a total of 17 types of USP8 variants in 67 of 108 ACTH-secreting PAs (62.04%). However, none of these mutations was detected in other types of PAs (n = 150). These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation. Accordingly, PAs with mutated USP8 display a higher incidence of EGFR expression, elevated EGFR protein abundance and mRNA expression levels of POMC, which encodes the precursor of ACTH. PAs with mutated USP8 are significantly smaller in size and have higher ACTH production than wild-type PAs. In surgically resected primary USP8-mutated tumor cells, USP8 knockdown or blocking EGFR effectively attenuates ACTH secretion. Taken together, somatic gain-of-function USP8 mutations are common and contribute to ACTH overproduction in Cushing's disease. Inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma. Our study highlights the potentially functional mutated gene in Cushing's disease and provides insights into the therapeutics of this disease. PMID:25675982

Connections of the Lateral Hypothalamic Area Juxtadorsomedial Region in the Male Rat

PubMed Central

Hahn, Joel D.; Swanson, Larry W.

2014-01-01

The connections of the lateral hypothalamic area juxtadorsomedial region (LHAjd) were investigated in a series of pathway-tracing experiments involving iontophoretic co-injection of the tracers Phaseolus vulgaris-leucoagglutinin (PHA-L; for outputs) and cholera toxin B subunit (CTB; for inputs). Results revealed that the LHAjd has connections with some 318 distinct gray matter regions encompassing all four subsystems—motor, sensory, cognitive, and behavioral state—included in a basic structure–function network model of the nervous system. Integration of these subsystems is necessary for the coordination and control of emotion and behavior, and in that regard the connections of the LHAjd indicate that it may have a prominent role. Furthermore, the LHAjd connections, together with the connections of other LHA differentiations studied similarly to date, indicate a distinct topographic organization that suggests each LHA differentiation has specifically differing degrees of involvement in the control of multiple behaviors. For the LHAjd, its involvement to a high degree in the control of defensive behavior, and to a lesser degree in the control of other behaviors, including ingestive and reproductive, is suggested. Moreover, the connections of the LHAjd suggest that its possible role in the control of these behaviors may be very broad in scope because they involve the somatic, neuroendocrine, and autonomic divisions of the nervous system. In addition, we suggest that connections between LHA differentiations may provide, at the level of the hypothalamus, a neuronal substrate for the coordinated control of multiple themes in the behavioral repertoire. PMID:22488503

Factors Associated With Suicidal Ideation and Quality of Life in Adolescents from Puerto Rico With Type 1 Diabetes

PubMed Central

Guerrero-Ramírez, Grace; Cumba-Avilés, Eduardo

2018-01-01

Objective People with type 1 diabetes (T1D) may experience significant changes in their daily routines due to this condition, which frequently results in depressive symptoms and the deterioration of their quality of life. We examined the factors associated with suicidal ideation (SI) and diabetes-related quality of life (DRQOL) in adolescents (aged 12 to 17) with T1D. Methods The sample consisted of 51 youths (29 girls) recruited during a treatment study for depression. They completed the Diabetes Quality of Life for Youth questionnaire, the Suicidal Ideation Questionnaire-Junior, and other measures that explore emotional, cognitive, somatic, behavioral, and relational aspects. Their caregivers completed the Barriers to Adherence Questionnaire and the Somatic Complaints subscale of the Child Behavior Checklist, among other measures. We used correlation and multiple linear regression analyses to identify the factors associated with the dependent variables. Results The variables associated with SI were depression, somatic complaints, perceived family emotional support, self-care for diabetes, self-deprecation, helplessness, and hopelessness, among others. In a multiple regression analysis, the first 3 accounted for 46% of the variance. Those related to DRQOL included cognitive alterations, barriers to adherence, perceived family emotional support, self-efficacy for diabetes and for depression, helplessness, anxiety, and self-deprecation, among others. The first 4 accounted for 61% of the variance. Conclusion Our findings highlight the impact of emotional, cognitive, somatic, behavioral, and relational aspects on the quality of mental health and the DRQOL of youth with T1D, as well as their pertinence for the development of psychosocial interventions for this population. PMID:29547680

Somatization: the under-recognized factor in nonspecific eczema. The Hordaland Health Study (HUSK).

PubMed

Klokk, M; Stansfeld, S; Overland, S; Wilhelmsen, I; Gotestam, K G; Steinshamn, S; Mykletun, A

2011-03-01

Psychodermatology has focused primarily on depression and anxiety in eczema. Skin symptoms are listed among many others for the ICD-10 diagnosis of somatization disorder. Somatization (unexplained somatic symptoms) is highly prevalent in the general population, but its association with eczema is yet to be empirically investigated. We therefore explored the association between somatization and eczema by examining the extent of somatization in eczema compared with allergic rhinitis, and by examining if eczema was more strongly associated with somatization than with anxiety and depression. Finally, we aimed to examine the relationship between the site of eczema and somatization for individual somatic symptoms and for somatic symptoms as a whole. For this population-based cross-sectional study we employed data from the Hordaland Health Study (HUSK) with 15,225 participants aged 41-48 years. Information on nonspecific eczema, allergic rhinitis, somatization, anxiety, depression and other covariates was obtained by self-report. The association between nonspecific eczema and somatization was strong and followed a dose-response pattern, as did all somatic symptoms in our index of somatization when analysed separately. The association between nonspecific eczema and somatization was stronger than that between rhinitis and somatization, and also the association between nonspecific eczema and anxiety and depression. In multivariate models, somatization accounted for most of the association between nonspecific eczema and anxiety/depression. In contrast, the association between nonspecific eczema and somatization was robust for adjustment for anxiety/depression. Somatization was strongly associated with nonspecific eczema. This applies to a whole range of somatic symptoms constituting the construct of somatization. There is hardly any mention of somatization in leading dermatological journals, in contrast to anxiety and depression which are frequently reported in eczema. We speculate that this under-recognition of somatization in the dermatological literature may correspond to under-recognition of this factor also in clinical practice. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Evolutionary immunology. A boost to immunity from nurse sharks.

PubMed

Parham, P

1995-07-01

A study of the nurse shark has revealed a type of rearranging gene that has yet to be seen in mammals; it encodes a secreted 'new antigen receptor' which, unlike shark immunoglobulin, revels in somatic hypermutation.

Mutational signatures associated with tobacco smoking in human cancer

DOE PAGES

Alexandrov, Ludmil B.; Ju, Young Seok; Haase, Kerstin; ...

2016-11-04

Tobacco smoking increases the risk of at least 17 classes of cancer. Here, we analyzed somatic mutations and DNA methylation in 5,243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA edi ting by APOBEC cytidine deaminases and of an endogenous clock-like mutational process.more » Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.« less

DNA Methylation Patterns in Normal Tissue Correlate more Strongly with Breast Cancer Status than Copy-Number Variants.

PubMed

Gao, Yang; Widschwendter, Martin; Teschendorff, Andrew E

2018-05-04

Normal tissue at risk of neoplastic transformation is characterized by somatic mutations, copy-number variation and DNA methylation changes. It is unclear however, which type of alteration may be more informative of cancer risk. We analyzed genome-wide DNA methylation and copy-number calls from the same DNA assay in a cohort of healthy breast samples and age-matched normal samples collected adjacent to breast cancer. Using statistical methods to adjust for cell type heterogeneity, we show that DNA methylation changes can discriminate normal-adjacent from normal samples better than somatic copy-number variants. We validate this important finding in an independent dataset. These results suggest that DNA methylation alterations in the normal cell of origin may offer better cancer risk prediction and early detection markers than copy-number changes. Copyright © 2018. Published by Elsevier B.V.

Mutational signatures associated with tobacco smoking in human cancer

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

Alexandrov, Ludmil B.; Ju, Young Seok; Haase, Kerstin

Tobacco smoking increases the risk of at least 17 classes of cancer. Here, we analyzed somatic mutations and DNA methylation in 5,243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA edi ting by APOBEC cytidine deaminases and of an endogenous clock-like mutational process.more » Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.« less

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2

PubMed Central

Bayne, Rosemary A.; Donnachie, Douglas J.; Kinnell, Hazel L.; Childs, Andrew J.; Anderson, Richard A.

2016-01-01

STUDY QUESTION Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? STUDY FINDING BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. WHAT IS KNOWN ALREADY Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. MAIN RESULTS AND THE ROLE OF CHANCE We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD  increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. LIMITATIONS, REASONS FOR CAUTION While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. WIDER IMPLICATIONS OF THE FINDINGS This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. LARGE SCALE DATA Not applicable. STUDY FUNDING/COMPETING INTERESTS This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. PMID:27385727

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2.

PubMed

Bayne, Rosemary A; Donnachie, Douglas J; Kinnell, Hazel L; Childs, Andrew J; Anderson, Richard A

2016-09-01

Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD  increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. Not applicable. This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy

NASA Astrophysics Data System (ADS)

Soundararajan, Venky; Aravamudan, Murali

2014-12-01

The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action - inspired by the Google page rank algorithm that unearths most ``globally connected'' websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs - up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site - encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows.

Brain Activity and Functional Connectivity Associated with Hypnosis.

PubMed

Jiang, Heidi; White, Matthew P; Greicius, Michael D; Waelde, Lynn C; Spiegel, David

2017-08-01

Hypnosis has proven clinical utility, yet changes in brain activity underlying the hypnotic state have not yet been fully identified. Previous research suggests that hypnosis is associated with decreased default mode network (DMN) activity and that high hypnotizability is associated with greater functional connectivity between the executive control network (ECN) and the salience network (SN). We used functional magnetic resonance imaging to investigate activity and functional connectivity among these three networks in hypnosis. We selected 57 of 545 healthy subjects with very high or low hypnotizability using two hypnotizability scales. All subjects underwent four conditions in the scanner: rest, memory retrieval, and two different hypnosis experiences guided by standard pre-recorded instructions in counterbalanced order. Seeds for the ECN, SN, and DMN were left and right dorsolateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and posterior cingulate cortex (PCC), respectively. During hypnosis there was reduced activity in the dACC, increased functional connectivity between the dorsolateral prefrontal cortex (DLPFC;ECN) and the insula in the SN, and reduced connectivity between the ECN (DLPFC) and the DMN (PCC). These changes in neural activity underlie the focused attention, enhanced somatic and emotional control, and lack of self-consciousness that characterizes hypnosis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Stem Cells in Mammalian Gonads.

PubMed

Wu, Ji; Ding, Xinbao; Wang, Jian

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

C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability.

PubMed

Korzelius, Jerome; The, Inge; Ruijtenberg, Suzan; Portegijs, Vincent; Xu, Huihong; Horvitz, H Robert; van den Heuvel, Sander

2011-02-15

DNA replication and its connection to M phase restraint are studied extensively at the level of single cells but rarely in the context of a developing animal. C. elegans lin-6 mutants lack DNA synthesis in postembryonic somatic cell lineages, while entry into mitosis continues. These mutants grow slowly and either die during larval development or develop into sterile adults. We found that lin-6 corresponds to mcm-4 and encodes an evolutionarily conserved component of the MCM2-7 pre-RC and replicative helicase complex. The MCM-4 protein is expressed in all dividing cells during embryonic and postembryonic development and associates with chromatin in late anaphase. Induction of cell cycle entry and differentiation continues in developing mcm-4 larvae, even in cells that went through abortive division. In contrast to somatic cells in mcm-4 mutants, the gonad continues DNA replication and cell division until late larval development. Expression of MCM-4 in the epidermis (also known as hypodermis) is sufficient to rescue the growth retardation and lethality of mcm-4 mutants. While the somatic gonad and germline show substantial ability to cope with lack of zygotic mcm-4 function, mcm-4 is specifically required in the epidermis for growth and survival of the whole organism. Thus, C. elegans mcm-4 has conserved functions in DNA replication and replication checkpoint control but also shows unexpected tissue-specific requirements. Copyright © 2010 Elsevier Inc. All rights reserved.

C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability

PubMed Central

Korzelius, Jerome; The, Inge; Ruijtenberg, Suzan; Portegijs, Vincent; Xu, Huihong; Horvitz, H. Robert; van den Heuvel, Sander

2012-01-01

DNA replication and its connection to M phase restraint are studied extensively at the level of single cells but rarely in the context of a developing animal. C. elegans lin-6 mutants lack DNA synthesis in postembryonic somatic cell lineages, while entry into mitosis continues. These mutants grow slowly and either die during larval development or develop into sterile adults. We found that lin-6 corresponds to mcm-4 and encodes an evolutionarily conserved component of the MCM2-7 pre-RC and replicative helicase complex. The MCM-4 protein is expressed in all dividing cells during embryonic and postembryonic development and associates with chromatin in late anaphase. Induction of cell-cycle entry and differentiation continues in developing mcm-4 larvae, even in cells that went through abortive division. In contrast to somatic cells in mcm-4 mutants, the gonad continues DNA replication and cell division until late larval development. Expression of MCM-4 in the epidermis (also known as hypodermis) is sufficient to rescue the growth retardation and lethality of mcm-4 mutants. While the somatic gonad and germline show substantial ability to cope with lack of zygotic mcm-4 function, mcm-4 is specifically required in the epidermis for growth and survival of the whole organism. Thus, C. elegans mcm-4 has conserved functions in DNA replication and replication checkpoint control but also shows unexpected tissue-specific requirements. PMID:21146520

DNA damage, EROD activity, condition indices, and their linkages with contaminants in female flounder (Platichthys flesus) from the southern Baltic Sea.

PubMed

Dabrowska, Henryka; Kopko, Orest; Góra, Agnieszka; Waszak, Ilona; Walkusz-Miotk, Jolanta

2014-10-15

The Baltic Sea is considered as one of the marine areas most exposed to human impacts. A variety of chemical contaminants pose a threat to the habitants. Female flounder (Platichthys flesus) collected from three locations in the southern Baltic Sea in February 2010 were examined for biomarkers of exposure to genotoxic agents (DNA damage), AhR-active contaminants (ethoxyresorufin-O-deethylase, EROD activity), and somatic condition indexes. Organochlorine contaminants (OCs) and polycyclic aromatic hydrocarbon (PAH) metabolites were also measured in individual flounder to evaluate the biological responses in the context of contaminant burden. The genotoxicity, mildly exceeding a background level, revealed a significant relationship with mono-ortho substituted PCB (m-oPCB). Hepatic EROD activity was highly induced, yet showed no association with any of the contaminants measured other than biliary 1-OH pyrene normalized to pigment absorbance. Significant negative relationships were observed for lipid-based OCs and the gonado-somatic index (GSI) as well as for Ʃm-oPCB concentrations and the condition factor (CF). Principal component analysis (PCA) revealed an overall connection between somatic condition indexes, biomarkers, and chemical variables. Of the three locations, flounder inhabiting the Gulf of Gdańsk had the greatest contaminant burden and appeared to be the most affected. Of great concern is the reduced GSI in this location which can be attributed to the effects of contaminants and warrants further investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory

PubMed Central

Kaji, Tomohiro; Ishige, Akiko; Hikida, Masaki; Taka, Junko; Hijikata, Atsushi; Kubo, Masato; Nagashima, Takeshi; Takahashi, Yoshimasa; Kurosaki, Tomohiro; Okada, Mariko; Ohara, Osamu

2012-01-01

One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell–dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell–dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen. PMID:23027924

Somatic embryogenesis in Carica papaya as affected by auxins and explants, and morphoanatomical-related aspects.

PubMed

Cipriano, Jamile L D; Cruz, Ana Cláudia F; Mancini, Karina C; Schmildt, Edilson R; Lopes, José Carlos; Otoni, Wagner C; Alexandre, Rodrigo S

2018-01-01

The aim of this study was to evaluate somatic embryogenesis in juvenile explants of the THB papaya cultivar. Apical shoots and cotyledonary leaves were inoculated in an induction medium composed of different concentrations of 2,4-D (6, 9, 12, 15 and 18 µM) or 4-CPA (19, 22, 25, 28 and 31 µM). The embryogenic calluses were transferred to a maturation medium for 30 days. Histological analysis were done during the induction and scanning electron microscopy after maturing. For both types of auxin, embryogenesis was achieved at higher frequencies with cotyledonary leaves incubated in induction medium than with apical shoots; except for callogenesis. The early-stage embryos (e.g., globular or heart-shape) predominated. Among the auxins, best results were observed in cotyledonary leaves induced with 4-CPA (25 µM). Histological analyses of the cotyledonary leaf-derived calluses confirmed that the somatic embryos (SEs) formed from parenchyma cells, predominantly differentiated via indirect and multicellular origin and infrequently via synchronized embryogenesis. The secondary embryogenesis was observed during induction and maturation phases in papaya THB cultivar. The combination of ABA (0.5 µM) and AC (15 g L-1) in maturation medium resulted in the highest somatic embryogenesis induction frequency (70 SEs callus-1) and the lowest percentage of early germination (4%).

Correlation of physical and genetic maps of human chromosome 16

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

Sutherland, G.R.

1991-01-01

This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentiallymore » 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.« less

Correlation of physical and genetic maps of human chromosome 16. Annual progress report, October 1, 1990--July 31, 1991

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

Sutherland, G.R.

1991-12-31

This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentiallymore » 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.« less

A framework for evaluating developmental defects at the cellular level: An example from ten maize anther mutants using morphological and molecular data.

PubMed

Egger, Rachel L; Walbot, Virginia

2016-11-01

In seed plants, anthers are critical for sexual reproduction, because they foster both meiosis and subsequent pollen development of male germinal cells. Male-sterile mutants are analyzed to define steps in anther development. Historically the major topics in these studies are meiotic arrest and post-meiotic gametophyte failure, while relatively few studies focus on pre-meiotic defects of anther somatic cells. Utilizing morphometric analysis we demonstrate that pre-meiotic mutants can be impaired in anticlinal or periclinal cell division patterns and that final cell number in the pre-meiotic anther lobe is independent of cell number changes of individual differentiated somatic cell types. Data derived from microarrays and from cell wall NMR analyses allow us to further refine our understanding of the onset of phenotypes. Collectively the data highlight that even minor deviations from the correct spatiotemporal pattern of somatic cell proliferation can result in male sterility in Zea mays. Copyright © 2016 Elsevier Inc. All rights reserved.

Male reproductive development: gene expression profiling of maize anther and pollen ontogeny

PubMed Central

Ma, Jiong; Skibbe, David S; Fernandes, John; Walbot, Virginia

2008-01-01

Background During flowering, central anther cells switch from mitosis to meiosis, ultimately forming pollen containing haploid sperm. Four rings of surrounding somatic cells differentiate to support first meiosis and later pollen dispersal. Synchronous development of many anthers per tassel and within each anther facilitates dissection of carefully staged maize anthers for transcriptome profiling. Results Global gene expression profiles of 7 stages representing 29 days of anther development are analyzed using a 44 K oligonucleotide array querying approximately 80% of maize protein-coding genes. Mature haploid pollen containing just two cell types expresses 10,000 transcripts. Anthers contain 5 major cell types and express >24,000 transcript types: each anther stage expresses approximately 10,000 constitutive and approximately 10,000 or more transcripts restricted to one or a few stages. The lowest complexity is present during meiosis. Large suites of stage-specific and co-expressed genes are identified through Gene Ontology and clustering analyses as functional classes for pre-meiotic, meiotic, and post-meiotic anther development. MADS box and zinc finger transcription factors with constitutive and stage-limited expression are identified. Conclusions We propose that the extensive gene expression of anther cells and pollen represents the key test of maize genome fitness, permitting strong selection against deleterious alleles in diploid anthers and haploid pollen. Because flowering plants show a substantial bias for male-sterile compared to female-sterile mutations, we propose that this fitness test is general. Because both somatic and germinal cells are transcriptionally quiescent during meiosis, we hypothesize that successful completion of meiosis is required to trigger maturation of anther somatic cells. PMID:19099579

Development of breast tumors in CHEK2, NBN/NBS1 and BLM mutation carriers does not commonly involve somatic inactivation of the wild-type allele.

PubMed

Suspitsin, Evgeny N; Yanus, Grigory A; Sokolenko, Anna P; Yatsuk, Olga S; Zaitseva, Olga A; Bessonov, Alexandr A; Ivantsov, Alexandr O; Heinstein, Valeria A; Klimashevskiy, Valery F; Togo, Alexandr V; Imyanitov, Evgeny N

2014-02-01

Somatic inactivation of the remaining allele is a characteristic feature of cancers arising in BRCA1 and BRCA2 mutation carriers, which determines their unprecedented sensitivity to some DNA-damaging agents. Data on tumor-specific status of the involved gene in novel varieties of hereditary breast cancer (BC) remain incomplete. We analyzed 32 tumors obtained from 30 patients with non-BRCA1/2 BC-associated germ-line mutations: 25 women were single mutation carriers (7 BLM, 15 CHEK2 and 3 NBN/NBS1) and 5 were double mutation carriers (2 BLM/BRCA1, 1 CHEK2/BLM, 1 CHEK2/BRCA1 and 1 NBN/BLM). Losses of heterozygosity affecting the wild-type allele were detected in none of the tumors from BLM mutation carriers, 3/18 (17 %) CHEK2-associated BC and 1/4 (25 %) NBN/NBS1-driven tumors. The remaining 28 BC were subjected to the sequence analysis of entire coding region of the involved gene; no somatic mutations were identified. We conclude that the tumor-specific loss of the wild-type allele is not characteristic for BC arising in CHEK2, NBN/NBS1 and BLM mutation carriers. Rarity of "second-hit" inactivation of the involved gene in CHEK2-, NBN/NBS1- and BLM-associated BC demonstrates their substantial biological difference from BRCA1/2-driven cancers and makes them poorly suitable for the clinical trials with cisplatin and PARP inhibitors.

Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells.

PubMed

Zhao, Ming-Tao; Shao, Ning-Yi; Hu, Shijun; Ma, Ning; Srinivasan, Rajini; Jahanbani, Fereshteh; Lee, Jaecheol; Zhang, Sophia L; Snyder, Michael P; Wu, Joseph C

2017-11-10

Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression. We profiled genome-wide transcriptional activity and a variety of epigenetic marks in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in human endothelial cells (CD31 + CD144 + ), cardiac progenitor cells (Sca-1 + ), fibroblasts (DDR2 + ), and their respective induced pluripotent stem cells. We uncovered 2 classes of regulatory DNA elements: class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. Both class I and class II regulatory elements exhibited stimulatory roles in nearby gene expression in a given cell type. However, class I promoters displayed more dominant regulatory effects on transcriptional abundance regardless of distal enhancers. Transcription factor network analysis indicated that human induced pluripotent stem cells and somatic cells from the heart selected their preferential regulatory elements to maintain cell type-specific gene expression. In addition, we validated the function of these enhancer elements in transgenic mouse embryos and human cells and identified a few enhancers that could possibly regulate the cardiac-specific gene expression. Given that a large number of genetic variants associated with human diseases are located in regulatory DNA elements, our study provides valuable resources for deciphering the epigenetic modulation of regulatory DNA elements that fine-tune spatiotemporal gene expression in human cardiac development and diseases. © 2017 American Heart Association, Inc.

Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family.

PubMed

Geyer, Felipe C; Berman, Samuel H; Marchiò, Caterina; Burke, Kathleen A; Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte Ky; Pareja, Fresia; Wen, Hannah Y; Hodi, Zoltan; Schnitt, Stuart J; Rakha, Emad A; Ellis, Ian O; Norton, Larry; Weigelt, Britta; Reis-Filho, Jorge S

2017-01-01

Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/ deletions, and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1-13) and 4.0 (1-7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA, and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12 or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions harboring frequent TP53 somatic mutations, and likely represent low-grade forms of triple-negative disease with no/minimal metastatic potential, of which a subset has the potential to progress to high-grade triple-negative breast cancer.

Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family

PubMed Central

Geyer, Felipe C; Berman, Samuel H.; Marchiò, Caterina; Burke, Kathleen A; Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte K Y; Pareja, Fresia; Wen, Hannah Y; Hodi, Zoltan; Schnitt, Stuart J; Rakha, Emad A; Ellis, Ian O; Norton, Larry; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1–13) and 4.0 (1–7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12, or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions harboring frequent TP53 somatic mutations, and likely represent low-grade forms of triple-negative disease with no/minimal metastatic potential, of which a subset has the potential to progress to high-grade triple-negative breast cancer. PMID:27713419

Antecedents and mediators of physical activity in endometrial cancer survivors: Increasing physical activity through Steps to Health

PubMed Central

Cox, Matthew; Carmack, Cindy; Hughes, Daniel; Baum, George; Brown, Jubilee; Jhingran, Anuja; Lu, Karen; Basen-Engquist, Karen

2015-01-01

OBJECTIVE Research shows that physical activity (PA) has a positive effect on cancer survivors including improving quality of life, improving physical fitness, and decreasing risk for cancer recurrence in some cancer types. Theory-based intervention approaches have identified self-efficacy as a potential mediator of PA interventions. This study examines the temporal relationships at four time points (T1–T4) between several social cognitive theory constructs and PA among a group of endometrial cancer survivors receiving a PA intervention. METHOD A sample of 98 sedentary women who were at least six months post treatment for endometrial cancer were given an intervention to increase their PA. The study tested whether modeling, physiological somatic sensations, and social support at previous time points predicted self-efficacy at later time points, which in turn predicted PA at later time points. RESULTS Results indicate that as physiological somatic sensations at T2 decrease, self-efficacy at T3 increases, which leads to an increase in PA at T4. This suggests that self-efficacy is a significant mediator between physiological somatic sensations and PA. Exploratory follow up models suggest model fit can be improved with the addition of contemporaneous effects between self-efficacy and PA at T3 and T4, changing the timing of the mediational relationships. CONCLUSIONS Physiological somatic sensations appear to be an important construct to target in order to increase PA in this population. While self-efficacy appeared to mediate the relationship between physiological somatic sensations and PA, the timing of this relationship is requires further study. PMID:25642840

Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations

PubMed Central

Yang, Fan; Petsalaki, Evangelia; Rolland, Thomas; Hill, David E.; Vidal, Marc; Roth, Frederick P.

2015-01-01

Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level. PMID:25794154

Is somatic comorbidity associated with more somatic symptoms, mental distress, or unhealthy lifestyle in elderly cancer survivors?

PubMed

Grov, Ellen Karine; Fosså, Sophie D; Dahl, Alv A

2009-06-01

The associations of lifestyle factors, somatic symptoms, mental distress, and somatic comorbidity in elderly cancer survivors have not been well studied. This study examines these associations among elderly cancer survivors (age >or=65 years) in a population-based sample. A cross-sectional comparative study of Norwegian elderly cancer survivors. Combining information from The Norwegian Cancer Registry, and by self-reporting, 972 elderly cancer survivors were identified, of whom 632 (65%) had somatic comorbidity and 340 did not. Elderly cancer survivors with somatic comorbidity had significantly higher BMI, more performed minimal physical activity, had more somatic symptoms, used more medication, and had more frequently seen a medical doctor than survivors without somatic comorbidity. In multivariable analyses, unhealthy lifestyle and higher somatic symptoms scores were significantly associated with cancer cases with somatic comorbidity. In univariate analyses those with somatic comorbidity were significantly older, had lower levels of education, higher proportions of BMI >or= 30, less physical activity, poorer self-rated health, higher somatic symptoms score, more mental distress, had more frequently seen a medical doctor last year, and more frequently used daily medication. Our outcome measures of lifestyle, somatic symptoms and mental distress were all significantly associated with somatic comorbidity in elderly cancer survivors, however only lifestyle and somatic symptoms were significant in multivariable analyses. In elderly cancer survivors not only cancer, but also somatic comorbidity, deserve attention. Such comorbidity is associated with unhealthy lifestyles, more somatic symptoms and mental distress which should be evaluated and eventually treated.

The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons.

PubMed

Albéri, Lavinia; Lintas, Alessandra; Kretz, Robert; Schwaller, Beat; Villa, Alessandro E P

2013-06-01

The reticular thalamic nucleus (RTN) of the mouse is characterized by an overwhelming majority of GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections mainly on thalamocortical neurons. The RTN neurons express high levels of the "slow Ca(2+) buffer" parvalbumin (PV) and are characterized by low-threshold Ca(2+) currents, I(T). We performed extracellular recordings in ketamine/xylazine anesthetized mice in the rostromedial portion of the RTN. In the RTN of wild-type and PV knockout (PVKO) mice we distinguished four types of neurons characterized on the basis of their firing pattern: irregular firing (type I), medium bursting (type II), long bursting (type III), and tonically firing (type IV). Compared with wild-type mice, we observed in the PVKOs the medium bursting (type II) more frequently than the long bursting type and longer interspike intervals within the burst without affecting the number of spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated with the kinetics of burst discharges. Ca(v)3.2 channels, which mediate the I(T) currents, were more localized to the somatic plasma membrane of RTN neurons in PVKO mice, whereas Ca(v)3.3 expression was similar in both genotypes. The immunoelectron microscopy analysis showed that Ca(v)3.2 channels were localized at active axosomatic synapses, thus suggesting that the differential localization of Ca(v)3.2 in the PVKOs may affect bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip showed that about one-third of the cell pairs tended to fire synchronously in both genotypes, independent of PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons but affects the distribution of Ca(v)3.2 channels and the dynamics of burst discharges of RTN cells, which in turn regulate the activity in the thalamocortical circuit.

[Value of the concept of attachment in somatic medicine].

PubMed

Attale, Catherine; M Consoli, Silla

2005-01-15

Since the nineteen nineties, the theory of attachment, initially developed in paedopsychiatry, has increasingly been applied to somatic medicine. The main fields explored have been the links between the individual's attachment style, response to stress and attitude towards health: seeking help from professionals, using health care systems and compliance to treatment. A so-called 'secure" attachment corresponds to an inner resource related to more constructive response to stressful events; an"insecure" attachment (including three categories: preoccupied,detached and fearful) can be considered a risk factor leading to less efficient adaptation to stress or "coping" with it. Attachment styles appear to influence attitudes towards health. Adults with secure attachment have positive expectations with regard to the help that care workers will provide and to the trust they can have in them. Detached-type insecure patients tend to minimize their signs of distress and do not necessarily seek help. Preoccupied-type insecure adults tend to maximize distress signals and excessively appeal to the medical corps. Fearful-type insecure patients only seek help in situations of great distress and rarely have faith in the health professionals.

The types of neurons of the somatic oculomotor nucleus in the European bison. Nissl and Golgi studies.

PubMed

Szteyn, S; Robak, A; Równiak, M

1997-01-01

The neuronal structure of the somatic oculomotor nucleus (SON) was studied on the basis of Nissl and Golgi preparations, obtained from mesencephalons of 4 European bisons. We distinguished four types of neurons in the investigated nucleus: 1. The large multipolar nerve cells with 5-8 thick dendritic trunks and a thin axon which emerges directly from the soma. These are the most numerous neurons in the SON. 2. The small multipolar neurons. These cells have 4-6 thick dendritic trunks. An axon arises mostly from initial segment of one of the dendrites. This type represents about 8% neurons of SON. 3. The triangular neurons. From perikaryon 3 thick dendritic trunks emerge. A thin axon arises directly from the cell body. These cells make about 10% neurons of SON. 4. The pear-shaped cells which have 1 or 2 dendritic trunks concentrate at one pole of the neurons. In the SON there are about 2% pear-shaped cells. Their features correspond to the features attributed by many authors to the interneurons.

Disposable Bioreactors for Plant Micropropagation and Mass Plant Cell Culture

NASA Astrophysics Data System (ADS)

Ducos, Jean-Paul; Terrier, Bénédicte; Courtois, Didier

Different types of bioreactors are used at Nestlé R&D Centre - Tours for mass propagation of selected plant varieties by somatic embryogenesis and for large scale culture of plants cells to produce metabolites or recombinant proteins. Recent studies have been directed to cut down the production costs of these two processes by developing disposable cell culture systems. Vegetative propagation of elite plant varieties is achieved through somatic embryogenesis in liquid medium. A pilot scale process has recently been set up for the industrial propagation of Coffea canephora (Robusta coffee). The current production capacity is 3.0 million embryos per year. The pre-germination of the embryos was previously conducted by temporary immersion in liquid medium in 10-L glass bioreactors. An improved process has been developed using a 10-L disposable bioreactor consisting of a bag containing a rigid plastic box ('Box-in-Bag' bioreactor), insuring, amongst other advantages, a higher light transmittance to the biomass due to its horizontal design. For large scale cell culture, two novel flexible plastic-based disposable bioreactors have been developed from 10 to 100 L working volumes, validated with several plant species ('Wave and Undertow' and 'Slug Bubble' bioreactors). The advantages and the limits of these new types of bioreactor are discussed, based mainly on our own experience on coffee somatic embryogenesis and mass cell culture of soya and tobacco.

Detection of mosaicism for the polymorphic variants in the 5'-UTR of hOGG1 by cloning and sequence analysis and pyrosequencing.

PubMed

Cao, Lili; Li, Tianfeng; Zhu, Yanbei; Zhou, Wei; Guo, Wenwen; Cai, Zhenming; Xie, Yuan; He, Xuan; Li, Xinxiu; Zhu, Dalong; Wang, Yaping

2013-04-01

Mosaicism refers to the presence of genetically distinct cell lines within an organism or a tissue. Somatic mosaicism exists in distinct populations of somatic cells and commonly arises as a result of somatic mutations, mainly in early embryonic development. SNPs are important markers that distinguish between different individuals in heterogeneous biological samples and contribute greatly to disease risk association studies. In this work, we investigated the relationship between the functional variants in the 5'-UTR of the hOGG1 gene and the risk of type 2 diabetes. Upon detection of the polymorphisms c.-53G>C, c.-23A>G, and c.-18G>T in the hOGG1 gene, we found that mosaicism was present in 3/28 (10.71%), 7/51 (13.73%), and 1/44 (2.27%) patients respectively, who were carriers of these single nucleotide variations, by cloning and sequence analysis and pyrosequencing. Statistical analysis showed that the frequency of the variation c.-23A>G in the hOGG1 5'-UTR in type 2 diabetic patients was significantly higher than that in healthy controls. However, sequencing of the mutant alleles in mosaic individuals showed weak peaks that may affect detection of the SNPs and impair association-based investigations. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC.

PubMed

Marcó, Sara; Pujol, Anna; Roca, Carles; Motas, Sandra; Ribera, Albert; Garcia, Miguel; Molas, Maria; Villacampa, Pilar; Melia, Cristian S; Sánchez, Víctor; Sánchez, Xavier; Bertolin, Joan; Ruberte, Jesús; Haurigot, Virginia; Bosch, Fatima

2016-09-01

Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches. © 2016. Published by The Company of Biologists Ltd.

Production of Prnp-/- goats by gene targeting in adult fibroblasts.

PubMed

Zhu, Caihong; Li, Bei; Yu, Guohua; Chen, Jianquan; Yu, Huiqing; Chen, Juan; Xu, Xujun; Wu, Youbing; Zhang, Aimin; Cheng, Guoxiang

2009-04-01

Homozygous mice devoid of functional Prnp are resistant to scrapie and prion propagation, but heterozygous mice for Prnp disruption still suffer from prion disease and prion deposition. We have previously generated heterozygous cloned goats with one allele of Prnp functional disruption. To obtain goats with both alleles of Prnp be disrupted which would be resistant to scrapie completely, a second-round gene targeting was applied to disrupt the wild type allele of Prnp in the heterozygous goats. By second-round gene targeting, we successfully disrupted the wild type allele of Prnp in primary Prnp (+/-) goat skin fibroblasts and obtained a Prnp (-/-) cell line without Prnp expression. This is the first report on successful targeting modification in primary adult somatic cells of animals. These cells were used as nuclear donors for somatic cell cloning to produce Prnp (-/-) goats. A total of 57 morulae or blastocytes developed from the reconstructed embryos were transferred to 31 recipients, which produced 7 pregnancies at day 35. At 73 days of gestation, we obtained one cloned fetus with Prnp (-/-) genotype. Our research not only indicated that multiple genetic modifications could be accomplished by multi-round gene targeting in primary somatic cells, but also provided strong evidence that gene targeting in adult cells other than fetal cells could be applied to introduce precise genetic modifications in animals without destroying the embryos.

Determining the Origin of Human Germinal Center B Cell-Derived Malignancies.

PubMed

Seifert, Marc; Küppers, Ralf

2017-01-01

Most human B cell lymphomas originate from germinal center (GC) B cells. This is partly caused by the high proliferative activity of GC B cells and the remodeling processes acting at the immunoglobulin (Ig) loci of these cells, i.e., somatic hypermutation and class-switching. Mistargeting of these processes can cause chromosomal translocations, and the hypermutation machinery may also target non-Ig genes. As somatic hypermutation is exclusively active in GC B cells, the presence of somatic mutations in rearranged IgV genes is a standard criterium for a GC or post-GC B cell origin of lymphomas. Beyond this, ongoing somatic hypermutation during lymphoma clone expansion indicates that the lymphoma has an active GC B cell differentiation program. The proto-oncogene BCL6 is specifically expressed in GC B cells and also acquires somatic mutations as a physiological by-product of the somatic hypermutation process, albeit at a lower level than IgV genes. Thus, detection of BCL6 mutations is a further genetic trait of a GC experience of a B cell lymphoma. Typically, B cell lymphomas retain key features of their specific cells of origin, including a differentiation stage-specific gene expression pattern. This is at least partly due to genetic lesions, which "freeze" the lymphoma cells at the differentiation stage at which the transformation occurred. Therefore, identification of the normal B cell subset with the most similar gene expression pattern to a particular type of B cell lymphoma has been instrumental to deduce the precise cell of origin of lymphomas.We present here protocols to analyze human B cell lymphomas for a potential origin from GC B cells by determining the presence of mutations in rearranged IgV genes and the BCL6 gene, and by comparing the gene expression pattern of lymphoma cells with those of normal B cell subsets by genechip or RNA-sequencing analysis.

Coevolution of female and male genital components to avoid genital size mismatches in sexually dimorphic spiders.

PubMed

Lupše, Nik; Cheng, Ren-Chung; Kuntner, Matjaž

2016-08-17

In most animal groups, it is unclear how body size variation relates to genital size differences between the sexes. While most morphological features tend to scale with total somatic size, this does not necessarily hold for genitalia because divergent evolution in somatic size between the sexes would cause genital size mismatches. Theory predicts that the interplay of female-biased sexual size dimorphism (SSD) and sexual genital size dimorphism (SGD) should adhere to the 'positive genital divergence', the 'constant genital divergence', or the 'negative genital divergence' model, but these models remain largely untested. We test their validity in the spider family Nephilidae known for the highest degrees of SSD among terrestrial animals. Through comparative analyses of sex-specific somatic and genital sizes, we first demonstrate that 99 of the 351 pairs of traits are phylogenetically correlated. Through factor analyses we then group these traits for MCMCglmm analyses that test broader correlation patterns, and these reveal significant correlations in 10 out of the 36 pairwise comparisons. Both types of analyses agree that female somatic and internal genital sizes evolve independently. While sizes of non-intromittent male genital parts coevolve with male body size, the size of the intromittent male genital parts is independent of the male somatic size. Instead, male intromittent genital size coevolves with female (external and, in part, internal) genital size. All analyses also agree that SGD and SSD evolve independently. Internal dimensions of female genitalia evolve independently of female body size in nephilid spiders, and similarly, male intromittent genital size evolves independently of the male body size. The size of the male intromittent organ (the embolus) and the sizes of female internal and external genital components thus seem to respond to selection against genital size mismatches. In accord with these interpretations, we reject the validity of the existing theoretical models of genital and somatic size dimorphism in spiders.

Billions of basepairs of recently expanded, repetitive sequences are eliminated from the somatic genome during copepod development.

PubMed

Sun, Cheng; Wyngaard, Grace; Walton, D Brian; Wichman, Holly A; Mueller, Rachel Lockridge

2014-03-11

Chromatin diminution is the programmed deletion of DNA from presomatic cell or nuclear lineages during development, producing single organisms that contain two different nuclear genomes. Phylogenetically diverse taxa undergo chromatin diminution--some ciliates, nematodes, copepods, and vertebrates. In cyclopoid copepods, chromatin diminution occurs in taxa with massively expanded germline genomes; depending on species, germline genome sizes range from 15 - 75 Gb, 12-74 Gb of which are lost from pre-somatic cell lineages at germline--soma differentiation. This is more than an order of magnitude more sequence than is lost from other taxa. To date, the sequences excised from copepods have not been analyzed using large-scale genomic datasets, and the processes underlying germline genomic gigantism in this clade, as well as the functional significance of chromatin diminution, have remained unknown. Here, we used high-throughput genomic sequencing and qPCR to characterize the germline and somatic genomes of Mesocyclops edax, a freshwater cyclopoid copepod with a germline genome of ~15 Gb and a somatic genome of ~3 Gb. We show that most of the excised DNA consists of repetitive sequences that are either 1) verifiable transposable elements (TEs), or 2) non-simple repeats of likely TE origin. Repeat elements in both genomes are skewed towards younger (i.e. less divergent) elements. Excised DNA is a non-random sample of the germline repeat element landscape; younger elements, and high frequency DNA transposons and LINEs, are disproportionately eliminated from the somatic genome. Our results suggest that germline genome expansion in M. edax reflects explosive repeat element proliferation, and that billions of base pairs of such repeats are deleted from the somatic genome every generation. Thus, we hypothesize that chromatin diminution is a mechanism that controls repeat element load, and that this load can evolve to be divergent between tissue types within single organisms.

Billions of basepairs of recently expanded, repetitive sequences are eliminated from the somatic genome during copepod development

PubMed Central

2014-01-01

Background Chromatin diminution is the programmed deletion of DNA from presomatic cell or nuclear lineages during development, producing single organisms that contain two different nuclear genomes. Phylogenetically diverse taxa undergo chromatin diminution — some ciliates, nematodes, copepods, and vertebrates. In cyclopoid copepods, chromatin diminution occurs in taxa with massively expanded germline genomes; depending on species, germline genome sizes range from 15 – 75 Gb, 12–74 Gb of which are lost from pre-somatic cell lineages at germline – soma differentiation. This is more than an order of magnitude more sequence than is lost from other taxa. To date, the sequences excised from copepods have not been analyzed using large-scale genomic datasets, and the processes underlying germline genomic gigantism in this clade, as well as the functional significance of chromatin diminution, have remained unknown. Results Here, we used high-throughput genomic sequencing and qPCR to characterize the germline and somatic genomes of Mesocyclops edax, a freshwater cyclopoid copepod with a germline genome of ~15 Gb and a somatic genome of ~3 Gb. We show that most of the excised DNA consists of repetitive sequences that are either 1) verifiable transposable elements (TEs), or 2) non-simple repeats of likely TE origin. Repeat elements in both genomes are skewed towards younger (i.e. less divergent) elements. Excised DNA is a non-random sample of the germline repeat element landscape; younger elements, and high frequency DNA transposons and LINEs, are disproportionately eliminated from the somatic genome. Conclusions Our results suggest that germline genome expansion in M. edax reflects explosive repeat element proliferation, and that billions of base pairs of such repeats are deleted from the somatic genome every generation. Thus, we hypothesize that chromatin diminution is a mechanism that controls repeat element load, and that this load can evolve to be divergent between tissue types within single organisms. PMID:24618421

Identification of Epigenetic Changes in Prostate Cancer using Induced Pluripotent Stem Cells

DTIC Science & Technology

2014-04-01

somatic cells in human iPS cells. Nat Cell Bioi, 13: 541, 2011 5. Polo, J. M., Liu, S., Figueroa , M. E. et al.: Cell type of origin influences the...human iPS cells. Nat Cell Bioi 13: 5•1 \\ - 5•19. 18. Poloj:\\ə, Lu S, Figueroa ME, Kulalert W, Eminli S, ct a!. (20 10) Cell type of origin

Mental and somatic health in a non-clinical sample 10 years after a diagnosis of encopresis.

PubMed

Hultén, Ib; Jonsson, Jakob; Jonsson, Carl-Otto

2005-12-01

The aim of this study was to assess the relation between the diagnosis of encopresis at 8 and 10 years of age, and mental and somatic health 10 years later. The importance of type of encopresis (primary or secondary) at 8 years was also studied. Subjects were a non-clinical encopretic sample (N=73) and control subjects (N=75) [2]. Seven assessment variables from conscription surveys provided information about mental and somatic health status at 18 years of age. Former encopretics (n=66) did not differ significantly from the controls (n=67) at 18 years of age, although there were consistent, small negative differences. The boys who at 10 years of age had still been encopretic did not differ significantly at 18 years of age from the boys who at 10 years had recovered from encopresis, and the signs indicating the small differences varied. For former primary and secondary encopretic boys, there were two significant differences, the men in the secondary group being more often exempted from conscription than the primary group and the control cases. The results indicate that boys with non-clinical encopresis show only small, if any, mental and somatic disturbances at the beginning of adulthood. Comprehensive investigations of encopretic patients are recommended as important clinical problems, in addition to encopresis, might be present.

Reproductive energy expenditure and changes in body morphology for a population of Chinook salmon Oncorhynchus tshawytscha with a long distance migration.

PubMed

Bowerman, T E; Pinson-Dumm, A; Peery, C A; Caudill, C C

2017-05-01

Energetic demands of a long freshwater migration, extended holding period, gamete development and spawning were evaluated for a population of stream-type Chinook salmon Oncorhynchus tshawytscha. Female and male somatic mass decreased by 24 and 21%, respectively, during migration and by an additional 18 and 12% during holding. Between freshwater entry and death after spawning, females allocated 14% of initial somatic energy towards gonad development and 78% for metabolism (46, 25 and 7% during migration, holding and spawning, respectively). Males used only 2% of initial somatic energy for gonad development and 80% on metabolic costs, as well as an increase in snout length (41, 28 and 11% during migration, holding and spawning, respectively). Individually marked O. tshawytscha took between 27 and 53 days to migrate 920 km. Those with slower travel times through the dammed section of the migration corridor arrived at spawning grounds with less muscle energy than faster migrants. Although energy depletion did not appear to be the proximate cause of death in most pre-spawn mortalities, average final post-spawning somatic energy densities were low at 3·6 kJ g -1 in females and 4·1 kJ g -1 in males, consistent with the concept of a minimum energy threshold required to sustain life in semelparous salmonids. © 2017 The Fisheries Society of the British Isles.

The Association Between Headaches and Temporomandibular Disorders is Confounded by Bruxism and Somatic Symptoms.

PubMed

van der Meer, Hedwig A; Speksnijder, Caroline M; Engelbert, Raoul H H; Lobbezoo, Frank; Nijhuis-van der Sanden, Maria W G; Visscher, Corine M

2017-09-01

The objective of this observational study was to establish the possible presence of confounders on the association between temporomandibular disorders (TMD) and headaches in a patient population from a TMD and Orofacial Pain Clinic. Several subtypes of headaches have been diagnosed: self-reported headache, (probable) migraine, (probable) tension-type headache, and secondary headache attributed to TMD. The presence of TMD was subdivided into 2 subtypes: painful TMD and function-related TMD. The associations between the subtypes of TMD and headaches were evaluated by single regression models. To study the influence of possible confounding factors on this association, the regression models were extended with age, sex, bruxism, stress, depression, and somatic symptoms. Of the included patients (n=203), 67.5% experienced headaches. In the subsample of patients with a painful TMD (n=58), the prevalence of self-reported headaches increased to 82.8%. The associations found between self-reported headache and (1) painful TMD and (2) function-related TMD were confounded by the presence of somatic symptoms. For probable migraine, both somatic symptoms and bruxism confounded the initial association found with painful TMD. The findings of this study imply that there is a central working mechanism overlapping TMD and headache. Health care providers should not regard these disorders separately, but rather look at the bigger picture to appreciate the complex nature of the diagnostic and therapeutic process.

Proteome analysis during pod, zygotic and somatic embryo maturation of Theobroma cacao.

PubMed

Niemenak, Nicolas; Kaiser, Edward; Maximova, Siela N; Laremore, Tatiana; Guiltinan, Mark J

2015-05-15

Two dimensional electrophoresis and nano-LC-MS were performed in order to identify alterations in protein abundance that correlate with maturation of cacao zygotic and somatic embryos. The cacao pod proteome was also characterized during development. The recently published cacao genome sequence was used to create a predicted proteolytic fragment database. Several hundred protein spots were resolved on each tissue analysis, of which 72 variable spots were subjected to MS analysis, resulting in 49 identifications. The identified proteins represent an array of functional categories, including seed storage, stress response, photosynthesis and translation factors. The seed storage protein was strongly accumulated in cacao zygotic embryos compared to their somatic counterpart. However, sucrose treatment (60 g L(-1)) allows up-regulation of storage protein in SE. A high similarity in the profiles of acidic proteins was observed in mature zygotic and somatic embryos. Differential expression in both tissues was observed in proteins having high pI. Several proteins were detected exclusively in fruit tissues, including a chitinase and a 14-3-3 protein. We also identified a novel cacao protein related to known mabinlin type sweet storage proteins. Moreover, the specific presence of thaumatin-like protein, another sweet protein, was also detected in fruit tissue. We discuss our observed correlations between protein expression profiles, developmental stage and stress responses. Copyright © 2015 Elsevier GmbH. All rights reserved.

Bluephage: A rapid method for the detection of somatic coliphages used as indicators of fecal pollution in water.

PubMed

Muniesa, M; Ballesté, E; Imamovic, L; Pascual-Benito, M; Toribio-Avedillo, D; Lucena, F; Blanch, A R; Jofre, J

2018-01-01

The use of somatic coliphages as indicators of fecal and viral pollution in water and food has great potential due to the reliability, reproducibility, speed and cost effectiveness of methods for their detection. Indeed, several countries already use this approach in their water management policies. Although standardized protocols for somatic coliphage detection are available, user-friendly commercial kits would facilitate their routine implementation in laboratories. The new method presented here allows detection of up to 1 somatic coliphage in under 3.5 h, well within one working day. The method is based on a modified Escherichia coli strain with knocked-out uidB and uidC genes, which encode the transport of glucuronic acid inside cells, and overexpressing uidA, which encodes the enzyme β-glucuronidase. The enzyme accumulated in the bacterial cells only has contact with its substrate after cell lysis, such as that caused by phages, since the strain cannot internalize the substrate. When the enzyme is released into the medium, which contains a chromogen analogous to glucuronic acid, it produces a change of color from yellow to dark blue. This microbiological method for the determination of fecal pollution via the detection of culturable microorganisms can be applied to diverse sample types and volumes for qualitative (presence/absence) and quantitative analysis and is the fastest reported to date. Copyright © 2017 Elsevier Ltd. All rights reserved.

Illness behavior.

PubMed

Sirri, Laura; Grandi, Silvana

2012-01-01

The term illness behavior was introduced by Mechanic and Volkart to describe the individuals' different ways to respond to their own health status. Pilowsky's concept of abnormal illness behavior encompasses several clinical conditions characterized by a maladaptive mode of experiencing, perceiving, evaluating and responding to one's own health status. The concept of somatization was criticized because it implies the presence of psychological distress or an underlying psychiatric disturbance when an organic cause for somatic symptoms is not found. Thus, more atheoretical terms , such as functional somatic symptoms and medically unexplained symptoms, were introduced. Both Kellner's Symptom Questionnaire and Derogatis' Symptom Checklist-90 include a scale for somatic symptoms, and other questionnaires were specifically designed to measure their frequency and severity. Kellner's Illness Attitude Scales appear to be the gold standard for the measurement of the hypochondriacal spectrum, which includes several clinical conditions, such as nosophobia, thanatophobia and health anxiety. The assessment of illness denial should consider that a certain degree of denial may sometimes prevent patients from overwhelming psychological distress resulting from life-threatening or stigmatized diseases. Denial may concern both physical and psychiatric symptoms. Specific instruments are available for both types of denial. The cognitive and emotional representations developed by subjects when they have to cope with an illness or a perceived health threat are subsumed under the concept of illness perception and may be assessed by the Brief Illness Perception Questionnaire. Copyright © 2012 S. Karger AG, Basel.

Epstein-Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction.

PubMed

Kurth, Julia; Hansmann, Martin-Leo; Rajewsky, Klaus; Küppers, Ralf

2003-04-15

To assess the impact of the germinal center (GC) reaction on viral spread in Epstein-Barr virus (EBV) infection, we isolated EBV(+) GC B cells from the tonsils of two infectious mononucleosis patients, sequenced their rearranged V genes, and determined expression of the EBV latency genes EBV nuclear antigen 2 and latent membrane protein 1. Most EBV(+) GC B cells belonged to clones of cells harboring somatically mutated V gene rearrangements. Ongoing somatic hypermutation, the hallmark of the GC reaction, was seen only in uninfected GC B cell clones, not in EBV(+) B cell clones. Thus, in infectious mononucleosis, GC and/or memory B cells are directly infected by EBV and expand without somatic hypermutation, whereas the GC passage of EBV-infected naive B cells does not contribute detectably to the generation of infected memory B cells, the main reservoir of EBV during persistence. Most, if not all, EBV-infected cells in GCs exhibited an unusual EBV gene expression pattern in that they were positive for EBV nuclear antigen 2 but negative for latent membrane protein 1. Although the three main types of EBV-associated B cell lymphomas (Burkitt's, Hodgkin's, and posttransplant lymphomas) presumably are derived from GC B cells, EBV(+) GC B cells resembling these EBV(+) GC B cell lymphomas in terms of EBV gene expression and somatic hypermutation pattern could not be identified.

Expression levels of DNA replication and repair genes predict regional somatic repeat instability in the brain but are not altered by polyglutamine disease protein expression or age.

PubMed

Mason, Amanda G; Tomé, Stephanie; Simard, Jodie P; Libby, Randell T; Bammler, Theodor K; Beyer, Richard P; Morton, A Jennifer; Pearson, Christopher E; La Spada, Albert R

2014-03-15

Expansion of CAG/CTG trinucleotide repeats causes numerous inherited neurological disorders, including Huntington's disease (HD), several spinocerebellar ataxias and myotonic dystrophy type 1. Expanded repeats are genetically unstable with a propensity to further expand when transmitted from parents to offspring. For many alleles with expanded repeats, extensive somatic mosaicism has been documented. For CAG repeat diseases, dramatic instability has been documented in the striatum, with larger expansions noted with advancing age. In contrast, only modest instability occurs in the cerebellum. Using microarray expression analysis, we sought to identify the genetic basis of these regional instability differences by comparing gene expression in the striatum and cerebellum of aged wild-type C57BL/6J mice. We identified eight candidate genes enriched in cerebellum, and validated four--Pcna, Rpa1, Msh6 and Fen1--along with a highly associated interactor, Lig1. We also explored whether expression levels of mismatch repair (MMR) proteins are altered in a line of HD transgenic mice, R6/2, that is known to show pronounced regional repeat instability. Compared with wild-type littermates, MMR expression levels were not significantly altered in R6/2 mice regardless of age. Interestingly, expression levels of these candidates were significantly increased in the cerebellum of control and HD human samples in comparison to striatum. Together, our data suggest that elevated expression levels of DNA replication and repair proteins in cerebellum may act as a safeguard against repeat instability, and may account for the dramatically reduced somatic instability present in this brain region, compared with the marked instability observed in the striatum.

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

PubMed

Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

2015-01-01

Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

No increase in prevalence of somatization in functional vs organic dyspepsia: a cross-sectional survey.

PubMed

Gracie, D J; Bercik, P; Morgan, D G; Bolino, C; Pintos-Sanchez, M I; Moayyedi, P; Ford, A C

2015-07-01

Psychological factors are associated with functional gastrointestinal (GI) disorders. Literature suggests that somatization is associated with functional dyspepsia (FD). However, the relationship between organic dyspepsia (OD), FD, and FD subtypes and somatization is poorly described. We aimed to examine this issue in a cross-sectional study of secondary care patients. Demographic and GI symptom data were collected from 4224 adult patients via the Rome III questionnaire. Somatization data were collected using the patient health questionnaire-12. Mean somatization score and number of somatic symptoms were compared between patients with organic and FD, and between FD subtypes using analysis of variance. The same comparison was undertaken for the proportion of patients reporting individual somatic symptoms. Exactly, 783 patients met criteria for dyspepsia, of whom 231 (29.5%) had organic disease following upper GI endoscopy. Mean somatization scores and number of somatic symptoms were no higher in functional vs OD (p = 0.23; p = 0.19). In addition, while the prevalence of somatization in FD was relatively high, there was no difference in severity of somatization in FD subgroups. Somatization is associated with functional and OD to the same degree. Overall severity of somatization did not appear to vary according to FD subtype. © 2015 John Wiley & Sons Ltd.

Identifying Candidate Reprogramming Genes in Mouse Induced Pluripotent Stem Cells.

PubMed

Gao, Fang; Li, Jingyu; Zhang, Heng; Yang, Xu; An, Tiezhu

2017-08-01

Factor-based induced reprogramming approaches have tremendous potential for human regenerative medicine, but the efficiencies of these approaches are still low. In this study, we analyzed the global transcriptional profiles of mouse induced pluripotent stem cells (miPSCs) and mouse embryonic stem cells (mESCs) from seven different labs and present here the first successful clustering according to cell type, not by lab of origin. We identified 2131 different expression genes (DEs) as candidate pluripotency-associated genes by comparing mESCs/miPSCs with somatic cells and 720 DEs between miPSCs and mESCs. Interestingly, there was a significant overlap between the two DE sets. Therefore, we defined the overlap DEs as "consensus DEs" including 313 miPSC-specific genes expressed at a higher level in miPSCs versus mESCs and 184 mESC-specific genes in total and reasoned that these may contribute to the differences in pluripotency between mESCs and miPSCs. A classification of "consensus DEs" according to their different expression levels between somatic cells and mESCs/miPSCs shows that 86% of the miPSC-specific genes are more highly expressed in somatic cells, while 73% of mESC-specific genes are highly expressed in mESCs/miPSCs, indicating that the miPSCs have not efficiently silenced the expression pattern of the somatic cells from which they are derived and failed to completely induce the genes with high expression levels in mESCs. We further revealed a strong correlation between oocyte-enriched factors and insufficiently induced mESC-specific genes and identified 11 hub genes via network analysis. In light of these findings, we postulated that these key hub genes might not only drive somatic cell nuclear transfer (SCNT) reprogramming but also augment the efficiency and quality of miPSC reprogramming.

Interspecies somatic cell nucleus transfer with porcine oocytes as recipients: A novel bioassay system for assessing the competence of canine somatic cells to develop into embryos.

PubMed

Sugimura, S; Narita, K; Yamashiro, H; Sugawara, A; Shoji, T; Terashita, Y; Nishimori, K; Konno, T; Yoshida, M; Sato, E

2009-09-01

Interspecies somatic cell nucleus transfer (iSCNT) could be a useful bioassay system for assessing the ability of mammalian somatic cells to develop into embryos. To examine this possibility, we performed canine iSCNT using porcine oocytes, allowed to mature in vitro, as recipients. Canine fibroblasts from the tail tips and dewclaws of a female poodle (Fp) and a male poodle (Mp) were used as donors. We demonstrated that the use of porcine oocytes induced blastocyst formation in the iSCNT embryos cultured in porcine zygote medium-3. In Fp and Mp, the rate of blastocyst formation from cleaved embryos (Fp: 6.3% vs. 22.4%; and Mp: 26.1% vs. 52.4%) and the number of cells at the blastocyst stage (Fp: 30.7 vs. 60.0; and Mp: 27.2 vs. 40.1) were higher in the embryos derived from dewclaw cells than in those derived from tail-tip cells (P<0.05). The use of donor cells of any type in later passages decreased the rate of blastocyst formation. Treatment with trichostatin-A did not improve the rate of blastocyst formation from cleaved dewclaw cell-derived embryos but did so in the embryos derived from the tail-tip cells of Fp. Only blastocysts derived from dewclaw cells of Mp developed outgrowths. However, outgrowth formation was retrieved in the embryos derived from dewclaw cells of Fp by aggregation at the 4-cell stage. We inferred that iSCNT performed using porcine oocytes as recipients could represent a novel bioassay system for evaluating the developmental competence of canine somatic cells.

Simultaneous Characterization of Somatic Events and HPV-18 Integration in a Metastatic Cervical Carcinoma Patient Using DNA and RNA Sequencing

PubMed Central

Liang, Winnie S.; Aldrich, Jessica; Nasser, Sara; Kurdoglu, Ahmet; Phillips, Lori; Reiman, Rebecca; McDonald, Jacquelyn; Izatt, Tyler; Christoforides, Alexis; Baker, Angela; Craig, Christine; Egan, Jan B.; Chase, Dana M.; Farley, John H.; Bryce, Alan H.; Stewart, A. Keith; Borad, Mitesh J.; Carpten, John D.; Craig, David W.; Monk, Bradley J.

2014-01-01

Objective Integration of carcinogenic human papillomaviruses (HPVs) into the host genome is a significant tumorigenic factor in specific cancers including cervical carcinoma. Although major strides have been made with respect to HPV diagnosis and prevention, identification and development of efficacious treatments for cervical cancer patients remains a goal and thus requires additional detailed characterization of both somatic events and HPV integration. Given this need, the goal of this study was to use the next generation sequencing to simultaneously evaluate somatic alterations and expression changes in a patient’s cervical squamous carcinoma lesion metastatic to the lung and to detect and analyze HPV infection in the same sample. Materials and Methods We performed tumor and normal exome, tumor and normal shallow whole-genome sequencing, and RNA sequencing of the patient’s lung metastasis. Results We generated over 1.2 billion mapped reads and identified 130 somatic point mutations and indels, 21 genic translocations, 16 coding regions demonstrating copy number changes, and over 36 genes demonstrating altered expression in the tumor (corrected P < 0.05). Sequencing also revealed the HPV type 18 (HPV-18) integration in the metastasis. Using both DNA and RNA reads, we pinpointed 3 major events indicating HPV-18 integration into an intronic region of chromosome 6p25.1 in the patient’s tumor and validated these events with Sanger sequencing. This integration site has not been reported for HPV-18. Conclusions We demonstrate that DNA and RNA sequencing can be used to concurrently characterize somatic alterations and expression changes in a biopsy and delineate HPV integration at base resolution in cervical cancer. Further sequencing will allow us to better understand the molecular basis of cervical cancer pathogenesis. PMID:24418928

[Pathomorphosis of anxiety disorder in patients with intestinal dysbiosis].

PubMed

Uspenskiĭ, Iu P; Balukova, E V

2009-01-01

It is known, that anxiety is one of the most wide-spread mental disorders in-between psychiatric state and it takes part in pathogenesis a lot of somatic diseases as well. At the same time the host bowel microbiota participates in metabolic control of vital human functions such as mood and behavioural reactions. This title connection reveals some new therapeutic opportunity in treatment of psychiatric disorders that based on using with probiotics. In case non-clinically significant anxiety it is claimed to use probiotic (Enterol) however in case clinically significant anxiety it is claimed to use non-benzodiazepine tranquilizer (Stresam).

Gene expression and metabolite profiling of gibberellin biosynthesis during induction of somatic embryogenesis in Medicago truncatula Gaertn

PubMed Central

Igielski, Rafał

2017-01-01

Gibberellins (GAs) are involved in the regulation of numerous developmental processes in plants including zygotic embryogenesis, but their biosynthesis and role during somatic embryogenesis (SE) is mostly unknown. In this study we show that during three week- long induction phase, when cells of leaf explants from non-embryogenic genotype (M9) and embryogenic variant (M9-10a) were forming the callus, all the bioactive gibberellins from non-13-hydroxylation (GA4, GA7) and 13-hydroxylation (GA1, GA5, GA3, GA6) pathways were present, but the contents of only a few of them differed between the tested lines. The GA53 and GA19 substrates synthesized by the 13-hydroxylation pathway accumulated specifically in the M9-10a line after the first week of induction; subsequently, among the bioactive gibberellins detected, only the content of GA3 increased and appeared to be connected with acquisition of embryogenic competence. We fully annotated 20 Medicago truncatula orthologous genes coding the enzymes which catalyze all the known reactions of gibberellin biosynthesis. Our results indicate that, within all the genes tested, expression of only three: MtCPS, MtGA3ox1 and MtGA3ox2, was specific to embryogenic explants and reflected the changes observed in GA53, GA19 and GA3 contents. Moreover, by analyzing expression of MtBBM, SE marker gene, we confirmed the inhibitory effect of manipulation in GAs metabolism, applying exogenous GA3, which not only impaired the production of somatic embryos, but also significantly decreased expression of this gene. PMID:28750086

Depression and hypochondriasis in family practice patients with somatization disorder.

PubMed

Oxman, T E; Barrett, J

1985-10-01

The relationships specified in DSM-III between somatization disorder and depression, and somatization disorder and hypochondriasis require further validation and easier methods of detection for use by primary care physicians. The authors investigated hypochondriacal and depressive symptoms in 13 family practice outpatients with somatization disorder. Pain complaints and depressive symptomatology were present in over 75% of this group, while hypochondriacal symptoms were present in 38%. The mean score on the somatization scale of the Hopkins Symptom Check List (HSCL-90) was greater than that reported for any other group. These findings support the separation of somatization disorder and hypochondriasis and suggest the need for better delineation of depressive subtypes in somatization disorder. The somatization scale of the HSCL-90 should be a useful screen for somatization disorder in future research.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases.

PubMed

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and "others"). We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and "true" effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. The differences in reliability between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

PubMed Central

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains. PMID:27336301

Induced adult stem (iAS) cells and induced transit amplifying progenitor (iTAP) cells-a possible alternative to induced pluripotent stem (iPS) cells?

PubMed

Heng, Boon Chin; Richards, Mark; Ge, Zigang; Shu, Yimin

2010-02-01

The successful derivation of iPSC lines effectively demonstrates that it is possible to reset the 'developmental clock' of somatic cells all the way back to the initial embryonic state. Hence, it is plausible that this clock may instead be turned back half-way to a less immature developmental stage that is more directly applicable to clinical therapeutic applications or for in vitro pharmacology/toxicology screening assays. Such a suitable developmental state is postulated to be either the putative transit amplifying progenitor stage or adult stem cell stage. It is hypothetically possible to reprogram mature and terminally differentiated somatic cells back to the adult stem cell or transit amplifying progenitor stage, in a manner similar to the derivation of iPSC. It is proposed that the terminology 'Induced Adult Stem Cells' (iASC) or 'Induced Transit Amplifying Progenitor Cells' (iTAPC) be used to described such reprogrammed somatic cells. Of particular interest, is the possibility of resetting the developmental clock of mature differentiated somatic cells of the mesenchymal lineage, explanted from adipose tissue, bone marrow and cartilage. The putative adult stem cell sub-population from which these cells are derived, commonly referred to as 'mesenchymal stem cells', are highly versatile and hold much therapeutic promise in regenerative medicine, as attested to by numerous human clinical trials and animal studies. Perhaps it may be appropriate to term such reprogrammed cells as 'Induced Mesenchymal Stem Cells' (iMSC) or as 'Induced Mesenchumal Progenitor Cells' (iMPC). Given that cells from the same organ/tissue will share some commonalities in gene expression, we hypothesize that the generation of iASC or iTAPC would be more efficient as compared to iPSC generation, since a common epigenetic program must exist between the reprogrammed cells, adult stem cell or progenitor cell types and terminally differentiated cell types from the same organ/tissue.

Differential contribution of Kv4-containing channels to A-type, voltage-gated potassium currents in somatic and visceral dorsal root ganglion neurons.

PubMed

Yunoki, Takakazu; Takimoto, Koichi; Kita, Kaori; Funahashi, Yasuhito; Takahashi, Ryosuke; Matsuyoshi, Hiroko; Naito, Seiji; Yoshimura, Naoki

2014-11-15

Little is known about electrophysiological differences of A-type transient K(+) (KA) currents in nociceptive afferent neurons that innervate somatic and visceral tissues. Staining with isolectin B4 (IB4)-FITC classifies L6-S1 dorsal root ganglion (DRG) neurons into three populations with distinct staining intensities: negative to weak, moderate, and intense fluorescence signals. All IB4 intensely stained cells are negative for a fluorescent dye, Fast Blue (FB), injected into the bladder wall, whereas a fraction of somatic neurons labeled by FB, injected to the external urethral dermis, is intensely stained with IB4. In whole-cell, patch-clamp recordings, phrixotoxin 2 (PaTx2), a voltage-gated K(+) (Kv)4 channel blocker, exhibits voltage-independent inhibition of the KA current in IB4 intensely stained cells but not the one in bladder-innervating cells. The toxin also shows voltage-independent inhibition of heterologously expressed Kv4.1 current, whereas its inhibition of Kv4.2 and Kv4.3 currents is voltage dependent. The swapping of four amino acids at the carboxyl portion of the S3 region between Kv4.1 and Kv4.2 transfers this characteristic. RT-PCRs detected Kv4.1 and the long isoform of Kv4.3 mRNAs without significant Kv4.2 mRNA in L6-S1 DRGs. Kv4.1 and Kv4.3 mRNA levels were higher in laser-captured, IB4-stained neurons than in bladder afferent neurons. These results indicate that PaTx2 acts differently on channels in the Kv4 family and that Kv4.1 and possibly Kv4.3 subunits functionally participate in the formation of KA channels in a subpopulation of somatic C-fiber neurons but not in visceral C-fiber neurons innervating the bladder. Copyright © 2014 the American Physiological Society.

Differential contribution of Kv4-containing channels to A-type, voltage-gated potassium currents in somatic and visceral dorsal root ganglion neurons

PubMed Central

Yunoki, Takakazu; Takimoto, Koichi; Kita, Kaori; Funahashi, Yasuhito; Takahashi, Ryosuke; Matsuyoshi, Hiroko; Naito, Seiji

2014-01-01

Little is known about electrophysiological differences of A-type transient K+ (KA) currents in nociceptive afferent neurons that innervate somatic and visceral tissues. Staining with isolectin B4 (IB4)-FITC classifies L6-S1 dorsal root ganglion (DRG) neurons into three populations with distinct staining intensities: negative to weak, moderate, and intense fluorescence signals. All IB4 intensely stained cells are negative for a fluorescent dye, Fast Blue (FB), injected into the bladder wall, whereas a fraction of somatic neurons labeled by FB, injected to the external urethral dermis, is intensely stained with IB4. In whole-cell, patch-clamp recordings, phrixotoxin 2 (PaTx2), a voltage-gated K+ (Kv)4 channel blocker, exhibits voltage-independent inhibition of the KA current in IB4 intensely stained cells but not the one in bladder-innervating cells. The toxin also shows voltage-independent inhibition of heterologously expressed Kv4.1 current, whereas its inhibition of Kv4.2 and Kv4.3 currents is voltage dependent. The swapping of four amino acids at the carboxyl portion of the S3 region between Kv4.1 and Kv4.2 transfers this characteristic. RT-PCRs detected Kv4.1 and the long isoform of Kv4.3 mRNAs without significant Kv4.2 mRNA in L6-S1 DRGs. Kv4.1 and Kv4.3 mRNA levels were higher in laser-captured, IB4-stained neurons than in bladder afferent neurons. These results indicate that PaTx2 acts differently on channels in the Kv4 family and that Kv4.1 and possibly Kv4.3 subunits functionally participate in the formation of KA channels in a subpopulation of somatic C-fiber neurons but not in visceral C-fiber neurons innervating the bladder. PMID:25143545

Human gene therapy and slippery slope arguments.

PubMed Central

McGleenan, T

1995-01-01

Any suggestion of altering the genetic makeup of human beings through gene therapy is quite likely to provoke a response involving some reference to a 'slippery slope'. In this article the author examines the topography of two different types of slippery slope argument, the logical slippery slope and the rhetorical slippery slope argument. The logical form of the argument suggests that if we permit somatic cell gene therapy then we are committed to accepting germ line gene therapy in the future because there is no logically sustainable distinction between them. The rhetorical form posits that allowing somatic cell therapy now will be taking the first step on a slippery slope which will ultimately lead to the type of genocide perpetrated by the Nazis. The author tests the validity of these lines of argument against the facts of human gene therapy and concludes that because of their dependence on probabilities that cannot be empirically proven they should be largely disregarded in the much more important debate on moral line-drawing in gene therapy. PMID:8778459

The mechanisms of repetitive spike generation in an axonless retinal interneuron

PubMed Central

Cembrowski, Mark S.; Logan, Stephen M.; Tian, Miao; Jia, Li; Li, Wei; Kath, William L.; Riecke, Hermann; Singer, Joshua H.

2012-01-01

SUMMARY Several types of retinal interneurons exhibit spikes but lack axons. One such neuron is the AII amacrine cell, in which spikes recorded at the soma exhibit small amplitudes (<10 mV) and broad time courses (>5 ms). Here, we used electrophysiological recordings and computational analysis to examine the mechanisms underlying this atypical spiking. We found that somatic spikes likely represent large, brief action potential-like events initiated in a single, electrotonically-distal dendritic compartment. In this same compartment, spiking undergoes slow modulation, likely by an M-type K conductance. The structural correlate of this compartment is a thin neurite that extends from the primary dendritic tree: local application of TTX to this neurite, or excision of it, eliminates spiking. Thus, the physiology of the axonless AII is much more complex than would be anticipated from morphological descriptions and somatic recordings; in particular, the AII possesses a single dendritic structure that controls its firing pattern. PMID:22832164

Human gene therapy and slippery slope arguments.

PubMed

McGleenan, T

1995-12-01

Any suggestion of altering the genetic makeup of human beings through gene therapy is quite likely to provoke a response involving some reference to a 'slippery slope'. In this article the author examines the topography of two different types of slippery slope argument, the logical slippery slope and the rhetorical slippery slope argument. The logical form of the argument suggests that if we permit somatic cell gene therapy then we are committed to accepting germ line gene therapy in the future because there is no logically sustainable distinction between them. The rhetorical form posits that allowing somatic cell therapy now will be taking the first step on a slippery slope which will ultimately lead to the type of genocide perpetrated by the Nazis. The author tests the validity of these lines of argument against the facts of human gene therapy and concludes that because of their dependence on probabilities that cannot be empirically proven they should be largely disregarded in the much more important debate on moral line-drawing in gene therapy.

From embryonic stem cells to functioning germ cells: science, clinical and ethical perspectives.

PubMed

Kiatpongsan, Sorapop

2007-10-01

Embryonic stem cells have been well recognized as cells having a versatile potential to differentiate into all types of cells in the body including germ cells. There are many research studies focusing on the differentiation processes and protocols to derive various types of somatic cells from embryonic stem cells. However, germ cells have unique differentiation process and developmental pathway compared with somatic cells. Consequently, they will require different differentiation protocols and special culture techniques. More understanding and established in vitro systems for gametogenesis will greatly contribute to further progression of knowledge and technology in germ cell biology, reproductive biology and reproductive medicine. Moreover if oocytes can be efficiently produced in vitro, this will play an important role on progression in nuclear transfer and nuclear reprogramming technology. The present article will provide concise review on past important discoveries, current ongoing studies and future views of this challenging research area. An ethical perspective has also been proposed to give comprehensive summary and viewpoint for future clinical application.

Insights from Proteomic Studies into Plant Somatic Embryogenesis.

PubMed

Heringer, Angelo Schuabb; Santa-Catarina, Claudete; Silveira, Vanildo

2018-03-01

Somatic embryogenesis is a biotechnological approach mainly used for the clonal propagation of different plants worldwide. In somatic embryogenesis, embryos arise from somatic cells under appropriate culture conditions. This plasticity in plants is a demonstration of true cellular totipotency and is the best approach among the genetic transformation protocols used for plant regeneration. Despite the importance of somatic embryogenesis, knowledge regarding the control of the somatic embryogenesis process is limited. Therefore, the elucidation of both the biochemical and molecular processes is important for understanding the mechanisms by which a single somatic cell becomes a whole plant. Modern proteomic techniques rely on an alternative method for the identification and quantification of proteins with different abundances in embryogenic cell cultures or somatic embryos and enable the identification of specific proteins related to somatic embryogenesis development. This review focuses on somatic embryogenesis studies that use gel-free shotgun proteomic analyses to categorize proteins that could enhance our understanding of particular aspects of the somatic embryogenesis process and identify possible targets for future studies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Somatic Coliphage Profiles of Produce and Environmental Samples from Farms in Northern México.

PubMed

Bartz, Faith E; Hodge, Domonique Watson; Heredia, Norma; de Aceituno, Anna Fabiszewski; Solís, Luisa; Jaykus, Lee-Ann; Garcia, Santos; Leon, Juan S

2016-09-01

Somatic coliphages were quantified in 459 produce and environmental samples from 11 farms in Northern Mexico to compare amounts of somatic coliphages among different types of fresh produce and environmental samples across the production steps on farms. Rinsates from cantaloupe melons, jalapeño peppers, tomatoes, and the hands of workers, soil, and water were collected during 2011-2012 at four successive steps on each farm, from the field before harvest through the packing facility, and assayed by FastPhage MPN Quanti-tray method. Cantaloupe farm samples contained more coliphages than jalapeño or tomato (p range <0.01-0.03). Across production steps, jalapeños had higher coliphage percentages before harvest than during packing (p = 0.03), while tomatoes had higher coliphage concentrations at packing than all preceding production steps (p range <0.01-0.02). These findings support the use of targeted produce-specific interventions at multiple points in the process of growing and packing produce to reduce the risk of enteric virus contamination and improve food safety during fruit and vegetable production.

Production of cloned mice by somatic cell nuclear transfer.

PubMed

Kishigami, Satoshi; Wakayama, Sayaka; Thuan, Nguyen Van; Ohta, Hiroshi; Mizutani, Eiji; Hikichi, Takafusa; Bui, Hong-Thuy; Balbach, Sebastian; Ogura, Atsuo; Boiani, Michele; Wakayama, Teruhiko

2006-01-01

Although it has now been 10 years since the first cloned mammals were generated from somatic cells using nuclear transfer (NT), the success rate for producing live offspring by cloning remains < 5%. Nevertheless, the techniques have potential as important tools for future research in basic biology. We have been able to develop a stable NT method in the mouse, in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. Although manipulation of the piezo unit is complex, once mastered it is of great help not only in NT experiments but also in almost all other forms of micromanipulation. In addition to this technique, embryonic stem (ES) cell lines established from somatic cell nuclei by NT can be generated relatively easily from a variety of mouse genotypes and cell types. Such NT-ES cells can be used not only for experimental models of human therapeutic cloning but also as a backup of the donor cell's genome. Our most recent protocols for mouse cloning, as described here, will allow the production of cloned mice in > or = 3 months.

The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

PubMed

Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

2018-02-28

Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

The Relevance of Four Types of Knowledge for Leader Preparation in Radically Different Settings: Reflections on Data from a Case Study in Qatar and Teaching at a United States Military Academy

ERIC Educational Resources Information Center

Bakken, Richard; Dobbs, James

2016-01-01

Based on our experiences at a military service academy and the study of leadership informing administrators in overseas branch campuses, we propose a link between conceptual leadership development in these learning environments and the relevance of the four types of knowledge--declarative, procedural, contextual, and somatic for educational…

Adaption of cardio-respiratory balance during day-rest compared to deep sleep--an indicator for quality of life?

PubMed

von Bonin, Dietrich; Grote, Vincent; Buri, Caroline; Cysarz, Dirk; Heusser, Peter; Moser, Max; Wolf, Ursula; Laederach, Kurt

2014-11-30

Heart rate and breathing rate fluctuations represent interacting physiological oscillations. These interactions are commonly studied using respiratory sinus arrhythmia (RSA) of heart rate variability (HRV) or analyzing cardiorespiratory synchronization. Earlier work has focused on a third type of relationship, the temporal ratio of respiration rate and heart rate (HRR). Each method seems to reveal a specific aspect of cardiorespiratory interaction and may be suitable for assessing states of arousal and relaxation of the organism. We used HRR in a study with 87 healthy subjects to determine the ability to relax during 5 day-resting periods in comparison to deep sleep relaxation. The degree to which a person during waking state could relax was compared to somatic complaints, health-related quality of life, anxiety and depression. Our results show, that HRR is barely connected to balance (LF/HF) in HRV, but significantly correlates to the perception of general health and mental well-being as well as to depression. If relaxation, as expressed in HRR, during day-resting is near to deep sleep relaxation, the subjects felt healthier, indicated better mental well-being and less depressive moods. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Application of Somatic Embryogenesis in Woody Plants.

PubMed Central

Guan, Yuan; Li, Shui-Gen; Fan, Xiao-Fen; Su, Zhen-Hong

2016-01-01

Somatic embryogenesis is a developmental process where a plant somatic cell can dedifferentiate to a totipotent embryonic stem cell that has the ability to give rise to an embryo under appropriate conditions. This new embryo can further develop into a whole plant. In woody plants, somatic embryogenesis plays a critical role in clonal propagation and is a powerful tool for synthetic seed production, germplasm conservation, and cryopreservation. A key step in somatic embryogenesis is the transition of cell fate from a somatic cell to embryo cell. Although somatic embryogenesis has already been widely used in a number of woody species, propagating adult woody plants remains difficult. In this review, we focus on molecular mechanisms of somatic embryogenesis and its practical applications in economic woody plants. Furthermore, we propose a strategy to improve the process of somatic embryogenesis using molecular means. PMID:27446166

Is the replication of somatic coliphages in water environments significant?

PubMed

Jofre, J

2009-04-01

Somatic coliphages are amid several groups of bacteriophages that have been suggested as indicators in water quality assessment. One of the limitations frequently endorsed to somatic coliphages as indicators is that they can replicate in the water environment. This review intends to evaluate the significance of this potential replication. In view of: the threshold densities of somatic coliphages and host bacteria needed for productive infection to occur, the densities of both host cells supporting somatic coliphages replication and these phages in water environments, and the poor contribution of lysogenic induction to the free somatic coliphage numbers in water, it can be concluded that replication of somatic coliphages in waters is very unlikely. Consequently, the contribution of replication in the environment of somatic coliphages is expected to have a non-noticeable influence on the numbers of somatic coliphages detected in water environments. Thus, the replication in the environment should not be argued as a limitation to the use of somatic coliphages as indicators.

Reduction of spontaneous somatic mutation frequency by a low-dose X irradiation of Drosophila larvae and possible involvement of DNA single-strand damage repair.

PubMed

Koana, Takao; Takahashi, Takashi; Tsujimura, Hidenobu

2012-03-01

The third instar larvae of Drosophila were irradiated with X rays, and the somatic mutation frequency in their wings was measured after their eclosion. In the flies with normal DNA repair and apoptosis functions, 0.2 Gy irradiation at 0.05 Gy/min reduced the frequency of the so-called small spot (mutant cell clone with reduced reproductive activity) compared with that in the sham-irradiated flies. When apoptosis was suppressed using the baculovirus p35 gene, the small spot frequency increased four times in the sham-irradiated control group, but the reduction by the 0.2-Gy irradiation was still evident. In a non-homologous end joining-deficient mutant, the small spot frequency was also reduced by 0.2 Gy radiation. In a mutant deficient in single-strand break repair, no reduction in the small spot frequency by 0.2 Gy radiation was observed, and the small spot frequency increased with the radiation dose. Large spot (mutant cell clone with normal reproductive activity) frequency was not affected by suppression of apoptosis and increased monotonically with radiation dose in wild-type larvae and in mutants for single- or double-strand break repair. It is hypothesized that some of the small spots resulted from single-strand damage and, in wild-type larvae, 0.2 Gy radiation activated the normal single-strand break repair gene, which reduced the background somatic mutation frequency.

Dwarfism and increased adiposity in the gh1 mutant zebrafish vizzini.

PubMed

McMenamin, Sarah K; Minchin, James E N; Gordon, Tiffany N; Rawls, John F; Parichy, David M

2013-04-01

Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity.

Dwarfism and Increased Adiposity in the gh1 Mutant Zebrafish vizzini

PubMed Central

McMenamin, Sarah K.; Minchin, James E.N.; Gordon, Tiffany N.

2013-01-01

Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity. PMID:23456361

Spectrum of somatic EGFR, KRAS, BRAF, PTEN mutations and TTF-1 expression in Brazilian lung cancer patients.

PubMed

Carneiro, Juliana G; Couto, Patricia G; Bastos-Rodrigues, Luciana; Bicalho, Maria Aparecida C; Vidigal, Paula V; Vilhena, Alyne; Amaral, Nilson F; Bale, Allen E; Friedman, Eitan; De Marco, Luiz

2014-01-01

Lung cancer is the leading global cause of cancer-related mortality. Inter-individual variability in treatment response and prognosis has been associated with genetic polymorphisms in specific genes: EGFR, KRAS, BRAF, PTEN and TTF-1. Somatic mutations in EGFR and KRAS genes are reported at rates of 15-40% in non-small cell lung cancer (NSCLC) in ethnically diverse populations. BRAF and PTEN are commonly mutated genes in various cancer types, including NSCLC, with PTEN mutations exerting an effect on the therapeutic response of EGFR/AKT/PI3K pathway inhibitors. TTF-1 is expressed in approximately 80% of lung adenocarcinomas and its positivity correlates with higher prevalence of EGFR mutation in this cancer type. To determine molecular markers for lung cancer in Brazilian patients, the rate of the predominant EGFR, KRAS, BRAF and PTEN mutations, as well as TTF-1 expression, was assessed in 88 Brazilian NSCLC patients. EGFR exon 19 deletions (del746-750) were detected in 3/88 (3·4%) patients. Activating KRAS mutations in codons 12 and 61 were noted in five (5·7%) and two (2·3%) patients, respectively. None of the common somatic mutations were detected in either the BRAF or PTEN genes. TTF-1 was overexpressed in 40·7% of squamous-cell carcinoma (SCC). Our findings add to a growing body of data that highlights the genetic heterogeneity of the abnormal EGFR pathway in lung cancer among ethnically diverse populations.

Growth and Development Symposium: Development, characterization, and use of a porcine epiblast-derived liver stem cell line: ARS-PICM-19.

PubMed

Talbot, N C; Caperna, T J; Garrett, W M

2013-01-01

Totipotent embryonic stem cell lines have not been established from ungulates; however, we have developed a somatic stem cell line from the in vitro culture of pig epiblast cells. The cell line, ARS-PICM-19, was isolated via colony cloning and was found to spontaneously differentiate into hepatic parenchymal epithelial cell types, namely hepatocytes and bile duct cells. Hepatocytes form as monolayers and bile duct cells as 3-dimensional bile ductules. Transmission electron microscopy revealed that the ductules were composed of radially arranged, monociliated cells with their cilia projecting into the lumen of the ductule whereas hepatocytes were arranged in monolayers with lateral canalicular structures containing numerous microvilli and connected by tight junctions and desmosomes. Extensive Golgi and rough endoplasmic reticulum networks were also present, indicative of active protein synthesis. Analysis of conditioned medium by 2-dimensional electrophoresis and mass spectrometry indicated a spectrum of serum-protein secretion by the hepatocytes. The PICM-19 cell line maintains a range of inducible cytochrome P450 activities and, most notably, is the only nontransformed cell line that synthesizes urea in response to ammonia challenge. The PICM-19 cell line has been used for several biomedical- and agricultural-related purposes, such as the in vitro replication of hepatitis E virus, a zoonotic virus of pigs, and a spaceflight experiment to evaluate somatic stem cell differentiation and liver cell function in microgravity. The cell line was also evaluated as a platform for toxicity testing and has been used in a commercial artificial liver rescue device bioreactor. A PICM-19 subclone, PICM-19H, which only differentiates into hepatocytes, was isolated and methods are currently under development to grow PICM-19 cells without feeder cells. Feeder-cell-independent growth will facilitate the study of mesenchymal-parenchymal interactions that influence the divergent differentiation of the PICM-19 cells, enhance our ability to genetically modify the cells, and provide a better model system to investigate porcine hepatic metabolism.

Distribution of L-type calcium channels in rat thalamic neurones.

PubMed

Budde, T; Munsch, T; Pape, H C

1998-02-01

One major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution to neuronal function. Electrophysiological recordings from thalamic cells in situ and after acute isolation demonstrated the presence of high-voltage activated calcium currents. The use of specific L-type calcium channel agonists and antagonists of the dihydropyridine type revealed an about 40% contribution of L-type channels to the total high-voltage-activated calcium current. In order to localize L-type calcium channels in thalamic neurones, fluorescent dihydropyridines were used. They were combined with the fluorescent dye RH414, which allowed the use of a ratio technique and thereby the determination of channel density. The distribution of L-type channels was analysed in the three main thalamic cell types: thalamocortical relay cells, local interneurones and reticular thalamic neurones. While channel density was highest in the soma and decreased significantly in the dendritic region, channels appeared to be clustered differentially in the three types of cells. In thalamocortical cells, L-type channels were clustered in high density around the base of dendrites, while they were more evenly distributed on the soma of interneurones. Reticular thalamic neurones exhibited high density of L-type channels in more central somatic regions. The differential localization of L-type calcium channels found in this study implies their predominate involvement in the regulation of somatic and proximal dendritic calcium-dependent processes, which may be of importance for specific thalamic functions, such as those mediating the transition from rhythmic burst activity during sleep to single spike activity during wakefulness or regulating the relay of visual information.

Bioengineering resistance to phytoene desaturase inhibitors in Arabidopsis thaliana

USDA-ARS?s Scientific Manuscript database

Three natural somatic mutations at codon 304 of the phytoene desaturase gene (pds) of Hydrilla verticillata ( L. f. Royle) have been reported to provide resistance to the herbicide fluridone. We substituted the arginine 304 present in the wild-type H. verticillata phytoene desaturase (PDS) with all...

Mind-body interface: the role of n-3 fatty acids in psychoneuroimmunology, somatic presentation, and medical illness comorbidity of depression.

PubMed

Su, Kuan-Pin

2008-01-01

With the unsatisfaction of monoamine-based pharmacotherapy and the high comorbidity of other medical illness in depression, the serotonin hypothesis seems to fail in approaching the aetiology of depression. Based upon the evidence from epidemiological data, case-control studies of phospholipid polyunsaturated fatty acids (PUFAs) levels in human tissues, and antidepressant effect in clinical trials, PUFAs have shed a light to discover the unsolved of depression and connect the mind and body. Briefly, the deficit of n-3 PUFAs has been reported to be associated with neurological, cardiovascular, cerebrovascular, autoimmune, metabolic diseases and cancers. Recent studies revealed that the deficit of n-3 PUFAs is also associated with depression. For example, societies that consume a small amount of omega-3 PUFAs appear to have a higher prevalence of major depressive disorder. In addition, depressive patients had showed a lower level of omega-3 PUFAs; and the antidepressant effect of PUFAs had been reported in a number of clinical trials. The PUFAs are classified into n-3 (or omega-3) and n-6 (or omega-6) groups. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major bioactive components of n-3 PUFAs, are not synthesized in human body and can only be obtained directly from the diet, particularly by consuming fish. DHA deficit is associated with dysfunctions of neuronal membrane stability and transmission of serotonin, norepinephrine and dopamine, which might connect to the aetiology of mood and cognitive dysfunction of depression. On the other hand, EPA is important in balancing the immune function and physical healthy by reducing arachidonic acid (AA, an n-6 PUFA) level on cell membrane and prostaglandin E2 (PGE2) synthesis. Interestingly, animals fed with high AA diet or treated with PGE2 were observed to present sickness behaviours of anorexia, low activity, change in sleep pattern and attention, which are similar to somatic symptoms of depression in human. Therefore, the deficit of EPA and DHA in depression might be associated with mood disturbance, cognitive dysfunction, medical comorbidity and somatic symptoms in depression. Indeed, the role of n-3 PUFAs in immunity and mood function supports the promising psychoneuroimmunologic hypothesis of depression and provides an excellent interface shared by body and mind.

Somatization symptoms in pediatric abdominal pain patients: relation to chronicity of abdominal pain and parent somatization.

PubMed

Walker, L S; Garber, J; Greene, J W

1991-08-01

Symptoms of somatization were investigated in pediatric patients with recurrent abdominal pain (RAP) and comparison groups of patients with organic etiology for abdominal pain and well patients. Somatization scores were higher in RAP patients than well patients at the clinic visit, and higher than in either well patients or organic patients at a 3-month followup. Higher somatization scores in mothers and fathers were associated with higher somatization scores in RAP patients, but not in organic or well patients. Contrary to the findings of Ernst, Routh, and Harper (1984), chronicity of abdominal pain in RAP patients was not significantly associated with their level of somatization symptoms. Psychometric information about the Children's Somatization Inventory is presented.

Cortisol and somatization.

PubMed

Rief, W; Auer, C

2000-05-01

Somatization symptoms are frequently associated with depression, anxiety, and feelings of distress. These features interact with the activity of the HPA-axis. Therefore we investigated relationships between somatization symptoms and cortisol. Seventy-seven participants were classified into three groups: somatization syndrome (at least eight physical symptoms from the DSM-IV somatization disorder list), somatization syndrome combined with major depression, and healthy controls. The following data were collected: salivary cortisol at three time points (morning, afternoon, evening), nighttime urinary cortisol, serum cortisol after the dexamethasone suppression test (DST), and psychological variables such as depression, anxiety, somatization, and hypochondriasis. Salivary cortisol showed typical diurnal variations. However, the groups did not differ on any of the cortisol variables. A possible explanation may be counteracting effects of somatization and depression. Exploratory correlational analyses revealed that associations between cortisol and psychopathological variables were time-dependent. DST results correlated with psychological aspects of somatization, but not with the number of somatoform symptoms per se.

Integrated genomics for pinpointing survival loci within arm-level somatic copy number alterations

PubMed Central

Roy, David M.; Walsh, Logan A.; Desrichard, Alexis; Huse, Jason T.; Wu, Wei; Gao, JianJiong; Bose, Promita; Lee, William; Chan, Timothy A.

2016-01-01

SUMMARY The identification of driver loci underlying arm-level somatic copy number alterations (SCNAs) in cancer has remained challenging and incomplete. Here we assess the relative impact and present a detailed landscape of arm-level SCNAs in 10985 patient samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Further, using chromosome 9p loss in lower grade glioma (LGG) as a model, we employ a unique multi-tiered genomic dissection strategy using 540 patients from 3 independent LGG datasets to identify genetic loci that govern tumor aggressiveness and poor survival. This comprehensive approach uncovered several 9p loss-specific prognostic markers, validated existing ones, and re-defined the impact of CDKN2A loss in LGG. PMID:27165745

De novo generation of HSCs from somatic and pluripotent stem cell sources

PubMed Central

Vo, Linda T.

2015-01-01

Generating human hematopoietic stem cells (HSCs) from autologous tissues, when coupled with genome editing technologies, is a promising approach for cellular transplantation therapy and for in vitro disease modeling, drug discovery, and toxicology studies. Human pluripotent stem cells (hPSCs) represent a potentially inexhaustible supply of autologous tissue; however, to date, directed differentiation from hPSCs has yielded hematopoietic cells that lack robust and sustained multilineage potential. Cellular reprogramming technologies represent an alternative platform for the de novo generation of HSCs via direct conversion from heterologous cell types. In this review, we discuss the latest advancements in HSC generation by directed differentiation from hPSCs or direct conversion from somatic cells, and highlight their applications in research and prospects for therapy. PMID:25762177

Distinct Functional Connectivities Predict Clinical Response with Emotion Regulation Therapy

PubMed Central

Fresco, David M.; Roy, Amy K.; Adelsberg, Samantha; Seeley, Saren; García-Lesy, Emmanuel; Liston, Conor; Mennin, Douglas S.

2017-01-01

Despite the success of available medical and psychosocial treatments, a sizable subgroup of individuals with commonly co-occurring disorders, generalized anxiety disorder (GAD) and major depressive disorder (MDD), fail to make sufficient treatment gains thereby prolonging their deficits in life functioning and satisfaction. Clinically, these patients often display temperamental features reflecting heightened sensitivity to underlying motivational systems related to threat/safety and reward/loss (e.g., somatic anxiety) as well as inordinate negative self-referential processing (e.g., worry, rumination). This profile may reflect disruption in two important neural networks associated with emotional/motivational salience (e.g., salience network) and self-referentiality (e.g., default network, DN). Emotion Regulation Therapy (ERT) was developed to target this hypothesized profile and its neurobehavioral markers. In the present study, 22 GAD patients (with and without MDD) completed resting state MRI scans before receiving 16 sessions of ERT. To test study these hypotheses, we examined the associations between baseline patterns of intrinsic functional connectivity (iFC) of the insula and of hubs within the DN (anterior and dorsal medial prefrontal cortex [MPFC] and posterior cingulate cortex [PCC]) and treatment-related changes in worry, somatic anxiety symptoms and decentering. Results suggest that greater treatment linked reductions in worry were associated with iFC clusters in both the insular and parietal cortices. Greater treatment linked gains in decentering, a metacognitive process that involves the capacity to observe items that arise in the mind with healthy psychological distance that is targeted by ERT, was associated with iFC clusters in the anterior and posterior DN. The current study adds to the growing body of research implicating disruptions in the default and salience networks as promising targets of treatment for GAD with and without co-occurring MDD. PMID:28316567

[Smartphone usage among adolescents].

PubMed

Körmendi, Attila

2015-01-01

Among our technological gadgets smartphones play the most important role, new generation devices offer other functions beyond calling (internet availability, computer games, music player, camera functions etc.) In everydays can be experienced that youth spend more and more time with their smartphones and despite the actuality of this issue there are no studies on the excessive smartphone usage in Hungary and we can find only a few international studies. Our goal is to examine smartphone usage in primary and secondary schools in Hajdu-Bihar county, Hungary and its relationship with personality traits. Our sample consist of 263 youth from primary and secondary schools. We measured the characteristics of smartphone using and attitudes with a Mobilephone Using Questionnare. Personality traits are measured with Impulsiveness, Venturesomeness, Empathy Scale. The Child Behavior Checklist gives information about peer relationships, mental state and emotions. Average phone using time is 4,48 hours per day regarding the whole sample. This mean for boys is 3,40 hour for girls 5,39 hour. Average phone using time is higher at 16 (6,35 hour per day). The most frequent used applications are calling and visiting community sites. There is no connection between phone using and grades. The smartphone using time per day shows a significant positive relationship with Impulsivity, Anxiety and Depression, Attention deficits and Somatic problems within 17-19 ages. One of the explanation of excessive smartphone using may be the frequent visiting of community sites. Mobile phones in this case raise the availability of addictive object (community site) therefore contribute to the development of community site addiction. The connection with impulsivity, somatic problems and attention deficits refer to the anxiety reducing role of smartphones within 17-19 ages.

Emergence and patterning of the five cell types of the Zea mays anther locule

PubMed Central

Kelliher, Timothy; Walbot, Virginia

2011-01-01

One fundamental difference between plants and animals is the existence of a germ-line in animals and its absence in plants. In flowering plants the sexual organs (stamens and carpels) are composed almost entirely of somatic cells, a small subset of which switch to meiosis, however, the mechanism of meiotic cell fate acquisition is a long-standing botanical mystery. In the maize (Zea mays) anther microsporangium the somatic tissues consist of four concentric cell layers which surround and support reproductive cells as they progress through meiosis and pollen maturation. Male sterility, defined as the absence of viable pollen, is a common phenotype in flowering plants, and many male sterile mutants have defects in somatic and reproductive cell fate acquisition. However, without a robust model of anther cell fate acquisition based on careful observation of wild type anther ontogeny, interpretation of cell fate mutants is limited. To address this, the pattern of cell proliferation, expansion, and differentiation was tracked in three dimensions over thirty days of wild type (W23) anther development, using anthers stained with propidium iodide (PI) and/or 5-ethynyl-2′-deoxyuridine (EdU) (S-phase label) and imaged by confocal microscopy. The pervading lineage model of anther development claims that new cell layers are generated by coordinated, oriented cell divisions in transient precursor cell types. In reconstructing anther cell division patterns, however, we can only confirm this for the origin of the middle layer (ml) and tapetum, while young anther development appears more complex. We find that each anther cell type undergoes a burst of cell division after specification with a characteristic pattern of both cell expansion and division. Comparisons between two inbreds lines and between ab- and adaxial anther florets indicated near identity: anther development is highly canalized and synchronized. Three classical models of plant organ development are tested and ruled out; however, local clustering of developmental events was identified for several processes, including the first evidence for a direct relationship between the development of ml and tapetal cells. We speculate that small groups of ml and tapetum cells function as a developmental unit dedicated to the development of a single pollen grain. PMID:21070762

Germline contamination and leakage in whole genome somatic single nucleotide variant detection.

PubMed

Sendorek, Dorota H; Caloian, Cristian; Ellrott, Kyle; Bare, J Christopher; Yamaguchi, Takafumi N; Ewing, Adam D; Houlahan, Kathleen E; Norman, Thea C; Margolin, Adam A; Stuart, Joshua M; Boutros, Paul C

2018-01-31

The clinical sequencing of cancer genomes to personalize therapy is becoming routine across the world. However, concerns over patient re-identification from these data lead to questions about how tightly access should be controlled. It is not thought to be possible to re-identify patients from somatic variant data. However, somatic variant detection pipelines can mistakenly identify germline variants as somatic ones, a process called "germline leakage". The rate of germline leakage across different somatic variant detection pipelines is not well-understood, and it is uncertain whether or not somatic variant calls should be considered re-identifiable. To fill this gap, we quantified germline leakage across 259 sets of whole-genome somatic single nucleotide variant (SNVs) predictions made by 21 teams as part of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge. The median somatic SNV prediction set contained 4325 somatic SNVs and leaked one germline polymorphism. The level of germline leakage was inversely correlated with somatic SNV prediction accuracy and positively correlated with the amount of infiltrating normal cells. The specific germline variants leaked differed by tumour and algorithm. To aid in quantitation and correction of leakage, we created a tool, called GermlineFilter, for use in public-facing somatic SNV databases. The potential for patient re-identification from leaked germline variants in somatic SNV predictions has led to divergent open data access policies, based on different assessments of the risks. Indeed, a single, well-publicized re-identification event could reshape public perceptions of the values of genomic data sharing. We find that modern somatic SNV prediction pipelines have low germline-leakage rates, which can be further reduced, especially for cloud-sharing, using pre-filtering software.

The Effectiveness of Somatization in Communicating Distress in Korean and American Cultural Contexts

PubMed Central

Choi, Eunsoo; Chentsova-Dutton, Yulia; Parrott, W. Gerrod

2016-01-01

Previous research has documented that Asians tend to somatize negative experiences to a greater degree than Westerners. It is posited that somatization may be a more functional communication strategy in Korean than American context. We examined the effects of somatization in communications of distress among participants from the US and Korea. We predicted that the communicative benefits of somatic words used in distress narratives would depend on the cultural contexts. In Study 1, we found that Korean participants used more somatic words to communicate distress than US participants. Among Korean participants, but not US participants, use of somatic words predicted perceived effectiveness of the communication and expectations of positive reactions (e.g., empathy) from others. In Study 2, we found that when presented with distress narratives of others, Koreans (but not Americans) showed more sympathy in response to narratives using somatic words than narratives using emotional words. These findings suggest that cultural differences in use of somatization may reflect differential effectiveness of somatization in communicating distress across cultural contexts. PMID:27047414

Somatic comorbidity in anorexia nervosa: First results of a 21-year follow-up study on female inpatients

PubMed Central

2012-01-01

Background Anorexia nervosa is a severe psychosomatic disease with somatic complications in the long-term course and a high mortality rate. Somatic comorbidities independent of anorexia nervosa have rarely been studied, but pose a challenge to clinical practitioners. We investigated somatic comorbidities in an inpatient cohort and compared somatically ill anorexic patients and patients without a somatic comorbidity. In order to evaluate the impact of somatic comorbidity for the long-term course of anorexia nervosa, we monitored survival in a long-term follow-up. Method One hundred and sixty-nine female inpatients with anorexia nervosa were treated at the Charité University Medical Centre, Campus Benjamin Franklin, Berlin, between 1979 and 2011. We conducted retrospective analyses using patient's medical and psychological records. Information on survival and mortality were required through the local registration office and was available for one hundred patients. The mean follow-up interval for this subgroup was m = 20.9 years (sd = 4.7, min = 13.3, max = 31.6, range = 18.3). We conducted survival analysis using cox regression and included somatic comorbidity in a multivariate model. Results N = 41 patients (24.3%) showed a somatic comorbidity, n = 13 patients (7.7%) showed somatic comorbidities related to anorexia nervosa and n = 26 patients (15.4%) showed somatic comorbidities independent of anorexia nervosa, n = 2 patients showed somatic complications related to other psychiatric disorders. Patients with a somatic comorbidity were significantly older (m = 29.5, sd = 10.3 vs m = 25.0, sd = 8.7; p = .006), showed a later anorexia nervosa onset (m = 24.8, sd = 9.9 vs. m = 18.6, sd = 5.1; p < .000) and a longer duration of treatment in our clinic (m = 66.6, sd = 50.3 vs. m = 50.0, sd = 47; p = .05) than inpatients without somatic comorbidity. Out of 100 patients, 9 patients (9%) had died, on average at age of m = 37 years (sd = 9.5). Mortality was more common among inpatients with somatic comorbidity (n = 6, 66.7%) than among inpatients without a somatic disease (n = 3, 33.3%; p = .03). Somatic comorbidity was a significant coefficient in a multivariate survival model (B = 2.32, p = .04). Conclusion Somatic comorbidity seems to be an important factor for anorexia nervosa outcome and should be included in multivariate analyses on the long-term course of anorexia nervosa as an independent variable. Further investigations are needed in order to understand in which way anorexia nervosa and a somatic disease can interact. PMID:22300749

Further evidence for a broader concept of somatization disorder using the somatic symptom index.

PubMed

Hiller, W; Rief, W; Fichter, M M

1995-01-01

Somatization syndromes were defined in a sample of 102 psychosomatic inpatients according to the restrictive criteria of DSM-III-R somatization disorder and the broader diagnostic concept of the Somatic Symptom Index (SSI). Both groups showed a qualitatively similar pattern of psychopathological comorbidity and had elevated scores on measures of depression, hypochondriasis, and anxiety. A good discrimination between mild and severe forms of somatization was found by using the SSI criterion. SSI use accounted for a substantial amount of comorbidity variance, with rates of 15%-20% for depression, 16% for hypochondriasis, and 13% for anxiety. The results provide further evidence for the validity of the SSI concept, which reflects the clinical relevance of somatization in addition to the narrow definition of somatization disorder.

Hemoglobin promotes somatic embryogenesis in peanut cultures.

PubMed

Jayabalan, N; Anthony, P; Davey, M R; Power, J B; Lowe, K C

2004-02-01

Critical parameters influencing somatic embryogenesis include growth regulators and oxygen supply. Consequently, the present investigation has focused on optimization of a somatic embryogenic system for peanut (Arachis hypogaea L.) through media supplementation with the auxin, picloram. The latter at 30 mg L(-1) was optimal for inducing regeneration of somatic embryos from cultured explants of zygotic embryos. In contrast, somatic embryogenesis did not occur in the absence of this growth regulator. An assessment has also been made of the beneficial effect on somatic embryogenesis and plant regeneration of the commercial hemoglobin (Hb) solution, Erythrogen. Hemoglobin at 1:50 and 1:100 (v:v) stimulated increases in mean fresh weight (up to a maximum of 57% over control), mean number of explants producing somatic embryos (15%) and mean number of somatic embryos per explant (29%).

Genome-wide analysis reveals divergent patterns of gene expression during zygotic and somatic embryo maturation of Theobroma cacao L., the chocolate tree.

PubMed

Maximova, Siela N; Florez, Sergio; Shen, Xiangling; Niemenak, Nicolas; Zhang, Yufan; Curtis, Wayne; Guiltinan, Mark J

2014-07-16

Theobroma cacao L. is a tropical fruit tree, the seeds of which are used to create chocolate. In vitro somatic embryogenesis (SE) of cacao is a propagation system useful for rapid mass-multiplication to accelerate breeding programs and to provide plants directly to farmers. Two major limitations of cacao SE remain: the efficiency of embryo production is highly genotype dependent and the lack of full cotyledon development results in low embryo to plant conversion rates. With the goal to better understand SE development and to improve the efficiency of SE conversion we examined gene expression differences between zygotic and somatic embryos using a whole genome microarray. The expression of 28,752 genes was determined at 4 developmental time points during zygotic embryogenesis (ZE) and 2 time points during cacao somatic embryogenesis (SE). Within the ZE time course, 10,288 differentially expressed genes were enriched for functions related to responses to abiotic and biotic stimulus, metabolic and cellular processes. A comparison ZE and SE expression profiles identified 10,175 differentially expressed genes. Many TF genes, putatively involved in ethylene metabolism and response, were more strongly expressed in SEs as compared to ZEs. Expression levels of genes involved in fatty acid metabolism, flavonoid biosynthesis and seed storage protein genes were also differentially expressed in the two types of embryos. Large numbers of genes were differentially regulated during various stages of both ZE and SE development in cacao. The relatively higher expression of ethylene and flavonoid related genes during SE suggests that the developing tissues may be experiencing high levels of stress during SE maturation caused by the in vitro environment. The expression of genes involved in the synthesis of auxin, polyunsaturated fatty acids and secondary metabolites was higher in SEs relative to ZEs despite lack of lipid and metabolite accumulation. These differences in gene transcript levels associated with critical processes during seed development are consistent with the fact that somatic embryos do not fully develop the large storage cotyledons found in zygotic embryos. These results provide insight towards design of improved protocols for cacao somatic embryogenesis.

Genome-wide analysis reveals divergent patterns of gene expression during zygotic and somatic embryo maturation of Theobroma cacao L., the chocolate tree

PubMed Central

2014-01-01

Background Theobroma cacao L. is a tropical fruit tree, the seeds of which are used to create chocolate. In vitro somatic embryogenesis (SE) of cacao is a propagation system useful for rapid mass-multiplication to accelerate breeding programs and to provide plants directly to farmers. Two major limitations of cacao SE remain: the efficiency of embryo production is highly genotype dependent and the lack of full cotyledon development results in low embryo to plant conversion rates. With the goal to better understand SE development and to improve the efficiency of SE conversion we examined gene expression differences between zygotic and somatic embryos using a whole genome microarray. Results The expression of 28,752 genes was determined at 4 developmental time points during zygotic embryogenesis (ZE) and 2 time points during cacao somatic embryogenesis (SE). Within the ZE time course, 10,288 differentially expressed genes were enriched for functions related to responses to abiotic and biotic stimulus, metabolic and cellular processes. A comparison ZE and SE expression profiles identified 10,175 differentially expressed genes. Many TF genes, putatively involved in ethylene metabolism and response, were more strongly expressed in SEs as compared to ZEs. Expression levels of genes involved in fatty acid metabolism, flavonoid biosynthesis and seed storage protein genes were also differentially expressed in the two types of embryos. Conclusions Large numbers of genes were differentially regulated during various stages of both ZE and SE development in cacao. The relatively higher expression of ethylene and flavonoid related genes during SE suggests that the developing tissues may be experiencing high levels of stress during SE maturation caused by the in vitro environment. The expression of genes involved in the synthesis of auxin, polyunsaturated fatty acids and secondary metabolites was higher in SEs relative to ZEs despite lack of lipid and metabolite accumulation. These differences in gene transcript levels associated with critical processes during seed development are consistent with the fact that somatic embryos do not fully develop the large storage cotyledons found in zygotic embryos. These results provide insight towards design of improved protocols for cacao somatic embryogenesis. PMID:25030026

Impact of germline and somatic missense variations on drug binding sites.

PubMed

Yan, C; Pattabiraman, N; Goecks, J; Lam, P; Nayak, A; Pan, Y; Torcivia-Rodriguez, J; Voskanian, A; Wan, Q; Mazumder, R

2017-03-01

Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and germline nsSNVs that disrupt these binding sites can provide valuable knowledge for personalized medicine treatment. A web portal is available where nsSNVs from individual patient can be checked by scanning against DrugVar to determine whether any of the SNVs affect the binding of any drug in the database.

Editorial: Emerging approaches for typing, detection, characterization, and traceback of Escherichia coli

USDA-ARS?s Scientific Manuscript database

Commensal E. coli inhabit the large intestines of humans and animals and are important in maintaining normal intestinal homeostasis. There are also many groups of disease-causing E. coli, including diarrheagenic and extra-intestinal pathogenic E. coli (ExPEC). There are approximately O188 somatic O...

Lamarck Will Not Lie Down.

ERIC Educational Resources Information Center

Lewin, Roger

1981-01-01

Describes recent research by Edward Steele appearing to support the Lamarckian theory of inheritance. Steele suggests that a mutant somatic cell favored by the environment will undergo clonal expansion. Altered genetic materials from these cells is then picked up by C-type viruses and inserted into the germ line genome. (CS)

Application of genomic technologies for characterization, typing, and detection of E. coli

USDA-ARS?s Scientific Manuscript database

Serotyping using polyclonal antibodies raised in rabbits has been the gold standard for classification of E. coli based on the O- (somatic) and H- (flagellar) antigens; however, problems associated with serotyping are that the procedure is time consuming and labor intensive, cross reactions among di...

Chromosomal mutagenesis in human somatic cells: 30-year cytogenetic monitoring after Chornobyl accident.

PubMed

Pilinska, M A; Shemetun, G M; Shemetun, O V; Dybsky, S S; Dybska, O B; Talan, O O; Pedan, L R; Kurinnyi, D А

2016-12-01

In the lecture we have generalized and analyzed the data of cytogenetic laboratory of National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine on 30-year selective cytogenetic monitoring among the priority contingents of different ages exposed to radiation after Chornobyl accident in Ukraine. It is highlighted that not only targeted but also untargeted radiation-induced cytogenetic effects should be explored, especially in delayed terms following radiation exposure. The new methodical approaches for studying "bystander effect", individual radiosensitivity, and various forms of radiation-induced chromosomal instability (delayed, hidden, transmissible) have been proposed. These approaches proved to be advantageous for analyzing cytogenetic patterns of induction and persistence of chromosomal instability in human somatic cells because of "bystander effect" and "bystander type effect". The phenomenon of positive "reverse" bystander effect has been found. The possibility of modifying the inherited individual human susceptibility to mutagenic exposure by ionizing radiation has been estimated. Finally, the association between hypersensitivity to radiation exposure and realization of oncopathology in exposed individuals has been revealed. The increased intensity of human somatic chromosomal mutagenesis was confirmed not only in the nearest but in the delayed terms following Chornobyl accident as a result of radiation-induced both targeted and untargeted cytogenetic effects. Such effects can be considered as risk factors for malignant transformation of cells, hereditary diseases, birth defects, and multifactorial somatic pathology. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Psychological Distress in Young Adult Males with Atopic Dermatitis: A Cross-Sectional Study.

PubMed

Kim, Si-Heon; Hur, Jae; Jang, Jae-Yeon; Park, Hae-Sim; Hong, Chang Hyung; Son, Sang Joon; Chang, Ki Jung

2015-06-01

The relationship between atopic dermatitis (AD) and psychological distress has been well established for children and adolescents. However, it is unclear whether this relationship exists in young adults. This study aimed to assess the relationship between AD and psychological distress in young male adults in South Korea. A cross-sectional study was conducted using regional conscription data from 2008 to 2012. A dermatologist diagnosed AD based on historical and clinical features, and determined severity using the eczema area and severity index. A psychiatrist used medical records, an interview, and a psychological test to examine psychological distress (depression, anxiety, and somatization). The relationship between psychological distress and AD was assessed by multivariate logistic regression analyses. Among the 120,508 conscripts, 1517 (1.2%) presented with AD. The odds of having each type of psychological distress were significantly greater for individuals with AD compared with those without AD. The adjusted odds ratios for depression, anxiety, and somatization were 1.79 (95% CI 1.40-2.29), 1.38 (95% CI 1.08-1.76), and 1.75 (95% CI 1.40-2.20), respectively. Moderate-to-severe AD was significantly related to depression and somatization to a greater extent compared with mild AD. Depression, anxiety, and somatization are strongly and independently associated with AD in young adult males. Early treatment of skin inflammation might modify the risk of psychiatric problems. Prospective cohort studies are needed to verify causal relationships.

The clonal and mutational evolution spectrum of primary triple-negative breast cancers.

PubMed

Shah, Sohrab P; Roth, Andrew; Goya, Rodrigo; Oloumi, Arusha; Ha, Gavin; Zhao, Yongjun; Turashvili, Gulisa; Ding, Jiarui; Tse, Kane; Haffari, Gholamreza; Bashashati, Ali; Prentice, Leah M; Khattra, Jaswinder; Burleigh, Angela; Yap, Damian; Bernard, Virginie; McPherson, Andrew; Shumansky, Karey; Crisan, Anamaria; Giuliany, Ryan; Heravi-Moussavi, Alireza; Rosner, Jamie; Lai, Daniel; Birol, Inanc; Varhol, Richard; Tam, Angela; Dhalla, Noreen; Zeng, Thomas; Ma, Kevin; Chan, Simon K; Griffith, Malachi; Moradian, Annie; Cheng, S-W Grace; Morin, Gregg B; Watson, Peter; Gelmon, Karen; Chia, Stephen; Chin, Suet-Feung; Curtis, Christina; Rueda, Oscar M; Pharoah, Paul D; Damaraju, Sambasivarao; Mackey, John; Hoon, Kelly; Harkins, Timothy; Tadigotla, Vasisht; Sigaroudinia, Mahvash; Gascard, Philippe; Tlsty, Thea; Costello, Joseph F; Meyer, Irmtraud M; Eaves, Connie J; Wasserman, Wyeth W; Jones, Steven; Huntsman, David; Hirst, Martin; Caldas, Carlos; Marra, Marco A; Aparicio, Samuel

2012-04-04

Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.

Tinnitus: Distinguishing between Subjectively Perceived Loudness and Tinnitus-Related Distress

PubMed Central

Wallhäusser-Franke, Elisabeth; Brade, Joachim; Balkenhol, Tobias; D'Amelio, Roberto; Seegmüller, Andrea; Delb, Wolfgang

2012-01-01

Objectives Overall success of current tinnitus therapies is low, which may be due to the heterogeneity of tinnitus patients. Therefore, subclassification of tinnitus patients is expected to improve therapeutic allocation, which, in turn, is hoped to improve therapeutic success for the individual patient. The present study aims to define factors that differentially influence subjectively perceived tinnitus loudness and tinnitus-related distress. Methods In a questionnaire-based cross-sectional survey, the data of 4705 individuals with tinnitus were analyzed. The self-report questionnaire contained items about subjective tinnitus loudness, type of onset, awareness and localization of the tinnitus, hearing impairment, chronic comorbidities, sleep quality, and psychometrically validated questionnaires addressing tinnitus-related distress, depressivity, anxiety, and somatic symptom severity. In a binary step-wise logistic regression model, we tested the predictive power of these variables on subjective tinnitus loudness and tinnitus-related distress. Results The present data contribute to the distinction between subjective tinnitus loudness and tinnitus-related distress. Whereas subjective loudness was associated with permanent awareness and binaural localization of the tinnitus, tinnitus-related distress was associated with depressivity, anxiety, and somatic symptom severity. Conclusions Subjective tinnitus loudness and the potential presence of severe depressivity, anxiety, and somatic symptom severity should be assessed separately from tinnitus-related distress. If loud tinnitus is the major complaint together with mild or moderate tinnitus-related distress, therapies should focus on auditory perception. If levels of depressivity, anxiety or somatic symptom severity are severe, therapies and further diagnosis should focus on these symptoms at first. PMID:22529921

Prevalence and Characteristics of Work Anxiety in Medical Rehabilitation Patients: A Cross-Sectional Observation Study.

PubMed

Muschalla, Beate; Jöbges, Michael

2018-01-01

To investigate frequency, type, and characteristics of work anxieties in patients with somatic illness. Cross-sectional observation study. Neurology, orthopedic, and cardiology rehabilitation clinics. Patients (N=1610; age, 18-65y) with work anxieties. Not applicable. Patients who scored high on at least 2 of 9 items in the work-anxiety screening questionnaire and who reported impairment were investigated with a differential diagnostic interview on work anxieties and with the Mini-International Neuropsychiatric Interview on non-work-related common mental disorders. Patients also filled out a self-rating questionnaire on their subjective symptom load and sociodemographic data. Approximately 20% to 27% of the investigated inpatients in somatic rehabilitation (altogether n=393) received a work-anxiety diagnosis. Patients with orthopedic illness report highest work anxiety and have previous longest sick leave (20.6wk in the past 12mo). Patients with orthopedic illness suffer from work-related adjustment disorder with anxiety, social anxieties, and workplace phobias, whereas patients with cardiac illness are more often affected by hypochondriac anxieties. Anxieties of insufficiency and worrying occur equally in all indications. About a quarter of patients in somatic rehabilitation are in need of additional diagnostic attention owing to work anxieties. Differential diagnostic of work anxiety is needed for initiating adequate therapeutic action. Somatic rehabilitation physicians should be aware of work anxieties in their patients, especially in patients with orthopedic illness with previous long-term sick leave. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Multiple physical healthcare needs among outpatients with schizophrenia: findings from a health examination study.

PubMed

Eskelinen, Saana; Sailas, Eila; Joutsenniemi, Kaisla; Holi, Matti; Koskela, Tuomas H; Suvisaari, Jaana

2017-08-01

Despite the abundant literature on physical comorbidity, the full range of the concurrent somatic healthcare needs among individuals with schizophrenia has rarely been studied. This observational study aimed to assess the distressing somatic symptoms and needs for physical health interventions in outpatients with schizophrenia, and factors predicting those needs. A structured, comprehensive health examination was carried out, including a visit to a nurse and a general practitioner on 275 outpatients with schizophrenia. The required interventions were classified by type of disease. Logistic regression was used to assess the influence of sociodemographic factors, lifestyle, functional limitations, factors related to psychiatric disorder, and healthcare use on the need for interventions. In total, 44.9% of the patients (mean age 44.9 years) reported somatic symptoms affecting daily life; 87.6% needed specific interventions for a disease or condition, most commonly for cardiovascular, dermatological, dental, ophthalmological, and gastrointestinal conditions, and for altered glucose homeostasis. Smoking and obesity predicted significantly a need of any intervention, but the predictors varied in each disease category. Strikingly, use of general practitioner services during the previous year did not reduce the need for interventions. Health examinations for outpatients with schizophrenia revealed numerous physical healthcare needs. The health examinations for patients with schizophrenia should contain a medical history taking and a physical examination, in addition to basic measurements and laboratory tests. Prevention and treatment of obesity and smoking should be given priority in order to diminish somatic comorbidities in schizophrenia.

Relationships Among Microbial Communities, Maternal Cells, Oligosaccharides, and Macronutrients in Human Milk.

PubMed

Williams, Janet E; Price, William J; Shafii, Bahman; Yahvah, Katherine M; Bode, Lars; McGuire, Mark A; McGuire, Michelle K

2017-08-01

Human milk provides all essential nutrients necessary for early life and is rich in nonnutrients, maternally derived (host) cells, and bacteria, but almost nothing is known about the interplay among these components. Research aim: The primary objective of this research was to characterize relationships among macronutrients, maternal cells, and bacteria in milk. Milk samples were collected from 16 women and analyzed for protein, lipid, fatty acid, lactose, and human milk oligosaccharide concentrations. Concentrations of maternal cells were determined using microscopy, and somatic cell counts were enumerated. Microbial ecologies were characterized using culture-independent methods. Absolute and relative concentrations of maternal cells were mostly consistent within each woman as were relative abundances of bacterial genera, and there were many apparent relationships between these factors. For instance, relative abundance of Serratia was negatively associated with somatic cell counts ( r = -.47, p < .0001) and neutrophil concentration ( r = -.38, p < .0006). Concentrations of several oligosaccharides were correlated with maternally derived cell types as well as somatic cell counts; for example, lacto-N-tetraose and lacto-N-neotetraose were inversely correlated with somatic cell counts ( r = -.64, p = .0082; r = -.52, p = .0387, respectively), and relative abundance of Staphylococcus was positively associated with total oligosaccharide concentration ( r = .69, p = .0034). Complex relationships between milk nutrients and bacterial community profile, maternal cells, and milk oligosaccharides were also apparent. These data support the possibility that profiles of maternally derived cells, nutrient concentrations, and the microbiome of human milk might be interrelated.

Personalized genomic analyses for cancer mutation discovery and interpretation

PubMed Central

Jones, Siân; Anagnostou, Valsamo; Lytle, Karli; Parpart-Li, Sonya; Nesselbush, Monica; Riley, David R.; Shukla, Manish; Chesnick, Bryan; Kadan, Maura; Papp, Eniko; Galens, Kevin G.; Murphy, Derek; Zhang, Theresa; Kann, Lisa; Sausen, Mark; Angiuoli, Samuel V.; Diaz, Luis A.; Velculescu, Victor E.

2015-01-01

Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to select therapies based on the identified mutations. A major question in these analyses is the extent to which these methods identify clinically actionable alterations and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues, we comprehensively evaluated 815 tumor-normal paired samples from patients of 15 tumor types. We identified genomic alterations using next-generation sequencing of whole exomes or 111 targeted genes that were validated with sensitivities >95% and >99%, respectively, and specificities >99.99%. These analyses revealed an average of 140 and 4.3 somatic mutations per exome and targeted analysis, respectively. More than 75% of cases had somatic alterations in genes associated with known therapies or current clinical trials. Analyses of matched normal DNA identified germline alterations in cancer-predisposing genes in 3% of patients with apparently sporadic cancers. In contrast, a tumor-only sequencing approach could not definitively identify germline changes in cancer-predisposing genes and led to additional false-positive findings comprising 31% and 65% of alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes. These data suggest that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of somatic and germline alterations and have important implications for the diagnostic and therapeutic management of cancer patients. PMID:25877891

Longitudinal analysis of head and somatic growth in fetuses with congenital heart defects.

PubMed

Turan, Sifa; Rosenbloom, Joshua I; Hussein, Mostafa; Berg, Christoph; Gembruch, Ulrich; Baschat, Ahmet A; Turan, Ozhan M

2017-02-01

Fetal head and somatic growth dynamics differs in fetuses with congenital heart defects (CHD). We longitudinally characterized fetal head and somatic growth in relation to the type of CHD. Four hundred eleven exams from isolated CHD were compared with 1,219 controls. Head and somatic growth was assessed using head circumference (HC), brain volume (BrV = 1/6 × π × (HC/π)3)/2), fetal cephalization index (FCI = BrV/[estimated fetal weight]), and growth percentile. Umbilical and middle cerebral artery Doppler indices were obtained. CHD were grouped as: (1) d-transposition of great arteries (n = 11); (2) left ventricular outflow tract obstruction with retrograde isthmic flow (n = 18); (3) left ventricular outflow tract obstruction with antegrade isthmic flow (n = 16); (4) pulmonary outflow tract obstructions (n = 22). The smallest head size was seen in group 1. Growth asymmetry was diagnosed in group 2. Brain sparing was seen in groups 2 and 4 (p < 0.0001). HC and BrV percentiles decreased with advancing gestational age (p < 0.001) in group 2, and a significant drop was observed around 28 weeks. d-Transposition of great arteries and left-sided CHD leading to isthmic blood flow reversal are associated with delayed head growth. Prenatal evaluation of central hemodynamics in CHD may be contributive for predicting neurodevelopmental risks in CHD and help directing prenatal interventions. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:96-104, 2017. © 2016 Wiley Periodicals, Inc.

Optimally achieving milk bulk tank somatic cell count thresholds.

PubMed

Troendle, Jason A; Tauer, Loren W; Gröhn, Yrjo T

2017-01-01

High somatic cell count in milk leads to reduced shelf life in fluid milk and lower processed yields in manufactured dairy products. As a result, farmers are often penalized for high bulk tank somatic cell count or paid a premium for low bulk tank somatic cell count. Many countries also require all milk from a farm to be lower than a specified regulated somatic cell count. Thus, farms often cull cows that have high somatic cell count to meet somatic cell count thresholds. Rather than naïvely cull the highest somatic cell count cows, a mathematical programming model was developed that determines the cows to be culled from the herd by maximizing the net present value of the herd, subject to meeting any specified bulk tank somatic cell count level. The model was applied to test-day cows on 2 New York State dairy farms. Results showed that the net present value of the herd was increased by using the model to meet the somatic cell count restriction compared with naïvely culling the highest somatic cell count cows. Implementation of the model would be straightforward in dairy management decision software. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The role played by depression associated with somatic symptomatology in accounting for the gender difference in the prevalence of depression.

PubMed

Silverstein, B; Edwards, T; Gamma, A; Ajdacic-Gross, V; Rossler, W; Angst, J

2013-02-01

A variety of studies suggest the existence of a distinct phenotype of somatic depression, i.e., depression accompanied by significant somatic symptomatology. Previous research suggests that the gender difference in the prevalence of depression is primarily due to a difference in somatic depression. The aim of this study was to compare the gender difference in the prevalence of somatic depression and of depression not accompanied by significant somatic symptomatology (labelled "pure" depression) in two representative samples, the National Comorbidity Survey-Replication (NCS-R) and the Zurich Study. The gender difference in lifetime somatic depression was compared to that of pure depression based on analyses weighted back to the general population in two representative samples. The NCS-R analyses involved a narrow definition of somatic depression with items from the DSM criteria for depression--appetite, sleep, and fatigue. The analysis of the Zurich study added headaches, body image issues, and breathing difficulties to the criteria and comparison to atypical depression. In both samples, the gender difference in depressive prevalence was due to a large difference in somatic depression with other phenotypes showing little or no gender difference. The gender differences were found to be due to the somatic symptoms rather than the number of symptoms and were much larger for somatic than for atypical depression. The gender difference in the prevalence of depression results from the higher prevalence among women of a specific phenotype, somatic depression.

Golgi-type I and Golgi-type II neurons in the ventral anterior thalamic nucleus of the adult human: morphological features and quantitative analysis.

PubMed

Al-Hussain Bani Hani, Saleh M; El-Dwairi, Qasim A; Bataineh, Ziad M; Al-Haidari, Mohammad S; Al-Alami, Jamil

2008-05-01

The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic mean diameter of 30.8 microm (+/-9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 3.1 microm (+/-1, n = 80), 1.85 microm (+/-0.8, n = 145), and 1.5 microm (+/-0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 microm (+/-5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 1.6 microm (+/-0.86, n = 70), 1.15 microm (+/-0.55, n = 118), and 1 microm (+/-0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic neurons.

Multi-type Childhood Abuse, Strategies of Coping, and Psychological Adaptations in Young Adults

PubMed Central

Sesar, Kristina; Šimić, Nataša; Barišić, Marijana

2010-01-01

Aim To retrospectively analyze the rate of multi-type abuse in childhood and the effects of childhood abuse and type of coping strategies on the psychological adaptation of young adults in a sample form the student population of the University of Mostar. Methods The study was conducted on a convenience sample of 233 students from the University of Mostar (196 female and 37 male), with a median age of 20 (interquartile range, 2). Exposure to abuse was determined using the Child Maltreatment Scales for Adults, which assesses emotional, physical, and sexual abuse, neglect, and witnessing family violence. Psychological adaptation was explored by the Trauma Symptom Checklist, which assesses anxiety/depression, sexual problems, trauma symptoms, and somatic symptoms. Strategies of coping with stress were explored by the Coping Inventory for Stressful Situations. Results Multi-type abuse in childhood was experienced by 172 participants (74%) and all types of abuse by 11 (5%) participants. Emotional and physical maltreatment were the most frequent types of abuse and mostly occurred together with other types of abuse. Significant association was found between all types of abuse (r = 0.436-0.778, P < 0.050). Exposure to sexual abuse in childhood and coping strategies were significant predictors of anxiety/depression (R2 = 0.3553), traumatic symptoms (R2 = 0.2299), somatic symptoms (R2 = 0.2173), and sexual problems (R2 = 0.1550, P < 0.001). Conclusion Exposure to multi-type abuse in childhood is a traumatic experience with long-term negative effects. Problem-oriented coping strategies ensure a better psychosocial adaptation than emotion-oriented strategies. PMID:20960590

Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary.

PubMed

Färkkilä, Anniina; Haltia, Ulla-Maija; Tapper, Johanna; McConechy, Melissa K; Huntsman, David G; Heikinheimo, Markku

2017-08-01

Adult-type granulosa cell tumor is a clinically and molecularly unique subtype of ovarian cancer. These tumors originate from the sex cord stromal cells of the ovary and represent 3-5% of all ovarian cancers. The majority of adult-type granulosa cell tumors are diagnosed at an early stage with an indolent prognosis. Surgery is the cornerstone for the treatment of both primary and relapsed tumor, while chemotherapy is applied only for advanced or non-resectable cases. Tumor stage is the only factor consistently associated with prognosis. However, every third of the patients relapse, typically in 4-7 years from diagnosis, leading to death in 50% of these patients. Anti-Müllerian Hormone and inhibin B are currently the most accurate circulating biomarkers. Adult-type granulosa cell tumors are molecularly characterized by a pathognomonic somatic missense point mutation 402C->G (C134W) in the transcription factor FOXL2. The FOXL2 402C->G mutation leads to increased proliferation and survival of granulosa cells, and promotes hormonal changes. Histological diagnosis of adult-type granulosa cell tumor is challenging, therefore testing for the FOXL2 mutation is crucial for differential diagnosis. Large international collaborations utilizing molecularly defined cohorts are essential to improve and validate new treatment strategies for patients with high-risk or relapsed adult-type granulosa cell tumor. Key Messages: Adult-type granulosa cell tumor is a unique ovarian cancer with an indolent, albeit unpredictable disease course. Adult-type granulosa cell tumors harbor a pathognomonic somatic missense mutation in transcription factor FOXL2. The key challenges in the treatment of patients with adult-type granulosa cell tumor lie in the identification and management of patients with high-risk or relapsed disease.

[Direct and indirect somatic embryogenesis in Freesia refracta].

PubMed

Wang, L; Duan, X G; Hao, S

1999-06-01

Somatic embryogenesis can be induced in tissue cultures of Freesia refracta either directly from the epidermal cells of explant, or indirectly via intervening callus. In direct pathway, somatic embryos were in contact with maternal tissue in a suspensor-like structure. In indirect pathway, the explants first proliferacted to give rise to calluses before embryoids were induced. The two sorts of calluses were defined to embryogenic callus and non-embryogenic callus according to producing of somatic embryos. An indirect somatic embryo is developed from a pre-embryogenically determined cell. This kind of somatic embryo has no suspensor structure instead of a complex with maternal tissue. Somatic embryos have their own vascular tissues, and can develop new plantlets independently.

Morphological analyses and variation in carbohydrate content during the maturation of somatic embryos of Carica papaya.

PubMed

Vale, Ellen Moura; Reis, Ricardo Souza; Passamani, Lucas Zanchetta; Santa-Catarina, Claudete; Silveira, Vanildo

2018-03-01

Efficient protocols for somatic embryogenesis of papaya ( Carica papaya L.) have great potential for selecting elite hybrid genotypes. Addition of polyethylene glycol (PEG), a nonplasmolyzing osmotic agent, to a maturation medium increases the production of somatic embryos in C . papaya . To study the effects of PEG on somatic embryogenesis of C . papaya , we analyzed somatic embryo development and carbohydrate profile changes during maturation treatments with PEG (6%) or without PEG (control). PEG treatment (6%) increased the number of normal mature somatic embryos followed by somatic plantlet production. In both control and PEG treatments, pro-embryogenic differentiation to the cotyledonary stage was observed and was significantly higher with PEG treatment. Histomorphological analysis of embryonic cultures with PEG revealed meristematic centers containing small isodiametric cells with dense cytoplasm and evident nuclei. Concomitant with the increase in the differentiation of somatic embryos in PEG cultures, there was an increase in the endogenous content of sucrose and starch, which appears to be related to a rising demand for energy, a key point in the conversion of C . papaya somatic embryos. The endogenous carbohydrate profile may be a valuable parameter for developing optimized protocols for the maturation of somatic embryos in papaya.

Oral health-related quality of life and somatization in the elderly.

PubMed

Hassel, Alexander J; Rolko, Claudia; Leisen, Joachim; Schmitter, Marc; Rexroth, Walter; Leckel, Michael

2007-03-01

Somatization disorders are frequent in the elderly, and previous studies have revealed that psychological factors affect the outcome of measurement of oral health-related quality of life (OHRQoL). The objective of this study was, therefore, to investigate the correlation between OHRQoL and somatization. One-hundred and twenty-five participants aged 60 years or older (mean age 76.6 years; 40 males) from a primary geriatric medical hospital participated in this cross-sectional study. OHRQoL was assessed by using the Oral Health Impact Profile (OHIP), somatization by using the somatization subscale of the Symptom Check List (SCL-90-R). To obtain dental data we performed a clinical dental examination. In bivariate analyses the most consistent correlation with somatization was found for overall OHIP sum score and the subscales physical pain and functional limitation (r > 0.4). Participants with high somatization scores had high OHIP sum scores. In multivariate analysis somatization led to additional explanation of the variance of the OHIP sum score and of all OHIP subscales. There is consistent correlation between OHRQoL and somatization. When evaluating OHRQoL in the elderly (using the OHIP) further evaluation of somatization should be considered for thorough interpretation of the results.

Assessment of Somatization and Medically Unexplained Symptoms in Later Life

PubMed Central

van Driel, T. J. W.; Hilderink, P. H.; Hanssen, D. J. C.; de Boer, P.; Rosmalen, J. G. M.; Oude Voshaar, R. C.

2017-01-01

The assessment of medically unexplained symptoms and “somatic symptom disorders” in older adults is challenging due to somatic multimorbidity, which threatens the validity of somatization questionnaires. In a systematic review study, the Patient Health Questionnaire–15 (PHQ-15) and the somatization subscale of the Symptom Checklist 90-item version (SCL-90 SOM) are recommended out of 40 questionnaires for usage in large-scale studies. While both scales measure physical symptoms which in younger persons often refer to unexplained symptoms, in older persons, these symptoms may originate from somatic diseases. Using empirical data, we show that PHQ-15 and SCL-90 SOM among older patients correlate with proxies of somatization as with somatic disease burden. Updating the previous systematic review, revealed six additional questionnaires. Cross-validation studies are needed as none of 46 identified scales met the criteria of suitability for an older population. Nonetheless, specific recommendations can be made for studying older persons, namely the SCL-90 SOM and PHQ-15 for population-based studies, the Freiburg Complaint List and somatization subscale of the Brief Symptom Inventory 53-item version for studies in primary care, and finally the Schedule for Evaluating Persistent Symptoms and Somatic Symptom Experiences Questionnaire for monitoring treatment studies. PMID:28745072

Somatization in survivors of catastrophic trauma: a methodological review.

PubMed Central

North, Carol S

2002-01-01

The literature on mental health effects of catastrophic trauma such as community disasters focuses on posttraumatic stress disorder. Somatization disorder is not listed among the classic responses to disaster, nor have other somatoform disorders been described in this literature. Nondiagnostic "somatization," "somatization symptoms," and "somatic symptoms" form the basis of most information about somatization in the literature. However, these concepts have not been validated, and therefore this work suffers from multiple methodological problems of ascertainment and interpretation. Future research is encouraged to consider many methodological issues in obtaining adequate data to address questions about the association of somatization with traumatic events, including a) appropriate comparison groups, b) satisfactory definition and measurement of somatization, c) exclusion of medical explanations for the symptoms, d) recognition of somatizers' spurious attribution of symptoms to medical causes, e) collection of data from additional sources beyond single-subject interviews, f) validation of diagnosis-unrelated symptom reporting or reconsideration of symptoms within diagnostic frameworks, g) separation of somatization after an event into new (incident) and preexisting categories, h) development of research models that include sufficient variables to examine the broader scope of potential relationships, and i) novel consideration of alternative causal directionalities. PMID:12194899

The pathway to femaleness: current knowledge on embryonic development of the ovary

PubMed Central

Yao, Humphrey Hung-Chang

2014-01-01

Increasing evidence indicates that organogenesis of the ovary is not a passive process arising by default in the absence of the testis pathway. A coordinated interaction is actually in force between somatic cells and female germ cells in embryonic ovaries, thus creating a unique microenvironment that facilitates the formation of follicles. Identification of the functional roles of several novel regulatory elements such as Figα, Foxl2, follistatin, and Wnt4 reveals the complexity of early ovarian organization. Challenges await us to establish the molecular connections of these molecules as well as to discover new candidates in the pathway of early ovarian development. PMID:15664455

Microbiological and experimental-histological investigations of lunar samples returned by the Lunar 16 automatic station

NASA Technical Reports Server (NTRS)

Kaulen, D. R.; Bulatova, T. I.; Fridenshteyn, A. Y.; Skvortsova, Y. B.

1974-01-01

Lunar surface material was studied for its content of viable microorganisms (aerobic and anaerobic, fungi, and viruses); the effect of the lunar surface material on the growth of microorganisms and its interaction with somatic cells of mammals was also observed. No viable microorganisms were detected; the samples exhibited neither stimulant or inhibitory action on the growth of microorganisms, and also showed no cytopathogenic action on tissue cultures. A suspension of lunar surface material particles was not toxic when parenterally administered to certain laboratory animals. The particles were subjected to intense phagocytosis by connective tissue cells in vivo and in vitro.

Development of ovary structures in the last larval and adult stages of psyllids (Insecta, Hemiptera, Sternorrhyncha: Psylloidea).

PubMed

Kot, Marta; Büning, Jürgen; Jankowska, Władysława; Drohojowska, Jowita; Szklarzewicz, Teresa

2016-07-01

The development and organization of the ovaries of ten species from four Psylloidea families (Psyllidae, Triozidae, Aphalaridae and Liviidae) have been investigated. The ovaries of the last larval stage (i.e. fifth instar) of all examined species are filled with numerous clusters of cystocytes which undergo synchronous incomplete mitotic division. Cystocytes of the given cluster are arranged into a rosette with polyfusome in the centre. These clusters are associated with single somatic cells. At the end of the fifth instar, the clusters begin to separate from each other, forming spherical ovarioles which are surrounded by a single layer of somatic cells. In the ovarioles of very young females all cystocytes enter the prophase of meiosis and differentiate shortly thereafter into oocytes and trophocytes (nurse cells). Meanwhile, somatic cells differentiate into cells of the inner epithelial sheath surrounding the trophocytes and into the prefollicular cells that encompass the oocytes. During this final differentiation, the trophocytes lose their cell membranes and become syncytial. Oocytes remain cellular and most of them (termed arrested oocytes) do not grow. In the ovarioles of older females, one oocyte encompassed by its follicle cells starts growing, still connected to the syncytial tropharium by a nutritive cord. After the short phase of previtellogenesis alone, the oocyte enters its vitellogenic the growth phase in the vitellarium. At that time, the second oocyte may enter the vitellarium and start its previtellogenic growth. In the light of the obtained results, the phylogeny of psyllids, as well as phylogenetic relationships between taxa of Hemiptera: Sternorrhyncha are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

The epidemiology of the comorbidity of epilepsy in the general population.

PubMed

Gaitatzis, Athanasios; Carroll, Kevin; Majeed, Azeem; W Sander, Josemir

2004-12-01

To describe the epidemiology of somatic and psychiatric conditions in adults with epilepsy in the community and compare it to that of people without epilepsy. A cross-sectional population-based study extracting data from the UK General Practice Research Database for the period 1995-1998. Age- and sex-standardized prevalence rates were estimated for selected conditions and groups of conditions (categorized by ICD-9 chapters) in adults with epilepsy registered with primary care physicians. Results were compared with those in adults without epilepsy in the cohort, and prevalence ratios were calculated according to two broad age groups (16-64 and older than 64 years). Conditions common in the general population also were common in adults with epilepsy. Psychiatric disorders occurred twice as often, and the risk of somatic disorders was increased in people with epilepsy, with the exception of musculoskeletal and connective tissue disorders in older adults. The prevalence ratio of neoplasia, excluding intracranial tumors, was not increased in epilepsy. The prevalence ratio of brain tumors was particularly increased in young adults [prevalence ratio (PR), 70.7] and of meningiomas in older adults (PR, 91.9). Neurodegenerative conditions, particularly dementias and Alzheimer' disease (PR, 6.3 and 8, respectively) and Parkinson' disease (PR, 3.2), appeared more frequently in people with epilepsy. Upper gastrointestinal bleed occurred more frequently in epilepsy (PR, 4.3), as did cardio- and cerebrovascular disorders, fractures, pneumonia and chronic lung diseases, and diabetes. Eczema, osteoarthritis, and rheumatoid arthritis did not occur more frequently in epilepsy. The prevalence ratio of many common psychiatric and somatic conditions is increased in adults with epilepsy who consult a primary care physician in the U.K. These findings may have implications in the diagnosis and management of epilepsy and coexisting conditions, as well as in health care provision.

Mutation-induced protein interaction kinetics changes affect apoptotic network dynamic properties and facilitate oncogenesis

PubMed Central

Zhao, Linjie; Sun, Tanlin; Pei, Jianfeng; Ouyang, Qi

2015-01-01

It has been a consensus in cancer research that cancer is a disease caused primarily by genomic alterations, especially somatic mutations. However, the mechanism of mutation-induced oncogenesis is not fully understood. Here, we used the mitochondrial apoptotic pathway as a case study and performed a systematic analysis of integrating pathway dynamics with protein interaction kinetics to quantitatively investigate the causal molecular mechanism of mutation-induced oncogenesis. A mathematical model of the regulatory network was constructed to establish the functional role of dynamic bifurcation in the apoptotic process. The oncogenic mutation enrichment of each of the protein functional domains involved was found strongly correlated with the parameter sensitivity of the bifurcation point. We further dissected the causal mechanism underlying this correlation by evaluating the mutational influence on protein interaction kinetics using molecular dynamics simulation. We analyzed 29 matched mutant–wild-type and 16 matched SNP—wild-type protein systems. We found that the binding kinetics changes reflected by the changes of free energy changes induced by protein interaction mutations, which induce variations in the sensitive parameters of the bifurcation point, were a major cause of apoptosis pathway dysfunction, and mutations involved in sensitive interaction domains show high oncogenic potential. Our analysis provided a molecular basis for connecting protein mutations, protein interaction kinetics, network dynamics properties, and physiological function of a regulatory network. These insights provide a framework for coupling mutation genotype to tumorigenesis phenotype and help elucidate the logic of cancer initiation. PMID:26170328

The amygdala and decision-making.

PubMed

Gupta, Rupa; Koscik, Timothy R; Bechara, Antoine; Tranel, Daniel

2011-03-01

Decision-making is a complex process that requires the orchestration of multiple neural systems. For example, decision-making is believed to involve areas of the brain involved in emotion (e.g., amygdala, ventromedial prefrontal cortex) and memory (e.g., hippocampus, dorsolateral prefrontal cortex). In this article, we will present findings related to the amygdala's role in decision-making, and differentiate the contributions of the amygdala from those of other structurally and functionally connected neural regions. Decades of research have shown that the amygdala is involved in associating a stimulus with its emotional value. This tradition has been extended in newer work, which has shown that the amygdala is especially important for decision-making, by triggering autonomic responses to emotional stimuli, including monetary reward and punishment. Patients with amygdala damage lack these autonomic responses to reward and punishment, and consequently, cannot utilize "somatic marker" type cues to guide future decision-making. Studies using laboratory decision-making tests have found deficient decision-making in patients with bilateral amygdala damage, which resembles their real-world difficulties with decision-making. Additionally, we have found evidence for an interaction between sex and laterality of amygdala functioning, such that unilateral damage to the right amygdala results in greater deficits in decision-making and social behavior in men, while left amygdala damage seems to be more detrimental for women. We have posited that the amygdala is part of an "impulsive," habit type system that triggers emotional responses to immediate outcomes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Linking Anger Trait with Somatization in Low-Grade College Students: Moderating Roles of Family Cohesion and Adaptability.

PubMed

Liu, Liang; Liu, Cuilian; Zhao, Xudong

2017-02-25

Between 22% and 58% of patients in primary care settings complain of somatic symptoms. Previous research has found that somatization was associated with anger traits and family functions. However, studies that specifically assess the moderating effect of family function in how anger traits become somatic complaints are lacking. This study was designed to examine whether the variances in family cohesion and family adaptability moderated the strength of the relationship between anger traits and somatization. A cross-section design was conducted and 2008 college students were recruited from a comprehensive university in Shanghai. All participants finished questionnaires including Symptom Check List- 90 (SCL-90), State-Trait Anger Expression Inventory 2 (STAXI-2, Chinese version) and Family Adaptability and Cohesion Scale, second edition (FACES II, Chinese Version) to assess their degree of current somatization, anger trait and family function. Hierarchical linear regression analysis (Enter) was conducted respectively for men and women to examine the moderation effect of family cohesion and family adaptability in the association between anger and somatization. Somatic symptoms were significantly linked in the expected directions with depression and anger trait for both genders. Family cohesion and family adaptability were negatively associated with somatic symptoms. For female college students family cohesion was found to moderate the link between anger trait and somatization, but for male college students the moderation effect of family cohesion was marginally significant. The moderating role of family adaptability was significant for neither male nor female after current depressive symptoms were accounted for. Proneness to anger is an independent predictor of somatization. For women, a high level of family cohesion was a protective factor which could reduce the influence of anger trait on somatic symptoms. Without comorbidity of current depression, family adaptability to some degree exempted individuals with anger proneness from developing somatic complaints. Interventions that integrate family cohesion cultivation, family flexibility fostering and depression treatment might be more effective for somatic patients high in anger trait.

[Hypochondriac symptoms in late-onset depression: the relationship between hypochondria and somatic state of patients].

PubMed

Ivanets, N N; Avdeeva, T I; Kinkul'kina, M A

2013-01-01

Authors studied 276 women with late-onset depression. Concomitant chronic somatic diseases were identified in 90%. The presence of disease and its nosological definition did not impact on the development of hypochondriac symptoms in patients with late-onset depression. Patients with hypochondriac late-onset depression more often had disability pension due to somatic disease because they more often referred to internists in case of similar objective severity of somatic pathology. It was singled out three variants of the relationship between hypochondria and somatic state: hypernosognostic (a complete coincidence of hypochondria content with actual somatic pathology; anosognostic (a lack of coincidence) and disharmonic (a partial coincidence). The themes of hypochondria in late-nset depressions were correlated with a total number of somatic diseases and their severity. At the same time, there was no correlation between the content of hypochondria and the character of somatic disease.

[Somatization disorders of the urogenital tract].

PubMed

Günthert, E A

2002-11-01

Diffuse symptoms in the urogenital region can frequently be explained by somatization disorders. Since they cannot be proven either by laboratory tests or with common technical diagnostic methods, somatization disorders should always be taken into consideration. Somatization disorders are to be considered functional disorders. Since somatization disorders due to muscular tension prevail in the urogenital region, the functional disturbance can be explained by the muscular tension. Subsequently, muscular tension causes the pathophysiological development of symptoms. As a rule they appear as myofascial pain or disorder. Muscular tension can have a psychic origin. The absence of urological findings is typical. Males and females between the ages of 16 and 75 can be affected by somatization disorders in the urogenital region. Somatization disorders due to muscular tension belong to the large group of symptoms due to tension. Diagnostic and therapeutic procedures as well as the pathophysiology of somatization disorders due to muscular tension are illustrated by two detailed case-reports.

When the human spirit helps? The moderating role of somatization on the association between Olympic game viewing and the will-to-live.

PubMed

Palgi, Yuval; Grossman, Ephraim S; Hoffman, Yaakov S G; Pitcho-Prelorentzos, Shani; David, Udi Y; Ben-Ezra, Menachem

2017-11-01

This study examined whether participants with low somatization (no bodily manifestations of anxiety) who are assumed to identify with- and be inspired- by the Olympic-Games-spirit will present a stronger association between their Olympic-game viewing hours and their will-to-live, than persons with high somatization. One hundred and thirty seven participants reported their daily Olympic-game viewing hours, somatization and will-to-live levels. Results show that while among those with low somatization symptoms level, the relationships between Olympic game viewing hours and will-to-live was positive, the opposite was found among those with high somatization symptoms level. Viewing the Olympic Games may be beneficial for individuals with low somatization level but less so to individuals with higher somatization. Copyright © 2017 Elsevier B.V. All rights reserved.

Somatization among older primary care attenders.

PubMed

Sheehan, B; Bass, C; Briggs, R; Jacoby, R

2003-07-01

The importance of somatization among older primary care attenders is unclear. We aimed to establish the prevalence, persistence and associations of somatization among older primary care attenders, and the associations of frequent attendance. One hundred and forty primary care attenders over 65 years were rated twice, 10 months apart, on measures of somatization, psychiatric status, physical health and attendance. The syndrome of GMS hypochondriacal neurosis had a prevalence of 5% but was transient. Somatized symptoms and attributions were persistent and associated with depression, physical illness and perceived poor social support. Frequent attenders (top third) had higher rates of depression, physical illness and somatic symptoms, and lower perceived support. Somatization is common among older primary care attenders and has similar correlates to younger primary care somatizers. Psychological distress among older primary care attenders is associated with frequent attendance. Improved recognition should result in benefits to patients and services.

Cognitive-affective depression and somatic symptoms clusters are differentially associated with maternal parenting and coparenting.

PubMed

Lamela, Diogo; Jongenelen, Inês; Morais, Ana; Figueiredo, Bárbara

2017-09-01

Both depressive and somatic symptoms are significant predictors of parenting and coparenting problems. However, despite clear evidence of their co-occurrence, no study to date has examined the association between depressive-somatic symptoms clusters and parenting and coparenting. The current research sought to identify and cross-validate clusters of cognitive-affective depressive symptoms and nonspecific somatic symptoms, as well as to test whether clusters would differ on parenting and coparenting problems across three independent samples of mothers. Participants in Studies 1 and 3 consisted of 409 and 652 community mothers, respectively. Participants in Study 2 consisted of 162 mothers exposed to intimate partner violence. All participants prospectively completed self-report measures of depressive and nonspecific somatic symptoms and parenting (Studies 1 and 2) or coparenting (Study 3). Across studies, three depression-somatic symptoms clusters were identified: no symptoms, high depression and low nonspecific somatic symptoms, and high depression and nonspecific somatic symptoms. The high depression-somatic symptoms cluster was associated with the highest levels of child physical maltreatment risk (Study 1) and overt-conflict coparenting (Study 3). No differences in perceived maternal competence (Study 2) and cooperative and undermining coparenting (Study 3) were found between the high depression and low somatic symptoms cluster and the high depression-somatic symptoms cluster. The results provide novel evidence for the strong associations between clusters of depression and nonspecific somatic symptoms and specific parenting and coparenting problems. Cluster stability across three independent samples suggest that they may be generalizable. The results inform preventive approaches and evidence-based psychotherapeutic treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

[Criteria for somatization studied in an outpatient clinic for general internal medicine].

PubMed

van Hemert, A M; Speckens, A E; Rooijmans, H G; Bolk, J H

1996-06-08

To compare the evolution of bodily symptoms and the frequency of medical consultation using three different operational definitions of 'somatization'. Descriptive follow-up study. General Internal Medicine Outpatient Clinic of Leiden University Hospital, the Netherlands. Information about physical and psychic symptoms and about the somatic-medical diagnosis was collected in a group of 158 newly referred patients. The concept of 'somatization' was operationalized in three ways: a) seeking medical consultation for somatically unexplained symptoms; b) seeking medical consultation for somatically unexplained symptoms combined with an anxiety disorder or a depressive disorder according to the 'present state examination'; c) seeking medical consultation for somatically unexplained symptoms combined with a somatization disorder or hypochondria according to the Diagnostic and statistical manual of mental disorders (DSM) III R criteria. After a follow-up period of 1.2 years, information was collected from the entire study group about the evolution of the physical symptoms and the frequency of medical consultation. Patients with somatically unexplained symptoms combined with a somatization disorder or hypochondria were characterized in the follow-up by numerous physical symptoms and a high frequency of medical consultation. Compared with the other patients with unexplained symptoms, they visited the general practitioner during the follow-up period 2.5 times as often, saw specialists twice as often and were admitted to a 'somatic' hospital, 6 times as often. Using criteria of low restrictiveness for somatization, a large group of patients were identified with a relatively normal (average) illness behaviour. Using more restrictive criteria led to identification of a smaller group with more extreme illness behaviour.

Extending a structural model of somatization to South Koreans: Cultural values, somatization tendency, and the presentation of depressive symptoms.

PubMed

Zhou, Xiaolu; Min, Seongho; Sun, Jiahong; Kim, Se Joo; Ahn, Joung-Sook; Peng, Yunshi; Noh, Samuel; Ryder, Andrew G

2015-05-01

Somatization refers to the tendency to emphasize somatic symptoms when experiencing a psychiatric disturbance. This tendency has been widely reported in patients from East Asian cultural contexts suffering from depression. Recent research in two Chinese samples have demonstrated that the local cultural script for depression, involving two aspects-the experience and expression of distress (EED) and conceptualization and communication of distress (CCD)-can be evoked to help explain somatization. Given the beliefs and practices broadly shared across Chinese and South Korean cultural contexts, the current study seeks to replicate this explanatory model in South Koreans. Our sample included 209 psychiatric outpatients from Seoul and Wonju, South Korea. Self-report questionnaires were used to assess somatization tendency, adherence to traditional values, and psychological and somatic symptoms of depression. Results from SEM showed that the EED and CCD factors of somatization tendency were differently associated with cultural values and somatic symptoms, replicating our previous findings in Chinese outpatients. The reliance on a brief self-report measure of somatization tendency, not originally designed to assess separate EED and CCD factors, highlights the need for measurement tools for the assessment of cultural scripts in cross-cultural depression research. The replication of the Chinese structural model of somatization in South Korea lends empirical support to the view that somatization can be understood as the consequence of specific cultural scripts. These scripts involve the experience and expression of distress as well as culturally meaningful ways in which this distress is conceptualized and communicated to others. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrated Molecular Characterization of Uterine Carcinosarcoma.

PubMed

Cherniack, Andrew D; Shen, Hui; Walter, Vonn; Stewart, Chip; Murray, Bradley A; Bowlby, Reanne; Hu, Xin; Ling, Shiyun; Soslow, Robert A; Broaddus, Russell R; Zuna, Rosemary E; Robertson, Gordon; Laird, Peter W; Kucherlapati, Raju; Mills, Gordon B; Weinstein, John N; Zhang, Jiashan; Akbani, Rehan; Levine, Douglas A

2017-03-13

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified. Copyright © 2017 Elsevier Inc. All rights reserved.

A temporary immersion system improves in vitro regeneration of peach palm through secondary somatic embryogenesis

PubMed Central

Steinmacher, D. A.; Guerra, M. P.; Saare-Surminski, K.; Lieberei, R.

2011-01-01

Background and Aims Secondary somatic embryogenesis has been postulated to occur during induction of peach palm somatic embryogenesis. In the present study this morphogenetic pathway is described and a protocol for the establishment of cycling cultures using a temporary immersion system (TIS) is presented. Methods Zygotic embryos were used as explants, and induction of somatic embryogenesis and plantlet growth were compared in TIS and solid culture medium. Light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to describe in vitro morphogenesis and accompany morpho-histological alterations during culture. Key Results The development of secondary somatic embryos occurs early during the induction of primary somatic embryos. Secondary somatic embryos were observed to develop continually in culture, resulting in non-synchronized development of these somatic embryos. Using these somatic embryos as explants allowed development of cycling cultures. Somatic embryos had high embryogenic potential (65·8 ± 3·0 to 86·2 ± 5·0 %) over the period tested. The use of a TIS greatly improved the number of somatic embryos obtained, as well as subsequent plantlet growth. Histological analyses showed that starch accumulation precedes the development of somatic embryos, and that these cells presented high nucleus/cytoplasm ratios and high mitotic indices, as evidenced by DAPI staining. Morphological and SEM observations revealed clusters of somatic embryos on one part of the explants, while other parts grew further, resulting in callus tissue. A multicellular origin of the secondary somatic embryos is hypothesized. Cells in the vicinity of callus accumulated large amounts of phenolic substances in their vacuoles. TEM revealed that these cells are metabolically very active, with the presence of numerous mitochondria and Golgi apparatuses. Light microscopy and TEM of the embryogenic sector revealed cells with numerous amyloplasts, large nuclei and nucleoli, and numerous plasmodesmata. Plantlets were obtained and after 3 months in culture their growth was significantly better in TIS than on solid culture medium. However, during acclimatization the survival rate of TIS-grown plantlets was lower. Conclusions The present study confirms the occurrence of secondary somatic embryos in peach palm and describes a feasible protocol for regeneration of peach palm in vitro. Further optimizations include the use of explants obtained from adult palms and improvement of somatic embryo conversion rates. PMID:21355009

Subjective health complaints and exposure to peer victimization among disabled and non-disabled adolescents: A population-based study in Sweden.

PubMed

Fridh, Maria; Köhler, Marie; Modén, Birgit; Lindström, Martin; Rosvall, Maria

2018-03-01

To investigate subjective health complaints (SHCs) (psychological and somatic, respectively) among disabled and non-disabled adolescents, focusing on the impact of traditional bullying and cyber harassment, and furthermore to report psychological and somatic SHCs across different types of disability. Data from the public health survey of children and adolescents in Scania, Sweden, 2012 was used. A questionnaire was answered anonymously in school by 9791 students in the 9th grade (response rate 83%), and 7533 of these with valid answers on key questions were included in this study. Associations with daily SHCs were investigated by multi-adjusted logistic regression analyses. Any disability was reported by 24.1% of boys and 22.0% of girls. Disabled students were more exposed to cyber harassment (boys: 20.0%; girls: 28.2%) than non-disabled peers (boys: 11.8%; girls: 18.1%). Exposure to traditional bullying showed the same pattern but with a lower prevalence. Disabled students had around doubled odds of both daily psychological SHCs and daily somatic SHCs in the fully adjusted models. In general, the odds increased with exposure to cyber harassment or traditional bullying and the highest odds were seen among disabled students exposed to both cyber harassment and traditional bullying. Students with ADHD/ADD had the highest odds of daily psychological SHCs as well as exposure to traditional bullying across six disability types. Disabled adolescents report poorer health and are more exposed to both traditional bullying and cyber harassment. This public health issue needs more attention in schools and in society in general.

Prevalence of Mental and Social Disorders in Adults Attending Primary Care Centers in Bosnia and Herzegovina

PubMed Central

Broers, Teresa; Hodgetts, Geoffrey; Batić-Mujanović, Olivera; Petrović, Verica; Hasanagić, Melida; Godwin, Marshall

2006-01-01

Aim To determine the prevalence of mental and social disorders in adults who attend primary care health centers in Bosnia and Herzegovina. Methods Sixty-nine family physicians from the Primary Care Research Network in Bosnia and Herzegovina each invited 20 randomly selected patients from their practices to complete the Patient Health Questionnaire (PHQ), which consists of 26-58 questions about symptoms and signs of depression, anxiety, somatization disorder, eating disorders, and alcoholism. A total of 1574 patients were invited to participate in the study. Physicians reviewed the PHQ and calculated the final score, which determined a provisional diagnosis. Definitive diagnosis was determined by further questioning and clinical knowledge of the patient. Data collection was performed between November 2003 and January 2004. Lists of non-participants were maintained by the physicians. Results The response rate was 82%. Of 1285 respondents, 61% were women. At least one type of mental or social disorder was found in 26% of the respondents, and 12% had more than one disorder. Somatization disorder, major depression syndrome, and panic syndrome were experienced by 16%, 10%, and 14% of respondents, respectively, while 5% or less were suffering from eating disorders or alcohol abuse. More women than men had somatization disorder, panic syndrome, and binge eating disorder, while more men than women reported alcohol abuse. Conclusion More than one-quarter of all adults who attended family medicine centers in Bosnia and Herzegovina presented with at least one type of mental or social disturbance. New health policies, strengthened professional training, and accessible support networks need to be developed throughout the country. PMID:16758527

Generation of peanut mutants by fast neutron irradiation combined with in vitro culture

PubMed Central

Wang, Jing-Shan; Sui, Jiong-Ming; Xie, Yong-Dun; Guo, Hui-Jun; Qiao, Li-Xian; Zhao, Li-Lan; Yu, Shan-Lin; Liu, Lu-Xiang

2015-01-01

Induced mutations have played an important role in the development of new plant varieties. In this study, we investigated the effects of fast neutron irradiation on somatic embryogenesis combined with plant regeneration in embryonic leaflet culture to develop new peanut (Arachis hypogaea L.) germplasm for breeding. The dry seeds of the elite cultivar Luhua 11 were irradiated with fast neutrons at dosages of 9.7, 14.0 and 18.0 Gy. The embryonic leaflets were separated and incubated in a medium with 10.0-mg/l 2,4-D to induce somatic embryogenesis. Next, they were incubated in a medium with 4.0-mg/l BAP for plant regeneration. As the irradiation dosage increased, the frequency of both somatic embryo formation and plantlet regeneration decreased. The regenerated plantlets were grafted onto rootstocks and were transplanted into the field. Later, the mature seeds of the regenerated plants were harvested. The M2 generation plants from most of the regenerated cultivars exhibited variations and segregation in vigor, plant height, branch and pod number, pod size, and pod shape. To determine whether the phenotypes were associated with genomic modification, we compared the DNA polymorphisms between the wild-type plants and 19 M3-generation individuals from different regenerated plants. We used 20 pairs of simple sequence repeat (SSR) primers and detected polymorphisms between most of the mutants and the wild-type plants (Luhua 11). Our results indicate that using a combination of fast neutron irradiation and tissue culture is an effective approach for creating new peanut germplasm. PMID:25653418

DSM-5 PTSD's symptom dimensions and relations with major depression's symptom dimensions in a primary care sample.

PubMed

Contractor, Ateka A; Durham, Tory A; Brennan, Julie A; Armour, Cherie; Wutrick, Hanna R; Frueh, B Christopher; Elhai, Jon D

2014-01-30

Existing literature indicates significant comorbidity between posttraumatic stress disorder (PTSD) and major depression. We examined whether PTSD's dysphoria and mood/cognitions factors, conceptualized by the empirically supported four-factor DSM-5 PTSD models, account for PTSD's inherent relationship with depression. We hypothesized that depression's somatic and non-somatic factors would be more related to PTSD's dysphoria and mood/cognitions factors than other PTSD model factors. Further, we hypothesized that PTSD's arousal would significantly mediate relations between PTSD's dysphoria and somatic/non-somatic depression. Using 181 trauma-exposed primary care patients, confirmatory factor analyses (CFA) indicated a well-fitting DSM-5 PTSD dysphoria model, DSM-5 numbing model and two-factor depression model. Both somatic and non-somatic depression factors were more related to PTSD's dysphoria and mood/cognitions factors than to re-experiencing and avoidance factors; non-somatic depression was more related to PTSD's dysphoria than PTSD's arousal factor. PTSD's arousal did not mediate the relationship between PTSD's dysphoria and somatic/non-somatic depression. Implications are discussed. © 2013 Published by Elsevier Ireland Ltd.

The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

DTIC Science & Technology

2016-04-01

somatic mutations of RhoA in peripheral T cell lymphomas (PTCLs) (16-18) and in diffuse-type gastric carcinomas (19-21). Surprisingly, unlike Rac1...Diffuse-type gastric cancers exhibited mutations in the effector binding domain of RhoA, most commonly Y42C (19-21), which prevents binding to the...Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas . Nat Genet 2014;46

Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA).

PubMed

Hotta, Osamu; Tanaka, Ayaki; Torigoe, Akira; Imai, Kazuaki; Ieiri, Norio

2017-02-01

The epipharynx is an immunologically active site even under normal conditions, and enhanced immunologic activation is prone to occur in response to an upper respiratory infection, air pollution, and possibly to vaccine adjuvants. Due to the potential link between the central nervous system and immune function, a relationship between epipharyngitis and autonomic nervous disturbance as well as autoimmune disease has been suggested. Various functional somatic symptoms have been described after human papillomavirus (HPV) vaccination, although a causal relationship has not been established. We examined the epipharynx in young women showing functional somatic symptoms following HPV vaccination. Surprisingly, despite having minimal symptoms involving the pharynx, all patients were found to have severe epipharyngitis. In addition, significant improvement in symptoms was seen in most patients who underwent epipharyngeal treatment. Thus, we speculate that the chronic epipharyngitis potentially caused by the vaccine adjuvant may be involved in the pathogenesis of functional somatic syndrome (FSS) post-HPV vaccination. Further, we suggest that epipharyngeal treatment may be effective for various types of FSS regardless of the initial cause, as well as for some autoimmune diseases, and that this may be an important direction in future research.

A comprehensive characterization of rare mitochondrial DNA variants in neuroblastoma.

PubMed

Calabrese, Francesco Maria; Clima, Rosanna; Pignataro, Piero; Lasorsa, Vito Alessandro; Hogarty, Michael D; Castellano, Aurora; Conte, Massimo; Tonini, Gian Paolo; Iolascon, Achille; Gasparre, Giuseppe; Capasso, Mario

2016-08-02

Neuroblastoma, a tumor of the developing sympathetic nervous system, is a common childhood neoplasm that is often lethal. Mitochondrial DNA (mtDNA) mutations have been found in most tumors including neuroblastoma. We extracted mtDNA data from a cohort of neuroblastoma samples that had undergone Whole Exome Sequencing (WES) and also used snap-frozen samples in which mtDNA was entirely sequenced by Sanger technology. We next undertook the challenge of determining those mutations that are relevant to, or arisen during tumor development. The bioinformatics pipeline used to extract mitochondrial variants from matched tumor/blood samples was enriched by a set of filters inclusive of heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. Our in silico multistep workflow applied both on WES and Sanger-sequenced neuroblastoma samples, allowed us to identify a limited burden of somatic and germline mitochondrial mutations with a potential pathogenic impact. The few singleton germline and somatic mitochondrial mutations emerged, according to our in silico analysis, do not appear to impact on the development of neuroblastoma. Our findings are consistent with the hypothesis that most mitochondrial somatic mutations can be considered as 'passengers' and consequently have no discernible effect in this type of cancer.

Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells.

PubMed

Shipony, Zohar; Mukamel, Zohar; Cohen, Netta Mendelson; Landan, Gilad; Chomsky, Elad; Zeliger, Shlomit Reich; Fried, Yael Chagit; Ainbinder, Elena; Friedman, Nir; Tanay, Amos

2014-09-04

Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type-specific gene expression. Here we develop new methods for quantitative inference of DNA methylation turnover rates, and show that human embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells. In contrast, somatic cells transmit considerable epigenetic information to progenies. Paradoxically, the persistence of the somatic epigenome makes it more vulnerable to noise, since random epimutations can accumulate to massively perturb the epigenomic ground state. The rate of epigenetic perturbation depends on the genomic context, and, in particular, DNA methylation loss is coupled to late DNA replication dynamics. Epigenetic perturbation is not observed in the pluripotent state, because the rapid turnover-based equilibrium continuously reinforces the canonical state. This dynamic epigenetic equilibrium also explains how the epigenome can be reprogrammed quickly and to near perfection after induced pluripotency.

Using computer simulations to determine the limitations of dynamic clamp stimuli applied at the soma in mimicking distributed conductance sources.

PubMed

Lin, Risa J; Jaeger, Dieter

2011-05-01

In previous studies we used the technique of dynamic clamp to study how temporal modulation of inhibitory and excitatory inputs control the frequency and precise timing of spikes in neurons of the deep cerebellar nuclei (DCN). Although this technique is now widely used, it is limited to interpreting conductance inputs as being location independent; i.e., all inputs that are biologically distributed across the dendritic tree are applied to the soma. We used computer simulations of a morphologically realistic model of DCN neurons to compare the effects of purely somatic vs. distributed dendritic inputs in this cell type. We applied the same conductance stimuli used in our published experiments to the model. To simulate variability in neuronal responses to repeated stimuli, we added a somatic white current noise to reproduce subthreshold fluctuations in the membrane potential. We were able to replicate our dynamic clamp results with respect to spike rates and spike precision for different patterns of background synaptic activity. We found only minor differences in the spike pattern generation between focal or distributed input in this cell type even when strong inhibitory or excitatory bursts were applied. However, the location dependence of dynamic clamp stimuli is likely to be different for each cell type examined, and the simulation approach developed in the present study will allow a careful assessment of location dependence in all cell types.

Somatic Symptom and Related Disorders

MedlinePlus

... caused by somatic symptom and related disorders are real, they are not imagined. Like many medical problems, somatic symptom and related disorders often run in families. They also tend to come and go over time. How is somatic symptom and related disorders diagnosed? ...

[Comorbide somatic pathology in servicemen with neurotic disorders].

PubMed

Kurasov, E S; Marchenko, A A; Krasnov, A A; Golovach, I G; Kozlova, S N

2012-04-01

Prevalence and structure of comorbidity a somatic pathology in military men with neurotic disorders was studied. It was established that 40,4% of surveyed noted concomitant somatic pathology, the structure of which was dominated by gastro-intestinal tract (26,8%), and pathology of the cardiovascular system (21,6%). It is shown that concomitant somatic pathology provided aggravating effect on clinic neurotic disorders in serviceman, making it difficult to diagnose mental disorders. The greatest risk concomitant a somatic pathology was marked in patients with depressive and somatoform disorders. Indicates the need for specialized standards of care for persons with comorbid mental and somatic disorders.

The Importance of Somatic Symptoms in Depression in Primary Care

PubMed Central

Tylee, André; Gandhi, Paul

2005-01-01

Objective: Patients with depression present with psychological and somatic symptoms, including general aches and pains. In primary care, somatic symptoms often dominate. A review of the literature was conducted to ascertain the importance of somatic symptoms in depression in primary care. Data sources and extraction: MEDLINE, EMBASE, and PsychLIT/PsychINFO databases (1985–January 2004) were searched for the terms depression, depressive, depressed AND physical, somatic, unexplained symptoms, complaints, problems; somatised, somatized symptoms; somatisation, somatization, somatoform, psychosomatic; pain; recognition, underrecognition; diagnosis, underdiagnosis; acknowledgment, underacknowledgment; treatment, undertreatment AND primary care, ambulatory care; primary physician; office; general practice; attribution, reattribution; and normalising, normalizing. Only English-language publications and abstracts were considered. Study selection: More than 80 papers related to somatic symptoms in depression were identified using the content of their titles and abstracts. Data synthesis: Approximately two thirds of patients with depression in primary care present with somatic symptoms. These patients are difficult to diagnose, feel an increased burden of disease, rely heavily on health care services, and are harder to treat. Patient and physician factors that prevent discussion of psychological symptoms during consultations must be overcome. Conclusions: Educational initiatives that raise awareness of somatic symptoms in depression and help patients to reattribute these symptoms should help to improve the recognition of depression in primary care. PMID:16163400

Characterization of a higher plant herbicide-resistant phytoene desaturase and its use as a selectable marker

USDA-ARS?s Scientific Manuscript database

Three natural somatic mutations at codon 304 of the phytoene desaturase gene (pds) of Hydrilla verticillata ( L. f. Royle) have been reported to provide resistance to the herbicide fluridone. We substituted the arginine 304 present in the wild-type H. verticillata phytoene desaturase (PDS) with all...

Cleft Type, Age, and Sex Differences in Teen-Agers' Ratings of Their Own Behavior, Self-Esteem, and Attitude toward Clefting.

ERIC Educational Resources Information Center

Starr, Philip

1980-01-01

The behavior, self-esteem, and attitude toward clefting of 94 adolescents being treated at a clinic for oral-facial anomalies and communicative disorders were examined. Younger teenagers were more aggressive, more active, and had more somatic complaints than did the older teenagers. (SBH)

Long interspersed element-1 protein expression is a hallmark of many human cancers.

PubMed

Rodić, Nemanja; Sharma, Reema; Sharma, Rajni; Zampella, John; Dai, Lixin; Taylor, Martin S; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Maitra, Anirban; Torbenson, Michael S; Goggins, Michael; Shih, Ie-Ming; Duffield, Amy S; Montgomery, Elizabeth A; Gabrielson, Edward; Netto, George J; Lotan, Tamara L; De Marzo, Angelo M; Westra, William; Binder, Zev A; Orr, Brent A; Gallia, Gary L; Eberhart, Charles G; Boeke, Jef D; Harris, Chris R; Burns, Kathleen H

2014-05-01

Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Rabbit embryonic stem cell lines derived from fertilized, parthenogenetic or somatic cell nuclear transfer embryos

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

Fang, Zhen F.; Gai, Hui; Huang, You Z.

2006-11-01

Embryonic stem cells were isolated from rabbit blastocysts derived from fertilization (conventional rbES cells), parthenogenesis (pES cells) and nuclear transfer (ntES cells), and propagated in a serum-free culture system. Rabbit ES (rbES) cells proliferated for a prolonged time in an undifferentiated state and maintained a normal karyotype. These cells grew in a monolayer with a high nuclear/cytoplasm ratio and contained a high level of alkaline phosphate activity. In addition, rbES cells expressed the pluripotent marker Oct-4, as well as EBAF2, FGF4, TDGF1, but not antigens recognized by antibodies against SSEA-1, SSEA-3, SSEA-4, TRA-1-10 and TRA-1-81. All 3 types of ESmore » cells formed embryoid bodies and generated teratoma that contained tissue types of all three germ layers. rbES cells exhibited a high cloning efficiency, were genetically modified readily and were used as nuclear donors to generate a viable rabbit through somatic cell nuclear transfer. In combination with genetic engineering, the ES cell technology should facilitate the creation of new rabbit lines.« less

Complex Mental Health Sequelae of Psychological Trauma Among Women in Prenatal Care

PubMed Central

Seng, Julia S.; D’Andrea, Wendy; Ford, Julian D.

2014-01-01

Pregnancy is a critical time to identify and address maternal mental health problems, for the health of both mother and child. Pregnant women with histories of exposure to interpersonal psychological trauma may experience a range of mental health problems including but not limited to posttraumatic stress disorder (PTSD). In a community sample of 1,581 pregnant women, 25% reported symptoms consistent with at least one of six syndromes, including PTSD, major depressive disorder (MDD), generalized anxiety disorder (GAD), or clinically significant dissociation, somatization, or affect dysregulation. Six sub-groups with distinct mental health problem profiles were identified by cluster analysis. Controlling for sociodemographic risk factors, women with histories of interpersonal trauma were over-represented in four sub-groups characterized by: (1) PTSD comorbid with depression (childhood sexual abuse), (2) PTSD comorbid with affect/interpersonal dysregulation (childhood physical or emotional abuse), (3) somatization (adult abuse), and (4) GAD (foster/adoptive placement). Findings suggest risk relationships warranting further study between different types of interpersonal trauma exposure and psychiatric outcomes in pregnant women, including PTSD with two types of comorbidity. PMID:25558308

Germline and somatic genetic predictors of pathological response in neoadjuvant settings of rectal and esophageal cancers: systematic review and meta-analysis.

PubMed

Salnikova, L E; Kolobkov, D S

2016-06-01

Oncologists have pointed out an urgent need for biomarkers that can be useful for clinical application to predict the susceptibility of patients to preoperative therapy. This review collects, evaluates and combines data on the influence of reported somatic and germline genetic variations on histological tumor regression in neoadjuvant settings of rectal and esophageal cancers. Five hundred and twenty-seven articles were identified, 204 retrieved and 61 studies included. Among 24 and 14 genetic markers reported for rectal and esophageal cancers, respectively, significant associations in meta-analyses were demonstrated for the following markers. In rectal cancer, major response was more frequent in carriers of the TYMS genotype 2 R/2 R-2 R/3 R (rs34743033), MTHFR genotype 677C/C (rs1801133), wild-type TP53 and KRAS genes. In esophageal cancer, successful therapy appeared to correlate with wild-type TP53. These results may be useful for future research directions to translate reported data into practical clinical use.

Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines.

PubMed

Ellrott, Kyle; Bailey, Matthew H; Saksena, Gordon; Covington, Kyle R; Kandoth, Cyriac; Stewart, Chip; Hess, Julian; Ma, Singer; Chiotti, Kami E; McLellan, Michael; Sofia, Heidi J; Hutter, Carolyn; Getz, Gad; Wheeler, David; Ding, Li

2018-03-28

The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls for the TCGA data to enable robust cross-tumor-type analyses. Our approach accounts for variance and batch effects introduced by the rapid advancement of DNA extraction, hybridization-capture, sequencing, and analysis methods over time. We present best practices for applying an ensemble of seven mutation-calling algorithms with scoring and artifact filtering. The dataset created by this analysis includes 3.5 million somatic variants and forms the basis for PanCan Atlas papers. The results have been made available to the research community along with the methods used to generate them. This project is the result of collaboration from a number of institutes and demonstrates how team science drives extremely large genomics projects. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

In situ mutation detection and visualization of intratumor heterogeneity for cancer research and diagnostics

PubMed Central

Grundberg, Ida; Kiflemariam, Sara; Mignardi, Marco; Imgenberg-Kreuz, Juliana; Edlund, Karolina; Micke, Patrick; Sundström, Magnus; Sjöblom, Tobias

2013-01-01

Current assays for somatic mutation analysis are based on extracts from tissue sections that often contain morphologically heterogeneous neoplastic regions with variable contents of genetically normal stromal and inflammatory cells, obscuring the results of the assays. We have developed an RNA-based in situ mutation assay that targets oncogenic mutations in a multiplex fashion that resolves the heterogeneity of the tissue sample. Activating oncogenic mutations are targets for a new generation of cancer drugs. For anti-EGFR therapy prediction, we demonstrate reliable in situ detection of KRAS mutations in codon 12 and 13 in colon and lung cancers in three different types of routinely processed tissue materials. High-throughput screening of KRAS mutation status was successfully performed on a tissue microarray. Moreover, we show how the patterns of expressed mutated and wild-type alleles can be studied in situ in tumors with complex combinations of mutated EGFR, KRAS and TP53. This in situ method holds great promise as a tool to investigate the role of somatic mutations during tumor progression and for prediction of response to targeted therapy. PMID:24280411

Flow cytometry sorting of nuclei enables the first global characterization of Paramecium germline DNA and transposable elements.

PubMed

Guérin, Frédéric; Arnaiz, Olivier; Boggetto, Nicole; Denby Wilkes, Cyril; Meyer, Eric; Sperling, Linda; Duharcourt, Sandra

2017-04-26

DNA elimination is developmentally programmed in a wide variety of eukaryotes, including unicellular ciliates, and leads to the generation of distinct germline and somatic genomes. The ciliate Paramecium tetraurelia harbors two types of nuclei with different functions and genome structures. The transcriptionally inactive micronucleus contains the complete germline genome, while the somatic macronucleus contains a reduced genome streamlined for gene expression. During development of the somatic macronucleus, the germline genome undergoes massive and reproducible DNA elimination events. Availability of both the somatic and germline genomes is essential to examine the genome changes that occur during programmed DNA elimination and ultimately decipher the mechanisms underlying the specific removal of germline-limited sequences. We developed a novel experimental approach that uses flow cell imaging and flow cytometry to sort subpopulations of nuclei to high purity. We sorted vegetative micronuclei and macronuclei during development of P. tetraurelia. We validated the method by flow cell imaging and by high throughput DNA sequencing. Our work establishes the proof of principle that developing somatic macronuclei can be sorted from a complex biological sample to high purity based on their size, shape and DNA content. This method enabled us to sequence, for the first time, the germline DNA from pure micronuclei and to identify novel transposable elements. Sequencing the germline DNA confirms that the Pgm domesticated transposase is required for the excision of all ~45,000 Internal Eliminated Sequences. Comparison of the germline DNA and unrearranged DNA obtained from PGM-silenced cells reveals that the latter does not provide a faithful representation of the germline genome. We developed a flow cytometry-based method to purify P. tetraurelia nuclei to high purity and provided quality control with flow cell imaging and high throughput DNA sequencing. We identified 61 germline transposable elements including the first Paramecium retrotransposons. This approach paves the way to sequence the germline genomes of P. aurelia sibling species for future comparative genomic studies.

Experimentally Manipulated Somatic Information and Somatization Tendencies and their Impact on Physical Symptom Reporting and Performance in a Physically Strenuous Task

PubMed Central

CASTO, KATHLEEN; LECCI, LEN

2012-01-01

This study attempts to determine whether the presentation of an experimentally manipulated somatic experience during a physically strenuous task can influence physical performance and symptom reporting. The study also compares the relative influence of experimentally manipulated somatic information (state somatization) with stable individual differences in the tendency to amplify physical symptoms (trait somatization) on performance and symptom reporting. 194 participants completed standardized measures of somatization tendencies, state anxiety, neuroticism and conscientiousness. Participants where then given a mock physical exam, with individuals randomly assigned to receive either favorable or unfavorable somatic information. All participants then had their body mass index assessed and completed a rigorous exercise task, with quantification of performance. Physiological measures of blood pressure and pulse were also assessed before and after the exercise task. The experimentally manipulated presentation of somatic information predicted both performance and physical symptoms, even after controlling for BMI, neuroticism, conscientiousness, and state anxiety. Moreover, expected performance uniquely and significantly predicted performance above and beyond condition, anxiety, BMI, neuroticism, and conscientiousness. Somatosensory amplification tendencies also predicted symptom endorsement, but not performance. Findings suggest that both state and trait expectations with respect to somatic experiences influence symptom reporting and to a lesser extent performance, even after controlling for variables known to strongly influence each of these outcomes. Results are consistent with the cognitive-perceptual and the cognitive-appraisal models of somatic interpretation. PMID:27182375

Somatic Symptom Disorder in Semantic Dementia: The Role of Alexisomia.

PubMed

Gan, Joanna J; Lin, Andrew; Samimi, Mersal S; Mendez, Mario F

Semantic dementia (SD) is a neurodegenerative disorder characterized by loss of semantic knowledge. SD may be associated with somatic symptom disorder due to excessive preoccupation with unidentified somatic sensations. To evaluate the frequency of somatic symptom disorder among patients with SD in comparison to comparably demented patients with Alzheimer׳s disease. A retrospective cohort study was conducted using clinical data from a referral-based behavioral neurology program. Fifty-three patients with SD meeting criteria for imaging-supported semantic variant primary progressive aphasia (another term for SD) were compared with 125 patients with clinically probable Alzheimer disease. Logistic regression controlled for sex, age, disease duration, education, overall cognitive impairment, and depression. The prevalence of somatic symptom disorder was significantly higher among patients with SD (41.5%) compared to patients with Alzheimer disease (11.2%) (odds ratio = 6:1; p < 0.001). Somatic symptom disorder was associated with misidentification and preoccupation with normal bodily sensations such as hunger, bladder filling, borborygmi, rhinorrhea, and reflux; excessive concern over the incompletely understood meaning or source of pain or other symptoms; and Cotard syndrome or the delusion that unidentified somatic symptoms signify death or deterioration. SD, a disorder of semantic knowledge, is associated with somatic symptom disorder from impaired identification of somatic sensations. Their inability to read and name somatic sensations, or "alexisomia," results in disproportionate and persistent concern about somatic sensations with consequent significant disability. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.

PubMed

Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne-Vibeke; Kruse, Torben A; Larsen, Martin Jakob

2016-01-01

Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths.

Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data

PubMed Central

Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne-Vibeke; Kruse, Torben A.; Larsen, Martin Jakob

2016-01-01

Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths. PMID:27002637

[Somatic complaints, emotional awareness and maladjustment in schoolchildren].

PubMed

Ordóñez, A; Maganto, C; González, R

2015-05-01

Somatic complaints are common in childhood. Research has shown their relationship with emotional awareness and maladjustment. The study had three objectives: 1) to analyze the prevalence of somatic complaints; 2) To explore the relationships between the variables evaluated: somatic complaints, differentiating emotions, verbal sharing of emotions, not hiding emotions, body awareness, attending to others' emotions, analysis of emotions, and personal, social, family, and school maladjustments; and 3) To identify predictors of somatic complaints. The study included a total of 1,134 randomly selected schoolchildren of both sexes between 10-12 years old (M=10.99; SD=0.88). The Somatic Complaint List, Emotional Awareness Questionnaire, and Self-reported Multifactor Test of Childhood Adaptation were used to gather information. The results showed that the prevalence of somatic complaints was 90.2%, with fatigue, headache and stomachache being the most frequently. Dizziness and headache were more common in girls, and the frequency of complaints decreases with age. Somatic complaints are negatively related to emotional awareness, and positively related to maladjustment. The variables that contribute the most to the prediction of somatic complaints are personal maladjustment (25.1%) and differentiating emotions (2.5%). The study shows that personal maladjustment is the best predictor of somatic complaints; the more emotional awareness and better adapted the child, the fewer somatic complaints they lodge. Childhood is a stage with significant physical discomfort. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Zygotic and somatic embryo morphogenesis in Pinus pinaster: comparative histological and histochemical study.

PubMed

Tereso, Susana; Zoglauer, Kurt; Milhinhos, Ana; Miguel, Célia; Oliveira, M Margarida

2007-05-01

We compared morphogenesis and accumulation of storage proteins and starch in Pinus pinaster Ait. zygotic embryos with those in somatic embryos grown with different carbohydrate sources. The maturation medium for somatic embryos included 80 microM abscisic acid (ABA), 9 g l(-1) gellam gum and either glucose, sucrose or maltose at 44, 88, 175 or 263 mM in the presence or absence of 6% (w/v) polyethylene glycol (PEG) 4000 MW. Maturation medium containing 44 or 88 mM of a carbohydrate source produced only one or no cotyledonary somatic embryos per 0.6 g fresh mass of culture. The addition of PEG to the basal maturation medium resulted in a low yield of cotyledonary somatic embryos that generally showed incomplete development and anatomical abnormalities such as large intercellular spaces and large vacuoles. High concentrations of maltose also induced large intercellular spaces in the somatic embryonic cells, and 263 mM sucrose produced fewer and less developed cotyledonary somatic embryos compared with 175 mM sucrose, indicating that the effect of carbohydrate source is partially osmotic. Zygotic embryos had a lower dry mass than somatic embryos at the same stage of development. Starch granules followed a similar accumulation pattern in zygotic and somatic embryos. A low starch content was found in cotyledonary zygotic embryos and in somatic embryos developed in the presence of 175 mM maltose or 263 mM glucose. In zygotic embryos and in PEG-treated somatic embryos, protein bodies appeared later and were smaller and fewer than in well-developed somatic embryos grown without PEG. We propose that storage protein concentration might be a marker of embryo quality.

Personality traits influencing somatization symptoms and social inhibition in the elderly

PubMed Central

Wongpakaran, Tinakon; Wongpakaran, Nahathai

2014-01-01

Purpose Somatization is a common symptom among the elderly, and even though personality disorders have been found to be associated with somatization, personality traits have not yet been explored with regard to this symptom. The aim of this study is to investigate the relationship between personality traits and somatization, and social inhibition. Patients and methods As part of a cross-sectional study of a community sample, 126 elderly Thais aged 60 years or over completed self-reporting questionnaires related to somatization and personality traits. Somatization was elicited from the somatization subscale when using the Symptom Checklist SCL-90 instrument. Personality traits were drawn from the 16 Personality Factor Questionnaire and social inhibition was identified when using the inventory of interpersonal problems. In addition, path analysis was used to establish the influence of personality traits on somatization and social inhibition. Results Of the 126 participants, 51% were male, 55% were married, and 25% were retired. The average number of years in education was 7.6 (standard deviation =5.2). “Emotional stability” and “dominance” were found to have a direct effect on somatization, as were age and number of years in education, but not sex. Also, 35% of the total variance could be explained by the model, with excellent fit statistics. Dominance was found to have an indirect effect, via vigilance, on social inhibition, which was also influenced by number of years in education and emotional stability. Social inhibition was not found to have any effect on somatization, although hypothetically it should. Conclusion “Emotional stability”, “dominance”, and “vigilance”, as well as age and the number of years in education, were found to have an effect on somatization. Attention should be paid to these factors in the elderly with somatization. PMID:24477217

Personality traits influencing somatization symptoms and social inhibition in the elderly.

PubMed

Wongpakaran, Tinakon; Wongpakaran, Nahathai

2014-01-01

Somatization is a common symptom among the elderly, and even though personality disorders have been found to be associated with somatization, personality traits have not yet been explored with regard to this symptom. The aim of this study is to investigate the relationship between personality traits and somatization, and social inhibition. As part of a cross-sectional study of a community sample, 126 elderly Thais aged 60 years or over completed self-reporting questionnaires related to somatization and personality traits. Somatization was elicited from the somatization subscale when using the Symptom Checklist SCL-90 instrument. Personality traits were drawn from the 16 Personality Factor Questionnaire and social inhibition was identified when using the inventory of interpersonal problems. In addition, path analysis was used to establish the influence of personality traits on somatization and social inhibition. Of the 126 participants, 51% were male, 55% were married, and 25% were retired. The average number of years in education was 7.6 (standard deviation =5.2). "Emotional stability" and "dominance" were found to have a direct effect on somatization, as were age and number of years in education, but not sex. Also, 35% of the total variance could be explained by the model, with excellent fit statistics. Dominance was found to have an indirect effect, via vigilance, on social inhibition, which was also influenced by number of years in education and emotional stability. Social inhibition was not found to have any effect on somatization, although hypothetically it should. "Emotional stability", "dominance", and "vigilance", as well as age and the number of years in education, were found to have an effect on somatization. Attention should be paid to these factors in the elderly with somatization.

Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy

PubMed Central

Soundararajan, Venky; Aravamudan, Murali

2014-01-01

The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action – inspired by the Google page rank algorithm that unearths most “globally connected” websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs – up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site – encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows. PMID:25465236

The Effects of Prior Combat Experience on the Expression of Somatic and Affective Symptoms in Deploying Soldiers

DTIC Science & Technology

2006-01-01

Journal of Psychosomatic ResThe effects of prior combat experience on the expression of somatic and affective symptoms in deploying soldiers William...rates of somatic complaints compared with combat-naive soldiers. Methods: Self-reports of posttraumatic stress disorder (PTSD) and affective and somatic ...identical for the experienced and inexperienced groups, scores on the Affective and Somatic scales differed as a function of prior combat history. Previous

Acculturation, self-construal, mental and physical health: an explorative study of East Asian students in Germany.

PubMed

Shim, Gayoung; Freund, Henning; Stopsack, Malte; Kämmerer, Annette; Barnow, Sven

2014-08-01

The present study explores acculturation and its associated aspects of two East Asian student groups with different levels of exposure to German culture (100 international students from East Asian countries [IS]; 61 second generation students of East Asian descent [SGS]). First, we investigated the relationships between acculturation, self-construal, depressive and somatic symptoms, and differences between the student groups in these variables. Second, the four acculturation types (integration, assimilation, separation and marginalization) were examined regarding their relationship to self-construal and health outcomes. The results showed that the acculturation dimensions (mainstream, heritage) were relevant to the level of depressive symptoms for IS which was not the case for SGS. Furthermore, IS reported more somatic symptoms whereas there was no difference between the two groups in the level of depressive symptoms. In the analysis of acculturation types, assimilated and integrated students were characterized by high independent self-construal, while separated and integrated students showed high interdependent self-construal. Assimilated students displayed the least depressive symptoms of all acculturation groups. This study highlights different characteristics of East Asian students in acculturation, self-construal and health outcomes, and discusses the complexity of the relationships between acculturation types and health. © 2013 International Union of Psychological Science.

Incidence of adverse events in Sweden during 2013–2016: a cohort study describing the implementation of a national trigger tool

PubMed Central

Nilsson, Lena; Borgstedt-Risberg, Madeleine; Soop, Michael; Nylén, Urban; Ålenius, Carina; Rutberg, Hans

2018-01-01

Objectives To describe the implementation of a trigger tool in Sweden and present the national incidence of adverse events (AEs) over a 4-year period during which an ongoing national patient safety initiative was terminated. Design Cohort study using retrospective record review based on a trigger tool methodology. Setting and participants Patients ≥18 years admitted to all somatic acute care hospitals in Sweden from 2013 to 2016 were randomised into the study. Primary and secondary outcome measures Primary outcome measure was the incidence of AEs, and secondary measures were type of injury, severity of harm, preventability of AEs, estimated healthcare cost of AEs and incidence of AEs in patients cared for in another type of unit than the one specialised for their medical needs (‘off-site’). Results In a review of 64 917 admissions, the average AE rates in 2014 (11.6%), 2015 (10.9%) and 2016 (11.4%) were significantly lower than in 2013 (13.1%). The decrease in the AE rates was seen in different age groups, in both genders and for preventable and non-preventable AEs. The decrease comprised only the least severe AEs. The types of AEs that decreased were hospital-acquired infections, urinary bladder distention and compromised vital signs. Patients cared for ‘off-site’ had 84% more preventable AEs than patients cared for in the appropriate units. The cost of increased length of stay associated with preventable AEs corresponded to 13%–14% of the total cost of somatic hospital care in Sweden. Conclusions The rate of AEs in Swedish somatic hospitals has decreased from 2013 to 2016. Retrospective record review can be used to monitor patient safety over time, to assess the effects of national patient safety interventions and analyse challenges to patient safety such as the increasing care of patients ‘off-site’. It was found that the economic burden of preventable AEs is high. PMID:29602858

Cytoplasmic RNA Granules in Somatic Maintenance.

PubMed

Moujaber, Ossama; Stochaj, Ursula

2018-05-30

Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional "operons". RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies. © 2018 S. Karger AG, Basel.

Linking Anger Trait with Somatization in Low-Grade College Students: Moderating Roles of Family Cohesion and Adaptability

PubMed Central

LIU, Liang; LIU, Cuilian; ZHAO, Xudong

2017-01-01

Background Between 22% and 58% of patients in primary care settings complain of somatic symptoms. Previous research has found that somatization was associated with anger traits and family functions. However, studies that specifically assess the moderating effect of family function in how anger traits become somatic complaints are lacking. Aim This study was designed to examine whether the variances in family cohesion and family adaptability moderated the strength of the relationship between anger traits and somatization. Methods A cross-section design was conducted and 2008 college students were recruited from a comprehensive university in Shanghai. All participants finished questionnaires including Symptom Check List- 90 (SCL-90), State-Trait Anger Expression Inventory 2 (STAXI-2, Chinese version) and Family Adaptability and Cohesion Scale, second edition (FACES II, Chinese Version) to assess their degree of current somatization, anger trait and family function. Hierarchical linear regression analysis (Enter) was conducted respectively for men and women to examine the moderation effect of family cohesion and family adaptability in the association between anger and somatization. Results Somatic symptoms were significantly linked in the expected directions with depression and anger trait for both genders. Family cohesion and family adaptability were negatively associated with somatic symptoms. For female college students family cohesion was found to moderate the link between anger trait and somatization, but for male college students the moderation effect of family cohesion was marginally significant. The moderating role of family adaptability was significant for neither male nor female after current depressive symptoms were accounted for. Conclusion Proneness to anger is an independent predictor of somatization. For women, a high level of family cohesion was a protective factor which could reduce the influence of anger trait on somatic symptoms. Without comorbidity of current depression, family adaptability to some degree exempted individuals with anger proneness from developing somatic complaints. Interventions that integrate family cohesion cultivation, family flexibility fostering and depression treatment might be more effective for somatic patients high in anger trait. PMID:28769543

[Therapeutic cloning: far from application at this stage].

PubMed

De Both, N J

2001-11-03

Therapeutic cloning has become possible since the discovery that nuclei from somatic cells of adult animal tissue can successfully be used for cloning and the fact that human embryonic stem cell lines have been established from preimplantation embryos. When nuclei from healthy tissue of a patient are transplanted into enucleated oocytes, these oocytes can be artificially activated so that embryos develop from which embryonic stem cells of the donor can be derived. These embryonic stem cells can be cultured as permanent lines in unlimited numbers and remain pluripotent, i.e. they can be induced to differentiate into the required cell type by adding one or more specific factors. These cells can then be transplanted back into the patient suffering from either a lack or dysfunction of these cells. This approach prevents the rejection of the transplanted cells by the patient's immunological system. As this type of cloning has a very low efficiency, a large number of unfertilized donor oocytes is required. It is questionable whether enough donors are or will be available for this purpose. The cultured cells must satisfy certain conditions before they can be used for transplantation. They must be checked for chromosomal abnormalities, and a complete differentiation of the embryonic stem cells into the cells types needed by the patient is necessary as after the transplantation, undifferentiated stem cells will form teratomas. Furthermore, it is difficult to ensure that the cells end up in the right place and to ensure that they fully integrate into the existing tissue to form functional connections. Due to this array of technical problems the question remains as to whether therapeutic cloning will become feasible in the near future.

Somatic Mutation Allelic Ratio Test Using ddPCR (SMART-ddPCR): An Accurate Method for Assessment of Preferential Allelic Imbalance in Tumor DNA.

PubMed

de Smith, Adam J; Walsh, Kyle M; Hansen, Helen M; Endicott, Alyson A; Wiencke, John K; Metayer, Catherine; Wiemels, Joseph L

2015-01-01

The extent to which heritable genetic variants can affect tumor development has yet to be fully elucidated. Tumor selection of single nucleotide polymorphism (SNP) risk alleles, a phenomenon called preferential allelic imbalance (PAI), has been demonstrated in some cancer types. We developed a novel application of digital PCR termed Somatic Mutation Allelic Ratio Test using Droplet Digital PCR (SMART-ddPCR) for accurate assessment of tumor PAI, and have applied this method to test the hypothesis that heritable SNPs associated with childhood acute lymphoblastic leukemia (ALL) may demonstrate tumor PAI. These SNPs are located at CDKN2A (rs3731217) and IKZF1 (rs4132601), genes frequently lost in ALL, and at CEBPE (rs2239633), ARID5B (rs7089424), PIP4K2A (rs10764338), and GATA3 (rs3824662), genes located on chromosomes gained in high-hyperdiploid ALL. We established thresholds of AI using constitutional DNA from SNP heterozygotes, and subsequently measured allelic copy number in tumor DNA from 19-142 heterozygote samples per SNP locus. We did not find significant tumor PAI at these loci, though CDKN2A and IKZF1 SNPs showed a trend towards preferential selection of the risk allele (p = 0.17 and p = 0.23, respectively). Using a genomic copy number control ddPCR assay, we investigated somatic copy number alterations (SCNA) underlying AI at CDKN2A and IKZF1, revealing a complex range of alterations including homozygous and hemizygous deletions and copy-neutral loss of heterozygosity, with varying degrees of clonality. Copy number estimates from ddPCR showed high agreement with those from multiplex ligation-dependent probe amplification (MLPA) assays. We demonstrate that SMART-ddPCR is a highly accurate method for investigation of tumor PAI and for assessment of the somatic alterations underlying AI. Furthermore, analysis of publicly available data from The Cancer Genome Atlas identified 16 recurrent SCNA loci that contain heritable cancer risk SNPs associated with a matching tumor type, and which represent candidate PAI regions warranting further investigation.

Factors affecting the electrofusion of mouse and ferret oocytes with ferret somatic cells.

PubMed

Li, Ziyi; Sun, Xingshen; Chen, Juan; Leno, Gregory H; Engelhardt, John F

2005-09-01

The domestic ferret, Mustela putorius furos, holds great promise as a genetic model for human lung disease, provided that key technologies for somatic cell nuclear transfer (SCNT) are developed. In this report, we extend our understanding of SCNT in this species by defining conditions for efficient cell fusion by electrical pulse. Two experimental systems were employed in this study. First, in vivo-matured mouse oocytes and ferret somatic cells were used to establish general parameters for fusion. One fibroblast, or cumulus cell, was agglutinated to nucleate, zona pellucida-free, mouse oocytes, and subjected to an electrical pulse. Similar electrical pulse conditions were also tested with 1 or 2 somatic cells inserted into the perivitelline space (PVS) of intact mouse oocytes. The fusion rate for a single fibroblast with a zona-free oocyte was 80.2%, significantly higher (P < 0.05) than that observed for 1, or 2, fibroblasts placed in the PVS (52.0% and 63.8%, respectively). The fusion rate (44.1%) following insertion of two cumulus cells was significantly higher (P < 0.05) than that following insertion of one cumulus cell (25.1%). Second, in vitro-matured ferret oocytes were enucleated, and one to three fibroblasts or cumulus cells were inserted into the PVS. Zona pellucida-free ferret oocytes were fragile and excluded from the study. The fusion rates with two or three fibroblasts were 71.4% and 76.8%, respectively; significantly higher (P < 0.05) than that for one fibroblast (48.6%). This cell number-dependent difference in fusion efficiency was also observed with cumulus cells. Fusion-derived (ferret-ferret) NT embryos cleaved, formed blastocysts in vitro, and underwent early-stage fetal development following embryo transfer. The rate of development was cell type-independent, in contrast to the cell type-dependent differences observed in fusion efficiency. In conclusion, fibroblasts fused more efficiently than cumulus cells and the efficiency of single cell fusions was improved when two or more cells were inserted into the PVS. These studies define conditions for efficient cell fusion with ferret oocytes and should facilitate SCNT and the development of genetically defined animal models in this species.

Novel APC gene mutations associated with protein alteration in diffuse type gastric cancer.

PubMed

Ghatak, Souvik; Chakraborty, Payel; Sarkar, Sandeep Roy; Chowdhury, Biswajit; Bhaumik, Arup; Kumar, Nachimuthu Senthil

2017-06-02

The role of adenomatous polyposis coli (APC) gene in mitosis might be critical for regulation of genomic stability and chromosome segregation. APC gene mutations have been associated to have a role in colon cancer and since gastric and colon tumors share some common genetic lesions, it is relevant to investigate the role of APC tumor suppressor gene in gastric cancer. We investigated for somatic mutations in the Exons 14 and 15 of APC gene from 40 diffuse type gastric cancersamples. Rabbit polyclonal anti-APC antibody was used, which detects the wild-type APC protein and was recommended for detection of the respective protein in human tissues. Cell cycle analysis was done from tumor and adjacent normal tissue. APC immunoreactivity showed positive expression of the protein in stages I, II, III and negative expression in Stages III and IV. Two novel deleterious variations (g.127576C > A, g.127583C > T) in exon 14 sequence were found to generate stop codon (Y622* and Q625*)in the tumor samples. Due to the generation of stop codon, the APC protein might be truncated and all the regulatory features could be lost which has led to the down-regulation of protein expression. Our results indicate that aneuploidy might occurdue to the codon 622 and 625 APC-driven gastric tumorigenesis, in agreement with our cell cycle analysis. The APC gene function in mitosis and chromosomal stability might be lost and G1 might be arrested with high quantity of DNA in the S phase. Six missense somatic mutations in tumor samples were detected in exon 15 A-B, twoof which showed pathological and disease causing effects based on SIFT, Polyphen2 and SNPs & GO score and were not previously reported in the literature or the public mutation databases. The two novel pathological somatic mutations (g.127576C > A, g.127583C > T) in exon 14 might be altering the protein expression leading to development of gastric cancer in the study population. Our study showed that mutations in the APC gene alter the protein expression and cell cycle regulation in diffuse type gastric adenocarcinoma.

Production of cloned mice and ES cells from adult somatic cells by nuclear transfer: how to improve cloning efficiency?

PubMed

Wakayama, Teruhiko

2007-02-01

Although it has now been 10 years since the first cloned mammals were generated from somatic cells using nuclear transfer (NT), most cloned embryos usually undergo developmental arrest prior to or soon after implantation, and the success rate for producing live offspring by cloning remains below 5%. The low success rate is believed to be associated with epigenetic errors, including abnormal DNA hypermethylation, but the mechanism of "reprogramming" is unclear. We have been able to develop a stable NT method in the mouse in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. Especially in the mouse, only a few laboratories can make clones from adult somatic cells, and cloned mice are never successfully produced from most mouse strains. However, this technique promises to be an important tool for future research in basic biology. For example, NT can be used to generate embryonic stem (NT-ES) cell lines from a patient's own somatic cells. We have shown that NT-ES cells are equivalent to ES cells derived from fertilized embryos and that they can be generated relatively easily from a variety of mouse genotypes and cell types of both sexes, even though it may be more difficult to generate clones directly. In general, NT-ES cell techniques are expected to be applied to regenerative medicine; however, this technique can also be applied to the preservation of genetic resources of mouse strain instead of embryos, oocytes and spermatozoa. This review describes how to improve cloning efficiency and NT-ES cell establishment and further applications.

A SOMATIC-MARKER THEORY OF ADDICTION

PubMed Central

Verdejo-García, Antonio; Bechara, Antoine

2009-01-01

Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic-marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. A growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of “craving”, including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker theory of addiction. We conclude that there are at least two underlying types of dysfunctions where emotional signals (somatic-markers) turns in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action. PMID:18722390

Pulmonary Neoplasms in Patients with Birt-Hogg-Dubé Syndrome: Histopathological Features and Genetic and Somatic Events.

PubMed

Furuya, Mitsuko; Tanaka, Reiko; Okudela, Koji; Nakamura, Satoko; Yoshioka, Hiromu; Tsuzuki, Toyonori; Shibuya, Ryo; Yatera, Kazuhiro; Shirasaki, Hiroki; Sudo, Yoshiko; Kimura, Naoko; Yamada, Kazuaki; Uematsu, Shugo; Kunimura, Toshiaki; Kato, Ikuma; Nakatani, Yukio

2016-01-01

Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder caused by genetic mutations in the folliculin (FLCN) gene. Individuals with BHD have multiple pulmonary cysts and are at a high risk for developing renal cell carcinomas (RCCs). Currently, little information is available about whether pulmonary cysts are absolutely benign or if the lungs are at an increased risk for developing neoplasms. Herein, we describe 14 pulmonary neoplastic lesions in 7 patients with BHD. All patients were confirmed to have germline FLCN mutations. Neoplasm histologies included adenocarcinoma in situ (n = 2), minimally invasive adenocarcinoma (n = 1), papillary adenocarcinoma (n = 1), micropapillary adenocarcinoma (n = 1), atypical adenomatous hyperplasia (n = 8), and micronodular pneumocyte hyperplasia (MPH)-like lesion (n = 1). Five of the six adenocarcinoma/MPH-like lesions (83.3%) demonstrated a loss of heterozygosity (LOH) of FLCN. All of these lesions lacked mutant alleles and preserved wild-type alleles. Three invasive adenocarcinomas possessed additional somatic events: 2 had a somatic mutation in the epidermal growth factor receptor gene (EGFR) and another had a somatic mutation in KRAS. Immunohistochemical analysis revealed that most of the lesions were immunostained for phospho-mammalian target of rapamycin (p-mTOR) and phospho-S6. Collective data indicated that pulmonary neoplasms of peripheral adenocarcinomatous lineage in BHD patients frequently exhibit LOH of FLCN with mTOR pathway signaling. Additional driver gene mutations were detected only in invasive cases, suggesting that FLCN LOH may be an underlying abnormality that cooperates with major driver gene mutations in the progression of pulmonary adenocarcinomas in BHD patients.

Somatic, hematologic phenotype, long-term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology-Oncology).

PubMed

Svahn, Johanna; Bagnasco, Francesca; Cappelli, Enrico; Onofrillo, Daniela; Caruso, Silvia; Corsolini, Fabio; De Rocco, Daniela; Savoia, Anna; Longoni, Daniela; Pillon, Marta; Marra, Nicoletta; Ramenghi, Ugo; Farruggia, Piero; Locasciulli, Anna; Addari, Carmen; Cerri, Carla; Mastrodicasa, Elena; Casazza, Gabriella; Verzegnassi, Federico; Riccardi, Francesca; Haupt, Riccardo; Barone, Angelica; Cesaro, Simone; Cugno, Chiara; Dufour, Carlo

2016-07-01

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy-two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow-up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow-up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666-671, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Upper thoracic respiratory interneurons integrate noxious somatic and visceral information in rats.

PubMed

Qin, Chao; Chandler, Margaret J; Foreman, Robert D; Farber, Jay P

2002-11-01

The aim of this study was to determine if thoracic respiratory interneurons (TRINs) might receive peripheral noxious somatic and visceral inputs. Extracellular potentials of 78 respiration-related T(3) neurons, whose activity was driven by central respiratory output, were recorded from the intermediate zone in pentobarbital anesthetized, paralyzed, and ventilated male rats. These neurons were identified as interneurons by their locations and by the absence of antidromic activation from the cervical sympathetic trunk and cerebellum. Thoracic esophageal distension (ED) was produced by water inflation of a latex balloon (0.1-0.5 ml, 20 s). A catheter was placed in the pericardial sac to administer 0.2 ml bradykinin (10(-5) M) for noxious cardiac stimulation. Of 78 TRINs examined for ED, activity of 24 TRINs increased and activity of 8 TRINs decreased. Intrapericardial bradykinin increased activity in 26/65 TRINs tested and decreased activity in 5 TRINs. Seventy-four TRINs were tested for effects of brush, pressure, and pinch of the chest and upper back areas. No TRINs responded to brushing hair. Low-threshold responses to pressure were observed in 27 TRINs. Fourteen TRINs were wide dynamic range and 4 TRINs had high-threshold responses. Peripheral stimuli affected all types of TRINs, including inspiratory, expiratory, and biphasic neurons. Simultaneous phrenic recordings showed that effects of various somatic and visceral stimuli on TRINs were independent of central respiratory drive. Various somatovisceral and viscerovisceral patterns of input were observed in TRINs. The results suggested that TRINs participate in intraspinal processing and integration of nociceptive information from somatic fields and visceral organs.

Are we Genomic Mosaics? Variations of the Genome of Somatic Cells can Contribute to Diversify our Phenotypes.

PubMed

Astolfi, P A; Salamini, F; Sgaramella, V

2010-09-01

Theoretical and experimental evidences support the hypothesis that the genomes and the epigenomes may be different in the somatic cells of complex organisms. In the genome, the differences range from single base substitutions to chromosome number; in the epigenome, they entail multiple postsynthetic modifications of the chromatin. Somatic genome variations (SGV) may accumulate during development in response both to genetic programs, which may differ from tissue to tissue, and to environmental stimuli, which are often undetected and generally irreproducible. SGV may jeopardize physiological cellular functions, but also create novel coding and regulatory sequences, to be exposed to intraorganismal Darwinian selection. Genomes acknowledged as comparatively poor in genes, such as humans', could thus increase their pristine informational endowment. A better understanding of SGV will contribute to basic issues such as the "nature vs nurture" dualism and the inheritance of acquired characters. On the applied side, they may explain the low yield of cloning via somatic cell nuclear transfer, provide clues to some of the problems associated with transdifferentiation, and interfere with individual DNA analysis. SGV may be unique in the different cells types and in the different developmental stages, and thus explain the several hundred gaps persisting in the human genomes "completed" so far. They may compound the variations associated to our epigenomes and make of each of us an "(epi)genomic" mosaic. An ensuing paradigm is the possibility that a single genome (the ephemeral one assembled at fertilization) has the capacity to generate several different brains in response to different environments.

Effect of Salicylic Acid on Somatic Embryogenesis and Plant Regeneration in Hedychium bousigonianum

USDA-ARS?s Scientific Manuscript database

The objective of this study was to induce somatic embryogenesis in Hedychium bousigonianum Pierre ex Gagnepain and assess the influence of salicylic acid (S) on somatic embryogenesis. Somatic embryos and subsequently regenerated plants were successfully obtained 30 days after transfer of embryogenic...

Research on Somatization and Somatic Symptom Disorders: Ars longa, vita brevis.

PubMed

Dimsdale, Joel E

The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition defines somatic symptom and related disorders as long-standing somatic symptoms that are associated with disproportionate thoughts, feelings, and behaviors, irrespective of whether or not a medical cause for these symptoms can be determined. In this Special Section of Psychosomatic Medicine, several articles address diagnostic issues and the central nervous system correlates of somatic symptom and related disorder and document new developments in its treatment.

[Effects of death anxiety and meaning of life on somatization of grandparent raising grandchildren].

PubMed

Kim, Se-Young

2015-04-01

This study was conducted in order to examine the effects of death anxiety and meaning of life on somatization of grandparents raising grandchildren. A convenience sample of 92 elderly grandparents raising grandchildren was recruited. The study instrument for death anxiety was the 5-point 15 items scale designed by Templer and translated by Ko, Choi, & Lee and for meaning of life, the 7-point 10-items scale by Steger, Frazier, Oishi & Kaler and translated by Won, Kim & Kwon. For somatization, the 5-point 12 items scale designed by Derogatis and translated by Kim, Kim & Won was used. Collected data were analyzed with descriptive statistics, independent t-test, one-way ANOVA, Pearson Correlation and regression using the SPSS 21.0 program. Average scores were 3.55 for death anxiety, 3.43 for meaning of life, and 2.74 for somatization. Death anxiety had the highest positive correlation with somatization. Meaning of life was negatively correlated with death anxiety and somatization. Death anxiety and health status were shown to influence somatization but meaning of life was not shown to influence somatization. The research results indicate that death anxiety and health status influence somatization in grandparents raising grandchildren. These results also provide basic information on the importance of nursing interventions in which the variables influencing somatization in grandparents raising grandchildren are considered.

Beyond abuse: the association among parenting style, abdominal pain, and somatization in IBS patients.

PubMed

Lackner, Jeffrey M; Gudleski, Gregory D; Blanchard, Edward B

2004-01-01

This study assessed the relative strength of the association between abuse, negative parenting style, and somatization in irritable bowel syndrome (IBS) patients. Drawing from preclinical stress physiology and abuse research identifying the family social climate as a frequently stronger and independent determinant of long-term health effects than abuse-specific variables, we predicted that negative parenting behaviors would more strongly correlate with somatization than abuse. Subjects were 81 consecutively evaluated patients, who at baseline underwent psychological testing, measuring perceived parental style, abuse history, somatization, and pain. Although abuse correlated with maternal and paternal rejection, abuse was not associated with somatization. Higher levels of rejection and/or hostility among fathers (not mothers) were more strongly correlated with somatization than was abuse. Further, paternal parenting behaviors were more predictive of somatization than abuse, age, and gender. The lack of an association between abuse and somatization is discussed in light of limitations of biopsychosocial IBS models, whose strong focus on "pathological stressors" (e.g., abuse, trauma) as risk factors may overlook the importance of "less extreme" parenting variables in influencing somatic complaints. The relationship between parenting and somatization is discussed in the context of broader behavioral science research linking disruptions in the quality of parenting to dramatic and long-term changes in patterns of stress reactivity and brain abnormalities seen in IBS patients.

Somatization Increases Disability Independent of Comorbidity

PubMed Central

Orav, E. John; Bates, David W.; Barsky, Arthur J.

2008-01-01

Background Somatoform disorders are an important factor in functional disability and role impairment, though their independent contribution to disability has been unclear because of prevalent medical and psychiatric comorbidity. Objectives To assess the extent of the overlap of somatization with other psychiatric disorders and medical problems, to compare the functional disability and role impairment of somatizing and non-somatizing patients, and to determine the independent contribution of somatization to functional disability and role impairment. Design Patients were surveyed with self-report questionnaires assessing somatization, psychiatric disorder, and role impairment. Medical morbidity was indexed with a computerized medical record audit. Participants Consecutive adults making scheduled visits to their primary care physicians at two hospital-affiliated primary care practices on randomly chosen days. Measurements Intermediate activities of daily living, social activities, and occupational disability. Results Patients with somatization, as well as those with serious medical and psychiatric illnesses, had significantly more impairment of activities of daily life and social activities. When these predictors were considered simultaneously in a multivariable regression, the association with somatization remained highly significant and was comparable to or greater than many major medical conditions. Conclusions Patients with somatization had substantially greater functional disability and role impairment than non-somatizing patients. The degree of disability was equal to or greater than that associated with many major, chronic medical disorders. Adjusting the results for psychiatric and medical co-morbidity had little effect on these findings. PMID:19031038

Unexplained somatic symptoms during major depression: prevalence and clinical impact in a national sample of Italian psychiatric outpatients.

PubMed

Perugi, Giulio; Canonico, Pier Luigi; Carbonato, Paolo; Mencacci, Claudio; Muscettola, Giovanni; Pani, Luca; Torta, Riccardo; Vampini, Claudio; Fornaro, Michele; Parazzini, Fabio; Dumitriu, Arina

2011-01-01

The aim of this study was to explore the prevalence and impact of unexplained somatic symptoms during major depression. A total of 560 consecutive outpatients with a major depressive episode according to the DSM-IV (text revision) were evaluated in 30 psychiatric facilities throughout Italy. 'Unexplained' somatic symptoms were evaluated using the 30-item Somatic Symptoms Checklist (SSCL-30). Somatic symptoms were considered explained if they were best accounted for as coming from a concomitant physical illness or side effects. Patients evaluated their own mood symptomatology using the Zung questionnaires for depression and anxiety and the Hypomania Checklist-32. According to the SSCL-30, only 90 subjects (16.1%) had no unexplained somatic symptoms, while 231 (41.3%) had 1-5 unexplained symptoms and 239 (42.7%) had more than 5. Asthenia was the most commonly observed unexplained somatic symptom (53% of patients). Unexplained somatic symptoms were more common in females and among those suffering from major depression and depression not otherwise specified rather than in patients with recurrent major depression and bipolar disorders. No relationship between unexplained somatic symptoms and hypomanic features was observed. The presence of a large number of unexplained somatic symptoms is associated with more severe depression and higher rates of misdiagnosis and inappropriate treatment. Copyright © 2011 S. Karger AG, Basel.

Structural Brain Connectivity Constrains within-a-Day Variability of Direct Functional Connectivity

PubMed Central

Park, Bumhee; Eo, Jinseok; Park, Hae-Jeong

2017-01-01

The idea that structural white matter connectivity constrains functional connectivity (interactions among brain regions) has widely been explored in studies of brain networks; studies have mostly focused on the “average” strength of functional connectivity. The question of how structural connectivity constrains the “variability” of functional connectivity remains unresolved. In this study, we investigated the variability of resting state functional connectivity that was acquired every 3 h within a single day from 12 participants (eight time sessions within a 24-h period, 165 scans per session). Three different types of functional connectivity (functional connectivity based on Pearson correlation, direct functional connectivity based on partial correlation, and the pseudo functional connectivity produced by their difference) were estimated from resting state functional magnetic resonance imaging data along with structural connectivity defined using fiber tractography of diffusion tensor imaging. Those types of functional connectivity were evaluated with regard to properties of structural connectivity (fiber streamline counts and lengths) and types of structural connectivity such as intra-/inter-hemispheric edges and topological edge types in the rich club organization. We observed that the structural connectivity constrained the variability of direct functional connectivity more than pseudo-functional connectivity and that the constraints depended strongly on structural connectivity types. The structural constraints were greater for intra-hemispheric and heterologous inter-hemispheric edges than homologous inter-hemispheric edges, and feeder and local edges than rich club edges in the rich club architecture. While each edge was highly variable, the multivariate patterns of edge involvement, especially the direct functional connectivity patterns among the rich club brain regions, showed low variability over time. This study suggests that structural connectivity not only constrains the strength of functional connectivity, but also the within-a-day variability of functional connectivity and connectivity patterns, particularly the direct functional connectivity among brain regions. PMID:28848416

Desiccation and Cold Hardening of Date Palm Somatic Embryos Improve Germination.

PubMed

Shareef, Hussein J

2017-01-01

Embryogenic suspension cultures of date palm are ideal for mass propagation of somatic embryos; however, the low percentage of germination of somatic embryos (SE) remains an impediment. This chapter focuses on two important physical factors to improve germination of date palm somatic embryos: the use of partial desiccation (3 h) of somatic embryos and the exposure to low temperature (4 °C for 24 h). High germination percentage (41%) is achieved by desiccation for 3 h. Moreover, adding 0.3 g/L activated charcoal (AC) to the liquid medium further improves somatic embryo number and weight as well as the percentage of germination. Moreover, partial desiccation and low temperature exposure tend to increase proline content. This improved protocol for somatic embryo germination is potentially applicable for commercial micropropagation of date palm.

Pathogenesis and Consequences of Uniparental Disomy in Cancer

PubMed Central

Makishima, Hideki; Maciejewski, Jaroslaw P.

2012-01-01

Systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity (LOH) without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had remained unrecognized as it cannot be detected using routine cytogenetic technologies. Random and recurrent patterns of copy-neutral LOH, also referred to as uniparental disomy (UPD), can be found in specific cancer types and probably contribute to clonal outgrowth owing to various mechanisms. In this review we explore the types, topography, genesis, pathophysiological consequences and clinical implications of UPD. PMID:21518781

Effects of religion and type of religious internalization on the mental health of Iranian adolescents.

PubMed

Mazidi, Mohammad; Ostovar, Soghra

2006-08-01

This study was designed to assess the effects of religion and two types of religious internalization on the mental health of Iranian adolescents. High school students (82 Moslem and 37 Christian) were selected randomly from four high schools in Shiraz and completed the Religious Self-regulation Questionnaire and the General Health Questionnaire. Analysis showed that main effects of types of religious internalization measured on four subscales of the General Health Questionnaire were significant. Religion was significantly associated only with somatic symptoms. For other scales no main effects of religion, types of religious internalization, or their interactions were significant.

Which somatic symptoms are associated with an unfavorable course in Chinese patients with major depressive disorder?

PubMed

Novick, Diego; Montgomery, William S; Aguado, Jaume; Peng, Xiaomei; Brugnoli, Roberto; Haro, Josep Maria

2015-12-01

This was an analysis of the impact of somatic symptoms on the severity and course of depression in Chinese patients treated for an acute episode of major depressive disorder (MDD). Data were extracted from a 3-month prospective observational study which enrolled 909 patients with MDD in psychiatric care settings; this analysis focused on the Chinese patients (n=300). Depression severity was assessed using the Clinical Global Impression of Severity (CGI-S) and 17-item Hamilton Depression Rating Scale (HAMD-17); somatic symptoms were assessed using the patient-rated 28-item Somatic Symptom Inventory (SSI). Cluster analysis using baseline SSI scores grouped patients into three clusters with no/mild, moderate, or severe somatic symptoms. Four SSI factors (pain, autonomic symptoms, energy, and central nervous system) were defined, and regression analyses identified which factors were associated with remission at 3 months. More than 70% of the patients had moderate or severe somatic symptoms. Baseline depression severity (HAMD-17 and CGI-S scores) was associated with more severe somatic symptoms. Remission rates differed between clusters of patients: 84.1%, 72.0%, and 55.3% for no/mild, moderate, and severe somatic symptoms, respectively (P=0.0034). Pain symptoms were the somatic symptoms more strongly associated with lower remission rates at 3 months. Somatic symptoms are associated with greater clinical severity and lower remission rates. Among somatic symptoms, pain symptoms have the greatest prognostic value and should be taken into account when treating patients with depression. © 2015 Wiley Publishing Asia Pty Ltd.

Effect of Cryopreservation and Post-Cryopreservation Somatic Embryogenesis on the Epigenetic Fidelity of Cocoa (Theobroma cacao L.).

PubMed

Adu-Gyamfi, Raphael; Wetten, Andy; Marcelino Rodríguez López, Carlos

2016-01-01

While cocoa plants regenerated from cryopreserved somatic embryos can demonstrate high levels of phenotypic variability, little is known about the sources of the observed variability. Previous studies have shown that the encapsulation-dehydration cryopreservation methodology imposes no significant extra mutational load since embryos carrying high levels of genetic variability are selected against during protracted culture. Also, the use of secondary rather than primary somatic embryos has been shown to further reduce the incidence of genetic somaclonal variation. Here, the effect of in vitro conservation, cryopreservation and post-cryopreservation generation of somatic embryos on the appearance of epigenetic somaclonal variation were comparatively assessed. To achieve this we compared the epigenetic profiles, generated using Methylation Sensitive Amplified Polymorphisms, of leaves collected from the ortet tree and from cocoa somatic embryos derived from three in vitro conditions: somatic embryos, somatic embryos cryopreserved in liquid nitrogen and somatic embryos generated from cryoproserved somatic embryos. Somatic embryos accumulated epigenetic changes but these were less extensive than in those regenerated after storage in LN. Furthermore, the passage of cryopreserved embryos through another embryogenic stage led to further increase in variation. Interestingly, this detected variability appears to be in some measure reversible. The outcome of this study indicates that the cryopreservation induced phenotypic variability could be, at least partially, due to DNA methylation changes. Phenotypic variability observed in cryostored cocoa somatic-embryos is epigenetic in nature. This variability is partially reversible, not stochastic in nature but a directed response to the in-vitro culture and cryopreservation.

Effect of Cryopreservation and Post-Cryopreservation Somatic Embryogenesis on the Epigenetic Fidelity of Cocoa (Theobroma cacao L.)

PubMed Central

Adu-Gyamfi, Raphael; Wetten, Andy; Marcelino Rodríguez López, Carlos

2016-01-01

While cocoa plants regenerated from cryopreserved somatic embryos can demonstrate high levels of phenotypic variability, little is known about the sources of the observed variability. Previous studies have shown that the encapsulation-dehydration cryopreservation methodology imposes no significant extra mutational load since embryos carrying high levels of genetic variability are selected against during protracted culture. Also, the use of secondary rather than primary somatic embryos has been shown to further reduce the incidence of genetic somaclonal variation. Here, the effect of in vitro conservation, cryopreservation and post-cryopreservation generation of somatic embryos on the appearance of epigenetic somaclonal variation were comparatively assessed. To achieve this we compared the epigenetic profiles, generated using Methylation Sensitive Amplified Polymorphisms, of leaves collected from the ortet tree and from cocoa somatic embryos derived from three in vitro conditions: somatic embryos, somatic embryos cryopreserved in liquid nitrogen and somatic embryos generated from cryoproserved somatic embryos. Somatic embryos accumulated epigenetic changes but these were less extensive than in those regenerated after storage in LN. Furthermore, the passage of cryopreserved embryos through another embryogenic stage led to further increase in variation. Interestingly, this detected variability appears to be in some measure reversible. The outcome of this study indicates that the cryopreservation induced phenotypic variability could be, at least partially, due to DNA methylation changes. Key message: Phenotypic variability observed in cryostored cocoa somatic-embryos is epigenetic in nature. This variability is partially reversible, not stochastic in nature but a directed response to the in-vitro culture and cryopreservation. PMID:27403857

Substance-related disorders and somatic symptoms: how should clinicians understand the associations?

PubMed

Yoshimasu, Kouichi

2012-12-01

There are five major patterns which explain the associations between somatic symptoms and substance-related disorders (SRD) in patients without organic disorders. They are withdrawal somatic symptoms, somatic symptoms related to co-morbid mental disorders, those related to co-morbid infectious diseases, functional intractable somatic symptoms (including somatoform disorders), and symptoms associated with intoxication. Those somatic symptoms that occur according to those five patterns might overlap each other, making it difficult for physicians to precisely grasp the associations between somatic symptoms and SRD. This results in a very complicated formation of various kinds of symptoms (syndrome). Furthermore, the clinical and social features of those patterns of associations differ between legal and illicit substances users. It should also be noted that such somatic symptoms associated with SRD may be affected by social factors such as cultural backgrounds or legal restrictions on such substances. Those factors differ according to each country, area, or community whose cultural backgrounds are somewhat specific. In those areas, psychosocial factors such as stigmas, prejudices, or feeling ashamed of one's mental disorder (including SRD) also differ. Thus, it is important to take into account the effects of social or psychosocial backgrounds when evaluating and studying the associations between somatic symptoms and SRD. When clinicians confront patients with somatic symptoms and suspected SRD, they should presume which association pattern is the most significant problem for the patients, based on those psychosocial and biological information obtained from the patients themselves and their surroundings. This procedure might give an opportunity to clinicians for elucidating complicated associations between somatic complaints and SRD.

A Comparison of Somatic Compliants among Depressed and Non-Depressed Older Persons.

ERIC Educational Resources Information Center

Waxman, Howard; And Others

1985-01-01

Examined the relationship among somatic complaints, chronic medical illness, and depression in 127 community elderly. Depression and chronic medical illness were significant contributors to somatic complaining both alone and in interaction. Demographic variables and social supports were largely unrelated to depression, somatic complaints, or…

Somatic Point Mutation Calling in Low Cellularity Tumors

PubMed Central

Kassahn, Karin S.; Holmes, Oliver; Nones, Katia; Patch, Ann-Marie; Miller, David K.; Christ, Angelika N.; Harliwong, Ivon; Bruxner, Timothy J.; Xu, Qinying; Anderson, Matthew; Wood, Scott; Leonard, Conrad; Taylor, Darrin; Newell, Felicity; Song, Sarah; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Steptoe, Anita; Pajic, Marina; Cowley, Mark J.; Pinese, Mark; Chang, David K.; Gill, Anthony J.; Johns, Amber L.; Wu, Jianmin; Wilson, Peter J.; Fink, Lynn; Biankin, Andrew V.; Waddell, Nicola; Grimmond, Sean M.; Pearson, John V.

2013-01-01

Somatic mutation calling from next-generation sequencing data remains a challenge due to the difficulties of distinguishing true somatic events from artifacts arising from PCR, sequencing errors or mis-mapping. Tumor cellularity or purity, sub-clonality and copy number changes also confound the identification of true somatic events against a background of germline variants. We have developed a heuristic strategy and software (http://www.qcmg.org/bioinformatics/qsnp/) for somatic mutation calling in samples with low tumor content and we show the superior sensitivity and precision of our approach using a previously sequenced cell line, a series of tumor/normal admixtures, and 3,253 putative somatic SNVs verified on an orthogonal platform. PMID:24250782

Stem cells in dentistry--review of literature.

PubMed

Dziubińska, P; Jaskólska, M; Przyborowska, P; Adamiak, Z

2013-01-01

Stem cells have been successfully isolated from a variety of human and animal tissues, including dental pulp. This achievement marks progress in regenerative dentistry. This article reviews the latest improvements made in regenerative dental medicine with the involvement of stem cells. Although, various types of multipotent somatic cells can be applied in dentistry, two types of cells have been investigated in this review. Dental pulp cells are classified as: DPSCs, SCAPs and SHEDs.The third group includes two types of cell associated with the periodontium: PDL and DFPC. This review aims to systematize basic knowledge about cellular engineering in dentistry.

Somatic INK4a-ARF locus mutations: a significant mechanism of gene inactivation in squamous cell carcinomas of the head and neck.

PubMed

Poi, M J; Yen, T; Li, J; Song, H; Lang, J C; Schuller, D E; Pearl, D K; Casto, B C; Tsai, M D; Weghorst, C M

2001-01-01

The INK4a-ARF locus is located on human chromosome 9p21 and is known to encode two functionally distinct tumor-suppressor genes. The p16(INK4a) (p16) tumor-suppressor gene product is a negative regulator of cyclin-dependent kinases 4 and 6, which in turn positively regulate progression of mammalian cells through the cell cycle. The p14(ARF) tumor-suppressor gene product specifically interacts with human double minute 2, leading to the subsequent stabilization of p53 and G(1) arrest. Previous investigations analyzing the p16 gene in squamous cell carcinomas of the head and neck (SCCHNs) have suggested the predominate inactivating events to be homozygous gene deletions and hypermethylation of the p16 promoter. Somatic mutational inactivation of p16 has been reported to be low (0-10%, with a combined incidence of 25 of 279, or 9%) and to play only a minor role in the development of SCCHN. The present study examined whether this particular mechanism of INK4a/ARF inactivation, specifically somatic mutation, has been underestimated in SCCHN by determining the mutational status of the p16 and p14(ARF) genes in 100 primary SCCHNs with the use of polymerase chain reaction technology and a highly sensitive, nonradioactive modification of single-stranded conformational polymorphism (SSCP) analysis termed "cold" SSCP. Exons 1alpha, 1beta, and 2 of INK4a/ARF were amplified using intron-based primers or a combination of intron- and exon-based primers. A total of 27 SCCHNs (27%) exhibited sequence alterations in this locus, 22 (22%) of which were somatic sequence alterations and five (5%) of which were a single polymorphism in codon 148. Of the 22 somatic alterations, 20 (91%) directly or indirectly involved exon 2, and two (9%) were located within exon 1alpha. No mutations were found in exon 1beta. All 22 somatic mutations would be expected to yield altered p16 proteins, but only 15 of them should affect p14(ARF) proteins. Specific somatic alterations included microdeletions or insertions (nine of 22, 41%), a microrearrangement (one of 22, 5%), and single nucleotide substitutions (12 of 22, 56%). In addition, we analyzed the functional characteristics of seven unique mutant p16 proteins identified in this study by assessing their ability to inhibit cyclin-dependent kinase 4 activity. Six of the seven mutant proteins tested exhibited reduced function compared with wild-type p16, ranging from minor decreases of function (twofold to eightfold) in four samples to total loss of function (29- to 38-fold decrease) in two other samples. Overall, somatic mutation of the INK4a/ARF tumor suppressor locus, resulting in functionally deficient p16 and possibly p14(ARF) proteins, seems to be a prevalent event in the development of SCCHN. Mol. Carcinog. 30:26-36, 2001. Copyright 2001 Wiley-Liss, Inc.

Associations between low back pain and depression and somatization in a Canadian emerging adult population

PubMed Central

Robertson, David; Kumbhare, Dinesh; Nolet, Paul; Srbely, John; Newton, Genevieve

2017-01-01

Introduction The association between depression, somatization and low back pain has been minimally investigated in a Canadian emerging adult population. Methods 1013 first year Canadian university students completed the Modified Zung Depression Index, the Modified Somatic Perception Questionnaire, and a survey about low back pain frequency and intensity. Multinomial logistic regression was used to measure associations between low back pain and depression and somatization, both independently and co-occurring. Results Over 50% of subjects reported low back pain across grades, and both depression and somatization were significantly positively associated with low back pain. Several positive associations between the cooccurrence of somatization and depression with various grades of low back pain were observed. Discussion These results suggest that low back pain, depression and somatization are relatively common at the onset of adulthood, and should be considered an important focus of public health. PMID:28928493

Recent advances in the study of somatic mosaicism and diseases other than cancer.

PubMed

Erickson, Robert P

2014-06-01

Somatic mosaicism is well appreciated as a cause of cancer and, possibly, aging. Somatic mosaicism as the cause of other diseases is becoming more appreciated. It is especially important in the causation of deforming diseases (e.g., Proteus syndrome; Sturge-Weber syndrome) which are not inherited because early developmental expression is lethal. It also known to make an important contribution to neurological, dermatological, hematological and other diseases (and probably all diseases but many in which it is harder to detect). There have been exciting recent advances in the detection of somatic mosaicism. In particular, for many diseases of somatic overgrowth in which somatic mosaicism as the sole cause was predicted, the gene somatically mutated has been found. A limited number of pathways seem involved in these disorders, some of which are also implicated in cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Elevated levels of psychophysiological arousal and cortisol in patients with somatization syndrome.

PubMed

Rief, W; Shaw, R; Fichter, M M

1998-01-01

This study investigates psychological and psychobiological processes in patients with somatization syndrome. We compared physiological measures (heart rate, finger pulse volume, electrodermal activity, electromyography), cortisol levels, and subjective well-being during rest and during a mental stress task as well as selective attention and memory for illness-related words in 58 patients with somatization syndrome and 21 healthy controls. The somatization group had higher morning salivary cortisol concentrations, higher heart rates, and lower levels of finger pulse volume. During the mental stress task, patients with somatization syndrome felt more distressed and had higher heart rates, whereas controls showed habituation to the experimental situation. We were unable to demonstrate an attention or memory bias specific for somatization. The results point to several psychological, psychophysiological, and psychobiological mechanisms that might be involved in the maintenance of somatization syndrome. These results are discussed from a cognitive-psychobiological perspective.

Predictive factors for somatization in a trauma sample

PubMed Central

2009-01-01

Background Unexplained somatic symptoms are common among trauma survivors. The relationship between trauma and somatization appears to be mediated by posttraumatic stress disorder (PTSD). However, only few studies have focused on what other psychological risk factors may predispose a trauma victim towards developing somatoform symptoms. Methods The present paper examines the predictive value of PTSD severity, dissociation, negative affectivity, depression, anxiety, and feeling incompetent on somatization in a Danish sample of 169 adult men and women who were affected by a series of explosions in a firework factory settled in a residential area. Results Negative affectivity and feelings of incompetence significantly predicted somatization, explaining 42% of the variance. PTSD was significant until negative affectivity was controlled for. Conclusion Negative affectivity and feelings of incompetence significantly predicted somatization in the trauma sample whereas dissociation, depression, and anxiety were not associated with degree of somatization. PTSD as a risk factor was mediated by negative affectivity. PMID:19126224

Premenstrual dysphoric disorder--review of actual findings about mental disorders related to menstrual cycle and possibilities of their therapy.

PubMed

Zukov, I; Ptácek, R; Raboch, J; Domluvilová, D; Kuzelová, H; Fischer, S; Kozelek, P

2010-01-01

It is known that mood disorders in women explicitly relates to estrogen production. Except for these findings phenomenon as Premenstrual Syndrome and Premenstrual Dysphoric Disorder, directly connected to menstrual cycle in women, is widely discussed. Premenstrual dysphoric disorder (PMDD) is a set of subjectively unpleasant mental and somatic symptoms. It appears in luteal phase of ovarian cycle. During menstruation it remits and disappears up to one week from its termination. DSM IV classified PMDD into the category of "Other specific depressive disorders" and further revision DSM IV-TR classifies PMDD as a separate strictly defined psychiatric diagnosis. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) does not include any specific category as PMDD or similar. The closest category F38.8 does not represent the core of the phenomenon because it relates only to general depressive symptomatology and does not give specific diagnostic criteria to menstrual cycle related mood disorders (Grady-Weliky, 2003). In the presented article, possible effectivity of PMDD treatment with the focus to antidepressants of SSRI type (Serotonin selective reuptake inhibitors) is discussed. In spite of interesting and significant findings, the treatment of PMDD and accordingly PMS is above all multidisciplinary question and it must be treated like that.

Gene expression profiling of bovine ovarian follicular and luteal cells provides insight into cellular identities and functions

USDA-ARS?s Scientific Manuscript database

After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

Micropropagation of Citrus spp. by organogenesis and somatic embryogenesis.

PubMed

Chiancone, Benedetta; Germanà, Maria Antonietta

2013-01-01

Citrus spp., the largest fruit crops produced worldwide, are usually asexually propagated by cuttings or grafting onto seedling rootstocks. Most of Citrus genotypes are characterized by polyembryony due to the occurrence of adventive nucellar embryos, which lead to the production of true-to-type plants by seed germination. Tissue culture and micropropagation, in particular, are valuable alternatives to traditional propagation to obtain a high number of uniform and healthy plants in a short time and in a small space. Moreover, in vitro propagation provides a rapid system to multiply the progeny obtained by breeding programs, allows the use of monoembryonic and seedless genotypes as rootstocks, and it is very useful also for breeding and germplasm preservation.In this chapter, two protocols regarding organogenesis of a rootstock and somatic embryogenesis of a cultivar have been described.

Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

DOEpatents

Jensen, Ronald H.; Vanderlaan, Martin; Bigbee, William L.; Stanker, Larry H.; Branscomb, Elbert W.; Grabske, Robert J.

1988-01-01

The present invention provides monoclonal antibodies specific to and distinguish between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype.

Programmable genetic switches to control transcriptional machinery of pluripotency.

PubMed

Pandian, Ganesh N; Sugiyama, Hiroshi

2012-06-01

Transcriptional activators play a central role in the regulation of gene expression and have the ability to manipulate the specification of cell fate. Pluripotency is a transient state where a cell has the potential to develop into more than one type of mature cell. The induction of pluripotency in differentiated cells requires extensive chromatin reorganization regulated by core transcriptional machinery. Several small molecules have been shown to enhance the efficiency of somatic cell reprogramming into pluripotent stem cells. However, entirely chemical-based reprogramming remains elusive. Recently, we reported that selective DNA-binding hairpin pyrrole-imidazole polyamides conjugated with histone deacetylase inhibitor could mimic natural transcription factors and epigenetically activate certain pluripotency-associated genes. Here, we review the need to develop selective chromatin-modifying transcriptional activators for somatic genome reprogramming. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dimensional structure of bodily panic attack symptoms and their specific connections to panic cognitions, anxiety sensitivity and claustrophobic fears.

PubMed

Drenckhan, I; Glöckner-Rist, A; Rist, F; Richter, J; Gloster, A T; Fehm, L; Lang, T; Alpers, G W; Hamm, A O; Fydrich, T; Kircher, T; Arolt, V; Deckert, J; Ströhle, A; Wittchen, H-U; Gerlach, A L

2015-06-01

Previous studies of the dimensional structure of panic attack symptoms have mostly identified a respiratory and a vestibular/mixed somatic dimension. Evidence for additional dimensions such as a cardiac dimension and the allocation of several of the panic attack symptom criteria is less consistent. Clarifying the dimensional structure of the panic attack symptoms should help to specify the relationship of potential risk factors like anxiety sensitivity and fear of suffocation to the experience of panic attacks and the development of panic disorder. In an outpatient multicentre study 350 panic patients with agoraphobia rated the intensity of each of the ten DSM-IV bodily symptoms during a typical panic attack. The factor structure of these data was investigated with nonlinear confirmatory factor analysis (CFA). The identified bodily symptom dimensions were related to panic cognitions, anxiety sensitivity and fear of suffocation by means of nonlinear structural equation modelling (SEM). CFA indicated a respiratory, a vestibular/mixed somatic and a cardiac dimension of the bodily symptom criteria. These three factors were differentially associated with specific panic cognitions, different anxiety sensitivity facets and suffocation fear. Taking into account the dimensional structure of panic attack symptoms may help to increase the specificity of the associations between the experience of panic attack symptoms and various panic related constructs.

Somatic twist: a model for the evolution of decussation.

PubMed

Kinsbourne, Marcel

2013-09-01

In the chordate and vertebrate central nervous system, sensory and motor nerve tracts cross from one side to the other as they connect the brain with sensory receptors and motor neurons. These "decussations," crossings in the form of an X, relate each side of the brain to the opposite side of the body. The protochordates derive from an invertebrate ancestor, but no such contralateral arrangement occurs in any invertebrate phylum. No adaptive benefit of decussation has been established. What might explain the evolution of decussation? A brief review of relevant features of comparative morphology of invertebrates, chordates and vertebrates leads to an explanatory model of decussation. A "somatic twist model" of invertebrate-vertebrate transition accounts for decussations as byproducts of a more momentous change; the relocation of the neuraxis from the ventral to the dorsal aspect of the body. Evidence is presented that this inversion proceeded by means of a twisting of the body 180 degrees on its axis just behind its anterior pole. This rotation aligned the neuraxis with the dorsal head ganglia and brain and by twisting the nerve tracts it brought decussation in its wake. Decussation evolved as a byproduct of a genetically determined partial inversion of the body plan, which resulted in a 180 degree rotation posterior to the brain and oropharynx.

High-frequency plant regeneration through cyclic secondary somatic embryogenesis in black pepper (Piper nigrum L.).

PubMed

Nair, R Ramakrishnan; Dutta Gupta, S

2006-01-01

A high-frequency plantlet regeneration protocol was developed for black pepper (Piper nigrum L.) through cyclic secondary somatic embryogenesis. Secondary embryos formed from the radicular end of the primary somatic embryos which were originally derived from micropylar tissues of germinating seeds on growth regulator-free SH medium in the absence of light. The process of secondary embryogenesis continued in a cyclic manner from the root pole of newly formed embryos resulting in clumps of somatic embryos. Strength of the medium and sucrose concentration influenced the process of secondary embryogenesis and fresh weight of somatic embryo clumps. Full-strength SH medium supplemented with 1.5% sucrose produced significantly higher fresh weight and numbers of secondary somatic embryos while 3.0 and 4.5% sucrose in the medium favored further development of proliferated embryos into plantlets. Ontogeny of secondary embryos was established by histological analysis. Secondary embryogenic potential was influenced by the developmental stage of the explanted somatic embryo and stages up to "torpedo" were more suitable. A single-flask system was standardized for proliferation, maturation, germination and conversion of secondary somatic embryos in suspension cultures. The system of cyclic secondary somatic embryogenesis in black pepper described here represents a permanent source of embryogenic material that can be used for genetic manipulations of this crop species.

Is the impact of depressive complaints on the use of general health care services dependent on severity of somatic morbidity?

PubMed

Koopmans, Gerrit T; Lamers, Leida M

2006-07-01

The aim of this study was to examine the effects of depressive complaints and chronic medical illnesses on prospective somatic health care utilization and the possible heterogeneity of the effect of depressive complaints across levels of medical illness severity. Data from a community-based sample of adults (n=9428) were used, of whom a health survey and claims data, indicating health care use, were available. Assessments of depressive complaints and somatic illnesses were based on self-report. Binomial regression analyses were used to study the expected relations. Depressive complaints and somatic morbidity were both positively related to general health care utilization. Somatic morbidity has an attenuating effect on the impact of depressive complaints: If it becomes more severe, the impact of depressive complaints on utilization is reduced. Depressive complaints are especially related to the use of paramedic services, use of prescription drugs, and consultations of medical specialists. Depressive complaints predict somatic health care utilization, but somatic morbidity attenuates this relation. Future research on this subject should include interaction effects of depressive complaints and somatic morbidity. Interventions aiming to reduce excess use related to mental distress should be primarily targeted on subjects with mental distress who have no comorbid somatic morbidity.

Relationships between psychological state, abuse, somatization and visceral pain sensitivity in irritable bowel syndrome

PubMed Central

Grinsvall, Cecilia; Törnblom, Hans; Tack, Jan; Van Oudenhove, Lukas; Simrén, Magnus

2018-01-01

Background and objective Psychological states may interfere with visceral sensitivity. Here we investigate associations between psychosocial factors and visceral sensitivity in irritable bowel syndrome (IBS). Methods Two IBS patient cohorts (Cohort 1: n = 231, Rome II; Cohort 2: n = 141, Rome III) underwent rectal barostat testing, and completed questionnaires for anxiety, depression, somatization, and abuse. The associations between questionnaire measures and visceral sensitivity parameters were analyzed in three-step general linear models (step1: demographic and abuse variables; step 2: anxiety and depression; step 3: somatization). Results Cohort 1. Pain threshold was positively associated with age and female gender, and negatively with adult sexual abuse and somatization. Pain referral area was negatively associated with age and positively with somatization and GI-specific anxiety, the latter effect mediated by somatization. Cohort 2. Pain threshold was positively associated with age and male gender, and negatively with adult sexual abuse. Pain intensity ratings were positively associated with somatization, female gender and depression, the latter effect mediated by somatization. Conclusion Somatization is associated with most visceral sensitivity parameters, and mediates the effect of some psychological factors on visceral sensitivity. It may reflect a psychobiological sensitization process driving symptom generation in IBS. In addition, abuse history was found to independently affect some visceral sensitivity parameters. PMID:29511560

Effects of copper and arsenic stress on the development of Norway spruce somatic embryos and their visualization with the environmental scanning electron microscope.

PubMed

Đorđević, Biljana; Neděla, Vilém; Tihlaříková, Eva; Trojan, Václav; Havel, Ladislav

2018-05-18

Somatic embryogenesis is an important biotechnological technique which can be used in studies associated with environmental stress. Four embryogenic cell lines of Norway spruce were grown on media enriched with copper and arsenic in concentration ranges 50-500 μM and 10-50 μM, respectively. The effects were observed during subsequent stages of somatic embryogenesis, the characteristics evaluated being proliferation potential, average number of somatic embryos obtained per g/fresh weight, morphology of developed somatic embryos, metal uptake, and microanalysis of macro- and micronutrients uptake. Copper and arsenic at higher concentrations significantly reduced the growth of early somatic embryos. In almost all treatments, the cell line V-1-3 showed the best performance compared with the other lines tested. Environmental scanning electron microscopy was used to visualize and identify morphological abnormalities in the development of somatic embryos. Abnormalities observed were classified into several categories: meristemless somatic embryos, somatic embryos with disrupted meristem, reduced number of cotyledons, single cotyledon and fused cotyledons. With the application of a low temperature method for the environmental scanning electron microscope, samples were stabilized and whole meristems could be investigated in their native state. As far as we are aware, this is the first report of the effect of copper and arsenic during the process of somatic embryogenesis and the first to evaluate the content of macro and micronutrients uptake in Norway spruce. Copyright © 2018 Elsevier B.V. All rights reserved.

Prognostic significance of functional somatic symptoms in adolescence: a 15-year community-based follow-up study of adolescents with depression compared with healthy peers

PubMed Central

2012-01-01

Background There is a lack of population-based long-term longitudinal research on mental health status and functional physical/somatic symptoms. Little is known about the long-term mental health outcomes associated with somatic symptoms or the temporal relationship between depression and such symptoms. This 15-year study followed up adolescents with depression and matched controls, screened from a population-based sample, who reported different numbers of somatic symptoms. Methods The total population of 16–17-year-olds in Uppsala, Sweden, was screened for depression in 1991–1993. Adolescents who screened positive and an equal number of healthy controls took part in a semi-structured diagnostic interview. In addition, 21 different self-rated somatic symptoms were assessed. Sixty-four percent of those adolescents participated in a follow-up structured interview 15 years later. Results Somatic symptoms in adolescence predicted depression and other adult mental disorders regardless of the presence of adolescent depression. In adolescents with depression, the number of functional somatic symptoms predicted, in a dose response relationship, suicidal behavior, bipolar episodes, and psychotic episodes as well as chronic and recurrent depression. Contrary to expectations, the somatic symptoms of abdominal pain and perspiration without exertion better predicted depression than all DSM-IV depressive symptoms. Abdominal pain persisted as an independent strong predictor of depression and anxiety, even after controlling for other important confounders. Conclusions Somatic symptoms in adolescence can predict severe adult mental health disorders. The number of somatic symptoms concurrent with adolescent depression is, in a stepwise manner, linked to suicidal attempts, bipolar disorders, psychotic disorders, and recurrent and chronic depression. These findings can be useful in developing treatment guidelines for patients with somatic symptoms. PMID:22839681

Somatic symptoms evoked by exam stress in university students: the role of alexithymia, neuroticism, anxiety and depression.

PubMed

Zunhammer, Matthias; Eberle, Hanna; Eichhammer, Peter; Busch, Volker

2013-01-01

The etiology of somatization is incompletely understood, but could be elucidated by models of psychosocial stress. Academic exam stress has effectively been applied as a naturalistic stress model, however its effect on somatization symptoms according to ICD-10 and DSM-IV criteria has not been reported so far. Baseline associations between somatization and personality traits, such as alexithymia, have been studied exhaustively. Nevertheless, it is largely unknown if personality traits have an explanatory value for stress induced somatization. This longitudinal, quasi-experimental study assessed the effects of university exams on somatization - and the reversal of effects after an exam-free period. Repeated-observations were obtained within 150 students, measuring symptom intensity before, during and after an exam period, according to the Screening for Somatoform Symptoms 7-day (SOMS-7d). Additionally, self-reports on health status were used to differentiate between medically explained and medically unexplained symptoms. Alexithymia, neuroticism, trait-anxiety and baseline depression were surveyed using the Toronto-Alexithymia Scale (TAS-20), the Big-Five Personality Interview (NEO-FFI), the State Trait Anxiety Inventory (STAI) and Beck's Depression Inventory (BDI-II). These traits were competitively tested for their ability to explain somatization increases under exam stress. Somatization significantly increased across a wide range of symptoms under exam stress, while health reports pointed towards a reduction in acute infections and injuries. Neuroticism, alexithymia, trait anxiety and depression explained variance in somatization at baseline, but only neuroticism was associated with symptom increases under exam stress. Exam stress is an effective psychosocial stress model inducing somatization. A comprehensive quantitative description of bodily symptoms under exam stress is supplied. The results do not support the stress-alexithymia hypothesis, but favor neuroticism as a personality trait of importance for somatization.

Somatic symptoms and psychological concerns in a general adolescent population: Exploring the relevance of DSM-5 somatic symptom disorder.

PubMed

van Geelen, Stefan M; Rydelius, Per-Anders; Hagquist, Curt

2015-10-01

DSM-5 somatic symptom disorder (SSD) constitutes a major change for psychosomatic medicine and psychiatry, as well as for epidemiological research in these fields. This study investigates somatic symptoms and psychological concerns among adolescents in order to systematically explore the relevance of SSD for general adolescent populations. A cross-sectional population-based design, with a symptoms-based strategy and a symptom-and-psychological-concern-based strategy, was used to estimate the prevalence of somatic symptoms and psychological concerns in a general adolescent population (n=2476, mean age=16years, 49% boys, 51% girls). Somatic symptoms and psychological concerns in relation to gender, and self-reported medical and psychiatric conditions were investigated. The association between somatic symptoms, psychological concerns, and functional impairment in school-, family-, peer- and physical activities was studied. Reporting 3+ persistent distressing somatic symptoms was significantly more common than reporting one or more persistent distressing somatic symptom(s) combined with serious psychological concern. The prevalence of such complaints was significantly higher in girls. The proportion of medical and psychiatric conditions was highest in the group reporting 3+ persistent distressing somatic symptoms combined with serious psychological concern. Belonging to this group most significantly increased odds ratios for functional impairment. For large-scale studies on SSD, results suggest the use of measures based on multiple somatic items in combination with psychological concerns, and a methodologically sound standardized measure of functional impairment. To further enhance clinical decision-making, the relation of symptoms to functional impairment, and the substantial overlap of SSD with medical and psychiatric conditions during adolescence should be addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship of Somatic Symptoms With Depression Severity, Quality of Life, and Health Resources Utilization in Patients With Major Depressive Disorder Seeking Primary Health Care in Spain

PubMed Central

García-Campayo, Javier; Ayuso-Mateos, José Luis; Caballero, Luis; Romera, Irene; Aragonés, Enric; Rodríguez-Artalejo, Fernando; Quail, Deborah; Gilaberte, Inmaculada

2008-01-01

Objective: To investigate the relationship between the characteristics of somatic symptoms and depression severity, quality of life (QOL), and health resources utilization in patients with major depressive disorder (MDD) in primary care setting. Method: This cross-sectional, nationwide epidemiologic study, carried out in 1150 primary care patients with DSM-IV–defined MDD, evaluated the characteristics of somatic symptoms by means of the Standardized Polyvalent Psychiatric Interview. Depression severity and QOL were evaluated by means of the Zung Self-Rating Depression Scale (SDS) and the Physical and Mental Component Summaries of the Medical Outcomes Study 12-item Short-Form Health Survey. Health resources utilization was measured in terms of doctor consultations and hospitalizations. The associations were assessed by means of adjusted analyses. The study was carried out from April 2004 to July 2004. Results: Disability associated with somatic symptoms and number of somatic symptoms were strongly associated with increased depression severity (2.45 and 0.29 increase in SDS score, respectively) and health resources utilization (odds ratios of 1.42 and 1.04, respectively). Associated disability, frequency, and persistence during leisure time of somatic symptoms were strongly associated with poorer QOL. In contrast, we found a weaker relationship between duration and intensity of somatic symptoms and depression severity, QOL, and health resources utilization. Conclusions: Of the studied somatic symptom characteristics, somatic symptom–associated disability and number of somatic symptoms are strongly associated with increased depression severity and health resources utilization, as well as with decreased QOL. Our results may help physicians identify relevant characteristics of somatic symptoms to more effectively diagnose and treat depression in primary care patients. PMID:19158973

Somatic Symptoms Evoked by Exam Stress in University Students: The Role of Alexithymia, Neuroticism, Anxiety and Depression

PubMed Central

Zunhammer, Matthias; Eberle, Hanna; Eichhammer, Peter; Busch, Volker

2013-01-01

Objective The etiology of somatization is incompletely understood, but could be elucidated by models of psychosocial stress. Academic exam stress has effectively been applied as a naturalistic stress model, however its effect on somatization symptoms according to ICD-10 and DSM-IV criteria has not been reported so far. Baseline associations between somatization and personality traits, such as alexithymia, have been studied exhaustively. Nevertheless, it is largely unknown if personality traits have an explanatory value for stress induced somatization. Methods This longitudinal, quasi-experimental study assessed the effects of university exams on somatization — and the reversal of effects after an exam-free period. Repeated-observations were obtained within 150 students, measuring symptom intensity before, during and after an exam period, according to the Screening for Somatoform Symptoms 7-day (SOMS-7d). Additionally, self-reports on health status were used to differentiate between medically explained and medically unexplained symptoms. Alexithymia, neuroticism, trait-anxiety and baseline depression were surveyed using the Toronto-Alexithymia Scale (TAS-20), the Big-Five Personality Interview (NEO-FFI), the State Trait Anxiety Inventory (STAI) and Beck’s Depression Inventory (BDI-II). These traits were competitively tested for their ability to explain somatization increases under exam stress. Results Somatization significantly increased across a wide range of symptoms under exam stress, while health reports pointed towards a reduction in acute infections and injuries. Neuroticism, alexithymia, trait anxiety and depression explained variance in somatization at baseline, but only neuroticism was associated with symptom increases under exam stress. Conclusion Exam stress is an effective psychosocial stress model inducing somatization. A comprehensive quantitative description of bodily symptoms under exam stress is supplied. The results do not support the stress-alexithymia hypothesis, but favor neuroticism as a personality trait of importance for somatization. PMID:24367700

Relationship between chronic nonurological associated somatic syndromes and symptom severity in urological chronic pelvic pain syndromes: baseline evaluation of the MAPP study.

PubMed

Krieger, John N; Stephens, Alisa J; Landis, J Richard; Clemens, J Quentin; Kreder, Karl; Lai, H Henry; Afari, Niloofar; Rodríguez, Larissa; Schaeffer, Anthony; Mackey, Sean; Andriole, Gerald L; Williams, David A

2015-04-01

We used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria. Self-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors. Of 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome compared to 59 of 191 males (31%) (p = 0.006). Participants with a nonurological associated somatic syndrome had more severe urological symptoms and more frequent depression and anxiety. Of 424 participants 228 (54%) met RICE criteria. Of 228 RICE positive participants 108 (47%) had a nonurological associated somatic syndrome compared to 54 of 203 RICE negative patients (28%) with a nonurological associated somatic syndrome (p < 0.001). Nonurological associated somatic syndromes represent important clinical characteristics of urological chronic pelvic pain syndromes. Participants with a nonurological associated somatic syndrome have more severe symptoms, longer duration and higher rates of depression and anxiety. RICE positive patients are more likely to have a nonurological associated somatic syndrome and more severe symptoms. Because nonurological associated somatic syndromes are more common in women, future studies must account for this potential confounding factor in urological chronic pelvic pain syndromes. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Meta-Synthesis of Qualitative Findings About Dance/Movement Therapy for Individuals With Trauma.

PubMed

Levine, Brooklyn; Land, Helen M

2016-02-01

The therapeutic potential of using dance/movement therapy is being increasingly recognized. Preliminary interdisciplinary research findings suggest engaging the body in trauma treatment might reduce the length of treatment by addressing the connections among thoughts, feelings, neurobiology, and somatic responses in the survivor. Unfortunately, empirical research investigating its effectiveness as a psychotherapeutic intervention has been limited due to the lack of a clear manual for mental health care practitioners. The present study aims to synthesize findings from the existing qualitative literature in a qualitative meta-synthesis. Our findings will contribute to the development of a body-oriented intervention for mental health care practitioners to use for trauma. © The Author(s) 2015.

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PubMed

Wada, Akihiko; Shizukuishi, Takashi; Kikuta, Junko; Yamada, Haruyasu; Watanabe, Yusuke; Imamura, Yoshiki; Shinozaki, Takahiro; Dezawa, Ko; Haradome, Hiroki; Abe, Osamu

2017-05-01

Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Effects of cellular origin on differentiation of human induced pluripotent stem cell–derived endothelial cells

PubMed Central

Zhao, Ming-Tao; Jahanbani, Fereshteh; Lee, Won Hee; Snyder, Michael P.

2016-01-01

Human induced pluripotent stem cells (iPSCs) can be derived from various types of somatic cells by transient overexpression of 4 Yamanaka factors (OCT4, SOX2, C-MYC, and KLF4). Patient-specific iPSC derivatives (e.g., neuronal, cardiac, hepatic, muscular, and endothelial cells [ECs]) hold great promise in drug discovery and regenerative medicine. In this study, we aimed to evaluate whether the cellular origin can affect the differentiation, in vivo behavior, and single-cell gene expression signatures of human iPSC–derived ECs. We derived human iPSCs from 3 types of somatic cells of the same individuals: fibroblasts (FB-iPSCs), ECs (EC-iPSCs), and cardiac progenitor cells (CPC-iPSCs). We then differentiated them into ECs by sequential administration of Activin, BMP4, bFGF, and VEGF. EC-iPSCs at early passage (10 < P < 20) showed higher EC differentiation propensity and gene expression of EC-specific markers (PECAM1 and NOS3) than FB-iPSCs and CPC-iPSCs. In vivo transplanted EC-iPSC–ECs were recovered with a higher percentage of CD31+ population and expressed higher EC-specific gene expression markers (PECAM1, KDR, and ICAM) as revealed by microfluidic single-cell quantitative PCR (qPCR). In vitro EC-iPSC–ECs maintained a higher CD31+ population than FB-iPSC–ECs and CPC-iPSC–ECs with long-term culturing and passaging. These results indicate that cellular origin may influence lineage differentiation propensity of human iPSCs; hence, the somatic memory carried by early passage iPSCs should be carefully considered before clinical translation. PMID:27398408

Elimination of Grapevine leafroll associated virus-3, Grapevine rupestris stem pitting associated virus and Grapevine virus A from a Tunisian Cultivar by Somatic Embryogenesis and Characterization of the Somaclones Using Ampelographic Descriptors

PubMed Central

Bouamama-Gzara, Badra; Selmi, Ilhem; Chebil, Samir; Melki, Imene; Mliki, Ahmed; Ghorbel, Abdelwahed; Carra, Angela; Carimi, Francesco; Mahfoudhi, Naima

2017-01-01

Prospecting of local grapevine (Vitis vinifera L.) germplasm revealed that Tunisia possesses a rich patrimony which presents diversified organoleptic characteristics. However, viral diseases seriously affect all local grapevine cultivars which risk a complete extinction. Sanitation programs need to be established to preserve and exploit, as a gene pool, the Tunisian vineyards areas. The presence of the Grapevine leafroll associated virus-3 (GLRaV-3), Grapevine stem pitting associated virus (GRSPaV) and Grapevine virus A (GVA), were confirmed in a Tunisian grapevine cultivar using serological and molecular analyses. The association between GRSPaV and GVA viruses induces more rugose wood symptoms and damages. For this reason the cleansing of the infected cultivar is highly advisable. Direct and recurrent somatic embryos of cv. ‘Hencha’ were successfully induced from filament, when cultured on Chée and Pool (1987). based-medium, enriched with 2 mg 1−1 of 2,4-dichlorophenoxyacetic acid and 2.5 mg 1−1 of Thidiazuron, after 36 weeks of culture. After six months of acclimatization, RT-PCR carried on 50 somaplants confirmed the absence of GVA, GRSPa-V as well as GLRaV-3 viruses in all somaplants. Ampelographic analysis, based on eight OIV descriptors, was carried out on two years acclimated somaplants, compared to the mother plant. Results demonstrated that the shape and contours of 46 somaclones leaves are identical to mother plant leaves and four phenotypically off-type plants were observed. The healthy state of 100% ‘Hencha’ somaclones and the high percentage of phenotypically true-to-type plants demonstrate that somatic embryogenesis is a promising technique to adopt for grapevine viruses elimination. PMID:29238279

Elimination of Grapevine leafroll associated virus-3, Grapevine rupestris stem pitting associated virus and Grapevine virus A from a Tunisian Cultivar by Somatic Embryogenesis and Characterization of the Somaclones Using Ampelographic Descriptors.

PubMed

Bouamama-Gzara, Badra; Selmi, Ilhem; Chebil, Samir; Melki, Imene; Mliki, Ahmed; Ghorbel, Abdelwahed; Carra, Angela; Carimi, Francesco; Mahfoudhi, Naima

2017-12-01

Prospecting of local grapevine ( Vitis vinifera L.) germplasm revealed that Tunisia possesses a rich patrimony which presents diversified organoleptic characteristics. However, viral diseases seriously affect all local grapevine cultivars which risk a complete extinction. Sanitation programs need to be established to preserve and exploit, as a gene pool, the Tunisian vineyards areas. The presence of the Grapevine leafroll associated virus-3 (GLRaV-3), Grapevine stem pitting associated virus (GRSPaV) and Grapevine virus A (GVA), were confirmed in a Tunisian grapevine cultivar using serological and molecular analyses. The association between GRSPaV and GVA viruses induces more rugose wood symptoms and damages. For this reason the cleansing of the infected cultivar is highly advisable. Direct and recurrent somatic embryos of cv. 'Hencha' were successfully induced from filament, when cultured on Chée and Pool (1987). based-medium, enriched with 2 mg 1 -1 of 2,4-dichlorophenoxyacetic acid and 2.5 mg 1 -1 of Thidiazuron, after 36 weeks of culture. After six months of acclimatization, RT-PCR carried on 50 somaplants confirmed the absence of GVA, GRSPa-V as well as GLRaV-3 viruses in all somaplants. Ampelographic analysis, based on eight OIV descriptors, was carried out on two years acclimated somaplants, compared to the mother plant. Results demonstrated that the shape and contours of 46 somaclones leaves are identical to mother plant leaves and four phenotypically off-type plants were observed. The healthy state of 100% 'Hencha' somaclones and the high percentage of phenotypically true-to-type plants demonstrate that somatic embryogenesis is a promising technique to adopt for grapevine viruses elimination.

Multiplex Droplet Digital PCR Quantification of Recurrent Somatic Mutations in Diffuse Large B-Cell and Follicular Lymphoma.

PubMed

Alcaide, Miguel; Yu, Stephen; Bushell, Kevin; Fornika, Daniel; Nielsen, Julie S; Nelson, Brad H; Mann, Koren K; Assouline, Sarit; Johnson, Nathalie A; Morin, Ryan D

2016-09-01

A plethora of options to detect mutations in tumor-derived DNA currently exist but each suffers limitations in analytical sensitivity, cost, or scalability. Droplet digital PCR (ddPCR) is an appealing technology for detecting the presence of specific mutations based on a priori knowledge and can be applied to tumor biopsies, including formalin-fixed paraffin embedded (FFPE) tissues. More recently, ddPCR has gained popularity in its utility in quantifying circulating tumor DNA. We have developed a suite of novel ddPCR assays for detecting recurrent mutations that are prevalent in common B-cell non-Hodgkin lymphomas (NHLs), including diffuse large B-cell lymphoma, follicular lymphoma, and lymphoplasmacytic lymphoma. These assays allowed the differentiation and counting of mutant and wild-type molecules using one single hydrolysis probe. We also implemented multiplexing that allowed the simultaneous detection of distinct mutations and an "inverted" ddPCR assay design, based on employing probes matching wild-type alleles, capable of detecting the presence of multiple single nucleotide polymorphisms. The assays successfully detected and quantified somatic mutations commonly affecting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) (Y641) and signal transducer and activator of transcription 6 (STAT6) (D419) hotspots in fresh tumor, FFPE, and liquid biopsies. The "inverted" ddPCR approach effectively reported any single nucleotide variant affecting either of these 2 hotspots as well. Finally, we could effectively multiplex hydrolysis probes targeting 2 additional lymphoma-related hotspots: myeloid differentiation primary response 88 (MYD88; L265P) and cyclin D3 (CCND3; I290R). Our suite of ddPCR assays provides sufficient analytical sensitivity and specificity for either the invasive or noninvasive detection of multiple recurrent somatic mutations in B-cell NHLs. © 2016 American Association for Clinical Chemistry.

Management of somatic pain induced by head-and-neck cancer treatment: definition and assessment. Guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (SFORL).

PubMed

Binczak, M; Navez, M; Perrichon, C; Blanchard, D; Bollet, M; Calmels, P; Couturaud, C; Dreyer, C; Espitalier, F; Testelin, S; Albert, S; Morinière, S

2014-09-01

The authors present the guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (Société Française d'Oto-rhino-Laryngologie et de Chirurgie de la Face et du Cou [SFORL]) for the management of somatic pain induced by head-and-neck cancer treatment, and in particular the instruments needed for the definition and initial assessment of the various types of pain. A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. The priority is to eliminate tumoral recurrence when pain reappears or changes following head-and-neck cancer treatment. Neuropathic pain screening instruments and pain assessment scales should be used to assess pain intensity and treatment efficacy. Functional rehabilitation sessions should be prescribed to reduce musculoskeletal pain and prevent ankylosis and postural disorder. Psychotherapy and mind-body therapy, when available, should be provided in case of chronic pain. In case of recalcitrant complex pain, referral should be made to a multidisciplinary pain structure. The management of somatic pain induced by head-and-neck cancer treatment above all requires identifying and assessing the intensity of the various types of pain involved, their functional impact and their emotional component. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

FOXL2 impairment in human disease.

PubMed

Verdin, Hannah; De Baere, Elfride

2012-01-01

FOXL2 encodes a forkhead transcription factor that plays important roles in the ovary during development and in post-natal, adult life. Here, we focus on the clinical consequences of FOXL2 impairment in human disease. In line with other forkhead transcription factors, its constitutional genetic defects and a somatic mutation lead to developmental disease and cancer, respectively. More than 100 unique constitutional mutations and regulatory defects have been found in blepharophimosis syndrome (BPES), a complex eyelid malformation associated (type I) or not (type II) with premature ovarian failure (POF). In agreement with the BPES phenotype, FOXL2 is expressed in the developing eyelids and in fetal and adult ovaries. Two knock-out mice and at least one natural animal model, the Polled Intersex Syndrome goat, are known. They recapitulate the BPES phenotype and have provided many insights into the ovarian pathology. Only a few constitutional mutations have been described in nonsyndromic POF. Moreover, a recurrent somatic mutation p.C134W was found to be specific for adult ovarian granulo-sa cell tumors. Functional studies investigating the consequences of FOXL2 mutations or regulatory defects have shed light on the molecular pathogenesis of the aforementioned conditions, and contributed considerably to genotype-phenotype correlations. Recently, a conditional knock-out of Foxl2 in the mouse induced somatic transdifferentiation of ovary into testis in adult mice, suggesting that Foxl2 has an anti-testis function in the adult ovary. This changed our view on the ovary and testis as terminally differentiated organs in adult mammals. Finally, this might have potential implications for the understanding and treatment of frequent conditions such as POF and polycystic ovary syndrome. Copyright © 2012 S. Karger AG, Basel.

Psychiatric comorbidity in new daily persistent headache: A cross-sectional study.

PubMed

Uniyal, R; Paliwal, V K; Tripathi, A

2017-07-01

New daily persistent headache (NDPH) is a type of chronic daily headache. NDPH can have migrainous (NDPH-CM) or tension-type character (NDPH-CTTH). Recently, NDPH patients have shown to have associated anxiety and depression. We compared anxiety, depressive symptoms, somatization and pain catastrophization among NDPH, healthy controls and patients with chronic low-back pain and between NDPH-CM and NDPH-CTTH. We assessed the study population for depressive symptoms by Patient Health Questionnaire-9, anxiety by Generalized Anxiety Disorder Scale - 7, somatoform disorder using DSM IV (TR) criteria and pain catastrophizing by using Pain Catastrophizing Scale. Fifty-five patients each with NDPH (mean age 28.24 ± 12.05 years, 45.5% females) and age/sex matched healthy individuals and patients with chronic low-back pain were enrolled. Among NDPH patients, somatoform disorder was seen in 32.7%, severe anxiety in 65.5%, severe depressive symptoms in 40%, significant pain catastrophization in 85.5%. NDPH patients had significantly higher frequency of all psychiatric co-morbidities as compared to healthy controls and patients with chronic low-back pain. NDPH-CM patients had significantly higher frequency of depression and pain catastrophizing behaviour as compared to NDPH-CTTH. Anxiety, depressive symptoms, somatization and pain catastrophizing were significantly more prevalent in NDPH when compared to healthy individuals and patients with chronic low back pain. Such effects should be sought for, as they might contribute to refractoriness to treatment. Anxiety, depressive symptoms, somatization and pain catastrophizing were significantly more prevalent in new daily persistent headache when compared to healthy individuals and patients with chronic low back pain. Such effects should be sought for, as they might contribute to refractoriness to treatment. © 2017 European Pain Federation - EFIC®.

Comparative marker analysis after isolation and culture of testicular cells from the immature marmoset.

PubMed

Albert, Silvia; Wistuba, Joachim; Eildermann, Katja; Ehmcke, Jens; Schlatt, Stefan; Gromoll, Joerg; Kossack, Nina

2012-01-01

The marmoset monkey is a valuable model in reproductive medicine. While previous studies have evaluated germ cell dynamics in the postnatal marmoset, the features of testicular somatic cells remain largely unknown. Therefore, the aim of this study was to establish marmoset-specific markers for Sertoli and peritubular cells (PTCs) and to compare protocols for the enrichment and culture of testicular cell types. Immunohistochemistry of Sertoli and PTC-specific markers - anti-müllerian hormone (AMH), vimentin (VIM), α-smooth muscle actin (SMA) - was performed and corresponding RNA expression profiles were established by quantitative PCR analysis (SOX9,AMH, FSHR,VIM, and SMA). For these analyses, testicular tissue from newborn (n = 4), 8-week-old (n = 4) and adult (n = 3) marmoset monkeys was used. Protocols for the enrichment and culture of testicular cell fractions from the 8-week-old marmoset monkeys (n = 3) were evaluated and cells were analyzed using germ cell- and somatic cell-specific markers. The expression of AMH, VIM and SMA reflects the proportion and differentiation status of Sertoli and PTCs at the RNA and the protein levels. While applied protocols did not support the propagation of germ cells in vitro, our analyses revealed that PTCs maintain their proliferative potential and constitute the dominant cell type after short- and long-term culture. Expression of functionally meaningful testicular somatic markers is similar in the human and the marmoset monkey, indicating that this primate can indeed be used as model for human testicular development. The PTC culture system established in this study will facilitate the identification of factors influencing male sex differentiation and spermatogenesis. Copyright © 2012 S. Karger AG, Basel.

Changing Nuclear Landscape and Unique PML Structures During Early Epigenetic Transitions of Human Embryonic Stem Cells

PubMed Central

Butler, John T.; Hall, Lisa L.; Smith, Kelly P.; Lawrence, Jeanne B.

2010-01-01

The complex nuclear structure of somatic cells is important to epigenomic regulation, yet little is known about nuclear organization of human embryonic stem cells (hESC). Here we surveyed several nuclear structures in pluripotent and transitioning hESC. Observations of centromeres, telomeres, SC35 speckles, Cajal Bodies, lamin A/C and emerin, nuclear shape and size demonstrate a very different “nuclear landscape” in hESC. This landscape is remodeled during a brief transitional window, concomitant with or just prior to differentiation onset. Notably, hESC initially contain abundant signal for spliceosome assembly factor, SC35, but lack discrete SC35 domains; these form as cells begin to specialize, likely reflecting cell-type specific genomic organization. Concomitantly, nuclear size increases and shape changes as lamin A/C and emerin incorporate into the lamina. During this brief window, hESC exhibit dramatically different PML-defined structures, which in somatic cells are linked to gene regulation and cancer. Unlike the numerous, spherical somatic PML bodies, hES cells often display ~1–3 large PML structures of two morphological types: long linear “rods” or elaborate “rosettes”, which lack substantial SUMO-1, Daxx, and Sp100.These occur primarily between Day 0–2 of differentiation and become rare thereafter. PML rods may be “taut” between other structures, such as centromeres, but clearly show some relationship with the lamina, where PML often abuts or fills a “gap” in early lamin A/C staining. Findings demonstrate that pluripotent hES cells have a markedly different overall nuclear architecture, remodeling of which is linked to early epigenomic programming and involves formation of unique PML-defined structures. PMID:19449340

Teachers' Recognition of Anxiety and Somatic Symptoms in Their Pupils

ERIC Educational Resources Information Center

Neil, Louise; Smith, Marjorie

2017-01-01

Anxiety and somatic symptoms in children are common and debilitating, yet frequently go unidentified and untreated. This study investigated whether teachers can recognize children's anxiety and somatic symptoms, and how they identify children they perceive to be anxious or somatizing. A sample of 1,346 7- to 11-year-old children, their 51 class…

Emotional distress in the Hebrew Bible. Somatic or psychological?

PubMed

Mumford, D B

1992-01-01

A systematic search was made in the Hebrew Bible for expressions of emotional distress. A wide range of somatic and psychological vocabulary was found, especially in the Psalms and other poetic literature. Somatic expressions most frequently involved the heart, bowels, belly, bones, and eyes. Head symptoms were rare. Metaphors referring to the heart were common; other somatic expressions appeared to be descriptions of actual physical sensations. Usually somatic and psychological expressions were paired together, utilising the 'parallelism' of Hebrew verse form. Biblical Hebrew thus incorporated a powerful and sophisticated language of emotional expression.

ECONOMIC STRESSORS AND ALCOHOL-RELATED OUTCOMES: EXPLORING GENDER DIFFERENCES IN THE MEDIATING ROLE OF SOMATIC COMPLAINTS

PubMed Central

BROWN, ROBYN LEWIS; RICHMAN, JUDITH A.; ROSPENDA, KATHLEEN M.

2015-01-01

This study examined processes linking economic stressors, somatic complaints, and two alcohol-related outcomes (past-month drinking and problematic drinking). Structural equation models of data from a national survey revealed that somatic complaints partly explain the association between economic stressors and problematic drinking. The associations of both economic stressors and somatic complaints with problematic drinking were significantly greater for men than women. However, the association between economic stressors and somatic complaints was greater for women. These findings clarify the circumstances in which gender matters most for the associations among economy-related stressors, somatic complaints, and drinking. They highlight the significance of difficult economic circumstances for physical health and, in turn, problematic drinking – particularly among men. PMID:25310370

Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma

PubMed Central

Totoki, Yasushi; Yoshida, Akihiko; Hosoda, Fumie; Nakamura, Hiromi; Hama, Natsuko; Ogura, Koichi; Yoshida, Aki; Fujiwara, Tomohiro; Arai, Yasuhito; Toguchida, Junya; Tsuda, Hitoshi; Miyano, Satoru; Kawai, Akira

2014-01-01

Chondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors. PMID:25024164

A medical record review for functional somatic symptoms in children.

PubMed

Rask, Charlotte Ulrikka; Borg, Carsten; Søndergaard, Charlotte; Schulz-Pedersen, Søren; Thomsen, Per Hove; Fink, Per

2010-04-01

The objectives of this study were to develop and test a systematic medical record review for functional somatic symptoms (FSSs) in paediatric patients and to estimate the inter-rater reliability of paediatricians' recognition of FSSs and their associated impairments while using this method. We developed the Medical Record Review for Functional Somatic Symptoms in Children (MRFC) for retrospective medical record review. Described symptoms were categorised as probably, definitely, or not FSSs. FSS-associated impairment was also determined. Three paediatricians performed the MRFC on the medical records of 54 children with a diagnosed, well-defined physical disease and 59 with 'symptom' diagnoses. The inter-rater reliabilities of the recognition and associated impairment of FSSs were tested on 20 of these records. The MRFC allowed identification of subgroups of children with multisymptomatic FSSs, long-term FSSs, and/or impairing FSSs. The FSS inter-rater reliability was good (combined kappa=0.69) but only fair as far as associated impairment was concerned (combined kappa=0.29). In the hands of skilled paediatricians, the MRFC is a reliable method for identifying paediatric patients with diverse types of FSSs for clinical research. However, additional information is needed for reliable judgement of impairment. The method may also prove useful in clinical practice. Copyright 2010 Elsevier Inc. All rights reserved.

A comprehensive characterization of rare mitochondrial DNA variants in neuroblastoma

PubMed Central

Pignataro, Piero; Lasorsa, Vito Alessandro; Hogarty, Michael D.; Castellano, Aurora; Conte, Massimo; Tonini, Gian Paolo; Iolascon, Achille; Gasparre, Giuseppe; Capasso, Mario

2016-01-01

Background Neuroblastoma, a tumor of the developing sympathetic nervous system, is a common childhood neoplasm that is often lethal. Mitochondrial DNA (mtDNA) mutations have been found in most tumors including neuroblastoma. We extracted mtDNA data from a cohort of neuroblastoma samples that had undergone Whole Exome Sequencing (WES) and also used snap-frozen samples in which mtDNA was entirely sequenced by Sanger technology. We next undertook the challenge of determining those mutations that are relevant to, or arisen during tumor development. The bioinformatics pipeline used to extract mitochondrial variants from matched tumor/blood samples was enriched by a set of filters inclusive of heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. Results Our in silico multistep workflow applied both on WES and Sanger-sequenced neuroblastoma samples, allowed us to identify a limited burden of somatic and germline mitochondrial mutations with a potential pathogenic impact. Conclusions The few singleton germline and somatic mitochondrial mutations emerged, according to our in silico analysis, do not appear to impact on the development of neuroblastoma. Our findings are consistent with the hypothesis that most mitochondrial somatic mutations can be considered as ‘passengers’ and consequently have no discernible effect in this type of cancer. PMID:27351283

Generation of biallelic knock-out sheep via gene-editing and somatic cell nuclear transfer

PubMed Central

Li, Honghui; Wang, Gui; Hao, Zhiqiang; Zhang, Guozhong; Qing, Yubo; Liu, Shuanghui; Qing, Lili; Pan, Weirong; Chen, Lei; Liu, Guichun; Zhao, Ruoping; Jia, Baoyu; Zeng, Luyao; Guo, Jianxiong; Zhao, Lixiao; Zhao, Heng; Lv, Chaoxiang; Xu, Kaixiang; Cheng, Wenmin; Li, Hushan; Zhao, Hong-Ye; Wang, Wen; Wei, Hong-Jiang

2016-01-01

Transgenic sheep can be used to achieve genetic improvements in breeds and as an important large-animal model for biomedical research. In this study, we generated a TALEN plasmid specific for ovine MSTN and transfected it into fetal fibroblast cells of STH sheep. MSTN biallelic-KO somatic cells were selected as nuclear donor cells for SCNT. In total, cloned embryos were transferred into 37 recipient gilts, 28 (75.7%) becoming pregnant and 15 delivering, resulting in 23 lambs, 12 of which were alive. Mutations in the lambs were verified via sequencing and T7EI assay, and the gene mutation site was consistent with that in the donor cells. Off-target analysis was performed, and no off-target mutations were detected. MSTN KO affected the mRNA expression of MSTN relative genes. The growth curve for the resulting sheep suggested that MSTN KO caused a remarkable increase in body weight compared with those of wild-type sheep. Histological analyses revealed that MSTN KO resulted in muscle fiber hypertrophy. These findings demonstrate the successful generation of MSTN biallelic-KO STH sheep via gene editing in somatic cells using TALEN technology and SCNT. These MSTN mutant sheep developed and grew normally, and exhibited increased body weight and muscle growth. PMID:27654750

Berwald-type and Yano-type connections on Lie algebroids

NASA Astrophysics Data System (ADS)

Peyghan, E.

2015-09-01

In a new approach, by using the exact sequences, semisprays on the prolongation of a Lie algebroids are introduced and many important results on the semisprays and sprays are obtained. Also, the horizontal endomorphisms, almost complex structures, vertical, horizontal and complete lifts on the prolongation of a Lie algebroid are considered. Then the distinguished connections on the prolongation of a Lie algebroid are introduced and the torsion and curvature tensors of these connections are considered. In particular, the Berwald-type and Yano-type connections are studied.

Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin.

PubMed

Fujii, Kaho; Yamashita, Yoriko; Yamamoto, Toshimichi; Takahashi, Koji; Hashimoto, Katsunori; Miyata, Tomoko; Kawai, Kumi; Kikkawa, Fumitaka; Toyokuni, Shinya; Nagasaka, Tetsuro

2014-04-01

Mucinous tumors of the ovary are frequently associated with mature cystic teratomas, and it has been speculated that the mucinous tumors arise from teratoma components. The cellular origins of mature cystic teratomas are believed to be post-meiotic ovarian germ cells, and the analysis of microsatellite markers such as short tandem repeats is suitable for determining the cellular origin of tumors. In this study, we analyzed 3 ovarian mature cystic teratomas, all of which were associated with simultaneous ovarian mucinous tumors within the same ovary. Two of the 3 mucinous tumors were intestinal-type and the other was endocervical type. A laser capture microdissection technique was used to separate the epithelial component of the mucinous tumor, the components of the mature cystic teratoma, and control ovarian somatic tissue. Using short tandem repeat analysis based on 6 markers (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290), we could distinguish the germ cell (homozygous) or somatic (heterozygous) origin of a given component in each sample. The epithelial components of the intestinal-type mucinous tumors in cases 1 and 2 were homozygous, and the epithelial component in case 3 (endocervical type) was heterozygous. All teratomatous components were homozygous, and the control components were heterozygous. In addition, we analyzed 3 mature cystic teratomas without mucinous tumors, and all 3 were homozygous in the tumor component. Our data suggest that the origin of mucinous tumors in the ovary may differ among histological subtypes, and intestinal-type mucinous tumors may arise from mature cystic teratomas, although endocervical-type mucinous tumors may not. Copyright © 2014 Elsevier Inc. All rights reserved.

Survival of ovarian somatic cells during sex change in the protogynous wrasse, Halichoeres trimaculatus.

PubMed

Nozu, Ryo; Horiguchi, Ryo; Murata, Ryosuke; Kobayashi, Yasuhisa; Nakamura, Masaru

2013-02-01

The three-spot wrasse (Halichoeres trimaculatus), which inhabits the coral reefs of Okinawa, changes sex from female to male. Sex change in this species is controlled by a social system. Oocytes disappear completely from the ovary, and male germ cells and somatic cells comprising testicular tissue arise a new during the sex change process. However, little is known of the fate and origin of the gonadal tissue-forming cells during sex change. In particular, the fate of ovarian somatic cells has not been determined, although the ovarian tissue regresses histologically. To approach this question, we analyzed apoptosis and cell proliferation in the sex-changing gonads. Unexpectedly, we found that few apoptotic somatic cells were present during sex change, suggesting that ovarian somatic cells might survive during the regression of the ovarian tissue. On the other hand, cell proliferation was detected in many granulosa cells surrounding the degenerating oocytes, a few epithelial cells covering ovigerous lamella and a few somatic cells associated with gonial germ cells at an early stage of sex change. Then, we found that proliferative ovarian somatic cells remained in the gonads late in the sex change process. Based on these results, we concluded that some functional somatic cells of the ovary are reused as testicular somatic cells during the gonadal sex change in the three-spot wrasse.

Influence of Abscisic Acid and Sucrose on Somatic Embryogenesis in Cactus Copiapoa tenuissima Ritt. forma mostruosa

PubMed Central

Lema-Rumińska, J.; Goncerzewicz, K.; Gabriel, M.

2013-01-01

Having produced the embryos of cactus Copiapoa tenuissima Ritt. forma monstruosa at the globular stage and callus, we investigated the effect of abscisic acid (ABA) in the following concentrations: 0, 0.1, 1, 10, and 100 μM on successive stages of direct (DSE) and indirect somatic embryogenesis (ISE). In the indirect somatic embryogenesis process we also investigated a combined effect of ABA (0, 0.1, 1 μM) and sucrose (1, 3, 5%). The results showed that a low concentration of ABA (0-1 μM) stimulates the elongation of embryos at the globular stage and the number of correct embryos in direct somatic embryogenesis, while a high ABA concentration (10–100 μM) results in growth inhibition and turgor pressure loss of somatic embryos. The indirect somatic embryogenesis study in this cactus suggests that lower ABA concentrations enhance the increase in calli fresh weight, while a high concentration of 10 μM ABA or more changes calli color and decreases its proliferation rate. However, in the case of indirect somatic embryogenesis, ABA had no effect on the number of somatic embryos and their maturation. Nevertheless, we found a positive effect of sucrose concentration for both the number of somatic embryos and the increase in calli fresh weight. PMID:23843737

[Somatic disorders in outpatient psychiatry: the added value of a standard physical examination during the intake of outpatients].

PubMed

van den Berg, K E M; Rijnders, C A Th; van Dam, A; van de Ven, A L M; van der Feltz-Cornelis, C M; Graafsma, S J

2014-01-01

It is well-known that psychiatric patients often suffer from severe somatic problems, such as diabetes mellitus and cardiovascular disease. Up till now, research has concentrated almost exclusively on the inpatient setting, but there is strong evidence that the correlation also exists in psychiatric patients who are outpatients. In the Netherlands there are, as yet, no clear recommendations regarding a standard form of somatic screening for the outpatient population. A pilot study performed by GGz Breburg has shown that somatic screening (without a physical examination) gave substantial additional value to treatment planning. To investigate the added value that a physical examination can provide when new psychiatric patients are screened for aspects of somatic concern (ASC). Newly referred outpatients (n = 70) were screened somatically by means of a questionnaire and supplementary medical interview, and by laboratory tests and physical examination. If a somatic problem was found which had not been detected previously, the patient was referred back to to the general practitioner. At least one ASC was found in 81,4% of all patients. In 45,7% of all patients the asc had not been detected. 12% of all the newly discovered somatic problems were found exclusively via the physical examination. A physical examination provides substantial information and adds value to the somatic screening of psychiatric outpatients.

An algorithm to predict the connectome of neural microcircuits

PubMed Central

Reimann, Michael W.; King, James G.; Muller, Eilif B.; Ramaswamy, Srikanth; Markram, Henry

2015-01-01

Experimentally mapping synaptic connections, in terms of the numbers and locations of their synapses and estimating connection probabilities, is still not a tractable task, even for small volumes of tissue. In fact, the six layers of the neocortex contain thousands of unique types of synaptic connections between the many different types of neurons, of which only a handful have been characterized experimentally. Here we present a theoretical framework and a data-driven algorithmic strategy to digitally reconstruct the complete synaptic connectivity between the different types of neurons in a small well-defined volume of tissue—the micro-scale connectome of a neural microcircuit. By enforcing a set of established principles of synaptic connectivity, and leveraging interdependencies between fundamental properties of neural microcircuits to constrain the reconstructed connectivity, the algorithm yields three parameters per connection type that predict the anatomy of all types of biologically viable synaptic connections. The predictions reproduce a spectrum of experimental data on synaptic connectivity not used by the algorithm. We conclude that an algorithmic approach to the connectome can serve as a tool to accelerate experimental mapping, indicating the minimal dataset required to make useful predictions, identifying the datasets required to improve their accuracy, testing the feasibility of experimental measurements, and making it possible to test hypotheses of synaptic connectivity. PMID:26500529

Somatic Complaints in Pediatric Patients: A Prospective Study of the Role of Negative Life Events, Child Social and Academic Competence, and Parental Somatic Symptoms.

ERIC Educational Resources Information Center

Walker, Linda S.; And Others

1994-01-01

Results indicated among children in low social competence at initial clinic visit, higher levels of subsequent negative life events predicted higher levels of somatic complaints at follow-up. Life events and somatic complaints were also related to characteristics exhibited by patient's parents. (53 references) (BF)

Characteristics of somatic tinnitus patients with and without hyperacusis

PubMed Central

Salvi, Richard J.; Greco, Antonio; Turchetta, Rosaria; De Virgilio, Armando; Altissimi, Giancarlo; Attanasio, Giuseppe; Cianfrone, Giancarlo; de Vincentiis, Marco

2017-01-01

Objective Determine if somatic tinnitus patients with hyperacusis have different characteristics from those without hyperacusis. Patients and methods 172 somatic tinnitus patients with (n = 82) and without (n = 90) hyperacusis referred to the Tinnitus Unit of Sapienza University of Rome between June 2012 and June 2016 were compared for demographic characteristics, tinnitus features, self-administered questionnaire scores, nature of somatic modulation and history. Results Compared to those without hyperacusis, patients with somatic tinnitus and hyperacusis: (a) were older (43.38 vs 39.12 years, p = 0.05), (b) were more likely to have bilateral tinnitus (67.08% vs 55.56%, p = 0.04), (c) had a higher prevalence of somatic modulation of tinnitus (53.65% vs 36.66%, p = 0.02) and (d) scored significantly worse on tinnitus annoyance (39.34 vs 22.81, p<0.001) and subjective hearing level (8.04 vs 1.83, p<0.001). Conclusion Our study shows significantly higher tinnitus modulation and worse self-rating of tinnitus and hearing ability in somatic tinnitus patients with hyperacusis versus somatic tinnitus patients without hyperacusis. These differences could prove useful in developing a better understanding of the pathophysiology and establishing a course of treatment for these two groups of patients. PMID:29161302

Characteristics of somatic tinnitus patients with and without hyperacusis.

PubMed

Ralli, Massimo; Salvi, Richard J; Greco, Antonio; Turchetta, Rosaria; De Virgilio, Armando; Altissimi, Giancarlo; Attanasio, Giuseppe; Cianfrone, Giancarlo; de Vincentiis, Marco

2017-01-01

Determine if somatic tinnitus patients with hyperacusis have different characteristics from those without hyperacusis. 172 somatic tinnitus patients with (n = 82) and without (n = 90) hyperacusis referred to the Tinnitus Unit of Sapienza University of Rome between June 2012 and June 2016 were compared for demographic characteristics, tinnitus features, self-administered questionnaire scores, nature of somatic modulation and history. Compared to those without hyperacusis, patients with somatic tinnitus and hyperacusis: (a) were older (43.38 vs 39.12 years, p = 0.05), (b) were more likely to have bilateral tinnitus (67.08% vs 55.56%, p = 0.04), (c) had a higher prevalence of somatic modulation of tinnitus (53.65% vs 36.66%, p = 0.02) and (d) scored significantly worse on tinnitus annoyance (39.34 vs 22.81, p<0.001) and subjective hearing level (8.04 vs 1.83, p<0.001). Our study shows significantly higher tinnitus modulation and worse self-rating of tinnitus and hearing ability in somatic tinnitus patients with hyperacusis versus somatic tinnitus patients without hyperacusis. These differences could prove useful in developing a better understanding of the pathophysiology and establishing a course of treatment for these two groups of patients.

Identification of novel candidate drivers connecting different dysfunctional levels for lung adenocarcinoma using protein-protein interactions and a shortest path approach

NASA Astrophysics Data System (ADS)

Chen, Lei; Huang, Tao; Zhang, Yu-Hang; Jiang, Yang; Zheng, Mingyue; Cai, Yu-Dong

2016-07-01

Tumors are formed by the abnormal proliferation of somatic cells with disordered growth regulation under the influence of tumorigenic factors. Recently, the theory of “cancer drivers” connects tumor initiation with several specific mutations in the so-called cancer driver genes. According to the differentiation of four basic levels between tumor and adjacent normal tissues, the cancer drivers can be divided into the following: (1) Methylation level, (2) microRNA level, (3) mutation level, and (4) mRNA level. In this study, a computational method is proposed to identify novel lung adenocarcinoma drivers based on dysfunctional genes on the methylation, microRNA, mutation and mRNA levels. First, a large network was constructed using protein-protein interactions. Next, we searched all of the shortest paths connecting dysfunctional genes on different levels and extracted new candidate genes lying on these paths. Finally, the obtained candidate genes were filtered by a permutation test and an additional strict selection procedure involving a betweenness ratio and an interaction score. Several candidate genes remained, which are deemed to be related to two different levels of cancer. The analyses confirmed our assertions that some have the potential to contribute to the tumorigenesis process on multiple levels.

Physiological and psychological correlates of attention-related body sensations (tingling and warmth).

PubMed

Tihanyi, B T; Köteles, F

2017-09-01

Body sensations play an essential role in the subjective evaluation of our physical health, illness, and healing. They are impacted by peripheral somatic and external processes, but they are also heavily modulated by mental processes, e.g., attention, motor control, and emotion. Body sensations, such as tingling, numbness, pulse, and warmth, can emerge due to simply focusing attention on a body part. It is however an open question, if these sensations are connected with actual peripheral changes or happen "only in the mind." Here, we first tested whether the intensity of such attention-related body sensations is related to autonomic and somatomotor physiological processes and to psychological traits. In this study, attention-related body sensations were not significantly connected to changes in physiology, except warmth sensation, which was linked to decrease in muscle tension. Overall intensity of tingling significantly correlated with body awareness and tendentiously with body-mind practice. This strengthened the hypothesis that attention-related body sensations are more the result of top-down functions, and the connection with peripheral processes is weak. Here, we suggested a novel protocol to examine the effect of manipulating attention on body sensations, which together with our results and discussion can inspire future researches.

Photoanthropometric study of dysmorphic features of the face in children with autism and asperger syndrome.

PubMed

Gorczyca, Piotr; Kapinos-Gorczyca, Agnieszka; Ziora, Katarzyna; Oświęcimska, Joanna

2012-01-01

Childhood autism is a neurodevelopmental disorder characterized by impairments in social interactions, verbal and non-verbal communication and by a pattern of stereotypical behaviors and interests. The aim of this study was to estimate the dysmorphic facial features of children with autism and children with Asperger syndrome. The examination was conducted on 60 children (30 with childhood autism and 30 with Asperger syndrome). The photo anthropometric method used in this study followed the protocol established by Stengel-Rutkowski et al. The performed statistical analysis showed that in patients with childhood autism, the anteriorly rotated ears and the long back of the nose appeared more often. In the group of children with autism, there was a connection between the amount of dysmorphies and the presence of some somatic diseases in the first-degree relatives. There was also a connection between the motor coordination and the age the child began to walk. In patients with childhood autism, there were certain dysmorphies (like the anterior rotated ears and the long back of the nose) which appeared more often. Although the connection was not statistically significant, it seemed to concur with data from the literature. Formulation of the other conclusions would require broader studies e.g. dealing with a familial analysis of dysmorphic features.

Recent advancements in cloning by somatic cell nuclear transfer.

PubMed

Ogura, Atsuo; Inoue, Kimiko; Wakayama, Teruhiko

2013-01-05

Somatic cell nuclear transfer (SCNT) cloning is the sole reproductive engineering technology that endows the somatic cell genome with totipotency. Since the first report on the birth of a cloned sheep from adult somatic cells in 1997, many technical improvements in SCNT have been made by using different epigenetic approaches, including enhancement of the levels of histone acetylation in the chromatin of the reconstructed embryos. Although it will take a considerable time before we fully understand the nature of genomic programming and totipotency, we may expect that somatic cell cloning technology will soon become broadly applicable to practical purposes, including medicine, pharmaceutical manufacturing and agriculture. Here we review recent progress in somatic cell cloning, with a special emphasis on epigenetic studies using the laboratory mouse as a model.

Recent advancements in cloning by somatic cell nuclear transfer

PubMed Central

Ogura, Atsuo; Inoue, Kimiko; Wakayama, Teruhiko

2013-01-01

Somatic cell nuclear transfer (SCNT) cloning is the sole reproductive engineering technology that endows the somatic cell genome with totipotency. Since the first report on the birth of a cloned sheep from adult somatic cells in 1997, many technical improvements in SCNT have been made by using different epigenetic approaches, including enhancement of the levels of histone acetylation in the chromatin of the reconstructed embryos. Although it will take a considerable time before we fully understand the nature of genomic programming and totipotency, we may expect that somatic cell cloning technology will soon become broadly applicable to practical purposes, including medicine, pharmaceutical manufacturing and agriculture. Here we review recent progress in somatic cell cloning, with a special emphasis on epigenetic studies using the laboratory mouse as a model. PMID:23166393

Somatic and Depressive Symptoms in Female Japanese and American Students: A Preliminary Investigation

PubMed Central

Arnault, Denise Saint; Sakamoto, Shinji; Moriwaki, Aiko

2007-01-01

The present study examined the relationship between common somatic symptoms and depression in samples of Japanese and American college students. Fifty Japanese and 44 American women completed the Beck Depression Inventory (BDI) and rated 56 somatic-distress items for 7 days. Japanese had higher levels of somatic distress than Americans. ANOVA of somatic distress by BDI-level revealed that the High BDI Japanese group reported 26 somatic symptoms (including stomach ache, dizziness, and shoulder pain) with significantly higher means when compared with the low BDI group. High BDI Americans had a significantly higher mean for joint pain compared to the Low BDI group. The importance of the body in transcultural psychiatry is explored, and implications for primary and mental health care are discussed. PMID:16893876

Masked depression: its interrelations with somatization, hypochondriasis and conversion.

PubMed

Fisch, R Z

1987-01-01

Masked depression appears to be a common clinical phenomenon. Most depressions present with some somatic complaints in addition to affective and cognitive ones. About one half of all depressions seen by primary care physicians initially present predominantly or exclusively with somatic symptoms. Many of these depressions are not recognized or are misdiagnosed and mistreated. The possible reasons for this are discussed here. The phenomenon of somatization in depressions and other conditions is reviewed and the interface with other related clinical problems like hypochondriasis and conversion is delineated. It is hypothesized that the proportion of depressions that are masked is positively correlated to the patients' tendency to somatize and negatively correlated to the doctors' ability to recognize depressions that hide behind somatic complaints. Suggestions for the diagnosis and treatment of masked depressions are given.

Immunohistochemical and ultrastructural characteristics of interstitial cells of Cajal in the rabbit duodenum. Presence of a single cilium

PubMed Central

Junquera, Concepción; Martínez-Ciriano, Carmen; Castiella, Tomás; Serrano, Pedro; Azanza, María Jesús; Ramón y Cajal Junquera, Santiago

2007-01-01

Abstract Santiago Ramón y Cajal discovered a new type of cell related to the myenteric plexus and also to the smooth muscle cells of the circular muscle layer of the intestine. Based on their morphology, relationships and staining characteristics, he considered these cells as primitive neurons. One century later, despite major improvements in cell biology, the interstitial cells of Cajal (ICCs) are still controversial for many researchers. The aim of study was to perform an immunohistochemical and ultrastructural characterization of the ICCs in the rabbit duo-denum. We have found interstitial cells that are positive for c-Kit, CD34 and nestin and are also positive for Ki67 protein, tightly associated with somatic cell proliferation. By means of electron microscopy, we describe ICCs around enteric ganglia. They present triangular or spindle forms and a very voluminous nucleus with scarce per-inuclear chromatin surrounded by a thin perinuclear cytoplasm that expands with long cytoplasmic processes. ICC processes penetrate among the smooth muscle cells and couple with the processes of other ICCs located in the connective tissue of the circular muscle layer and establish a three-dimensional network. Intercellular con-tacts by means of gap-like junctions are frequent. ICCs also establish gap-like junctions with smooth muscle cells. We also observe a population of interstitial cells of stellate morphology in the connective tissue that sur-rounds the muscle bundles in the circular muscle layer, usually close to nervous trunks. These cells establish different types of contacts with the muscle cells around them. In addition, the presence of a single cilium show-ing a structure 9 + 0 in an ICC is demonstrated for the first time. In conclusion, we report positive staining c-kit, CD34, nestin and Ki 67. ICCs fulfilled the usual transmission electron microscopy (TEM) criteria. A new ultrastructural characteristic of at least some ICCs is demonstrated: the presence of a single cilium. Some populations of ICCs in the rabbit duodenum present certain immunohistochemical and ultrastructural characteristics that often are present in progenitor cells. PMID:17760839

The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies.

PubMed

Muldoon, P P; Jackson, K J; Perez, E; Harenza, J L; Molas, S; Rais, B; Anwar, H; Zaveri, N T; Maldonado, R; Maskos, U; McIntosh, J M; Dierssen, M; Miles, M F; Chen, X; De Biasi, M; Damaj, M I

2014-08-01

Recent data have indicated that α3β4* neuronal nicotinic (n) ACh receptors may play a role in morphine dependence. Here we investigated if nACh receptors modulate morphine physical withdrawal. To assess the role of α3β4* nACh receptors in morphine withdrawal, we used a genetic correlation approach using publically available datasets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Male and female European-American (n = 2772) and African-American (n = 1309) subjects from the Study of Addiction: Genetics and Environment dataset were assessed for possible associations of polymorphisms in the 15q25 gene cluster and opioid dependence. BXD recombinant mouse lines demonstrated an increased expression of α3, β4 and α5 nACh receptor mRNA in the forebrain and midbrain, which significantly correlated with increased defecation in mice undergoing morphine withdrawal. Mice overexpressing the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal. Furthermore, α5 and β4 nACh receptor knockout mice expressed decreased somatic withdrawal signs compared with their wild-type counterparts. Moreover, selective α3β4* nACh receptor antagonists, α-conotoxin AuIB and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nACh receptor subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nACh receptor subtype is not involved in morphine somatic withdrawal signs. Overall, our findings suggest an important role for the α3β4* nACh receptor subtype in morphine physical dependence. © 2014 The British Pharmacological Society.

Recurrent ETNK1 mutations in atypical chronic myeloid leukemia.

PubMed

Gambacorti-Passerini, Carlo B; Donadoni, Carla; Parmiani, Andrea; Pirola, Alessandra; Redaelli, Sara; Signore, Giovanni; Piazza, Vincenzo; Malcovati, Luca; Fontana, Diletta; Spinelli, Roberta; Magistroni, Vera; Gaipa, Giuseppe; Peronaci, Marco; Morotti, Alessandro; Panuzzo, Cristina; Saglio, Giuseppe; Usala, Emilio; Kim, Dong-Wook; Rea, Delphine; Zervakis, Konstantinos; Viniou, Nora; Symeonidis, Argiris; Becker, Heiko; Boultwood, Jacqueline; Campiotti, Leonardo; Carrabba, Matteo; Elli, Elena; Bignell, Graham R; Papaemmanuil, Elli; Campbell, Peter J; Cazzola, Mario; Piazza, Rocco

2015-01-15

Despite the recent identification of recurrent SETBP1 mutations in atypical chronic myeloid leukemia (aCML), a complete description of the somatic lesions responsible for the onset of this disorder is still lacking. To find additional somatic abnormalities in aCML, we performed whole-exome sequencing on 15 aCML cases. In 2 cases (13.3%), we identified somatic missense mutations in the ETNK1 gene. Targeted resequencing on 515 hematological clonal disorders revealed the presence of ETNK1 variants in 6 (8.8%) of 68 aCML and 2 (2.6%) of 77 chronic myelomonocytic leukemia samples. These mutations clustered in a small region of the kinase domain, encoding for H243Y and N244S (1/8 H243Y; 7/8 N244S). They were all heterozygous and present in the dominant clone. The intracellular phosphoethanolamine/phosphocholine ratio was, on average, 5.2-fold lower in ETNK1-mutated samples (P < .05). Similar results were obtained using myeloid TF1 cells transduced with ETNK1 wild type, ETNK1-N244S, and ETNK1-H243Y, where the intracellular phosphoethanolamine/phosphocholine ratio was significantly lower in ETNK1-N244S (0.76 ± 0.07) and ETNK1-H243Y (0.37 ± 0.02) than in ETNK1-WT (1.37 ± 0.32; P = .01 and P = .0008, respectively), suggesting that ETNK1 mutations may inhibit the catalytic activity of the enzyme. In summary, our study shows for the first time the evidence of recurrent somatic ETNK1 mutations in the context of myeloproliferative/myelodysplastic disorders. © 2015 by The American Society of Hematology.

Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments.

PubMed

Perez, M; Pacchiarotti, A; Frontani, M; Pescarmona, E; Caprini, E; Lombardo, G A; Russo, G; Faraggiana, T

2010-03-01

Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1.6% to 21%, with a median rate of 9.8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series. Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.

Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.

PubMed

Moncada-Vélez, M; Vélez-Ortega, A; Orrego, J; Santisteban, I; Jagadeesh, J; Olivares, M; Olaya, N; Hershfield, M; Candotti, F; Franco, J

2011-11-01

Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in Peripheral blood lymphocytes (PBL), as a result of somatic mosaicism caused by monoallelic reversion of the causative mutation in the ADA gene. He was not eligible for haematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore he was placed on enzyme replacement therapy (ERT) with bovine PEG-ADA. The follow-up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, and sustained expansion of TCRγδ+ T cells. This was accompanied by the disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient's clinical condition improved marginally, he later developed a germinal cell tumour and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Somatic mosaicism due to monoallelic reversion of a mutation in T cells of an ADA-SCID patient and the effects of enzyme replacement therapy on the revertant phenotype

PubMed Central

Moncada-Vélez, Marcela; Vélez-Ortega, Alejandra C.; Orrego, Julio C.; Santisteban, Inés; Jagadeesh, Jayashree; Olivares, Margarita; Olaya, Natalia; Hershfield, Michael S.; Candotti, Fabio; Franco, Jose L.

2011-01-01

Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B-NK- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in PBL, as a result of somatic mosaicism due to monoallelic reversion of the causative mutation in the ADA gene. Our patient was not eligible for hematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore enzyme replacement therapy (ERT) with bovine PEG-ADA was initiated. The follow up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, with sustained expansion of TCRγδ+ T cells. This was accompanied by disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient’s clinical condition improved marginally, he later developed a germinal cell tumor and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion. PMID:21671975

Somatic mutation profiles of clear cell endometrial tumors revealed by whole exome and targeted gene sequencing.

PubMed

Le Gallo, Matthieu; Rudd, Meghan L; Urick, Mary Ellen; Hansen, Nancy F; Zhang, Suiyuan; Lozy, Fred; Sgroi, Dennis C; Vidal Bel, August; Matias-Guiu, Xavier; Broaddus, Russell R; Lu, Karen H; Levine, Douglas A; Mutch, David G; Goodfellow, Paul J; Salvesen, Helga B; Mullikin, James C; Bell, Daphne W

2017-09-01

The molecular pathogenesis of clear cell endometrial cancer (CCEC), a tumor type with a relatively unfavorable prognosis, is not well defined. We searched exome-wide for novel somatically mutated genes in CCEC and assessed the mutational spectrum of known and candidate driver genes in a large cohort of cases. We conducted whole exome sequencing of paired tumor-normal DNAs from 16 cases of CCEC (12 CCECs and the CCEC components of 4 mixed histology tumors). Twenty-two genes-of-interest were Sanger-sequenced from another 47 cases of CCEC. Microsatellite instability (MSI) and microsatellite stability (MSS) were determined by genotyping 5 mononucleotide repeats. Two tumor exomes had relatively high mutational loads and MSI. The other 14 tumor exomes were MSS and had 236 validated nonsynonymous or splice junction somatic mutations among 222 protein-encoding genes. Among the 63 cases of CCEC in this study, we identified frequent somatic mutations in TP53 (39.7%), PIK3CA (23.8%), PIK3R1 (15.9%), ARID1A (15.9%), PPP2R1A (15.9%), SPOP (14.3%), and TAF1 (9.5%), as well as MSI (11.3%). Five of 8 mutations in TAF1, a gene with no known role in CCEC, localized to the putative histone acetyltransferase domain and included 2 recurrently mutated residues. Based on patterns of MSI and mutations in 7 genes, CCEC subsets molecularly resembled serous endometrial cancer (SEC) or endometrioid endometrial cancer (EEC). Our findings demonstrate molecular similarities between CCEC and SEC and EEC and implicate TAF1 as a novel candidate CCEC driver gene. Cancer 2017;123:3261-8. © 2017 American Cancer Society. © 2017 American Cancer Society.

Life events and difficulties and their association with antenatal distress in White and South Asian women in the UK.

PubMed

Traviss, Gemma D; Meer, Shaista; West, Robert M; House, Allan O

2013-05-01

Symptoms of distress during pregnancy are common and often go unnoticed. There is a well-established relation between life events and depression. The current study aims to explore the association between life events and difficulties, and symptoms of emotional and somatic distress during pregnancy in White and South Asian women in the UK. 100 pregnant women attending routine antenatal appointments were interviewed using the Life Events and Difficulties Schedule (LEDS). We investigated the frequency and type of events experienced in the year prior to conception and during pregnancy, as predictors for somatic and emotional distress, measured using the GHQ-28. Non-severe stressors accounted for over 90 % of those reported, half of which (43-53 %) were health and reproduction-related. Somatic symptoms were associated with the number of non-severe events, and number of children and emotional symptoms were associated with non-marked difficulties. There was little evidence of an association between severe events and distress. Ethnicity had little effect on any associations although South Asian women were at slightly higher odds of experiencing emotional symptoms, which appear to be buffered by social support. In routine antenatal care it is important to assess both emotional and somatic symptoms. Health professionals need to be sensitive to the health, social, cultural and environmental circumstances of women during pregnancy and ensure appropriate support is in place, particularly for multi-parous women. Regression models explained a small but significant amount of the variance in distress symptoms. Further work is necessary to explore other contributory factors and also the mechanisms through which stressors have their effect.

Towards a cognitive robotics methodology for reward-based decision-making: dynamical systems modelling of the Iowa Gambling Task

NASA Astrophysics Data System (ADS)

Lowe, Robert; Ziemke, Tom

2010-09-01

The somatic marker hypothesis (SMH) posits that the role of emotions and mental states in decision-making manifests through bodily responses to stimuli of import to the organism's welfare. The Iowa Gambling Task (IGT), proposed by Bechara and Damasio in the mid-1990s, has provided the major source of empirical validation to the role of somatic markers in the service of flexible and cost-effective decision-making in humans. In recent years the IGT has been the subject of much criticism concerning: (1) whether measures of somatic markers reveal that they are important for decision-making as opposed to behaviour preparation; (2) the underlying neural substrate posited as critical to decision-making of the type relevant to the task; and (3) aspects of the methodological approach used, particularly on the canonical version of the task. In this paper, a cognitive robotics methodology is proposed to explore a dynamical systems approach as it applies to the neural computation of reward-based learning and issues concerning embodiment. This approach is particularly relevant in light of a strongly emerging alternative hypothesis to the SMH, the reversal learning hypothesis, which links, behaviourally and neurocomputationally, a number of more or less complex reward-based decision-making tasks, including the 'A-not-B' task - already subject to dynamical systems investigations with a focus on neural activation dynamics. It is also suggested that the cognitive robotics methodology may be used to extend systematically the IGT benchmark to more naturalised, but nevertheless controlled, settings that might better explore the extent to which the SMH, and somatic states per se, impact on complex decision-making.

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma.

PubMed

Qamra, Aditi; Xing, Manjie; Padmanabhan, Nisha; Kwok, Jeffrey Jun Ting; Zhang, Shenli; Xu, Chang; Leong, Yan Shan; Lee Lim, Ai Ping; Tang, Qianqao; Ooi, Wen Fong; Suling Lin, Joyce; Nandi, Tannistha; Yao, Xiaosai; Ong, Xuewen; Lee, Minghui; Tay, Su Ting; Keng, Angie Tan Lay; Gondo Santoso, Erna; Ng, Cedric Chuan Young; Ng, Alvin; Jusakul, Apinya; Smoot, Duane; Ashktorab, Hassan; Rha, Sun Young; Yeoh, Khay Guan; Peng Yong, Wei; Chow, Pierce K H; Chan, Weng Hoong; Ong, Hock Soo; Soo, Khee Chee; Kim, Kyoung-Mee; Wong, Wai Keong; Rozen, Steven G; Teh, Bin Tean; Kappei, Dennis; Lee, Jeeyun; Connolly, John; Tan, Patrick

2017-06-01

Promoter elements play important roles in isoform and cell type-specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary gastric cancers, gastric cancer lines, and nonmalignant gastric tissues. We identified nearly 2,000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms ( RASA3 ). Somatic promoter-associated N-terminal peptides displaying relative depletion in tumors exhibited high-affinity MHC binding predictions and elicited potent T-cell responses in vitro , suggesting a mechanism for reducing tumor antigenicity. In multiple patient cohorts, gastric cancers with high somatic promoter usage also displayed reduced T-cell cytolytic marker expression. Somatic promoters are enriched in PRC2 occupancy, display sensitivity to EZH2 therapeutic inhibition, and are associated with novel cancer-associated transcripts. By generating tumor-specific isoforms and decreasing tumor antigenicity, epigenomic promoter alterations may thus drive intrinsic tumorigenesis and also allow nascent cancers to evade host immunity. Significance: We apply epigenomic profiling to demarcate the promoter landscape of gastric cancer. Many tumor-specific promoters activate different promoters in the same gene, some generating pro-oncogenic isoforms. Tumor-specific promoters also reduce tumor antigenicity by causing relative depletion of immunogenic peptides, contributing to cancer immunoediting and allowing tumors to evade host immune attack. Cancer Discov; 7(6); 630-51. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 539 . ©2017 American Association for Cancer Research.

Somatic dysfunction and its association with chronic low back pain, back-specific functioning, and general health: results from the OSTEOPATHIC Trial.

PubMed

Licciardone, John C; Kearns, Cathleen M

2012-07-01

Somatic dysfunction is diagnosed by the presence of any of 4 TART criteria: tissue texture abnormality, asymmetry, restriction of motion, or tenderness. To measure the prevalence of somatic dysfunction in patients with chronic low back pain (LBP) and to study the associations of somatic dysfunction with LBP severity, back-specific functioning, and general health. Cross-sectional study nested within a randomized controlled trial. University-based study in Dallas-Fort Worth, Texas. A total of 455 adult research patients with non-specific chronic LBP. Somatic dysfunction in the lumbar, sacrum/pelvis, and pelvis/innominate regions, including key lesions representing severe somatic dysfunction. A 10-cm visual analog scale (VAS), the Roland-Morris Disability Questionnaire (RMDQ), and the Medical Outcomes Study Short Form-36 Health Survey (SF-36) were used to measure LBP severity, back-specific functioning, and general health, respectively. Severe somatic dysfunction was most prevalent in the lumbar (225 [49%]), sacrum/pelvis (129 [28%]), and pelvis/innominate (48 [11%]) regions. Only 30 patients (7%) had no somatic dysfunction in the lumbar, sacrum/pelvis, or pelvis/innominate regions. There were 4 statistically significant pairwise correlations for severe somatic dysfunction: thoracic (T) 10-12 with ribs; T10-12 with lumbar; lumbar with sacrum/pelvis; and sacrum/pelvis with pelvis/innominate. Having a key lesion in the lumbar region (ρ=0.80) or sacrum/pelvis region (ρ=0.71) was strongly correlated with the overall number of key lesions. There were no consistent demographic or clinical predictors of somatic dysfunction. The presence (vs absence) of severe somatic dysfunction in the lumbar region was associated with greater LBP severity (median VAS score, 4.7 vs 3.8, respectively; P=.003) and greater back-specific disability (median RMDQ score, 6 vs 4, respectively; P=.01). The presence (vs absence) of severe somatic dysfunction in the sacrum/pelvis region was associated with greater back-specific disability (median RMDQ score, 6 vs 5, respectively; P=.02) and poorer general health (median SF-36 score, 62 vs 72, respectively; P=.002). An increasing number of key lesions was associated with back-specific disability (P=.009) and poorer general health (P=.02). The present study demonstrates that somatic dysfunction, particularly in the lumbar and sacrum/pelvis regions, is common in patients with chronic LBP. Forthcoming extensions of the OSTEOPATHIC Trial will assess the efficacy of OMT according to baseline levels of somatic dysfunction.

Detection of somatic, subclonal and mosaic CNVs from sequencing | Division of Cancer Prevention

Cancer.gov

Progress in technology has made individual genome sequencing a clinical reality, with partial genome sequencing already in use in clinical care. In fact, it is expected that within a few years whole genome sequencing will be a standard procedure that will allow discovering personal genomic variants of all types and thus greatly facilitate individualized medicine. However, fast

Growth and wood properties of genetically improved loblolly pine: propagation type comparison and genetic parameters

Treesearch

Finto Antony; Laurence Schimleck; Lewis Jordan; Benjamin Hornsby; Joseph Dahlen; Richard Daniels; Alexander Clark; Luis Apiolaza; Dudley Huber

2013-01-01

The use of clonal varieties in forestry offers great potential to improve growth traits (quantity) and wood properties (quality) of loblolly pine (Pinus taeda L.). Loblolly pine trees established via somatic embryogenesis (clones), full-sib zygotic crosses, and half-sib zygotic open-pollinated families were sampled to identify variation in growth and wood properties...

Somatic Cells Become Cancer’s “Starter Dough” | Center for Cancer Research

Cancer.gov

Cancer stem cells (CSCs) is a term that sparks animated differences of opinions among researchers in the oncology community.  Much of the disagreement comes from the difficulty involved in isolating these cells and manipulating them ex vivo. When putative CSCs are isolated from clinical samples, researchers are unable to retrospectively identify the cell type that suffered the

Termini of human chromosomes display elevated rates of mitotic recombination.

PubMed

Cornforth, M N; Eberle, R L

2001-01-01

The strand-specific in situ hybridization technique of CO-FISH was used to probe telomeres of human mitotic cells in order to determine the spontaneous frequency of crossover. This approach allowed the detection of recombinational crossovers occurring anywhere along the length of individual chromosomes, including reciprocal events taking place between sister chromatids. Although the process of sister chromatid exchange (SCE) is the most prominent type of recombination in somatic mammalian cells, our results show that SCEs accounted for less than a third of the recombinational events revealed by CO-FISH. It is concluded that chromosomal regions near the termini of chromosome arms undergo extraordinarily high rates of spontaneous recombination, producing terminal crossovers whose small size precludes detection by standard cytogenetic methods. That similar results were observed for transformed epithelial cells, as well as primary fibroblasts, suggests that the phenomenon is a common characteristic of human cells. These findings are noteworthy because, although telomeric and subtelomeric DNA is known to be preferentially involved in certain types of recombination, the tips of somatic mammalian chromosomes have not previously been identified as preferred sites for crossover. Implications of these results are discussed in terms of limitations imposed on CO-FISH for its proposed use in directional hybridization mapping.

The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Drosophila Ovary

PubMed Central

Sarikaya, Didem P.; Extavour, Cassandra G.

2015-01-01

The Hippo pathway regulates organ size, stem cell proliferation and tumorigenesis in adult organs. Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size, however, has received little attention. Here, we ask whether Hippo signaling influences the number of stem cell niches that are established during development of the Drosophila larval ovary, and whether it interacts with the same or different effector signaling pathways in different cell types. We demonstrate that canonical Hippo signaling regulates autonomous proliferation of the soma, while a novel hippo-independent activity of Yorkie regulates autonomous proliferation of the germ line. Moreover, we demonstrate that Hippo signaling mediates non-autonomous proliferation signals between germ cells and somatic cells, and contributes to maintaining the correct proportion of these niche precursors. Finally, we show that the Hippo pathway interacts with different growth pathways in distinct somatic cell types, and interacts with EGFR and JAK/STAT pathways to regulate non-autonomous proliferation of germ cells. We thus provide evidence for novel roles of the Hippo pathway in establishing the precise balance of soma and germ line, the appropriate number of stem cell niches, and ultimately regulating adult female reproductive capacity. PMID:25643260

Induced neural stem cells as a means of treatment in Huntington's disease.

PubMed

Choi, Kyung-Ah; Hong, Sunghoi

2017-11-01

Huntington's disease (HD) is an inherited neurodegenerative disease characterized by chorea, dementia, and depression caused by progressive nerve cell degeneration, which is triggered by expanded CAG repeats in the huntingtin (Htt) gene. Currently, there is no cure for this disease, nor is there an effective medicine available to delay or improve the physical, mental, and behavioral severities caused by it. Areas covered: In this review, the authors describe the use of induced neural stem cells (iNSCs) by direct conversion technology, which offers great advantages as a therapeutic cell type to treat HD. Expert opinion: Cell conversion of somatic cells into a desired stem cell type is one of the most promising treatments for HD because it could be facilitated for the generation of patient-specific neural stem cells. The induced pluripotent stem cells (iPSCs) have a powerful potential for differentiation into neurons, but they may cause teratoma formation due to an undifferentiated pluripotent stem cell after transplantation Therefore, direct conversion of somatic cells into iNSCs is a promising alternative technology in regenerative medicine and the iNSCs may be provided as a therapeutic cell source for Huntington's disease.

Knock-in of large reporter genes in human cells via CRISPR/Cas9-induced homology-dependent and independent DNA repair

PubMed Central

He, Xiangjun; Tan, Chunlai; Wang, Feng; Wang, Yaofeng; Zhou, Rui; Cui, Dexuan; You, Wenxing; Zhao, Hui; Ren, Jianwei; Feng, Bo

2016-01-01

CRISPR/Cas9-induced site-specific DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. Extensive efforts have been made to knock-in exogenous DNA to a selected genomic locus in human cells; which, however, has focused on HDR-based strategies and was proven inefficient. Here, we report that NHEJ pathway mediates efficient rejoining of genome and plasmids following CRISPR/Cas9-induced DNA DSBs, and promotes high-efficiency DNA integration in various human cell types. With this homology-independent knock-in strategy, integration of a 4.6 kb promoterless ires-eGFP fragment into the GAPDH locus yielded up to 20% GFP+ cells in somatic LO2 cells, and 1.70% GFP+ cells in human embryonic stem cells (ESCs). Quantitative comparison further demonstrated that the NHEJ-based knock-in is more efficient than HDR-mediated gene targeting in all human cell types examined. These data support that CRISPR/Cas9-induced NHEJ provides a valuable new path for efficient genome editing in human ESCs and somatic cells. PMID:26850641

Knock-in of large reporter genes in human cells via CRISPR/Cas9-induced homology-dependent and independent DNA repair.

PubMed

He, Xiangjun; Tan, Chunlai; Wang, Feng; Wang, Yaofeng; Zhou, Rui; Cui, Dexuan; You, Wenxing; Zhao, Hui; Ren, Jianwei; Feng, Bo

2016-05-19

CRISPR/Cas9-induced site-specific DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. Extensive efforts have been made to knock-in exogenous DNA to a selected genomic locus in human cells; which, however, has focused on HDR-based strategies and was proven inefficient. Here, we report that NHEJ pathway mediates efficient rejoining of genome and plasmids following CRISPR/Cas9-induced DNA DSBs, and promotes high-efficiency DNA integration in various human cell types. With this homology-independent knock-in strategy, integration of a 4.6 kb promoterless ires-eGFP fragment into the GAPDH locus yielded up to 20% GFP+ cells in somatic LO2 cells, and 1.70% GFP+ cells in human embryonic stem cells (ESCs). Quantitative comparison further demonstrated that the NHEJ-based knock-in is more efficient than HDR-mediated gene targeting in all human cell types examined. These data support that CRISPR/Cas9-induced NHEJ provides a valuable new path for efficient genome editing in human ESCs and somatic cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Practical use of advanced mouse models for lung cancer.

PubMed

Safari, Roghaiyeh; Meuwissen, Ralph

2015-01-01

To date a variety of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) mouse models have been developed that mimic human lung cancer. Chemically induced or spontaneous lung cancer in susceptible inbred strains has been widely used, but the more recent genetically engineered somatic mouse models recapitulate much better the genotype-phenotype correlations found in human lung cancer. Additionally, improved orthotopic transplantation of primary human cancer tissue fragments or cells into lungs of immune-compromised mice can be valuable tools for preclinical research such as antitumor drug tests. Here we give a short overview of most somatic mouse models for lung cancer that are currently in use. We accompany each different model with a description of its practical use and application for all major lung tumor types, as well as the intratracheal injection or direct injection of fresh or freeze-thawed tumor cells or tumor cell lines into lung parenchyma of recipient mice. All here presented somatic mouse models are based on the ability to (in) activate specific alleles at a time, and in a tissue-specific cell type, of choice. This spatial-temporal controlled induction of genetic lesions allows the selective introduction of main genetic lesions in an adult mouse lung as found in human lung cancer. The resulting conditional somatic mouse models can be used as versatile powerful tools in basic lung cancer research and preclinical translational studies alike. These distinctively advanced lung cancer models permit us to investigate initiation (cell of origin) and progression of lung cancer, along with response and resistance to drug therapy. Cre/lox or FLP/frt recombinase-mediated methods are now well-used techniques to develop tissue-restricted lung cancer in mice with tumor-suppressor gene and/or oncogene (in)activation. Intranasal or intratracheal administration of engineered adenovirus-Cre or lentivirus-Cre has been optimized for introducing Cre recombinase activity into pulmonary tissues, and we discuss here the different techniques underlying these applications. Concomitant with Cre/Flp recombinase-based models are the tetracycline (Tet)-inducible bitransgenic systems in which presence or absence of doxycycline can turn the expression of a specific oncogene on or off. The use of several Tet-inducible lung cancer models for NSCLC is presented here in which the reversal of oncogene expression led to complete tumor regression and provided us with important insight of how oncogene dependence influence lung cancer survival and growth. As alternative to Tet-inducible models, we discuss the application of reversible expressed, transgenic mutant estrogen receptor (ER) fusion proteins, which are regulated via systemic tamoxifen administration. Most of the various lung cancer models can be combined through the generation of transgenic compound mice so that the use of these somatic mouse models can be even more enhanced for the study of specific molecular pathways that facilitate growth and maintenance of lung cancer. Finally, this description of the practical application and methodology of mouse models for lung cancer should be helpful in assisting researchers to make the best choices and optimal use of (existing) somatic models that suits the specific experimental needs in their study of lung cancer.