Biology and clinical relevance of noncoding sno/scaRNAs.

PubMed

Cao, Thuy; Rajasingh, Sheeja; Samanta, Saheli; Dawn, Buddhadeb; Bittel, Douglas C; Rajasingh, Johnson

2018-02-01

Small nucleolar RNAs (snoRNAs) are a group of noncoding RNAs that perform various biological functions, including biochemical modifications of other RNAs, precursors of miRNA, splicing, and telomerase activity. The small Cajal body-associated RNAs (scaRNAs) are a subset of the snoRNA family and collect in the Cajal body where they perform their canonical function to biochemically modify spliceosomal RNAs prior to maturation. Failure of sno/scaRNAs have been implicated in pathology such as congenital heart anomalies, neuromuscular disorders, and various malignancies. Thus, understanding of sno/scaRNAs demonstrates the clinical value. Copyright © 2018 Elsevier Inc. All rights reserved.

Cajal and the discovery of a new artistic world: the neuronal forest.

PubMed

DeFelipe, Javier

2013-01-01

The introduction of the staining method of Camillo Golgi in 1873 represented a giant step for neuroscience. Prior to this development, the visualization of neurons with the available histological techniques had been incomplete; it was only feasible to observe the cell body and the proximal portions of the dendrites and axon. However, with the Golgi method it was possible to observe neurons and glia with all their parts (cell body, dendrites, and axon in the case of neurons; cell body and processes in the case of glia). Due to the advantages of this method, all of a sudden it was possible to begin studying one of the great mysteries and critical issues of the organization of the nervous system-the tracing of the connections between neurons. Nevertheless, this method was not fully exploited until Santiago Ramón y Cajal arrived on the scene in 1888. It should be noted that, in Cajal's day, drawing was the most common method of describing microscopic images in the absence of the highly developed microphotography and other imaging techniques commonly available in today's laboratories. As a consequence, most scientific figures presented by the early neuroanatomists were their own drawings, providing an outlet for these scientists to express and develop their artistic talent. In the hands of Cajal, the Golgi method represented not only the principal tool that was to change the course of the history of neuroscience but also the discovery of a new artistic world, the neuronal forest. © 2013 Elsevier B.V. All rights reserved.

Localization of α-Dystrobrevin in Cajal Bodies and Nucleoli: A New Role for α-Dystrobrevin in the Structure/Stability of the Nucleolus.

PubMed

Hernández-Ibarra, Jose Anselmo; Laredo-Cisneros, Marco Samuel; Mondragón-González, Ricardo; Santamaría-Guayasamín, Natalie; Cisneros, Bulmaro

2015-12-01

α-Dystrobrevin (α-DB) is a cytoplasmic component of the dystrophin-associated complex involved in cell signaling; however, its recently revealed nuclear localization implies a role for this protein in the nucleus. Consistent with this, we demonstrated, in a previous work that α-DB1 isoform associates with the nuclear lamin to maintain nuclei morphology. In this study, we show the distribution of the α-DB2 isoform in different subnuclear compartments of N1E115 neuronal cells, including nucleoli and Cajal bodies, where it colocalizes with B23/nucleophosmin and Nopp140 and with coilin, respectively. Recovery in a pure nucleoli fraction undoubtedly confirms the presence of α-DB2 in the nucleolus. α-DB2 redistributes in a similar fashion to that of fibrillarin and Nopp140 upon actinomycin-mediated disruption of nucleoli and to that of coilin after disorganization of Cajal bodies through ultraviolet-irradiation, with relocalization of the proteins to the corresponding reassembled structures after cessation of the insults, which implies α-DB2 in the plasticity of these nuclear bodies. That localization of α-DB2 in the nucleolus is physiologically relevant is demonstrated by the fact that downregulation of α-DB2 resulted in both altered nucleoli structure and decreased levels of B23/nucleophosmin, fibrillarin, and Nopp140. Since α-DB2 interacts with B23/nucleophosmin and overexpression of the latter protein favors nucleolar accumulation of α-DB2, it appears that targeting of α-DB2 to the nucleolus is dependent on B23/nucleophosmin. In conclusion, we show for the first time localization of α-DB2 in nucleoli and Cajal bodies and provide evidence that α-DB2 is involved in the structure of nucleoli and might modulate nucleolar functions. © 2015 Wiley Periodicals, Inc.

Validity and test-retest reliability in assessing current body size with figure drawings in Chinese adolescents.

PubMed

Lo, Wing-Sze; Ho, Sai-Yin; Wong, Bonny Yee-Man; Mak, Kwok-Kei; Lam, Tai-Hing

2011-06-01

The reliability and validity of Stunkard's Figure Rating Scale (FRS) as a measure of current body size (CBS) was established in Western adolescent girls but not in non-Western population. We examined the validity and test-retest reliability of Stunkard's FRS in assessing CBS among Chinese adolescents. Methods. In a school-based survey in Hong Kong, 5666 adolescents (boys: 45.1%; mean age 14.7 years) provided data on self-reported height and weight, CBS, perceived weight status, and health-related quality of life using the Medical Outcomes Study Short-Form version 2 (SF-12v2). Height and weight were also objectively measured. Spearman's correlation was used to assess construct validity, concurrent validity and test-retest reliability. Convergent and discriminant validity were good: CBS correlated strongly with weight and self-reported/measured BMI, but only weakly with SF-12v2. CBS correlated strongly with perceived weight status, showing concurrent validity. Spearman's correlation (r) for CBS was 0.78 for girls and 0.72 for boys indicating good test-retest reliability. Validity and reliability results did not differ significantly between senior and junior grade adolescents. Our findings support the use of Stunkard's FRS to measure body size among Chinese adolescents.

Structures of ribonucleoprotein particle modification enzymes

PubMed Central

Liang, Bo; Li, Hong

2016-01-01

Small nucleolar and Cajal body ribonucleoprotein particles (RNPs) are required for the maturation of ribosomes and spliceosomes. They consist of small nucleolar RNA or Cajal body RNA combined with partner proteins and represent the most complex RNA modification enzymes. Recent advances in structure and function studies have revealed detailed information regarding ribonucleoprotein assembly and substrate binding. These enzymes form intertwined RNA–protein assemblies that facilitate reversible binding of the large ribosomal RNA or small nuclear RNA. These revelations explain the specificity among the components in enzyme assembly and substrate modification. The multiple conformations of individual components and those of complete RNPs suggest a dynamic assembly process and justify the requirement of many assembly factors in vivo. PMID:21108865

Coilin association with Box C/D scaRNA suggests a direct role for the Cajal body marker protein in scaRNP biogenesis

PubMed Central

Enwerem, Isioma I.; Velma, Venkatramreddy; Broome, Hanna J.; Kuna, Marija; Begum, Rowshan A.; Hebert, Michael D.

2014-01-01

ABSTRACT Spliceosomal small nuclear ribonucleoproteins (snRNPs) are enriched in the Cajal body (CB). Guide RNAs, known as small Cajal body-specific RNAs (scaRNAs), direct modification of the small nuclear RNA (snRNA) component of the snRNP. The protein WRAP53 binds a sequence motif (the CAB box) found in many scaRNAs and the RNA component of telomerase (hTR) and targets these RNAs to the CB. We have previously reported that coilin, the CB marker protein, associates with certain non-coding RNAs. For a more comprehensive examination of the RNAs associated with coilin, we have sequenced the RNA isolated from coilin immunocomplexes. A striking preferential association of coilin with the box C/D scaRNAs 2 and 9, which lack a CAB box, was observed. This association varied by treatment condition and WRAP53 knockdown. In contrast, reduction of WRAP53 did not alter the level of coilin association with hTR. Additional studies showed that coilin degrades/processes scaRNA 2 and 9, associates with active telomerase and can influence telomerase activity. These findings suggest that coilin plays a novel role in the biogenesis of box C/D scaRNPs and telomerase. PMID:24659245

Chromatoid Body Protein TDRD6 Supports Long 3’ UTR Triggered Nonsense Mediated mRNA Decay

PubMed Central

Fanourgakis, Grigorios; Akpinar, Müge; Dahl, Andreas; Jessberger, Rolf

2016-01-01

Chromatoid bodies (CBs) are spermiogenesis-specific organelles of largely unknown function. CBs harbor various RNA species, RNA-associated proteins and proteins of the tudor domain family like TDRD6, which is required for a proper CB architecture. Proteome analysis of purified CBs revealed components of the nonsense-mediated mRNA decay (NMD) machinery including UPF1. TDRD6 is essential for UPF1 localization to CBs, for UPF1-UPF2 and UPF1-MVH interactions. Upon removal of TDRD6, the association of several mRNAs with UPF1 and UPF2 is disturbed, and the long 3’ UTR-stimulated but not the downstream exon-exon junction triggered pathway of NMD is impaired. Reduced association of the long 3’ UTR mRNAs with UPF1 and UPF2 correlates with increased stability and enhanced translational activity. Thus, we identified TDRD6 within CBs as required for mRNA degradation, specifically the extended 3’ UTR-triggered NMD pathway, and provide evidence for the requirement of NMD in spermiogenesis. This function depends on TDRD6-promoted assembly of mRNA and decay enzymes in CBs. PMID:27149095

Human intron-encoded Alu RNAs are processed and packaged into Wdr79-associated nucleoplasmic box H/ACA RNPs

PubMed Central

Jády, Beáta E.; Ketele, Amandine; Kiss, Tamás

2012-01-01

Alu repetitive sequences are the most abundant short interspersed DNA elements in the human genome. Full-length Alu elements are composed of two tandem sequence monomers, the left and right Alu arms, both derived from the 7SL signal recognition particle RNA. Since Alu elements are common in protein-coding genes, they are frequently transcribed into pre-mRNAs. Here, we demonstrate that the right arms of nascent Alu transcripts synthesized within pre-mRNA introns are processed into metabolically stable small RNAs. The intron-encoded Alu RNAs, termed AluACA RNAs, are structurally highly reminiscent of box H/ACA small Cajal body (CB) RNAs (scaRNAs). They are composed of two hairpin units followed by the essential H (AnAnnA) and ACA box motifs. The mature AluACA RNAs associate with the four H/ACA core proteins: dyskerin, Nop10, Nhp2, and Gar1. Moreover, the 3′ hairpin of AluACA RNAs carries two closely spaced CB localization motifs, CAB boxes (UGAG), which bind Wdr79 in a cumulative fashion. In contrast to canonical H/ACA scaRNPs, which concentrate in CBs, the AluACA RNPs accumulate in the nucleoplasm. Identification of 348 human AluACA RNAs demonstrates that intron-encoded AluACA RNAs represent a novel, large subgroup of H/ACA RNAs, which are apparently confined to human or primate cells. PMID:22892240

Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel Prize award to Santiago Ramón y Cajal.

PubMed

López-Muñoz, Francisco; Boya, Jesús; Alamo, Cecilio

2006-10-16

Exactly 100 years ago, the Nobel Prize for Physiology and Medicine was awarded to Santiago Ramón y Cajal, "in recognition of his meritorious work on the structure of the nervous system". Cajal's great contribution to the history of science is undoubtedly the postulate of neuron theory. The present work makes a historical analysis of the circumstances in which Cajal formulated his theory, considering the authors and works that influenced his postulate, the difficulties he encountered for its dissemination, and the way it finally became established. At the time when Cajal began his neurohistological studies, in 1887, Gerlach's reticular theory (a diffuse protoplasmic network of the grey matter of the nerve centres), also defended by Golgi, prevailed among the scientific community. In the first issue of the Revista Trimestral de Histología Normal y Patológica (May, 1888), Cajal presented the definitive evidence underpinning neuron theory, thanks to staining of the axon of the small, star-shaped cells of the molecular layer of the cerebellum of birds, whose collaterals end up surrounding the Purkinje cell bodies, in the form of baskets or nests. He thus demonstrated once and for all that the relationship between nerve cells was not one of continuity, but rather of contiguity. Neuron theory is one of the principal scientific conquests of the 20th century, and which has withstood, with scarcely any modifications, the passage of more than a 100 years, being reaffirmed by new technologies, as the electron microscopy. Today, no neuroscientific discipline could be understood without recourse to the concept of neuronal individuality and nervous transmission at a synaptic level, as basic units of the nervous system.

[The neurological and embryological studies of Santiago Ramon y Cajal].

PubMed

Baratas Diaz, L A

1997-01-01

The neurological and embryological work of Santiago Ramon y Cajal appeared in three stages: a) Between 1888 and 1893 observations on the development of neuron prolongations led to the observation of the growth cone and formulation of the neurotropic hypothesis. b) Between 1905 and 1908 the study of regenerative phenomena in nerves and nervours centers presented a large body of evidence consistent with the neurotropic hypothesis. c)Between 1910 and 1914 an experimental program was undertaken to test the neurotropic hypothesis; this program led to conclusions on the origin and chemical nature of the growth stimulating factor. These contributions initiated an important line of research that none of Ramon y Cajal's disciples could continue. In the nineteen fifties a group of researchers from three disciplines (biochemistry, embryology and neurohistology) discovered the existence of nerve growth factor (NGF), thus initiating a fertile new field of knowledge in cell biology.

Compulsive buying: relationship with body mass index.

PubMed

Sansone, Randy A; Chang, Joy; Jewell, Bryan; Marion, Brandee E

2013-01-01

Compulsive buying has historically been associated with various self-regulatory disturbances, including eating pathology (e.g., binge eating). Therefore, a relationship between scores on a measure of compulsive buying, the Compulsive Buying Scale (CBS), and body mass index (BMI) in adulthood was hypothesized. Using a self-report survey methodology in a cross-sectional consecutive sample of convenience of 373 obstetrics/gynecology patients, correlations between CBS scores and BMI, both generally and with regard to race were examined. A modest general correlation between CBS scores and BMI (r = 0.17, P < 0.01) was found. However, when these data were examined by race, CBS scores and BMI were significantly related among Caucasian women (r = 0.25, P < 0.01), but not in African American women (r = 0.04, P = n.s.). Findings indicate that compulsive buying is associated with increasing BMI in adulthood, particularly among Caucasian women. Copyright © 2013 The Obesity Society.

Important casual association of carotid body and glossopharyngeal nerve and lung following experimental subarachnoid hemorrhage in rabbits. First report.

PubMed

Yolas, Coskun; Kanat, Ayhan; Aydin, Mehmet Dumlu; Turkmenoglu, Osman Nuri; Gundogdu, Cemal

2014-01-15

The glossopharyngeal nerves (GPNs) and carotid bodies (CBs) have an important role in the continuation of the cerebral autoregulation and cardiorespiratory functions. The relationship between degenerative injury of CB and the GPN in subarachnoid hemorrhage (SAH) was studied. Twenty rabbits were included in this study. Five of them (n=5) were used as control group. The remaining animals (n=15) were exposed to experimental SAH. In the six animals of the SAH group, severe signs of illness were observed, and these six animals were killed in the first week after SAH. Others animals (n=9) were followed for 20 days and then sacrificed. GPNs and CBs were examined and, the live and degenerated GPN axon number, and of CB neuron numbers were stereologically estimated. The mean number of live neurons in CBs was 4206.67±148.35 and live axons of GPNs were 1211.66±14.29 in the animals of the control group. The number of degenerated neurons of CBs was 2065±110.27 and the number of degenerated axons of GPNs was 530.83±43.48 in early killed animals with SAH. The number of degenerated neurons of CBs and the number of degenerated axons of GPNs were found as 1013.89±4184 and 2270.5±134.38 in the living animals with SAH, respectively. High number of degenerated axons of GPN and neurons of CBs of the early killed animals suggest that the mortality in early SAH might be due to GPNs injury secondary to compression of their axons or supplying vessels by the probably herniated brainstem, and secondary denervation injury of CBs, and lung. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

The Histological Slides and Drawings of Cajal

PubMed Central

Garcia-Lopez, Pablo; Garcia-Marin, Virginia; Freire, Miguel

2009-01-01

Ramón y Cajal's studies in the field of neuroscience provoked a radical change in the course of its history. For this reason he is considered as the father of modern neuroscience. Some of his original preparations are housed at the Cajal Museum (Cajal Institute, CSIC, Madrid, Spain). In this article, we catalogue and analyse more than 4,500 of Cajal's histological preparations, the same preparations he used during his scientific career. Furthermore, we catalogued Cajal's original correspondence, both manuscripts and personal letters, drawings and plates. This is the first time anyone has compiled an account of Cajal's enormous scientific production, offering some curious insights into his work and his legacy. PMID:20339483

Vasopressin V1a receptors are present in the carotid body and contribute to the control of breathing in male Sprague-Dawley rats.

PubMed

Żera, Tymoteusz; Przybylski, Jacek; Grygorowicz, Tomasz; Kasarełło, Kaja; Podobińska, Martyna; Mirowska-Guzel, Dagmara; Cudnoch-Jędrzejewska, Agnieszka

2018-04-01

Vasopressin (AVP) maintains body homeostasis by regulating water balance, cardiovascular system and stress response. AVP inhibits breathing through central vasopressin 1a receptors (V1aRs). Chemoreceptors within carotid bodies (CBs) detect chemical and hormonal signals in the bloodstream and provide sensory input to respiratory and cardiovascular centers of the brainstem. In the study we investigated if CBs contain V1aRs and how the receptors are involved in the regulation of ventilation by AVP. We first immunostained CBs for V1aRs and tyrosine hydroxylase, a marker of chemoreceptor type I (glomus) cells. In urethane-anesthetized adult Sprague-Dawley male rats, we then measured hemodynamic and respiratory responses to systemic (intravenous) or local (carotid artery) administration of AVP prior and after systemic blockade of V1aRs. Immunostaining of CBs showed colocalization of V1aRs and tyrosine hydroxylase within glomus cells. Systemic administration of AVP increased mean arterial blood pressure (MABP) and decreased respiratory rate (RR) and minute ventilation (MV). Local administration of AVP increased MV and RR without significant changes in MABP or heart rate. Pretreatment with V1aR antagonist abolished responses to local and intravenous AVP administration. Our findings show that chemosensory cells within CBs express V1aRs and that local stimulation of the CB with AVP increases ventilation, which is contrary to systemic effects of AVP manifested by decreased ventilation. The responses are mediated by V1aRs, as blockade of the receptors prevents changes in ventilation. We hypothesize that excitatory effects of AVP within the CB provide a counterbalancing mechanism for the inhibitory effects of systemically acting AVP on the respiration. Copyright © 2018 Elsevier Inc. All rights reserved.

Dynamics of Human Telomerase Holoenzyme Assembly and Subunit Exchange across the Cell Cycle*

PubMed Central

Vogan, Jacob M.; Collins, Kathleen

2015-01-01

Human telomerase acts on telomeres during the genome synthesis phase of the cell cycle, accompanied by its concentration in Cajal bodies and transient colocalization with telomeres. Whether the regulation of human telomerase holoenzyme assembly contributes to the cell cycle restriction of telomerase function is unknown. We investigated the steady-state levels, assembly, and exchange dynamics of human telomerase subunits with quantitative in vivo cross-linking and other methods. We determined the physical association of telomerase subunits in cells blocked or progressing through the cell cycle as synchronized by multiple protocols. The total level of human telomerase RNA (hTR) was invariant across the cell cycle. In vivo snapshots of telomerase holoenzyme composition established that hTR remains bound to human telomerase reverse transcriptase (hTERT) throughout all phases of the cell cycle, and subunit competition assays suggested that hTERT-hTR interaction is not readily exchangeable. In contrast, the telomerase holoenzyme Cajal body-associated protein, TCAB1, was released from hTR in mitotic cells coincident with TCAB1 delocalization from Cajal bodies. This telomerase holoenzyme disassembly was reversible with cell cycle progression without any change in total TCAB1 protein level. Consistent with differential cell cycle regulation of hTERT-hTR and TCAB1-hTR protein-RNA interactions, overexpression of hTERT or TCAB1 had limited if any influence on hTR assembly of the other subunit. Overall, these findings revealed a cell cycle regulation that disables human telomerase association with telomeres while preserving the co-folded hTERT-hTR ribonucleoprotein catalytic core. Studies here, integrated with previous work, led to a unifying model for telomerase subunit assembly and trafficking in human cells. PMID:26170453

Is obesity contagious by way of body image? A study on Japanese female students in the United States.

PubMed

Bagrowicz, Rinako; Watanabe, Chiho; Umezaki, Masahiro

2013-10-01

Although it has been suggested that obesity is 'contagious' within the social network, direct cause of this spread of obesity remains unclear. This study hypothesized that Body Image (BI), the perception of one's own body size, may play a role in this obesity spread, since a high prevalence of obesity could shift people's perception of 'what is normal'. Young Japanese females (n = 53) were interviewed within 1 month after moving to New York City, where the prevalence of obesity is substantially higher than that of their home country, Japan. Each participant was examined for her BI in terms of current body size (CBS) and ideal body size (IBS). They were interviewed again 2 months after the first examination. Between the two interviews, the participants' CBS was decreased (having thinner self-image), while the IBS increased (having fatter ideal-image), leading to less dissatisfaction (smaller CBS-IBS) with their body size. These results suggest that one's BI could change in a period as short as 2 months, possibly because of being surrounded by more obese people. The IBS change was positively associated with BMI change (increased by 0.4 ± 0.6 kg/m²), warranting further study on the role of BI in the spread of obesity.

Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling.

PubMed

Borrell, Víctor; Marín, Oscar

2006-10-01

Cajal-Retzius cells are critical in the development of the cerebral cortex, but little is known about the mechanisms controlling their development. Three focal sources of Cajal-Retzius cells have been identified in mice-the cortical hem, the ventral pallium and the septum-from where they migrate tangentially to populate the cortical surface. Using a variety of tissue culture assays and in vivo manipulations, we demonstrate that the tangential migration of cortical hem-derived Cajal-Retzius cells is controlled by the meninges. We show that the meningeal membranes are a necessary and sufficient substrate for the tangential migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical surface, while retaining them within the marginal zone in a CXCR4-dependent manner. Thus, the meningeal membranes are fundamental in the development of Cajal-Retzius cells and, hence, in the normal development of the cerebral cortex.

Effects of 4-week self cross body stretching with scapular stabilization on shoulder motions and horizontal adductor strength in subjects with limited shoulder horizontal adduction.

PubMed

Joung, Ha-Na; Yi, Chung-Hwi; Jeon, Hye-Seon; Hwang, Ui-Jae; Kwon, Oh-Yun

2018-05-29

Posterior shoulder tightness (PST) is related to shoulder conditions such as shoulder impingement and limited shoulder horizontal adduction (SHA). The purpose of this study was to compare the effects of self cross body stretching (CBS) with and without scapular stabilization (SS) on SHA and shoulder internal rotation (SIR) range of motion (ROM) and shoulder horizontal adductor strength (SHAS) in subjects with limited SHA. Twenty-six subjects (14 males, 12 females) with limited SHA was participated in this study. The SS group and without stabilization (WS) group were assigned randomly. The SS group performed self CBS with SS by applying belt just under the subject's axilla. The subjects were asked to perform self CBS in 4 times a week for 4 weeks. SHA and SIR RM were measured by Clinometer smartphone application, and SHAS by hand-held dynamometer (HHD) before and after 4-week self CBS. 2 × 2 mixed analysis of variance (ANOVA) was used to identify the significance. If there was an interaction effect, t-test was used to confirm the simple effect. There was a significant interaction in SHA ROM and SHAS. The post-test value of SHA ROM was significantly greater in SS group than WS group (p < 0.0125). In SHAS, there was no significant difference between groups (p > 0.0125). SS during self CBS could enhance to improve SHA, SIR ROM, and SHAS in individuals with limited SHA.

Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease.

PubMed

Porcher, Christophe; Baldo, Marjolaine; Henry, Monique; Orsoni, Pierre; Julé, Yvon; Ward, Sean M

2002-01-01

Interstitial cells of Cajal are critical for the generation of electrical slow waves that regulate the phasic contractile activity of the tunica muscularis of the GI tract. Under certain pathophysiological conditions loss of interstitial cells of Cajal may play a role in the generation of certain motility disorders. The aim of the present study was to determine if there is an abnormality in the density or distribution of interstitial cells of Cajal from patients with Crohn's disease. Small intestines from control subjects and patients with Crohn's disease were examined using immunohistochemistry and antibodies against the Kit receptor, which is expressed in interstitial cells of Cajal within the tunica muscularis of the GI tract. The density and distribution of interstitial cells of Cajal were assessed in the longitudinal and circular muscle layers and in the myenteric and deep muscular plexus regions of Crohn's and control tissues. Tissues from Crohn's disease patients showed an almost complete abolition of interstitial cells of Cajal within the longitudinal and circular muscle layers and a significant reduction in numbers at the level of the myenteric and deep muscular plexuses. In tissues from Crohn's disease patients, the density of interstitial cells of Cajal was reduced throughout the tunica muscularis in comparison to control small intestines. The disturbance of intestinal motility that occurs in patients with Crohn's disease may be a consequence of the loss of or defects in specific populations of interstitial cells of Cajal within the tunica muscularis.

[Culture-bound syndromes: pertinence as a diagnostic category].

PubMed

Perez, S; Junod, A; Pilard, M

2000-01-01

Culture-bound syndromes (CBS) are supposedly confined to one specific cultural areas. These syndromes were first studied by western anthropologists and psychiatrists working overseas, and later by practitioners treating patients from societies with traditional customs and values. The latest edition of the American Psychiatry Association classification (DSM IV) includes an annex on CBS. This report gives a concise background of the process that led to the inclusion of this annex. Then using Koro (a sudden and intense fear that the genitals organs will recede into the body) as an example, a number psychopathological parallels are drawn between CBS and classic manifestations of individual and mass hysteria. The pertinence of individualizing the CBS in the psychiatric nosography including the epistemologic implications is analyzed with reference to the concepts of the French and American Schools of Anthropology. Since attitudes toward mental illness are culturally determined and subject to variation in time and space, we feel that this debate should be placed within the context of a general dialectic between etic (universality) and emic (cultural specificity) rather than a controversy on the need for an annex on CBS in the DSM IV.

Epilog: Cajal's unique and legitimated school.

PubMed

Lerma, Juan; De Carlos, Juan A

2014-01-01

Santiago Ramón y Cajal is recognized as the founder of modern neuroscience, his discoveries representing the fundamental pillars of our current understanding of the nervous system. As Cajal's career spanned a critical period in Spanish history, he witnessed strong social demands for progress in culture, education, and science. Indeed, the life of Santiago Ramón y Cajal can be considered to reflect the gradual development of Spanish science from the last third of the 19th century. Cajal promoted a national movement that had important consequences for Spanish science, mainly triggered by the creation of the "Junta para Ampliación de Estudios e Investigaciones Científicas," an instrument he established to enrich scientific research and that was later to bear such abundant fruit. The school generated by Cajal profited from this development, through which all Cajal's disciples received fellowships to train in laboratories across Europe. Unfortunately, the Spanish Civil War disrupted this revitalization of Spanish science and provoked the diaspora of many Spanish scientists. However, a political impulse, mostly following this spirit, was resumed in Spain during the eighties that successfully led to a renaissance in Spanish science.

Endocannabinoids in Body Weight Control.

PubMed

Horn, Henrike; Böhme, Beatrice; Dietrich, Laura; Koch, Marco

2018-05-30

Maintenance of body weight is fundamental to maintain one's health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing. Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis. Initially, blocking of eCB signaling by first generation cannabinoid type 1 receptor (CB1) inverse agonists such as rimonabant revealed body weight-reducing effects in laboratory animals and men. Unfortunately, rimonabant also induced severe psychiatric side effects. At this point, it became clear that future cannabinoid research has to decipher more precisely the underlying central and peripheral mechanisms behind eCB-driven control of feeding behavior and whole body energy metabolism. Here, we will summarize the most recent advances in understanding how central eCBs interfere with circuits in the brain that control food intake and energy expenditure. Next, we will focus on how peripheral eCBs affect food digestion, nutrient transformation and energy expenditure by interfering with signaling cascades in the gastrointestinal tract, liver, pancreas, fat depots and endocrine glands. To finally outline the safe future potential of cannabinoids as medicines, our overall goal is to address the molecular, cellular and pharmacological logic behind central and peripheral eCB-mediated body weight control, and to figure out how these precise mechanistic insights are currently transferred into the development of next generation cannabinoid medicines displaying clearly improved safety profiles, such as significantly reduced side effects.

The Cajal school and the physiological role of astrocytes: a way of thinking

PubMed Central

Navarrete, Marta; Araque, Alfonso

2014-01-01

Cajal is widely recognized by the scientific community for his important contributions to our knowledge of the neuronal organization of the nervous system. His studies on neuroglial cells are less recognized, yet they are no less relevant to our current understanding of the cellular bases of brain structure. Two pioneering studies published a century ago –“Something about the physiological significance of neuroglia” (Ramón y Cajal, 1897) and “A contribution to the understanding of neuroglia in the human brain” (Ramón y Cajal, 1913)—focused on glial cells and their role in brain physiology. Novel findings obtained using state-of-the-art and sophisticated technologies largely confirm many of the groundbreaking hypotheses proposed by Cajal related to the structural-functional properties of neuroglia. Here we propose to the reader a journey guided by the ideas of Cajal through the recent findings on the functional significance of astrocytes, the most abundant neuroglial cell type in the nervous system. Astrocyte–neuron interaction, which represents an emerging field in current neuroscience with important implications for our understanding of the cellular processes underlying brain function, has its roots in many of the original concepts proposed by Cajal. PMID:24904302

Pre-neurodegeneration of mitral cells in the pcd mutant mouse is associated with DNA damage, transcriptional repression, and reorganization of nuclear speckles and Cajal bodies.

PubMed

Valero, Jorge; Berciano, Maria T; Weruaga, Eduardo; Lafarga, Miguel; Alonso, José R

2006-11-01

DNA damage and impairment of its repair underlie several neurodegenerative diseases. The Purkinje cell degeneration (pcd) mutation causes the loss of Nna1 expression and is associated with a selective and progressive degeneration of specific neuronal populations, including mitral cells in the olfactory bulb. Using an in situ transcription assay, molecular markers for both nuclear compartments and components of the DNA damage/repair pathway, and ultrastructural analysis, here we demonstrate that the pcd mutation induces the formation of DNA damage/repair foci in mitral cells. Furthermore, this effect is associated with transcriptional inhibition, heterochromatinization, nucleolar segregation and the reorganization of nuclear speckles of splicing factors and Cajal bodies. The most significant cytoplasmic alteration observed was a partial replacement of rough endoplasmic reticulum cisternae by a larger amount of free ribosomes, while other organelles were structurally preserved. The tools employed in this work may be of use for the early detection of predegenerative processes in neurodegenerative disorders and for validating rescue strategies.

Santiago Ramón y Cajal and Harvey Cushing: two forefathers of neuroscience and neurosurgery.

PubMed

Zamora-Berridi, Grettel J; Pendleton, Courtney; Ruiz, Gabriel; Cohen-Gadol, Aaron A; Quiñones-Hinojosa, Alfredo

2011-11-01

To summarize the extraordinary accomplishments, and the commonalities, between Santiago Ramon y Cajal and Harvey Williams Cushing. Existing literature describing the lives and achievements of Ramón y Cajal and Cushing, as well as personal communication, and the surgical records of the Johns Hopkins Hospital, from 1896 to 1912, were reviewed. Both Ramón y Cajal and Cushing were men of unusually broad interests and talents, and these shared characteristics undoubtedly influenced the career paths and scientific investigations they pursued. Although Santiago Ramón y Cajal and Harvey Williams Cushing never directly interacted, the links between them can be traced through some of their disciples, including Pío del Río Hortega, Wilder Penfield, and Percival Bailey. Ramón y Cajal and Cushing are widely considered the forefathers of neuroscience and neurosurgery, respectively, and their discoveries have made lasting impressions on both the scientific and medical communities. Copyright © 2011 Elsevier Inc. All rights reserved.

[Women the thought and works of Cajal (remembrances on the 100th anniversary of the Nobel Prize Award)].

PubMed

Cruz Hermida, Julio

2006-01-01

This conference begins with a personal evocation of the author's grandfather, Gaspar Cruz y Martín, Anatomic Sculptor at the Faculty of Medicine of San Carlos--the commemorative medal depicting Cajal that can be seen today at the Cajal Teaching Room Museum in the Medical College of Madrid is due to his hand. The talk goes on to compile a little anthology of texts on women by Cajal, chosen as literary counterparts to his scientific writings. Women are seen by Cajal under the light of beauty, love, marriage, family and even feminism. The anthology ends with a series of "misogynistic stings"--as Dr. Cruz y Hermida calls them--which alternate negative criticism with open praise, mostly showing the admiration that women caused in the sensitive intelligence of the great humanist. The conference finishes with an account of the last moments of Cajal and the moving words by D. Teófilo Hernando, who was at the side of the Maestro when he passed away.

Development and Validation of the Body Size Scale for Assessing Body Weight Perception in African Populations

PubMed Central

Cohen, Emmanuel; Bernard, Jonathan Y.; Ponty, Amandine; Ndao, Amadou; Amougou, Norbert; Saïd-Mohamed, Rihlat; Pasquet, Patrick

2015-01-01

Background The social valorisation of overweight in African populations could promote high-risk eating behaviours and therefore become a risk factor of obesity. However, existing scales to assess body image are usually not accurate enough to allow comparative studies of body weight perception in different African populations. This study aimed to develop and validate the Body Size Scale (BSS) to estimate African body weight perception. Methods Anthropometric measures of 80 Cameroonians and 81 Senegalese were used to evaluate three criteria of adiposity: body mass index (BMI), overall percentage of fat, and endomorphy (fat component of the somatotype). To develop the BSS, the participants were photographed in full face and profile positions. Models were selected for their representativeness of the wide variability in adiposity with a progressive increase along the scale. Then, for the validation protocol, participants self-administered the BSS to assess self-perceived current body size (CBS), desired body size (DBS) and provide a “body self-satisfaction index.” This protocol included construct validity, test-retest reliability and convergent validity and was carried out with three independent samples of respectively 201, 103 and 1115 Cameroonians. Results The BSS comprises two sex-specific scales of photos of 9 models each, and ordered by increasing adiposity. Most participants were able to correctly order the BSS by increasing adiposity, using three different words to define body size. Test-retest reliability was consistent in estimating CBS, DBS and the “body self-satisfaction index.” The CBS was highly correlated to the objective BMI, and two different indexes assessed with the BSS were consistent with declarations obtained in interviews. Conclusion The BSS is the first scale with photos of real African models taken in both full face and profile and representing a wide and representative variability in adiposity. The validation protocol proved its reliability for estimating body weight perception in Africans. PMID:26536030

[Historical meanings of Santiago Ramón y Cajal's Rétine des vertébrés. Summary of his first scientific].

PubMed

Baratas Díaz, L A

1994-01-01

The retina was one of the main objects of study in the first stage of the scientific work of Ramón y Cajal. As culmination of his previous works Cajal published in 1893 in the journal La Cellule an article titled "La rétine des Vertébrés". This article on the retina is a perfect example of Cajal's ability for the systematic study of the cellular types of the nervous centers, its morphological description and its intercellular contacts, as well as for the formulation of physiological interpretations and hypothesis on the development of the neuronal prolongations. Finally some comments are made on the influence of the evolutionary thinking of Haeckel and Herbert Spencer on the work of Ramón y Cajal.

The structure of Lippmann heliochromes: Cajal and the 1908 Nobel Prize in Physics.

PubMed

Triarhou, Lazaros C; del Cerro, Manuel

2008-01-01

The 1908 Nobel Prize in Physics was awarded to Luxembourgeois Gabriel Lippmann (1848-1921), Professor of Mathematical and Experimental Physics at la Sorbonne, for his method of reproducing colors photographically based on the theory of wave interference. In the preceding several years, the eminent neurohistologist - and avid photographer - Santiago Ramón y Cajal (1852-1934) had been experimenting with Lippmann heliochromes, studying under the microscope the structure of the laminae of Zenker that produce mixed colors, and especially white. Those studies led to a series of technical papers by Cajal, the culmination being an article published 100 years ago in the Annual Report of the Board of Regents of the Smithsonian Institution in Washington, DC. A few years later, Cajal published Photography in Colors, his classic monograph on the physicochemical principles of the 'art of Daguerre,' bearing further testimony to his exuberant productivity, far-reaching interests, and scientific genius. The present article reflects on the workings of the mind of Cajal and his fundamental knowledge that was a precondition for his success in neurohistology. It highlights the links between the early photographic studies of Cajal and Lippmann, masters of the biological and physical sciences, respectively. Special emphasis is placed on Lippmann's discovery of heliochromes and the microscopic analyses performed on them by Cajal, including elements from relevant contemporary studies and discoveries.

Differentiating between visual hallucination-free dementia with Lewy bodies and corticobasal syndrome on the basis of neuropsychology and perfusion single-photon emission computed tomography.

PubMed

Misch, Michael R; Mitchell, Sara; Francis, Philip L; Sherborn, Kayla; Meradje, Katayoun; McNeely, Alicia A; Honjo, Kie; Zhao, Jiali; Scott, Christopher Jm; Caldwell, Curtis B; Ehrlich, Lisa; Shammi, Prathiba; MacIntosh, Bradley J; Bilbao, Juan M; Lang, Anthony E; Black, Sandra E; Masellis, Mario

2014-01-01

Dementia with Lewy bodies (DLB) and Corticobasal Syndrome (CBS) are atypical parkinsonian disorders with fronto-subcortical and posterior cognitive dysfunction as common features. While visual hallucinations are a good predictor of Lewy body pathology and are rare in CBS, they are not exhibited in all cases of DLB. Given the clinical overlap between these disorders, neuropsychological and imaging markers may aid in distinguishing these entities. Prospectively recruited case-control cohorts of CBS (n =31) and visual hallucination-free DLB (n =30), completed neuropsychological and neuropsychiatric measures as well as brain perfusion single-photon emission computed tomography and structural magnetic resonance imaging (MRI). Perfusion data were available for forty-two controls. Behavioural, perfusion, and cortical volume and thickness measures were compared between the groups to identify features that serve to differentiate them. The Lewy body with no hallucinations group performed more poorly on measures of episodic memory compared to the corticobasal group, including the delayed and cued recall portions of the California Verbal Learning Test (F (1, 42) =23.1, P <0.001 and F (1, 42) =14.0, P =0.001 respectively) and the delayed visual reproduction of the Wechsler Memory Scale-Revised (F (1, 36) =9.7, P =0.004). The Lewy body group also demonstrated reduced perfusion in the left occipital pole compared to the corticobasal group (F (1,57) =7.4, P =0.009). At autopsy, the Lewy body cases all demonstrated mixed dementia with Lewy bodies, Alzheimer's disease and small vessel arteriosclerosis, while the corticobasal cases demonstrated classical corticobasal degeneration in five, dementia with agyrophilic grains + corticobasal degeneration + cerebral amyloid angiopathy in one, Progressive Supranuclear Palsy in two, and Frontotemporal Lobar Degeneration-Ubiquitin/TAR DNA-binding protein 43 proteinopathy in one. MRI measures were not significantly different between the patient groups. Reduced perfusion in the left occipital region and worse episodic memory performance may help to distinguish between DLB cases who have never manifested with visual hallucinations and CBS at earlier stages of the disease. Development of reliable neuropsychological and imaging markers that improve diagnostic accuracy will become increasingly important as disease modifying therapies become available.

Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

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

Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna

2013-02-01

HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies includingmore » Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies. -- Highlights: ► We produce and validate new antibody reagents for the ubiquitin-protein ligase HHARI. ► HHARI colocalizes with nuclear bodies including Cajal, PML and SC35 bodies. ► We establish new functions in cell proliferation regulation for HHARI. ► Increased HHARI expression associates with squamous cell carcinoma and proliferation.« less

The evaluation of interstitial Cajal cells distribution in non-tumoral colon disorders.

PubMed

Becheanu, G; Manuc, M; Dumbravă, Mona; Herlea, V; Hortopan, Monica; Costache, Mariana

2008-01-01

Interstitial cells of Cajal (ICC) are pacemakers that generate electric waves recorded from the gut and are important for intestinal motility. The aim of the study was to evaluate the distribution of interstitial cells of Cajal in colon specimens from patients with idiopathic chronic pseudo-obstruction and other non-tumoral colon disorders as compared with samples from normal colon. The distribution pattern of ICC in the normal and pathological human colon was evaluated by immunohistochemistry using antibodies for CD117, CD34, and S-100. In two cases with intestinal chronic idiopathic pseudo-obstruction we found a diffuse or focal reducing number of Cajal cells, the loss of immunoreactivity for CD117 being correlated with loss of immunoreactivity for CD34 marker. Our study revealed that the number of interstitial cells of Cajal also decrease in colonic diverticular disease and Crohn disease (p<0.05), whereas the number of enteric neurones appears to be normal. These findings might explain some of the large bowel motor abnormalities known to occur in these disorders. Interstitial Cajal cells may play an important role in pathogenesis and staining for CD117 on transmural intestinal surgical biopsies could allow a more extensive diagnosis in evaluation of chronic intestinal pseudo-obstruction.

[The work of Santiago Ramón y Cajal in the Revista Trimestral Micrográfica (Trabajos del Laboratorio de Investigaciones Biológicas)].

PubMed

Gamundí, A; Timoner, G; Nicolau, M C; Rial, R V; Esteban, S; Langa, M A

This paper is based on a study of Revista Trimestral Micrografica (Trabajos del Laboratorio de Investigaciones Biologicas) between its creation by Santiago Ramon y Cajal in 1896 and his death in 1934. The journal Revista Trimestral Micrografica was the main way in which Santiago Ramon y Cajal and his school published their work since its creation. Ramon y Cajal created the journal for two main reasons: first, he needed a rapid system to publish his own work; second, the journal could serve to encourage his pupils. The journal published many important reports defending the neuronal theory which expanded the cellular one to include the nervous system.

The influence of James and Darwin on Cajal and his research into the neuron theory and evolution of the nervous system.

PubMed

Ferreira, Francisco R M; Nogueira, Maria I; Defelipe, Javier

2014-01-01

In this article we discuss the influence of William James and Charles Darwin on the thoughts of Santiago Ramón y Cajal concerning the structure, plasticity, and evolution of the nervous system at the cellular level. Here we develop Cajal's notion that neuronal theory is a necessary condition to explain the plasticity of neural connections. Although the roots of the term "plasticity" in reference to neuroscience are not completely clear, Cajal was an important figure in the propagation and popularization of its use. It is true that he carried out a large number of studies throughout his career in favor of the neuronal theory, but perhaps one of the most interesting aspects of his studies was his innovative capacity to interpret structure as being the result of evolutionary mechanisms, i.e., natural selection. This capacity would ultimately lead Cajal to the conclusion that, in relation to the histology of the nervous system, such selection occurs in the establishment of connections between cells. The present article is divided into five sections: (1) Learning and general notions of organic plasticity in the 19th century; (2) The idea of "mental" plasticity proposed by James; (3) Neuronal theory and "structural" plasticity: general considerations; (4) Evolutionary factors of the nervous system in Cajal's work; and (5) Final considerations.

[Santiago Ramon y Cajal in literature, cinema and television].

PubMed

Collado-Vazquez, S; Carrillo, J M

2016-11-16

The life and work of Santiago Ramon y Cajal has been portrayed in scientific papers, biographical and autobiographical works, comics, films, television series or documentaries that have attempted to reflect upon his life or his contributions to science and to bring him closer to the general public. To analyse the different ways Santiago Ramon y Cajal has been represented in literature, cinema and television, and to become more closely acquainted with this scientist through his fictional writings. A number of biographical works have been written about Santiago Ramon y Cajal, including scientific papers, comics, books for children and youngsters, as well as the autobiographical writings, essays and even science fiction stories, which provide a good introduction to the life of the scientist and his work. His life has also been adapted to film (Leap to fame) or television (Ramon y Cajal, historia de una voluntad; The butterflies of the soul), which have, with varying degrees of success and accuracy, made him better known to the general population. The numerous biographical writings, historical notes, articles, the scientific work itself, the essays and fictional works by Cajal, as well as the portrayals of the Spanish Nobel Prize winner produced for films and television, can be used to obtain some interesting insights into the scientist, teacher, science populariser, humanist physician and, in short, the man who made such important contributions to neuroscience.

Towards the Sensory Nature of the Carotid Body: Hering, De Castro and Heymans†

PubMed Central

de Castro, Fernando

2009-01-01

The carotid body or glomus caroticum is a chemosensory organ bilaterally located between the external and internal carotid arteries. Although known by anatomists since the report included by Von Haller and Taube in the mid XVIII century, its detailed study started the first quarter of the XX. The Austro-German physiologist Heinrich E. Hering studied the cardio-respiratory reflexes searched for the anatomical basis of this reflex in the carotid sinus, while the Ghent School leaded by the physio-pharmacologists Jean-François Heymans and his son Corneille focussed in the cardio-aortic reflexogenic region. In 1925, Fernando De Castro, one of the youngest and more brilliant disciples of Santiago Ramón y Cajal at the Laboratorio de Investigaciones Biológicas (Madrid, Spain), profited from some original novelties in histological procedures to study the fine structure and innervation of the carotid body. De Castro unravelled them in a series of scientific papers published between 1926 and 1929, which became the basis to consider the carotid body as a sensory receptor (or chemoreceptor) to detect the chemical changes in the composition of the blood. Indeed, this was the first description of arterial chemoreceptors. Impressed by the novelty and implications of the work of De Castro, Corneille Heymans invited the Spanish neurologist to visit Ghent on two occasions (1929 and 1932), where both performed experiences together. Shortly after, Heymans visited De Castro at the Instituto Cajal (Madrid). From 1932 to 1933, Corneille Heymans focused all his attention on the carotid body his physiological demonstration of De Castro's hypothesis regarding chemoreceptors was awarded with the Nobel Prize in Physiology or Medicine in 1938, just when Spain was immersed in its catastrophic Civil War. PMID:20057927

All Small Nuclear RNAs (snRNAs) of the [U4/U6.U5] Tri-snRNP Localize to Nucleoli; Identification of the Nucleolar Localization Element of U6 snRNA

PubMed Central

Gerbi, Susan A.; Lange, Thilo Sascha

2002-01-01

Previously, we showed that spliceosomal U6 small nuclear RNA (snRNA) transiently passes through the nucleolus. Herein, we report that all individual snRNAs of the [U4/U6.U5] tri-snRNP localize to nucleoli, demonstrated by fluorescence microscopy of nucleolar preparations after injection of fluorescein-labeled snRNA into Xenopus oocyte nuclei. Nucleolar localization of U6 is independent from [U4/U6] snRNP formation since sites of direct interaction of U6 snRNA with U4 snRNA are not nucleolar localization elements. Among all regions in U6, the only one required for nucleolar localization is its 3′ end, which associates with the La protein and subsequently during maturation of U6 is bound by Lsm proteins. This 3′-nucleolar localization element of U6 is both essential and sufficient for nucleolar localization and also required for localization to Cajal bodies. Conversion of the 3′ hydroxyl of U6 snRNA to a 3′ phosphate prevents association with the La protein but does not affect U6 localization to nucleoli or Cajal bodies. PMID:12221120

Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis

PubMed Central

2017-01-01

Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value. PMID:28930162

Lean Body Mass Harbors Sensing Mechanisms that Allow Safeguarding of Methionine Homeostasis.

PubMed

Ingenbleek, Yves

2017-09-20

Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value.

Dendritic Spines and Development: Towards a Unifying Model of Spinogenesis—A Present Day Review of Cajal's Histological Slides and Drawings

PubMed Central

García-López, Pablo; García-Marín, Virginia; Freire, Miguel

2010-01-01

Dendritic spines receive the majority of excitatory connections in the central nervous system, and, thus, they are key structures in the regulation of neural activity. Hence, the cellular and molecular mechanisms underlying their generation and plasticity, both during development and in adulthood, are a matter of fundamental and practical interest. Indeed, a better understanding of these mechanisms should provide clues to the development of novel clinical therapies. Here, we present original results obtained from high-quality images of Cajal's histological preparations, stored at the Cajal Museum (Instituto Cajal, CSIC), obtained using extended focus imaging, three-dimensional reconstruction, and rendering. Based on the data available in the literature regarding the formation of dendritic spines during development and our results, we propose a unifying model for dendritic spine development. PMID:21584262

Neuroanatomy: Cajal and after Cajal.

PubMed

Jones, Edward G

2007-10-01

This essay commences with a consideration of the relative contributions of Cajal and Golgi to the study of the anatomy of the nervous system. It demonstrates the extent to which Cajal depended upon Golgi's work and how his modifications of the Golgi technique permitted a remarkable series of investigations in which the foundations of the neuron doctrine were laid and in which the intrinsic connectivity of virtually every part of the central nervous system was charted. Cajal's readiness to seize on and develop new techniques was one of the many keys to his success. After him, neuroanatomical studies tended to be focused more on long tract connectivity, using techniques such as those of Nissl and Marchi that had been in place before Cajal commenced his studies. Development of degeneration-based techniques of tracing connections in the late 1950s spearheaded a revolution in neuroanatomy while introduction of mixed aldehyde fixation made possible similarly intensive studies of the fine structure of the nervous system. At this time, the Golgi technique experienced a brief resurgence as neuroanatomists made efforts to bridge the gap between light and electron microscopy. Later developments in techniques for tracing connections included anterograde tracing by autoradiography and retrograde tracing by horseradish peroxidase. These were soon superseded by tracing techniques of increasing sensitivity and specificity that rely upon the cellular and molecular biology of neurons. Although neuroanatomy in its traditional form is perhaps no longer fashionable as a discipline, the techniques of neuroanatomy remain preeminent in many, perhaps all areas of neuroscience.

Development of a new body image assessment scale in urban Cameroon: an anthropological approach.

PubMed

Cohen, Emmanuel; Pasquet, Patrick

2011-01-01

Develop and validate body image scales (BIS) presenting real human bodies adapted to the macroscopic phenotype of urban Cameroonian populations. Quantitative and qualitative analysis. Yaoundé, capital city of Cameroon. Four samples with balanced sex-ratio: the first (n=16) aged 18 to 65 years (qualitative study), the second (n=30) aged 25 to 40 years (photo database), the third (n=47) and fourth (n=181), > or =18 years (validation study). Construct validity, test retest reliability, concurrent and convergent validity of BIS. Body image scales present six Cameroonians of each sex arranged according to main body mass index (BMI) categories: underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity class I (30-34.9 kg/m2), obesity class II (35-39.9 kg/m2), and obesity class III (> or =40 kg/m2). Test-retest reliability correlations for current body size (CBS), desired body size and current desirable discrepancy (body self-satisfaction index) on BIS were never below .90. Plus, for the concurrent validity, we observed a significant correlation (r=0.67, P<.01) between measured BMI and CBS. Finally, the convergent validity between BIS and a female African American silhouettes scale, for different dimensions of body size perceptions, is acceptable. Body image scales are adapted to the phenotypic characteristics of urban Cameroonian populations. They are reliable and valid to assess body size perceptions and culturally adapted to the Cameroonian context.

Noncovalent Interactions of DNA Bases with Naphthalene and Graphene.

PubMed

Cho, Yeonchoo; Min, Seung Kyu; Yun, Jeonghun; Kim, Woo Youn; Tkatchenko, Alexandre; Kim, Kwang S

2013-04-09

The complexes of a DNA base bound to graphitic systems are studied. Considering naphthalene as the simplest graphitic system, DNA base-naphthalene complexes are scrutinized at high levels of ab initio theory including coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] at the complete basis set (CBS) limit. The stacked configurations are the most stable, where the CCSD(T)/CBS binding energies of guanine, adenine, thymine, and cytosine are 9.31, 8.48, 8.53, 7.30 kcal/mol, respectively. The energy components are investigated using symmetry-adapted perturbation theory based on density functional theory including the dispersion energy. We compared the CCSD(T)/CBS results with several density functional methods applicable to periodic systems. Considering accuracy and availability, the optB86b nonlocal functional and the Tkatchenko-Scheffler functional are used to study the binding energies of nucleobases on graphene. The predicted values are 18-24 kcal/mol, though many-body effects on screening and energy need to be further considered.

Imaging correlates of pathology in corticobasal syndrome(Podcast)

PubMed Central

Whitwell, J.L.; Jack, C.R.; Boeve, B.F.; Parisi, J.E.; Ahlskog, J.E.; Drubach, D.A.; Senjem, M.L.; Knopman, D.S.; Petersen, R.C.; Dickson, D.W.; Josephs, K.A.

2010-01-01

Background: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS. Methods: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls. Results: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD. Conclusions: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology. GLOSSARY AAL = automated anatomic labeling; AD = Alzheimer disease; CBD = corticobasal degeneration; CBS = corticobasal syndrome; CDR-SB = Clinical Dementia Rating sum of boxes; FDR = false discovery rate; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; PSP = progressive supranuclear palsy; ROI = region of interest; SMA = supplemental motor area; TDP = TDP-43 immunoreactivity; TIV = total intracranial volume; VBM = voxel-based morphometry. PMID:21098403

[Santiago Ramón y Cajal and cardiology: His little known discovery of sarcolemma in the cardiomyocytes].

PubMed

de Fuentes Sagaz, M

2001-08-01

The first description of sarcolemma in cardiomyocytes was reported by Ramón y Cajal in Textura de la fibra muscular del corazón, published in 1888. In this article, he summarized his observations of the structure of cardiac fibres applying gold chloride dyes and posterior corrosion by acids. The sarcolemma, the fundamental membrane of the cardiac muscle cell, which was not recognized at that time by other researchers, was demonstrated by Ramón y Cajal who provided the first evidence supporting its existence and hypothetized about its functional significance.

Santiago Ramón y Cajal and three-dimensional cinema.

PubMed

Santarén, Juan Fernández

2015-01-01

In this article, I present and comment on two unpublished letters written by the Spanish engineer Carlos Mendizábal Brunet to Santiago Ramón y Cajal informing him of the development of a new device for three-dimensional cinema and asking for his approval. Fortunately, the answers given by Cajal to these two letters have also been preserved, and they reveal his interest in three-dimensional cinema; in the letters, he reported that he himself had designed a prototype capable of creating on a screen a feeling of 3-D relief, a subject about which he was always passionate.

Unraveling Cajal's view of the olfactory system

PubMed Central

Figueres-Oñate, María; Gutiérrez, Yolanda; López-Mascaraque, Laura

2014-01-01

The olfactory system has a highly regular organization of interconnected synaptic circuits from the periphery. It is therefore an excellent model for understanding general principles about how the brain processes information. Cajal revealed the basic cell types and their interconnections at the end of the XIX century. Since his original descriptions, the observation and analysis of the olfactory system and its components represents a major topic in neuroscience studies, providing important insights into the neural mechanisms. In this review, we will highlight the importance of Cajal contributions and his legacy to the actual knowledge of the olfactory system. PMID:25071462

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

Hu, Yi, E-mail: yihooyi@gmail.com; Ericsson, Ida, E-mail: ida.ericsson@ntnu.no; Doseth, Berit, E-mail: berit.doseth@ntnu.no

Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and foundmore » that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation.« less

Therapeutic potential of cannabis in pain medicine.

PubMed

Hosking, R D; Zajicek, J P

2008-07-01

Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (Delta(9)-THC) was isolated in 1964 and the first CB receptor (CB(1)R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB(1)Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB(2) receptors (CB(2)R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB(1)R and CB(2)R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.

Changes in Structure, Interstitial Cajal-like Cells and Apoptosis of Smooth Muscle Cells in Congenital Ureteropelvic Junction Obstruction

PubMed Central

Mehrazma, Mitra; Tanzifi, Parin; Rakhshani, Naser

2014-01-01

Objective: The goal of this study is to evaluate some structural changes in muscular, collagenous and neural components as well as expression of Cajal-like cells and apoptosis of smooth muscle cells in congenital ureteropelvic junction obstruction (UPJO). Methods: Tissue specimens were obtained from 25 patients with UPJO and compared with normal ureteropelvic junction regions of 19 autopsies. In paraffin embedded sections the amount of Cajal-like cells, density of nerve fibers and smooth muscle cell apoptosis (using immunohistochemical staining) were determined. Collagen deposition and muscular components were stained by Trichrome-Masson staining and evaluated by image analysis techniques. Arrangement of muscular bundles was also evaluated qualitatively. Findings : The number of Cajal-like cells was significantly lower in patients than in controls. The apoptotic score and mean number of nerve fibers were not statistically different for the two groups. Arrangement of muscular fibers was more irregular in patients than in controls (P<0.001). Collagen deposition was significantly higher in patients than in controls (P<0.001). The mean amount of muscular component was lower in patients than in normal ones. (P= 0.09) Conclusion: We found significant pathologic changes in congenital ureteropelvic junction obstruction such as decrease in Cajal-like cells, increase in collagen deposition and irregular arrangement of muscle fibers. PMID:25793054

Acid Sphingomyelinase Gene Knockout Ameliorates Hyperhomocysteinemic Glomerular Injury in Mice Lacking Cystathionine-β-Synthase

PubMed Central

Boini, Krishna M.; Xia, Min; Abais, Justine M.; Xu, Ming; Li, Cai-xia; Li, Pin-Lan

2012-01-01

Acid sphingomyelinase (ASM) has been implicated in the development of hyperhomocysteinemia (hHcys)-induced glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and characterized the mice lacking cystathionine β-synthase (Cbs) and Asm mouse gene by cross breeding Cbs+/− and Asm+/− mice. Given that the homozygotes of Cbs−/−/Asm−/− mice could not survive for 3 weeks. Cbs+/−/Asm+/+, Cbs+/−/Asm+/− and Cbs+/−/Asm−/− as well as their Cbs wild type littermates were used to study the role of Asm−/− under a background of Cbs+/− with hHcys. HPLC analysis revealed that plasma Hcys level was significantly elevated in Cbs heterozygous (Cbs+/−) mice with different copies of Asm gene compared to Cbs+/+ mice with different Asm gene copies. Cbs+/−/Asm+/+ mice had significantly increased renal Asm activity, ceramide production and O2.− level compared to Cbs+/+/Asm+/+, while Cbs+/−/Asm−/− mice showed significantly reduced renal Asm activity, ceramide production and O2.− level due to increased plasma Hcys levels. Confocal microscopy demonstrated that colocalization of podocin with ceramide was much lower in Cbs+/−/Asm−/− mice compared to Cbs+/−/Asm+/+ mice, which was accompanied by a reduced glomerular damage index, albuminuria and proteinuria in Cbs+/−/Asm−/− mice. Immunofluorescent analyses of the podocin, nephrin and desmin expression also illustrated less podocyte damages in the glomeruli from Cbs+/−/Asm−/− mice compared to Cbs+/−/Asm+/+ mice. In in vitro studies of podocytes, hHcys-enhanced O2.− production, desmin expression, and ceramide production as well as decreases in VEGF level and podocin expression in podocytes were substantially attenuated by prior treatment with amitriptyline, an Asm inhibitor. In conclusion, Asm gene knockout or corresponding enzyme inhibition protects the podocytes and glomeruli from hHcys-induced oxidative stress and injury. PMID:23024785

Kinetics of Nitrite Reduction and Peroxynitrite Formation by Ferrous Heme in Human Cystathionine β-Synthase*

PubMed Central

Carballal, Sebastián; Cuevasanta, Ernesto; Yadav, Pramod K.; Gherasim, Carmen; Ballou, David P.; Alvarez, Beatriz; Banerjee, Ruma

2016-01-01

Cystathionine β-synthase (CBS) is a pyridoxal phosphate-dependent enzyme that catalyzes the condensation of homocysteine with serine or with cysteine to form cystathionine and either water or hydrogen sulfide, respectively. Human CBS possesses a noncatalytic heme cofactor with cysteine and histidine as ligands, which in its oxidized state is relatively unreactive. Ferric CBS (Fe(III)-CBS) can be reduced by strong chemical and biochemical reductants to Fe(II)-CBS, which can bind carbon monoxide (CO) or nitric oxide (NO•), leading to inactive enzyme. Alternatively, Fe(II)-CBS can be reoxidized by O2 to Fe(III)-CBS, forming superoxide radical anion (O2˙̄). In this study, we describe the kinetics of nitrite (NO2−) reduction by Fe(II)-CBS to form Fe(II)NO•-CBS. The second order rate constant for the reaction of Fe(II)-CBS with nitrite was obtained at low dithionite concentrations. Reoxidation of Fe(II)NO•-CBS by O2 showed complex kinetic behavior and led to peroxynitrite (ONOO−) formation, which was detected using the fluorescent probe, coumarin boronic acid. Thus, in addition to being a potential source of superoxide radical, CBS constitutes a previously unrecognized source of NO• and peroxynitrite. PMID:26867575

Cajal and consciousness. Introduction.

PubMed

Marijuán, P C

2001-04-01

One hundred years after Santiago Ramón Cajal established the bases of modern neuroscience in his masterpiece Textura del sistema nervioso del hombre y de los vertebrados, the question is stated again: What is the status of consciousness today? The responses in this book, by contemporary leading figures of neuroscience, evolution, molecular biology, computer science, and quantum physics, collectively compose a fascinating conceptual landscape. Both the evolutionary emergence of consciousness and its development towards the highest level may be analyzed by a wealth of new theories and hypotheses, including Cajal's prescient ones. Some noticeable gaps remain, however. Celebrating the centennial of Textura is a timely occasion to reassess how close--and how far--our system of the sciences is to explaining consciousness.

[La voluntad pedagógica de Cajal, presidente de la Jae].

PubMed

López-Ocón Cabrera, Leoncio

2007-01-01

This article has two aims. On one hand, it tries to point out the role of the Santiago Ramón y Cajal in the establishment and development of the "Junta para Ampiación de Estudios e Investigaciones Cientificas" (JAE). On the other hand, it links the leadership of Cajal in this Institution to his teaching authority of young scientifics. This pedagogical will was showed with various facts along his intellectual path. It is appropriate to underline among them his effort in spreading science, his enthusiasm and engagement in order to change the educational structures of Spanish Society and his 25 year long Presidency of JAE, from 1907 until 1932.

The snoRNA domain of vertebrate telomerase RNA functions to localize the RNA within the nucleus.

PubMed Central

Lukowiak, A A; Narayanan, A; Li, Z H; Terns, R M; Terns, M P

2001-01-01

Telomerase RNA is an essential component of the ribonucleoprotein enzyme involved in telomere length maintenance, a process implicated in cellular senescence and cancer. Vertebrate telomerase RNAs contain a box H/ACA snoRNA motif that is not required for telomerase activity in vitro but is essential in vivo. Using the Xenopus oocyte system, we have found that the box H/ACA motif functions in the subcellular localization of telomerase RNA. We have characterized the transport and biogenesis of telomerase RNA by injecting labeled wild-type and variant RNAs into Xenopus oocytes and assaying nucleocytoplasmic distribution, intranuclear localization, modification, and protein binding. Although yeast telomerase RNA shares characteristics of spliceosomal snRNAs, we show that human telomerase RNA is not associated with Sm proteins or efficiently imported into the nucleus. In contrast, the transport properties of vertebrate telomerase RNA resemble those of snoRNAs; telomerase RNA is retained in the nucleus and targeted to nucleoli. Furthermore, both nuclear retention and nucleolar localization depend on the box H/ACA motif. Our findings suggest that the H/ACA motif confers functional localization of vertebrate telomerase RNAs to the nucleus, the compartment where telomeres are synthesized. We have also found that telomerase RNA localizes to Cajal bodies, intranuclear structures where it is thought that assembly of various cellular RNPs takes place. Our results identify the Cajal body as a potential site of telomerase RNP biogenesis. PMID:11780638

Identification and characterization of Clonorchis sinensis cathepsin B proteases in the pathogenesis of clonorchiasis.

PubMed

Chen, Wenjun; Ning, Dan; Wang, Xiaoyun; Chen, Tingjin; Lv, Xiaoli; Sun, Jiufeng; Wu, De; Huang, Yan; Xu, Jin; Yu, Xinbing

2015-12-21

Human clonorchiasis is a prevailing food-borne disease caused by Clonorchis sinensis infection. Functional characterizations of key molecules from C. sinensis could facilitate the intervention of C. sinensis associated diseases. In this study, immunolocalization of C. sinensis cathepsin B proteases (CsCBs) in C. sinensis worms was investigated. Four CsCBs were expressed in Pichia pastoris yeast cells. Purified yCsCBs were measured for enzymatic and hydrolase activities in the presence of various host proteins. Cell proliferation, wound-healing and transwell assays were performed to show the effect of CsCBs on human cells. CsCBs were localized in the excretory vesicle, oral sucker and intestinal tract of C. sinensis. Recombinant yCsCBs from yeast showed active enzymatic activity at pH 5.0-5.5 and at 37-42 °C. yCsCBs can degrade various host proteins including human serum albumin, human fibronectin, human hemoglobin and human IgG. CsCBs were detected in liver tissues of mice and cancer patients afflicted with clonorchiasis. Various bioassays collectively demonstrated that CsCBs could promote cell proliferation, migration and invasion of human cancer cells. Our results demonstrated that CsCBs can degrade various human proteins and we proved that the secreted CsCBs are involved in the pathogenesis of clonorchiasis.

Hypnoanalgesia and the study of pain experience: from Cajal to modern neuroscience

PubMed Central

Lanfranco, Renzo C.; Canales-Johnson, Andrés; Huepe, David

2014-01-01

Santiago Ramón y Cajal (1852–1934) did not only contribute to neurobiology and neurohistology. At the end of the 19th century, he published one of the first clinical reports on the employment of hypnotic suggestion to induce analgesia (hypnoanalgesia) in order to relieve pain in childbirth. Today, the clinical application of hypnoanalgesia is considered an effective technique for the treatment of pain in medicine, dentistry, and psychology. However, the knowledge we have today on the neural and cognitive underpinnings of hypnotic suggestion has increased dramatically since Cajal’s times. Here we review the main contributions of Cajal to hypnoanalgesia and the current knowledge we have about hypnoanalgesia from neural and cognitive perspectives. PMID:25324822

Santiago Ramón y Cajal and the Spanish school of neurology.

PubMed

Andres-Barquin, Pedro J

2002-11-01

Advances in neurology are now possible thanks to the endeavours of a few scientists who in the past laid firm foundations for the study of the nervous system. Santiago Ramón y Cajal (1852-1934) was one such pioneer of brain exploration and is acknowledged as the founder of modern neuroscience. He described the structure and organisation of virtually all parts of the nervous system and developed theories, including the neuron doctrine and the law of functional polarisation, that are the cornerstones of neuroscience. In addition to devoting his life to research, Ramón y Cajal was a dedicated teacher and mentor and created a school that greatly contributed to the flourishing of neurology.

Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA*

PubMed Central

Karasawa, Akira; Erkens, Guus B.; Berntsson, Ronnie P.-A.; Otten, Renee; Schuurman-Wolters, Gea K.; Mulder, Frans A. A.; Poolman, Bert

2011-01-01

The cystathionine β-synthase module of OpuA in conjunction with an anionic membrane surface acts as a sensor of internal ionic strength, which allows the protein to respond to osmotic stress. We now show by chemical modification and cross-linking studies that CBS2-CBS2 interface residues are critical for transport activity and/or ionic regulation of transport, whereas CBS1 serves no functional role. We establish that Cys residues in CBS1, CBS2, and the nucleotide-binding domain are more accessible for cross-linking at high than low ionic strength, indicating that these domains undergo conformational changes when transiting between the active and inactive state. Structural analyses suggest that the cystathionine β-synthase module is largely unstructured. Moreover, we could substitute CBS1 by a linker and preserve ionic regulation of transport. These data suggest that CBS1 serves as a linker and the structured CBS2-CBS2 interface forms a hinge point for ionic strength-dependent rearrangements that are transmitted to the nucleotide-binding domain and thereby affect translocation activity. PMID:21878634

Influence of plasma treatment of carbon blacks on electrochemical activity of Pt/carbon blacks catalysts for DMFCs

NASA Astrophysics Data System (ADS)

Kim, Seok; Cho, Mi-Hwa; Lee, Jae-Rock; Park, Soo-Jin

In this work, in order to improve the dispersion of platinum catalysts deposited on carbon materials, the effects of surface plasma treatment of carbon blacks (CBs) were investigated. The surface characteristics of the CBs were determined by fourier transformed-infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), and Boehm's titration method. The electrochemical properties of the plasma-treated CBs-supported Pt (Pt/CBs) catalysts were analyzed by linear sweep voltammetry (LSV) experiments. From the results of FT-IR and acid-base values, N 2-plasma treatment of the CBs at 300 W intensity led to a formation of a free radical on the CBs. The peak intensity increased with increase of the treatment time, due to the formation of new basic functional groups (such as C-N, C dbnd N, -NH 3 +, -NH, and dbnd NH) by the free radical on the CBs. Accordingly, the basic values were enhanced by the basic functional groups. However, after a specific reaction time, N 2-plasma treatment could hardly influence on change of the surface functional groups of CBs, due to the disappearance of free radical. Consequently, it was found that optimal treatment time was 30 s for the best electro activity of Pt/CBs catalysts and the N 2-plasma treated Pt/CBs possessed the better electrochemical properties than the pristine Pt/CBs.

Axonal Regeneration in Mammals with Spinal Cord Injury

DTIC Science & Technology

1983-09-14

Cajal, S. 1905. Notas preventivas sobre la degeneracion y regeneracion las vias nerviosos centrales . Trab. Lab. Invest. Biol. Univ. Madrid, 4: 295-301...S. 1914. Degeneracion y Regeneration del Sistema Nervioso , Vol. 1, 2. (Nicolas Moya, Madrid), Ramon y Cajal, S. 1928. Degeneration and Regeneration...field of central nervous system (CNS) regeneration research. These developments have revealed important aspects regarding the histology and

Epilog: Cajal’s unique and legitimated school

PubMed Central

Lerma, Juan; De Carlos, Juan A.

2014-01-01

Santiago Ramón y Cajal is recognized as the founder of modern neuroscience, his discoveries representing the fundamental pillars of our current understanding of the nervous system. As Cajal’s career spanned a critical period in Spanish history, he witnessed strong social demands for progress in culture, education, and science. Indeed, the life of Santiago Ramón y Cajal can be considered to reflect the gradual development of Spanish science from the last third of the 19th century. Cajal promoted a national movement that had important consequences for Spanish science, mainly triggered by the creation of the “Junta para Ampliación de Estudios e Investigaciones Científicas,” an instrument he established to enrich scientific research and that was later to bear such abundant fruit. The school generated by Cajal profited from this development, through which all Cajal’s disciples received fellowships to train in laboratories across Europe. Unfortunately, the Spanish Civil War disrupted this revitalization of Spanish science and provoked the diaspora of many Spanish scientists. However, a political impulse, mostly following this spirit, was resumed in Spain during the eighties that successfully led to a renaissance in Spanish science. PMID:25071463

Insights into collaborative separation process of photogenerated charges and superior performance of solar cells

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

Liu, Xiangyang, E-mail: lxy081276@126.com; Wang, Shun; Zheng, Haiwu

2016-07-25

ZnO nanowires/Cu{sub 4}Bi{sub 4}S{sub 9} (ZnO/CBS) and ZnO nanowires/CBS-graphene nanoplates (ZnO/CBS-GNs), as well as two types of solar cells were prepared. The photovoltaic responses of CBS-GNs and ZnO/CBS-GNs can be improved with incorporation of GNs. The transient surface photovoltage (TPV) can provide detailed information on the separation and transport of photogenerated carriers. The multichannel separation process from the TPVs indicates that the macro-photoelectric signals can be attributed to the photogenerated charges separated at the interface of CBS/GNs, rather than CBS/ZnO. The multi-interfacial recombination is the major carrier loss, and the hole selective p-V{sub 2}O{sub 5} can efficiently accelerate the chargemore » extraction to the external circuit. The ZnO/CBS-GNs cell exhibits the superior performance, and the highest efficiency is 10.9%. With the adequate interfaces of CBS/GNs, GNs conductive network, energy level matching, etc., the excitons can easily diffuse to the interface of CBS/GNs, and the separated electrons and holes can be collected quickly, inducing the high photoelectric properties. Here, a facile strategy for solid state solar cells with superior performance presents a potential application.« less

Four new species of Metschnikowia and the transfer of seven Candida species to Metschnikowia and Clavispora as new combinations.

PubMed

Kurtzman, Cletus P; Robnett, Christie J; Basehoar, Eleanor; Ward, Todd J

2018-05-12

From comparisons of ITS1-5.8S-ITS2 and gene sequences for nuclear D1/D2 LSU rRNA, nuclear SSU (18S) rRNA, translation elongation factor 1-α (EF1-α) and RNA polymerase II subunit 2 (RPB2), the following four new ascosporogenous yeast species were resolved and are described as Metschnikowia anglica (NRRL Y-7298 T [type strain], CBS 15342, MycoBank MB 823167), Metschnikowia leonuri (NRRL Y-6546 T , CBS 15341, MB 823166), Metschnikowia peoriensis (NRRL Y-5942 T , CBS 15345, MB 823164) and Metschnikowia rubicola (NRRL Y-6064 T , CBS 15344, MB 823165). The following six species of Candida are members of the Metschnikowia clade and are proposed for transfer to Metschnikowia as new combinations: Candida chrysomelidarum (NRRL Y-27749 T , CBS 9904, MB 823223), Candida gelsemii (NRRL Y-48212 T , CBS 10509, MB 823192), Candida kofuensis (NRRL Y-27226 T , CBS 8058, MB 823195), Candida picachoensis (NRRL Y-27607 T , CBS 9804, MB 823197), Candida pimensis (NRRL Y-27619 T , CBS 9805, MB 823205) and Candida rancensis (NRRL Y-48702 T , CBS 8174, MB 823224). Candida fructus (NRRL Y-17072 T , CBS 6380, MB 823206) is transferred to Clavispora as a new combination, and Candida musae is shown to be a synonym of C. fructus. Apparent multiple alleles for ITS, D1/D2, EF1-α and RPB2 were detected in strains of some species.

Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome

PubMed Central

Tierney, Michael; Wassermann, Eric M.; Spina, Salvatore; Oblak, Adrian L.; Ghetti, Bernardino; Grafman, Jordan; Huey, Edward

2014-01-01

Objective: To use the Visual Object and Space Perception Battery (VOSP) to distinguish Alzheimer disease (AD) from non-AD pathology in corticobasal syndrome (CBS). Methods: This clinicopathologic study assessed 36 patients with CBS on the VOSP. All were autopsied. The primary dependent variable was a binary pathologic outcome: patients with CBS who had primary pathologic diagnosis of AD (CBS-AD, n = 10) vs patients with CBS without primary pathologic diagnosis of AD (CBS-nonAD, n = 26). We also determined sensitivity and specificity of individual VOSP subtests. Results: Patients with CBS-AD had younger onset (54.5 vs 63.6 years, p = 0.001) and lower memory scores on the Mattis Dementia Rating Scale–2 (16 vs 22 points, p = 0.003). Failure on the VOSP subtests Incomplete Letters (odds ratio [OR] 11.5, p = 0.006), Position Discrimination (OR 10.86, p = 0.008), Number Location (OR 12.27, p = 0.026), and Cube Analysis (OR 45.71 p = 0.0001) had significantly greater odds of CBS-AD than CBS-nonAD. These associations remained when adjusting for total Mattis Dementia Rating score, disease laterality, education, age, and sex. Receiver operating characteristic curves demonstrated significant accuracy for Incomplete Letters and all VOSP spatial subtests, with Cube Analysis performing best (area under the curve 0.91, p = 0.0004). Conclusions: In patients with CBS, failure on specific VOSP subtests is associated with greater odds of having underlying AD. There may be preferential involvement of the dorsal stream in CBS-AD. Classification of evidence: This study provides Class II evidence that some subtests of the VOSP accurately distinguish patients with CBS-AD from those without AD pathology (e.g., Cube Analysis sensitivity 100%, specificity 77%). PMID:24991033

Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

PubMed

Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

2010-03-01

Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation. (c) 2009 Elsevier Inc. All rights reserved.

SUMO regulates proteasome-dependent degradation of FLASH/Casp8AP2

PubMed Central

Vennemann, Astrid; Hofmann, Thomas G.

2013-01-01

FLASH/Casp8AP2 is a huge multifunctional protein involved in multiple cellular processes, reaching from death receptor signaling to regulation of histone gene transcription and histone mRNA processing. Previous work has shown that FLASH localizes to Cajal bodies and promyelocytic leukemia (PML) bodies. However, the function of its nuclear body association remains unclear. Here we demonstrate that murine FLASH is covalently modified by SUMO at Lys residue 1792. Interestingly, ectopic expression of SUMO results in proteasome-dependent degradation of FLASH. A point mutant of FLASH with a mutated SUMO acceptor lysine residue, FLASHK1792R, is resistant to SUMO-induced degradation. Finally, we show that arsenic trioxide, a drug known to potentiate SUMO modification and degradation of PML, triggers recruitment of FLASH to PML bodies and concomitant loss of FLASH protein. Our data suggest that SUMO targets FLASH for proteasome-dependent degradation, which is associated with recruitment of FLASH to PML bodies. PMID:23673342

[Compartmentalization of the cell nucleus and spatial organization of the genome].

PubMed

Gavrilov, A A; Razin, S V

2015-01-01

The eukaryotic cell nucleus is one of the most complex cell organelles. Despite the absence of membranes, the nuclear space is divided into numerous compartments where different processes in- volved in the genome activity take place. The most important nuclear compartments include nucleoli, nuclear speckles, PML bodies, Cajal bodies, histone locus bodies, Polycomb bodies, insulator bodies, transcription and replication factories. The structural basis for the nuclear compartmentalization is provided by genomic DNA that occupies most of the nuclear volume. Nuclear compartments, in turn, guide the chromosome folding by providing a platform for the spatial interaction of individual genomic loci. In this review, we discuss fundamental principles of higher order genome organization with a focus on chromosome territories and chromosome domains, as well as consider the structure and function of the key nuclear compartments. We show that the func- tional compartmentalization of the cell nucleus and genome spatial organization are tightly interconnected, and that this form of organization is highly dynamic and is based on stochastic processes.

Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions.

PubMed

Gregory, Jesse F; DeRatt, Barbara N; Rios-Avila, Luisa; Ralat, Maria; Stacpoole, Peter W

2016-07-01

The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine → cystathionine → cysteine) is largely maintained even during vitamin B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/h per kg body weight. The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B6 status suggests that the resulting modulation of H2S production may have physiological consequences in a subset of people. Supported by NIH grant DK072398. This paper refers to data from studies registered at clinicaltrials.gov as NCT01128244 and NCT00877812. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Mutant superoxide dismutase 1 (SOD1), a cause of amyotrophic lateral sclerosis, disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear Cajal bodies.

PubMed

Kariya, Shingo; Re, Diane B; Jacquier, Arnaud; Nelson, Katelyn; Przedborski, Serge; Monani, Umrao R

2012-08-01

Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are among the most common motor neuron diseases to afflict the human population. A deficiency of the survival of motor neuron (SMN) protein causes SMA and is also reported to be an exacerbating factor in the development of ALS. However, pathways linking the two diseases have yet to be defined and it is not clear precisely how the pathology of ALS is aggravated by reduced SMN or whether mutant proteins underlying familial forms of ALS interfere with SMN-related biochemical pathways to exacerbate the neurodegenerative process. In this study, we show that mutant superoxide dismutase-1 (SOD1), a cause of familial ALS, profoundly alters the sub-cellular localization of the SMN protein, preventing the formation of nuclear 'gems' by disrupting the recruitment of the protein to Cajal bodies. Overexpressing the SMN protein in mutant SOD1 mice, a model of familial ALS, alleviates this phenomenon, most likely in a cell-autonomous manner, and significantly mitigates the loss of motor neurons in the spinal cord and in culture dishes. In the mice, the onset of the neuromuscular phenotype is delayed and motor function enhanced, suggestive of a therapeutic benefit for ALS patients treated with agents that augment the SMN protein. Nevertheless, this finding is tempered by an inability to prolong survival, a limitation most likely imposed by the inexorable denervation that characterizes ALS and eventually disrupts the neuromuscular synapses even in the presence of increased SMN.

Pavlov and Cajal: Two different pathways to a Nobel Prize.

PubMed

Rozo, Jairo A; Andrade-Talavera, Yuniesky; Rodríguez-Moreno, Antonio

2017-01-01

Ivan Pavlov (1849-1936) and Santiago Ramón y Cajal (1852-1934) were two contemporary scientists who not only had a great impact on Russian and Spanish science but also on the international stage. Both shared several common features in their life and work, yet they followed fundamentally different paths during their training as scientists. While Pavlov received his laboratory training under the guidance of Ilya Tsion (1843-1912), Cajal did not receive any formal training within a particular laboratory nor did he have a mentor in the traditional sense, rather he was mainly self-taught, although he was supported by key figures like Maestre de San Juan (1828-1890) and Luis Simarro (1851-1921). In this article, we compare the scientific training of these two Nobel Prize laureates and the influences they received during their scientific lives.

The young Ramón y Cajal as a cell-theory dissenter.

PubMed

Iturbe, Ulises; Pretó, Juli; Lazcano, Antonio

2008-06-01

The intellectual development of scientists normally traverses several different phases as they mature in their professions. In many cases, strong support of certain ideas and theories gives way to more critical, productive views that set the stage for major theories and discoveries. This appears to have been the case of Santiago Ramón y Cajal (1852-1934). In his youth, he supported the protoplasmic theory of life, and as he matured he maintained a critical, yet open view of the cell theory, which postulated that life phenomena could not take place below the cellular level. In later years, however, an older and wiser Ramón y Cajal abandoned all traces of dissent and joined in fully supporting a refined version of cell theory, to which his own discoveries significantly contributed.

Deconvoluting AMP-activated protein kinase (AMPK) adenine nucleotide binding and sensing

PubMed Central

Gu, Xin; Yan, Yan; Novick, Scott J.; Kovach, Amanda; Goswami, Devrishi; Ke, Jiyuan; Tan, M. H. Eileen; Wang, Lili; Li, Xiaodan; de Waal, Parker W.; Webb, Martin R.; Griffin, Patrick R.; Xu, H. Eric

2017-01-01

AMP-activated protein kinase (AMPK) is a central cellular energy sensor that adapts metabolism and growth to the energy state of the cell. AMPK senses the ratio of adenine nucleotides (adenylate energy charge) by competitive binding of AMP, ADP, and ATP to three sites (CBS1, CBS3, and CBS4) in its γ-subunit. Because these three binding sites are functionally interconnected, it remains unclear how nucleotides bind to individual sites, which nucleotides occupy each site under physiological conditions, and how binding to one site affects binding to the other sites. Here, we comprehensively analyze nucleotide binding to wild-type and mutant AMPK protein complexes by quantitative competition assays and by hydrogen-deuterium exchange MS. We also demonstrate that NADPH, in addition to the known AMPK ligand NADH, directly and competitively binds AMPK at the AMP-sensing CBS3 site. Our findings reveal how AMP binding to one site affects the conformation and adenine nucleotide binding at the other two sites and establish CBS3, and not CBS1, as the high affinity exchangeable AMP/ADP/ATP-binding site. We further show that AMP binding at CBS4 increases AMP binding at CBS3 by 2 orders of magnitude and reverses the AMP/ATP preference of CBS3. Together, these results illustrate how the three CBS sites collaborate to enable highly sensitive detection of cellular energy states to maintain the tight ATP homeostastis required for cellular metabolism. PMID:28615457

Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice.

PubMed

Gupta, Sapna; Wang, Liqun; Kruger, Warren D

2016-01-01

Cystathionine beta synthase (CBS) deficiency is a recessive inborn error of metabolism characterized by elevated serum total homocysteine (tHcy). Betaine supplementation, which can lower tHcy by stimulating homocysteine remethylation to methionine, is often given to CBS deficient patients in combination with other treatments such as methionine restriction and supplemental B-vitamins. However, the effectiveness of betaine supplementation by itself in the treatment of CBS deficiency has not been well explored. Here, we have examined the effect of a betaine supplemented diet on the Tg-I278T Cbs (-/-) mouse model of CBS deficiency and compared its effectiveness to our previously published data using a methionine restricted diet. Tg-I278T Cbs (-/-) mice on betaine, from the time of weaning until for 240 days of age, had a 40 % decrease in mean tHcy level and a 137 % increase in serum methionine levels. Betaine-treated Tg-I278T Cbs (-/-) mice also exhibited increased levels of betaine-dependent homocysteine methyl transferase (BHMT), increased levels of the lipogenic enzyme stearoyl-coenzyme A desaturase (SCD-1), and increased lipid droplet accumulation in the liver. Betaine supplementation largely reversed the hair loss phenotype in Tg-I278T Cbs (-/-) animals, but was far less effective than methionine restriction in reversing the weight-loss, fat-loss, and osteoporosis phenotypes. Surprisingly, betaine supplementation had several negative effects in control Tg-I278T Cbs (+/-) mice including decreased weight gain, lean mass, and bone mineral density. Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice.

Beyond isolated cells: microfluidic transport of large tissue for pancreatic cancer diagnosis

NASA Astrophysics Data System (ADS)

Das, Ronnie; Murphy, Rachel G.; Seibel, Eric J.

2015-03-01

For cancer diagnoses, core biopsies (CBs) obtained from patients using coring needles (CNs) are traditionally visualized and assessed on microscope slides by pathologists after samples are processed and sectioned. A fundamental gain in optical information (i.e., diagnosis/staging) may be achieved when whole, unsectioned CBs (L = 5-20, D = 0.5-2.0 mm) are analyzed in 3D. This approach preserves CBs for traditional pathology and maximizes the diagnostic potential of patient samples. To bridge CNs/CBs with imaging, our group developed a microfluidic device that performs biospecimen preparation on unsectioned CBs for pathology. The ultimate goal is an automated and rapid point-of-care system that aids pathologists by processing tissue for advanced 3D imaging platforms. An inherent, but essential device feature is the microfluidic transport of CBs, which has not been previously investigated. Early experiments demonstrated proof-of-concept: pancreas CBs (D = 0.3-2.0 mm) of set lengths were transported in straight/curved microchannels, but dimensional tolerance and flow rates were variable, and preservation of CB integrity was uncontrolled. A second study used metal cylinder substitutes (L = 10, D = 1 mm) in microchannels to understand the transport mechanism. However, CBs are imperfectly shaped, rough, porous and viscoelastic. In this study, fresh/formalin-fixed porcine and human pancreas CBs were deposited into our device through a custom interface using clinical CNs. CB integrity (i.e., sample viability) may be assessed at every stage using an optomechanical metric: physical breaks were determined when specimen intensity profile data deviated beyond xavg + 2σ. Flow rates for human CBs were determined for several CNs, and microfluidic transport of fresh and formalin-fixed CBs was analyzed.

Cystathionine β-Synthase (CBS) Domain-containing Pyrophosphatase as a Target for Diadenosine Polyphosphates in Bacteria*

PubMed Central

Anashkin, Viktor A.; Salminen, Anu; Tuominen, Heidi K.; Orlov, Victor N.; Lahti, Reijo; Baykov, Alexander A.

2015-01-01

Among numerous proteins containing pairs of regulatory cystathionine β-synthase (CBS) domains, family II pyrophosphatases (CBS-PPases) are unique in that they generally contain an additional DRTGG domain between the CBS domains. Adenine nucleotides bind to the CBS domains in CBS-PPases in a positively cooperative manner, resulting in enzyme inhibition (AMP or ADP) or activation (ATP). Here we show that linear P1,Pn-diadenosine 5′-polyphosphates (ApnAs, where n is the number of phosphate residues) bind with nanomolar affinity to DRTGG domain-containing CBS-PPases of Desulfitobacterium hafniense, Clostridium novyi, and Clostridium perfringens and increase their activity up to 30-, 5-, and 7-fold, respectively. Ap4A, Ap5A, and Ap6A bound noncooperatively and with similarly high affinities to CBS-PPases, whereas Ap3A bound in a positively cooperative manner and with lower affinity, like mononucleotides. All ApnAs abolished kinetic cooperativity (non-Michaelian behavior) of CBS-PPases. The enthalpy change and binding stoichiometry, as determined by isothermal calorimetry, were ∼10 kcal/mol nucleotide and 1 mol/mol enzyme dimer for Ap4A and Ap5A but 5.5 kcal/mol and 2 mol/mol for Ap3A, AMP, ADP, and ATP, suggesting different binding modes for the two nucleotide groups. In contrast, Eggerthella lenta and Moorella thermoacetica CBS-PPases, which contain no DRTGG domain, were not affected by ApnAs and showed no enthalpy change, indicating the importance of the DTRGG domain for ApnA binding. These findings suggest that ApnAs can control CBS-PPase activity and hence affect pyrophosphate level and biosynthetic activity in bacteria. PMID:26400082

See-saw nystagmus and brainstem infarction: MRI findings

NASA Technical Reports Server (NTRS)

Kanter, D. S.; Ruff, R. L.; Leigh, R. J.; Modic, M.

1987-01-01

A patient with see-saw nystagmus had a lesion localized by Magnetic Resonance Imaging (MRI) to the paramedian ventral midbrain with involvement of the right interstitial nucleus of Cajal. This the first MRI study of see-saw nystagmus associated with a presumed brainstem vascular event. Our findings support animal and human studies suggesting that dysfunction of the interstitial nucleus of Cajal or its connections is central in this disorder.

Final Four Offers NCAA Respite from Criticism

ERIC Educational Resources Information Center

Sander, Libby

2009-01-01

When it's not staging any Final Four match-ups, the National Collegiate Athletic Association (NCAA) is the powerful governing body critics love to hate. The association's 11-year, $6-billion contract with CBS to televise the tournament has become a lightning rod for critics who say the association is all about making money off athletes. Not so,…

"The Strange Birth of 'CBS Reports'" Revisited.

ERIC Educational Resources Information Center

Baughman, James L.

Aired by the Columbia Broadcasting System (CBS) during the 1960s, "CBS Reports" proved to be one of that network's most honored efforts at television news coverage. CBS chairman, William S. Paley, based his decision to air the show on the presence of a sponsor and in response to the prospect of an open-ended Federal Communications…

Dopamine treatment attenuates acute kidney injury in a rat model of deep hypothermia and rewarming - The role of renal H2S-producing enzymes.

PubMed

Dugbartey, George J; Talaei, Fatemeh; Houwertjes, Martin C; Goris, Maaike; Epema, Anne H; Bouma, Hjalmar R; Henning, Robert H

2015-12-15

Hypothermia and rewarming produces organ injury through the production of reactive oxygen species. We previously found that dopamine prevents hypothermia and rewarming-induced apoptosis in cultured cells through increased expression of the H2S-producing enzyme cystathionine β-Synthase (CBS). Here, we investigate whether dopamine protects the kidney in deep body cooling and explore the role of H2S-producing enzymes in an in vivo rat model of deep hypothermia and rewarming. In anesthetized Wistar rats, body temperature was decreased to 15°C for 3h, followed by rewarming for 1h. Rats (n≥5 per group) were treated throughout the procedure with vehicle or dopamine infusion, and in the presence or absence of a non-specific inhibitor of H2S-producing enzymes, amino-oxyacetic acid (AOAA). Kidney damage and renal expression of three H2S-producing enzymes (CBS, CSE and 3-MST) was quantified and serum H2S level measured. Hypothermia and rewarming induced renal damage, evidenced by increased serum creatinine, renal reactive oxygen species production, KIM-1 expression and influx of immune cells, which was accompanied by substantially lowered renal expression of CBS, CSE, and 3-MST and lowered serum H2S levels. Infusion of dopamine fully attenuated renal damage and maintained expression of H2S-producing enzymes, while normalizing serum H2S. AOAA further decreased the expression of H2S-producing enzymes and serum H2S level, and aggravated renal damage. Hence, dopamine preserves renal integrity during deep hypothermia and rewarming likely by maintaining the expression of renal H2S-producing enzymes and serum H2S. Copyright © 2015 Elsevier B.V. All rights reserved.

Human telomerase: biogenesis, trafficking, recruitment, and activation.

PubMed

Schmidt, Jens C; Cech, Thomas R

2015-06-01

Telomerase is the ribonucleoprotein enzyme that catalyzes the extension of telomeric DNA in eukaryotes. Recent work has begun to reveal key aspects of the assembly of the human telomerase complex, its intracellular trafficking involving Cajal bodies, and its recruitment to telomeres. Once telomerase has been recruited to the telomere, it appears to undergo a separate activation step, which may include an increase in its repeat addition processivity. This review covers human telomerase biogenesis, trafficking, and activation, comparing key aspects with the analogous events in other species. © 2015 Schmidt and Cech Published by Cold Spring Harbor Laboratory Press.

Crystal structures of the CBS and DRTGG domains of the regulatory region of Clostridiumperfringens pyrophosphatase complexed with the inhibitor, AMP, and activator, diadenosine tetraphosphate.

PubMed

Tuominen, H; Salminen, A; Oksanen, E; Jämsen, J; Heikkilä, O; Lehtiö, L; Magretova, N N; Goldman, A; Baykov, A A; Lahti, R

2010-05-07

Nucleotide-binding cystathionine beta-synthase (CBS) domains serve as regulatory units in numerous proteins distributed in all kingdoms of life. However, the underlying regulatory mechanisms remain to be established. Recently, we described a subfamily of CBS domain-containing pyrophosphatases (PPases) within family II PPases. Here, we express a novel CBS-PPase from Clostridium perfringens (CPE2055) and show that the enzyme is inhibited by AMP and activated by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A). The structures of the AMP and AP(4)A complexes of the regulatory region of C. perfringens PPase (cpCBS), comprising a pair of CBS domains interlinked by a DRTGG domain, were determined at 2.3 A resolution using X-ray crystallography. The structures obtained are the first structures of a DRTGG domain as part of a larger protein structure. The AMP complex contains two AMP molecules per cpCBS dimer, each bound to a single monomer, whereas in the activator-bound complex, one AP(4)A molecule bridges two monomers. In the nucleotide-bound structures, activator binding induces significant opening of the CBS domain interface, compared with the inhibitor complex. These results provide structural insight into the mechanism of CBS-PPase regulation by nucleotides. Copyright 2010 Elsevier Ltd. All rights reserved.

Functional Assessment of Region-Specific Neglect: Are There Differential Behavioural Consequences of Peripersonal versus Extrapersonal Neglect?

PubMed Central

Nijboer, T. C. W.; ten Brink, A. F.; Kouwenhoven, M.; Visser-Meily, J. M. A.

2014-01-01

Background. Region-specific types of neglect (peripersonal and extrapersonal) have been dissociated, yet, differential behavioural consequences are unknown. Objective. The aim of the current study was to investigate behavioural consequences at the level of basic activities of daily living of region-specific neglect, using the Catherine Bergego Scale (CBS). Methods. 118 stroke patients were screened within the first two weeks after admission to the rehabilitation center for inpatient rehabilitation. Results. Patients with peripersonal neglect and patients with neglect for both regions had significantly higher total score on the CBS compared to nonneglect patients. Total scores for patients with extrapersonal neglect were comparable to non-neglect patients. ADL impairments were found across activities (e.g., looking towards one side, forgetting body parts, colliding) for both patients with peripersonal neglect and patients with neglect for both regions. Patients with extrapersonal neglect were only impaired on the item on way finding. Conclusions. When diagnosing neglect, it is relevant to distinguish the type of region-specific neglect and, where needed, to adjust the rehabilitation program accordingly. As the CBS is not developed to typically measure ADL in extrapersonal neglect, it would be of importance to add other (instrumental) activities that heavily rely on processing information in farther space. PMID:24825959

Chronic nerve compression alters Schwann cell myelin architecture in a murine model

PubMed Central

Gupta, Ranjan; Nassiri, Nima; Hazel, Antony; Bathen, Mary; Mozaffar, Tahseen

2011-01-01

Introduction Myelinating Schwann cells compartmentalize their outermost layer to form actin-rich channels known as Cajal bands. Here, we investigate changes in Schwann cell architecture and cytoplasmic morphology in a novel mouse model of carpal tunnel syndrome. Methods Chronic nerve compression (CNC) injury was created in wild-type and slow-Wallerian degeneration (WldS) mice. Over 12 weeks, nerves were electrodiagnostically assessed, and Schwann cell morphology was thoroughly evaluated. Results A decline in nerve conduction velocity and increase in g-ratio is observed without early axonal damage. Schwann cells display shortened internodal lengths and severely disrupted Cajal bands. Quite surprisingly, the latter is reconstituted without improvements to nerve conduction velocity. Discussion Chronic entrapment injuries like carpal tunnel syndrome are primarily mediated by the Schwann cell response, wherein decreases in internodal length and myelin thickness disrupt the efficiency of impulse propagation. Restitution of Cajal bands is not sufficient for remyelination post-CNC injury. PMID:22246880

Treating Individuals With Intellectual Disabilities and Challenging Behaviors With Adapted Dialectical Behavior Therapy

PubMed Central

Brown, Julie F.; Brown, Milton Z.; Dibiasio, Paige

2013-01-01

Approximately one third of adults with intellectual and developmental disabilities have emotion dysregulation and challenging behaviors (CBs). Although research has not yet confirmed that existing treatments adequately reduce CBs in this population, dialectical behavior therapy (DBT) holds promise, as it has been shown to effectively reduce CBs in other emotionally dysregulated populations. This longitudinal single-group pilot study examined whether individuals with impaired intellectual functioning would show reductions in CBs while receiving standard DBT individual therapy used in conjunction with the Skills System (DBT-SS), a DBT emotion regulation skills curriculum adapted for individuals with cognitive impairment. Forty adults with developmental disabilities (most of whom also had intellectual disabilities) and CBs, including histories of aggression, self-injury, sexual offending, or other CBs, participated in this study. Changes in their behaviors were monitored over 4 years while in DBT-SS. Large reductions in CBs were observed during the 4 years. These findings suggest that modified DBT holds promise for effectively treating individuals with intellectual and developmental disabilities. PMID:23914278

Evaluation of CBS 600 carburized steel as a gear material

NASA Technical Reports Server (NTRS)

Townsend, D. P.; Parker, R. J.; Zaretsky, E. V.

1979-01-01

Gear endurance tests were conducted with one lot of consumable-electrode vacuum-melted (CVM) AISI 9310 gears and one lot of air-melt CBS 600 gears. The gears were 8 pitch with a pitch diameter of 8.89 centimeters (3.5 in.). Bench-type rolling-element fatigue tests were also conducted with one lot of CVM AISI 9310, three lots of CVM CBS 600, and one of air-melt CBS 600 material. The rolling-element bars were 0.952 centimeter (0.375 in.) in diameter. The CBS 600 material exhibited pitting fatigue lives in both rolling-element specimens and gears at least equivalent to that of CVM AISI 9310. Tooth fracture failure occurred with the CBS 600 gears after overrunning a fatigue spall, but it did not occur with the CVM AISI 9310 gears. Tooth fracture in the CBS 600 was attributed to excessive carbon content in the case, excessive case depth, and a higher than normal core hardness.

The association between the 844ins68 polymorphism in the CBS gene and breast cancer

PubMed Central

Figuera-Villanueva, Luis Eduardo; Ramos-Silva, Adriana; Salas-González, Efraín; Puebla-Pérez, Ana María; Peralta-Leal, Valeria; García-Ortiz, José Elías; Dávalos-Rodríguez, Ingrid Patricia; Zúñiga-González, Guillermo Moisés

2014-01-01

Introduction The cystathionine beta synthase (CBS) gene plays an important role in homocysteine metabolism because it catalyzes the first step of the transsulfuration pathway, during which homocysteine is converted to cystathionine. Polymorphisms of CBS have been associated with cancer. Material and methods We examined the role of the 844ins68 polymorphism by comparing the genotypes of 371 healthy Mexican women with the genotypes of 323 Mexican women with breast cancer (BC). Results The observed genotype frequencies for controls and BC patients were 1% and 2% for Ins/Ins, 13% and 26% for W/Ins, and 86% and 72% for W/W, respectively. We found that the odds ratio (OR) was 2.2, with a 95% confidence interval (95% CI) of 1.5–3.3, p = 0.0001. The association was also evident when comparing the distribution of the W/Ins-Ins/Ins genotypes in patients in the following categories: 1) menopause and high γ-glutamyltransferase (GGT) levels (OR of 2.17, 95% CI: 1.17–4.26, p = 0.02), 2) chemotherapy response and high lactate dehydrogenase (LDH) levels (OR 2.2, 95% CI: 1.08–4.4, p = 0.027), 3) chemotherapy response and high GGT levels (OR 2.46, 95% CI: 1.2–4.8, p = 0.007), and 4) body mass index (BMI) and III–IV tumor stage (OR 3.2, 95% CI: 1.2–8.3, p = 0.013). Conclusions We conclude that the genotypes W/Ins-Ins/Ins of the 844ins68 polymorphism in the CBS gene contribute significantly to BC susceptibility in the analyzed sample from the Mexican population. PMID:25624861

Anti-inflammatory Effect of Astaxanthin on the Sickness Behavior Induced by Diabetes Mellitus.

PubMed

Ying, Chang-jiang; Zhang, Fang; Zhou, Xiao-yan; Hu, Xiao-tong; Chen, Jing; Wen, Xiang-ru; Sun, Ying; Zheng, Kui-yang; Tang, Ren-xian; Song, Yuan-jian

2015-10-01

Chronic inflammation appears to play a critical role in sickness behavior caused by diabetes mellitus. Astaxanthin has been used in treating diabetes mellitus and diabetic complications because of its neuroprotective and anti-inflammatory actions. However, whether astaxanthin can improve sickness behavior induced by diabetes and its potential mechanisms are still unknown. The aim of this study was to investigate the effects of astaxanthin on diabetes-elicited abnormal behavior in mice and its corresponding mechanisms. An experimental diabetic model was induced by streptozotocin (150 mg/kg) and astaxanthin (25 mg/kg/day) was provided orally for 10 weeks. Body weight and water consumption were measured, and the sickness behavior was evaluated by the open field test (OFT) and closed field test (CFT). The expression of glial fibrillary acidic protein (GFAP) was measured, and the frontal cortical cleaved caspase-3 positive cells, interleukin-6 (IL-6), and interleukin-1β (IL-1β) expression levels were also investigated. Furthermore, cystathionine β-synthase (CBS) in the frontal cortex was detected to determine whether the protective effect of astaxanthin on sickness behavior in diabetic mice is closely related to CBS. As expected, we observed that astaxanthin improved general symptoms and significantly increase horizontal distance and the number of crossings in the OFT and CFT. Furthermore, data showed that astaxanthin could decrease GFAP-positive cells in the brain and down-regulate the cleaved caspase-3, IL-6, and IL-1β, and up-regulate CBS in the frontal cortex. These results suggest that astaxanthin provides neuroprotection against diabetes-induced sickness behavior through inhibiting inflammation, and the protective effects may involve CBS expression in the brain.

Evaluation of Effectiveness and Cost‐Effectiveness of a Clinical Decision Support System in Managing Hypertension in Resource Constrained Primary Health Care Settings: Results From a Cluster Randomized Trial

PubMed Central

Anchala, Raghupathy; Kaptoge, Stephen; Pant, Hira; Di Angelantonio, Emanuele; Franco, Oscar H.; Prabhakaran, D.

2015-01-01

Background Randomized control trials from the developed world report that clinical decision support systems (DSS) could provide an effective means to improve the management of hypertension (HTN). However, evidence from developing countries in this regard is rather limited, and there is a need to assess the impact of a clinical DSS on managing HTN in primary health care center (PHC) settings. Methods and Results We performed a cluster randomized trial to test the effectiveness and cost‐effectiveness of a clinical DSS among Indian adult hypertensive patients (between 35 and 64 years of age), wherein 16 PHC clusters from a district of Telangana state, India, were randomized to receive either a DSS or a chart‐based support (CBS) system. Each intervention arm had 8 PHC clusters, with a mean of 102 hypertensive patients per cluster (n=845 in DSS and 783 in CBS groups). Mean change in systolic blood pressure (SBP) from baseline to 12 months was the primary endpoint. The mean difference in SBP change from baseline between the DSS and CBS at the 12th month of follow‐up, adjusted for age, sex, height, waist, body mass index, alcohol consumption, vegetable intake, pickle intake, and baseline differences in blood pressure, was −6.59 mm Hg (95% confidence interval: −12.18 to −1.42; P=0.021). The cost‐effective ratio for CBS and DSS groups was $96.01 and $36.57 per mm of SBP reduction, respectively. Conclusion Clinical DSS are effective and cost‐effective in the management of HTN in resource‐constrained PHC settings. Clinical Trial Registration URL: http://www.ctri.nic.in. Unique identifier: CTRI/2012/03/002476. PMID:25559011

Evaluation of background soil and air polychlorinated biphenyl (PCB) concentrations on a hill at the outskirts of a metropolitan city.

PubMed

Kuzu, S Levent; Saral, Arslan; Güneş, Gülten; Karadeniz, Aykut

2016-07-01

Air and soil sampling was conducted inside a forested area for 22 months. The sampling location is situated to the north of a metropolitan city. Average atmospheric gas and particle concentrations were found to be 180 and 28 pg m(-3) respectively, while that of soil phase was detected to be 3.2 ng g(-1) on dry matter, The congener pairs of PCB#4-10 had the highest contribution to each medium. TEQ concentration was 0.10 pg m(-3), 0.07 pg m(-3), 21.92 pg g(-1), for gas, particle and soil phases, respectively. PCB#126 and PCB#169 contributed to over 99% of the entire TEQ concentrations for each medium. Local sources were investigated by conditional probability function (CPF) and soil/air fugacity. Landfilling area and medical waste incinerator, located to the 8 km northeast, contributed to ambient concentrations, especially in terms of dioxin-like congeners. The industrial settlement (called Dilovasi being to the east southeast of 60 km distant) contributed from southeast direction. Further sources were identified by potential source contribution function (PSCF). Sources at close proximity had high contribution. Air mass transportation from Aliaga industrial region (being to the southwest of 300 km distant) moderately contributed to ambient concentrations. Low molecular weight congeners were released from soil body. 5-CBs and 6-CBs were close to equilibrium state between soil/air interfaces. PCB#171 was close to equilibrium and PCB#180 was likely to evaporate from soil, which constitute 7-CBs. PCB#199, representing 8-CBs deposited to soil. 9-CB (PCB#207) was in equilibrium between soil and air phases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ab Initio and Analytic Intermolecular Potentials for Ar-CF₄

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

Vayner, Grigoriy; Alexeev, Yuri; Wang, Jiangping

2006-03-09

Ab initio calculations at the CCSD(T) level of theory are performed to characterize the Ar + CF ₄ intermolecular potential. Extensive calculations, with and without a correction for basis set superposition error (BSSE), are performed with the cc-pVTZ basis set. Additional calculations are performed with other correlation consistent (cc) basis sets to extrapolate the Ar---CF₄potential energy minimum to the complete basis set (CBS) limit. Both the size of the basis set and BSSE have substantial effects on the Ar + CF₄ potential. Calculations with the cc-pVTZ basis set and without a BSSE correction, appear to give a good representation ofmore » the potential at the CBS limit and with a BSSE correction. In addition, MP2 theory is found to give potential energies in very good agreement with those determined by the much higher level CCSD(T) theory. Two analytic potential energy functions were determined for Ar + CF₄by fitting the cc-pVTZ calculations both with and without a BSSE correction. These analytic functions were written as a sum of two body potentials and excellent fits to the ab initio potentials were obtained by representing each two body interaction as a Buckingham potential.« less

Cajal's second great battle for the neuron doctrine: the nature and function of neurofibrils.

PubMed

Frixione, Eugenio

2009-03-01

One hundred years ago, a novel kind of reticularism threatened to displace the neuron doctrine as the established model of functional organization of the nervous system. The challenging paradigm, championed by Stephan von Apáthy and Albrecht Bethe, held that nerve impulses propagate along neurofibrils connected in a continuous network throughout all nerve cells. Santiago Ramón y Cajal, a leading figure in the conception of the neuron doctrine, headed again the battle against this return of reticularism. Dissatisfied with the available staining techniques, he devised the "reduced silver nitrate method" that even Camillo Golgi recognized as the best at the time for revealing the neurofibrils. In 1904 Cajal already published over a dozen papers in three languages describing neurofibril distributions in the nervous systems of diverse vertebrates and invertebrates, under both normal and experimental conditions. Next he investigated the involvement of neurofibrils in the process of nerve regeneration. This unprecedented survey led him to the conclusion that the neurofibrils are linear "colonies" of particles constituting a semi-solid, dynamic internal skeleton of the nerve cell. Apáthy reacted with a long invective paper that Cajal had no choice but acknowledging. His comprehensive reply, published in 1908, meant the effective end of the renewed reticularist campaign against the neuron doctrine. Along the way, a visionary and today almost forgotten chapter in the history of the cytoskeleton had also been written.

The influence of James and Darwin on Cajal and his research into the neuron theory and evolution of the nervous system

PubMed Central

Ferreira, Francisco R. M.; Nogueira, Maria I.; DeFelipe, Javier

2014-01-01

In this article we discuss the influence of William James and Charles Darwin on the thoughts of Santiago Ramón y Cajal concerning the structure, plasticity, and evolution of the nervous system at the cellular level. Here we develop Cajal’s notion that neuronal theory is a necessary condition to explain the plasticity of neural connections. Although the roots of the term “plasticity” in reference to neuroscience are not completely clear, Cajal was an important figure in the propagation and popularization of its use. It is true that he carried out a large number of studies throughout his career in favor of the neuronal theory, but perhaps one of the most interesting aspects of his studies was his innovative capacity to interpret structure as being the result of evolutionary mechanisms, i.e., natural selection. This capacity would ultimately lead Cajal to the conclusion that, in relation to the histology of the nervous system, such selection occurs in the establishment of connections between cells. The present article is divided into five sections: (1) Learning and general notions of organic plasticity in the 19th century; (2) The idea of “mental” plasticity proposed by James; (3) Neuronal theory and “structural” plasticity: general considerations; (4) Evolutionary factors of the nervous system in Cajal’s work; and (5) Final considerations. PMID:24523676

Human H/ACA Small Nucleolar RNPs and Telomerase Share Evolutionarily Conserved Proteins NHP2 and NOP10

PubMed Central

Pogacic, Vanda; Dragon, François; Filipowicz, Witold

2000-01-01

The H/ACA small nucleolar RNAs (snoRNAs) are involved in pseudouridylation of pre-rRNAs. In the yeast Saccharomyces cerevisiae, four common proteins are associated with H/ACA snoRNAs: Gar1p, Cbf5p, Nhp2p, and Nop10p. In vitro reconstitution studies showed that four proteins also specifically interact with H/ACA snoRNAs in mammalian cell extracts. Two mammalian proteins, NAP57/dyskerin (the ortholog of Cbf5p) and hGAR1, have been characterized. In this work we describe properties of hNOP10 and hNHP2, human orthologs of yeast Nop10p and Nhp2p, respectively, and further characterize hGAR1. hNOP10 and hNHP2 complement yeast cells depleted of Nhp2p and Nop10p, respectively. Immunoprecipitation experiments with extracts from transfected HeLa cells indicated that epitope-tagged hNOP10 and hNHP2 specifically associate with hGAR1 and H/ACA RNAs; they also interact with the RNA subunit of telomerase, which contains an H/ACA-like domain in its 3′ moiety. Immunofluorescence microscopy experiments showed that hGAR1, hNOP10, and hNHP2 are localized in the dense fibrillar component of the nucleolus and in Cajal (coiled) bodies. Deletion analysis of hGAR1 indicated that its evolutionarily conserved core domain contains all the signals required for localization, but progressive deletions from either the N or the C terminus of the core domain abolish localization in the nucleolus and/or the Cajal bodies. PMID:11074001

Effect of S-adenosyl-L-methionine (SAM), an allosteric activator of cystathionine-β-synthase (CBS) on colorectal cancer cell proliferation and bioenergetics in vitro.

PubMed

Módis, Katalin; Coletta, Ciro; Asimakopoulou, Antonia; Szczesny, Bartosz; Chao, Celia; Papapetropoulos, Andreas; Hellmich, Mark R; Szabo, Csaba

2014-09-15

Recent data show that colon cancer cells selectively overexpress cystathionine-β-synthase (CBS), which produces hydrogen sulfide (H2S), to maintain cellular bioenergetics, support tumor growth and stimulate angiogenesis and vasorelaxation in the tumor microenvironment. The purpose of the current study was to investigate the effect of the allosteric CBS activator S-adenosyl-L-methionine (SAM) on the proliferation and bioenergetics of the CBS-expressing colon cancer cell line HCT116. The non-transformed, non-tumorigenic colon epithelial cell line NCM356 was used as control. For assessment of cell proliferation, the xCELLigence system was used. Bioenergetic function was measured by Extracellular Flux Analysis. Experiments using human recombinant CBS or HCT116 homogenates complemented the cell-based studies. SAM markedly enhanced CBS-mediated H2S production in vitro, especially when a combination of cysteine and homocysteine was used as substrates. Addition of SAM (0.1-3 mM) to HCT116 cells induced a concentration-dependent increase H2S production. SAM exerted time- and concentration-dependent modulatory effects on cell proliferation. At 0.1-1 mM SAM increased HCT116 proliferation between 0 and 12 h, while the highest SAM concentration (3 mM) inhibited proliferation. Over a longer time period (12-24 h), only the lowest concentration of SAM used (0.1 mM) stimulated cell proliferation; higher SAM concentrations produced a concentration-dependent inhibition. The short-term stimulatory effects of SAM were attenuated by the CBS inhibitor aminooxyacetic acid (AOAA) or by stable silencing of CBS. In contrast, the inhibitory effects of SAM on cell proliferation was unaffected by CBS inhibition or CBS silencing. In contrast to HCT116 cells, the lower rate of proliferation of the low-CBS expressor NCM356 cells was unaffected by SAM. Short-term (1 h) exposure of HCT116 cells to SAM induced a concentration-dependent increase in oxygen consumption and bioenergetic function at 0.1-1 mM, while 3 mM was inhibitory. Longer-term (72 h) exposure of HCT116 cells to all concentrations of SAM tested suppressed mitochondrial oxygen consumption rate, cellular ATP content and cell viability. The stimulatory effect of SAM on bioenergetics was attenuated in cells with stable CBS silencing, while the inhibitory effects were unaffected. In NCM356 cells SAM exerted smaller effects on cellular bioenergetics than in HCT116 cells. We have also observed a downregulation of CBS in response to prolonged exposure of SAM both in HCT116 and NCM356 cells. Taken together, the results demonstrate that H2S production in HCT116 cells is stimulated by the allosteric CBS activator, SAM. At low-to intermediate levels and early time periods the resulting H2S serves as an endogenous cancer cell growth and bioenergetic factor. In contrast, the inhibition of cell proliferation and bioenergetic function by SAM does not appear to relate to adverse autocrine effects of H2S resulting from CBS over-stimulation but, rather to CBS-independent pharmacological effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Psychometric properties of Persian version of the Caregiver Burden Scale in Iranian caregivers of patients with spinal cord injury.

PubMed

Farajzadeh, Ata; Akbarfahimi, Malahat; Maroufizadeh, Saman; Rostami, Hamid Reza; Kohan, Amir Hassan

2018-02-01

To investigate the psychometric properties of the Persian version of Caregiver Burden Scale (CBS) in caregivers of patients with spinal cord injury. This is a cross-sectional study. After a forward-backward translation, the CBS was administered to 110 caregivers of patients with spinal cord injury (men = 60, women = 50). Factor structure was evaluated by confirmatory factor analysis. The Internal consistency and test-retest reliability of the CBS were examined using Cronbach's α and the intraclass correlation coefficient, respectively. Construct validity was assessed by examining the relationship among CBS and the World Health Organization Quality of Life, and the Beck Depression Inventory. The results of confirmatory factor analysis provided support for a five-factor model of CBS. All subscales of CBS revealed acceptable internal consistency (0.698-0.755), except for environment subscale (0.559). The CBS showed adequate test-retest reliability for its subscales (0.745-0.900). All subscales of CBS significantly correlated with both Beck Depression Inventory and World Health Organization Quality of Life, confirming construct validity. The Persian version of the CBS is a valid and reliable measure for assessing burden of care in caregivers of patients with spinal cord injury. Implications for Rehabilitation Spinal cord injury leads to depression, high levels of stress and diminished quality of life due to the high physical, emotional, and social burdens in caregivers. Persian version of the Caregiver Burden Scale is a valid and reliable tool for assessing burden in Iranian caregivers of patients with spinal cord injury.

The keto-enol equilibrium in substituted acetaldehydes: focal-point analysis and ab initio limit

NASA Astrophysics Data System (ADS)

Balabin, Roman M.

2011-10-01

High-level ab initio electronic structure calculations up to the CCSD(T) theory level, including extrapolations to the complete basis set (CBS) limit, resulted in high precision energetics of the tautomeric equilibrium in 2-substituted acetaldehydes (XH2C-CHO). The CCSD(T)/CBS relative energies of the tautomers were estimated using CCSD(T)/aug-cc-pVTZ, MP3/aug-cc-pVQZ, and MP2/aug-cc-pV5Z calculations with MP2/aug-cc-pVTZ geometries. The relative enol (XHC = CHOH) stabilities (ΔE e,CCSD(T)/CBS) were found to be 5.98 ± 0.17, -1.67 ± 0.82, 7.64 ± 0.21, 8.39 ± 0.31, 2.82 ± 0.52, 10.27 ± 0.39, 9.12 ± 0.18, 5.47 ± 0.53, 7.50 ± 0.43, 10.12 ± 0.51, 8.49 ± 0.33, and 6.19 ± 0.18 kcal mol-1 for X = BeH, BH2, CH3, Cl, CN, F, H, NC, NH2, OCH3, OH, and SH, respectively. Inconsistencies between the results of complex/composite energy computations methods Gn/CBS (G2, G3, CBS-4M, and CBS-QB3) and high-level ab initio methods (CCSD(T)/CBS and MP2/CBS) were found. DFT/aug-cc-pVTZ results with B3LYP, PBE0 (PBE1PBE), TPSS, and BMK density functionals were close to the CCSD(T)/CBS levels (MAD = 1.04 kcal mol-1).

Electron Microscopy Analysis of the Nucleolus of Trypanosoma cruzi

NASA Astrophysics Data System (ADS)

López-Velázquez, Gabriel; Hernández, Roberto; López-Villaseñor, Imelda; Reyes-Vivas, Horacio; Segura-Valdez, María De L.; Jiménez-García, Luis F.

2005-08-01

The nucleolus is the main site for synthesis and processing of ribosomal RNA in eukaryotes. In mammals, plants, and yeast the nucleolus has been extensively characterized by electron microscopy, but in the majority of the unicellular eukaryotes no such studies have been performed. Here we used ultrastructural cytochemical and immunocytochemical techniques as well as three-dimensional reconstruction to analyze the nucleolus of Trypanosoma cruzi, which is an early divergent eukaryote of medical importance. In T. cruzi epimastigotes the nucleolus is a spherical intranuclear ribonucleoprotein organelle localized in a relatively central position within the nucleus. Dense fibrillar and granular components but not fibrillar centers were observed. In addition, nuclear bodies resembling Cajal bodies were observed associated to the nucleolus in the surrounding nucleoplasm. Our results provide additional morphological data to better understand the synthesis and processing of the ribosomal RNA in kinetoplastids.

The maestro don Gonzalo Rodríguez-Lafora.

PubMed

Nanduri, Anish S; Kaushal, Neal; Clusmann, Hans; Binder, Devin K

2008-06-01

Gonzalo Rodríguez-Lafora (1886-1971) was an influential Spanish neurologist, and has been called the last of Cajal's great Spanish disciples. Of course, he is best known now for describing (in 1911) the intracytoplasmic inclusion bodies in "Lafora disease." In total, he published approximately 200 papers covering a wide range of subjects in neurology, psychiatry, and neuropathology. He made seminal contributions not only to the clinical and scientific literature but also to the training of many noted disciples who paid him due homage as a true "maestro." Throughout his intellectual endeavors, Lafora manifested a singular purpose and intensity and a burning devotion to scientific honesty.

Requirements for Information/Education Programs on Hypothermia.

DTIC Science & Technology

1979-10-23

NY (NBC) WEZF - Burlington, VT (ABC) Bangor, ME: 112,800 WLBZ - Bangor, ME (NBC) WABI - Bangor, ME (CBS) WVII - Bangor, ME (ABC) Presque Isle , ME...28,700 WAGM - Presque Isle , ME CBS(ABC-NBC) A-2 MID-ATLANTIC: 18,885,600 New York, NY: 6,375,500 Raleigh-Durham, NC: 451,800 WCBS - New York, NY (CBS...NY (ABC) WICZ - Binghamton, NY (NBC) WilingonNC: 135,300 WWAY -IWilmington, NC (ABC) WECT - Wilmington, NC NBC (CBS) Erie , PA: 132,600 WICU - Erie , PA

Automated Cellient(™) cytoblocks: better, stronger, faster?

PubMed

Prendeville, S; Brosnan, T; Browne, T J; McCarthy, J

2014-12-01

Cytoblocks (CBs), or cell blocks, provide additional morphological detail and a platform for immunocytochemistry (ICC) in cytopathology. The Cellient(™) system produces CBs in 45 minutes using methanol fixation, compared with traditional CBs, which require overnight formalin fixation. This study compares Cellient and traditional CB methods in terms of cellularity, morphology and immunoreactivity, evaluates the potential to add formalin fixation to the Cellient method for ICC studies and determines the optimal sectioning depth for maximal cellularity in Cellient CBs. One hundred and sixty CBs were prepared from 40 cytology samples (32 malignant, eight benign) using four processing methods: (A) traditional; (B) Cellient (methanol fixation); (C) Cellient using additional formalin fixation for 30 minutes; (D) Cellient using additional formalin fixation for 60 minutes. Haematoxylin and eosin-stained sections were assessed for cellularity and morphology. ICC was assessed on 14 cases with a panel of antibodies. Three additional Cellient samples were serially sectioned to determine the optimal sectioning depth. Scoring was performed by two independent, blinded reviewers. For malignant cases, morphology was superior with Cellient relative to traditional CBs (P < 0.001). Cellularity was comparable across all methods. ICC was excellent in all groups and the addition of formalin at any stage during the Cellient process did not influence the staining quality. Serial sectioning through Cellient CBs showed optimum cellularity at 30-40 μm with at least 27 sections obtainable. Cellient CBs provide superior morphology to traditional CBs and, if required, formalin fixation may be added to the Cellient process for ICC. Optimal Cellient CB cellularity is achieved at 30-40 μm, which will impact on the handling of cases in daily practice. © 2014 John Wiley & Sons Ltd.

Occurrence, distribution, and dechlorination of polychlorinated biphenyls and health risk assessment in Selangor River basin.

PubMed

Sakai, Nobumitsu; Dayana, Emmy; Abu Bakar, Azizi; Yoneda, Minoru; Nik Sulaiman, Nik Meriam; Ali Mohd, Mustafa

2016-10-01

Polychlorinated biphenyls (PCBs) were monitored in surface water collected in the Selangor River basin, Malaysia, to identify the occurrence, distribution, and dechlorination process as well as to assess the potential adverse effects to the Malaysian population. Ten PCB homologs (i.e., mono-CBs to deca-CBs) were quantitated by using gas chromatography-mass spectrometry (GC/MS). The total concentration of PCBs in the 10 sampling sites ranged from limit of detection to 7.67 ng L -1 . The higher chlorinated biphenyls (tetra-CBs to deca-CBs) were almost not detected in most of the sampling sites, whereas lower chlorinated biphenyls (mono-CBs, di-CBs, and tri-CBs) dominated more than 90 % of the 10 homologs in all the sampling sites. Therefore, the PCB load was estimated to be negligible during the sampling period because PCBs have an extremely long half-life. The PCBs, particularly higher chlorinated biphenyls, could be thoroughly dechlorinated to mono-CBs to tri-CBs by microbial decomposition in sediment or could still be accumulated in the sediment. The lower chlorinated biphenyls, however, could be resuspended or desorbed from the sediment because they have faster desorption rates and higher solubility, compared to the higher chlorinated biphenyls. The health risk for the Malaysia population by PCB intake that was estimated from the local fish consumption (7.2 ng kg -1 bw day -1 ) and tap water consumption (1.5 × 10 -3 -3.1 × 10 -3  ng kg -1 bw day -1 ) based on the detected PCB levels in the surface water was considered to be minimal. The hazard quotient based on the tolerable daily intake (20 ng kg -1 bw day -1 ) was estimated at 0.36.

Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression

PubMed Central

Lechuga, Thomas J.; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R.; Rosenfeld, Charles R.

2015-01-01

Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health. PMID:25825818

Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression.

PubMed

Lechuga, Thomas J; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R; Rosenfeld, Charles R; Chen, Dong-bao

2015-06-01

Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health.

Short-term hot-hardness characteristics of five case hardened steels

NASA Technical Reports Server (NTRS)

Anderson, N. E.; Zaretsky, E. V.

1975-01-01

Short-term hot-hardness studies were performed with carburized and hardened AISI 8620, CBS 1000, CBS 1000M, CBS 600, and Vasco X-2 steels. Case and core hardness measurements were made at temperatures from 294 to 811 K (70 to 1000 F). The data were compared with data for high-speed tool steels and AISI 52100. The materials tested can be ranked as follows in order of decreasing hot-hardness retention: (1) Vasco X-2; equivalent to through-hardened tool steels up to 644 K (700 F) above which Vasco X-2 is inferior; (2) CBS 1000, (3) CBS 1000M; (4) CBS 6000; better hardness retention at elevated temperatures than through-hardened AISI 52100; and (5) AISI 8620. For the carburized steels, the change in hardness with temperature of the case and core are similar for a given material. The short-term hot hardness of these materials can be predicted with + or - 1 point Rockwell C.

The effectiveness and cost-effectiveness of community-based support for adolescents receiving antiretroviral treatment: an operational research study in South Africa.

PubMed

Fatti, Geoffrey; Jackson, Debra; Goga, Ameena E; Shaikh, Najma; Eley, Brian; Nachega, Jean B; Grimwood, Ashraf

2018-02-01

Adolescents and youth receiving antiretroviral treatment (ART) in sub-Saharan Africa have high attrition and inadequate ART outcomes, and evaluations of interventions improving ART outcomes amongst adolescents are very limited. Sustainable Development Goal (SDG) target 3c is to substantially increase the health workforce in developing countries. We measured the effectiveness and cost-effectiveness of community-based support (CBS) provided by lay health workers for adolescents and youth receiving ART in South Africa. A retrospective cohort study including adolescents and youth who initiated ART at 47 facilities. Previously unemployed CBS-workers provided home-based ART-related education, psychosocial support, symptom screening for opportunistic infections and support to access government grants. Outcomes were compared between participants who received CBS plus standard clinic-based care versus participants who received standard care only. Cumulative incidences of all-cause mortality and loss to follow-up (LTFU), adherence measured using medication possession ratios (MPRs), CD4 count slope, and virological suppression were analysed using multivariable Cox, competing-risks regression, generalized estimating equations and mixed-effects models over five years of ART. An expenditure approach was used to determine the incremental cost of CBS to usual care from a provider perspective. Incremental cost-effectiveness ratios were calculated as annual cost per patient-loss (through death or LTFU) averted. Amongst 6706 participants included, 2100 (31.3%) received CBS. Participants who received CBS had reduced mortality, adjusted hazard ratio (aHR) = 0.52 (95% CI: 0.37 to 0.73; p < 0.0001). Cumulative LTFU was 40% lower amongst participants receiving CBS (29.9%) compared to participants without CBS (38.9%), aHR = 0.60 (95% CI: 0.51 to 0.71); p < 0.0001). The effectiveness of CBS in reducing attrition ranged from 42.2% after one year to 35.9% after five years. Virological suppression was similar after three years, but after five years 18.8% CBS participants versus 37.2% non-CBS participants failed to achieve viral suppression, adjusted odds ratio = 0.24 (95% CI: 0.06 to 1.03). There were no significant differences in MPR or CD4 slope. The cost of CBS was US$49.5/patient/year. The incremental cost per patient-loss averted was US$600 and US$776 after one and two years, respectively. CBS for adolescents and youth receiving ART was associated with substantially reduced patient attrition, and is a low-cost intervention with reasonable cost-effectiveness that can aid progress towards several health, economic and equality-related SDG targets. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Expression of TRPV1 channels by Cajal-Retzius cells and layer-specific modulation of synaptic transmission by capsaicin in the mouse hippocampus.

PubMed

Anstötz, Max; Lee, Sun Kyong; Maccaferri, Gianmaria

2018-05-28

By taking advantage of calcium imaging and electrophysiology, we provide direct pharmacological evidence for the functional expression of TRPV1 channels in hippocampal Cajal-Retzius cells. Application of the TRPV1 activator capsaicin powerfully enhances spontaneous synaptic transmission in the hippocampal layers that are innervated by the axons of Cajal-Retzius cells. Capsaicin-triggered calcium responses and membrane currents in Cajal-Retzius cells, as well as layer-specific modulation of spontaneous synaptic transmission, are absent when the drug is applied to slices prepared from TRPV1 - / - animals. We discuss the implications of the functional expression of TRPV1 channels in Cajal-Retzius cells and of the observed TRPV1-dependent layer-specific modulation of synaptic transmission for physiological and pathological network processing. The vanilloid receptor TRPV1 forms complex polymodal channels that are expressed by sensory neurons and play a critical role in nociception. Their distribution pattern and functions in cortical circuits are, however, much less understood. Although TRPV1 reporter mice have suggested that, in the hippocampus, TRPV1 is predominantly expressed by Cajal-Retzius cells (CRs), direct functional evidence is missing. As CRs powerfully excite GABAergic interneurons of the molecular layers, TRPV1 could play important roles in the regulation of layer-specific processing. Here, we have taken advantage of calcium imaging with the genetically encoded indicator GCaMP6s and patch-clamp techniques to study the responses of hippocampal CRs to the activation of TRPV1 by capsaicin, and have compared the effect of TRPV1 stimulation on synaptic transmission in layers innervated or non-innervated by CRs. Capsaicin induced both calcium responses and membrane currents in ∼50% of the cell tested. Neither increases of intracellular calcium nor whole-cell currents were observed in the presence of the TRPV1 antagonists capsazepine/Ruthenium Red or in slices prepared from TRPV1 knockout mice. We also report a powerful TRPV1-dependent enhancement of spontaneous synaptic transmission onto interneurons with dendritic trees confined to the layers innervated by CRs. In conclusion, our work establishes that functional TRPV1 is expressed by a significant fraction of CRs and we propose that TRPV1 activity may regulate layer-specific synaptic transmission in the hippocampus. Lastly, as CR density decreases during postnatal development, we also propose that functional TRPV1 receptors may be related to mechanisms involved in CR progressive reduction by calcium-dependent toxicity/apoptosis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats.

PubMed

Chen, Hai-Bo; Wu, Wen-Ning; Wang, Wei; Gu, Xun-Hu; Yu, Bin; Wei, Bo; Yang, Yuan-Jian

2017-04-01

Hydrogen sulfide (H 2 S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H 2 S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H 2 S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H 2 S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H 2 S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H 2 S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H 2 S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H 2 S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H 2 S might involve the regulation of NMDAR function. Copyright © 2017 Elsevier Inc. All rights reserved.

The protective activity of Conyza blinii saponin against acute gastric ulcer induced by ethanol.

PubMed

Ma, Long; Liu, Jiangguang

2014-12-02

Conyza blinii H.Lév., is a type of natural plant. Its dried overground section is used to treat infections and inflammations in traditional Chinese medicine. Triterpenoidal saponins have a wide range of bioactivities, for instance, anti-cancer, anti-virus and anti-anaphylaxis. Conyza blinii saponin (CBS), mainly composed of triterpenoidal saponins, is the total saponin of Conyza blinii H.Lév. It has been reported that CBS also has gastric mucous membrane protection activity. This study aims to test CBS׳s protective activity of gastric׳s mucous membrane against ethanol. This investigation may lead to the development of novel drug from natural products as anti-ulcer agent, or as gastric mucous protective against chemical damage. CBS (Conyza blinii saponin) is the total saponin of Conyza blinii H.Lév., which was obtained as described previously. We tested the protective activity of CBS against ethanol-induced ulcer. Thirty six rats were grouped randomly as 'NORMAL', 'CONTROL', 'MODEL', 'LOW DOSE', 'MEDIUM DOSE' and 'HIGH DOSE'. The 'NORMAL' group were rats with no pathological model established within it. The 'CONTROL' group was administrated with colloidal bismuth subcitrate, while 'MODEL' group was not given any active agents apart from absolute ethanol in order to obtain gastric ulcer model. The three 'DOSE' groups were treated with different concentrations of CBS (5, 10, 20mg/mL) before administration followed by absolute ethanol. All rats were sacrificed after the experiment to acquire the gastric tissue. The ulcer index (UI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to monitor the activity of CBS. Besides, the rat gastric tissue was made to paraffin section and stained using the Hematoxylin-Eosin (HE) method. The histopathology examination was carried out to examine CBS efficacy in terms of gastric mucous protection. We found that CBS had a profound protection activity against acute gastric ulcer induced by ethanol and this activity displayed a concentration-dependent manner. The efficacy of 10 and 20mg/mL CBS was comparable with colloidal bismuth subcitrate (P<0.05). All three level of CBS tested were able to significantly reduce UI, MDA and enhance SOD level (P<0.05). It was deduced that the mechanism for such activity would be anti-lipid peroxidation, facilitating free radicals clearance. In addition , histopathology examination of the gastric mucous membrane supported the same conclusion, that CBS can efficiently suppress the inflammatory reactions, bleeding and protect the gastric mucosa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Revisiting the 1981 Nobel Prize to Roger Sperry, David Hubel, and Torsten Wiesel on the occasion of the centennial of the Prize to Golgi and Cajal.

PubMed

Berlucchi, Giovanni

2006-12-01

In 1981 the Nobel Prize for Medicine or Physiology was awarded to Roger Sperry for his work on the functional specialization of the cerebral hemispheres, and to David Hubel and Torsten Wiesel for their work on information processing in the visual system. The present paper points to some important links between the work of Sperry and that of Hubel and Wiesel and to their influences on neuroscience in the best tradition going back to Cajal.

Five novel Wickerhamomyces- and Metschnikowia-related yeast species, Wickerhamomyces chaumierensis sp. nov., Candida pseudoflosculorum sp. nov., Candida danieliae sp. nov., Candida robnettiae sp. nov. and Candida eppingiae sp. nov., isolated from plants.

PubMed

Groenewald, Marizeth; Robert, Vincent; Smith, Maudy Th

2011-08-01

On the basis of nucleotide divergences in the D1/D2 domain of the 26S rRNA gene and the internal transcribed spacers (ITS) domain of the rRNA gene, five novel yeast species, Wickerhamomyces chaumierensis sp. nov. (CBS 8565(T)  = JCM 17246(T)), Candida pseudoflosculorum sp. nov. (CBS 8584(T)  = JCM 17242(T)), Candida danieliae sp. nov. (CBS 8533(T)  = JCM 17247(T)), Candida robnettiae sp. nov. (CBS 8580(T)  = JCM 17243(T)) and Candida eppingiae sp. nov. (CBS 8586(T)  = JCM 17241(T)), isolated from plants in Thailand and Guyana, are proposed in this study.

Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury

PubMed Central

Chan, Su Jing; Chai, Chou; Lim, Tze Wei; Yamamoto, Mie; Lo, Eng H; Lai, Mitchell Kim Peng

2015-01-01

Hydrogen sulfide (H2S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS) has been implicated as the predominant H2S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H2S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD) together with high substrate concentrations, indicating that H2S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H2S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment. PMID:25873304

Investigation of the synergistic effects of haloperidol combined with Calculus Bovis Sativus in treating MK-801-induced schizophrenia in rats

PubMed Central

Lei, Kai; He, Guo-Fang; Zhang, Cheng-Liang; Liu, Ya-Nan; Li, Juan; He, Guang-Zhao; Li, Xi-Ping; Ren, Xiu-Hua; Liu, Dong

2017-01-01

Clinical studies that focused on treating schizophrenia showed that Calculus Bovis Sativus (CBS), a substitute of Calculus Bovis, when used in combination with haloperidol could significantly lower the dosage of haloperidol compared with treatment with haloperidol alone, whereas efficacy was maintained. The aim of this study was to investigate the synergetic anti-schizophrenia effects in rats using CBS in combination with haloperidol. An open field test was conducted to verify the pharmacodynamic effects of a combination treatment of CBS and haloperidol on MK-801-induced schizophrenic rats. Rat plasma concentrations of intragastric haloperidol and intravenous haloperidol were determined after oral administration of a single dose or 1-week of pretreatment with CBS (50 mg/kg). The pharmacodynamic data showed a significant decrease in locomotor activity and an increase in the percentage of the central distance when haloperidol was concomitantly administered with CBS compared with haloperidol administration alone. The AUC0-∞ and Cmax of haloperidol in the orally coadministered groups were significantly higher compared with the oral treatment with haloperidol alone. In conclusion, oral coadministration of CBS with haloperidol resulted in a synergistic effect in rats. The enhanced oral bioavailability of haloperidol when combined with CBS might be attributed to the interaction between them. PMID:29225304

Cystathionine beta synthase gene dose dependent vascular remodeling in murine model of hyperhomocysteinemia.

PubMed

Tyagi, Neetu; Qipshidze, Natia; Sen, Utpal; Rodriguez, Walter; Ovechkin, Alexander; Tyagi, Suresh C

2011-09-30

Although children born with severe homocystinurea (i.e. cystathionine beta synthase homozygote knockout, CBS-/-) develop deleterious vascular complications with structural malformation and do not live past teenage, the heterozygote (CBS-/+) lives with apparently normal phenotype. Interestingly, this differential role of CBS expression in vascular remodeling is unclear. Peroxisome proliferator activated receptor gamma (PPARγ) is nuclear transcription factor that mitigates vascular complications. The hypothesis was that homocysteine (Hcy) decreased thioredoxin (Trx), peroxiredoxin (Prx), increased NADPH oxidase (NOX1), mitochondrial nitric oxide synthase (mtNOS) activity and reactive oxygen species (ROS) in mitochondria in a CBS gene dose-dependent manner. ROS transduced matrix metalloproteinase (MMP) activation causing thickening (fibrosis) of the basement membrane, rendering ineffective endothelial nitric oxide synthase (eNOS) and promoted endothelial-smooth muscle disconnection/uncoupling by antagonizing PPARγ. Wild type (WT-CBS+/+), CBS-/+ and CBS -/- mice were treated with or without ciglitazone (CZ, a PPARγ agonist) in food at birth. Aortic nuclear PPARγ expression was measured by EMSA. Aortic mtNOS activity and ROS production was measured using NO- and H(2)O(2)-electrodes, respectively. Aorta was analyzed for Trx, Prx, by Western blot, and PCR. MMP activity was by in situ zymography. Aortic function was measured in tissue myobath. The results suggested 90% morbidity in CBS-/- allele at 12 wks. However, treatment with the PPARγ agonist, CZ significantly reduced the morbidity to 20%. In addition, CZ restored the PPARγ activity in CBS-/+ and -/- mice to normal levels. The oxidative stress was alleviated by CZ treatment. In situ labeling with mito-tracker suggests co-localization of ROS with mitochondrial mitophagy. The mtNOS activity was increased in HHcy compared to WT. The data support the notion that Hcy decreases redoxins, increases mtNOS activity and ROS/oxidase in mitochondrial mitophagy in a gene dose-dependent manner of CBS. ROS transduces MMP activation, rendering ineffective eNOS and promotes endothelial-smooth muscle disconnection/uncoupling by antagonizing PPARγ. We suggest that the children born with severe ho-mocystineurea may do better if treated with PPARγ agonist.

Hepatoprotective effect of calculus bovis sativus on nonalcoholic fatty liver disease in mice by inhibiting oxidative stress and apoptosis of hepatocytes

PubMed Central

He, Wenxi; Xu, Yanjiao; Zhang, Chengliang; Lu, Jingli; Li, Juan; Xiang, Dong; Yang, Jinyu; Chang, Mujun; Liu, Dong

2017-01-01

Calculus bovis (CB, niu-huang) is a high-class therapeutic drug that is often used in traditional Chinese medicine. CB helps to eliminate heat and toxic components, and prevents the accumulation of phlegm and blood stasis in the liver. In Asian countries, CB Sativus (CBS), an ideal substitute for natural CB, is presently extensively used for long-term treatment of chronic liver diseases. The present study aimed to evaluate the effects and potential mechanism(s) of action of CBS on mice with fructose-induced nonalcoholic fatty liver disease (NAFLD). The NAFLD model was established in C57BL/6 mice by exclusively feeding fluids containing 30% fructose for 8 consecutive weeks. After these 8 weeks, mice were given CBS (50 mg/kg/day or 100 mg/kg/day) for 2 consecutive weeks. Treatment with CBS reversed the fructose-induced impaired glucose tolerance. Compared with the model group, in which mice received 8 weeks of high-fructose diet and 2 weeks of 0.5% sodium carboxymethyl cellulose, CBS treatment significantly decreased the levels of fasting serum glucose, fasting insulin, triglyceride, and total cholesterol, and increased levels of high-density lipoprotein-cholesterol. CBS treatment also significantly decreased the levels of triglyceride, total cholesterol, and free fatty acid in the liver. The activity of superoxide dismutase in the liver was increased after treatment with CBS, however, levels of malondialdehyde and reactive oxygen species decreased. Histopathological examination showed that liver steatosis and injury were significantly reduced in CBS-treated mice. The expression of fatty acid synthase, nuclear factor kappa-light-chain-enhancer of activated B cells, Cysteinyl aspartate-specific proteinase-3, and synonyms B-cell leukemia/lymphoma-2 gene-associated X protein were downregulated after treatment with CBS, whereas the expression of nuclear factor erythroid-2-related factor 2 was upregulated. In conclusion, CBS treatment exerted therapeutic effects in the liver of mice with NAFLD, which may be associated with amelioration of metabolic disorders, enhanced antioxidant effects, and alleviation of apoptosis. PMID:29255346

Similar Outcomes for Contact Aspiration and Stent Retriever Use According to the Admission Clot Burden Score in ASTER.

PubMed

Zhu, François; Lapergue, Bertrand; Kyheng, Maéva; Blanc, Raphael; Labreuche, Julien; Ben Machaa, Malek; Duhamel, Alain; Marnat, Gautier; Saleme, Suzana; Costalat, Vincent; Bracard, Serge; Richard, Sébastien; Desal, Hubert; Mazighi, Mikael; Consoli, Arturo; Piotin, Michel; Gory, Benjamin

2018-07-01

The clot burden score (CBS) at admission reliably evaluates the thrombus burden in acute ischemic stroke patients with anterior circulation large vessel occlusion. Mechanical thrombectomy has been diversified, especially with contact aspiration technique, and its efficiency with respect to the thrombus burden is not known. We compared reperfusion, adverse events, neurological recovery, and 90-day functional outcome of stent retriever use versus contact aspiration according to the admission CBS. This is a post hoc analysis of the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) randomized trial. The primary outcome was successful reperfusion after all procedures, defined as modified Thrombolysis in Cerebral Infarction scores 2b/3. Secondary outcomes were 90-day functional outcome, assessed with the modified Rankin Scale. Safety outcomes included 90-day mortality and any intracerebral hemorrhage. A total of 231 randomized patients were included in this study: 114 patients had a CBS of 0 to 6 and 117 a CBS ≥7 at admission. Successful reperfusion at procedure end was achieved more frequently in patients with CBS ≥7 (88.9%) than patients with a CBS 0 to 6 (81.6%; fully adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.28). Favorable outcome (modified Rankin Scale score, 0-2) at 90 days was achieved in significantly more patients with CBS ≥7 (61.9%) than in patients with CBS 0 to 6 (41.8%; fully adjusted risk ratio, 1.19; 95% confidence interval, 1.02-1.40). No outcome differences of first-line mechanical thrombectomy strategy (aspiration versus stent) on any angiographic or clinical outcomes were observed between the 2 groups. We also found no evidence of interaction between first-line mechanical thrombectomy strategy and CBS groups regarding safety. First-line mechanical thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful reperfusion rate in acute ischemic stroke patients with large vessel occlusion of the anterior circulation according to the admission CBS. The latter, however, seems to be a reliable prognostic indicator of angiographic and clinical outcome. © 2018 American Heart Association, Inc.

Determination of Tinopal CBS-X in rice papers and rice noodles using HPLC with fluorescence detection and LC-MS/MS.

PubMed

Ko, Kyung Yuk; Lee, Chae A; Choi, Jae Chon; Kim, Meehye

2014-01-01

To date there have been no reports of methods to determine Tinopal CBS-X. We developed a rapid and simple method to determine the Tinopal CBS-X content in rice noodles and rice papers using HPLC equipped with fluorescence detection. Heating the rice noodles and rice papers to 80°C after adding 75% methanol solution induced the release of Tinopal CBS-X from processed rice products. Tinopal CBS-X was separated using an isocratic mobile phase comprising 50% acetonitrile/water containing 0.4% tetrabutyl ammonium hydrogen sulphate at pH 8.0. The samples suspected to be positive by HPLC analysis were then confirmed by LC-MS/MS analysis. This study also investigated the Tinopal CBS-X content of three rice noodle products and two rice papers. The limits of quantification for rice papers and rice noodles were 1.58 and 1.51 µg kg(-1), respectively, and their correlation curves showed good linearity with r(2) ≥ 0.9997 and ≥ 0.9998, respectively. Moreover, rice papers had recoveries of 70.3-83.3% with precision ranging from 5.0% to 7.9%, whereas rice noodles had slightly lower recoveries of 63.4-78.7% and precisions of 8.5-11.5%. Only one rice noodle product contained Tinopal CBS-X, at around 2.1 mg kg(-1), whereas it was not detected in four other samples. Consequently, Tinopal CBS-X from rice noodles and rice papers can be successfully detected using the developed pre-treatment and ion-pairing HPLC system coupled with fluorescence detection.

Impact Analysis of Flow Shaping in Ethernet-AVB/TSN and AFDX from Network Calculus and Simulation Perspective

PubMed Central

He, Feng; Zhao, Lin; Li, Ershuai

2017-01-01

Ethernet-AVB/TSN (Audio Video Bridging/Time-Sensitive Networking) and AFDX (Avionics Full DupleX switched Ethernet) are switched Ethernet technologies, which are both candidates for real-time communication in the context of transportation systems. AFDX implements a fixed priority scheduling strategy with two priority levels. Ethernet-AVB/TSN supports a similar fixed priority scheduling with an additional Credit-Based Shaper (CBS) mechanism. Besides, TSN can support time-triggered scheduling strategy. One direct effect of CBS mechanism is to increase the delay of its flows while decreasing the delay of other priority ones. The former effect can be seen as the shaping restriction and the latter effect can be seen as the shaping benefit from CBS. The goal of this paper is to investigate the impact of CBS on different priority flows, especially on the intermediate priority ones, as well as the effect of CBS bandwidth allocation. It is based on a performance comparison of AVB/TSN and AFDX by simulation in an automotive case study. Furthermore, the shaping benefit is modeled based on integral operation from network calculus perspective. Combing with the analysis of shaping restriction and shaping benefit, some configuration suggestions on the setting of CBS bandwidth are given. Results show that the effect of CBS depends on flow loads and CBS configurations. A larger load of high priority flows in AVB tends to a better performance for the intermediate priority flows when compared with AFDX. Shaping benefit can be explained and calculated according to the changing from the permitted maximum burst. PMID:28531158

IMPAIRED VERBAL COMPREHENSION OF QUANTIFIERS IN CORTICOBASAL SYNDROME

PubMed Central

Troiani, Vanessa; Clark, Robin; Grossman, Murray

2011-01-01

Objective Patients with Corticobasal Syndrome (CBS) have atrophy in posterior parietal cortex. This region of atrophy has been previously linked with their quantifier comprehension difficulty, but previous studies used visual stimuli, making it difficult to account for potential visuospatial deficits in CBS patients. The current study evaluated comprehension of generalized quantifiers using strictly verbal materials. Method CBS patients, a brain-damaged control group (consisting of Alzheimer's Disease and frontotemporal dementia), and age-matched controls participated in this study. We assessed familiar temporal, spatial, and monetary domains of verbal knowledge comparatively. Judgment accuracy was only evaluated in statements for which patients demonstrated accurate factual knowledge about the target domain. Results We found that patients with CBS are significantly impaired in their ability to evaluate quantifiers compared to healthy seniors and a brain-damaged control group, even in this strictly visual task. This impairment was seen in the vast majority of individual CBS patients. Conclusions These findings offer additional evidence of quantifier impairment in CBS patients and emphasize that this impairment cannot be attributed to potential spatial processing impairments in patients with parietal disease. PMID:21381823

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

Eriguchi, Takahisa; Takeda, Atsuya; Sanuki, Naoko

Purpose: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. Methods and Materials: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. Results: Fifty patients with 55 tumors weremore » irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. Conclusions: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.« less

Bandoniozyma gen. nov., a Genus of Fermentative and Non-Fermentative Tremellaceous Yeast Species

PubMed Central

Landell, Melissa Fontes; Crestani, Juliana; Pagnocca, Fernando Carlos; Sette, Lara Durães; Passarini, Michel Rodrigo Zambrano; Rosa, Carlos Augusto; Brandão, Luciana R.; Pimenta, Raphael S.; Ribeiro, José Roberto; Garcia, Karina Marques; Lee, Ching-Fu; Suh, Sung-Oui; Péter, Gábor; Dlauchy, Dénes; Fell, Jack W.; Scorzetti, Gloria; Theelen, Bart; Vainstein, Marilene H.

2012-01-01

Background Independent surveys across the globe led to the proposal of a new basidiomycetous yeast genus within the Bulleromyces clade of the Tremellales, Bandoniozyma gen. nov., with seven new species. Methodology/Principal Findings The species were characterized by multiple methods, including the analysis of D1/D2 and ITS nucleotide sequences, and morphological and physiological/biochemical traits. Most species can ferment glucose, which is an unusual trait among basidiomycetous yeasts. Conclusions/Significance In this study we propose the new yeast genus Bandoniozyma, with seven species Bandoniozyma noutii sp. nov. (type species of genus; CBS 8364T  =  DBVPG 4489T), Bandoniozyma aquatica sp. nov. (UFMG-DH4.20T  =  CBS 12527T  =  ATCC MYA-4876T), Bandoniozyma complexa sp. nov. (CBS 11570T  =  ATCC MYA-4603T  =  MA28aT), Bandoniozyma fermentans sp. nov. (CBS 12399T  =  NU7M71T  =  BCRC 23267T), Bandoniozyma glucofermentans sp. nov. (CBS 10381T  =  NRRL Y-48076T  =  ATCC MYA-4760T  =  BG 02-7-15-015A-1-1T), Bandoniozyma tunnelae sp. nov. (CBS 8024T  =  DBVPG 7000T), and Bandoniozyma visegradensis sp. nov. (CBS 12505T  =  NRRL Y-48783T  =  NCAIM Y.01952T). PMID:23056233

[Dynamics of morphological changes in the spinal cord following exposure to non-ionizing microwave radiation].

PubMed

Belokrinitskiĭ, V S

1983-05-01

The structure of different portions (cervical, thoracic, lumbar, sacral and coccygeal) of the spinal cord were studied in the experiments on 50 animals with the use of the Nissl, Zimmermann, Cajal and other methods on days 1, 10, 20 and 30 after exposure to non-ionizing microwave radiation (NMI). Single exposure to NMI (wave length 12.6 cm, intensity 400-500 mW/cm2) for one hour (cats) or four hours (dogs) produces a severe distress of glial neurones and cells, which is marked by the appearance of dystrophic processes along the entire spinal cord. The disease progresses, leading to abnormalities of motor and other physiological functions of the body.

Description of Hyphopichia buzzinii f.a., sp. nov. and Hyphopichia homilentoma comb. nov., the teleomorph of Candida homilentoma.

PubMed

Ribeiro, Lucas R; Santos, Ana R O; Groenewald, Marizeth; Smith, Maudy Th H; Lara, Carla A; Góes-Neto, Aristóteles; Jacques, Noémie; Grondin, Cécile; Casaregola, Serge; Lachance, Marc-André; Rosa, Carlos A

2017-07-01

During studies of the yeast diversity associated with rotting wood in Brazil and fruits, plants and insects in French Guiana, three strains of a new species were isolated. Analysis of the sequences of the internal transcribed spacer (ITS)-5.8S and D1/D2 domains of the large subunit of the rRNA gene showed that this species belongs to the genus Hyphopichia and its closest relative is Candida homilentoma. These species differ by 44 nucleotide substitutions in D1/D2 sequences. A new species Hyphopichia buzzinii f. a., sp. nov., is proposed to accommodate these isolates. The type strain of Hyphopichia buzzinii sp. nov. is CLIB 1739 T (=CBS 14300 T  = UFMG-CM-Y6121 T ; MycoBank number is MB 815609). In addition, we isolated 11 strains of C. homilentoma from rotting wood, leaf surfaces, and water bodies in Brazil, and these strains when crossed among one another and with the type strain (CBS 6312 T ) of this species, produced hat-shaped ascospores typical of the genus Hyphopichia. We describe the teleomorph of C. homilentoma as a new combination, Hyphopichia homilentoma comb. nov. (type strain CBS 6312 T ; MycoBank number is MB 820009). We also propose to transfer the other six Candida species of the Hyphopichia clade to this genus as new combinations. Hyphopichia homilentoma produced ethanol and xylitol from D-xylose whereas H. buzzinii was only able to convert this pentose to xylitol.

Temperature and host preferences drive the diversification of Saccharomyces and other yeasts: a survey and the discovery of eight new yeast species.

PubMed

Sylvester, Kayla; Wang, Qi-Ming; James, Brielle; Mendez, Russell; Hulfachor, Amanda Beth; Hittinger, Chris Todd

2015-05-01

Compared to its status as an experimental model system and importance to industry, the ecology and genetic diversity of the genus Saccharomyces has received less attention. To investigate systematically the biogeography, community members and habitat of these important yeasts, we isolated and identified nearly 600 yeast strains using sugar-rich enrichment protocols. Isolates were highly diverse and contained representatives of more than 80 species from over 30 genera, including eight novel species that we describe here: Kwoniella betulae f.a. (yHKS285(T) = NRRL Y-63732(T) = CBS 13896(T)), Kwoniella newhampshirensis f.a. (yHKS256(T) = NRRL Y-63731(T) = CBS 13917(T)), Cryptococcus wisconsinensis (yHKS301(T) = NRRL Y-63733(T) = CBS 13895(T)), Cryptococcus tahquamenonensis (yHAB242(T) = NRRL Y-63730(T) = CBS 13897(T)), Kodamaea meredithiae f.a. (yHAB239(T) = NRRL Y-63729(T) = CBS 13899(T)), Blastobotrys buckinghamii (yHAB196(T) = NRRL Y-63727(T) = CBS 13900(T)), Candida sungouii (yHBJ21(T) = NRRL Y-63726(T) = CBS 13907(T)) and Cyberlindnera culbertsonii f.a. (yHAB218(T) = NRRL Y-63728(T) = CBS 13898(T)), spp. nov. Saccharomyces paradoxus was one of the most frequently isolated species and was represented by three genetically distinct lineages in Wisconsin alone. We found a statistically significant association between Quercus (oak) samples and the isolation of S. paradoxus, as well as several novel associations. Variation in temperature preference was widespread across taxonomic ranks and evolutionary timescales. This survey highlights the genetic and taxonomic diversity of yeasts and suggests that host and temperature preferences are major ecological factors. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Limb immobilization and corticobasal syndrome.

PubMed

Graff-Radford, Jonathan; Boeve, Bradley F; Drubach, Daniel A; Knopman, David S; Ahlskog, J Eric; Golden, Erin C; Drubach, Dina I; Petersen, Ronald C; Josephs, Keith A

2012-12-01

Recently, we evaluated two patients with corticobasal syndrome (CBS) who reported symptom onset after limb immobilization. Our objective was to investigate the association between trauma, immobilization and CBS. The charts of forty-four consecutive CBS patients seen in the Mayo Clinic Alzheimer Disease Research Center were reviewed with attention to trauma and limb immobilization. 10 CBS patients (23%) had immobilization or trauma on the most affected limb preceding the onset or acceleration of symptoms. The median age at onset was 61. Six patients manifested their first symptoms after immobilization from surgery or fracture with one after leg trauma. Four patients had pre-existing symptoms of limb dysfunction but significantly worsened after immobilization or surgery. 23 percent of patients had immobilization or trauma of the affected limb. This might have implications for management of CBS, for avoiding injury, limiting immobilization and increasing movement in the affected limb. Copyright © 2012 Elsevier Ltd. All rights reserved.

Does powder and granular activated carbon perform equally in immobilizing chlorobenzenes in soil?

PubMed

Song, Yang; Wang, Fang; Kengara, Fredrick Orori; Bian, Yongrong; Yang, Xinglun; Gu, Chenggang; Ye, Mao; Jiang, Xin

2015-01-01

The objective of this study is to compare the efficacies of powder activated carbon (PAC) and granular activated carbon (GAC) as amendments for the immobilization of volatile compounds in soil. Soil artificially-spiked with chlorobenzenes (CBs) was amended with either PAC or GAC to obtain an application rate of 1%. The results showed that the dissipation and volatilization of CBs from the amended soil significantly decreased compared to the unamended soil. The bioavailabilities of CBs, which is expressed as butanol extraction and earthworm accumulation, were significantly reduced in PAC and GAC amended soils. The lower chlorinated and hence more volatile CBs experienced higher reductions in both dissipation and bioavailability in the amended soils. The GAC and PAC equally immobilized more volatile CBs in soil. Therefore, it could be concluded that along with environmental implication, applying GAC was the more promising approach for the effective immobilization of volatile compounds in soil.

Endocannabinoid hydrolases in avian HD11 macrophages identified by chemoproteomics: inactivation by small molecule inhibitors and pathogen-induced downregulation of their activity.

USDA-ARS?s Scientific Manuscript database

The endocannabinoids (eCBs) are endogenous arachidonoyl-containing lipid mediators with important roles in host defense. Macrophages are first-line defenders of the innate immune system and biosynthesize large amounts of eCBs when activated. The cellular levels of eCBs are controlled by the activiti...

Plasma Screening for Progranulin Mutations in Patients with Progressive Supranuclear Palsy and Corticobasal Syndromes.

PubMed

Galimberti, Daniela; Bertram, Kelly; Formica, Alessandra; Fenoglio, Chiara; Cioffi, Sara M G; Arighi, Andrea; Scarpini, Elio; Colosimo, Carlo

2016-05-04

Progranulin gene (GRN) mutations are characterized by heterogeneous presentations. Corticobasal syndrome (CBS) is often associated with GRN mutations, whereas association with progressive supranuclear palsy syndrome (PSPS) is rare. Plasma progranulin levels were evaluated in 34 patients, including 19 with PSPS, 12 with CBS, and 3 with mixed signs, with the purpose to screen for the presence of causal mutations, associated with low levels. We found undetectable levels in a patient with CBS. Sequencing confirmed the presence of the Thr272fs deletion. Progranulin mutation screening is suggested in cases of CBS, even in the absence of positive family history for dementia and/or movement disorders.

Optical–Mid-infrared Period–Luminosity Relations for W UMa-type Contact Binaries Based on Gaia DR 1: 8% Distance Accuracy

NASA Astrophysics Data System (ADS)

Chen, Xiaodian; Deng, Licai; de Grijs, Richard; Wang, Shu; Feng, Yuting

2018-06-01

W Ursa Majoris (W UMa)-type contact binary systems (CBs) are useful statistical distance indicators because of their large numbers. Here, we establish (orbital) period–luminosity relations (PLRs) in 12 optical to mid-infrared bands (GBVRIJHK s W1W2W3W4) based on 183 nearby W UMa-type CBs with accurate Tycho–Gaia parallaxes. The 1σ dispersion of the PLRs decreases from optical to near- and mid-infrared wavelengths. The minimum scatter, 0.16 mag, implies that W UMa-type CBs can be used to recover distances to 7% precision. Applying our newly determined PLRs to 19 open clusters containing W UMa-type CBs demonstrates that the PLR and open cluster CB distance scales are mutually consistent to within 1%. Adopting our PLRs as secondary distance indicators, we compiled a catalog of 55,603 CB candidates, of which 80% have distance estimates based on a combination of optical, near-infrared, and mid-infrared photometry. Using Fourier decomposition, 27,318 high-probability W UMa-type CBs were selected. The resulting 8% distance accuracy implies that our sample encompasses the largest number of objects with accurate distances within a local volume with a radius of 3 kpc available to date. The distribution of W UMa-type CBs in the Galaxy suggests that in different environments, the CB luminosity function may be different: larger numbers of brighter (longer-period) W UMa-type CBs are found in younger environments.

Microwave thawing and green tea extract efficiency for the formation of acrylamide throughout the production process of chicken burgers and chicken nuggets.

PubMed

Soncu, Eda Demirok; Kolsarici, Nuray

2017-04-01

Initially, we measured the acrylamide (AA) levels of chicken burgers (CBs) and chicken nuggets (CNs) purchased from fast food restaurants. After the determination of AA in these products, we aimed to investigate whether the use of green tea extract in the covering material, and microwave thawing before frying, mitigated the formation of AA in CBs and CNs during the production process. According to our study, AA concentrations of CBs and CNs purchased from fast food restaurants were in the range of 13.43-118.97 and 32.92-134.90 ng g -1 coating, respectively. In our experiment, AA levels varied between 19.61 and 40.08 ng g -1 coating for CBs and 7.92-49.60 ng g -1 coating for CNs. Green tea extract reduced the AA formation in CBs and CNs at the pan frying and steam oven cooking heat treatment steps (P < 0.05). However, microwave thawing did not affect AA level of CBs and CNs. When the AA levels of commercial CBs and CNs are compared with those produced in our experiment, the use of green tea extract could be a novel, easy and practical application for fast food producers to minimise AA levels in the first two steps of the production without changes to the sensory properties of the final products. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Coastal erosion vs riverline sediment discharge in the Arctic shelfx seas

USGS Publications Warehouse

Rachold, V.; Grigoriev, M.N.; Are, F.E.; Solomon, Sean C.; Reimnitz, E.; Kassens, H.; Antonow, M.

2000-01-01

This article presents a comparison of sediment input by rivers and by coastal erosion into both the Laptev Sea and the Canadian Beaufort Sea (CBS). New data on coastal erosion in the Laptev Sea, which are based on field measurements and remote sensing information and existing data on coastal erosion in the CBS as well as riverine sediment discharge into both the Laptev Sea and the CBS are included. Strong regional differences in the percentages of coastal ero- sion and riverine sediment supply are observed. The CBS is dominated by the riverine sediment discharge (64.45x106 t a-1) mainly of the Mackenzie River. which is the largest single source of sediments in the Arctic. Riverine sediment discharge into the Laptev Sea amounts to 24.10x106 t a-1, more than 70% of which are related to the Lena River. In comparison with the CBS. the Laptev Sea coast on average delivers approximately twice as much sediment mass per kilometer, a result of higher erosion rates due to higher cliffs and seasonal ice melting. In the Laptev Sea sediment input by coastal erosion (58.4x106 t a-1) is therefore more important than in the CBS and the ratio between riverine and coastal sediment input amounts to 0.4. Coastal erosion supplying 5.6x106 t a-1 is less significant for the sediment budget of the CBS where riverine sediment discharge exceeds coastal sediment input by a factor of ca. 10.

The impact of communication barriers on diagnostic confidence and ancillary testing in the emergency department.

PubMed

Garra, Gregory; Albino, Hiram; Chapman, Heather; Singer, Adam J; Thode, Henry C

2010-06-01

Communication barriers (CBs) compromise the diagnostic power of the medical interview and may result in increased reliance on diagnostic tests or incorrect test ordering. The prevalence and degree to which these barriers affect diagnosis, testing, and treatment are unknown. To quantify and characterize CBs encountered in the Emergency Department (ED), and assess the effect of CBs on initial diagnosis and perceived reliance on ancillary testing. This was a prospective survey completed by emergency physicians after initial adult patient encounters. CB severity, diagnostic confidence, and reliance on ancillary testing were quantified on a 100-mm Visual Analog Scale (VAS) from least (0) to most (100). Data were collected on 417 ED patient encounters. CBs were reported in 46%; with a mean severity of 50 mm on a 100-mm VAS with endpoints of "perfect communication and "no communication." Language was the most commonly reported form of CB (28%). More than one CB was identified in 6%. The 100-mm VAS rating of diagnostic confidence was lower in patients with perceived CBs (64 mm) vs. those without CBs (80 mm), p < 0.001. VAS ratings of physician reliance on ancillary testing was higher in patients with perceived CBs (50 mm) vs. patients without a perceived CB (38 mm), p < 0.001. Communication barriers in our ED setting were common, and resulted in lower diagnostic confidence and increased perception that ancillary tests are needed to narrow the diagnosis. Copyright 2010 Elsevier Inc. All rights reserved.

Chemical Composition and Medicinal Value of the New Ganoderma tsugae var. jannieae CBS-120304 Medicinal Higher Basidiomycete Mushroom.

PubMed

Chan, Jannie Siew Lee; Asatiani, Mikheil D; Sharvit, Lital E; Trabelcy, Beny; Barseghyan, Gayane S; Wasser, Solomon P

2015-01-01

In this research, the chemical composition and anticancer and antioxidant activity of the new medicinal mushroom Ganoderma tsugae var. jannieae CBS-120304 were evaluated. The chemical composition assay includes amounts of total carbohydrates and proteins, amino acids, fatty acids, micro- and macroelements, and vitamins. The investigated medicinal mushroom seemed to be a rich source of nutritional components. Mycelium accumulated more than 2-fold more total protein compared with the fruiting body and reached 37% and 16% of dry weight, respectively. Carbohydrate content in the fruiting body seemed to be conspicuously higher than in the mycelium (50% of dry weight) and reached 80% of dry weight. Quantification of the identified fatty acids indicated that, in general, palmitic acid, oleic acid, and linoleic acid were the major fatty acids. Toxic elements, such as silver, arsenic, cadmium, and mercury, were found only in trace amounts in mycelium and were not detected in the fruiting body. Furthermore, the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay was used to evaluate antioxidant activity. The highest radical scavenging activity was 9.0 mg/mL (65.9%) by ethanol extract. In addition, mycelial extracts were tested to inhibit MCF7 breast cancer cells. Ganoderma tsugae var. jannieae ethyl acetate extract (GTEAE) extract showed high potential by inhibiting reporter activity by more than 70%. Results demonstrated that GTEAE had a strong effect on inhibitory protein κΒα level in the higher concentration used (200 gg/mL), which could be compared with the effect of parthenolide. Furthermore, GTEAE demonstrated strong inhibition of IκΒα phosphorylation.

Perspective on recent developments on sulfur-containing agents and hydrogen sulfide signaling.

PubMed

Jacob, Claus; Anwar, Awais; Burkholz, Torsten

2008-10-01

The last couple of years have witnessed the coming together of several initially unconnected lines of investigation which now link natural sulfur products to hydrogen sulfide release and wide ranging cardiovascular protection. It has become apparent that sulfur compounds contained within garlic, onions, mushrooms and various edible beans and fruits may be transformed chemically or enzymatically in the human body with subsequent formation of hydrogen sulfide. The latter has emerged during the last decade from a shadowy existence as toxic gas to be recognized as the third gaseous transmitter besides nitric oxide ( (.)NO) and carbon monoxide (CO). Hydrogen sulfide is formed endogenously in the human body by enzymes such as cystathionine beta-synthase (CBS) in the brain and cystathionine gamma-lyase (CSE) in liver, vascular and non-vascular smooth muscle. Although its exact chemical and biochemical modes of action are still not fully understood, levels of hydrogen sulfide in the brain and vasculature have unambiguously been associated with human health and disease. Not surprisingly, agents releasing hydrogen sulfide, as well as inhibitors of hydrogen sulfide synthesis (CBS and CSE inhibitors) have been investigated. Apart from linking our daily diet to a healthy brain and cardiovasculature, these findings may also provide new leads for drug design. Future studies will therefore need to focus on how such compounds are formed and transformed in the relevant plants, how food processing affects their chemical constitution, and how they release hydrogen sulfide (or control its levels) in the human body. Such multidisciplinary research should ultimately answer the all-important question if a hearty diet is also good for the heart.

Effectiveness of community-based support for pregnant women living with HIV: a cohort study in South Africa.

PubMed

Fatti, Geoffrey; Shaikh, Najma; Eley, Brian; Grimwood, Ashraf

2016-01-01

Antiretroviral treatment (ART) initiation in HIV-infected pregnant women in sub-Saharan Africa (SSA) remains inadequate, and there is a severe shortage of professional healthcare workers in the region. The effectiveness of community support programmes for HIV-infected pregnant women and their infants in SSA is unclear. This study compared initiation of maternal antiretrovirals and infant outcomes amongst HIV-infected pregnant women and their infants who received and did not receive community-based support (CBS) in a high HIV-prevalence setting in South Africa. A cohort study, including HIV-infected pregnant women and their infants, was conducted at three sentinel surveillance facilities between January 2009 and June 2012, utilising enhanced routine clinical data. Through home visits, CBS workers encouraged uptake of interventions in the ART cascade, provided HIV-related education, ART initiation counselling and psychosocial support. Outcomes were compared using Kaplan-Meier analyses and multivariable Cox and log-binomial regression. Amongst 1105 mother-infant pairs included, 264 (23.9%) received CBS. Amongst women eligible to start ART antenatally, women who received CBS had a reduced risk of not initiating antenatal ART, 5.4% vs. 30.3%; adjusted risk ratio (aRR) = 0.18 (95% CI: 0.08-0.44; P < .0001). Women who received CBS initiated antenatal ART with less delay after the first antenatal visit, median 26 days vs. 39 days; adjusted hazard ratio (aHR) = 1.57 (95% CI: 1.15-2.14; P = .004). Amongst women who initiated antenatal zidovudine (ZDV) to prevent vertical transmission, women who received CBS initiated ZDV with less delay, aHR = 1.52 (95% CI: 1.18-2.01; P = .001). Women who received CBS had a lower risk of stillbirth, 1.5% vs. 5.4%; aRR = 0.24 (95% CI: 0.07-1.00; P = .050). Pregnant women living with HIV who received CBS had improved antenatal triple ART initiation in eligible women, women initiated ART and ZDV with shorter delays, and had a lower risk of stillbirth. CBS is an intervention that shows promise in improving maternal and infant health in high HIV-prevalence settings.

Development of AN Innovative Three-Dimensional Complete Body Screening Device - 3D-CBS

NASA Astrophysics Data System (ADS)

Crosetto, D. B.

2004-07-01

This article describes an innovative technological approach that increases the efficiency with which a large number of particles (photons) can be detected and analyzed. The three-dimensional complete body screening (3D-CBS) combines the functional imaging capability of the Positron Emission Tomography (PET) with those of the anatomical imaging capability of Computed Tomography (CT). The novel techniques provide better images in a shorter time with less radiation to the patient. A primary means of accomplishing this is the use of a larger solid angle, but this requires a new electronic technique capable of handling the increased data rate. This technique, combined with an improved and simplified detector assembly, enables executing complex real-time algorithms and allows more efficiently use of economical crystals. These are the principal features of this invention. A good synergy of advanced techniques in particle detection, together with technological progress in industry (latest FPGA technology) and simple, but cost-effective ideas provide a revolutionary invention. This technology enables over 400 times PET efficiency improvement at once compared to two to three times improvements achieved every five years during the past decades. Details of the electronics are provided, including an IBM PC board with a parallel-processing architecture implemented in FPGA, enabling the execution of a programmable complex real-time algorithm for best detection of photons.

A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

PubMed

Pastor, Antoni; Fernández-Aranda, Fernando; Fitó, Montserrat; Jiménez-Murcia, Susana; Botella, Cristina; Fernández-Real, Jose M; Frühbeck, Gema; Tinahones, Francisco J; Fagundo, Ana B; Rodriguez, Joan; Agüera, Zaida; Langohr, Klaus; Casanueva, Felipe F; de la Torre, Rafael

2016-01-01

The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.

Using synchrotron X-ray microtomography to characterize the pore network of reservoir rocks: A case study on carbonates

NASA Astrophysics Data System (ADS)

Arzilli, F.; Cilona, A.; Mancini, L.; Tondi, E.

2016-09-01

In this work we propose a new methodology to calculate pore connectivity in granular rocks. This method is useful to characterize the pore networks of natural and laboratory compaction bands (CBs), and compare them with the host rock pore network. Data were collected using the synchrotron X-ray microtomography technique and quantitative analyses were carried out using the Pore3D software library. The porosity was calculated from segmented tridimensional images of deformed and pristine rocks. A process of skeletonization of the pore space was used to obtain the number of connected pores within the rock volume. By analyzing the skeletons the differences between natural and laboratory CBs were highlighted. The natural CB has a lower porosity than to the laboratory one. In natural CBs, the grain contacts appear welded, whereas laboratory CBs show irregular pore shape. Moreover, we assessed for the first time how pore connectivity evolves as a function of deformation, documenting the mechanism responsible for pore connectivity drop within the CBs.

Novel cystathionine β-synthase gene mutations in a Filipino patient with classic homocystinuria.

PubMed

Silao, Catherine Lynn T; Fabella, Terence Diane F; Rama, Kahlil Izza D; Estrada, Sylvia C

2015-10-01

Classic homocystinuria due to cystathionine β-synthase (CBS) deficiency is an autosomal recessive disorder of sulfur metabolism. Clinical manifestations include mental retardation, dislocation of the optic lens (ectopia lentis), skeletal abnormalities and a tendency to thromboembolic episodes. We present the first mutational analysis of CBS in a Filipino patient with classic homocystinuria. Genomic DNA was extracted from peripheral blood collected from a diagnosed Filipino patient with classic homocystinuria. The entire coding region of CBS (17 exons) was amplified using polymerase chain reaction and bidirectionally sequenced using standard protocols. The patient was found to be compound heterozygous for two novel mutations, g.13995G>A [c.982G>A; p.D328K] and g.15860-15868dupGCAGGAGCT [c.1083-1091dupGCAGGAGCT; p. Q362-L364dupQEL]. Four known single-nucleotide polymorphisms (rs234706, rs1801181, rs706208 and rs706209) were also detected in the present patient's CBS. The patient was heterozygous for all the identified alleles. This is the first mutational analysis of CBS done in a Filipino patient with classic homocystinuria who presented with a novel duplication mutation and a novel missense mutation. Homocystinuria due to CBS deficiency is a heterogeneous disorder at the molecular level. © 2015 Japan Pediatric Society.

Blink reflex recovery cycle to differentiate Progressive Supranuclear Palsy from Cortico-basal syndrome.

PubMed

Sciacca, Giorgia; Nicoletti, Alessandra; Mostile, Giovanni; Luca, Antonina; Raciti, Loredana; Dibilio, Valeria; Drago, Filippo; Salomone, Salvatore; Zappia, Mario

2018-05-13

Progressive Supranuclear Palsy (PSP) and Cortico-basal syndrome (CBS) may share similar clinical findings and peculiar tests to distinguish between the two disorders could be useful. We evaluated Blink Reflex (BR) and R2 Blink Reflex Recovery Cycle (R2BRRC), determining diagnostic sensitivity, specificity, positive and negative predictive value of R2BRRC in differentiating PSP from CBS patients. This was a prospective data collection study investigating BR and R2BRRC at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500, 750 ms in 12 PSP patients, 8 CBS patients, and 10 controls. Patients with PSP have earlier recruitment of R2BRRC as compared to patients with CBS (ISI 100: p=0.002; ISI 150: p<0.001; ISI 200: p<0.001; ISI 300: p=0.02) and controls (ISI 100: p<0.001; ISI 150: p<0.001; ISI 200: p<0.001; ISI 300: p=0.004). The presence of an early recovery of the R2 differentiated PSP from CBS with specificity and sensitivity of 87.5% and 91.7% respectively. R2BRRC curve might be considered a useful tool in differentiating PSP from CBS patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Role of nuclear bodies in apoptosis signalling.

PubMed

Krieghoff-Henning, Eva; Hofmann, Thomas G

2008-11-01

Promyelocytic leukemia nuclear bodies (PML NBs) are dynamic macromolecular multiprotein complexes that recruit and release a plethora of proteins. A considerable number of PML NB components play vital roles in apoptosis, senescence regulation and tumour suppression. The molecular basis by which PML NBs control these cellular responses is still just beginning to be understood. In addition to PML itself, numerous further tumour suppressors including transcriptional regulator p53, acetyl transferase CBP (CREB binding protein) and protein kinase HIPK2 (homeodomain interacting protein kinase 2) are recruited to PML NBs in response to genotoxic stress or oncogenic transformation and drive the senescence and apoptosis response by regulating p53 activity. Moreover, in response to death-receptor activation, PML NBs may act as nuclear depots that release apoptotic factors, such as the FLASH (FLICE-associated huge) protein, to amplify the death signal. PML NBs are also associated with other nuclear domains including Cajal bodies and nucleoli and share apoptotic regulators with these domains, implying crosstalk between NBs in apoptosis regulation. In conclusion, PML NBs appear to regulate cell death decisions through different, pathway-specific molecular mechanisms.

Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., sp. nov., Starmerella opuntiae f.a., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a., sp. nov., isolated from flowers and bees, and transfer of related Candida species to the genus Starmerella as new combinations.

PubMed

Santos, Ana Raquel O; Leon, Marina P; Barros, Katharina O; Freitas, Larissa F D; Hughes, Alice F S; Morais, Paula B; Lachance, Marc-André; Rosa, Carlos A

2018-04-01

Six novel yeast species, Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., Starmerella opuntiae f.a., sp. nov., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a, sp. nov. are proposed to accommodate 19 isolates recovered from ephemeral flowers or bees in Brazil, Costa Rica and Belize. Sequence analysis of the ITS-5.8S region (when available) and the D1/D2 domains of the large subunit of the rRNA gene showed that the six novel yeasts are phylogenetically related to several species of the Starmerella clade. The type strains are Starmerella camargoi f.a., sp. nov. UFMG-CM-Y595 T (=CBS 14130 T ; Mycobank number MB 822640), Starmerella ilheusensis f.a., sp. nov. UFMG-CM-Y596 T (=CBS CBS14131 T ; MB 822641), Starmerella litoralis f.a., sp. nov. UFMG-CM-Y603 T (=CBS14104 T ; MB 822642), Starmerella opuntiae f.a., sp. nov. UFMG-CM-Y286 T (=CBS 13466 T ; MB 822643), Starmerella roubikii f.a., sp. nov. UWOPS 01-191.1 (=CBS 15148; MB 822645) and Starmerella vitae f.a., sp. nov. UWOPS 00-107.2 (=CBS 15147 T ; MB 822646). In addition, 25 species currently assigned to the genus Candida are reassigned formally to the genus Starmerella.

Yamadazyma kitorensis f.a., sp. nov. and Zygoascus biomembranicola f.a., sp. nov., novel yeasts from the stone chamber interior of the Kitora tumulus, and five novel combinations in Yamadazyma and Zygoascus for species of Candida.

PubMed

Nagatsuka, Yuka; Ninomiya, Shinya; Kiyuna, Tomohiko; Kigawa, Rika; Sano, Chie; Sugiyama, Junta

2016-04-01

Analysis of D1/D2 large-subunit (LSU) rRNA gene sequences predicted that 17 yeast isolates, mainly from viscous gels (biofilms) taken from the stone chamber interior of the Kitora tumulus in Nara, Japan, were placed in the Yamadazyma and Zygoascus clades. Polyphasic characterization, including morphological, physiological and chemotaxonomic characteristics, multigene sequence divergence and DNA-DNA hybridization, strongly suggested the assignment of one novel species to each of the clades; these are Yamadazyma kitorensis f.a., sp. nov., with the type strain JCM 31005T (ex-type CBS 14158T=isolate K8617-6-8T), and Zygoascus biomembranicola f.a., sp. nov., with the type strain JCM 31007T (ex-type CBS 14157T=isolate K61208-2-11T). Furthermore, the transfer of five known species of the genus Candida as novel combinations to the genera Yamadazyma and Zygoascus is proposed; these are Yamadazyma olivae f.a., comb. nov. (type strain CBS 11171T=ATCC MYA-4568T), Yamadazyma tumulicola f.a., comb. nov. (type strain JCM 15403T=ex-type CBS 10917T=isolate T6517-9-5T), Yamadazyma takamatsuzukensis f.a., comb. nov. (type strain JCM 15410T=CBS 10916T = isolate T4922-1-1T), Zygoascus polysorbophila f.a., comb. nov. (type strain NRRL Y-27161T=CBS 7317T) and Zygoascus bituminiphila f.a., comb. nov. (type strain CBS 8813T=MUCL 41424T).

Hallucinatory experiences in visually impaired individuals: Charles Bonnet syndrome - implications for research and clinical practice.

PubMed

Jurišić, Darija; Sesar, Irena; Ćavar, Ivan; Sesar, Antonio; Živković, Maja; Ćurković, Marko

2018-06-01

Charles Bonnet syndrome (CBS) refers to visual hallucinations that occur in individuals with preserved cognitive functions associated with visual impairment. This article reviews occurence of visual hallucinations in subjects with CBS by journals published in English in the Pubmed database in the period 1992-2018. Criteria for selection of appropriate papers were sufficient information and perspicuous view on pathogenesis, epidemiology, clinical presentation and treatment possibilities of CBS. Most commonly, visual hallucinations in patients with CBS are complex, repetitive and stereotyped. Such individuals have preserved insight that those percepts are not real, and there is an absence of secondary explanatory delusions and hallucinations within other modalities. Seeing as the aforementioned percepts do not share all the characteristics of hallucinations, it remains unresolved how they should be referred to. Terms as release hallucinations, one that is reflecting its underlying pathogenesis, or confabulatory hallucinatory experiences have been proposed. Moreover, CBS has also been referred to as phantom vision syndrome and may occur in any ophthalmological disease. It is not particularly connected with loss of function along any level of the visual pathway. Although this syndrome is mostly associated with age-related macular degeneration, glaucoma and cataract, it could be related to almost any other ophthalmological conditions. The incidence of CBS alongside with mostly other ocular pathology is rising as population is ageing. Nonetheless, CBS remains commonly underreported, under recognized and/or misrecognized. Albeit the treatment recommendations and guidelines are not yet fully established, it is important to raise awareness of this specific and distinct condition, which inevitably implicates many differential diagnostic deliberations.

Charles Bonnet Syndrome: Evidence for a Generative Model in the Cortex?

PubMed Central

Reichert, David P.; Seriès, Peggy; Storkey, Amos J.

2013-01-01

Several theories propose that the cortex implements an internal model to explain, predict, and learn about sensory data, but the nature of this model is unclear. One condition that could be highly informative here is Charles Bonnet syndrome (CBS), where loss of vision leads to complex, vivid visual hallucinations of objects, people, and whole scenes. CBS could be taken as indication that there is a generative model in the brain, specifically one that can synthesise rich, consistent visual representations even in the absence of actual visual input. The processes that lead to CBS are poorly understood. Here, we argue that a model recently introduced in machine learning, the deep Boltzmann machine (DBM), could capture the relevant aspects of (hypothetical) generative processing in the cortex. The DBM carries both the semantics of a probabilistic generative model and of a neural network. The latter allows us to model a concrete neural mechanism that could underlie CBS, namely, homeostatic regulation of neuronal activity. We show that homeostatic plasticity could serve to make the learnt internal model robust against e.g. degradation of sensory input, but overcompensate in the case of CBS, leading to hallucinations. We demonstrate how a wide range of features of CBS can be explained in the model and suggest a potential role for the neuromodulator acetylcholine. This work constitutes the first concrete computational model of CBS and the first application of the DBM as a model in computational neuroscience. Our results lend further credence to the hypothesis of a generative model in the brain. PMID:23874177

Cajal and the Conceptual Weakness of Neural Sciences

PubMed Central

Delgado-García, José M.

2015-01-01

The experimental and conceptual contributions of Santiago Ramón y Cajal remain almost as fresh and valuable as when his original proposals were published more than a century ago—a rare example, contrasting with other related sciences. His basic concepts on the neuron as the main building block of the central nervous system, the dynamic polarization principle as a way to understand how neurons deal with ongoing active processes, and brain local structural arrangements as a result of the functional specialization of selected neural circuits are concepts still surviving in present research papers dealing with brain function during the performance of cognitive and/or behavioral activities. What is more, the central dogma of the Neuroscience of today, i.e., brain plasticity as the morpho-functional substrate of memory and learning processes, was already proposed and documented with notable insights by Ramón y Cajal. From this background, I will try to discuss in this chapter which new functional and structural concepts have been introduced in contemporary Neuroscience and how we will be able to construct a set of basic principles underlying brain functions for the twenty-first century. PMID:26483644

Santiago Ramón y Cajal and Ivan Petrovic Pavlov: their parallel scientific lives, schools and nobel prizes.

PubMed

Rozo, Jairo A; Rodríguez-Moreno, Antonio

2015-01-01

Santiago Ramón y Cajal was not only a great scientist but he was also a dedicated teacher who managed to create his own School in Spain. Cajal was active at the end of the XIX and the beginning of the XX century, a period in which Ivan Petrovich Pavlov, another great contemporary scientist, also established a strong School in Russia. While these two acclaimed scientists shared a similar vision on science, a view they also conveyed to their disciples, they applied quite distinct criteria in the way they dealt with their followers. Interestingly, despite the geographic and idiomatic barriers that had to be overcome, the paths of these two great figures of XX century science crossed at least three times. First when they competed for the City of Moscow Prize, second when they both attended the "Congreso Internacional de Medicina de Madrid" (Medicine International Congress in Madrid) in 1903 and finally, they competed on four consecutive occasions for the Nobel Prize in Physiology or Medicine. Here we discuss their scientific vision, their different attitudes in the interaction with disciples and the distinct circumstances in which their paths crossed.

Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel.

PubMed

Yamada, Toshiki; Krzeminski, Mickael; Bozoky, Zoltan; Forman-Kay, Julie D; Strange, Kevin

2016-11-01

Eukaryotic CLC anion channels and transporters are homodimeric proteins composed of multiple α-helical membrane domains and large cytoplasmic C-termini containing two cystathionine-β-synthase domains (CBS1 and CBS2) that dimerize to form a Bateman domain. The Bateman domains of adjacent CLC subunits interact to form a Bateman domain dimer. The functions of CLC CBS and Bateman domains are poorly understood. We utilized the Caenorhabditis elegans CLC-1/2/Ka/Kb anion channel homolog CLH-3b to characterize the regulatory roles of CLC cytoplasmic domains. CLH-3b activity is reduced by phosphorylation or deletion of a 14-amino-acid activation domain (AD) located on the linker connecting CBS1 and CBS2. We demonstrate here that phosphorylation-dependent reductions in channel activity require an intact Bateman domain dimer and concomitant phosphorylation or deletion of both ADs. Regulation of a CLH-3b AD deletion mutant is reconstituted by intracellular perfusion with recombinant 14-amino-acid AD peptides. The sulfhydryl reactive reagent 2-(trimethylammonium)ethyl methanethiosulfonate bromide (MTSET) alters in a phosphorylation-dependent manner the activity of channels containing single cysteine residues that are engineered into the short intracellular loop connecting membrane α-helices H and I (H-I loop), the AD, CBS1, and CBS2. In contrast, MTSET has no effect on channels in which cysteine residues are engineered into intracellular regions that are dispensable for regulation. These studies together with our previous work suggest that binding and unbinding of the AD to the Bateman domain dimer induces conformational changes that are transduced to channel membrane domains via the H-I loop. Our findings provide new, to our knowledge, insights into the roles of CLC Bateman domains and the structure-function relationships that govern the regulation of CLC protein activity by diverse ligands and signaling pathways. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Characterization of the secreted cathepsin B cysteine proteases family of the carcinogenic liver fluke Clonorchis sinensis.

PubMed

Chen, Wenjun; Wang, Xiaoyun; Lv, Xiaoli; Tian, Yanli; Xu, Yanquan; Mao, Qiang; Shang, Mei; Li, Xuerong; Huang, Yan; Yu, Xinbing

2014-09-01

Clonorchis sinensis excretory/secretory products (ESP) have gained high attentions because of their potential to be vaccine candidates and drug targets in C. sinensis prevention. In this study, we extensively profiled the characteristics of four C. sinensis cathepsin B cysteine proteases (CsCB1, CsCB2, CsCB3, and CsCB4). Bioinformatics analysis showed all CsCBs contained signal peptides at the N-terminal. Functional domains and residues were found in CsCB sequences. We expressed four CsCBs and profiled immune responses followed by vaccine trials. Recombinant CsCBs could induce high IgG titers, indicating high immunogenicity of CsCB family. Additionally, ELISA results showed that both IgG1 and IgG2a levels apparently increased post-immunization with all four CsCBs, showing that combined Th1/Th2 immune responses were triggered by CsCB family. Both Real-time polymerase chain reaction (RT-PCR) and Western blotting confirmed that four CsCBs have distinct expression patterns in C. sinensis life stages. More importantly, we validated our hypothesis that CsCBs were C. sinensis excretory/secretory products. CsCBs could be recognized by C. sinensis-infected sera throughout the infection period, indicating that secreted CsCBs are immune triggers during C. sinensis infection. The protective effect was assessed by comparing the worm burden and egg per gram (EPG) between CsCB group and control group, showing that worm burden (P < 0.01) and EPG (P < 0.01) in CsCB2 and CsCB3 groups were significantly lower than in control group. In conclusion, we profiled secreted cathepsin B cysteine proteases family for the first time and demonstrated that all CsCB family were C. sinensis excretory/secretory products that may regulate host immune responses.

Heterozygous carriers of classical homocystinuria tend to have higher fasting serum homocysteine concentrations than non-carriers in the presence of folate deficiency.

PubMed

Lu, Yung-Hsiu; Cheng, Li-Mei; Huang, Yu-Hsiu; Lo, Ming-Yu; Wu, Tina Jui-Ting; Lin, Hsiang-Yu; Hsu, Ting-Rong; Niu, Dau-Ming

2015-12-01

Many studies have reported that serum total homocysteine (tHcy) levels in cystathionine-beta-synthase (CBS) carriers are usually normal and only elevated after a methionine load. However, the amount of methionine required for a loading test is non-physiological and is never reached with regular feeding. Therefore, CBS carriers do not seem to be at an increased risk of cardiovascular diseases. However, the risk of cardiovascular diseases of CBS carriers with folate deficiency has not been studied. We recently found an extraordinarily high carrier rate (1/7.78) of a novel CBS mutation (p.D47E, c.T141A) in an Austronesian Taiwanese Tao tribe who live in a geographic area with folate deficiency. We evaluated if the CBS carriers tend to have higher fasting serum tHcy concentrations than non-carriers in presence of folate deficiency. The serum tHcy and folate levels before and after folate replacement were measured in 48 adult Tao carriers, 40 age-matched Tao non-carriers and 40 age-matched Han Taiwanese controls. The serum tHcy level of the Tao CBS carriers (17.9 ± 3.8 μmol/l) was significantly higher than in Tao non-carriers (15.7 ± 3.5 μmol/l; p < 0.008) and Taiwanese controls (11.8 ± 2.9 μmol/l; p < 0.001). Furthermore, a high prevalence of folate deficiency in the Tao compared with the Taiwanese controls (4.9 ± 1.8 ng/ml vs. 10.6 ± 5.5 ng/ml; p < 0.001) was also noted. Of note, the difference in tHcy levels between the carriers and non-carriers was eliminated by folate supplementation. (carriers:13.65 ± 2.13 μmol/l; non-carriers:12.39 ± 3.25 μmol/l, p = 0.321). CBS carriers tend to have a higher tHcy level in the presence of folate deficiency than non-carriers. Although many reports have indicated that CBS carriers are not associated with cardiovascular disease, the risk for CBS carriers with folate deficiency has not been well studied. Owing to a significantly elevated level of fasting tHcy without methionine loading, it is important to evaluate the risk of cardiovascular disease in CBS carriers with folate deficiency. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

High homocysteine induces betaine depletion

PubMed Central

Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J.

2015-01-01

Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI—LC–MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. PMID:26182429

High homocysteine induces betaine depletion.

PubMed

Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

2015-04-28

Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. © 2015 Author(s).

A Practical Note on Transferring Ideas and Methods from Consultancy Practice to the MPA Classroom: A Personal Account from a Danish Case Study

ERIC Educational Resources Information Center

Nielsen, J. C. Ry; Quinn, Brid

2016-01-01

At the lead author's home institution--Copenhagen Business School (CBS)--the combination of theory and practice is seen as very important in teaching. Research-based teaching is the slogan. In this respect, CBS has the same ambition as other universities. But it seems as if CBS has an advantage at the master's level, because students come with a…

Culture-Bound Syndromes of a Brazilian Amazon Riverine population: Tentative correspondence between traditional and conventional medicine terms and possible ethnopharmacological implications.

PubMed

Pagani, E; Santos, J de F L; Rodrigues, E

2017-05-05

It is not always possible to correlate the "emic" terms to the "etic" ones during ethnopharmacological surveys, especially regarding those related to Culture-Bound Syndromes (CBS). Nevertheless, it is the role of ethnopharmacology to address these correlations, since they are the basis for the understanding of potential bioactives. This study reports the clinical manifestations and therapeutic resources used for the treatment of CBS among some riverine inhabitants of Brazilian Amazonia. An effort was made to establish a correspondence between the local "emic" terms of traditional medicine and the symptoms or diseases known by conventional medicine ("etic" terms). The ultimate goal was to gain insights to suggest further pharmacological studies with the local resources. Fieldwork was guided by methods of anthropology, botany and zoology-with the assistance of a doctor-among the traditional healing experts in Jaú National Park (during 199 days in 1995) and Unini River Extractive Reserve (210 days from 2008 to 2012). Fifty-nine healers of different kinds were interviewed: a prayer-maker, medium, natural resource expert, massage therapist, midwife and snakebite healer. The clinical manifestations and healing resources of the following CBS were collected: "mau olhado" (evil eye), "quebrante" (chipping); "espante" (fright or susto); "doença do ar" (air diseases); "vento caído" (fallen wind); "derrame" (leakage); "mãe do corpo" (mother of the body) and "panema" (unlucky). The first three seem to be local variations of other CBSs already described in Latin America. "doença do ar", "vento caído", "derrame" and "mãe do corpo" seem to be folk terms for known conventional medical disorders, while "panema" is a yet undescribed Brazilian CBS that is possibly related to dysthymic disorder or depression and deserves further investigation. Treatments included prayer rituals, fumigation, baths and oral remedies using 25 plants and 10 animals. It was possible to establish hypothetical correlations between CBS as described by the riverine population studied and some "etic" terms. The main importance of this is to help the proposition of target-oriented pharmacological studies of the natural resources used by these communities. Accordingly, the following plants are suggested to be submitted to further studies for antidepressant and anxiolytic activities: Siparuna guianensis, Mansoa alliacea, Leucas martinicensis, Petiveria alliacea, Annona montana and Alpinia nutans; for anti-seizure activity: Protium amazonicum, Protium aracouchini and Protium heptaphyllum; finally for antispasmodic activity: Leucas martinicensis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Yeasts associated with the curculionid beetle Xyloterinus politus: Candida xyloterini sp. nov., Candida palmyrensis sp. nov. and three common ambrosia yeasts.

PubMed

Suh, Sung-Oui; Zhou, Jianlong

2010-07-01

Seven yeast strains were isolated from the body surface and galleries of Xyloterinus politus, the ambrosia beetle that attacks black oak trees. Based on rDNA sequence comparisons and other taxonomic characteristics, five of the strains were identified as members of the species Saccharomycopsis microspora, Wickerhamomyces hampshirensis and Candida mycetangii, which have been reported previously as being associated with insects. The remaining two yeast strains were proposed as representatives of two novel species, Candida xyloterini sp. nov. (type strain ATCC 62898(T)=CBS 11547(T)) and Candida palmyrensis sp. nov. (type strain ATCC 62899(T)=CBS 11546(T)). C. xyloterini sp. nov. is a close sister taxon to Ogataea dorogensis and assimilates methanol as a sole carbon source but lacks ascospores. On the other hand, C. palmyrensis sp. nov. is phylogenetically distinct from any other ambrosia yeast reported so far. The species was placed near Candida sophiae-reginae and Candida beechii based on DNA sequence analyses, but neither of these were close sister taxa to C. palmyrensis sp. nov.

Scientific progress and the prospects for culture-bound syndromes.

PubMed

Blease, Charlotte

2010-12-01

This paper aims to show that the classification by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual of Mental Disorders (DSM) of a distinct listing of disorders known as Culture-Bound Syndromes (CBS) is misguided. I argue that the list of CBS (in Appendix I of the manual) comprises either (a) genuine disorders that should be included within the main body of the DSM; or (b) ersatz-disorders that serve a practical role for psychiatrists dealing with patients from certain cultures but will one day be eliminated or assimilated by bona fide DSM classifications. In support of these views I draw on claims from two key themes in the philosophy of science: (1) the claim that all folk (that is, non-scientific) explanations for phenomena are thoroughly theoretical and therefore fallible; and (2) the occurrence of theoretical elimination in the history of science. I contend that any ersatz-disorders located in the DSM that are judged to be radically false do not differ in kind from eliminated theories in the history of pre-science. Copyright © 2010 Elsevier Ltd. All rights reserved.

Candida oceani sp. nov., a novel yeast isolated from a Mid-Atlantic Ridge hydrothermal vent (-2300 meters).

PubMed

Burgaud, Gaëtan; Arzur, Danielle; Sampaio, José Paulo; Barbier, Georges

2011-06-01

A novel species in the genus Candida was obtained from deep-sea hydrothermal fields on the Mid-Atlantic Ridge. Strains Mo39, MARY089 and CBS 5307, respectively, isolated from an unidentified deep-sea coral collected near Rainbow hydrothermal vent, from water samples near Menez Gwen hydrothermal field and from the stomach of a marine fish are considered as a novel taxon. Sequence similarities in the D1/D2 region of the 26S rRNA gene indicated that strains Mo39, MARY089 and CBS 5307 have for closest neighbors Candida spencermartinsiae, Candida taylorii, Candida atmosphaerica and Candida atlantica. The strains, respectively, differ from C. spencermartinsiae, C. taylorii, C. atmosphaerica andCandida atlantica by 4, 4.3, 4.3 and 4.7% in the D1/D2 domain. Strains Mo39, MARY089 and CBS 5307 were differentiated from others by differences in the ability to assimilate D: -Gluconate and in the ability to grow at relatively high temperature. Only strain Mo39 displays an optimal growth at 3% sea salts, indicating that this strain is clearly adapted to live in marine conditions. Sequence similarities between strains Mo39, MARY089 and CBS 5307 and related species and differences in the ability to utilize specific carbon compounds revealed that these strains represent a hitherto unknown species. Sexual reproduction was not observed in strains Mo39, MARY089 and CBS 5307. An anamorphic name Candida oceani sp. nov. is proposed for the type strain Mo39(T) (= CBS 11857(T) = DSM 23777(T)) and the two other strains MARY089 and CBS 5307. To our knowledge, this is the first description of a micro-eukaryotic organism including a strain isolated from a deep-sea coral near a hydrothermal ecosystem.

Crystallographic and mutational analyses of cystathionine β-synthase in the H2 S-synthetic gene cluster in Lactobacillus plantarum.

PubMed

Matoba, Yasuyuki; Yoshida, Tomoki; Izuhara-Kihara, Hisae; Noda, Masafumi; Sugiyama, Masanori

2017-04-01

Cystathionine β-synthase (CBS) catalyzes the formation of l-cystathionine from l-serine and l-homocysteine. The resulting l-cystathionine is decomposed into l-cysteine, ammonia, and α-ketobutylic acid by cystathionine γ-lyase (CGL). This reverse transsulfuration pathway, which is catalyzed by both enzymes, mainly occurs in eukaryotic cells. The eukaryotic CBS and CGL have recently been recognized as major physiological enzymes for the generation of hydrogen sulfide (H 2 S). In some bacteria, including the plant-derived lactic acid bacterium Lactobacillus plantarum, the CBS- and CGL-encoding genes form a cluster in their genomes. Inactivation of these enzymes has been reported to suppress H 2 S production in bacteria; interestingly, it has been shown that H 2 S suppression increases their susceptibility to various antibiotics. In the present study, we characterized the enzymatic properties of the L. plantarum CBS, whose amino acid sequence displays a similarity with those of O-acetyl-l-serine sulfhydrylase (OASS) that catalyzes the generation of l-cysteine from O-acetyl-l-serine (l-OAS) and H 2 S. The L. plantarum CBS shows l-OAS- and l-cysteine-dependent CBS activities together with OASS activity. Especially, it catalyzes the formation of H 2 S in the presence of l-cysteine and l-homocysteine, together with the formation of l-cystathionine. The high affinity toward l-cysteine as a first substrate and tendency to use l-homocysteine as a second substrate might be associated with its enzymatic ability to generate H 2 S. Crystallographic and mutational analyses of CBS indicate that the Ala70 and Glu223 residues at the substrate binding pocket are important for the H 2 S-generating activity. © 2017 The Protein Society.

D-Xylose fermentation, xylitol production and xylanase activities by seven new species of Sugiyamaella.

PubMed

Sena, Letícia M F; Morais, Camila G; Lopes, Mariana R; Santos, Renata O; Uetanabaro, Ana P T; Morais, Paula B; Vital, Marcos J S; de Morais, Marcos A; Lachance, Marc-André; Rosa, Carlos A

2017-01-01

Sixteen yeast isolates identified as belonging to the genus Sugiyamaella were studied in relation to D-xylose fermentation, xylitol production, and xylanase activities. The yeasts were recovered from rotting wood and sugarcane bagasse samples in different Brazilian regions. Sequence analyses of the internal transcribed spacer (ITS) region and the D1/D2 domains of large subunit rRNA gene showed that these isolates belong to seven new species. The species are described here as Sugiyamaella ayubii f.a., sp. nov. (UFMG-CM-Y607 T  = CBS 14108 T ), Sugiyamaella bahiana f.a., sp. nov. (UFMG-CM-Y304 T  = CBS 13474 T ), Sugiyamaella bonitensis f.a., sp. nov. (UFMG-CM-Y608 T  = CBS 14270 T ), Sugiyamaella carassensis f.a., sp. nov. (UFMG-CM-Y606 T  = CBS 14107 T ), Sugiyamaella ligni f.a., sp. nov. (UFMG-CM-Y295 T  = CBS 13482 T ), Sugiyamaella valenteae f.a., sp. nov. (UFMG-CM-Y609 T  = CBS 14109 T ) and Sugiyamaella xylolytica f.a., sp. nov. (UFMG-CM-Y348 T  = CBS 13493 T ). Strains of the described species S. boreocaroliniensis, S. lignohabitans, S. novakii and S. xylanicola, isolated from rotting wood of Brazilian ecosystems, were also compared for traits relevant to xylose metabolism. S. valenteae sp. nov., S. xylolytica sp. nov., S. bahiana sp. nov., S. bonitensis sp. nov., S. boreocarolinensis, S. lignohabitans and S. xylanicola were able to ferment D-xylose to ethanol. Xylitol production was observed for all Sugiyamaella species studied, except for S. ayubii sp. nov. All species studied showed xylanolytic activity, with S. xylanicola, S. lignohabitans and S. valenteae sp. nov. having the highest values. Our results suggest these Sugiyamaella species have good potential for biotechnological applications.

Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats.

PubMed

Koch, Diana A; Silva, Rodrigo B M; de Souza, Alessandra H; Leite, Carlos E; Nicoletti, Natália F; Campos, Maria M; Laufer, Stefan; Morrone, Fernanda B

2014-03-01

Mitogen-activated protein kinase (MAPK) p38 inhibitors have entered the clinical phase, although many of them have failed due to high toxicity and lack of efficacy. In the present study we compared the effects of the selective p38 inhibitor ML3403 and the dual p38-PDE4 inhibitor CBS-3595, on inflammatory and nociceptive parameters in a model of polyarthritis in rats. Male Wistar rats (180-200 g) were used for the complete Freund's adjuvant (CFA)-induced arthritis model and they were evaluated at 14-21 days. We also analysed the effects of these pharmacological tools on liver and gastrointestinal toxicity and on cytokine levels. Repeated CBS-3595 (3 mg/kg) or ML3403 (10 mg/kg) administration produced significant anti-inflammatory actions in the chronic arthritis model induced by CFA. CBS-3595 and ML3403 treatment also markedly reduced the production of the proinflammatory cytokine IL-6 in the paw tissue, whereas it widely increased the levels of the anti-inflammatory cytokine IL-10. Moreover, CBS-3595 produced partial anti-allodynic effects in the CFA model at 4 and 8 days after treatment. Notably, ML3403 and CBS-3595 did not show marked signs of hepatoxicity, as supported by unaltered histological observations in the liver sections. Finally, both compounds were safe in the gastrointestinal tract, according to evaluation of intestinal biopsies. CBS-3595 displayed a superior profile regarding its anti-inflammatory effects. Thus p38 MAPK/PDE4 blocking might well constitute a relevant strategy for the treatment of RA.

Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

PubMed Central

Beard, Richard S.

2011-01-01

Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is converted to hydrogen sulfide (H2S) through the transsulfuration pathway. H2S has attracted considerable attention in recent years for many positive effects on vascular health and homeostasis. Cystathionine β-synthase (CBS) is the first, and rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene decrease enzymatic activity, which increases the plasma Hcy concentration, a condition called hyperhomocysteinemia (HHcy). Animal models of CBS deficiency have provided invaluable insights into the pathological effects of transsulfuration impairment and of both mild and severe HHcy. However, studies have also highlighted the complexity of HHcy and the need to explore the specific details of Hcy metabolism in addition to Hcy levels per se. There has been a relative paucity of work addressing the dysfunctional H2S production in CBS deficiency that may contribute to, or even create, HHcy-associated pathologies. Experiments using CBS knockout mice, both homozygous (−/−) and heterozygous (+/−), have provided 15 years of new knowledge and are the focus of this review. These murine models present the opportunity to study a specific mechanism for HHcy that matches one of the etiologies in many human patients. Therefore, the goal of this review was to integrate and highlight the critical information gained thus far from models of CBS deficiency and draw attention to critical gaps in knowledge, with particular emphasis on the modulation of H2S metabolism. We include findings from human and animal studies to identify important opportunities for future investigation that should be aimed at generating new basic and clinical understanding of the role of CBS and transsulfuration in cardiovascular and neurovascular disease. PMID:20971760

A Model for the Stop Planning and Timetables of Customized Buses

PubMed Central

Yang, Yang

2017-01-01

Customized buses (CBs) are a new mode of public transportation and an important part of diversified public transportation, providing advanced, attractive and user-led service. The operational activity of a CB is planned by aggregating space–time demand and similar passenger travel demands. Based on an analysis of domestic and international research and the current development of CBs in China and considering passenger travel data, this paper studies the problems associated with the operation of CBs, such as stop selection, line planning and timetables, and establishes a model for the stop planning and timetables of CBs. The improved immune genetic algorithm (IIGA) is used to solve the model with regard to the following: 1) multiple population design and transport operator design, 2) memory library design, 3) mutation probability design and crossover probability design, and 4) the fitness calculation of the gene segment. Finally, a real-world example in Beijing is calculated, and the model and solution results are verified and analyzed. The results illustrate that the IIGA solves the model and is superior to the basic genetic algorithm in terms of the number of passengers, travel time, average passenger travel time, average passenger arrival time ahead of schedule and total line revenue. This study covers the key issues involving operational systems of CBs, combines theoretical research and empirical analysis, and provides a theoretical foundation for the planning and operation of CBs. PMID:28056041

A Model for the Stop Planning and Timetables of Customized Buses.

PubMed

Ma, Jihui; Zhao, Yanqing; Yang, Yang; Liu, Tao; Guan, Wei; Wang, Jiao; Song, Cuiying

2017-01-01

Customized buses (CBs) are a new mode of public transportation and an important part of diversified public transportation, providing advanced, attractive and user-led service. The operational activity of a CB is planned by aggregating space-time demand and similar passenger travel demands. Based on an analysis of domestic and international research and the current development of CBs in China and considering passenger travel data, this paper studies the problems associated with the operation of CBs, such as stop selection, line planning and timetables, and establishes a model for the stop planning and timetables of CBs. The improved immune genetic algorithm (IIGA) is used to solve the model with regard to the following: 1) multiple population design and transport operator design, 2) memory library design, 3) mutation probability design and crossover probability design, and 4) the fitness calculation of the gene segment. Finally, a real-world example in Beijing is calculated, and the model and solution results are verified and analyzed. The results illustrate that the IIGA solves the model and is superior to the basic genetic algorithm in terms of the number of passengers, travel time, average passenger travel time, average passenger arrival time ahead of schedule and total line revenue. This study covers the key issues involving operational systems of CBs, combines theoretical research and empirical analysis, and provides a theoretical foundation for the planning and operation of CBs.

Driving towards malaria elimination in Botswana by 2018: progress on case-based surveillance, 2013–2014

PubMed Central

Edwards, J.; Namboze, J.; Butt, W.; Moakofhi, K.; Obopile, M.; Manzi, M.; Takarinda, K. C.; Zachariah, R.; Owiti, P.; Oumer, N.; Mosweunyane, T.

2018-01-01

Background: Reliable information reporting systems ensure that all malaria cases are tested, treated and tracked to avoid further transmission. Botswana aimed to eliminate malaria by 2018, and surveillance is key. This study focused on assessing the uptake of the new malaria case-based surveillance (CBS) system introduced in 2012, which captures information on malaria cases reported in the Integrated Disease Surveillance and Response (IDSR) system. Methods: This was a retrospective descriptive study based on routine data focusing on Ngami, Chobe and Okavango, three high-risk districts in Botswana. Aggregated data variables were extracted from the IDSR and compared with data from the CBS. Results: The IDSR reported 456 malaria cases in 2013 and 1346 in 2014, of which respectively only 305 and 884 were reported by the CBS. The CBS reported 34% fewer cases than the IDSR system, indicating substantial differences between the two systems. The key malaria indicators with the greatest variability among the districts included in the study were case identification number and date of diagnosis. Conclusion: The IDSR and CBS systems are essential for malaria elimination, as shown by the significant gaps in reporting between the two systems. These findings highlight the need for further investigation into these discrepancies. Strengthening the CBS system will help to reach the objective of malaria elimination in Botswana. PMID:29713590

The role of surface electrostatics on the stability, function and regulation of human cystathionine β-synthase, a complex multidomain and oligomeric protein.

PubMed

Pey, Angel L; Majtan, Tomas; Kraus, Jan P

2014-09-01

Human cystathionine β-synthase (hCBS) is a key enzyme of sulfur amino acid metabolism, controlling the commitment of homocysteine to the transsulfuration pathway and antioxidant defense. Mutations in hCBS cause inherited homocystinuria (HCU), a rare inborn error of metabolism characterized by accumulation of toxic homocysteine in blood and urine. hCBS is a complex multidomain and oligomeric protein whose activity and stability are independently regulated by the binding of S-adenosyl-methionine (SAM) to two different types of sites at its C-terminal regulatory domain. Here we study the role of surface electrostatics on the complex regulation and stability of hCBS using biophysical and biochemical procedures. We show that the kinetic stability of the catalytic and regulatory domains is significantly affected by the modulation of surface electrostatics through noticeable structural and energetic changes along their denaturation pathways. We also show that surface electrostatics strongly affect SAM binding properties to those sites responsible for either enzyme activation or kinetic stabilization. Our results provide new insight into the regulation of hCBS activity and stability in vivo with implications for understanding HCU as a conformational disease. We also lend experimental support to the role of electrostatic interactions in the recently proposed binding modes of SAM leading to hCBS activation and kinetic stabilization. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcultural validation of the ALS-CBS Cognitive Section for the Brazilian population.

PubMed

Branco, Lucas M T; Zanao, Tamires; De Rezende, Thiago J; Casseb, Raphael F; Balthazar, Marcio F; Woolley, Susan C; França, Marcondes C

2017-02-01

Cognitive decline (CD) is common but often under-recognized in ALS due to the scarcity of adequate cognitive screening methods. In this scenario, the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) is the most investigated instrument and presents high sensitivity to identify CD. Currently, there are no validated cognitive screening tools for ALS patients in the Brazilian population and little is known about the frequency of ALS related CD in the country. We assessed the accuracy of the Brazilian Portuguese version of ALS-CBS Cognitive Section (ALS-CBS-Br) for classifying the cognitive status of Brazilian patients compared to a standard neuropsychological battery, and estimated the prevalence of CD in the Brazilian ALS population. Among 73 initially recruited ALS patients, 49 were included. Twenty-four patients were excluded due to severe motor disability, FTD diagnosis or non-acceptance. Ten healthy controls were also included. Ten ALS patients (20%) were diagnosed with executive dysfunction (ALSci) based on the battery results. ALS-CBS-Br scores were significantly lower in the ALSci group (p < 0.001). The scale accuracy in detecting executive dysfunction was 0.906. Optimal cut-off score was 10/20 (specificity 0.872 and sensitivity 0.900). In conclusion, the ALS-CBS-Br may facilitate the recognition of CD in routine clinical care and complement future studies in our population.

THE ENDOCANNABINOID SYSTEM MODULATES THE VALENCE OF THE EMOTION ASSOCIATED TO FOOD INGESTION

PubMed Central

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, O.

2010-01-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant, or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide and if such CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. PMID:21182571

Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

PubMed Central

Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

2016-01-01

Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

PubMed

Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

2016-05-01

Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders.

Driving towards malaria elimination in Botswana by 2018: progress on case-based surveillance, 2013-2014.

PubMed

Motlaleng, M; Edwards, J; Namboze, J; Butt, W; Moakofhi, K; Obopile, M; Manzi, M; Takarinda, K C; Zachariah, R; Owiti, P; Oumer, N; Mosweunyane, T

2018-04-25

Background: Reliable information reporting systems ensure that all malaria cases are tested, treated and tracked to avoid further transmission. Botswana aimed to eliminate malaria by 2018, and surveillance is key. This study focused on assessing the uptake of the new malaria case-based surveillance (CBS) system introduced in 2012, which captures information on malaria cases reported in the Integrated Disease Surveillance and Response (IDSR) system. Methods: This was a retrospective descriptive study based on routine data focusing on Ngami, Chobe and Okavango, three high-risk districts in Botswana. Aggregated data variables were extracted from the IDSR and compared with data from the CBS. Results: The IDSR reported 456 malaria cases in 2013 and 1346 in 2014, of which respectively only 305 and 884 were reported by the CBS. The CBS reported 34% fewer cases than the IDSR system, indicating substantial differences between the two systems. The key malaria indicators with the greatest variability among the districts included in the study were case identification number and date of diagnosis. Conclusion: The IDSR and CBS systems are essential for malaria elimination, as shown by the significant gaps in reporting between the two systems. These findings highlight the need for further investigation into these discrepancies. Strengthening the CBS system will help to reach the objective of malaria elimination in Botswana.

Container-based sanitation: assessing costs and effectiveness of excreta management in Cap Haitien, Haiti

PubMed Central

Tilmans, Sebastien; Russel, Kory; Sklar, Rachel; Page, Leah; Kramer, Sasha

2015-01-01

Container-based sanitation (CBS) – in which wastes are captured in sealable containers that are then transported to treatment facilities – is an alternative sanitation option in urban areas where on-site sanitation and sewerage are infeasible. This paper presents the results of a pilot household CBS service in Cap Haitien, Haiti. We quantify the excreta generated weekly in a dense urban slum,(1) the proportion safely removed via container-based public and household toilets, and the costs associated with these systems. The CBS service yielded an approximately 3.5-fold decrease in the unmanaged share of faeces produced, and nearly eliminated the reported use of open defecation and “flying toilets” among service recipients. The costs of this pilot small-scale service were higher than those of large-scale waterborne sewerage, but economies of scale have the potential to reduce CBS costs over time. The paper concludes with a discussion of planning and policy implications of incorporating CBS into the menu of sanitation options for rapidly growing cities. PMID:26097288

The mass spectrum of the white dwarfs in cataclysmic binaries - Supplementary computations

NASA Astrophysics Data System (ADS)

Ritter, H.; Ozkan, M. T.

1986-10-01

Numerical computations supplementing those of Ritter and Burkert (1986) for the study of observational selection in favor of massive white dwarfs among cataclysmic binaries (CBs) are presented. In particular the contribution of CBs beyond the period minimum and the influence of the inclination and of limb-darkening of the accretion disk are investigated. It is found that: (1) the main conclusions of Ritter and Burkert remain unchanged; (2) neither the inclusion of CBs containing a black-dwarf secondary nor the variation of the inclination or limb-darkening change the selection significantly; (3) in a magnitude-limited sample, about 22 percent of the ultra-short-period CBs contain a degenerate secondary; (4) the mean inclination of the accretion disk in a magnitude-limited sample is always close to 60 deg; (5) the fraction of eclipsing systems is of order 10-15 percent at m(v) = 10.0; (6) the mean inclination and the fraction of eclipsing systems increases with the limiting magnitude; and (7) the intrinsic space density of CBs is n(CB) approximately .0001-.0002/cu pc.

Endurance and failure characteristics of modified Vasco X-2, CBS 600 and AISI 9310 spur gears. [aircraft construction materials

NASA Technical Reports Server (NTRS)

Townsend, D. P.; Zaretsky, E. V.

1980-01-01

Gear endurance tests and rolling-element fatigue tests were conducted to compare the performance of spur gears made from AISI 9310, CBS 600 and modified Vasco X-2 and to compare the pitting fatigue lives of these three materials. Gears manufactured from CBS 600 exhibited lives longer than those manufactured from AISI 9310. However, rolling-element fatigue tests resulted in statistically equivalent lives. Modified Vasco X-2 exhibited statistically equivalent lives to AISI 9310. CBS 600 and modified Vasco X-2 gears exhibited the potential of tooth fracture occurring at a tooth surface fatigue pit. Case carburization of all gear surfaces for the modified Vasco X-2 gears results in fracture at the tips of the gears.

Is plasticity within the retrotrapezoid nucleus responsible for the recovery of the PCO2 set‐point after carotid body denervation in rats?

PubMed Central

Basting, Tyler M.; Abe, Chikara; Viar, Kenneth E.; Stornetta, Ruth L.

2016-01-01

Key points Arterial PCO2 is kept constant via breathing adjustments elicited, at least partly, by central chemoreceptors (CCRs) and the carotid bodies (CBs).The CBs may be active in a normal oxygen environment because their removal reduces breathing. Thereafter, breathing slowly returns to normal. In the present study, we investigated whether an increase in the activity of CCRs accounts for this return.One week after CB excision, the hypoxic ventilatory reflex was greatly reduced as expected, whereas ventilation and blood gases at rest under normoxia were normal.Optogenetic inhibition of Phox2b‐expressing neurons including the retrotrapezoid nucleus, a cluster of CCRs, reduced breathing proportionally to arterial pH. The hypopnoea was greater after CB excision but only in a normal or hypoxic environment. The difference could be simply explained by the loss of fast feedback from the CBs.We conclude that, in rats, CB denervation may not produce CCR plasticity. We also question whether the transient hypoventilation elicited by CB denervation means that these afferents are active under normoxia. Abstract Carotid body denervation (CBD) causes hypoventilation and increases the arterial PCO2 set‐point; these effects eventually subside. The hypoventilation is attributed to reduced CB afferent activity and the PCO2 set‐point recovery to CNS plasticity. In the present study, we investigated whether the retrotrapezoid nucleus (RTN), a group of non‐catecholaminergic Phox2b‐expressing central respiratory chemoreceptors (CCRs), is the site of such plasticity. We evaluated the contribution of the RTN to breathing frequency (F R), tidal volume (V T) and minute volume (V E) by inhibiting this nucleus optogenetically for 10 s (archaerhodopsinT3.0) in unanaesthetized rats breathing various levels of O2 and/or CO2. The measurements were made in seven rats before and 6–7 days after CBD and were repeated in seven sham‐operated rats. Seven days post‐CBD, blood gases and ventilation in 21% O2 were normal, whereas the hypoxic ventilatory reflex was still depressed (95.3%) and hypoxia no longer evoked sighs. Sham surgery had no effect. In normoxia or hypoxia, RTN inhibition produced a more sustained hypopnoea post‐CBD than before; in hyperoxia, the responses were identical. Post‐CBD, RTN inhibition reduced F R and V E in proportion to arterial pH or PCO2 (ΔV E: 3.3 ± 1.5% resting V E/0.01 pHa). In these rats, 20.7 ± 8.9% of RTN neurons expressed archaerhodopsinT3.0. Hypercapnia (3–6% FiCO2) increased F R and V T in CBD rats (n = 4). In conclusion, RTN regulates F R and V E in a pH‐dependent manner after CBD, consistent with its postulated CCR function. RTN inhibition produces a more sustained hypopnoea after CBD than before, although this change may simply result from the loss of the fast feedback action of the CBs. PMID:26842799

An exploratory study on low-concentration hexavalent chromium adsorption by Fe(III)-cross-linked chitosan beads

PubMed Central

Zhang, Yuanjing; Qian, Jin; Xin, Xu; Hu, Sihai; Zhang, Shuai; Wei, Jianguo

2017-01-01

In this study, Fe(III)-cross-linked chitosan beads (Fe(III)-CBs) were synthesized and employed to explore the characteristics and primary mechanism of their hexavalent chromium (Cr(VI)) adsorption under low concentration Cr(VI) (less than 20.0 mg l−1) and a pH range from 2.0 to 8.0. Batch tests were conducted to determine the Cr(VI) adsorption capacity and kinetics, and the effects of pH and temperature on the adsorption under low concentration Cr(VI) and a pH range from 2.0 to 8.0. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy were employed to explore the characteristics of Fe(III)-CBs and their Cr(VI) adsorption mechanisms. The results show that, unlike the adsorption of other absorbents, the Cr(VI) adsorption was efficient in a wide pH range from 2.0 to 6.0, and well described by the pseudo-first-order model and the Langmuir–Freundlich isotherm model. The capacity of Cr(VI) adsorption by Fe(III)-CBs was as high as 166.3 mg g−1 under temperature 25°C and pH 6.0. The desorption test was also carried out by 0.1 mol l−1 NaOH solution for Fe(III)-CBs regeneration. It was found that Fe(III)-CBs could be re-used for five adsorption–desorption cycles without significant decrease in Cr(VI) adsorption capacity. Ion exchange was confirmed between functional groups (i.e. amino group) and Cr(VI) anions (i.e. CrO42−). The amino-like functional groups played a key role in Cr(VI) distribution on the Fe(III)-CBs surface; Cr(VI) adsorbed on Fe(III)-CBs was partially reduced to Cr(III) with alcoholic group served as electron donor, and then formed another rate-limiting factor. So, Fe(III)-CBs has a good prospect in purifying low concentration Cr(VI) water with a pH range from 2.0 to 6.0. PMID:29291084

The role of Cajal cells in chronic prostatitis.

PubMed

Haki Yuksel, Ozgur; Urkmez, Ahmet; Verit, Ayhan

2016-07-04

Types of prostatitis can be defined as groups of syndromes in adult men associated with infectious and noninfectious causes characterized frequently by lower abdominal and perineal signs and diverse clinical symptoms and complications. Etiopathogenesis of chronic prostatitis is not well defined. Moreover, its treatment outcomes are not satisfactory. Presence of c-kit positive interstitial cells in human prostate is already known. It has been demonstrated that these cells can be pacemaker cells which trigger spontaneous slow-wave electrical activity in the prostate and can be responsible for the transport of glandular secretion from acinar cells into major and minor prostatic ducts and finally into urethra. In the light of all these data, when presence of a possible inflammatory pathology is thought to involve prostate that secretes and has a reservoir which drains its secretion (for prostate, prostatic urethra), two points are worth mentioning. Impairment of secretion mechanism and collection of secretion within the organ with reflux of the microbial material from its reservoir back into prostate gland. Both of these potential conditions can be explained by ductal neuromuscular mechanism, which induces secretion. We think that in this neuromuscular mechanism interstitial Cajal cells have an important role in chronic prostatitis. Our hypothesis is that curability of prostatitis is correlated with the number of Cajal cells not subjected to apoptosis.

The endocannabinoid system modulates the valence of the emotion associated to food ingestion.

PubMed

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, Oscar

2012-07-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive-valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide, and if such, CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. © 2010 The Authors. Addiction Biology © 2010 Society for the Study of Addiction.

Rhodotorula bloemfonteinensis sp. nov., Rhodotorula eucalyptica sp. nov., Rhodotorula orientis sp. nov. and Rhodotorula pini sp. nov., yeasts isolated from monoterpene-rich environments.

PubMed

Pohl, Carolina H; Smit, Martha S; Albertyn, Jacobus

2011-09-01

Recent rDNA sequencing of 25 isolates from a previous study, during which limonene-utilizing yeasts were isolated from monoterpene-rich environments by using 1,4-disubstituted cyclohexanes as sole carbon sources, led to the identification of four hitherto unknown Rhodotorula species. Analyses of the 26S rDNA D1/D2 region as well as the internal transcribed spacer (ITS) domain indicated that two isolates (CBS 8499(T) and CBS 10736) were identical and were closely related to Rhodotorula cycloclastica, a previously described limonene-utilizing yeast. These novel isolates differed from known yeast species and could be distinguished from R. cycloclastica by standard physiological tests. The other three isolates represent three novel Rhodotorula species, closely related to Sporobolomyces magnisporus. These three species could also be distinguished from other Rhodotorula species by standard physiological tests. Based on these results, we suggest that the new isolates represent novel species, for which the names Rhodotorula eucalyptica sp. nov. (type strain CBS 8499(T)  = NRRL Y-48408(T)), Rhodotorula pini sp. nov. (type strain CBS 10735(T)  = NRRL Y-48410(T)), Rhodotorula bloemfonteinensis sp. nov. (type strain CBS 8598(T)  = NRRL Y-48407(T)) and Rhodotorula orientis sp. nov. (type strain CBS 8594(T)  = NRRL Y-48719(T)) are proposed. R. eucalyptica and R. pini can also utilize limonene.

High fat diet blunts the effects of leptin on ventilation and on carotid body activity.

PubMed

Ribeiro, Maria J; Sacramento, Joana F; Gallego-Martin, Teresa; Olea, Elena; Melo, Bernardete F; Guarino, Maria P; Yubero, Sara; Obeso, Ana; Conde, Silvia V

2017-12-22

Leptin plays a role in the control of breathing, acting mainly on central nervous system; however, leptin receptors have been recently shown to be expressed in the carotid body (CB), and this finding suggests a physiological role for leptin in the regulation of CB function. Leptin increases minute ventilation in both basal and hypoxic conditions in rats. It increases the frequency of carotid sinus nerve discharge in basal conditions, as well as the release of adenosine from the CB. However, in a metabolic syndrome animal model, the effects of leptin in ventilatory control, carotid sinus nerve activity and adenosine release by the CB are blunted. Although leptin may be involved in triggering CB overactivation in initial stages of obesity and dysmetabolism, resistance to leptin signalling and blunting of responses develops in metabolic syndrome animal models. Leptin plays a role in the control of breathing, acting mainly on central nervous system structures. Leptin receptors are expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism, here we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation in both basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not modify intracellular Ca 2+ in CB chemoreceptor cells, but it produced an increase in the release of adenosine from the whole CB. We conclude that CBs represent an important target for leptin signalling, not only to coordinate peripheral ventilatory chemoreflexive drive, but probably also to modulate metabolic variables. We also concluded that leptin signalling is mediated by adenosine release and that HF diets blunt leptin responses in the CB, compromising ventilatory adaptation. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Biomechanical comparison of 3.0 mm headless compression screw and 3.5 mm cortical bone screw in a canine humeral condylar fracture model.

PubMed

Gonsalves, Mishka N; Jankovits, Daniel A; Huber, Michael L; Strom, Adam M; Garcia, Tanya C; Stover, Susan M

2016-09-20

To compare the biomechanical properties of simulated humeral condylar fractures reduced with one of two screw fixation methods: 3.0 mm headless compression screw (HCS) or 3.5 mm cortical bone screw (CBS) placed in lag fashion. Bilateral humeri were collected from nine canine cadavers. Standardized osteotomies were stabilized with 3.0 mm HCS in one limb and 3.5 mm CBS in the contralateral limb. Condylar fragments were loaded to walk, trot, and failure loads while measuring construct properties and condylar fragment motion. The 3.5 mm CBS-stabilized constructs were 36% stiffer than 3.0 mm HCS-stabilized constructs, but differences were not apparent in quality of fracture reduction nor in yield loads, which exceeded expected physiological loads during rehabilitation. Small residual fragment displacements were not different between CBS and HCS screws. Small fragment rotation was not significantly different between screws, but was weakly correlated with moment arm length (R² = 0.25). A CBS screw placed in lag fashion provides stiffer fixation than an HCS screw, although both screws provide similar anatomical reduction and yield strength to condylar fracture fixation in adult canine humeri.

Density functional Theory Based Generalized Effective Fragment Potential Method (Postprint)

DTIC Science & Technology

2014-07-01

is acceptable for other applications) leads to induced dipole moments within 10−6 to 10−7 au of the precise values . Thus, the applied field of 10−4...noncovalent interactions. The water-benzene clusters17 and WATER2711 reference values were also ob- tained at the CCSD(T)/CBS level, except for the clusters...with n = 20,42 where MP2/CBS was used. The n-alkane dimers18 benchmark values were CCSD(T)/CBS for ethane to butane and a linear extrapolation method

A comparative study of shear bond strength between metal and ceramic brackets and artificially aged composite restorations using different surface treatments.

PubMed

Eslamian, Ladan; Borzabadi-Farahani, Ali; Mousavi, Nasim; Ghasemi, Amir

2012-10-01

This in vitro study evaluated the shear bond strength (SBS) between ceramic brackets (CBs) and resin composite restorations (RCRs) prepared using different surface treatments. The findings were also compared with a similar study that used stainless steel brackets (SSBs). Forty-five premolars were restored with a nano-hybrid composite resin (Tetric EvoCeram) and randomly assigned to three surface treatment groups: group 1, 5 per cent hydrofluoric acid (HF); group 2, air abrasion (50 μm alumina particles); and group 3, diamond bur. Specimens were bonded with CBs (Fascination) and exposed to thermo-cycling (500 cycles). The shear force at a crosshead speed of 1 mm/minute was transmitted to brackets. The adhesive remnant index (ARIs) scores were recorded after bracket failure. The analysis of SBS variance (P < 0.01) and chi-square test of ARIs scores (P < 0.01) revealed significant differences among three groups tested. The SBS in group 3 (mean: 26.34 ± 4.76 MPa) and group 2 (mean: 26.68 ± 5.93 MPa) was significantly higher than group 1 (mean: 16.25 ± 5.42 MPa). The SBS was significantly higher in CBs (mean: 23.09 ± 7.19 MPa) compared to SSBs (mean: 15.56 ± 5.13 MPa). High ARIs (100 per cent) occurred in SSBs treated with a diamond bur, whereas CBs primarily failed at the resin-adhesive interface (P < 0.01). In two-thirds of the specimens (SSBs or CBs), no adhesive was left on the restoration after HF conditioning. The ARIs profile of CBs and SSBs that received surface treatments with air abrasion were similar (P > 0.05) and bond failure occurred mainly in adhesive-bracket base and resin-adhesive interfaces. The diamond bur surface treatment is recommended as a safe and cost-effective method of bonding CBs to RCRs.

Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation.

PubMed

Sheibani, Lili; Lechuga, Thomas J; Zhang, Honghai; Hameed, Afshan; Wing, Deborah A; Kumar, Sathish; Rosenfeld, Charles R; Chen, Dong-Bao

2017-03-01

Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P >NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P > NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

New transmitters and new targets in the autonomic nervous system.

PubMed

Barajas-López, C; Huizinga, J D

1993-12-01

Several recent findings have made research into the autonomic nervous system even more exciting, such as the revelation that nitric oxide is a major neurotransmitter, the delineation of the physiological roles for purines and vasoactive intestinal peptide, and the discovery that the interstitial cells of Cajal are major target cells for enteric innervation. Nitric oxide is probably the major neurotransmitter evoking inhibitory junction potentials in smooth muscle. ATP is a mediator of non-adrenergic non-cholinergic enteric innervation, as well as being a fast neurotransmitter in peripheral and autonomic neuro-neuronal synapses. The interactions between enteric nerves and both immune cells and interstitial cells of Cajal (as pacemaker cells of gut smooth muscle) are forcing a rethink of many aspects of gut physiology.

Resistance of Loblolly Pine Sources to Fusiform Rust in Field Progeny Tests

Treesearch

H.R. Powers; E.G. Kuhlman

1987-01-01

Results of concentrated basidiospore spray (CBS) inoculations correlated well with field infection. Generally, the CBS system correctly classified resistant and susceptible sources, but it classed seven sources with field resistance as susceptible.

Two new species of the genus Candida in the Zygoascus clade, Candida lundiana sp. nov. and Candida suthepensis sp. nov., isolated from raw honey in Thailand.

PubMed

Saksinchai, Sujinan; Suzuki, Motofumi; Lumyong, Saisamorn; Ohkuma, Moriya; Chantawannakul, Panuwan

2012-03-01

During a survey of yeasts associated with raw honey collected in Thailand, two strains of the Zygoascus clade were isolated from the Asian cavity-nesting honeybee Apis cerana and the stingless bee Homotrigona fimbriata. Phylogeny based on 26S rDNA D1/D2 sequences placed these yeasts as members of a clade including Candida bituminiphila, Candida patagonica and Candida polysorbophila. The strains of the two novel species, CBS 12271(T) and CBS 12270(T), respectively, could be unquestionably distinguished from their relatives by rDNA sequences and other taxonomic characteristics. Therefore, the novel anamorphic species, Candida lundiana sp. nov. (type strain CBS 12271(T) = JCM 16823(T)) and Candida suthepensis sp. nov. (type strain CBS 12270(T) = JCM 16822(T)) are described.

Charles Bonnet syndrome: three cases in the emergency department.

PubMed

Frost, Elizabeth J; Mottley, J Lawrence; Edlow, Jonathan A

2012-05-01

Charles Bonnet Syndrome (CBS) is a cause of visual hallucinations in elderly patients that is often unrecognized by emergency physicians and has a relatively benign course. As the population ages, it is likely that the number of cases of CBS will increase (and thus, the numbers of those who present to an Emergency Department [ED] will be increasing). The case reports presented in this article will facilitate the recognition of CBS by the emergency physician. We describe 3 patients who presented to one ED for visual disturbances and were diagnosed with CBS in a 4-month time period. Recognition of this unusual but stereotypical cause of visual disturbances facilitates an accurate diagnosis, and spares patients the time and expense of blood testing, imaging, and consultations. If emergency physicians begin to recognize this benign entity, we can provide improved (and safer) patient care with appropriate ED interventions. Copyright © 2012 Elsevier Inc. All rights reserved.

Charles Bonnet Syndrome in a Patient With Right Medial Occipital Lobe Infarction: Epileptic or Deafferentation Phenomenon?

PubMed

Kumral, Emre; Uluakay, Arzu; Dönmez, İlknur

2015-07-01

Charles Bonnet syndrome (CBS) is an uncommon disorder characterized by complex and recurrent visual hallucinations in patients with visual pathway pathologic defects. To describe a patient who experienced complex visual hallucinations following infarction in the right occipital lobe and epileptic seizure who was diagnosed as having CBS. A 65-year-old man presented acute ischemic stroke caused by artery to artery embolism involving the right occipital lobe. Following ischemic stroke, complex visual hallucinations in the left visual field not associated with loss of consciousness or delusion developed in the patient. Hallucinations persisted for >1 month and during hallucination, no electrographic seizures were recorded through 24 hours of videoelectroencephalographic monitoring. CBS may develop in a patient with occipital lobe infarction following an embolic event. CBS associated with medial occipital lobe infarction and epilepsy may coexist and reflects the abnormal functioning of an integrated neuronal network.

Progression of brain atrophy in PSP and CBS over 6 months and 1 year.

PubMed

Dutt, Shubir; Binney, Richard J; Heuer, Hilary W; Luong, Phi; Attygalle, Suneth; Bhatt, Priyanka; Marx, Gabe A; Elofson, Jonathan; Tartaglia, Maria C; Litvan, Irene; McGinnis, Scott M; Dickerson, Bradford C; Kornak, John; Waltzman, Dana; Voltarelli, Lisa; Schuff, Norbert; Rabinovici, Gil D; Kramer, Joel H; Jack, Clifford R; Miller, Bruce L; Rosen, Howard J; Boxer, Adam L

2016-11-08

To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents. Six- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial. Patients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale. Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects. © 2016 American Academy of Neurology.

Molecular testing guidelines for lung adenocarcinoma: Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples

PubMed Central

Heymann, Jonas J.; Bulman, William A.; Maxfield, Roger A.; Powell, Charles A.; Halmos, Balazs; Sonett, Joshua; Beaubier, Nike T.; Crapanzano, John P.; Mansukhani, Mahesh M.; Saqi, Anjali

2014-01-01

Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs) are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA) CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) virus homolog testing between FNA CBs and histology samples from the same patients. Materials and Methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22) and KRAS (17/17) mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology. PMID:24987443

Many-body calculations of molecular electric polarizabilities in asymptotically complete basis sets

NASA Astrophysics Data System (ADS)

Monten, Ruben; Hajgató, Balázs; Deleuze, Michael S.

2011-10-01

The static dipole polarizabilities of Ne, CO, N2, F2, HF, H2O, HCN, and C2H2 (acetylene) have been determined close to the Full-CI limit along with an asymptotically complete basis set (CBS), according to the principles of a Focal Point Analysis. For this purpose the results of Finite Field calculations up to the level of Coupled Cluster theory including Single, Double, Triple, Quadruple and perturbative Pentuple excitations [CCSDTQ(P)] were used, in conjunction with suited extrapolations of energies obtained using augmented and doubly-augmented Dunning's correlation consistent polarized valence basis sets of improving quality. The polarizability characteristics of C2H4 (ethylene) and C2H6 (ethane) have been determined on the same grounds at the CCSDTQ level in the CBS limit. Comparison is made with results obtained using lower levels in electronic correlation, or taking into account the relaxation of the molecular structure due to an adiabatic polarization process. Vibrational corrections to electronic polarizabilities have been empirically estimated according to Born-Oppenheimer Molecular Dynamical simulations employing Density Functional Theory. Confrontation with experiment ultimately indicates relative accuracies of the order of 1 to 2%.

Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells.

PubMed

Sekiguchi, Fumiko; Sekimoto, Teruki; Ogura, Ayaka; Kawabata, Atsufumi

2016-01-01

Hydrogen sulfide (H2S), the third gasotransmitter, is endogenously generated by certain H2S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H2S affects the proliferation of cancer cells, although the effects of H2S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H2S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and β-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H2S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H2S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions.

A mathematical model of single target site location by Brownian movement in subcellular compartments.

PubMed

Kuthan, Hartmut

2003-03-07

The location of distinct sites is mandatory for many cellular processes. In the subcompartments of the cell nucleus, only very small numbers of diffusing macromolecules and specific target sites of some types may be present. In this case, we are faced with the Brownian movement of individual macromolecules and their "random search" for single/few specific target sites, rather than bulk-averaged diffusion and multiple sites. In this article, I consider the location of a distant central target site, e.g. a globular protein, by individual macromolecules executing unbiased (i.e. drift-free) random walks in a spherical compartment. For this walk-and-capture model, the closed-form analytic solution of the first passage time probability density function (p.d.f.) has been obtained as well as the first and second moment. In the limit of a large ratio of the radii of the spherical diffusion space and central target, well-known relations for the variance and the first two moments for the exponential p.d.f. were found to hold with high accuracy. These calculations reinforce earlier numerical results and Monte Carlo simulations. A major implication derivable from the model is that non-directed random movement is an effective means for locating single sites in submicron-sized compartments, even when the diffusion coefficients are comparatively small and the diffusing species are present in one copy only. These theoretical conclusions are underscored numerically for effective diffusion constants ranging from 0.5 to 10.0 microm(2) s(-1), which have been reported for a couple of nuclear proteins in their physiological environment. Spherical compartments of submicron size are, for example, the Cajal bodies (size: 0.1-1.0 microm), which are present in 1-5 copies in the cell nucleus. Within a small Cajal body of radius 0.1 microm a single diffusing protein molecule (with D=0.5 microm(2) s(-1)) would encounter a medium-sized protein of radius 2.5 nm within 1 s with a probability near certainty (p=0.98).

Fusarium MLST database

USDA-ARS?s Scientific Manuscript database

The CBS-KNAW Fungal Biodiversity Centre’s Fusarium MLST website (http://www.cbs.knaw.nl/Fusarium), and the corresponding Fusarium-ID site hosted at the Pennsylvania State University (http://isolate.fusariumdb.org; Geiser et al. 2004, Park et al. 2010) were constructed to facilitate identification of...

Magnolol pretreatment prevents sepsis-induced intestinal dysmotility by maintaining functional interstitial cells of Cajal.

PubMed

Miao, Bin; Zhang, Shuwen; Wang, Hong; Yang, Tiecheng; Zhou, Deshan; Wang, Bao-en

2013-08-01

The purpose of this study was to investigate the mechanism by which magnolol treatment prevents lipopolysaccharide (LPS)-induced septic dysmotility in mice. Sepsis was induced by intravenous tail vein injection of LPS (4 mg/kg body weight). Animals were divided into three groups: the magnolol-treated septic group, the placebo-treated septic group, and the control group. Intestinal transit and circular smooth muscle contraction were measured 12 h after LPS injection, and immunocytochemisty was performed to study the morphology of interstitial cells of Cajal (ICCs). Stem cell factor (SCF) expression and c-kit phosphorylation were determined by Western blot analysis, and the mRNA levels of inducible NO synthase (iNOS) were determined by RT-PCR. Nitric oxide (NO) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration were detected using commercial kits. Intestinal transit and muscular contractility were significantly lower in the LPS-treated group than in the control group. Immunocytochemical experiments showed that the total number of ICCs, and the total and average lengths of the ICC processes were significantly decreased in the LPS-treated group compared with those in the control group. In LPS-treated animals, magnolol pretreatment significantly accelerated intestinal transit, increased circular muscle contraction, and prevented ICC morphology changes. Phosphorylation of c-kit and expression of SCF were significantly downregulated in LPS-treated animals compared with control animals. Magnolol pretreatment prevented sepsis-induced decreases in c-kit phosphorylation and SCF expression in LPS-treated animals. Magnolol pretreatment prevented the sepsis-induced increase in NO concentration, iNOS expression, and MDA concentration, and decrease in SOD activity in LPS-treated animals. Our results suggest that magnolol treatment prevents sepsis-induced intestinal dysmotility by regulating SCF/c-kit and NO signaling to maintain functional ICCs.

Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny

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

Ahituv, Nadav; Prabhakar, Shyam; Poulin, Francis

2005-06-13

Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A totalmore » of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.« less

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

PubMed

Sandler, Roman A; Fetterhoff, Dustin; Hampson, Robert E; Deadwyler, Sam A; Marmarelis, Vasilis Z

2017-07-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3

PubMed Central

Fetterhoff, Dustin; Hampson, Robert E.; Deadwyler, Sam A.; Marmarelis, Vasilis Z.

2017-01-01

Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs. PMID:28686594

Association between Hcy levels and the CBS844ins68 and MTHFR C677T polymorphisms with essential hypertension.

PubMed

Cai, Weijuan; Yin, Liang; Yang, Fang; Zhang, Lei; Cheng, Jiang

2014-11-01

The aim of the present study was to investigate the association between the homocysteine (Hcy) levels and polymorphisms of the CBS844ins68 and MTHFR C677T genes in essential hypertension (EH). The effects of the MTHFR C677T and CBS844ins68 haploid genotypes and the combined genotypes on EH and levels of Hcy were further explored. The polymorphisms of CBS844ins68 and MTHFR C677T genes in 200 EH and 200 normal tensive (NT) patients were detected using polymerase chain reaction-restriction fragment length polymorphism and analysis of the distribution of genotypes. An automated biochemical analyzer was used to measure the plasma Hcy levels and the clinical biochemistry data. The plasma Hcy levels in EH were significantly higher than those of the NT group (P<0.05). There were no significant differences (P>0.05) between males and females. Two genotypes, deletion/deletion (DD) and deletion/insertion (DI), of the CBS844ins68 polymorphism were found in two groups with no clear differences in two genotypes and allele frequency distribution (P>0.05). There were significant differences in the three genotype frequencies (χ 2 =6.658, χ 2 =4.410, P<0.05) for MTHFR C677T locus genotypes CC, CT and TT. The Hcy levels in genotypes DD and DI had no significant differences (P>0.05) and the CT and TT types were significantly higher compared to the CC genotype (P<0.05). The CC/DD combined genotype in the two groups was significantly different (P<0.05), and the odds ratio (OR), 0.569 showed that the CC/DD genotype may be a protective factor of hypertension. In the two groups, the Hcy levels for combined genotypes CC/DD, CT/DD, TT/DD and TT/DI were significantly different (P<0.05). The SHEsis software analysis linkage disequilibrium coefficient=0.216, indicates that there is probably a weak linkage for MTHFR C677T and CBS844ins68 . Haplotype analysis suggested that the C-D haplotype was negatively correlated with EH (OR, 0.727) and that there was a positive correlation between T-D haplotype and EH (OR, 1.376). MTHFR C677T and CBS844ins68 polymorphisms were present in the populations studied and the CBS844ins68 homozygous mutation was not present. Therefore, there is a correlation between the polymorphisms of the MTHFR C677T gene and EH, and allele T may be one of the predisposing factors. MTHFR C677T and CBS844ins68 may exist with a certain linkage and the T-D haplotype may be a risk factor for EH.

Association between Hcy levels and the CBS844ins68 and MTHFR C677T polymorphisms with essential hypertension

PubMed Central

CAI, WEIJUAN; YIN, LIANG; YANG, FANG; ZHANG, LEI; CHENG, JIANG

2014-01-01

The aim of the present study was to investigate the association between the homocysteine (Hcy) levels and polymorphisms of the CBS844ins68 and MTHFR C677T genes in essential hypertension (EH). The effects of the MTHFR C677T and CBS844ins68 haploid genotypes and the combined genotypes on EH and levels of Hcy were further explored. The polymorphisms of CBS844ins68 and MTHFR C677T genes in 200 EH and 200 normal tensive (NT) patients were detected using polymerase chain reaction-restriction fragment length polymorphism and analysis of the distribution of genotypes. An automated biochemical analyzer was used to measure the plasma Hcy levels and the clinical biochemistry data. The plasma Hcy levels in EH were significantly higher than those of the NT group (P<0.05). There were no significant differences (P>0.05) between males and females. Two genotypes, deletion/deletion (DD) and deletion/insertion (DI), of the CBS844ins68 polymorphism were found in two groups with no clear differences in two genotypes and allele frequency distribution (P>0.05). There were significant differences in the three genotype frequencies (χ2=6.658, χ2=4.410, P<0.05) for MTHFR C677T locus genotypes CC, CT and TT. The Hcy levels in genotypes DD and DI had no significant differences (P>0.05) and the CT and TT types were significantly higher compared to the CC genotype (P<0.05). The CC/DD combined genotype in the two groups was significantly different (P<0.05), and the odds ratio (OR), 0.569 showed that the CC/DD genotype may be a protective factor of hypertension. In the two groups, the Hcy levels for combined genotypes CC/DD, CT/DD, TT/DD and TT/DI were significantly different (P<0.05). The SHEsis software analysis linkage disequilibrium coefficient=0.216, indicates that there is probably a weak linkage for MTHFR C677T and CBS844ins68. Haplotype analysis suggested that the C-D haplotype was negatively correlated with EH (OR, 0.727) and that there was a positive correlation between T-D haplotype and EH (OR, 1.376). MTHFR C677T and CBS844ins68 polymorphisms were present in the populations studied and the CBS844ins68 homozygous mutation was not present. Therefore, there is a correlation between the polymorphisms of the MTHFR C677T gene and EH, and allele T may be one of the predisposing factors. MTHFR C677T and CBS844ins68 may exist with a certain linkage and the T-D haplotype may be a risk factor for EH. PMID:25279160

A distinct type of cell in myocardium: interstitial Cajal-like cells (ICLCs)

PubMed Central

Kostin, S; Popescu, L M

2009-01-01

Abstract The existence of a novel type of interstitial cells in the heart, interstitial Cajal-like cells (ICLCs), had been described for the first time in 2005. Their identification was mainly based on ultrastructural criteria: very long (tens up to hundreds of micrometres) and moniliform prolongations, which are extremely thin (less than 0.2 μm), below the resolving power of light microscopy. Myocardial ICLCs were also identified by methylene-blue vital staining, silver impregnation, and immunoreactivity for CD 34, vimentin, CD117/c-kit, etc. Although a series of studies provided evidence for the existence of ICLCs in human atria and rat ventricles, further investigations in other laboratories, using additional techniques, are required to substantiate the consistency of these findings. Here we provide further evidence for the existence of ICLCs in human and mammalian hearts (by transmission and scanning electron microscopy, as well as confocal laser scanning microscopy). Noteworthy, we confirm that ICLCs communicate with neighbouring cells via shedding (micro)vesicles. Although these so-called ICLCs represent a distinct type of cells, different from classical interstitial cells of Cajal, or fibroblasts, their role(s) in myocardium remain(s) to be established. Several hypotheses are proposed: (i) adult stromal (mesenchymal) stem cells, which might participate in cardiac repair/remodelling; (ii) intercellular signalling (e.g. via shedding microvesicles); (iii) chemo-mechanical transducers and (iv) players in pacemaking and/or arrhytmogenesis, and so on. PMID:19183408

[The meeting of Einstein with Cajal (Madrid, 1923): a lost tide of fortune].

PubMed

Montes-Santiago, J

The year 2005 was the centennial year of the Albert Einstein's transcendental works that changed forever the humans thoughts on the universe. It is also celebrated the 50th anniversary of his death. It was proclaimed 'World Year of Physics' and a multiplicity of celebrations have exhaustively analyzed Einstein's cardinals contributions. However, among these, the meeting of Einstein with another titanic of science, Santiago Ramon y Cajal, has passed some unnoticed. In this study the circumstances of this meeting are evoked. The parallelisms between the lives of both prominent figures awarded with the Nobel Prize are highlighted. They are the 'classic' authors most widely cited in the current scientific literature. The events and persons who made possible that shining but forgotten interview are detailed. Such a meeting took place in Madrid, on the occasion of the Einstein's trip to Spain in 1923. That travel exceeded his primary scientific nature, reaching the category of a social phenomenon and was widely covered by the printed mass media at that time. Finally, the curious coincidence of the invocation of Cajal's theories to justify the genius of the German physicist nearly 75 years after their meeting is mentioned. Although it was a brief meeting and the circumstances surrounding it largely unknown, it produced a great impression to Einstein and constitutes a supreme instant in the history of the 20th century.

Static and dynamic views of visual cortical organization.

PubMed

Casagrande, Vivien A; Xu, Xiangmin; Sáry, Gyula

2002-01-01

Without the aid of modern techniques Cajal speculated that cells in the visual cortex were connected in circuits. From Cajal's time until fairly recently, the flow of information within the cells and circuits of visual cortex has been described as progressing from input to output, from sensation to action. In this chapter we argue that a paradigm shift in our concept of the visual cortical neuron is under way. The most important change in our view concerns the neuron's functional role. Visual cortical neurons do not have static functional signatures but instead function dynamically depending on the ongoing activity of the networks to which they belong. These networks are not merely top-down or bottom-up unidirectional transmission lines, but rather represent machinery that uses recurrent information and is dynamic and highly adaptable. With the advancement of technology for analyzing the conversations of multiple neurons at many levels in the visual system and higher resolution imaging, we predict that the paradigm shift will progress to the point where neurons are no longer viewed as independent processing units but as members of subsets of networks where their role is mapped in space-time coordinates in relationship to the other neuronal members. This view moves us far from Cajal's original views of the neuron. Nevertheless, we believe that understanding the basic morphology and wiring of networks will continue to contribute to our overall understanding of the visual cortex.

Bioconversion of giant reed (Arundo donax L.) hemicellulose hydrolysate to ethanol by Scheffersomyces stipitis CBS6054

Treesearch

Danilo Scordia; Salvatore L. Cosentino; Jae-Won Lee; Thomas W. Jeffries

2012-01-01

The objective of this study was to evaluate the production of ethanol by Scheffersomyces (Pichia) stipitis CBS6054, a native xylose fermenting yeast, from sugars contained in the giant reed (Arundo donax L.) hemicellulosic hydrolysate.

Disorders of interstitial cells of Cajal in a neonate with segmental dilatation of the intestine.

PubMed

Okada, Tadao; Sasaki, Fumiaki; Honda, Shohei; Cho, Kazutosi; Matsuno, Yoshihiro; Itoh, Tomoo; Kubota, Kanako C; Todo, Satoru

2010-06-01

Localized myopathy of the muscular layers may be an important factor contributing to segmental dilatation of the intestine (SDI). Only one report has described SDI of the jejunum in a neonate showing no abnormality of the interstitial cells of Cajal (ICC). The present report describes the very rare case of a neonatal girl with segmental dilatation of the distal duodenum and proximal jejunum with irregular arrangements of Auerbach's plexus and ICC and the successful surgical treatment of SDI. We review the literature on this type of relationship between abnormality of ICC and SDI and discuss the clinical features of this complication. Furthermore, the possible neuropathic cause of SDI complicated with disorders of ICC was explored in this report. Copyright 2010 Elsevier Inc. All rights reserved.

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body.

PubMed

Ortega-Sáenz, Patricia; Villadiego, Javier; Pardal, Ricardo; Toledo-Aral, Juan José; López-Barneo, José

2015-01-01

The carotid body (CB) is a polymodal chemoreceptor that triggers the hyperventilatory response to hypoxia necessary for the maintenance of O(2) homeostasis essential for the survival of organs such as the brain or heart. Glomus cells, the sensory elements in the CB, are also sensitive to hypercapnia, acidosis and, although less generally accepted, hypoglycemia. Current knowledge on CB function is mainly based on studies performed on lower mammals, but the information on the human CB is scant. Here we describe the structure, neurotrophic properties, and cellular responses to hypoxia and hypoglycemia of CBs dissected from human cadavers. The adult CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. As reported for other mammalian species, glomus cells responded to hypoxia by external Ca(2+)-dependent increase of cytosolic [Ca(2+)] and quantal catecholamine release. Human glomus cells are also responsive to hypoglycemia and together the two stimuli, hypoxia and hypoglycemia, can potentiate each other's effects. The chemo-sensory responses of glomus cells are also preserved at an advanced age. Interestingly, a neurogenic niche similar to that recently described in rodents is also preserved in the adult human CB. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans.

Tetrodotoxin as a Tool to Elucidate Sensory Transduction Mechanisms: The Case for the Arterial Chemoreceptors of the Carotid Body

PubMed Central

Rocher, Asuncion; Caceres, Ana Isabel; Obeso, Ana; Gonzalez, Constancio

2011-01-01

Carotid bodies (CBs) are secondary sensory receptors in which the sensing elements, chemoreceptor cells, are activated by decreases in arterial PO2 (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and glomus cells) increase their rate of release of neurotransmitters that drive the sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem where reflex responses are coordinated. When challenged with hypoxic hypoxia, the physiopathologically most relevant stimulus to the CBs, they are activated and initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute volume ventilation promotes CO2 removal from alveoli and a decrease in alveolar PCO2 ensues. Reduced alveolar PCO2 makes possible alveolar and arterial PO2 to increase minimizing the intensity of hypoxia. The ventilatory effect, in conjunction the cardiocirculatory components of the CB chemoreflex, tend to maintain an adequate supply of oxygen to the tissues. The CB has been the focus of attention since the discovery of its nature as a sensory organ by de Castro (1928) and the discovery of its function as the origin of ventilatory reflexes by Heymans group (1930). A great deal of effort has been focused on the study of the mechanisms involved in O2 detection. This review is devoted to this topic, mechanisms of oxygen sensing. Starting from a summary of the main theories evolving through the years, we will emphasize the nature and significance of the findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of current models of O2-sensing. PMID:22363245

Dual Influence of Endocannabinoids on Long-Term Potentiation of Synaptic Transmission

PubMed Central

Silva-Cruz, Armando; Carlström, Mattias; Ribeiro, Joaquim A.; Sebastião, Ana M.

2017-01-01

Cannabinoid receptor 1 (CB1R) is widely distributed in the central nervous system, in excitatory and inhibitory neurons, and in astrocytes. CB1R agonists impair cognition and prevent long-term potentiation (LTP) of synaptic transmission, but the influence of endogenously formed cannabinoids (eCBs) on hippocampal LTP remains ambiguous. Based on the knowledge that eCBs are released upon high frequency neuronal firing, we hypothesized that the influence of eCBs upon LTP could change according to the paradigm of LTP induction. We thus tested the influence of eCBs on hippocampal LTP using two θ-burst protocols that induce either a weak or a strong LTP. LTP induced by a weak-θ-burst protocol is facilitated while preventing the endogenous activation of CB1Rs. In contrast, the same procedures lead to inhibition of LTP induced by the strong-θ-burst protocol, suggestive of a facilitatory action of eCBs upon strong LTP. Accordingly, an inhibitor of the metabolism of the predominant eCB in the hippocampus, 2-arachidonoyl-glycerol (2-AG), facilitates strong LTP. The facilitatory action of endogenous CB1R activation does not require the activity of inhibitory A1 adenosine receptors, is not affected by inhibition of astrocytic metabolism, but involves inhibitory GABAergic transmission. The continuous activation of CB1Rs via exogenous cannabinoids, or by drugs known to prevent metabolism of the non-prevalent hippocampal eCB, anandamide, inhibited LTP. We conclude that endogenous activation of CB1Rs by physiologically formed eCBs exerts a fine-tune homeostatic control of LTP in the hippocampus, acting as a high-pass filter, therefore likely reducing the signal-to-noise ratio of synaptic strengthening. PMID:29311928

Cdc42 is required in a genetically distinct subset of cardiac cells during Drosophila dorsal vessel closure

PubMed Central

Swope, David; Kramer, Joseph; King, Tiffany R.; Cheng, Yi-Shan; Kramer, Sunita G.

2017-01-01

The embryonic heart tube is formed by the migration and subsequent midline convergence of two bilateral heart fields. In Drosophila the heart fields are organized into two rows of cardioblasts (CBs). While morphogenesis of the dorsal ectoderm, which lies directly above the Drosophila dorsal vessel (DV), has been extensively characterized, the migration and concomitant fundamental factors facilitating DV formation remain poorly understood. Here we provide evidence that DV closure occurs at multiple independent points along the A-P axis of the embryo in a “buttoning” pattern, divergent from the zippering mechanism observed in the overlying epidermis during dorsal closure. Moreover, we demonstrate that a genetically distinct subset of CBs is programmed to make initial contact with the opposing row. To elucidate the cellular mechanisms underlying this process, we examined the role of Rho GTPases during cardiac migration using inhibitory and overexpression approaches. We found that Cdc42 shows striking cell-type specificity during DV formation. Disruption of Cdc42 function specifically prevents CBs that express the homeobox gene tinman from completing their dorsal migration, resulting in a failure to make connections with their partnering CBs. Conversely, neighboring CBs that express the orphan nuclear receptor, seven-up, are not sensitive to Cdc42 inhibition. Furthermore, this phenotype was specific to Cdc42 and was not observed upon perturbation of Rac or Rho function. Together with the observation that DV closure occurs through the initial contralateral pairing of tinman-expressing CBs, our studies suggest that the distinct buttoning mechanism we propose for DV closure is elaborated through signaling pathways regulating Cdc42 activity in this cell type. PMID:24949939

The Future of the Air National Guard

DTIC Science & Technology

2013-04-30

41 Keteyian, Armen , CBS Evening News, (August 2, 2012), accessed February 23, 2013, www.cbsnews.com/8301-18563_162-57485847/ex-official-chemical...Avgar. Crisis as an Opportunity. New York: University Press of America, Inc., 2011. Keteyian, Armen . "CBS Evening News." August 2, 2012

Clinical, cognitive and anatomical evolution from nonfluent progressive aphasia to corticobasal syndrome: a case report.

PubMed

Gorno-Tempini, Maria Luisa; Murray, Ryan C; Rankin, Katherine P; Weiner, Michael W; Miller, Bruce L

2004-12-01

Recent clinical and pathological studies have suggested that frontotemporal lobar degeneration (FTLD) and corticobasal syndrome (CBS) show clinical and pathological overlap. We present four years of longitudinal clinical, cognitive and anatomical data in the case of a 56-year-old woman, AS, whose clinical picture evolved from FTLD to CBS. For the first three years, AS showed a progressive speech and language disorder compatible with a diagnosis of the nonfluent aphasia variant of FTLD. At year four, 10 years after her first symptom, AS developed the classical clinical signs of CBS, including alien limb phenomenon and dystonia. Voxel-based morphometry (VBM) applied to AS's four annual scans showed progression of atrophy from the inferior posterior frontal gyrus, to the left insula and finally to the medial frontal lobe. This case demonstrates the clinical overlap between FTLD and CBS and shows that the two can appear in the same patient at different stages of the disease in relation to the progression of anatomical damage.

Comparative Proteome Analysis between High Lipid-Producing Strain Mucor circinelloides WJ11 and Low Lipid-Producing Strain CBS 277.49.

PubMed

Tang, Xin; Chen, Haiqin; Gu, Zhennan; Zhang, Hao; Chen, Yong Q; Song, Yuanda; Chen, Wei

2017-06-21

Mucor circinelloides is one of few oleaginous fungi that produces a useful oil rich in γ-linolenic acid, but it usually only produces <25% total lipid. Nevertheless, we isolated a new strain WJ11 that can produce up to 36% lipid of cell dry weight. In this study, we have systematically analyzed the global changes in protein levels between the high lipid-producing strain WJ11 and the low lipid-producing strain CBS 277.49 (15%, lipid/cell dry weight) at lipid accumulation phase through comparative proteome analysis. Proteome analysis demonstrated that the branched-chain amino acid and lysine metabolism, glycolytic pathway, and pentose phosphate pathway in WJ11 were up-regulated, while the activities of tricarboxylic acid cycle and branch point enzyme for synthesis of isoprenoids were retarded compared with CBS 277.49. The coordinated regulation at proteome level indicate that more acetyl-CoA and NADPH are provided for fatty acid biosynthesis in WJ11 compared with CBS 277.49.

Endurance tests with large-bore tapered-roller bearings to 2.2 million DN

NASA Technical Reports Server (NTRS)

Parker, R. J.; Signer, H. R.; Pinel, S. I.

1981-01-01

Endurance life tests were run with standard design and optimized high-speed design 120.65-mm-(4.750-in.-) bore tapered-roller bearings at shaft speeds of 12,500 and 18,500 rpm, respectively. Standard design bearings of vacuum melted AISI 4320 and CBS-1000M, and high-speed design bearings of CBS-1000M and through-hardened AISI M-50 were run under heavy combined radial and thrust load until fatigue failure or until a preset cutoff time of 1100 hours was reached. Standard design bearings made from CBS 1000M material ran to a 10 percent life approximately six times rated catalog life. Twelve identical bearings of AISI 4320 material ran to ten times rated catalog life without failure. Cracking and fracture of the cones of AISI M-50 high-speed design bearings occurred at 18,500 rpm due to high tensile hoop stresses. Four CBS 1000M high-speed design bearings ran to twenty-four times rated catalog life without any spalling, cracking or fracture failures.

[The Charles Bonnet syndrome: a case report and a brief review].

PubMed

Saiz Gonzáles, D; Diaz Marsá, M

2003-01-01

The Charles Bonnet syndrome (CBS) is a rare disease that also seems to be generally misdiagnosed. Initially described in the XVIII century by the philosopher with the same name, it consist in complex visual hallucinations in elderly people who suffer sensory deprivation with no other psychopathology. The hypothesis on the neurophysiology of hallucinations suggests, as in other diseases that present hallucinations, some implication of thalamus-cortex pathway release. Some authors have proposed CBS as an early marker of dementia and Parkinson's disease. Nevertheless, the results in functional neuroimaging are not conclusive. Regarding treatment, typical and atypical neuroleptics do not seem to be useful and recent studies suggest that the new anticonvulsants could be effcient. The patient should be informed about CBS as a . In the case reported, the patient presented complex hallucinations with normal SPECT and neuropsychological examinations. The patient did not respond to treatment with risperidone, presenting a favorable evolucion with valpromide. Although further research is needed, this case report supports the efficacy of valpromide in CBS.

Making Sense for Society

NASA Astrophysics Data System (ADS)

van der Heide, J. J.; Grus, M. M.; Nouwens, J. C. A. J.

2017-09-01

The Netherlands is a densely populated country. Cities in the metropolitan area (Randstad) will be growing at a fast pace in the coming decades1. Cities like Amsterdam and Rotterdam are being overrun by tourists. Climate change effects are noticed in cities (heavy rains for instance). Call for circular economy rises. Traffic increases. People are more self-reliant. Public space is shared by many functions. These challenges call for smart answers, more specific and directly than ever before. Sensor data is a cornerstone of these answers. In this paper we'll discuss the approaches of Dutch initiatives using sensor data as the new language to live a happy life in our cities. Those initiatives have been bundled in a knowledge platform called "Making sense for society" 1 https://www.cbs.nl/nl-nl/nieuws/2016/37/pbl-cbs-prognose-groei-steden-zet-door (in dutch)

User perceptions of and willingness to pay for household container-based sanitation services: experience from Cap Haitien, Haiti

PubMed Central

Russel, Kory; Tilmans, Sebastien; Kramer, Sasha; Sklar, Rachel; Tillias, Daniel; Davis, Jennifer

2015-01-01

Household-level container-based sanitation (CBS) services may help address the persistent challenge of providing effective, affordable sanitation services for which low-income urban households are willing to pay. Little is known, however, about user perceptions of and demand for household CBS services. This study presents the results of a pilot CBS service programme in Cap Haitien, Haiti. One hundred and eighteen households were randomly selected to receive toilets and a twice-weekly collection service. After three months, changes in these households’ satisfaction with their sanitation situation, along with feelings of pride, modernity and personal safety, were compared to 248 households in two comparison cohorts. Following the service pilot, 71 per cent of participating households opted to continue with the container-based sanitation service as paying subscribers. The results from this study suggest that, in the context of urban Haiti, household CBS systems have the potential to satisfy many residents’ desire for safe, convenient and modern sanitation services. PMID:26640322

Active dendrites: colorful wings of the mysterious butterflies.

PubMed

Johnston, Daniel; Narayanan, Rishikesh

2008-06-01

Santiago Ramón y Cajal had referred to neurons as the 'mysterious butterflies of the soul.' Wings of these butterflies--their dendrites--were traditionally considered as passive integrators of synaptic information. Owing to a growing body of experimental evidence, it is now widely accepted that these wings are colorful, endowed with a plethora of active conductances, with each family of these butterflies made of distinct hues and shades. Furthermore, rapidly evolving recent literature also provides direct and indirect demonstrations for activity-dependent plasticity of these active conductances, pointing toward chameleonic adaptability in these hues. These experimental findings firmly establish the immense computational power of a single neuron, and thus constitute a turning point toward the understanding of various aspects of neuronal information processing. In this brief historical perspective, we track important milestones in the chameleonic transmogrification of these mysterious butterflies.

Endogenous TRIM5α Function Is Regulated by SUMOylation and Nuclear Sequestration for Efficient Innate Sensing in Dendritic Cells

PubMed Central

Portilho, Débora M.; Fernandez, Juliette; Ringeard, Mathieu; Machado, Anthony K.; Boulay, Aude; Mayer, Martha; Müller-Trutwin, Michaela; Beignon, Anne-Sophie; Kirchhoff, Frank; Nisole, Sébastien; Arhel, Nathalie J.

2015-01-01

Summary During retroviral infection, viral capsids are subject to restriction by the cellular factor TRIM5α. Here, we show that dendritic cells (DCs) derived from human and non-human primate species lack efficient TRIM5α-mediated retroviral restriction. In DCs, endogenous TRIM5α accumulates in nuclear bodies (NB) that partly co-localize with Cajal bodies in a SUMOylation-dependent manner. Nuclear sequestration of TRIM5α allowed potent induction of type I interferon (IFN) responses during infection, mediated by sensing of reverse transcribed DNA by cGAS. Overexpression of TRIM5α or treatment with the SUMOylation inhibitor ginkgolic acid (GA) resulted in enforced cytoplasmic TRIM5α expression and restored efficient viral restriction but abrogated type I IFN production following infection. Our results suggest that there is an evolutionary trade-off specific to DCs in which restriction is minimized to maximize sensing. TRIM5α regulation via SUMOylation-dependent nuclear sequestration adds to our understanding of how restriction factors are regulated. PMID:26748714

``Phantom'' Modes in Ab Initio Tunneling Calculations: Implications for Theoretical Materials Optimization, Tunneling, and Transport

NASA Astrophysics Data System (ADS)

Barabash, Sergey V.; Pramanik, Dipankar

2015-03-01

Development of low-leakage dielectrics for semiconductor industry, together with many other areas of academic and industrial research, increasingly rely upon ab initio tunneling and transport calculations. Complex band structure (CBS) is a powerful formalism to establish the nature of tunneling modes, providing both a deeper understanding and a guided optimization of materials, with practical applications ranging from screening candidate dielectrics for lowest ``ultimate leakage'' to identifying charge-neutrality levels and Fermi level pinning. We demonstrate that CBS is prone to a particular type of spurious ``phantom'' solution, previously deemed true but irrelevant because of a very fast decay. We demonstrate that (i) in complex materials, phantom modes may exhibit very slow decay (appearing as leading tunneling terms implying qualitative and huge quantitative errors), (ii) the phantom modes are spurious, (iii) unlike the pseudopotential ``ghost'' states, phantoms are an apparently unavoidable artifact of large numerical basis sets, (iv) a presumed increase in computational accuracy increases the number of phantoms, effectively corrupting the CBS results despite the higher accuracy achieved in resolving the true CBS modes and the real band structure, and (v) the phantom modes cannot be easily separated from the true CBS modes. We discuss implications for direct transport calculations. The strategy for dealing with the phantom states is discussed in the context of optimizing high-quality high- κ dielectric materials for decreased tunneling leakage.

Effects of self-ligating brackets on oral hygiene and discomfort: a systematic review and meta-analysis of randomized controlled clinical trials.

PubMed

Yang, X; Su, N; Shi, Z; Xiang, Z; He, Y; Han, X; Bai, D

2017-02-01

Self-ligating brackets (SLBs) are widely adopted in clinic owing to their claimed superiorities. Here, we collected and analysed all randomized controlled clinical trials (RCTs) comparing SLBs with conventional brackets (CBs) and thereby investigated whether SLBs can relieve discomfort or promote oral hygiene. Electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese BioMedical Literature Database and the China National Knowledge Infrastructure were searched to find out RCTs comparing active or passive SLBs with CBs. Two reviewers extracted the data and assessed risks of bias independently. Any disagreement between them was resolved through discussion with a third reviewer. Meta-analysis was conducted on Review Manager 5.3. A total of 12 RCTs with 575 participants were included, and eight of the trials were synthesized quantitatively. Two trials were assessed as low risk of bias, whereas others as unclear risk of bias. Passive SLBs and CBs are not significantly different in plaque control. SLBs and CBs are not significantly different in discomfort reduction at any of four time points (4 h, 24 h, 3 days and 7 days). Clinical evidences from existing RCTs suggest that SLBs do not outperform CBs in reliving discomfort or promoting oral health in clinic. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intrahippocampal administration of anandamide increases REM sleep.

PubMed

Rueda-Orozco, Pavel Ernesto; Soria-Gómez, Edgar; Montes-Rodríguez, Corinne Jennifer; Pérez-Morales, Marcel; Prospéro-García, Oscar

2010-04-05

A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light-dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep-waking cycle at two points of the light-dark cycle. Our data indicate that the administration of ANA directly into the hippocampus increases REMs in a dose dependent manner during the dark but not during the light phase of the cycle. The increase of REMs was blocked by the CB1 antagonist AM251. This effect was specific for the hippocampus since ANA administrations in the surrounding cortex did not elicit any change in REMs. These results support the idea of a direct relationship between hippocampal activity and sleep mechanisms by means of eCBs. The data presented here show, for the first time that eCBs administered into the hippocampus trigger REMs and support previous studies where chemical stimulation of limbic areas triggered sleep.

Investigation on the preparation and chromatographic behavior of a new para-tert-butylcalix[4]arene-1,2-crown-4 stationary phase for high performance liquid chromatography.

PubMed

Hu, Kai; Zhao, Wenjie; Wen, Fuyong; Liu, Junwei; Zhao, Xiaolan; Xu, Zhanhui; Niu, Bailin; Ye, Baoxian; Wu, Yangjie; Zhang, Shusheng

2011-07-15

In the present work, a new para-tert-butylcalix[4]arene-1,2-crown-4 bonded silica stationary phase (CBS4-4) was synthesized, structurally characterized, and employed to separate polycyclic aromatic hydrocarbons (PAHs), phenols, aromatic amines, benzoic acid and its derivatives. The chromatographic behaviors of the prepared stationary phase were investigated and compared with ODS. The effects of methanol concentrations on the retention index show that CBS4-4 exhibits high selectivity for the above analytes. The separation mechanisms based on the different interactions between calixarene and the analytes were discussed. With the assistance of quantum chemistry calculation, the interaction Gibbs free energy change ΔG(solv) (in the mobile phase) of p, m and o-phenylenediamine positional isomers and para-tert-butylcalix[4]arene-1,2-crown-4 were obtained. The ΔG(solv) values were consistent with the retention behavior of p, m and o-phenylenediamine on the CBS4-4. According to the chromatographic data, it can be concluded that the selectivity of CBS4-4 for analytes is mainly ascribed to hydrophobic interaction, accompanied by other effects such as hydrogen bonding interaction, π-π and inclusion interaction. The CBS4-4 column has been successfully employed for the analysis of benzoic acid in Sprite drink. Copyright © 2011 Elsevier B.V. All rights reserved.

Surface fatigue life and failure characteristics of EX-53, CBS 1000M, and AISI 9310 gear materials

NASA Technical Reports Server (NTRS)

Townsend, D. P.

1985-01-01

Spur gear endurance tests and rolling-element surface fatigue tests are conducted to investigate EX-53 and CBS 1000M steels for use as advanced application gear materials, to determine their endurance characteristics, and to compare the results with the standard AISI 9310 gear material. The gear pitch diameter is 8.89 cm (3.50 in). Gear test conditions are an oil inlet temperature of 320 K (116 F), an oil outlet temperature of 350 K (170 F), a maximum Hertz stress of 1.71 GPa (248 ksi), and a speed of 10,000 rpm. Bench-type rolling-element fatigue tests are conducted at ambient temperature with a bar specimen speed of 12,500 rpm and a maximum Hertz stress of 4.83 GPa (700 ksi). The EX-53 test gears have a surface fatigue life of twice that of the AISI 9310 spur gears. The CBS 1000M test gears have a surface fatigue life of more than twice that of the AISI 9310 spur gears. However, the CBS 1000M gears experience a 30-percent tooth fracture failure which limits its use as a gear material. The rolling-contact fatigue lines of RC bar specimens of EX-53 and ASISI 9310 are approximately equal. However, the CBS 1000M RC specimens have a surface fatigue life of about 50 percent that of the AISI 9310.

CBS mutations and MTFHR SNPs causative of hyperhomocysteinemia in Pakistani children.

PubMed

Ibrahim, Shahnaz; Maqbool, Saadia; Azam, Maleeha; Iqbal, Mohammad Perwaiz; Qamar, Raheel

2018-03-29

Three index patients with hyperhomocysteinemia and ocular anomalies were screened for cystathionine beta synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Genotyping of hyperhomocysteinemia associated MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) was done by PCR-restriction fragment length polymorphism. Sanger sequencing was performed for CBS exonic sequences along with consensus splice sites. In the case of MTHFR polymorphisms, all the patients were heterozygous CT for the single nucleotide polymorphism (SNP) C677T and were therefore carriers of the risk allele (T), while the patients were homozygous CC for the risk genotype of the SNP A1298C. CBS sequencing resulted in the identification of two novel mutations, a missense change (c.467T>C; p.Leu156Pro) in exon 7 and an in-frame deletion (c.808_810del; p.Glu270del) in exon 10. In addition, a recurrent missense mutation (c.770C>T; p.Thr257Met) in exon 10 of the gene was also identified. The mutations were present homozygously in the patients and were inherited from the carrier parents. This is the first report from Pakistan where novel as well as recurrent CBS mutations causing hyperhomocysteinemia and lens dislocation in three patients from different families are being reported with the predicted effect of the risk allele of the MTHFR SNP in causing hyperhomocysteinemia.

Transversal changes, space closure, and efficiency of conventional and self-ligating appliances : A quantitative systematic review.

PubMed

Yang, Xianrui; Xue, Chaoran; He, Yiruo; Zhao, Mengyuan; Luo, Mengqi; Wang, Peiqi; Bai, Ding

2018-01-01

Self-ligating brackets (SLBs) were compared to conventional brackets (CBs) regarding their effectiveness on transversal changes and space closure, as well as the efficiency of alignment and treatment time. All previously published randomized controlled clinical trials (RCTs) dealing with SLBs and CBs were searched via electronic databases, e.g., MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. In addition, relevant journals were searched manually. Data extraction was performed independently by two reviewers and assessment of the risk of bias was executed using Cochrane Collaboration's tool. Discrepancies were resolved by discussion with a third reviewer. Meta-analyses were conducted using Review Manager (version 5.3). A total of 976 patients in 17 RCTs were included in the study, of which 11 could be produced quantitatively and 2 showed a low risk of bias. Meta-analyses were found to favor CB for mandibular intercanine width expansion, while passive SLBs were more effective in posterior expansion. Moreover, CBs had an apparent advantage during short treatment periods. However, SLBs and CBs did not differ in closing spaces. Based on current clinical evidence obtained from RCTs, SLBs do not show clinical superiority compared to CBs in expanding transversal dimensions, space closure, or orthodontic efficiency. Further high-level studies involving randomized, controlled, clinical trials are warranted to confirm these results.

FUS and TDP43 genetic variability in FTD and CBS

PubMed Central

Huey, Edward D.; Ferrari, Raffaele; Moreno, Jorge H.; Jensen, Christopher; Morris, Christopher M.; Potocnik, Felix; Kalaria, Rajesh N.; Tierney, Michael; Wassermann, Eric M.; Hardy, John; Grafman, Jordan; Momeni, Parastoo

2015-01-01

This study aimed to evaluate genetic variability in the FUS and TDP-43 genes, known to be mainly associated with amyotrophic lateral sclerosis (ALS), in patients with the diagnoses of frontotemporal lobar degeneration (FTLD) and corticobasal syndrome (CBS). We screened the DNA of 228 patients for all the exons and flanking introns of FUS and TDP-43 genes. We identified 2 novel heterozygous missense mutations in FUS: P106L (g.22508384>T) in a patient with behavioral variant frontotemporal dementia (bvFTD) and Q179H in several members of a family with behavioral variant FTD. We also identified the N267S mutation in TDP-43 in a CBS patient, previously only reported in 1 ALS family and 1 FTD patient. Additionally, we identified 2 previously reported heterozygous insertion and deletion mutations in Exon 5 of FUS; Gly174-Gly175 del GG (g. 4180–4185 delGAGGTG) in an FTD patient and Gly175-Gly176 ins GG (g. 4185–4186 insGAGGTG) in a patient with diagnosis of CBS. Not least, we have found a series of variants in FUS also in neurologically normal controls. In summary, we report that genetic variability in FUS and TDP-43 encompasses a wide range of phenotypes (including ALS, FTD, and CBS) and that there is substantial genetic variability in FUS gene in neurologically normal controls. PMID:21943958

Oculomotor Function in Frontotemporal Lobar Degeneration, Related Disorders and Alzheimer's Disease

ERIC Educational Resources Information Center

Garbutt, Siobhan; Matlin, Alisa; Hellmuth, Joanna; Schenk, Ana K.; Johnson, Julene K.; Rosen, Howard; Dean, David; Kramer, Joel; Neuhaus, John; Miller, Bruce L.; Lisberger, Stephen G.; Boxer, Adam L.

2008-01-01

Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were…

Anxiety and Charles Bonnet Syndrome

ERIC Educational Resources Information Center

Geueke, Anna; Morley, Michael G.; Morley, Katharine; Lorch, Alice; Jackson, MaryLou; Lambrou, Angeliki; Wenberg, June; Oteng-Amoako, Afua

2012-01-01

Introduction: Some persons with Charles Bonnet syndrome (CBS) suffer significant anxiety because of their visual hallucinations, while others do not. The aim of the study presented here was to compare levels of anxiety in persons with low vision with and without CBS. Methods: This retrospective study compared the level of anxiety in 31 persons…

Cajal, Psychologist of Science.

PubMed

Anaya-Reig, Nuria; Romo, Manuela

2017-12-04

This paper presents abundant empirical evidence to support the view that Santiago Ramón y Cajal was a pioneer of the emerging Psychology of Science discipline. Narrative analysis of his autobiography (Recollections of my Life) and some of his unspecialized works (Advice for a Young Investigator, The World from an Eighty-Year-Old's Point of View, and Café Chats) revealed that the Spanish histologist's interest in the psychology of scientists was part and parcel of a high-level, intellectual self-regulation strategy he applied on his path to success. This research led him to document various psychological conclusions about scientists in writing, so as to encourage, guide, and facilitate the work of junior researchers. Current knowledge of the Psychology of Science has confirmed many of the Nobel laureate's observations about psychosocial aspects of scientists, scientific reasoning, and creativity.

Rhodotorula rosulata sp. nov., Rhodotorula silvestris sp. nov. and Rhodotorula straminea sp. nov., novel myo-inositol-assimilating yeast species in the Microbotryomycetes.

PubMed

Golubev, Wladyslav I; Scorzetti, Gloria

2010-10-01

Three novel species are described as Rhodotorula rosulata sp. nov. (type strain VKM Y-2962(T) =CBS 10977(T)), Rhodotorula silvestris sp. nov. (type strain VKM Y-2971(T) =CBS 11420(T)) and Rhodotorula straminea sp. nov. (type strain VKM Y-2964(T) =CBS 10976(T)) based on the study of eight isolates from needle litter. The new species, phylogenetically located within the Microbotryomycetes, are related to glucuronate-assimilating species of the genus Rhodotorula. Sequencing of the D1/D2 domains of the LSU rDNA gene and the internal transcribed spacer (ITS) region, as well as physiological characterization, revealed their distinct taxonomic positions.

Crowding Effects on the Formation and Maintenance of Nuclear Bodies: Insights from Molecular-Dynamics Simulations of Simple Spherical Model Particles

PubMed Central

Cho, Eun Jin; Kim, Jun Soo

2012-01-01

The physics of structure formation and maintenance of nuclear bodies (NBs), such as nucleoli, Cajal bodies, promyelocytic leukemia bodies, and speckles, in a crowded nuclear environment remains largely unknown. We investigate the role of macromolecular crowding in the formation and maintenance of NBs using computer simulations of a simple spherical model, called Lennard-Jones (LJ) particles. LJ particles form a one-phase, dilute fluid when the intermolecular interaction is weaker than a critical value, above which they phase separate and form a condensed domain. We find that when volume-exclusive crowders exist in significant concentrations, domain formation is induced even for weaker intermolecular interactions, and the effect is more pronounced with increasing crowder concentration. Simulation results show that a previous experimental finding that promyelocytic leukemia bodies disappear in the less-crowded condition and reassemble in the normal crowded condition can be interpreted as a consequence of the increased intermolecular interactions between NB proteins due to crowding. Based on further analysis of the simulation results, we discuss the acceleration of macromolecular associations that occur within NBs, and the delay of diffusive transport of macromolecules within and out of NBs when the crowder concentration increases. This study suggests that in a polydisperse nuclear environment that is enriched with a variety of macromolecules, macromolecular crowding not only plays an important role in the formation and maintenance of NBs, but also may perform some regulatory functions in response to alterations in the crowding conditions. PMID:22947858

Identification of genes that function in the biogenesis and localization of small nucleolar RNAs in Saccharomyces cerevisiae.

PubMed

Qiu, Hui; Eifert, Julia; Wacheul, Ludivine; Thiry, Marc; Berger, Adam C; Jakovljevic, Jelena; Woolford, John L; Corbett, Anita H; Lafontaine, Denis L J; Terns, Rebecca M; Terns, Michael P

2008-06-01

Small nucleolar RNAs (snoRNAs) orchestrate the modification and cleavage of pre-rRNA and are essential for ribosome biogenesis. Recent data suggest that after nucleoplasmic synthesis, snoRNAs transiently localize to the Cajal body (in plant and animal cells) or the homologous nucleolar body (in budding yeast) for maturation and assembly into snoRNPs prior to accumulation in their primary functional site, the nucleolus. However, little is known about the trans-acting factors important for the intranuclear trafficking and nucleolar localization of snoRNAs. Here, we describe a large-scale genetic screen to identify proteins important for snoRNA transport in Saccharomyces cerevisiae. We performed fluorescence in situ hybridization analysis to visualize U3 snoRNA localization in a collection of temperature-sensitive yeast mutants. We have identified Nop4, Prp21, Tao3, Sec14, and Htl1 as proteins important for the proper localization of U3 snoRNA. Mutations in genes encoding these proteins lead to specific defects in the targeting or retention of the snoRNA to either the nucleolar body or the nucleolus. Additional characterization of the mutants revealed impairment in specific steps of U3 snoRNA processing, demonstrating that snoRNA maturation and trafficking are linked processes.

A convenient enantioselective CBS-reduction of arylketones in flow-microreactor systems.

PubMed

De Angelis, Sonia; De Renzo, Maddalena; Carlucci, Claudia; Degennaro, Leonardo; Luisi, Renzo

2016-05-04

A convenient, versatile, and green CBS-asymmetric reduction of aryl and heteroaryl ketones has been developed by using the microreactor technology. The study demonstrates that it is possible to handle borane solution safely within microreactors and that the reaction performs well using 2-MeTHF as a greener solvent.

School Engagement and Parental Involvement: The Case of Cross-Border Students in Singapore

ERIC Educational Resources Information Center

Yuen, Celeste Y. M.; Cheung, Alan C. K.

2014-01-01

The primary purpose of this paper is to examine the mutual relationship between school engagement of cross-border students (CBS) from Malaysia in Singapore and parental involvement in education. Focus-group interviews were conducted with school personnel, CBS and their non-local counterparts to provide a comprehensive understanding of the…

Long-term performance of thermoplastic composite material with cotton burr and stem (CBS) as a partial filler

USDA-ARS?s Scientific Manuscript database

Rationale: Cotton burr and stem (CBS) fraction of cotton gin byproducts has shown promise as a fiber filler in thermoplastic composites, with physical and mechanical properties comparable to that made with wood fiber fillers. However, the long-term performance of this composite material is not known...

New anamorphic yeast species: Candida infanticola sp. nov., Candida polysorbophila sp. nov., Candida transvaalensis sp. nov. and Trigonopsis californica sp. nov.

PubMed

Kurtzman, Cletus P

2007-08-01

Three new species of Candida and a new species of Trigonopsis are described based on their recognition from phylogenetic analysis of gene sequences from large subunit ribosomal RNA, ITS1/ITS2 rRNA, mitochondrial small subunit rRNA and cytochrome oxidase II. Candida infanticola sp. nov. (type strain NRRL Y-17858, CBS 7922) was isolated from the ear of an infant in Germany and is closely related to Candida sorbophila. Candida polysorbophila sp. nov. (type strain NRRL Y-27161, CBS 7317) is a member of the Zygoascus clade and was isolated in South Africa as a contaminant from an emulsion of white oil and polysorbate. Candida transvaalensis sp. nov. (type strain NRRL Y-27140, CBS 6663) was obtained from forest litter, the Transvaal, South Africa, and forms an isolated clade with Candida santjacobensis. Trigonopsis californica sp. nov. (type strain NRRL Y-27307, CBS 10351) represents a contaminant from wine in California, and forms a well-supported clade with Trigonopsis cantarellii, Trigonopsis variabilis and Trigonopsis vinaria.

Charles Bonnet syndrome in hemianopia, following antero-mesial temporal lobectomy for drug-resistant epilepsy.

PubMed

Contardi, Sara; Rubboli, Guido; Giulioni, Marco; Michelucci, Roberto; Pizza, Fabio; Gardella, Elena; Pinardi, Federica; Bartolomei, Ilaria; Tassinari, Carlo Alberto

2007-09-01

Charles Bonnet syndrome (CBS) is a disorder characterized by the occurrence of complex visual hallucinations in patients with acquired impairment of vision and without psychiatric disorders. In spite of the high incidence of visual field defects following antero-mesial temporal lobectomy for refractory temporal lobe epilepsy, reports of CBS in patients who underwent this surgical procedure are surprisingly rare. We describe a patient operated on for drug-resistant epilepsy. As a result of left antero-mesial temporal resection, she presented right homonymous hemianopia. A few days after surgery, she started complaining of visual hallucinations, such as static or moving "Lilliputian" human figures, or countryside scenes, restricted to the hemianopic field. The patient was fully aware of their fictitious nature. These disturbances disappeared progressively over a few weeks. The incidence of CBS associated with visual field defects following epilepsy surgery might be underestimated. Patients with post-surgical CBS should be reassured that it is not an epileptic phenomenon, and that it has a benign, self-limiting, course which does not usually require treatment.

Prosopo-affective agnosia associated with chronic organic brain syndrome.

PubMed

Kurucz, J; Feldmar, G; Werner, W

1979-02-01

Impairment of the ability to recognize facially expressed emotions was studied in 14 chronically disoriented patients with chronic organic brain syndrome (CBS). This impairment was named prosopo-affective agnosia (PAA). A diagnostic requirement was relatively intact neurologic functioning in underlying perceptual-verbal-motor processing. A test was designed for facial-affect recognition in the accurate differentiation of normal persons from chronically disoriented CBS patients. No normal subject made any errors in this test. Despite decades of illness and hospital living, patients with a history of schizophrenia or major affective disorders scored almost at a normal level (95 vs. 100 percent) in this test, and significantly higher (95 vs. 66 percent) than did the disoriented CBS patients. The social and therapeutic implications of the findings are stressed. CBS patients may be impaired with respect to receiving and appreciating elementary aspects of social communications such as recognizing a smile, anger, sadness or disapproval on the faces of people who surround them. This disability requires understanding and a special attitude on the part of the therapeutic team toward such patients.

In vitro hypoglycemic and cholesterol lowering effects of dietary fiber prepared from cocoa (Theobroma cacao L.) shells.

PubMed

Nsor-Atindana, John; Zhong, Fang; Mothibe, Kebitsamang Joseph

2012-10-01

Three dietary fiber (DF) powders; soluble dietary fiber (SDF), insoluble dietary fiber (IDF) and total dietary fiber (TDF) were prepared from cocoa bean shells (CBS) by enzymatic treatment. These DFs were evaluated for their effects on glucose adsorption, glucose diffusion, starch hydrolysis, cholesterol binding, sodium cholate binding and oil binding capacities using in vitro model systems by simulating gastric intestinal conditions. The results showed that SDF generally exhibited significantly (p < 0.05) higher glucose adsorption capacity (GAC), α-amylase inhibition activity, cholesterol and sodium cholate binding capacity, but less significant (>0.05) glucose dialysis retardation index (GDRI) and oil binding capacity, when compared with IDF and TDF which both showed similar effects. Moreover, it was discovered that the three CBS dietary fiber powders contained intrinsic antioxidants (phenolic compounds). The study suggested that CBS could be an alternative cheap source of DF with additional benefits. Thus, CBS fibers could be incorporated as low calorie bulk ingredients in high-fiber diet to reduce calorie and cholesterol levels and control blood glucose level.

Treatments for the challenging behaviours of adults with intellectual disabilities.

PubMed

Matson, Johnny L; Neal, Daniene; Kozlowski, Alison M

2012-10-01

To provide an overview and critical assessment of common problems and best evidence practice in treatments for the challenging behaviours (CBs) of adults with intellectual disabilities (IDs). Commonly observed problems that present obstacles to successful treatment plans are discussed, followed by an analysis of available research on the efficacy of behavioural and pharmacological therapies. Behavioural and pharmacological interventions are most commonly used when addressing CBs in people with IDs. However, within each of these techniques, there are methods that have support in the literature for efficacy and those that do not. As clinicians, it is important to follow research so that we are engaging in best practices when developing treatment plans for CBs. One of the most consuming issues for psychiatrists and other mental health professionals who work with people who evince developmental disabilities, such as IDs, are CBs. These problems are very dangerous and are a major impediment to independent, less restrictive living. However, there is a major gap between what researchers show is effective and much of what occurs in real-world settings.

The effects of daily supplementation of Dendrobium huoshanense polysaccharide on ethanol-induced subacute liver injury in mice by proteomic analysis.

PubMed

Wang, Xiao-Yu; Luo, Jian-Ping; Chen, Rui; Zha, Xue-Qiang; Wang, He

2014-09-01

Polysaccharides isolated from edible Dendrobium huoshanense have been shown to possess a hepatoprotection function for selenium- and carbon tetrachloride-induced liver injury. In this study, we investigated the preventive effects of daily supplementation with an homogeneous polysaccharide (DHP) purified from D. huoshanense on ethanol-induced subacute liver injury in mice and its potential mechanisms in liver protection by a proteomic approach. DHP was found to effectively depress the increased ratio of liver weight to body weight, reduce the elevated levels of serum aspartate aminotransferase, total cholesterol, total bilirubin and low density lipoprotein, and alleviate hepatic steatosis in mice with ethanol-induced subacute liver injury. Hepatic proteomics analysis performed by two-dimensional difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) revealed that cystathionine beta-synthase (Cbs) and D-lactate dehydrogenase (Ldhd) were two key proteins regulated by daily DHP intervention, which may assist in correcting the abnormal hepatic methionine metabolism pathway and decreasing the level of hepatic methylglyoxal generated from disordered metabolic pathways caused by ethanol. Our data suggest that DHP can protect liver function from alcoholic injury with complicated molecular mechanisms involving regulation of Cbs and Ldhd.

The effect of virtual reality training on unilateral spatial neglect in stroke patients.

PubMed

Kim, Yong Mi; Chun, Min Ho; Yun, Gi Jeong; Song, Young Jin; Young, Han Eun

2011-06-01

To investigate the effect of virtual reality training on unilateral spatial neglect in stroke patients. Twenty-four stroke patients (14 males and 10 females, mean age=64.7) who had unilateral spatial neglect as a result of right hemisphere stroke were recruited. All patients were randomly assigned to either the virtual reality (VR) group (n=12) or the control group (n=12). The VR group received VR training, which stimulated the left side of their bodies. The control group received conventional neglect therapy such as visual scanning training. Both groups received therapy for 30 minutes a day, five days per week for three weeks. Outcome measurements included star cancellation test, line bisection test, Catherine Bergego scale (CBS), and the Korean version of modified Barthel index (K-MBI). These measurements were taken before and after treatment. There were no significant differences in the baseline characteristics and initial values between the two groups. The changes in star cancellation test results and CBS in the VR group were significantly higher than those of the control group after treatment. The changes in line bisection test score and the K-MBI in the VR group were not statistically significant. This study suggests that virtual reality training may be a beneficial therapeutic technique on unilateral spatial neglect in stroke patients.

Comparison of Biochemical Activities between High and Low Lipid-Producing Strains of Mucor circinelloides: An Explanation for the High Oleaginicity of Strain WJ11.

PubMed

Tang, Xin; Chen, Haiqin; Chen, Yong Q; Chen, Wei; Garre, Victoriano; Song, Yuanda; Ratledge, Colin

2015-01-01

The oleaginous fungus, Mucor circinelloides, is one of few fungi that produce high amounts of γ-linolenic acid (GLA); however, it usually only produces <25% lipid. Nevertheless, a new strain (WJ11) isolated in this laboratory can produce lipid up to 36% (w/w) cell dry weight (CDW). We have investigated the potential mechanism of high lipid accumulation in M. circinelloides WJ11 by comparative biochemical analysis with a low lipid-producing strain, M. circinelloides CBS 277.49, which accumulates less than 15% (w/w) lipid. M. circinelloides WJ11 produced more cell mass than that of strain CBS 277.49, although with slower glucose consumption. In the lipid accumulation phase, activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in strain WJ11 were greater than in CBS 277.49 by 46% and 17%, respectively, and therefore may provide more NADPH for fatty acid biosynthesis. The activities of NAD+:isocitrate dehydrogenase and NADP+:isocitrate dehydrogenase, however, were 43% and 54%, respectively, lower in WJ11 than in CBS 277.49 and may retard the tricarboxylic acid cycle and thereby provide more substrate for ATP:citrate lyase (ACL) to produce acetyl-CoA. Also, the activities of ACL and fatty acid synthase in the high lipid-producing strain, WJ11, were 25% and 56%, respectively, greater than in strain CBS 277.49. These enzymes may therefore cooperatively regulate the fatty acid biosynthesis in these two strains.

Primary hepatocytes from mice lacking cysteine dioxygenase show increased cysteine concentrations and higher rates of metabolism of cysteine to hydrogen sulfide and thiosulfate

PubMed Central

Jurkowska, Halina; Roman, Heather B.; Hirschberger, Lawrence L.; Sasakura, Kiyoshi; Nagano, Tetsuo; Hanaoka, Kenjiro; Krijt, Jakub

2016-01-01

The oxidation of cysteine in mammalian cells occurs by two routes: a highly regulated direct oxidation pathway in which the first step is catalyzed by cysteine dioxygenase (CDO) and by desulfhydration-oxidation pathways in which the sulfur is released in a reduced oxidation state. To assess the effect of a lack of CDO on production of hydrogen sulfide (H2S) and thiosulfate (an intermediate in the oxidation of H2S to sulfate) and to explore the roles of both cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS) in cysteine desulfhydration by liver, we investigated the metabolism of cysteine in hepatocytes isolated from Cdo1-null and wild-type mice. Hepatocytes from Cdo1-null mice produced more H2S and thiosulfate than did hepatocytes from wild-type mice. The greater flux of cysteine through the cysteine desulfhydration reactions catalyzed by CTH and CBS in hepatocytes from Cdo1-null mice appeared to be the consequence of their higher cysteine levels, which were due to the lack of CDO and hence lack of catabolism of cysteine by the cysteinesulfinate-dependent pathways. Both CBS and CTH appeared to contribute substantially to cysteine desulfhydration, with estimates of 56 % by CBS and 44 % by CTH in hepatocytes from wild-type mice, and 63 % by CBS and 37 % by CTH in hepatocytes from Cdo1-null mice. PMID:24609271

Starmerella reginensis f.a., sp. nov. and Starmerella kourouensis f.a., sp. nov., isolated from flowers in French Guiana.

PubMed

Amoikon, Tiemele Laurent Simon; Grondin, Cécile; Djéni, Théodore N'Dédé; Jacques, Noémie; Casaregola, Serge

2018-05-21

Analysis of yeasts isolated from various biotopes in French Guiana led to the identification of two strains isolated from flowers and designated CLIB 1634 T and CLIB 1707 T . Comparison of the D1/D2 domain of the large subunit (LSU D1/D2) rRNA gene sequences of CLIB 1634 T and CLIB 1707 T to those in the GenBank database revealed that these strains belong to the Starmerella clade. Strain CLIB 1634 T was shown to diverge from the closely related Starmerella apicola type strain CBS 2868 T with a sequence divergence of 1.34 and 1.30 %, in the LSU D1/D2 rRNA gene and internal transcribed spacer (ITS) sequences respectively. Strain CLIB 1634 T and Candida apicola CBS 2868 T diverged by 3.81 and 14.96 % at the level of the protein-coding gene partial sequences EF-1α and RPB2, respectively. CLIB 1707 T was found to have sequence divergence of 3.88 and 9.16 % in the LSU D1/D2 rRNA gene and ITS, respectively, from that of the most closely related species Starmerella ratchasimensis type strain CBS 10611 T . The species Starmerella reginensis f.a., sp. nov. and Starmerella kourouensis f.a., sp. nov. are proposed to accommodate strains CLIB 1634 T (=CBS 15247 T ) and CLIB 1707 T (=CBS 15257 T ), respectively.

Penicillium araracuarense sp. nov., Penicillium elleniae sp. nov., Penicillium penarojense sp. nov., Penicillium vanderhammenii sp. nov. and Penicillium wotroi sp. nov., isolated from leaf litter.

PubMed

Houbraken, Jos; López-Quintero, Carlos A; Frisvad, Jens C; Boekhout, Teun; Theelen, Bart; Franco-Molano, Ana Esperanza; Samson, Robert A

2011-06-01

Several species of the genus Penicillium were isolated during a survey of the mycobiota of leaf litter and soil in Colombian Amazon forest. Five species, Penicillium penarojense sp. nov. (type strain CBS 113178(T) = IBT 23262(T)), Penicillium wotroi sp. nov. (type strain CBS 118171(T) = IBT 23253(T)), Penicillium araracuarense sp. nov. (type strain CBS 113149(T) = IBT 23247(T)), Penicillium elleniae sp. nov. (type strain CBS 118135(T) = IBT 23229(T)) and Penicillium vanderhammenii sp. nov. (type strain CBS 126216(T) = IBT 23203(T)) are described here as novel species. Their taxonomic novelty was determined using a polyphasic approach, combining phenotypic, molecular (ITS and partial β-tubulin sequences) and extrolite data. Phylogenetic analyses showed that each novel species formed a unique clade for both loci analysed and that they were most closely related to Penicillium simplicissimum, Penicillium janthinellum, Penicillium daleae and Penicillium brasilianum. An overview of the phylogeny of this taxonomically difficult group is presented, and 33 species are accepted. Each of the five novel species had a unique extrolite profile of known and uncharacterized metabolites and various compounds, such as penicillic acid, andrastin A, pulvilloric acid, paxillin, paspaline and janthitrem, were commonly produced by these phylogenetically related species. The novel species had a high growth rate on agar media, but could be distinguished from each other by several macro- and microscopical characteristics.

A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme Cystathionine β-Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?

PubMed Central

Malagrinò, Francesca; Santo, Paulo E.; Gutierres, André; Bandeiras, Tiago M.; Leandro, Paula

2017-01-01

The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5′-phosphate- (PLP-) dependent cystathionine β-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenic CBS mutations is not yet fully understood. Here we found that the ferrous heme of the reportedly mild p.P49L CBS variant has altered spectral properties and markedly increased affinity for CO, making the protein much more prone than wild type (WT) CBS to inactivation at physiological CO levels. The higher CO affinity could result from the slightly higher flexibility in the heme surroundings revealed by solving at 2.80-Å resolution the crystallographic structure of a truncated p.P49L. Additionally, we report that p.P49L displays impaired H2S-generating activity, fully rescued by PLP supplementation along the purification, despite a minor responsiveness to AdoMet. Altogether, the results highlight how increased propensity to CO inactivation of an otherwise WT-like variant may represent a novel pathogenic mechanism in classical homocystinuria. PMID:28421128

Consequences of the trans-Atlantic slave trade on medicinal plant selection: plant use for cultural bound syndromes affecting children in Suriname and Western Africa.

PubMed

Vossen, Tessa; Towns, Alexandra; Ruysschaert, Sofie; Quiroz, Diana; van Andel, Tinde

2014-01-01

Folk perceptions of health and illness include cultural bound syndromes (CBS), ailments generally confined to certain cultural groups or geographic regions and often treated with medicinal plants. Our aim was to compare definitions and plant use for CBS regarding child health in the context of the largest migration in recent human history: the trans-Atlantic slave trade. We compared definitions of four CBS (walk early, evil eye, atita and fontanels) and associated plant use among three Afro-Surinamese populations and their African ancestor groups in Ghana, Bénin and Gabon. We expected plant use to be similar on species level, and assumed the majority to be weedy or domesticated species, as these occur on both continents and were probably recognized by enslaved Africans. Data were obtained by identifying plants mentioned during interviews with local women from the six different populations. To analyse differences and similarities in plant use we used Detrended Component Analysis (DCA) and a Wald Chi-square test. Definitions of the four cultural bound syndromes were roughly the same on both continents. In total, 324 plant species were used. There was little overlap between Suriname and Africa: 15 species were used on two continents, of which seven species were used for the same CBS. Correspondence on family level was much higher. Surinamese populations used significantly more weedy species than Africans, but equal percentages of domesticated plants. Our data indicate that Afro-Surinamers have searched for similar plants to treat their CBS as they remembered from Africa. In some cases, they have found the same species, but they had to reinvent the largest part of their herbal pharmacopeia to treat their CBS using known plant families or trying out new species. Ideas on health and illness appear to be more resilient than the use of plants to treat them.

Efficacy of ultraviolet light exposure against survival of Listeria monocytogenes on conveyor belts.

PubMed

Morey, Amit; McKee, Shelly R; Dickson, James S; Singh, Manpreet

2010-06-01

Listeria monocytogenes has been repeatedly isolated from foods and food-processing facilities including food contact surfaces such as conveyor belts (CB). CBs are often difficult to clean and require rigorous sanitation programs for decontamination. Ultraviolet (UV) light has exhibited microbicidal properties on food contact surfaces and this study was conducted to determine the efficacy of UV against L. monocytogenes on CB made of different materials. A four-strain cocktail of L. monocytogenes (serotypes 3A, 4A, 4B, and 4C) was made to give a suspension of approximately 10(7) CFU/mL. CBs made from four different types of materials, (1) Ropanyl DM 8/2 A2 + 04 (belt 1), (2) Volta FRMW-3.0 (belt 2), (3) Volta FRMB-3.0 (belt 3), and (4) Ropanyl DM (belt 4), were inoculated with 1 mL of the four-strain cocktail (approximately 10(7) CFU/mL) of the bacterial suspension. CBs were treated with UV light (254 nm) for 1 and 3 sec at 5.53 and 5.95 mW/cm(2). Three replications of the experiments were conducted. Two-way analysis of variance of survival populations of L. monocytogenes showed that bacterial counts were significantly reduced (p < 0.05) on all belt types irrespective of UV light intensities and times of exposure. L. monocytogenes populations were reduced (p < 0.05) to below detection limits on belts 1, 2, and 3 after exposure to 5.95 mW/cm(2) UV light intensity for 3 sec. L. monocytogenes-inoculated CBs that were exposed to 5.53 mW/cm(2) showed higher (p < 0.05) survival populations of L. monocytogenes compared with 5.95 mW/cm(2) on all the four CBs. Belt 4 showed survival populations of L. monocytogenes ranging from 1.42 to 1.73 log(10) CFU/cm(2) after UV light treatment for 1 and 3 sec. UV light can be effectively used to reduce L. monocytogenes contamination on CBs.

Thermochemistry of C7H16 to C10H22 alkane isomers: primary, secondary, and tertiary C-H bond dissociation energies and effects of branching.

PubMed

Hudzik, Jason M; Bozzelli, Joseph W; Simmie, John M

2014-10-09

Standard enthalpies of formation (ΔH°f 298) of methyl, ethyl, primary and secondary propyl, and n-butyl radicals are evaluated and used in work reactions to determine internal consistency. They are then used to calculate the enthalpy of formation for the tert-butyl radical. Other thermochemical properties including standard entropies (S°(T)), heat capacities (Cp(T)), and carbon-hydrogen bond dissociation energies (C-H BDEs) are reported for n-pentane, n-heptane, 2-methylhexane, 2,3-dimethylpentane, and several branched higher carbon number alkanes and their radicals. ΔH°f 298 and C-H BDEs are calculated using isodesmic work reactions at the B3LYP (6-31G(d,p) and 6-311G(2d,2p) basis sets), CBS-QB3, CBS-APNO, and G3MP2B3 levels of theory. Structures, moments of inertia, vibrational frequencies, and internal rotor potentials are calculated at the B3LYP/6-31G(d,p) level for contributions to entropy and heat capacities. Enthalpy calculations for these hydrocarbon radical species are shown to have consistency with the CBS-QB3 and CBS-APNO methods using all work reactions. Our recommended ideal gas phase ΔH°f 298 values are from the average of all CBS-QB3, CBS-APNO, and for G3MP2B3, only where the reference and target radical are identical types, and are compared with literature values. Calculated values show agreement between the composite calculation methods and the different work reactions. Secondary and tertiary C-H bonds in the more highly branched alkanes are shown to have bond energies that are several kcal mol(-1) lower than the BDEs in corresponding smaller molecules often used as reference species. Entropies and heat capacities are calculated and compared to literature values (when available) when all internal rotors are considered.

Comparative Effects of Parathion and Chlorpyrifos on Endocannabinoid and Endocannabinoid-Like Lipid Metabolites in Rat Striatum

PubMed Central

Liu, Jing; Parsons, Loren; Pope, Carey

2015-01-01

Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications. PMID:26215119

Comparative effects of parathion and chlorpyrifos on endocannabinoid and endocannabinoid-like lipid metabolites in rat striatum.

PubMed

Liu, Jing; Parsons, Loren; Pope, Carey

2015-09-01

Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications. Copyright © 2015 Elsevier Inc. All rights reserved.

A practical proposal for solving the world's cigarette butt problem: Recycling in fired clay bricks.

PubMed

Mohajerani, Abbas; Kadir, Aeslina Abdul; Larobina, Luke

2016-06-01

The disposal and littering of cigarette butts (CBs) is a serious environmental problem. Trillions of cigarettes are produced every year worldwide, resulting in millions of tonnes of toxic waste being dumped into the environment in the form of cigarette butts. As CBs have poor biodegradability, it can take many years for them to break down. This paper reviews and presents some of the results of a study on the recycling of CBs into fired clay bricks. Bricks with 2.5%, 5%, 7.5%, and 10% CB content by weight were manufactured and tested, and then compared against control clay bricks with 0% CB content. The results showed that the dry density decreased by up to 30% and the compressive strength decreased by 88% in bricks with 10% CBs. The calculated compressive strength of bricks with 1% CBs was determined to be 19.53Mpa. To investigate the effect of mixing time, bricks with 7.5% CB content were manufactured with different mixing times of 5, 10, and 15min. To test the effect of heating time on the properties of CB bricks, the heating rate used during manufacturing was changed to 0.7, 2, 5, and 10°Cmin(-1). Bricks with 0% and 5% CB content were fired with these heating rates. Leachate tests were carried out for bricks with 0%, 2.5%, 5%, and 10% CB content. The emissions released during firing were tested for bricks with 0% and 5% CB content using heating rates of 0.7, 2, 5, and 10°Cmin(-1). The gases tested were carbon monoxide (CO), carbon dioxide (CO2), chlorine (Cl2), nitrogen oxide (NO), and hydrogen cyanide (HCN). Finally, estimations were made for the energy that could be saved by firing bricks incorporating CBs. Calculations showed that up to 58% of the firing energy could potentially be saved. Bricks were shown to be a viable solution for the disposal of CBs. They can reduce contamination caused by cigarette butts and provide a masonry construction material that can be either loadbearing or non-loadbearing, depending on the quantity of CBs incorporated. This paper proposes the use of bricks with 1% CB content throughout the brick-manufacturing industry. If bricks contained as little as 1% CB content, they would still provide a solution for the issue of CB recycling while maintaining properties very similar to those of a non-CB brick. Our calculations show that, theoretically, only 2.5% of the world's annual brick production is necessary to completely offset the worldwide, annual cigarette production. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-level ab initio predictions for the ionization energies and heats of formation of five-membered-ring molecules: thiophene, furan, pyrrole, 1,3-cyclopentadiene, and borole, C4H4X/C4H4X+ (X = S, O, NH, CH2, and BH).

PubMed

Lo, Po-Kam; Lau, Kai-Chung

2011-02-10

The ionization energies (IEs) and heats of formation (ΔH°(f0)/ΔH°(f298)) for thiophene (C(4)H(4)S), furan (C(4)H(4)O), pyrrole (C(4)H(4)NH), 1,3-cyclopentadiene (C(4)H(4)CH(2)), and borole (C(4)H(4)BH) have been calculated by the wave function-based ab initio CCSD(T)/CBS approach, which involves the approximation to the complete basis set (CBS) limit at the coupled-cluster level with single and double excitations plus a quasi-perturbative triple excitation [CCSD(T)]. Where appropriate, the zero-point vibrational energy correction (ZPVE), the core-valence electronic correction (CV), and the scalar relativistic effect (SR) are included in these calculations. The respective CCSD(T)/CBS predictions for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), being 8.888, 8.897, 8.222, and 8.582 eV, are in excellent agreement with the experimental values obtained from previous photoelectron and photoion measurements. The ΔH°(f0)/ΔH°(f298) values for the aforementioned molecules and their corresponding cations have also been predicted by the CCSD(T)/CBS method, and the results are compared with the available experimental data. The comparisons between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2) suggest that the CCSD(T)/CBS procedure is capable of predicting reliable IE values for five-membered-ring molecules with an uncertainty of ±13 meV. In view of the excellent agreements between the CCSD(T)/CBS predictions and the experimental values for C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, and C(4)H(4)CH(2), the similar CCSD(T)/CBS IE and ΔH°(f0)/ΔH°(f298) predictions for C(4)H(4)BH, whose thermochemical data are not readily available due to its reactive nature, should constitute a reliable data set. The CCSD(T)/CBS IE(C(4)H(4)BH) value is 8.868 eV, and ΔH°(f0)/ΔH°(f298) values for C(4)H(4)BH and C(4)H(4)BH(+) are 269.5/258.6 and 1125.1/1114.6 kJ/mol, respectively. The highest occupied molecular orbitals (HOMO) of C(4)H(4)S, C(4)H(4)O, C(4)H(4)NH, C(4)H(4)CH(2), and C(4)H(4)BH have also been studied by the natural bond orbital (NBO) method, and the extent of π-electron delocalization in these five-membered rings are discussed in correlation with their molecular structures and orbitals.

News Source Use in the Crash of 1987: A Study of Four National Media.

ERIC Educational Resources Information Center

Lasorsa, Dominic L.; Reese, Stephen D.

1990-01-01

Examines coverage of the stock market crash in 1987 by CBS Evening News, "Newsweek," the "New York Times," and "Wall Street Journal." Finds that print media favored Wall Street sources whereas CBS favored government sources. Finds that news media favor high prestige sources and that use of different sources results in…

Genome Sequence of the Yeast Clavispora lusitaniae Type Strain CBS 6936.

PubMed

Durrens, Pascal; Klopp, Christophe; Biteau, Nicolas; Fitton-Ouhabi, Valérie; Dementhon, Karine; Accoceberry, Isabelle; Sherman, David J; Noël, Thierry

2017-08-03

Clavispora lusitaniae , an environmental saprophytic yeast belonging to the CTG clade of Candida , can behave occasionally as an opportunistic pathogen in humans. We report here the genome sequence of the type strain CBS 6936. Comparison with sequences of strain ATCC 42720 indicates conservation of chromosomal structure but significant nucleotide divergence. Copyright © 2017 Durrens et al.

Genome Sequence of the Yeast Clavispora lusitaniae Type Strain CBS 6936

PubMed Central

Klopp, Christophe; Biteau, Nicolas; Fitton-Ouhabi, Valérie; Dementhon, Karine; Accoceberry, Isabelle; Sherman, David J.; Noël, Thierry

2017-01-01

ABSTRACT Clavispora lusitaniae, an environmental saprophytic yeast belonging to the CTG clade of Candida, can behave occasionally as an opportunistic pathogen in humans. We report here the genome sequence of the type strain CBS 6936. Comparison with sequences of strain ATCC 42720 indicates conservation of chromosomal structure but significant nucleotide divergence. PMID:28774979

Rhodotorula portillonensis sp. nov., a basidiomycetous yeast isolated from Antarctic shallow-water marine sediment.

PubMed

Laich, Federico; Vaca, Inmaculada; Chávez, Renato

2013-10-01

During the characterization of the mycobiota associated with shallow-water marine environments from Antarctic sea, a novel pink yeast species was isolated. Sequence analysis of the D1/D2 domain of the LSU rDNA gene and 5.8S-ITS regions revealed that the isolated yeast was closely related to Rhodotorula pallida CBS 320(T) and Rhodotorula benthica CBS 9124(T). On the basis of morphological, biochemical and physiological characterization and phylogenetic analyses, a novel basidiomycetous yeast species, Rhodotorula portillonensis sp. nov., is proposed. The type strain is Pi2(T) ( = CBS 12733(T)  = CECT 13081(T)) which was isolated from shallow-water marine sediment in Fildes Bay, King George Island, Antarctica.

[Santiago Ramón y Cajal: his activity as a military doctor (1873-1875)].

PubMed

Moreno Martinez, J M; Martin Araguz, A

Santiago Ram n y Cajal entered the Medical Corps after graduating in Medicine in 1873. His marked Spanish nationalist character and his excellent physical condition led him to serve in the third Carlist war as a medical lieutenant and later in the Cuban War as a captain. His stay in Cuba, however, was marked by hardship and illness. The decline of Spain s colonialist policy, the war that was fought in a hostile climate and atmosphere, and the corruption of the military officers led to Santiago being posted to the frontlines on a fixed logistics system of trails. All this was to end in military failure and the subsequent loss of the colony. Disillusioned and seriously ill from malaria, which nearly killed him, he returned to Spain after being discharged for illness. Shortly afterwards, thanks to Dr. Jenaro Casas, he became a university lecturer, which put an end to his military career

A Contractile Network of Interstitial Cells of Cajal in the Supratarsal Mueller's Smooth Muscle Fibers With Sparse Sympathetic Innervation

PubMed Central

Yuzuriha, Shunsuke; Matsuo, Kiyoshi; Ban, Ryokuya; Yano, Shiharu; Moriizumi, Tetsuji

2012-01-01

Background: We previously reported that the supratarsal Mueller's muscle is innervated by both sympathetic efferent fibers and trigeminal proprioceptive afferent fibers, which function as mechanoreceptors-inducing reflexive contractions of both the levator and frontalis muscles. Controversy still persists regarding the role of the mechanoreceptors in Mueller's muscle; therefore, we clinically and histologically investigated Mueller's muscle. Methods: We evaluated the role of phenylephrine administration into the upper fornix in contraction of Mueller's smooth muscle fibers and how intraoperative stretching of Mueller's muscle alters the degree of eyelid retraction in 20 patients with aponeurotic blepharoptosis. In addition, we stained Mueller's muscle in 7 cadavers with antibodies against α-smooth muscle actin, S100, tyrosine hydroxylase, c-kit, and connexin 43. Results: Maximal eyelid retraction occurred approximately 3.8 minutes after administration of phenylephrine and prolonged eyelid retraction for at least 20 minutes after administration. Intraoperative stretching of Mueller's muscle increased eyelid retraction due to its reflexive contraction. The tyrosine hydroxylase antibody sparsely stained postganglionic sympathetic nerve fibers, whereas the S100 and c-kit antibodies densely stained the interstitial cells of Cajal (ICCs) among Mueller's smooth muscle fibers. A connexin 43 antibody failed to stain Mueller's muscle. Conclusions: A contractile network of ICCs may mediate neurotransmission within Mueller's multiunit smooth muscle fibers that are sparsely innervated by postganglionic sympathetic fibers. Interstitial cells of Cajal may also serve as mechanoreceptors that reflexively contract Mueller's smooth muscle fibers, forming intimate associations with intramuscular trigeminal proprioceptive fibers to induce reflexive contraction of the levator and frontalis muscles. PMID:22359687

Role of hydrogen sulfide within the dorsal motor nucleus of the vagus in the control of gastric function in rats.

PubMed

Sun, H-Z; Yu, K-H; Ai, H-B

2015-05-01

Hydrogen sulfide (H2 S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. This study aimed to clarify the role of H2 S within the dorsal motor nucleus of the vagus (DMV) in the control of gastric function in rats. Cystathionine β-synthetase (CBS) is an important generator of endogenous H2 S in the brain. We investigated the distribution of CBS in the DMV using immunohistochemical method, and the effects of H2 S on gastric motility and on gastric acid secretion. CBS-immunoreactive (IR) neurons were detected in the rostral, intermediate and caudal DMV, with the highest number of CBS-IR neurons in the caudal DMV, and the lowest in the intermediate DMV. We also found that microinjection of the exogenous H2 S donor NaHS (0.04 and 0.08 mol/L; 0.1 μL; n = 6; p < 0.05) into the DMV significantly inhibited gastric motility with a dose-dependent trend, and promoted gastric acid secretion in Wistar rats. Microinjection of the same volume of physiological saline (PS; 0.1 μL, n = 6, p > 0.05) at the same location did not noticeably change gastric motility and acid secretion. The data from these experiments suggest that the CBS that produces H2 S is present in the DMV, and microinjection of NaHS into the DMV inhibited gastric motility and enhanced gastric acid secretion in rats. © 2015 John Wiley & Sons Ltd.

Cigarette Butt Decomposition and Associated Chemical Changes Assessed by 13C CPMAS NMR

PubMed Central

Bonanomi, Giuliano; Incerti, Guido; Cesarano, Gaspare; Gaglione, Salvatore A.; Lanzotti, Virginia

2015-01-01

Cigarette butts (CBs) are the most common type of litter on earth, with an estimated 4.5 trillion discarded annually. Apart from being unsightly, CBs pose a serious threat to living organisms and ecosystem health when discarded in the environment because they are toxic to microbes, insects, fish and mammals. In spite of the CB toxic hazard, no studies have addressed the effects of environmental conditions on CB decomposition rate. In this study we investigate the interactive effects of substrate fertility and N transfer dynamics on CB decomposition rate and carbon quality changes. We carried out an experiment using smoked CBs and wood sticks, used as a slow decomposing standard organic substrate, incubated in both laboratory and field conditions for two years. CB carbon quality changes during decomposition was assessed by 13C CPMAS NMR. Our experiment confirmed the low degradation rate of CBs which, on average, lost only 37.8% of their initial mass after two years of decomposition. Although a net N transfer occurred from soil to CBs, contrary to our hypothesis, mass loss in the medium-term (two years) was unaffected by N availability in the surrounding substrate. The opposite held for wood sticks, in agreement with the model that N-rich substrates promote the decomposition of other N-poor natural organic materials with a high C/N ratio. As regards CB chemical quality, after two years of decomposition 13C NMR spectroscopy highlighted very small changes in C quality that are likely to reflect a limited microbial attack. PMID:25625643

Symmetric corticobasal degeneration (S-CBD).

PubMed

Hassan, Anhar; Whitwell, Jennifer L; Boeve, Bradley F; Jack, Clifford R; Parisi, Joseph E; Dickson, Dennis W; Josephs, Keith A

2010-03-01

Corticobasal degeneration (CBD) is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome (CBS) and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction. Asymmetry is also emphasized on neuroimaging. To describe a series of cases of CBD with symmetric clinical features and to compare clinical and imaging features of these symmetric CBD cases (S-CBD) to typical cases of CBS with CBD pathology. All cases of pathologically confirmed CBD from the Mayo Clinic Rochester database were identified. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed. Subjects were classified as S-CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. S-CBD cases were compared to 10 randomly selected typical CBS cases. Five cases (2 female) met criteria for S-CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena. S-CBD cases had significantly less asymmetric atrophy when compared with CBS cases (p=0.009); they were also younger at onset (median 61 versus 66 years, p<0.05) and death (67 versus 73 years, p<0.05). Family history was present in 40% of S-CBD cases. CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Effects of RAMEB and/or mechanical mixing on the bioavailability and biodegradation of PCBs in soil/slurry.

PubMed

Hu, Jinxing; Wang, Yalin; Su, Xiaomei; Yu, Chunna; Qin, Zhihui; Wang, Hui; Hashmi, Muhammad Z; Shi, Jiyan; Shen, Chaofeng

2016-07-01

Microbial remediation is preferred as a clean and cost-effective method for restoring environments polluted by organics. But the biodegradation rates of hydrophobic organic contaminants (HOCs) are usually extremely restricted by their low bioavailability, especially in soil. Here, a physical method (mechanical mixing) and a chemical method (randomly methylated-β-cyclodextrins, RAMEB) were adopted to improve the bioavailability and biodegradation of polychlorinated biphenyls (PCBs) of an aged soil. The bioavailability of tri-CBs was increased by adding RAMEB in soil/slurry or assisting mechanical mixing in slurry, but these methods had no effects on the bioavailability of tetra-CBs and high chlorinated PCBs (Cl > 4). The degradation rate of tri-CBs could be obviously enhanced by adding RAMEB in soil or assisting mechanical mixing in slurry. The highest removal amount of tri-CBs reached 43.8% in 100 d with a first-order decay kinetics constant of 0.0059 d(-1). But the removal of tetra-CBs and high chlorinated PCBs (Cl > 4) were not significant in all mesocosms, possibly due to the lack or weakness of the native degrading microflora. Based on the analysis of the richness and diversity of bacterial communities, the characteristics of the heatmap and the variation of bphC copy numbers in the soil/slurry mesocosms, it could be inferred that there was no obvious corresponding relationship between the variation of the bacterial communities and the physical/chemical measures. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytologic assessment of estrogen receptor, progesterone receptor, and HER2 status in metastatic breast carcinoma.

PubMed

Pareja, Fresia; Murray, Melissa P; Jean, Ryan Des; Konno, Fumiko; Friedlander, Maria; Lin, Oscar; Edelweiss, Marcia

2017-01-01

Discordance in the receptor status between primary breast carcinomas (PBC) and corresponding metastasis is well documented. Interrogation of the receptor status of metastatic breast carcinoma (MBC) in cytology material is common practice; however, its utility has not been thoroughly validated. We studied patients with MBC, and evaluated the concordance rates of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between PBC surgical specimens and corresponding MBC cell blocks (CBs). We correlated the findings with clinicopathologic variables and with the fixation methods used. We searched for patients with MBC diagnosed on cytology from 2007 to 2009 and selected those with ER, PR and HER2 tested in both the PBC surgical specimens and the MBC CBs. We included CBs fixed in formalin and methanol based solution (CytoLyt®). All slides were reevaluated by cytopathologists. Clinical information was retrieved from the medical records. We studied 65 patients with PBC and MBC paired specimens. The concordance rates between PBC and MBC were 78.5%, 58.5% and 96.9%, for ER, PR and HER2, respectively. When discordant, PR status switched from positive (PBC) to negative (MBC) in most cases (23/27). The PR concordance rate was 45.2% for CBs fixed in formalin and 70.6% for those fixed with CytoLyt® (p=0.047). The ER, PR and HER2 concordance rates between the PBC and MBC CBs are similar to those reported in paired surgical specimens. PR status was the most prevalent discordance and was not accompanied by a switch in ER.

Ionization potential and electron affinity for six common explosive compounds by DFT, MP2, and CBS-QB3

DOE PAGES

Cooper, Jason K.; Grant, Christian D.; Zhang, Jin Z.

2012-07-20

The vertical and adiabatic ionization potential (IP V and IP A) and vertical electron affinity (EA V) for six explosives (RDX, HMX, TNT, PETN, HMTD, and TATP) have been studied by ab initio computational methods. The IPV was calculated using MP2 and CBS-QB3 while the IP A was calculated with B3LYP, CAM-B3LYP, ω B97XD, B2PLYP, and MP2. RDX and TNT IP A’s were also reported using CBS -QB3. Excluding results by CBS-QB3, B3LYP and B2PLYPD provided superior and more consistent results for calculating the IP. The EA V were calculated using the same methods however B3LYP performed the worst inmore » this case with MP2 and B2PLYPD predicting values closest to those made by CBS-QB3, which was used a reference due to lacking experimental data. Basis set effects were evaluated using 6- 31+G(d,p), 6-311+G(d,p), and 6-311+(3df,2p) for both IP and EA. 6-31+G(d,p) gave satisfactory results for calculating both IP however 6-311+G(3df,2p) had improved results in calculating the EA. The four nitro containing compounds had exothermic reduction potentials while the peroxides were unfavorable. Additionally, it was seen that RDX, HMX, TATP and HMTD were unstable in their reduced forms. Results are aimed to assist detection and screening methods.« less

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators.

PubMed

Wei, Ruihan; Parsons, Sean P; Huizinga, Jan D

2017-03-01

What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ICC network as a two-dimensional network of weakly coupled oscillators with a frequency gradient and showed changes over time in video and graphical formats. Model parameters were obtained from slow-wave-driven contraction patterns in the mouse intestine and pacemaker slow-wave activities from the cat intestine. Marked changes in propagating oscillation patterns (including changes from propagation to non-propagating) were observed by changing network parameters (coupling strength between oscillators, the frequency gradient and frequency noise), which affected synchronization, propagation velocity and occurrence of dislocations (termination of an oscillation). Complete uncoupling of a circumferential ring of oscillators caused the proximal and distal section to desynchronize, but complete synchronization was maintained with only a single oscillator connecting the sections with high enough coupling. The network of oscillators could withstand loss; even with 40% of oscillators lost randomly within the network, significant synchronization and anterograde propagation remained. A local increase in pacemaker frequency diminished anterograde propagation; the effects were strongly dependent on location, frequency gradient and coupling strength. In summary, the model puts forth the hypothesis that fundamental changes in oscillation patterns (ICC slow-wave activity or circular muscle contractions) can occur through physiological modulation of network properties. Strong evidence is provided to accept the ICC network as a system of coupled oscillators. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Description of Martiniozyma gen. nov. and transfer of seven Candida species to Saturnispora as new combinations

USDA-ARS?s Scientific Manuscript database

DNA sequence analysis has shown Candida abiesophila (NRRL Y-11514T, CBS 5366T) and Candida asiatica (NRRL Y-63747T, CBS 10863T) to be members of a small clade that is phylogenetically separate from other yeasts. In view of their isolation from neighboring genera, such as Pichia and Saturnispora, the...

Towards Inclusion of Cross-Boundary Students from Mainland China in Educational Policies and Practices in Hong Kong

ERIC Educational Resources Information Center

Yuen, Celeste Yuet-Mui

2011-01-01

Every society has an obligation to provide quality education to children regardless of their socio-economic and cultural backgrounds. The number of cross-boundary students (CBS) from Mainland China in Hong Kong schools is increasing. This article reviews educational policy and provision for educating CBS, presenting data from an empirical study.…

What Factors Predict Middle School Students Sign Up for Washington's College Bound Scholarship Program? A Mixed Methods Evaluation. Working Paper 175

ERIC Educational Resources Information Center

Goldhaber, Dan; Long, Mark C.; Person, Ann E.; Rooklyn, Jordan

2017-01-01

We investigate factors influencing student sign-ups for Washington State's College Bound Scholarship (CBS) program. We find a substantial share of eligible middle school students fail to sign the CBS, forgoing college financial aid. Student characteristics associated with signing the scholarship parallel characteristics of low-income students who…

Endocannabinoid signaling at the periphery: 50 years after THC

PubMed Central

Maccarrone, Mauro; Bab, Itai; Bíró, Tamás; Cabral, Guy A.; Dey, Sudhansu K.; Di Marzo, Vincenzo; Konje, Justin C.; Kunos, George; Mechoulam, Raphael; Pacher, Pal; Sharkey, Keith A.; Zimmer, Andreas

2015-01-01

Fifty years ago (in 1964) the psychoactive ingredient of Cannabis sativa, Δ9-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide, AEA) in 1992, and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize and degrade them, and that altogether form the eCB system. eCBs control basic biological processes, including cell-choice between survival and death, and progenitor/stem cell proliferation and differentiation. Not surprisingly, in the past two decades, eCBs have been recognized as key mediators of several aspects of human pathophysiology, and thus have emerged among the most widespread and versatile signaling molecules ever discovered. Here, some of the pioneers of this research field review the state-of-the-art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral eCB system for human health and disease pathogenesis, as well as to highlight emerging challenges and therapeutic hopes. PMID:25796370

Endocannabinoid signaling at the periphery: 50 years after THC.

PubMed

Maccarrone, Mauro; Bab, Itai; Bíró, Tamás; Cabral, Guy A; Dey, Sudhansu K; Di Marzo, Vincenzo; Konje, Justin C; Kunos, George; Mechoulam, Raphael; Pacher, Pal; Sharkey, Keith A; Zimmer, Andreas

2015-05-01

In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize, and degrade them and that together form the eCB system (ECS). eCBs control basic biological processes including cell choice between survival and death and progenitor/stem cell proliferation and differentiation. Unsurprisingly, in the past two decades eCBs have been recognized as key mediators of several aspects of human pathophysiology and thus have emerged to be among the most widespread and versatile signaling molecules ever discovered. Here some of the pioneers of this research field review the state of the art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Candida spencermartinsiae sp. nov., Candida taylorii sp. nov. and Pseudozyma abaconensis sp. nov., novel yeasts from mangrove and coral reef ecosystems.

PubMed

Statzell-Tallman, Adele; Scorzetti, Gloria; Fell, Jack W

2010-08-01

Three species of yeasts are taxonomically described for strains isolated from marine environments. Candida spencermartinsiae sp. nov. (type strain CBS 10894T =NRRL Y-48663T) and Candida taylorii sp. nov. (type strain CBS 8508T =NRRL Y-27213T) are anamorphic ascomycetous yeasts in a phylogenetic cluster of marine yeasts in the Debaryomyces/Lodderomyces clade of the Saccharomycetales. The two species were isolated from multiple locations among coral reefs and mangrove habitats. Pseudozyma abaconensis sp. nov. (type strain CBS 8380T =NRRL Y-17380T) is an anamorphic basidiomycete that is related to the smut fungi of the genus Ustilago in the Ustilaginales. P. abaconensis was collected from waters adjacent to a coral reef.

Flow-diverter in radiation-induced skull base carotid blowout syndrome: do not write it off!

PubMed

Anil, Gopinathan; Zhang, Junwei; Ong, Yew Kwang; Hui, Francis

2017-10-01

Post-radiotherapy carotid blowout syndrome (CBS) of the skull base is a rare but often catastrophic complication of head and neck malignancies. The existing literature on the treatment of this condition with flow-diverting devices (FDD) is extremely limited and disappointing. We present a case of impending CBS in a patient previously irradiated for nasopharyngeal cancer that was successfully treated with use of multiple FDDs, adjunctive endonasal packing and delayed reinforcement with pedicled naso-septal flap, yielding an excellent outcome at 14-months follow-up. Notwithstanding the discouraging results in literature, our anecdotal experience suggests that endovascular reconstruction using FDD could be an option with long-term viability in post-radiotherapy CBS involving the skull base when reinforced with a vascularised naso-septal flap.

Description of Groenewaldozyma gen. nov. for placement of Candida auringiensis, Candida salmanticensis and Candida tartarivorans.

PubMed

Kurtzman, Cletus P

2016-07-01

DNA sequence analyses have demonstrated that species of the polyphyletic anamorphic ascomycete genus Candida may be members of described teleomorphic genera, members of the Candida tropicalis clade upon which the genus Candida is circumscribed, or members of isolated clades that represent undescribed genera. From phylogenetic analysis of gene sequences from nuclear large subunit rRNA, mitochondrial small subunit rRNA and cytochrome oxidase II, Candida auringiensis (NRRL Y-17674(T), CBS 6913(T)), Candida salmanticensis (NRRL Y-17090(T), CBS 5121(T)), and Candida tartarivorans (NRRL Y-27291(T), CBS 7955(T)) were shown to be members of an isolated clade and are proposed for reclassification in the genus Groenewaldozyma gen. nov. (MycoBank MB 815817). Neighbouring taxa include species of the Wickerhamiella clade and Candida blankii.

[RNA polymerase II and pre-mRNA splicing factors in diplotene oocyte nuclei of the giant African gastropod Achatina fulica].

PubMed

Stepanova, I S; Bogoliubov, D S

2003-01-01

The nuclear distribution of pre-mRNA splicing factors (snRNPs and SR-protein SC35) and unphosphorylated from of RNA polymerase II (Pol II) was studied using fluorescent and immunoelectron cytochemistry in diplotene oocytes of the gastropod Achatina fulica. Association of Pol II and splicing factors with oocyte nuclear structures was analysed. The antibodies against splicing factors and Pol II were shown to label perichromatin fibrils at the periphery of condensed chromatin blocks as well as those in interchromatin regions of nucleoplasm. The revealed character of distribution of snRNPs, SC35 protein, and Pol II, together with the decondensed chromatin and absence of karyosphere, enable us to suggest that oocyte chromosomes maintain their transcriptional activity at the diplotene stage of oogenesis. In A. fulica oocytes, sparse nuclear bodies (NBs) of a complex morphological structure were revealed. These NBs contain snRNPs rather than SC35 protein. NBs are associated with a fibrogranular material (FGM), which contains SC35 protein. No snRNPs were revealed in this material. Homology of A. fulica oocyte nuclear structures to Cajal bodies and interchromatin granule clusters is discussed.

Theoretical prediction of the ionization energies of the C4H7 radicals: 1-methylallyl, 2-methylallyl, cyclopropylmethyl, and cyclobutyl radicals.

PubMed

Lau, Kai-Chung; Zheng, Wenxu; Wong, Ning-Bew; Li, Wai-Kee

2007-10-21

The ionization energies (IEs) for the 1-methylallyl, 2-methylallyl, cyclopropylmethyl, and cyclobutyl radicals have been calculated by the wave function based ab initio CCSD(T)/CBS approach, which involves the approximation to the complete basis set (CBS) limit at the coupled cluster level with single and double excitations plus quasiperturbative triple excitation [CCSD(T)]. The zero-point vibrational energy correction, the core-valence electronic correction, and the scalar relativistic effect correction are included in these calculations. The present CCSD(T)/CBS results are then compared with the IEs determined in the photoelectron experiment by Schultz et al. [J. Am. Chem. Soc. 106, 7336 (1984)] The predicted IE value (7.881 eV) of 2-methylallyl radical is found to compare very favorably with the experimental value of 7.90+/-0.02 eV. Two ionization transitions for cis-1-methylallyl and trans-1-methylallyl radicals have been considered here. The comparison between the predicted IE values and the previous measurements shows that the photoelectron peak observed by Schultz et al. likely corresponds to the adiabatic ionization transition for the trans-1-methylallyl radical to form trans-1-methylallyl cation. Although a precise IE value for the cyclopropylmethyl radical has not been directly determined, the experimental value deduced indirectly using other known energetic data is found to be in good accord with the present CCSD(T)/CBS prediction. We expect that the Franck-Condon factor for ionization transition of c-C4H7-->bicyclobutonium is much less favorable than that for ionization transition of c-C4H7-->planar-C4H7+, and the observed IE in the previous photoelectron experiment is likely due to the ionization transition for c-C4H7-->planar-C4H7+. Based on our CCSD(T)/CBS prediction, the ionization transition of c-C4H7-->bicyclobutonium with an IE value around 6.92 eV should be taken as the adiabatic ionization transition for the cyclobutyl radical. The present study provides support for the conclusion that the CCSD(T)/CBS approach with high-level energetic corrections can be used to provide reliable IE predictions for C4 hydrocarbon radicals with an uncertainty of +/-22 meV. The CCSD(T)/CBS predictions to the heats of formation for the aforementioned radicals and cations are also presented.

Development of a "First Principles" Water Potential with Flexible Monomers: Dimer Potential Energy Surface, VRT Spectrum, and Second Virial Coefficient.

PubMed

Babin, Volodymyr; Leforestier, Claude; Paesani, Francesco

2013-12-10

The development of a "first principles" water potential with flexible monomers (MB-pol) for molecular simulations of water systems from gas to condensed phases is described. MB-pol is built upon the many-body expansion of the intermolecular interactions, and the specific focus of this study is on the two-body term (V2B) representing the full-dimensional intermolecular part of the water dimer potential energy surface. V2B is constructed by fitting 40,000 dimer energies calculated at the CCSD(T)/CBS level of theory and imposing the correct asymptotic behavior at long-range as predicted from "first principles". The comparison of the calculated vibration-rotation tunneling (VRT) spectrum and second virial coefficient with the corresponding experimental results demonstrates the accuracy of the MB-pol dimer potential energy surface.

Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure

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

Lee, Eunyoung

Low-level formaldehyde exposure is inevitable in industrialized countries. Although daily-life formaldehyde exposure level is practically impossible to induce cell death, most of mechanistic studies related to formaldehyde toxicity have been performed in cytotoxic concentrations enough to trigger cell death mechanism. Currently, toxicological mechanisms underlying the sub-cytotoxic exposure to formaldehyde are not clearly elucidated in skin cells. In this study, the genome-scale transcriptional analysis in normal human keratinocytes (NHKs) was performed to investigate cutaneous biological pathways associated with daily life formaldehyde exposure. We selected the 175 upregulated differentially expressed genes (DEGs) and 116 downregulated DEGs in NHKs treated with 200 μMmore » formaldehyde. In the Gene Ontology (GO) enrichment analysis of the 175 upregulated DEGs, the endoplasmic reticulum (ER) unfolded protein response (UPR) was identified as the most significant GO biological process in the formaldeyde-treated NHKs. Interestingly, the sub-cytotoxic formaldehyde affected NHKs to upregulate two enzymes important in the cellular transsulfuration pathway, cystathionine γ-lyase (CTH) and cystathionine-β-synthase (CBS). In the temporal expression analysis, the upregulation of the pro-inflammatory DEGs such as MMP1 and PTGS2 was detected earlier than that of CTH, CBS and other ER UPR genes. The metabolites of CTH and CBS, L-cystathionine and L-cysteine, attenuated the formaldehyde-induced upregulation of pro-inflammatory DEGs, MMP1, PTGS2, and CXCL8, suggesting that CTH and CBS play a role in the negative feedback regulation of formaldehyde-induced pro-inflammatory responses in NHKs. In this regard, the sub-cytotoxic formaldehyde-induced CBS and CTH may regulate inflammation fate decision to resolution by suppressing the early pro-inflammatory response. - Highlights: • Sub-cytotoxic formaldehyde upregulates ER UPR-associated genes in NHKs. • Formaldehyde-induced ER UPR genes includes cystathionine γ-lyase (CTH). • Sub-cytotoxic formaldehyde upregulates cystathionine-β-synthase (CBS) in NHKs. • Cystathionine metabolic enzymes may attenuate formaldehyde-induced inflammation in NHKs. • Cystathionine metabolic enzymes may play a role in the resolution of inflammation in NHKs.« less

Counting or Chunking?

PubMed Central

Spotorno, Nicola; McMillan, Corey T.; Powers, John P.; Clark, Robin; Grossman, Murray

2014-01-01

A growing amount of empirical data is showing that the ability to manipulate quantities in a precise and efficient fashion is rooted in cognitive mechanisms devoted to specific aspects of numbers processing. The Analog number system (ANS) has a reasonable representation of quantities up to about 4, and represents larger quantities on the basis of a numerical ratio between quantities. In order to represent the precise cardinality of a number, the ANS may be supported by external algorithms such as language, leading to a “Precise Number System”. In the setting of limited language, other number-related systems can appear. For example the Parallel Individuation system (PIS) supports a “chunking mechanism” that clusters units of larger numerosities into smaller subsets. In the present study we investigated number processing in non-aphasic patients with Corticobasal Syndrome (CBS) and Posterior Cortical Atrophy (PCA), two neurodegenerative conditions that are associated with progressive parietal atrophy. The present study investigated these number systems in CBS and PCA by assessing the property of the ANS associated with smaller and larger numerosities, and the chunking property of the PIS. The results revealed that CBS/PCA patients are impaired in simple calculations (e.g., addition and subtraction) and that their performance strongly correlates with the size of the numbers involved in these calculations, revealing a clear magnitude effect. This magnitude effect correlated with gray matter atrophy in parietal regions. Moreover, a numeral-dots transcoding task showed that CBS/PCA patients are able to take advantage of clustering in the spatial distribution of the dots of the array. The relative advantage associated with chunking compared to a random spatial distribution correlated with both parietal and prefrontal regions. These results shed light on the properties of systems for representing number knowledge in non-aphasic patients with CBS and PCA. PMID:25278132

Reduced Expression of Hydrogen Sulfide-Generating Enzymes Down-Regulates 15-Hydroxyprostaglandin Dehydrogenase in Chorion during Term and Preterm Labor.

PubMed

Sun, Qianqian; Chen, Zixi; He, Ping; Li, Yuan; Ding, Xiaoying; Huang, Ying; Gu, Hang; Ni, Xin

2018-01-01

Chorionic NAD-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) plays a pivotal role in controlling the amount of prostaglandins in the uterus and has been implicated in the process of labor. Prior studies identified hydrogen sulfide-generating enzymes cystathionine-β-synthetase (CBS) and cystathionine-γ-lyase (CSE) in fetal membranes. We investigated whether hydrogen sulfide is involved in the regulation of PGDH expression in the chorion during labor. The chorionic tissues were obtained from pregnant women at preterm in labor and at term in labor or not in labor at term. Levels of CSE and CBS and hydrogen sulfide production rate were down-regulated in term in labor and preterm in labor groups compared with not in labor at term group. The CBS level correlated to PGDH expression in the chorion. Hydrogen sulfide donor NaHS and precursor l-cysteine dose-dependently stimulated PGDH expression and activity in cultured chorionic trophoblasts. The effect of l-cysteine was blocked by CBS inhibitor and CBS siRNA but not by CSE inhibitor and CSE siRNA. Hydrogen sulfide treatment suppressed miR-26b and miR-199a expression in chorionic trophoblasts. miR-26b and miR-199a mimics blocked hydrogen sulfide upregulation of PGDH expression. Our results indicate that hydrogen sulfide plays pivotal roles in maintenance of PGDH expression in the chorion during human pregnancy. Reduced expression of hydrogen sulfide-generating enzymes contributes to an increased amount of prostaglandins in the uterus during labor. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The nature of working memory for Braille.

PubMed

Cohen, Henri; Voss, Patrice; Lepore, Franco; Scherzer, Peter

2010-05-26

Blind individuals have been shown on multiple occasions to compensate for their loss of sight by developing exceptional abilities in their remaining senses. While most research has been focused on perceptual abilities per se in the auditory and tactile modalities, recent work has also investigated higher-order processes involving memory and language functions. Here we examined tactile working memory for Braille in two groups of visually challenged individuals (completely blind subjects, CBS; blind with residual vision, BRV). In a first experimental procedure both groups were given a Braille tactile memory span task with and without articulatory suppression, while the BRV and a sighted group performed a visual version of the task. It was shown that the Braille tactile working memory (BrWM) of CBS individuals under articulatory suppression is as efficient as that of sighted individuals' visual working memory in the same condition. Moreover, the results suggest that BrWM may be more robust in the CBS than in the BRV subjects, thus pointing to the potential role of visual experience in shaping tactile working memory. A second experiment designed to assess the nature (spatial vs. verbal) of this working memory was then carried out with two new CBS and BRV groups having to perform the Braille task concurrently with a mental arithmetic task or a mental displacement of blocks task. We show that the disruption of memory was greatest when concurrently carrying out the mental displacement of blocks, indicating that the Braille tactile subsystem of working memory is likely spatial in nature in CBS. The results also point to the multimodal nature of working memory and show how experience can shape the development of its subcomponents.

The Nature of Working Memory for Braille

PubMed Central

Cohen, Henri; Voss, Patrice; Lepore, Franco; Scherzer, Peter

2010-01-01

Blind individuals have been shown on multiple occasions to compensate for their loss of sight by developing exceptional abilities in their remaining senses. While most research has been focused on perceptual abilities per se in the auditory and tactile modalities, recent work has also investigated higher-order processes involving memory and language functions. Here we examined tactile working memory for Braille in two groups of visually challenged individuals (completely blind subjects, CBS; blind with residual vision, BRV). In a first experimental procedure both groups were given a Braille tactile memory span task with and without articulatory suppression, while the BRV and a sighted group performed a visual version of the task. It was shown that the Braille tactile working memory (BrWM) of CBS individuals under articulatory suppression is as efficient as that of sighted individuals' visual working memory in the same condition. Moreover, the results suggest that BrWM may be more robust in the CBS than in the BRV subjects, thus pointing to the potential role of visual experience in shaping tactile working memory. A second experiment designed to assess the nature (spatial vs. verbal) of this working memory was then carried out with two new CBS and BRV groups having to perform the Braille task concurrently with a mental arithmetic task or a mental displacement of blocks task. We show that the disruption of memory was greatest when concurrently carrying out the mental displacement of blocks, indicating that the Braille tactile subsystem of working memory is likely spatial in nature in CBS. The results also point to the multimodal nature of working memory and show how experience can shape the development of its subcomponents. PMID:20520807

High-level ab initio calculations for the four low-lying families of minima of (H2O)(20): 1. Estimates of MP2/CBS binding energies and comparison with empirical potentials

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

Fanourgakis, Georgios S.; Apra, Edoardo; Xantheas, Sotiris S.

2004-08-08

We report estimates of complete basis set (CBS) limits at the second-order Møller-Plesset perturbation level of theory (MP2) for the binding energies of the lowest lying isomers within each of the four major families of minima of (H2O)20. These were obtained by performing MP2 calculations with the family of correlation-consistent basis sets up to quadruple zeta quality, augmented with additional diffuse functions (aug-cc-pVnZ, n=D, T, Q). The MP2/CBS estimates are: -200.1 kcal/mol (dodecahedron, 30 hydrogen bonds), -212.6 kcal/mol (fused cubes, 36 hydrogen bonds), -215.0 (face-sharing pentagonal prisms, 35 hydrogen bonds) and –217.9 kcal/mol (edge-sharing pentagonal prisms, 34 hydrogen bonds). Themore » energetic ordering of the various (H2O)20 isomers does not follow monotonically the number of hydrogen bonds as in the case of smaller clusters such as the different isomers of the water hexamer. The dodecahedron lies ca. 18 kcal/mol higher in energy than the most stable edge-sharing pentagonal prism isomer. The TIP4P, ASP-W4, TTM2-R, AMOEBA and TTM2-F empirical potentials also predict the energetic stabilization of the edge-sharing pentagonal prisms with respect to the dodecahedron, albeit they universally underestimate the cluster binding energies with respect to the MP2/CBS result. Among them, the TTM2-F potential was found to predict the absolute cluster binding energies to within < 1% from the corresponding MP2/CBS values, whereas the error for the rest of the potentials considered in this study ranges from 3-5%.« less

Assessing the dysexecutive syndrome in dementia.

PubMed

Gansler, David A; Huey, Edward D; Pan, Jessica J; Wasserman, Eric; Grafman, Jordan H

2017-03-01

We compared performance on tests of dysexecutive behaviour (DB) and executive function (EF) in patients with behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and corticobasal syndrome (CBS). Patients diagnosed with bvFTD (n=124), PPA (n=34) and CBS (n=85) were recruited. EF was measured with the Delis-Kaplan Executive Function System (DKEFS: performance based), and DB was measured with the Frontal Systems Behavior Scale (FrSBe: caregiver-report based). Confirmatory factor analysis characterised the relationship between EF and DB, binary logistic regression evaluated the incremental diagnostic utility of the measures and neuroimaging data from 110 patients identified neural correlates. EF was lowest and DB was highest in bvFTD participants. EF and DB were distinct but related (r=-0.48). Measures correctly classified 89% of bvFTD from CBS patients and 93% of bvFTD from PPA patients-30% and 13% above base rates (59%, 80%), respectively. All modalities were useful in identifying CBS and PPA, whereas DB alone was useful for identifying bvFTD. EF was uniquely associated with caudal left dorsolateral prefrontal and lateral temporo-parietal cortices. DB was uniquely associated with the cingulate (R>L), right subcallosal and right anterior frontal cortex. EF and DB were associated with the rostral dorsolateral prefrontal cortex bilaterally. EF and DB measures displayed criterion and construct validity, had incremental utility at low DB levels (CBS and PPA) and were associated with overlapping and distinct neural correlates. EF and DB procedures can conjointly provide useful diagnostic and descriptive information in identifying and ruling out the dysexecutive syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Polychlorinated biphenyls in Nepalese surface soils: Spatial distribution, air-soil exchange, and soil-air partitioning.

PubMed

Yadav, Ishwar Chandra; Devi, Ningombam Linthoingambi; Li, Jun; Zhang, Gan

2017-10-01

Regardless of the ban on the polychlorinated biphenyls (PCBs) decade ago, significant measures of PCBs are still transmitted from essential sources in cities and are all inclusive ecological contaminants around the world. In this study, the concentrations of PCBs in soil, the air-soil exchange of PCBs, and the soil-air partitioning coefficient (K SA ) of PCBs were investigated in four noteworthy urban areas in Nepal. Overall, the concentrations of ∑ 30 PCBs ranged from 10 to 59.4ng/g dry weight; dw (mean 12.2ng/g ±11.2ng/g dw). The hexa-CBs (22-31%) was most dominant among several PCB-homologues, followed by tetra-CBs (20-29%), hepta-CBs (12-21%), penta-CBs (15-17%) and tri-CBs (9-19%). The sources of elevated level of PCBs discharge in Nepalese soil was identified as emission from transformer oil, lubricants, breaker oil, cutting oil and paints, and cable insulation. Slightly strong correlation of PCBs with TOC than BC demonstrated that amorphous organic matter (AOM) assumes a more critical part in holding of PCBs than BC in Nepalese soil. The fugacity fraction (ff) results indicated the soil being the source of PCB in air through volatilization and net transport from soil to air. The soil-air partitioning coefficient study suggests the absorption by soil organic matter control soil-air partitioning of PCBs. Slightly weak but positive correlation of measured Log K SA with Log K OA (R 2 = 0.483) and Log K BC-A (R 2 = 0.438) suggests that both Log K OA and Log K BC-A can predict soil-air partitioning to lesser extent for PCBs. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired Heme Binding and Aggregation of Mutant Cystathionine β-Synthase Subunits in Homocystinuria

PubMed Central

Janošík, Miroslav; Oliveriusová, Jana; Janošíková, Bohumila; Sokolová, Jitka; Kraus, Eva; Kraus, Jan P.; Kožich, Viktor

2001-01-01

During the past 20 years, cystathionine β-synthase (CBS) deficiency has been detected in the former Czechoslovakia with a calculated frequency of 1:349,000. The clinical manifestation was typical of homocystinuria, and about half of the 21 patients were not responsive to pyridoxine. Twelve distinct mutations were detected in 30 independent homocystinuric alleles. One half of the alleles carried either the c.833 T→C or the IVS11−2A→C mutation; the remaining alleles contained private mutations. The abundance of five mutant mRNAs with premature stop codons was analyzed by PCR-RFLP. Two mRNAs, c.828_931ins104 (IVS7+1G→A) and c.1226 G→A, were severely reduced in the cytoplasm as a result of nonsense-mediated decay. In contrast, the other three mRNAs—c.19_20insC, c.28_29delG, and c.210_235del26 (IVS1−1G→C)—were stable. Native western blot analysis of 14 mutant fibroblast lines showed a paucity of CBS antigen, which was detectable only in aggregates. Five mutations—A114V (c.341C→T), A155T (c.463G→A), E176K (c.526G→A), I278T (c.833T→C), and W409_G453del (IVS11−2A→C)—were expressed in Escherichia coli. All five mutant proteins formed substantially more aggregates than did the wild-type CBS, and no aggregates contained heme. These data suggest that abnormal folding, impaired heme binding, and aggregation of mutant CBS polypeptides may be common pathogenic mechanisms in CBS deficiency. PMID:11359213

Are surgery training programs ready for virtual reality? A survey of program directors in general surgery.

PubMed

Haluck, R S; Marshall, R L; Krummel, T M; Melkonian, M G

2001-12-01

The use of advanced technology, such as virtual environments and computer-based simulators (VR/CBS), in training has been well established by both industry and the military. In contrast the medical profession, including surgery, has been slow to incorporate such technology in its training. In an attempt to identify factors limiting the regular incorporation of this technology into surgical training programs, a survey was developed and distributed to all general surgery program directors in the United States. A 22-question survey was sent to 254 general surgery program directors. The survey was designed to reflect attitudes of the program directors regarding the use of computer-based simulation in surgical training. Questions were scaled from 1 to 5 with 1 = strongly disagree and 5 = strongly agree. A total of 139 responses (55%) were returned. The majority of respondents (58%) had seen VR/CBS, but only 19% had "hands-on" experience with these systems. Respondents strongly agreed that there is a need for learning opportunities outside of the operating room and a role for VR/CBS in surgical training. Respondents believed both staff and residents would support this type of training. Concerns included VR/CBS' lack of validation and potential requirements for frequent system upgrades. Virtual environments and computer-based simulators, although well established training tools in other fields, have not been widely incorporated into surgical education. Our results suggest that program directors believe this type of technology would be beneficial in surgical education, but they lack adequate information regarding VR/CBS. Developers of this technology may need to focus on educating potential users and addressing their concerns.

Recovery of fermented inulin fiber by lactic acid bacteria (LAB) from inulin hydrolysate using fungi inulinase enzymes of Scopulariopsis sp.-CBS1 and class of Deuteromycetes-CBS4 as cholesterol binder

NASA Astrophysics Data System (ADS)

Susilowati, Agustine; Melanie, Hakiki; Maryati, Yati; Aspiyanto

2017-01-01

Fermentation of Lactobacillus Acid Bacteria (LAB) which are mixtures of Lactobacillus acidophilus, Bifidobacteriumbifidum, Lactobacillus bulgaricus and Streptococcus thermophillus on hydrolysate as a result of inulin hydrolysis using inulinase enzymes obtained from endophytic fungi ofScopulariopsis sp.-CBS1 (inulin hydrolysate of S) and Class of Deuteromycetes-CBS4 (inulin hydrolysate of D) generate potential fermented inulin fiber as cholesterol binder. Fermentation process was conducted under concentrations of inulin hydrolysate 50% (w/v), LAB 15% (v/v) and skim milk 12.5% (w/v) at room temperature and 40°C for 0, 12, 24, 36 and 48 hours, respectively. Result of experimental work showed that longer time of LAB fermentation increased total acids, TPC and CBC at pH 2, but decreased total sugar, reducing, IDF, SDF, CBC pH 2 and CBC pH 7. Based on Cholesterol Binding Capacity (CBC), optimization of fermentation process on inulin hydrolysate of S was achieved by combining treatment at 40°C for 24 hours resulted in CBC pH 2 of 19.11 mg/g TDF and inulin hydrolysate of D was achieved by fermentation at 40 °C for 48 hours resulted in CBC pH 2 of 24.28 mg/g TDF. Inulin hydrolysate of class of Deutrymecetes CBS4 fermented by LAB had better functional property as cholesterol binder than that inulin hydrolysate of S fermented by LAB. This is due to cholesterol binder and cholesterol derivatives as a result of degradation of LAB on digestive system (stomach) when compared to higher colon under optimal process condition.

Size distribution and sorption of polychlorinated biphenyls during haze episodes

NASA Astrophysics Data System (ADS)

Zhu, Qingqing; Liu, Guorui; Zheng, Minghui; Zhang, Xian; Gao, Lirong; Su, Guijin; Liang, Yong

2018-01-01

There is a lack of studies on the size distribution of polychlorinated biphenyls (PCBs) during haze days, and their sorption mechanisms on aerosol particles remain unclear. In this study, PCBs in particle-sized aerosols from urban atmospheres of Beijing, China were investigated during haze and normal days. The concentrations, gas/particle partitioning, size distribution, and associated human daily intake of PCBs via inhalation were compared during haze days and normal days. Compared with normal days, higher particle mass-associated PCB levels were measured during haze days. The concentrations of ∑PCBs in particulate fractions were 11.9-134 pg/m3 and 6.37-14.9 pg/m3 during haze days and normal days, respectively. PCBs increased with decreasing particle size (>10 μm, 10-2.5 μm, 2.5-1.0 μm, and ≤1.0 μm). During haze days, PCBs were overwhelmingly associated with a fine particle fraction of ≤1.0 μm (64.6%), while during normal days the contribution was 33.7%. Tetra-CBs were the largest contributors (51.8%-66.7%) both in the gas and particle fractions during normal days. The profiles in the gas fraction were conspicuously different than those in the PM fractions during haze days, with di-CBs predominating in the gas fraction and higher homologues (tetra-CBs, penta-CBs, and hexa-CBs) concurrently accounting for most of the PM fractions. The mean-normalized size distributions of particulate mass and PCBs exhibited unimodal patterns, and a similar trend was observed for PCBs during both days. They all tended to be in the PM fraction of 1.0-2.5 μm. Adsorption might be the predominating mechanism for the gas-particle partitioning of PCBs during haze days, whereas absorption might be dominative during normal days.

Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation.

PubMed

Macabenta, Frank D; Jensen, Amber G; Cheng, Yi-Shan; Kramer, Joseph J; Kramer, Sunita G

2013-08-15

Drosophila embryonic dorsal vessel (DV) morphogenesis is a highly stereotyped process that involves the migration and morphogenesis of 52 pairs of cardioblasts (CBs) in order to form a linear tube. This process requires spatiotemporally-regulated localization of signaling and adhesive proteins in order to coordinate the formation of a central lumen while maintaining simultaneous adhesion between CBs. Previous studies have shown that the Slit/Roundabout and Netrin/Unc5 repulsive signaling pathways facilitate site-specific loss of adhesion between contralateral CBs in order to form a luminal space. However, the concomitant mechanism by which attraction initiates CB outgrowth and discrete localization of adhesive proteins remains poorly understood. Here we provide genetic evidence that Netrin signals through DCC (Deleted in Colorectal Carcinoma)/UNC-40/Frazzled (Fra) to mediate CB outgrowth and attachment and that this function occurs prior to and independently of Netrin/UNC-5 signaling. fra mRNA is expressed in the CBs prior to and during DV morphogenesis. Loss-of-fra-function results in significant defects in cell shape and alignment between contralateral CB rows. In addition, CB outgrowth and attachment is impaired in both fra loss- and gain-of-function mutants. Deletion of both Netrin genes (NetA and NetB) results in CB attachment phenotypes similar to fra mutants. Similar defects are also seen when both fra and unc5 are deleted. Finally we show that Fra accumulates at dorsal and ventral leading edges of paired CBs, and this localization is dependent upon Netrin. We propose that while repulsive guidance mechanisms contribute to lumen formation by preventing luminal domains from coming together, site-specific Netrin/Frazzled signaling mediates CB attachment. Copyright © 2013 Elsevier Inc. All rights reserved.

Omics Analyses of Trichoderma reesei CBS999.97 and QM6a Indicate the Relevance of Female Fertility to Carbohydrate-Active Enzyme and Transporter Levels

DOE PAGES

Tisch, Doris; Pomraning, Kyle R.; Collett, James R.; ...

2017-09-15

Here, the filamentous fungus Trichoderma reesei is found predominantly in the tropics but also in more temperate regions, such as Europe, and is widely known as a producer of large amounts of plant cell wall-degrading enzymes. We sequenced the genome of the sexually competent isolate CBS999.97, which is phenotypically different from the female sterile strain QM6a but can cross sexually with QM6a. Transcriptome data for growth on cellulose showed that entire carbohydrate-active enzyme (CAZyme) families are consistently differentially regulated between these strains. We evaluated backcrossed strains of both mating types, which acquired female fertility from CBS999.97 but maintained a mostlymore » QM6a genetic background, and we could thereby distinguish between the effects of strain background and female fertility or mating type. We found clear regulatory differences associated with female fertility and female sterility, including regulation of CAZyme and transporter genes. Analysis of carbon source utilization, transcriptomes, and secondary metabolites in these strains revealed that only a few changes in gene regulation are consistently correlated with different mating types. Different strain backgrounds (QM6a versus CBS999.97) resulted in the most significant alterations in the transcriptomes and in carbon source utilization, with decreased growth of CBS999.97 on several amino acids (for example proline or alanine), which further correlated with the downregulation of genes involved in the respective pathways. In combination, our findings support a role of fertility-associated processes in physiology and gene regulation and are of high relevance for the use of sexual crossing in combining the characteristics of two compatible strains or quantitative trait locus (QTL) analysis.« less

Cytologic assessment of estrogen receptor, progesterone receptor, and HER2 status in metastatic breast carcinoma

PubMed Central

Pareja, Fresia; Murray, Melissa P; Jean, Ryan Des; Konno, Fumiko; Friedlander, Maria; Lin, Oscar; Edelweiss, Marcia

2016-01-01

BACKGROUND Discordance in the receptor status between primary breast carcinomas (PBC) and corresponding metastasis is well documented. Interrogation of the receptor status of metastatic breast carcinoma (MBC) in cytology material is common practice; however, its utility has not been thoroughly validated. We studied patients with MBC, and evaluated the concordance rates of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between PBC surgical specimens and corresponding MBC cell blocks (CBs). We correlated the findings with clinicopathologic variables and with the fixation methods used. METHODS We searched for patients with MBC diagnosed on cytology from 2007 to 2009 and selected those with ER, PR and HER2 tested in both the PBC surgical specimens and the MBC CBs. We included CBs fixed in formalin and methanol based solution (CytoLyt®). All slides were reevaluated by cytopathologists. Clinical information was retrieved from the medical records. RESULTS We studied 65 patients with PBC and MBC paired specimens. The concordance rates between PBC and MBC were 78.5%, 58.5% and 96.9%, for ER, PR and HER2, respectively. When discordant, PR status switched from positive (PBC) to negative (MBC) in most cases (23/27). The PR concordance rate was 45.2% for CBs fixed in formalin and 70.6% for those fixed with CytoLyt® (p=0.047). CONCLUSION The ER, PR and HER2 concordance rates between the PBC and MBC CBs are similar to those reported in paired surgical specimens. PR status was the most prevalent discordance and was not accompanied by a switch in ER. PMID:28529880

Omics Analyses of Trichoderma reesei CBS999.97 and QM6a Indicate the Relevance of Female Fertility to Carbohydrate-Active Enzyme and Transporter Levels

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

Tisch, Doris; Pomraning, Kyle R.; Collett, James R.

Here, the filamentous fungus Trichoderma reesei is found predominantly in the tropics but also in more temperate regions, such as Europe, and is widely known as a producer of large amounts of plant cell wall-degrading enzymes. We sequenced the genome of the sexually competent isolate CBS999.97, which is phenotypically different from the female sterile strain QM6a but can cross sexually with QM6a. Transcriptome data for growth on cellulose showed that entire carbohydrate-active enzyme (CAZyme) families are consistently differentially regulated between these strains. We evaluated backcrossed strains of both mating types, which acquired female fertility from CBS999.97 but maintained a mostlymore » QM6a genetic background, and we could thereby distinguish between the effects of strain background and female fertility or mating type. We found clear regulatory differences associated with female fertility and female sterility, including regulation of CAZyme and transporter genes. Analysis of carbon source utilization, transcriptomes, and secondary metabolites in these strains revealed that only a few changes in gene regulation are consistently correlated with different mating types. Different strain backgrounds (QM6a versus CBS999.97) resulted in the most significant alterations in the transcriptomes and in carbon source utilization, with decreased growth of CBS999.97 on several amino acids (for example proline or alanine), which further correlated with the downregulation of genes involved in the respective pathways. In combination, our findings support a role of fertility-associated processes in physiology and gene regulation and are of high relevance for the use of sexual crossing in combining the characteristics of two compatible strains or quantitative trait locus (QTL) analysis.« less

Molecular genetic analysis in mild hyperhomocysteinemia: A common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease

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

Kluijtmans, L.A.J.; Heuvel, L.P.W.J. van den; Stevens, E.M.B.

1996-01-01

Mild hyperhomocysteinemia is an established risk factor for cardiovascular disease. Genetic aberrations in the cystathionine P-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) genes may account for reduced enzyme activities and elevated plasma homocysteine levels. In 15 unrelated Dutch patients with homozygous CBS deficiency, we observed the 833T{yields}C (1278T) mutation in 50% of the alleles. Very recently, we identified a common mutation (677C{yields}T; A{yields}V) in the MTHFR gene, which, in homozygous state, is responsible for the thermolabile phenotype and which is associated with decreased specific MTHFR activity and elevated homocysteine levels. We screened 60 cardiovascular patients and 111 controls for these twomore » mutations, to determine whether these mutations are risk factors for premature cardiovascular disease. Heterozygosity for the 833T{yields}C mutation in the CBS gene was observed in one individual of the control group but was absent in patients with premature cardiovascular disease. Homozygosity for the 677C-{yields}T mutation in the MTHFR gene was found in 9 (15%) of 60 cardiovascular patients and in only 6 ({approximately}5%) of 111 control individuals (odds ratio 3.1 [95% confidence interval 1.0-9.21]). Because of both the high prevalence of the 833T-{yields}C mutation among homozygotes for CBS deficiency and its absence in 60 cardiovascular patients, we may conclude that heterozygosity for CBS deficiency does not appear to be involved in premature cardiovascular disease. However, a frequent homozygous mutation in the MTHFR gene is associated with a threefold increase in risk for premature cardiovascular disease. 35 refs., 3 figs., 1 tab.« less

Phytocannabinoids for Cancer Therapeutics: Recent Updates and Future Prospects.

PubMed

Patil, K R; Goyal, S N; Sharma, C; Patil, C R; Ojha, S

2015-01-01

Phytocannabinoids (pCBs) are lipid-soluble phytochemicals present in the plant, Cannabis sativa L. and non-cannabis plants which have a long history in recreation and traditional medicine. The plant and the constituents isolated were central in the discovery of the endocannabinoid system (ECS), the most new target for drug discovery. The ECS includes two G-protein-coupled receptors; the cannabinoid receptors-1 and -2 (CB1 and CB2) for marijuana's psychoactive principle Δ(9)-tetrahydrocannabinol (Δ(9)-THC), their endogenous small lipid ligands; namely anandamide (AEA) and 2-arachidonoylglycerol (2-AG), also known as endocannabinoids and the enzymes for endocannabinoid biosynthesis and degradation such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The ECS has been suggested as a pro-homeostatic and pleiotropic signaling system activated in a time- and tissue-specific way during pathological conditions including cancer. Targeting the CB1 receptors becomes a concern because of adverse psychotropic reactions. Hence, targeting the CB2 receptors or the endocannabinoid metabolizing enzymes by pCBs obtained from plants lacking psychotropic adverse reactions has garnered interest in drug discovery. These pCBs derived from plants appear safe and effective with a wider access and availability. In the recent years, several pCBs derived other than non-cannabinoid plants have been reported to bind to and functionally interact with cannabinoid receptors and appear promising candidate for drug development including cancer therapeutics. Several of them also targets the endocannabinoid metabolizing enzymes that control endocannabinoid levels. In this article, we summarize and critically discuss the updates and future prospects of the pCBs as novel and promising candidates for cancer therapeutics.

The Effect of Virtual Reality Training on Unilateral Spatial Neglect in Stroke Patients

PubMed Central

Kim, Yong Mi; Yun, Gi Jeong; Song, Young Jin; Young, Han Eun

2011-01-01

Objective To investigate the effect of virtual reality training on unilateral spatial neglect in stroke patients. Method Twenty-four stroke patients (14 males and 10 females, mean age=64.7) who had unilateral spatial neglect as a result of right hemisphere stroke were recruited. All patients were randomly assigned to either the virtual reality (VR) group (n=12) or the control group (n=12). The VR group received VR training, which stimulated the left side of their bodies. The control group received conventional neglect therapy such as visual scanning training. Both groups received therapy for 30 minutes a day, five days per week for three weeks. Outcome measurements included star cancellation test, line bisection test, Catherine Bergego scale (CBS), and the Korean version of modified Barthel index (K-MBI). These measurements were taken before and after treatment. Results There were no significant differences in the baseline characteristics and initial values between the two groups. The changes in star cancellation test results and CBS in the VR group were significantly higher than those of the control group after treatment. The changes in line bisection test score and the K-MBI in the VR group were not statistically significant. Conclusion This study suggests that virtual reality training may be a beneficial therapeutic technique on unilateral spatial neglect in stroke patients. PMID:22506138

Accurate prediction of bond dissociation energies of large n-alkanes using ONIOM-CCSD(T)/CBS methods

NASA Astrophysics Data System (ADS)

Wu, Junjun; Ning, Hongbo; Ma, Liuhao; Ren, Wei

2018-05-01

Accurate determination of the bond dissociation energies (BDEs) of large alkanes is desirable but practically impossible due to the expensive cost of high-level ab initio methods. We developed a two-layer ONIOM-CCSD(T)/CBS method which treats the high layer with CCSD(T) method and the low layer with DFT method, respectively. The accuracy of this method was validated by comparing the calculated BDEs of n-hexane with that obtained at the CCSD(T)-F12b/aug-cc-pVTZ level of theory. On this basis, the C-C BDEs of C6-C20 n-alkanes were calculated systematically using the ONIOM [CCSD(T)/CBS(D-T):M06-2x/6-311++G(d,p)] method, showing a good agreement with the data available in the literature.

Intercell scheduling: A negotiation approach using multi-agent coalitions

NASA Astrophysics Data System (ADS)

Tian, Yunna; Li, Dongni; Zheng, Dan; Jia, Yunde

2016-10-01

Intercell scheduling problems arise as a result of intercell transfers in cellular manufacturing systems. Flexible intercell routes are considered in this article, and a coalition-based scheduling (CBS) approach using distributed multi-agent negotiation is developed. Taking advantage of the extended vision of the coalition agents, the global optimization is improved and the communication cost is reduced. The objective of the addressed problem is to minimize mean tardiness. Computational results show that, compared with the widely used combinatorial rules, CBS provides better performance not only in minimizing the objective, i.e. mean tardiness, but also in minimizing auxiliary measures such as maximum completion time, mean flow time and the ratio of tardy parts. Moreover, CBS is better than the existing intercell scheduling approach for the same problem with respect to the solution quality and computational costs.

Ab initio calculations, structure, NBO and NCI analyses of Xsbnd H⋯π interactions

NASA Astrophysics Data System (ADS)

Wu, Qiyang; Su, He; Wang, Hongyan; Wang, Hui

2018-02-01

The performance of ab initio methods (MP2, DFT/B3LYP, random-phase approximation (RPA), CCSD(T) and QCISD(T)) in predicting interaction energy of Xsbnd H⋯π (Xsbnd H = HCCH, HCl, HF; π = C2H2, C2H4, C6H6) hydrogen complexes are assessed systematically. The CCSD(T)/CBS benchmarks of interaction energy are reported. It is found that RPA agrees well with CCSD(T)/CBS benchmarks and experimental results. CCSD(T) and QCISD(T) perform the best only when compared with CCSD(T)/CBS benchmarks, MP2 performs well only for experimental data. B3LYP provides the worst accuracy. Additionally, the equilibrium structure, interaction type of Xsbnd H⋯π hydrogen complexes are investigated by the natural bond orbital (NBO) and the non-covalent interaction index (NCI).

Dynamic expression of the p53 family members p63 and p73 in the mouse and human telencephalon during development and in adulthood.

PubMed

Hernández-Acosta, N Carolina; Cabrera-Socorro, Alfredo; Morlans, Mercedes Pueyo; Delgado, Francisco J González; Suárez-Solá, M Luisa; Sottocornola, Roberta; Lu, Xin; González-Gómez, Miriam; Meyer, Gundela

2011-02-04

p63 and p73, family members of the tumor suppressor p53, are critically involved in the life and death of mammalian cells. They display high homology and may act in concert. The p73 gene is relevant for brain development, and p73-deficient mice display important malformations of the telencephalon. In turn, p63 is essential for the development of stratified epithelia and may also play a part in neuronal survival and aging. We show here that p63 and p73 are dynamically expressed in the embryonic and adult mouse and human telencephalon. During embryonic stages, Cajal-Retzius cells derived from the cortical hem co-express p73 and p63. Comparison of the brain phenotypes of p63- and p73- deficient mice shows that only the loss of p73 function leads to the loss of Cajal-Retzius cells, whereas p63 is apparently not essential for brain development and Cajal-Retzius cell formation. In postnatal mice, p53, p63, and p73 are present in cells of the subventricular zone (SVZ) of the lateral ventricle, a site of continued neurogenesis. The neurogenetic niche is reduced in size in p73-deficient mice, and the numbers of young neurons near the ventricular wall, marked with doublecortin, Tbr1 and calretinin, are dramatically decreased, suggesting that p73 is important for SVZ proliferation. In contrast to their restricted expression during brain development, p73 and p63 are widely detected in pyramidal neurons of the adult human cortex and hippocampus at protein and mRNA levels, pointing to a role of both genes in neuronal maintenance in adulthood. Copyright © 2010 Elsevier B.V. All rights reserved.

Compensatory Beliefs about Glucose Testing are Associated with Low Adherence to Treatment and Poor Metabolic Control in Adolescents with Type 1 Diabetes

ERIC Educational Resources Information Center

Rabiau, Marjorie A.; Knauper, Barbel; Nguyen, Thien-Kim; Sufrategui, Maria; Polychronakos, Constantin

2009-01-01

The goal of this research was to investigate whether compensatory beliefs (CBs) regarding glucose testing predict blood glucose levels and adherence to treatment in adolescents with type 1 diabetes. CBs are convictions that the negative effects of one behavior (e.g. not testing one's glucose level) can be compensated for by engaging in another…

Candida dajiaensis sp. nov., Candida yuanshanicus sp. nov., Candida jianshihensis sp. nov., and Candida sanyiensis sp. nov., four anamorphic, ascomycetous yeast species isolated from soil in Taiwan.

PubMed

Liu, Chun-Hao; Young, Shuh-Sen; Chang, Tsung-Chain; Lee, Ching-Fu

2008-08-01

Nine anamorphic, ascomycetous yeast strains belonging to the Pichia anomala clade were recovered from forest soil in 2006 in Taiwan. The nine yeast strains represent four novel yeast species based on the sequences of their D1/D2 domain of the large subunit (LSU) rRNA gene and their physiological characteristics. The scientific names of Candida dajiaensis sp. nov., Candida yuanshanicus sp. nov., Candida jianshihensis sp. nov., and Candida sanyiensis sp. nov. are proposed for these novel yeast species. The type strains are C. dajiaensis SM11S03(T) (=CBS 10590(T)=BCRC 23099(T)), C. yuanshanicus SY3S02(T) (=CBS 10589(T)=BCRC 23100(T)), C. jianshihensis SM8S04(T) (=CBS 10591(T)=BCRC 23096(T)), and C. sanyiensis SA1S06(T) (=CBS 10592(T)=BCRC 23094(T)). Sequence analysis of the D1/D2 of the LSU rRNA gene revealed that the three species, C. dajiaensis, C. yuanshanicus and Pichia onychis, shared a separate branch in the phylogenetic tree, C. jianshihensis is phylogenetically related to Candida ulmi and Pichia alni, and the phylogenetically closest relative of C. sanyiensis is Pichia populi.

Trial-based psychotherapy and the efficacy of trial-based thought record in changing unhelpful core beliefs and reducing self-criticism.

PubMed

de Oliveira, Irismar Reis; Hemmany, Curt; Powell, Vania B; Bonfim, Thaís D; Duran, Erica P; Novais, Nilma; Velasquez, Michella; Di Sarno, Elaine; Alves, Gledson L; Cesnik, Joici A

2012-03-01

The best prevention against relapse results when patients are taught to restructure negative core beliefs (CBs). Efficacy of the trial-based thought record (TBTR) in decreasing the credit given by patients to negative CBs and corresponding emotions was evaluated. Patients (n = 166) were submitted to a simulation of a legal trial to assess their adherence to negative CBs and corresponding emotions after each cognitive therapy technique incorporated by TBTR. Significant reductions existed in percent values after the first and second defense attorney pleas, as well as after jury's verdict and initial preparation for the appeal (p < 0.001), relative to the investigation phase. Significant differences also emerged between the defense attorney's first and second pleas and between the defense attorney's second plea and jury's verdict, as well as preparation for the appeal (p < 0.001). There was no significant difference between percentages presented by patients submitted to TBTR used in the empty chair format relative to the conventional format. Similarly, there was no difference between outcomes, regardless of therapists' level of exposure to TBTR. TBTR may help patients reduce attachment to negative CBs and corresponding emotions. Outcomes were significantly favorable regardless of the format use and therapists' level of exposure to TBTR.

Experiences of Rehabilitation Professionals with the Implementation of a Back School for Patients with Chronic Low Back Pain: A Qualitative Study.

PubMed

Peters, Stefan; Faller, Hermann; Pfeifer, Klaus; Meng, Karin

2016-01-01

A standardized curriculum back school (CBS) has been recommended for further dissemination in medical rehabilitation in Germany. However, implementation of self-management education programs into practice is challenging. In low back pain care, individual factors of professionals could be decisive regarding implementation fidelity. The study aim was to explore attitudes and experiences of professionals who conducted the back school. Qualitative interviews were led with 45 rehabilitation professionals. The data were examined using thematic analysis. Three central themes were identified: (a) "back school as a common thread," (b) "theory versus practice," and (c) "participation and patient-centeredness." The CBS and its manual were frequently described positively because they provide structure. However, specified time was mentioned critically and there were heterogeneous perceptions regarding flexibility in conducting the CBS. Theory and practice in the CBS were discussed concerning amount, distribution, and conjunction. Participation and patient-centeredness were mainly mentioned in terms of amount and heterogeneity of participation as well as the demand for competences of professionals. Factors were detected that may either positively or negatively influence the implementation fidelity of self-management education programs. The results are explorative and provide potential explanatory mechanisms for behavior and acceptance of rehabilitation professionals regarding the implementation of biopsychosocial back schools.

Geometric Energy Derivatives at the Complete Basis Set Limit: Application to the Equilibrium Structure and Molecular Force Field of Formaldehyde.

PubMed

Morgan, W James; Matthews, Devin A; Ringholm, Magnus; Agarwal, Jay; Gong, Justin Z; Ruud, Kenneth; Allen, Wesley D; Stanton, John F; Schaefer, Henry F

2018-03-13

Geometric energy derivatives which rely on core-corrected focal-point energies extrapolated to the complete basis set (CBS) limit of coupled cluster theory with iterative and noniterative quadruple excitations, CCSDTQ and CCSDT(Q), are used as elements of molecular gradients and, in the case of CCSDT(Q), expansion coefficients of an anharmonic force field. These gradients are used to determine the CCSDTQ/CBS and CCSDT(Q)/CBS equilibrium structure of the S 0 ground state of H 2 CO where excellent agreement is observed with previous work and experimentally derived results. A fourth-order expansion about this CCSDT(Q)/CBS reference geometry using the same level of theory produces an exceptional level of agreement to spectroscopically observed vibrational band origins with a MAE of 0.57 cm -1 . Second-order vibrational perturbation theory (VPT2) and variational discrete variable representation (DVR) results are contrasted and discussed. Vibration-rotation, anharmonicity, and centrifugal distortion constants from the VPT2 analysis are reported and compared to previous work. Additionally, an initial application of a sum-over-states fourth-order vibrational perturbation theory (VPT4) formalism is employed herein, utilizing quintic and sextic derivatives obtained with a recursive algorithmic approach for response theory.

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

Miliordos, Evangelos; Aprà, Edoardo; Xantheas, Sotiris S.

We establish a new estimate for the binding energy between two benzene molecules in the parallel-displaced (PD) conformation by systematically converging (i) the intra- and intermolecular geometry at the minimum, (ii) the expansion of the orbital basis set, and (iii) the level of electron correlation. The calculations were performed at the second-order Møller–Plesset perturbation (MP2) and the coupled cluster including singles, doubles, and a perturbative estimate of triples replacement [CCSD(T)] levels of electronic structure theory. At both levels of theory, by including results corrected for basis set superposition error (BSSE), we have estimated the complete basis set (CBS) limit bymore » employing the family of Dunning’s correlation-consistent polarized valence basis sets. The largest MP2 calculation was performed with the cc-pV6Z basis set (2772 basis functions), whereas the largest CCSD(T) calculation was with the cc-pV5Z basis set (1752 basis functions). The cluster geometries were optimized with basis sets up to quadruple-ζ quality, observing that both its intra- and intermolecular parts have practically converged with the triple-ζ quality sets. The use of converged geometries was found to play an important role for obtaining accurate estimates for the CBS limits. Our results demonstrate that the binding energies with the families of the plain (cc-pVnZ) and augmented (aug-cc-pVnZ) sets converge [within <0.01 kcal/mol for MP2 and <0.15 kcal/mol for CCSD(T)] to the same CBS limit. In addition, the average of the uncorrected and BSSE-corrected binding energies was found to converge to the same CBS limit much faster than either of the two constituents (uncorrected or BSSE-corrected binding energies). Due to the fact that the family of augmented basis sets (especially for the larger sets) causes serious linear dependency problems, the plain basis sets (for which no linear dependencies were found) are deemed as a more efficient and straightforward path for obtaining an accurate CBS limit. We considered extrapolations of the uncorrected (ΔE) and BSSE-corrected (ΔE cp) binding energies, their average value (ΔE ave), as well as the average of the latter over the plain and augmented sets (Δ~E ave) with the cardinal number of the basis set n. Our best estimate of the CCSD(T)/CBS limit for the π–π binding energy in the PD benzene dimer is D e = -2.65 ± 0.02 kcal/mol. The best CCSD(T)/cc-pV5Z calculated value is -2.62 kcal/mol, just 0.03 kcal/mol away from the CBS limit. For comparison, the MP2/CBS limit estimate is -5.00 ± 0.01 kcal/mol, demonstrating a 90% overbinding with respect to CCSD(T). Finally, the spin-component-scaled (SCS) MP2 variant was found to closely reproduce the CCSD(T) results for each basis set, while scaled opposite spin (SOS) MP2 yielded results that are too low when compared to CCSD(T).« less

The cells of cajal-retzius: still a mystery one century after.

PubMed

Soriano, Eduardo; Del Río, José Antonio

2005-05-05

Cajal-Retzius (CR) cells are an enigmatic class of neurons located at the surface of the cerebral cortex, playing a major role in cortical development. In this review, we discuss several distinct features of these neurons and the mechanisms by which they regulate cortical development. Many CR cells likely have extracortical origin and undergo cell death during development. Recent genetic studies report unique patterns of gene expression in CR cells, which may help to explain the developmental processes in which they participate. Moreover, a number of studies indicate that CR cells, and their secreted gene product, reelin, are involved in neuronal migration by acting on two key partners, migrating neurons and radial glial cells. Emerging data show that these neurons are a critical part of an early and complex network of neural activity in layer I, supporting the notion that CR cells modulate cortical maturation. Given these key and complex developmental properties, it is therefore conceivable for CR cells to be implicated in the pathogenesis of a variety of neurological disorders.

Beyond disciplinary borders. H. A. Lorentz and S. Ramón y Cajal.

PubMed

Fernández Santarén, J; Kox, A J; Sánchez-Ron, J M

2014-01-01

Science is a multidisciplinary enterprise. Mathematics, physics, chemistry, biology, geology, and many other, perhaps not so " basic ", but not less interesting disciplines form what we call " science ". The task of history of science is to recover and put order in the past of such disciplines. Although, on most the occasions, those histories are limited by the territories of the different sciences, we know that their frontiers are not impermeable, that there are relationships between them. However, it is not frequent to find studies dealing with those relationships, especially dealing with relations among scientists belonging to different fields. In the present paper, we study a case in which two outstanding scientists, a physicist and a histologist (or neuroscientist, as we would say today), the Dutchman Hendrik A. Lorentz and the Spanish Santiago Ramón y Cajal, maintained a, albeit brief, relation. Both being such prominent scientific figures, of worldwide stature, the relation they maintained deserves to be known.

The impossible interview with the man of the hidden biological structures. Interview by Paolo Mazzarello.

PubMed

Golgi, Camillo

2006-12-01

This paper presents an "impossible interview" to Professor Camillo Golgi, placed in time in December 1906. The Italian Professor Golgi from Pavia has been awarded the Nobel Prize for Physiology or Medicine ex aequo with the Spanish anatomist Santiago Ramón y Cajal. Both scientists have obtained the award for their work on the anatomy of the nervous system. However, they have opposite views on the mechanisms underlying nervous functions. Golgi believes that the axons stained by his "black reaction" form a continuous anatomical or functional network along which nervous impulses propagate. Ramón y Cajal is the paladin of the neuron theory, a hypothesis questioned by Golgi in his Nobel lecture of Tuesday, December 11. After the ceremony, an independent journalist has interviewed Professor Golgi in the Grand Hotel in Stockholm. Excerpts about his education, his main scientific discoveries, and his personal life are here given (reconstructing the "impossible interview" on the basis of Golgi's original writings).

Roles of interleukin-9 in the growth and cholecystokinin-induced intracellular calcium signaling of cultured interstitial cells of Cajal.

PubMed

Gong, Yaoyao; Huang, Lei; Cheng, Wenfang; Li, Xueliang; Lu, Jia; Lin, Lin; Si, Xinmin

2014-01-01

Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract and loss of ICC is associated with many GI motility disorders. Previous studies have shown that ICC have the capacity to regenerate or restore, and several growth factors are critical to their growth, maintenance or regeneration. The present study aimed to investigate the roles of interleukin-9 (IL-9) in the growth, maintenance and pacemaker functions of cultured ICC. Here, we report that IL-9 promotes proliferation of ICC, and culturing ICC with IL-9 enhances cholecystokinin-8-induced Ca²⁺ transients, which is probably caused by facilitating maintenance of ICC functions under culture condition. We also show co-localizations of cholecystokinin-1 receptor and IL-9 receptor with c-kit by double-immunohistochemical labeling. In conclusion, IL-9 can promote ICC growth and help maintain ICC functions; IL-9 probably performs its functions via IL-9 receptors on ICC.

User's manual for CBS3DS, version 1.0

NASA Astrophysics Data System (ADS)

Reddy, C. J.; Deshpande, M. D.

1995-10-01

CBS3DS is a computer code written in FORTRAN 77 to compute the backscattering radar cross section of cavity backed apertures in infinite ground plane and slots in thick infinite ground plane. CBS3DS implements the hybrid Finite Element Method (FEM) and Method of Moments (MoM) techniques. This code uses the tetrahedral elements, with vector edge basis functions for FEM in the volume of the cavity/slot and the triangular elements with the basis functions for MoM at the apertures. By virtue of FEM, this code can handle any arbitrarily shaped three-dimensional cavities filled with inhomogeneous lossy materials; due to MoM, the apertures can be of any arbitrary shape. The User's Manual is written to make the user acquainted with the operation of the code. The user is assumed to be familiar with the FORTRAN 77 language and the operating environment of the computer the code is intended to run.

Momentum signatures of the Anderson transition

NASA Astrophysics Data System (ADS)

Sanjib, Ghosh

This thesis explores for possible signatures of Anderson localization and the Anderson metal-insulator transition (MIT) in momentum space. We find that an initial plane-wave propagating in a disordered medium exhibits a diffusive background and two interference peaks, the coherent backscattering (CBS) and the coherent forward scattering (CFS) peaks in the momentum distribution. We show, the signatures of Anderson localization and the Anderson transition are encoded in the dynamical properties of the two interference peaks, CBS and CFS. We develop finite-time scaling theory for the angular width of the CBS peak and in the height of the CFS peak. We demonstrate how to extract properties like critical exponent, the mobility edge and signatures of multifractality from this finite-time analysis. These momentum space signatures of the Anderson transition are novel and they promise to be experimental observables for wide range of systems, from cold atoms to classical waves or any wave systems where the momentum distribution is accessible.

Schematic for efficient computation of GC, GC3, and AT3 bias spectra of genome

PubMed Central

Rizvi, Ahsan Z; Venu Gopal, T; Bhattacharya, C

2012-01-01

Selection of synonymous codons for an amino acid is biased in protein translation process. This biased selection causes repetition of synonymous codons in structural parts of genome that stands for high N/3 peaks in DNA spectrum. Period-3 spectral property is utilized here to produce a 3-phase network model based on polyphase filterbank concepts for derivation of codon bias spectra (CBS). Modification of parameters in this model can produce GC, GC3, and AT3 bias spectra. Complete schematic in LabVIEW platform is presented here for efficient and parallel computation of GC, GC3, and AT3 bias spectra of genomes alongwith results of CBS patterns. We have performed the correlation coefficient analysis of GC, GC3, and AT3 bias spectra with codon bias patterns of CBS for biological and statistical significance of this model. PMID:22368390

Schematic for efficient computation of GC, GC3, and AT3 bias spectra of genome.

PubMed

Rizvi, Ahsan Z; Venu Gopal, T; Bhattacharya, C

2012-01-01

Selection of synonymous codons for an amino acid is biased in protein translation process. This biased selection causes repetition of synonymous codons in structural parts of genome that stands for high N/3 peaks in DNA spectrum. Period-3 spectral property is utilized here to produce a 3-phase network model based on polyphase filterbank concepts for derivation of codon bias spectra (CBS). Modification of parameters in this model can produce GC, GC3, and AT3 bias spectra. Complete schematic in LabVIEW platform is presented here for efficient and parallel computation of GC, GC3, and AT3 bias spectra of genomes alongwith results of CBS patterns. We have performed the correlation coefficient analysis of GC, GC3, and AT3 bias spectra with codon bias patterns of CBS for biological and statistical significance of this model.

Batch-Versuche zur Bestimmung der Sorption und Reaktionskinetik von fluoreszierenden Tracern

NASA Astrophysics Data System (ADS)

Vaitl, Tobias; Wohnlich, Stefan

2018-06-01

For many tracer experiments, prior determination of interaction between solid medium and used tracers is of major interest in order to achieve efficient, economic and successful field experiments. In the present study, three different types of batch experiments were performed with three fluorescent dyes (Na-Fluorescein, Amidorhodamin G and Tinopal CBS-X) and three different rock types (sandstone, claystone and limestone), to determine distribution coefficients and reaction kinetics. All three rock types were analysed for organic carbon content, specific surface area and mineralogical composition to identify the main sorption mechanisms. For all tracers, different sorption properties were found depending on the type of rock. The strongest sorption was observed for Tinopal CBS-X in contact with claystone. Only Na-Fluorescein showed sorption (albeit limited) in contact with the sandstones. The investigated limestones indicated a high sorption for the tracer Tinopal CBS-X. Regarding reaction kinetics, in most cases, thermodynamic equilibrium conditions were reached after two weeks.

Direct weak localization signature with ultracold atoms: the CBS revival

NASA Astrophysics Data System (ADS)

Josse, Vincent

2016-05-01

Ultracold atomic systems in presence of disorder have attracted a lot of interest over the past decade, in particular to study the physics of Anderson localization (AL) in a renewed perspective. Landmark experiments have been demonstrated, in 1D and 3D geometries. However many challenges remain and new ideas have emerged, as for instance the search for original signatures of Anderson localization in momentum space. Here I will describe our progresses along that line where a weak localization effect has been directly observed, i.e. the Coherent Backscattering (CBS) phenomenon. In particular I will report on the recent observation of suppression and revival of CBS when a controlled dephasing kick is applied to the system. This observation demonstrates a novel and general method, introduced by T. Micklitz and coworkers, to study probe phase coherence in disordered systems by manipulating time reversal symmetry.

Variability in the Milky Way: Contact Binaries as Diagnostic Tools

NASA Astrophysics Data System (ADS)

de Grijs, R.; Chen, X.; Deng, L.

2017-07-01

We used the 50 cm Binocular Network (50BiN) telescope at Delingha Station (Qinghai Province) of Purple Mountain Observatory (Chinese Academy of Sciences) to obtain simultaneous V- and R-band observations of the old open cluster NGC 188. Our aim was a search for populations of variable stars. We derived light-curve solutions for six W Ursae Majoris (W UMa) eclipsing-binary systems and estimated their orbital parameters. The resulting distance to the W UMas is independent of the physical characteristics of the host cluster. We next determined the current best period-luminosity relations for contact binaries (CBs; scatter σ<0.10 mag). We conclude that CBs can be used as distance tracers with better than 5% uncertainty. We apply our new relations to the 102 CBs in the Large Magellanic Cloud, which yields a distance modulus of (m-M)V,0=18.41±0.20 mag.

Reconstruction and visualization of carbohydrate, N-glycosylation pathways in Pichia pastoris CBS7435 using computational and system biology approaches.

PubMed

Srivastava, Akriti; Somvanshi, Pallavi; Mishra, Bhartendu Nath

2013-06-01

Pichia pastoris is an efficient expression system for production of recombinant proteins. To understand its physiology for building novel applications it is important to understand and reconstruct its metabolic network. The metabolic reconstruction approach connects genotype with phenotype. Here, we have attempted to reconstruct carbohydrate metabolism pathways responsible for high biomass density and N-glycosylation pathways involved in the post translational modification of proteins of P. pastoris CBS7435. Both these metabolic pathways play a crucial role in heterologous protein production. We report novel, missing and unannotated enzymes involved in the target metabolic pathways. A strong possibility of cellulose and xylose metabolic processes in P. pastoris CBS7435 suggests its use in the area of biofuels. The reconstructed metabolic networks can be used for increased yields and improved product quality, for designing appropriate growth medium, for production of recombinant therapeutics and for making biofuels.

Compulsive buying and borderline personality symptomatology.

PubMed

Sansone, Randy A; Chang, Joy; Jewell, Bryan; Sellbom, Martin; Bidwell, Mark

2013-04-01

In this study, the authors investigated the relationship between compulsive buying and borderline personality disorder (BPD) symptomatology--two disorders possibly linked through impulsivity. Using a survey methodology in a cross-sectional consecutive sample of nonemergent female outpatients from an obstetrics/gynecology clinic, the authors assessed compulsive buying with the compulsive buying scale (CBS) and BPD symptomatology through the BPD scale of the personality diagnostic questionnaire-4 (PDQ-4) and the self-harm Inventory (SHI). In this sample, 8% of Caucasian women and 9% of African-American women scored positively for compulsive buying. The correlations between scores on the CBS and the PDQ-4 and SHI were 0.43 and 0.41, respectively-both statistically significant at the p < .001 level. Compared to Caucasian women, African-American women demonstrated statistical associations between the BPD measures and the CBS scale scores that were significantly larger. Findings suggest relationships between compulsive buying and BPD, particularly among African-American women.

Childhood trauma and compulsive buying.

PubMed

Sansone, Randy A; Chang, Joy; Jewell, Bryan; Rock, Rachel

2013-02-01

Childhood trauma has been empirically associated with various types of self-regulatory difficulties in adulthood. However, according to the extant literature, no study has examined relationships between various types of childhood trauma and compulsive buying behavior in adulthood. Using a self-report survey methodology in a cross-sectional consecutive sample of 370 obstetrics/gynecology patients, we examined five types of childhood trauma before the age of 12 years (i.e. witnessing violence, physical neglect, emotional abuse, physical abuse, sexual abuse) in relationship to compulsive buying as assessed by the Compulsive Buying Scale (CBS). All forms of trauma demonstrated statistically significant correlations with the CBS. Using a linear regression analysis, both witnessing violence and emotional abuse significantly contributed to CBS scores. Further analyses indicated that race did not moderate the relationship between childhood trauma and compulsive buying. Findings indicate that various forms of childhood trauma are correlated with compulsive buying behavior, particularly witnessing violence and emotional abuse.

Crystallinity properties and crystallization behavior of chocolate fat blends.

PubMed

da Silva, Thais Lomonaco Teodoro; Grimaldi, Renato; Calligaris, Guilherme Andrade; Cardoso, Lisandro Pavie; Gonçalves, Lireny Aparecida Guaraldo

2017-06-01

Cocoa butter (CB) provides unique crystallization characteristics to chocolates and confectionary products; hence, it is an important value-add product. However, other alternative fats that minimally affect the crystallization behaviour of chocolates and confectionary products are now being increasingly used. This study analyzed the crystallization behaviour of CB, cocoa butter substitutes (CBSs), and their blends. Blends were prepared using CBS concentrations: 5, 10, 15, 20 and 37.5%. CB, CBS, and their blends were evaluated by following analysis: solid fat content, isothermal analysis, polarized light microscopic, thermal behaviour, X-ray diffraction and consistency. Crystallization analysis showed an incompatibility between the 2 fats, with a reduction in the crystallinity and increase in liquid content in all the blends. Eutectic crystallization at 20 °C was only observed for the blend containing 20% CBSs. This was considered as a positive result because previous studies have indicated that CBS concentration in CB blends should not be more than 5%.

Candida asparagi sp. nov., Candida diospyri sp. nov. and Candida qinlingensis sp. nov., novel anamorphic, ascomycetous yeast species.

PubMed

Lu, Hui-Zhong; Jia, Jian-Hua; Wang, Qi-Ming; Bai, Feng-Yan

2004-07-01

Among ascomycetous yeasts that were isolated from several nature reserve areas in China, three anamorphic strains isolated from soil (QL 5-5T) and fruit (QL 21-2T and SN 15-1T) were revealed, by conventional characterization and molecular phylogenetic analysis based on internal transcribed spacer and large subunit (26S) rRNA gene D1/D2 region sequencing, to represent three novel species in the genus Candida. Candida qinlingensis sp. nov. (type strain, QL 5-5T=AS 2.2524T=CBS 9768T) was related closely to a teleomorphic species, Williopsis pratensis. The close relatives of Candida diospyri sp. nov. (type strain, QL 21-2T=AS 2.2525T=CBS 9769T) are Candida friedrichii and Candida membranifaciens. Candida asparagi sp. nov. (type strain, SN 15-1T=AS 2.2526T=CBS 9770T) forms a clade with Candida fructus.

Omics Analyses of Trichoderma reesei CBS999.97 and QM6a Indicate the Relevance of Female Fertility to Carbohydrate-Active Enzyme and Transporter Levels.

PubMed

Tisch, Doris; Pomraning, Kyle R; Collett, James R; Freitag, Michael; Baker, Scott E; Chen, Chia-Ling; Hsu, Paul Wei-Che; Chuang, Yu Chien; Schuster, Andre; Dattenböck, Christoph; Stappler, Eva; Sulyok, Michael; Böhmdorfer, Stefan; Oberlerchner, Josua; Wang, Ting-Fang; Schmoll, Monika

2017-11-15

The filamentous fungus Trichoderma reesei is found predominantly in the tropics but also in more temperate regions, such as Europe, and is widely known as a producer of large amounts of plant cell wall-degrading enzymes. We sequenced the genome of the sexually competent isolate CBS999.97, which is phenotypically different from the female sterile strain QM6a but can cross sexually with QM6a. Transcriptome data for growth on cellulose showed that entire carbohydrate-active enzyme (CAZyme) families are consistently differentially regulated between these strains. We evaluated backcrossed strains of both mating types, which acquired female fertility from CBS999.97 but maintained a mostly QM6a genetic background, and we could thereby distinguish between the effects of strain background and female fertility or mating type. We found clear regulatory differences associated with female fertility and female sterility, including regulation of CAZyme and transporter genes. Analysis of carbon source utilization, transcriptomes, and secondary metabolites in these strains revealed that only a few changes in gene regulation are consistently correlated with different mating types. Different strain backgrounds (QM6a versus CBS999.97) resulted in the most significant alterations in the transcriptomes and in carbon source utilization, with decreased growth of CBS999.97 on several amino acids (for example proline or alanine), which further correlated with the downregulation of genes involved in the respective pathways. In combination, our findings support a role of fertility-associated processes in physiology and gene regulation and are of high relevance for the use of sexual crossing in combining the characteristics of two compatible strains or quantitative trait locus (QTL) analysis. IMPORTANCE Trichoderma reesei is a filamentous fungus with a high potential for secretion of plant cell wall-degrading enzymes. We sequenced the genome of the fully fertile field isolate CBS999.97 and analyzed its gene regulation characteristics in comparison with the commonly used laboratory wild-type strain QM6a, which is not female fertile. Additionally, we also evaluated fully fertile strains with genotypes very close to that of QM6a in order to distinguish between strain-specific and fertility-specific characteristics. We found that QM6a and CBS999.97 clearly differ in their growth patterns on different carbon sources, CAZyme gene regulation, and secondary metabolism. Importantly, we found altered regulation of 90 genes associated with female fertility, including CAZyme genes and transporter genes, but only minor mating type-dependent differences. Hence, when using sexual crossing in research and for strain improvement, it is important to consider female fertile and female sterile strains for comparison with QM6a and to achieve optimal performance. Copyright © 2017 Tisch et al.

Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology.

PubMed

Metzger, Gregory J; Kalavagunta, Chaitanya; Spilseth, Benjamin; Bolan, Patrick J; Li, Xiufeng; Hutter, Diane; Nam, Jung W; Johnson, Andrew D; Henriksen, Jonathan C; Moench, Laura; Konety, Badrinath; Warlick, Christopher A; Schmechel, Stephen C; Koopmeiners, Joseph S

2016-06-01

Purpose To develop multiparametric magnetic resonance (MR) imaging models to generate a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for detection of prostate cancer by using coregistered correlative histopathologic results, and to compare performance of CBS-based detection with that of single quantitative MR imaging parameters. Materials and Methods Institutional review board approval and informed consent were obtained. Patients with a diagnosis of prostate cancer underwent multiparametric MR imaging before surgery for treatment. All MR imaging voxels in the prostate were classified as cancer or noncancer on the basis of coregistered histopathologic data. Predictive models were developed by using more than one quantitative MR imaging parameter to generate CBS maps. Model development and evaluation of quantitative MR imaging parameters and CBS were performed separately for the peripheral zone and the whole gland. Model accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC), and confidence intervals were calculated with the bootstrap procedure. The improvement in classification accuracy was evaluated by comparing the AUC for the multiparametric model and the single best-performing quantitative MR imaging parameter at the individual level and in aggregate. Results Quantitative T2, apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), reflux rate constant (kep), and area under the gadolinium concentration curve at 90 seconds (AUGC90) were significantly different between cancer and noncancer voxels (P < .001), with ADC showing the best accuracy (peripheral zone AUC, 0.82; whole gland AUC, 0.74). Four-parameter models demonstrated the best performance in both the peripheral zone (AUC, 0.85; P = .010 vs ADC alone) and whole gland (AUC, 0.77; P = .043 vs ADC alone). Individual-level analysis showed statistically significant improvement in AUC in 82% (23 of 28) and 71% (24 of 34) of patients with peripheral-zone and whole-gland models, respectively, compared with ADC alone. Model-based CBS maps for cancer detection showed improved visualization of cancer location and extent. Conclusion Quantitative multiparametric MR imaging models developed by using coregistered correlative histopathologic data yielded a voxel-wise CBS that outperformed single quantitative MR imaging parameters for detection of prostate cancer, especially when the models were assessed at the individual level. (©) RSNA, 2016 Online supplemental material is available for this article.

Improving cyanobacterail O 2-tolerance using CBS hydrogenase for hydrogen production

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

Maness, Pin-Ching; Eckert, Carrie; Wawrousek, Karen

2016-11-11

Cyanobacterial H 2 production is a viable path to renewable H 2 with water serving as the electron donor and sunlight the energy source. A grand challenge is the sensitivity of the underlying hydrogenase to O 2, the latter an inherent byproduct of oxygenic photosynthesis. This challenge has been identified as a technical barrier in the Fuel Cell Technologies Office (FCTO) Multi-year Research, Development and Deployment Plan. One solution is to express in cyanobacterium an O 2-tolerant hydrogenase to circumvent this barrier. We have uncovered an O 2-tolerant hydrogenase from a photosynthetic bacterium Rubrivivax gelatinosus CBS (Casa Bonita Strain; hereaftermore » “CBS”) with a half-life near 21 h when exposed to ambient O 2. We sequenced the CBS genome and identified two sets of maturation machineries hyp1 and hyp2. Transcripts expression analysis and mutagenesis revealed that hyp1 is responsible for the assembly of the O 2-tolerant CO-oxidation (Coo) hydrogenase and hyp2 is involved in the maturation of a H 2-uptake hydrogenase. The structural genes encoding the O 2-tolerant hydrogenase (cooLXUH) and maturation genes hyp1FABCDE were therefore cloned and expressed in the model cyanobacterium Synechocystis sp. PCC 6803. We obtained several recombinants displaying hydrogenase activity in a Synechocystis host lacking background activity, suggesting that the CBS hydrogenase is active in Synechocystis. Yet the activity is extremely low. To ensure balanced protein expression, we systematically optimized heterologous expression of 10 CBS genes by using stronger promoters and better ribosome binding site. Moreover we attempted the expression of cooM and cooK genes, verified to be important in CBS to afford activity. CooM is a very large protein and both CooM and CooK are membrane-associated. These properties limited our success in expressing both genes in Synechocystis, although they were both expressed in E. coli yet with no activity. This project was terminated in FY2016 due to the inability to generate a Synechocystis strain with consistent and active H 2 production activity. Nevertheless the research has led to a few high-impact publications and numerous conference presentations to increase global visibility of the DOE-funded research.« less

Suppression of Ostwald Ripening by Chemical Reactions

NASA Astrophysics Data System (ADS)

Zwicker, David; Hyman, Anthony A.; Jülicher, Frank

2015-03-01

Emulsions consisting of droplets immersed in a fluid are typically unstable and coarsen over time. One important coarsening process is Ostwald ripening, which is driven by the surface tension of the droplets. Ostwald ripening must thus be suppressed to stabilize emulsions, e.g. to control the properties of pharmaceuticals, food, or cosmetics. Suppression of Ostwald ripening is also important in biological cells, which contain stable liquid-like compartments, e.g. germ granules, Cajal-bodies, and centrosomes. Such systems are often driven away from equilibrium by chemical reactions and can thus be called active emulsions. Here, we show that non-equilibrium chemical reactions can suppress Ostwald Ripening, leading to stable, monodisperse emulsions. We derive analytical approximations of the typical droplet size, droplet count, and time scale of the dynamics from a coarse-grained description of the droplet dynamics. We also compare these results to numerical simulations of the continuous concentration fields. Generally, we thus show how chemical reactions can be used to stabilize emulsions and to control their properties in technology and nature.

Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin

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

Lymberopoulos, Maria H.; Pearson, Angela

2007-07-05

UL24 of herpes simplex virus 1 is important for efficient viral replication, but its function is unknown. We generated a recombinant virus, vHA-UL24, encoding UL24 with an N-terminal hemagglutinin tag. By indirect immunofluorescence at 9 h post-infection (hpi), we detected HA-UL24 in nuclear foci and in cytoplasmic speckles. HA-UL24 partially co-localized with nucleolin, but not with ICP8 or coilin, markers for nucleoli, viral replication compartments, and Cajal bodies respectively. HA-UL24 staining was often juxtaposed to that of another nucleolar protein, fibrillarin. Analysis of HSV-1-induced nucleolar modifications revealed that by 18 hpi, nucleolin staining had dispersed, and fibrillarin staining went frommore » clusters of small spots to a few separate but prominent spots. Fibrillarin redistribution appeared to be independent of UL24. In contrast, cells infected with a UL24-deficient virus retained foci of nucleolin staining. Our results demonstrate involvement of UL24 in dispersal of nucleolin during infection.« less

In vitro organogenesis of gut-like structures from mouse embryonic stem cells.

PubMed

Kuwahara, M; Ogaeri, T; Matsuura, R; Kogo, H; Fujimoto, T; Torihashi, S

2004-04-01

Embryonic stem (ES) cells have pluripotency and give rise to many cell types and tissues, including representatives of all three germ layers in the embryo. We have reported previously that mouse ES cells formed contracting gut-like organs from embryoid bodies (EBs). These gut-like structures contracted spontaneously, and had large lumens surrounded by three layers, i.e. epithelium, lamina propria and muscularis. Ganglia were scattered along the periphery, and interstitial cells of Cajal (ICC) were distributed among the smooth muscle cells. In the present study, to determine whether they can be a model of gut organogenesis, we investigated the formation process of the gut-like structures in comparison with embryonic gut development. As a result, we found that the fundamental process of formation in vitro was similar to embryonic gut development in vivo. The result indicates that the gut-like structure is a useful tool not only for developmental study to determine the factors that induce gut organogenesis, but also for studies of enteric neurone and ICC development.

Military Personnel Dilemmas: Perspectives on Gender-Related Issues. A Selected List of Resource Materials.

DTIC Science & Technology

1981-05-01

34Army Discharges Wornan After MIarriaqe To Alleged Transsexual ." CBS NEWS. July 21, 1977. p.11. (Morning News). "Army Seeks Dismissal Of Woman...Married To Transsexual ." CBS NEWS. June 6, 1977. p.19. (Morninq News) Austen, Roger. "gut For Fate And Can: Homosexual Villains And Victims In The...identity and sexual behavior are markedly aberrant; homosexuality, transsexualism , and transvestism. For each disorder a psychodynamic analysis of the

Oilbirds produce echolocation signals beyond their best hearing range and adjust signal design to natural light conditions

PubMed Central

Brinkløv, Signe; Elemans, Coen P. H.

2017-01-01

Oilbirds are active at night, foraging for fruits using keen olfaction and extremely light-sensitive eyes, and echolocate as they leave and return to their cavernous roosts. We recorded the echolocation behaviour of wild oilbirds using a multi-microphone array as they entered and exited their roosts under different natural light conditions. During echolocation, the birds produced click bursts (CBs) lasting less than 10 ms and consisting of a variable number (2–8) of clicks at 2–3 ms intervals. The CBs have a bandwidth of 7–23 kHz at −6 dB from signal peak frequency. We report on two unique characteristics of this avian echolocation system. First, oilbirds reduce both the energy and number of clicks in their CBs under conditions of clear, moonlit skies, compared with dark, moonless nights. Second, we document a frequency mismatch between the reported best frequency of oilbird hearing (approx. 2 kHz) and the bandwidth of their echolocation CBs. This unusual signal-to-sensory system mismatch probably reflects avian constraints on high-frequency hearing but may still allow oilbirds fine-scale, close-range detail resolution at the upper extreme (approx. 10 kHz) of their presumed hearing range. Alternatively, oilbirds, by an as-yet unknown mechanism, are able to hear frequencies higher than currently appreciated. PMID:28573036

Compact tunable Compton x-ray source from laser-plasma accelerator and plasma mirror

NASA Astrophysics Data System (ADS)

Tsai, Hai-En; Wang, Xiaoming; Shaw, Joseph M.; Li, Zhengyan; Arefiev, Alexey V.; Zhang, Xi; Zgadzaj, Rafal; Henderson, Watson; Khudik, V.; Shvets, G.; Downer, M. C.

2015-02-01

We present an in-depth experimental-computational study of the parameters necessary to optimize a tunable, quasi-monoenergetic, efficient, low-background Compton backscattering (CBS) x-ray source that is based on the self-aligned combination of a laser-plasma accelerator (LPA) and a plasma mirror (PM). The main findings are (1) an LPA driven in the blowout regime by 30 TW, 30 fs laser pulses produce not only a high-quality, tunable, quasi-monoenergetic electron beam, but also a high-quality, relativistically intense (a0 ˜ 1) spent drive pulse that remains stable in profile and intensity over the LPA tuning range. (2) A thin plastic film near the gas jet exit retro-reflects the spent drive pulse efficiently into oncoming electrons to produce CBS x-rays without detectable bremsstrahlung background. Meanwhile, anomalous far-field divergence of the retro-reflected light demonstrates relativistic "denting" of the PM. Exploiting these optimized LPA and PM conditions, we demonstrate quasi-monoenergetic (50% FWHM energy spread), tunable (75-200 KeV) CBS x-rays, characteristics previously achieved only on more powerful laser systems by CBS of a split-off, counter-propagating pulse. Moreover, laser-to-x-ray photon conversion efficiency (˜6 × 10-12) exceeds that of any previous LPA-based quasi-monoenergetic Compton source. Particle-in-cell simulations agree well with the measurements.

Nutritional Status and Obesity Prevalence in People with Gender Dysphoria

PubMed Central

Vilas, María Victorina Aguilar; Rubalcava, Gabriela; Becerra, Antonio; Para, María Carmen Martínez

2014-01-01

Gender dysphoria is a condition that involves a failure to adapt and a body dissatisfaction that makes these individuals especially susceptible to eating disorders. The aim of this paper was to ascertain the nutritional status, dietary behaviour and lifestyle and their effect on overweight/obesity prevalence of the people with gender dysphoria. Methods A longitudinal study on 157 individuals from the Gender Disorder Unit at the Ramón y Cajal Hospital (Madrid) who are undergoing hormonal treatment has been carried out. Usual dietary intake, physical activity habits and socioeconomic parameters were evaluated. The anthropometric parameters determined were weight, height, body-mass index (BMI), waist and hip circumference and body fat content. Results The mean of the population eats a large number of servings of food, which leads to high levels of energy intake: 3,614.32 ± 1,314 kcal/day. These intakes are related to the physical activity performed. The average diet among this population is unbalanced, with a high consumption of fats, especially saturated fats and cholesterol. The breakfast is skipped by 16% of the population. Together with cross-hormone treatment, this dietary habitsand lifestylelead to an increase in body fat, especially in the female to male group whose overweight andobesity prevalence increase (22.72% vs 34.85%). Conclusion This population suffers a change of their nutritional status due to a variation in their eating behaviour and lifestyle. This increase in the obesity prevalencemake it susceptible to chronic diseases and cardiovascular disorders. It is therefore necessary to include nutrition education courses in the comprehensive treatment programme (anatomical, psychological, etc.) for these individuals. PMID:29546082

Molecular and Biochemical Characterization of a Cathepsin B-Like Protease Family Unique to Trypanosoma congolense▿ †

PubMed Central

Mendoza-Palomares, Carlos; Biteau, Nicolas; Giroud, Christiane; Coustou, Virginie; Coetzer, Theresa; Authié, Edith; Boulangé, Alain; Baltz, Théo

2008-01-01

Cysteine proteases have been shown to be essential virulence factors and drug targets in trypanosomatids and an attractive antidisease vaccine candidate for Trypanosoma congolense. Here, we describe an important amplification of genes encoding cathepsin B-like proteases unique to T. congolense. More than 13 different genes were identified, whereas only one or two highly homologous genes have been identified in other trypanosomatids. These proteases grouped into three evolutionary clusters: TcoCBc1 to TcoCBc5 and TcoCBc6, which possess the classical catalytic triad (Cys, His, and Asn), and TcoCBs7 to TcoCBs13, which contains an unusual catalytic site (Ser, Xaa, and Asn). Expression profiles showed that members of the TcoCBc1 to TcoCBc5 and the TcoCBs7 to TcoCBs13 groups are expressed mainly in bloodstream forms and localize in the lysosomal compartment. The expression of recombinant representatives of each group (TcoCB1, TcoCB6, and TcoCB12) as proenzymes showed that TcoCBc1 and TcoCBc6 are able to autocatalyze their maturation 21 and 31 residues, respectively, upstream of the predicted start of the catalytic domain. Both displayed a carboxydipeptidase function, while only TcoCBc1 behaved as an endopeptidase. TcoCBc1 exhibited biochemical differences regarding inhibitor sensitivity compared to that of other cathepsin B-like proteases. Recombinant pro-TcoCBs12 did not automature in vitro, and the pepsin-matured enzyme was inactive in tests with cathepsin B fluorogenic substrates. In vivo inhibition studies using CA074Me (a cell-permeable cathepsin B-specific inhibitor) demonstrated that TcoCB are involved in lysosomal protein degradation essential for survival in bloodstream form. Furthermore, TcoCBc1 elicited an important immune response in experimentally infected cattle. We propose this family of proteins as a potential therapeutic target and as a plausible antigen for T. congolense diagnosis. PMID:18281598

3-Mercaptopyruvate Sulfurtransferase, Not Cystathionine β-Synthase Nor Cystathionine γ-Lyase, Mediates Hypoxia-Induced Migration of Vascular Endothelial Cells.

PubMed

Tao, Beibei; Wang, Rui; Sun, Chen; Zhu, Yichun

2017-01-01

Hypoxia-induced angiogenesis is a common phenomenon in many physiological and patho-physiological processes. However, the potential differential roles of three hydrogen sulfide producing systems cystathionine γ-lyase (CSE)/H 2 S, cystathionine β-synthase (CBS)/H 2 S, and 3-mercaptopyruvate sulfurtransferase (MPST)/H 2 S in hypoxia-induced angiogenesis are still unknown. We found that minor hypoxia (10% oxygen) significantly increased the migration of vascular endothelial cells while hypoxia (8% oxygen) significantly inhibited cell migration. The present study was performed using cells cultured in 10% oxygen. RNA interference was used to block the endogenous generation of hydrogen sulfide by CSE, CBS, or MPST in a vascular endothelial cell migration model in both normoxia and hypoxia. The results showed that CBS had a promoting effect on the migration of vascular endothelial cells cultured in both normoxic and hypoxic conditions. In contrast, CSE had an inhibitory effect on cell migration. MPST had a promoting effect on the migration of vascular endothelial cells cultured in hypoxia; however, it had no effect on the cells cultured in normoxia. Importantly, it was found that the hypoxia-induced increase in vascular endothelial cell migration was mediated by MPST, but not CSE or CBS. The western blot analyses showed that hypoxia significantly increased MPST protein levels, decreased CSE protein levels and did not change CBS levels, suggesting that these three hydrogen sulfide-producing systems respond differently to hypoxic conditions. Interestingly, MPST protein levels were elevated by hypoxia in a bi-phasic manner and MPST mRNA levels increased later than the first stage elevation of the protein levels, implying that the expression of MPST induced by hypoxia was also regulated at a post-transcriptional level. RNA pull-down assay showed that some candidate RNA binding proteins, such as nucleolin and Annexin A2, were dissociated from the 3'-UTR of MPST mRNA in hypoxia which implied their involvement in MPST mRNA regulation.

CBS Genome Atlas Database: a dynamic storage for bioinformatic results and sequence data.

PubMed

Hallin, Peter F; Ussery, David W

2004-12-12

Currently, new bacterial genomes are being published on a monthly basis. With the growing amount of genome sequence data, there is a demand for a flexible and easy-to-maintain structure for storing sequence data and results from bioinformatic analysis. More than 150 sequenced bacterial genomes are now available, and comparisons of properties for taxonomically similar organisms are not readily available to many biologists. In addition to the most basic information, such as AT content, chromosome length, tRNA count and rRNA count, a large number of more complex calculations are needed to perform detailed comparative genomics. DNA structural calculations like curvature and stacking energy, DNA compositions like base skews, oligo skews and repeats at the local and global level are just a few of the analysis that are presented on the CBS Genome Atlas Web page. Complex analysis, changing methods and frequent addition of new models are factors that require a dynamic database layout. Using basic tools like the GNU Make system, csh, Perl and MySQL, we have created a flexible database environment for storing and maintaining such results for a collection of complete microbial genomes. Currently, these results counts to more than 220 pieces of information. The backbone of this solution consists of a program package written in Perl, which enables administrators to synchronize and update the database content. The MySQL database has been connected to the CBS web-server via PHP4, to present a dynamic web content for users outside the center. This solution is tightly fitted to existing server infrastructure and the solutions proposed here can perhaps serve as a template for other research groups to solve database issues. A web based user interface which is dynamically linked to the Genome Atlas Database can be accessed via www.cbs.dtu.dk/services/GenomeAtlas/. This paper has a supplemental information page which links to the examples presented: www.cbs.dtu.dk/services/GenomeAtlas/suppl/bioinfdatabase.

Therapeutic Effects of Rivastigmine and Alfa-Lipoic Acid Combination in the Charles Bonnet Syndrome: Electroencephalography Correlates.

PubMed

Hanoglu, Lutfu; Yildiz, Sultan; Polat, Burcu; Demirci, Sema; Tavli, Ahmet Mithat; Yilmaz, Nesrin; Yulug, Burak

2016-01-01

Charles Bonnet Syndrome (CBS) is a rare clinical condition which is characterized by complex hallucinations in visually impaired patients. The pathophysiology of this disorder remains largely unknown, and there is still no proven treatment for this disease. In our study, we aimed to investigate the neural activity through Electroencephalography (EEG) power and evaluate the effect of rivastigmine in combination with alpha-lipoic acid on hallucination in two CBS patients with diabetic retinopathy. EEG data was recorded with standard routine EEG protocols for both patients in our electrophysiological research laboratory (REMER Clinical Electrophysiology and Neuromodulation Research and Application Laboratory) with Brain Vision Recorder (Brainproduct, Munich, Germany). All spectral analyses were processed by BrainVision Analyzer 2 (Brainproduct, Munich, Germany, 2.0.4 Version) in 128 Hz sample rates and the EEG recording and analysis was performed before the administration of rivastigmine (4.5 mg/daily and five patch daily for the first and second patients, respectively) in combination with alpha-lipoic acid (600 mg/daily) for both patients while they were not hallucinated during the time period recordings. Based on our measurement protocol, we have compared the patients in the study group with the three control subjects who were found to be normal except of visual disturbances secondary to significant diabetic retinopathy. Highest theta power values were found in right occipital and left temporo-parietal regions for first and second CBS patients, respectively. Additionally, power spectra were lower in two cases as compared to their control groups in the alpha band for all electrodes. We have also shown that acid rivastigmine in combination with alpha-lipoic exerted significant anti-hallucinatory efficiency. Our present findings could support the hypothesis that increased activation of specific areas in the source monitoring system plays an important role in the pathogenesis of CBS. In addition, rivastigmine in combination with alpha-lipoic acid could be a new valuable option for CBS patients.

A Method to Retrieve Rainfall Rate over Land from TRMM Observations

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R., Jr.; Yoo, J.-M.

2002-01-01

Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) observations over mesoscale convective systems (MCSs) reveal that there are localized maxima in the rain rate with a scale of about 10 to 20 km that represent thunderstorms (Cbs). Some of these Cbs are developing or intense, while others are decaying or weak. These Cbs constitute only about 20 % of the rain area of a given MCS. Outside of Cbs, the average rain rate is much weaker than that within Cbs. From an analysis of the PR data, we find that the spatial distribution of rain and its character, convective or stratiform, is highly inhomogeneous. This complex nature of rain exists on a scale comparable to that of a Cb. The 85 GHz brightness temperature, T85, observations of the TRMM Microwave Imager (TMI) radiometer taken over an MCS reflect closely the PR rain rate pattern over land. Local maxima in rain rate shown by PR are observed as local minima in T85. Where there are no minima in T85, PR observations indicate there is light rain. However, the TMI brightness temperature measurements (Tbs) have poor ability to discriminate convective rain from stratiform rain. For this reason, a TMI rain retrieval procedure that depends primarily on the magnitude of Tbs performs poorly. In order to retrieve rain rate from TMI data on land one has to include the spatial distribution information deduced from the T85 data in the retrieval method. Then, quantitative estimation of rain rate can be accomplished. A TMI rain retrieval method developed along these lines can yield estimates of rain rate and its frequency distribution which agree closely with that given by PR. We find the current TRMM project TMI (Version 5) rain retrieval algorithm on land could be improved with the retrieval scheme developed here. To support the conceptual frame work of the rain retrieval method developed here, a theoretical analysis of the TMI brightness temperatures in convective and stratiform regions is presented.

Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study.

PubMed

Sun, Kexin; Song, Jing; Liu, Kuo; Fang, Kai; Wang, Ling; Wang, Xueyin; Li, Jing; Tang, Xun; Wu, Yiqun; Qin, Xueying; Wu, Tao; Gao, Pei; Chen, Dafang; Hu, Yonghua

2017-04-01

Carotid intima-media thickness (CIMT) is a good surrogate for atherosclerosis. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aim to investigate the relationships between homocysteine (Hcy) related biochemical indexes and CIMT, the associations between Hcy related SNPs and CIMT, as well as the potential gene-gene interactions. The present study recruited full siblings (186 eligible families with 424 individuals) with no history of cardiovascular events from a rural area of Beijing. We examined CIMT, intima-media thickness for common carotid artery (CCA-IMT) and carotid bifurcation, tested plasma levels for Hcy, vitamin B6 (VB6), vitamin B12 (VB12) and folic acid (FA), and genotyped 9 SNPs on MTHFR, MTR, MTRR, BHMT, SHMT1, CBS genes. Associations between SNPs and biochemical indexes and CIMT indexes were analyzed using family-based association test analysis. We used multi-level mixed-effects regression model to verify SNP-CIMT associations and to explore the potential gene-gene interactions. VB6, VB12 and FA were negatively correlated with CIMT indexes (p < 0.05). rs2851391 T allele was associated with decreased plasma VB12 levels (p = 0.036). In FABT, CBS rs2851391 was significantly associated with CCA-IMT (p = 0.021) and CIMT (p = 0.019). In multi-level mixed-effects regression model, CBS rs2851391 was positively significantly associated with CCA-IMT (Coef = 0.032, se = 0.009, raw p < 0.001) after Bonferoni correction (corrected α = 0.0056). Gene-gene interactions were found between CBS rs2851391 and BHMT rs10037045 for CCA-IMT (p = 0.011), as well as between CBS rs2851391 and MTR rs1805087 for CCA-IMT (p = 0.007) and CIMT (p = 0.022). Significant associations are found between Hcy metabolism related genetic polymorphisms, biochemical indexes and CIMT indexes. There are complex interactions between genetic polymorphisms for CCA-IMT and CIMT.

Phylogenetic analysis of phenotypically characterized Cryptococcus laurentii isolates reveals high frequency of cryptic species.

PubMed

Ferreira-Paim, Kennio; Ferreira, Thatiana Bragine; Andrade-Silva, Leonardo; Mora, Delio Jose; Springer, Deborah J; Heitman, Joseph; Fonseca, Fernanda Machado; Matos, Dulcilena; Melhem, Márcia Souza Carvalho; Silva-Vergara, Mario León

2014-01-01

Although Cryptococcus laurentii has been considered saprophytic and its taxonomy is still being described, several cases of human infections have already reported. This study aimed to evaluate molecular aspects of C. laurentii isolates from Brazil, Botswana, Canada, and the United States. In this study, 100 phenotypically identified C. laurentii isolates were evaluated by sequencing the 18S nuclear ribosomal small subunit rRNA gene (18S-SSU), D1/D2 region of 28S nuclear ribosomal large subunit rRNA gene (28S-LSU), and the internal transcribed spacer (ITS) of the ribosomal region. BLAST searches using 550-bp, 650-bp, and 550-bp sequenced amplicons obtained from the 18S-SSU, 28S-LSU, and the ITS region led to the identification of 75 C. laurentii strains that shared 99-100% identity with C. laurentii CBS 139. A total of nine isolates shared 99% identity with both Bullera sp. VY-68 and C. laurentii RY1. One isolate shared 99% identity with Cryptococcus rajasthanensis CBS 10406, and eight isolates shared 100% identity with Cryptococcus sp. APSS 862 according to the 28S-LSU and ITS regions and designated as Cryptococcus aspenensis sp. nov. (CBS 13867). While 16 isolates shared 99% identity with Cryptococcus flavescens CBS 942 according to the 18S-SSU sequence, only six were confirmed using the 28S-LSU and ITS region sequences. The remaining 10 shared 99% identity with Cryptococcus terrestris CBS 10810, which was recently described in Brazil. Through concatenated sequence analyses, seven sequence types in C. laurentii, three in C. flavescens, one in C. terrestris, and one in the C. aspenensis sp. nov. were identified. Sequencing permitted the characterization of 75% of the environmental C. laurentii isolates from different geographical areas and the identification of seven haplotypes of this species. Among sequenced regions, the increased variability of the ITS region in comparison to the 18S-SSU and 28S-LSU regions reinforces its applicability as a DNA barcode.

Natural and laboratory compaction bands in porous carbonates: a three-dimensional characterization using synchrotron X-ray computed microtomography

NASA Astrophysics Data System (ADS)

Cilona, A.; Arzilli, F.; Mancini, L.; Emanuele, T.

2014-12-01

Porous carbonates form important reservoirs for water and hydrocarbons. The fluid flow properties of carbonate reservoirs may be affected by post-depositional processes (e.g., mechanical and chemical), which need to be quantified. Field-based studies described bed-parallel compaction bands (CBs) within carbonates with a wide range of porosities. These burial-related structures accommodate volumetric strain by grain rotation, translation, pore collapse and pressure solution. Recently, the same structures have been reproduced for the first time in the laboratory by performing triaxial compaction experiments on porous grainstones. These laboratory studies characterized and compared the microstructures of natural and laboratory CBs, but no analysis of pore connectivity has been performed. In this paper, we use an innovative approach to characterize the pore networks (e.g. porosity, connectivity) of natural and laboratory CBs and compare them with the host rock one. We collected the data using the synchrotron X-ray computed microtomography technique at the SYRMEP beamline of the Elettra-Sincrotrone Trieste Laboratory (Italy). Quantitative analyses of the samples were performed with the Pore3D software library. The porosity was calculated from segmented 3D images of pristine and deformed carbonates. A process of skeletonization was then applied to quantify the number of connected pores within the rock volume. The analysis of the skeleton allowed us to highlight the differences between natural and laboratory CBs, and to investigate how pore connectivity evolves as a function of different deformation pathways. Both pore volume and connectivity are reduced within the CBs respect to the pristine rock and the natural CB has a lower porosity with respect to the laboratory one. The grain contacts in the natural CB are welded, whereas in the laboratory one they have more irregular shapes and grain crushing is the predominant process.

Quantum ratchets, the orbital Josephson effect, and chaos in Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Carr, Lincoln D.; Heimsoth, Martin; Creffield, Charles E.; Sols, Fernando

2014-03-01

In a system of ac-driven condensed bosons we study a new type of Josephson effect occurring between states sharing the same region of space and the same internal atom structure. We first develop a technique to calculate the long-time dynamics of a driven interacting many-body system. For resonant frequencies, this dynamics can be shown to derive from an effective time-independent Hamiltonian which is expressed in terms of standard creation and annihilation operators. Within the subspace of resonant states, and if the undriven states are plane waves, a locally repulsive interaction between bosons translates into an effective attraction. We apply the method to study the effect of interactions on the coherent ratchet current of an asymmetrically driven boson system. We find a wealth of dynamical regimes which includes Rabi oscillations, self-trapping and chaotic behavior. In the latter case, a full quantum many-body calculation deviates from the mean-field results by predicting large quantum fluctuations of the relative particle number. Moreover, we find that chaos and entanglement, as defined by a variety of widely used and accepted measures, are overlapping but distinct notions. Funded by Spanish MINECO, the Ramon y Cajal program (CEC), the Comunidad de Madrid through Grant Microseres, the Heidelberg Center for Quantum Dynamics, and the NSF.

Plant U13 orthologues and orphan snoRNAs identified by RNomics of RNA from Arabidopsis nucleoli

PubMed Central

Kim, Sang Hyon; Spensley, Mark; Choi, Seung Kook; Calixto, Cristiane P. G.; Pendle, Ali F.; Koroleva, Olga; Shaw, Peter J.; Brown, John W. S.

2010-01-01

Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs whose main function in eukaryotes is to guide the modification of nucleotides in ribosomal and spliceosomal small nuclear RNAs, respectively. Full-length sequences of Arabidopsis snoRNAs and scaRNAs have been obtained from cDNA libraries of capped and uncapped small RNAs using RNA from isolated nucleoli from Arabidopsis cell cultures. We have identified 31 novel snoRNA genes (9 box C/D and 22 box H/ACA) and 15 new variants of previously described snoRNAs. Three related capped snoRNAs with a distinct gene organization and structure were identified as orthologues of animal U13snoRNAs. In addition, eight of the novel genes had no complementarity to rRNAs or snRNAs and are therefore putative orphan snoRNAs potentially reflecting wider functions for these RNAs. The nucleolar localization of a number of the snoRNAs and the localization to nuclear bodies of two putative scaRNAs was confirmed by in situ hybridization. The majority of the novel snoRNA genes were found in new gene clusters or as part of previously described clusters. These results expand the repertoire of Arabidopsis snoRNAs to 188 snoRNA genes with 294 gene variants. PMID:20081206

Cost Structure and Life Cycle Costs for Military Systems

DTIC Science & Technology

2003-09-01

LCC 1-1 Chapter 2 – Scope of the Study 2-1 2.1 Contribution of other NATO Entities 2-1 2.2 Review of National Practises and CBS 2-1 2.3 Development...Office – NCO) gave a positive answer and designated a representative in the working group. 2.2 REVIEW OF NATIONAL PRACTISES AND CBS The two first...time preference when spending money obtained through taxation ) with the effectiveness of alternate ways of meeting an objective. By combining the

Simultaneous saccharification and fermentation (SSF) using cellobiose fermenting yeast Brettanomyces custersii (CBS 5512)

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

Spindler, D.D.; Grohmann, K.; Wyman, C.E.

1991-01-16

A process for producing ethanol from plant biomass includes forming a substrate from the biomass with the substrate including hydrolysates of cellulose and hemicellulose. A species of the yeast Brettanomyces custersii (CBS 5512), which has the ability to ferment both cellobiose and glucose to ethanol, is then selected and isolated. The substrate is inoculated with this yeast, and the inoculated substrate is then fermented under conditions favorable for cell viability and conversion of hydrolysates to ethanol.

Studies of the synthesis and deposition of Cu3BiS 3 for use in photovoltaic devices

NASA Astrophysics Data System (ADS)

Epstein, Joshua A.

As the world's climate continues to change, alternative energy is being adopted more and more. Solar energy is one extremely promising candidate to supplement our ever increasing energy needs. In order for it to be a viable solution, more efficient and less expensive solar panels must be made. While silicon solar panels are the current market leader their high manufacturing energy input and cost warrant looking into alternatives. Many thin film solar materials are being investigated such as CdTe, CIGS and CZTS, but all come with their own drawbacks. With a near ideal band gap, low toxicity and earth abundant elemental make up copper bismuth sulfide, Cu3BiS3, is a promising candidate for use in future photovoltaic devices. The research presented here details multiple methods to synthesize and deposit this material with an effort to keep the methods low cost, energy efficient and environmentally friendly. Multiple low temperature solvothermal routes to synthesizing copper bismuth sulfide, CBS, have been developed. The resulting powders have been verified as pure Cu3BiS3 via XRD peak matching. The precursor reactants tested for use were copper and bismuth nitrates, acetates, chlorides and hydroxides. L-cystine, L-cysteine, thiourea and CS2 have all been tested for use as sulfur sources. Seven of these combinations produced pure CBS powders. Two custom built benchtop reactors have been designed and fabricated with the aim of studying the possibility of a continuous flow reactor as a way to utilize these precipitation chemistries for making thin films of CBS. Heat and liquid flow simulations were performed in COMSOL multiphysics to assist in the reactor design process. The second reactor was designed to promote uniform liquid flow across the fluorine doped, tin oxide coated, FTO, glass. This reactor was also built with a temperature gradient transverse to the liquid flow so that the optimal temperature for the deposition of CBS could be evaluated. This reactor was also used to evaluate the deposition of CdS, an n-type semiconductor often used in thin film solar panels, onto FTO glass. CBS thin films were also prepared via electrodeposition and thermal treatment. The solution used was a mixture of copper nitrate, sodium sulfite and sodium citrate tribasic dihydrate dissolved in DI H2O and bismuth nitrate dissolved in ethylene glycol. To get the best coating it was found that the electrodeposition should be done at 1.2 V and last 5 minutes. Thermal treatment carried out in a 450°C tube furnace for 90 min in forming gas (95% N2 with 5% H2) along with sulfur vapor was proved best. No further treatment was required to obtain phase pure CBS coatings. This was verified with XRD peak analysis. Optical absorption, microstructural, and photoconductivity data are reported for CBS materials made using the above techniques.

Discriminative potential of some PCR-based and biochemical methods at Scedosporium strains.

PubMed

Kraková, Lucia; Pangallo, Domenico; Piecková, Elena; Majorošová, Mária

2016-02-01

Three innovative PCR-based methods (fluorescent-ITS, fluorescent-CBH and ITS-PCR DGGE) were tested using a reference set of nine strains of Scedosporium from the CBS fungal collection. Cellulolytic, lipolytic and proteolytic potential and the ability to dissolve CaCO3 of the strains were evaluated in vitro by means of agar assays. f-ITS profiles almost recognized main species, although included "Pseudallescheria" ellipsoidea and the Scedosporium boydii CBS 117432 and CBS 120157 in the same cluster. All strains successfully produced DNA polymorphisms by f-CBH amplification which divided them into three different groups. The DGGE approach separated the strains studied into other five clusters which in some case were not matching with species. Strains tested were monomorphic in possessing strong proteolytic and lipolytic activities. The comparison of the three PCR-based genotyping approaches, together with biodegradation ability screening, displayed an intraspecies variability in S. boydii, interfering with unambiguous species delimitation. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Simplified Modeling of Steady-State and Transient Brillouin Gain in Magnetoactive Non-Centrosymmetric Semiconductors

NASA Astrophysics Data System (ADS)

Singh, M.; Aghamkar, P.; Sen, P. K.

With the aid of a hydrodynamic model of semiconductor-plasmas, a detailed analytical investigation is made to study both the steady-state and the transient Brillouin gain in magnetized non-centrosymmetric III-V semiconductors arising from the nonlinear interaction of an intense pump beam with the internally-generated acoustic wave, due to piezoelectric and electrostrictive properties of the crystal. Using the fact that the origin of coherent Brillouin scattering (CBS) lies in the third-order (Brillouin) susceptibility of the medium, we obtained an expression of the gain coefficient of backward Stokes mode in steady-state and transient regimes and studied the dependence of piezoelectricity, magnetic field and pump pulse duration on its growth rate. The threshold-pump intensity and optimum pulse duration for the onset of transient CBS are estimated. The piezoelectricity and externally-applied magnetic field substantially enhances the transient CBS gain coefficient in III-V semiconductors which can be of great use in the compression of scattered pulses.

Involvement of mitochondrial Na+–Ca2+ exchange in intestinal pacemaking activity

PubMed Central

Kim, Byung Joo; Jun, Jae Yeoul; So, Insuk; Kim, Ki Whan

2006-01-01

AIM: Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We have aimed to investigate the involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity in cultured interstitial cells of Cajal. METHODS: Enzymatic digestions were used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane currents (voltage clamp) and potentials (current clamp) from cultured ICCs. RESULTS: Clonazepam and CGP37157 inhibited the pacemaking activity of ICCs in a dose-dependent manner. Clonazepam from 20 to 60 µmol/L and CGP37157 from 10 to 30 µmol/L effectively inhibited Ca2+ efflux from mitochondria in pacemaking activity of ICCs. The IC50s of clonazepam and CGP37157 were 37.1 and 18.2 µmol/L, respectively. The addition of 20 µmol/L NiCl2 to the internal solution caused a “wax and wane” phenomenon of pacemaking activity of ICCs. CONCLUSION: These results suggest that mitochondrial Na+-Ca2+ exchange has an important role in intestinal pacemaking activity. PMID:16521198

Hydrogen sulfide-mediated regulation of contractility in the mouse ileum with electrical stimulation: roles of L-cysteine, cystathionine β-synthase, and K+ channels.

PubMed

Yamane, Satoshi; Kanno, Toshio; Nakamura, Hiroyuki; Fujino, Hiromichi; Murayama, Toshihiko

2014-10-05

Hydrogen sulfide (H2S) is considered to be a signaling molecule. The precise mechanisms underlying H2S-related events, including the producing enzymes and target molecules in gastrointestinal tissues, have not been elucidated in detail. We herein examined the involvement of H2S in contractions induced by repeated electrical stimulations (ES). ES-induced contractions were neurotoxin-sensitive and increased by aminooxyacetic acid, an inhibitor of cystathionine β-synthase (CBS) and cystathionine γ-lyase, but not by D,L-propargylglycine, a selective inhibitor of cystathionine γ-lyase, in an ES trial-dependent manner. ES-induced contractions were markedly decreased in the presence of L-cysteine. This response was inhibited by aminooxyacetic acid and an antioxidant, and accelerated by L-methionine, an activator of CBS. The existence of CBS was confirmed. NaHS transiently inhibited ES- and acetylcholine-induced contractions, and sustainably decreased basal tone for at least 20 min after its addition. The treatment with glibenclamide, an ATP-sensitive K+ channel blocker, reduced both the L-cysteine response and NaHS-induced inhibition of contractions. The NaHS-induced decrease in basal tone was inhibited by apamin, a small conductance Ca2+-activated K+ channel blocker. These results suggest that H2S may be endogenously produced via CBS in ES-activated enteric neurons, and regulates contractility via multiple K+ channels in the ileum. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic basis of Bartter syndrome in Korea.

PubMed

Lee, Beom Hee; Cho, Hee Yeon; Lee, HyunKyung; Han, Kyoung Hee; Kang, Hee Gyung; Ha, Il Soo; Lee, Joo Hoon; Park, Young Seo; Shin, Jae Il; Lee, Dae-Yeol; Kim, Su-Yung; Choi, Yong; Cheong, Hae Il

2012-04-01

Bartter syndrome (BS) is clinically classified into antenatal or neonatal BS (aBS) and classic BS (cBS) as well as five subtypes based on the underlying mutant gene; SLC12A1 (BS I), KCNJ1 (BS II), CLCNKB (BS III), BSND (BS IV) and CASR (BS V). Clinico-genetic features of a nationwide cohort of 26 Korean children with BS were investigated. The clinical diagnosis was aBS in 8 (30.8%), cBS in 15 (57.7%) and mixed Bartter-Gitelman phenotype in 3 cases (11.5%). Five of eight patients with aBS and all 18 patients with either cBS or mixed Bartter-Gitelman phenotype had CLCNKB mutations. Among the 23 patients (46 alleles) with CLCNKB mutations, p.W610X and large deletions were detected in 25 (54.3%) and 10 (21.7%) alleles, respectively. There was no genotype-phenotype correlation in patients with CLCNKB mutations. Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB mutations. The p.W610X mutation and large deletion were two common types of mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous without a genotype-phenotype correlation, typically manifesting cBS phenotype but also aBS or mixed Bartter-Gitelman phenotypes. The molecular diagnostic steps for patients with BS in our population should be designed taking these peculiar genotype distributions into consideration, and a new more clinically relevant classification including BS and Gitelman syndrome is required.

Urothelium muscarinic activation phosphorylates CBS(Ser227) via cGMP/PKG pathway causing human bladder relaxation through H2S production.

PubMed

d'Emmanuele di Villa Bianca, Roberta; Mitidieri, Emma; Fusco, Ferdinando; Russo, Annapina; Pagliara, Valentina; Tramontano, Teresa; Donnarumma, Erminia; Mirone, Vincenzo; Cirino, Giuseppe; Russo, Giulia; Sorrentino, Raffaella

2016-08-11

The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders.

Compact tunable Compton x-ray source from laser-plasma accelerator and plasma mirror

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

Tsai, Hai-En; Wang, Xiaoming; Shaw, Joseph M.

2015-02-15

We present an in-depth experimental-computational study of the parameters necessary to optimize a tunable, quasi-monoenergetic, efficient, low-background Compton backscattering (CBS) x-ray source that is based on the self-aligned combination of a laser-plasma accelerator (LPA) and a plasma mirror (PM). The main findings are (1) an LPA driven in the blowout regime by 30 TW, 30 fs laser pulses produce not only a high-quality, tunable, quasi-monoenergetic electron beam, but also a high-quality, relativistically intense (a{sub 0} ∼ 1) spent drive pulse that remains stable in profile and intensity over the LPA tuning range. (2) A thin plastic film near the gas jetmore » exit retro-reflects the spent drive pulse efficiently into oncoming electrons to produce CBS x-rays without detectable bremsstrahlung background. Meanwhile, anomalous far-field divergence of the retro-reflected light demonstrates relativistic “denting” of the PM. Exploiting these optimized LPA and PM conditions, we demonstrate quasi-monoenergetic (50% FWHM energy spread), tunable (75–200 KeV) CBS x-rays, characteristics previously achieved only on more powerful laser systems by CBS of a split-off, counter-propagating pulse. Moreover, laser-to-x-ray photon conversion efficiency (∼6 × 10{sup −12}) exceeds that of any previous LPA-based quasi-monoenergetic Compton source. Particle-in-cell simulations agree well with the measurements.« less

Hoarding in a compulsive buying sample.

PubMed

Mueller, Astrid; Mueller, Ulrike; Albert, Patricia; Mertens, Christian; Silbermann, Andrea; Mitchell, James E; de Zwaan, Martina

2007-11-01

Previous research has indicated that many compulsive buyers also suffer from compulsive hoarding. The present work specifically examined hoarding in a compulsive buying sample. Sixty-six treatment-seeking compulsive buyers were assessed prior to entering a group therapy for compulsive buying using the Compulsive Buying Scale (CBS), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)-Shopping Version, the Compulsive Acquisition Scale (CAS), the German-CBS, the Saving Inventory-Revised (SI-R), the Maudsley Obsessive Compulsive Inventory (MOCI), the Barratt Impulsiveness Scale (BIS-11), and the Structured Clinical Interview for DSM-IV Axis I (SCID). Inclusion criteria were current problems with compulsive buying according to the proposed diagnostic criteria for compulsive buying by McElroy, Keck, Pope, Smith, and Strakowski [(1994). Compulsive buying: A report of 20 cases. Journal of Clinical Psychiatry, 55, 242-248]. Our results support the assumption that many but not all compulsive buyers suffer from compulsive hoarding. A significant association between the SI-R and the compulsive buying measures CBS, Y-BOCS-SV, German-CBS, and the CAS-Buy subscale was found, which is mostly caused by the SI-R subscale acquisition. The SI-R subscales clutter and difficulty discarding were more closely associated with the CAS-Free subscale and with obsessive-compulsive symptoms. Hoarding compulsive buyers reported more severe buying symptoms and obsessive-compulsive symptoms and presented with a higher psychiatric co-morbidity, especially any current affective, anxiety and eating disorder. Specific therapeutic interventions for compulsive buyers who also report compulsive hoarding appear indicated.

Insight into microtubule destabilization mechanism of 3,4,5-trimethoxyphenyl indanone derivatives using molecular dynamics simulation and conformational modes analysis

NASA Astrophysics Data System (ADS)

Tripathi, Shubhandra; Srivastava, Gaurava; Singh, Aastha; Prakasham, A. P.; Negi, Arvind S.; Sharma, Ashok

2018-03-01

Colchicine site inhibitors are microtubule destabilizers having promising role in cancer therapeutics. In the current study, four such indanone derivatives (t1, t9, t14 and t17) with 3,4,5-trimethoxyphenyl fragment (ring A) and showing significant microtubule destabilization property have been explored. The interaction mechanism and conformational modes triggered by binding of these indanone derivatives and combretastatin at colchicine binding site (CBS) of αβ-tubulin dimer were studied using molecular dynamics (MD) simulation, principle component analysis and free energy landscape analysis. In the MD results, t1 showed binding similar to colchicine interacting in the deep hydrophobic core at the CBS. While t9, t14 and t17 showed binding conformation similar to combretastatin, with ring A superficially binding at the CBS. Results demonstrated that ring A played a vital role in binding via hydrophobic interactions and got anchored between the S8 and S9 sheets, H8 helix and T7 loop at the CBS. Conformational modes study revealed that twisting and bending conformational motions (as found in the apo system) were nearly absent in the ligand bound systems. Absence of twisting motion might causes loss of lateral contacts in microtubule, thus promoting microtubule destabilization. This study provides detailed account of microtubule destabilization mechanism by indanone ligands and combretastatin, and would be helpful for designing microtubule destabilizers with higher activity.

A Comparison of Quantum and Molecular Mechanical Methods to Estimate Strain Energy in Druglike Fragments.

PubMed

Sellers, Benjamin D; James, Natalie C; Gobbi, Alberto

2017-06-26

Reducing internal strain energy in small molecules is critical for designing potent drugs. Quantum mechanical (QM) and molecular mechanical (MM) methods are often used to estimate these energies. In an effort to determine which methods offer an optimal balance in accuracy and performance, we have carried out torsion scan analyses on 62 fragments. We compared nine QM and four MM methods to reference energies calculated at a higher level of theory: CCSD(T)/CBS single point energies (coupled cluster with single, double, and perturbative triple excitations at the complete basis set limit) calculated on optimized geometries using MP2/6-311+G**. The results show that both the more recent MP2.X perturbation method as well as MP2/CBS perform quite well. In addition, combining a Hartree-Fock geometry optimization with a MP2/CBS single point energy calculation offers a fast and accurate compromise when dispersion is not a key energy component. Among MM methods, the OPLS3 force field accurately reproduces CCSD(T)/CBS torsion energies on more test cases than the MMFF94s or Amber12:EHT force fields, which struggle with aryl-amide and aryl-aryl torsions. Using experimental conformations from the Cambridge Structural Database, we highlight three example structures for which OPLS3 significantly overestimates the strain. The energies and conformations presented should enable scientists to estimate the expected error for the methods described and we hope will spur further research into QM and MM methods.

Fungicide resistance and genetic variability in plant pathogenic strains of Guignardia citricarpa

PubMed Central

Possiede, Y.M.; Gabardo, J.; Kava-Cordeiro, V.; Galli-Terasawa, L.V.; Azevedo, J.L.; Glienke, C.

2009-01-01

Citrus black spot (CBS) is a plant disease of worldwide occurrence, affecting crops in Africa, Oceania, and South America. In Brazil, climate provides favorable conditions and CBS has spread to the Southeast and South regions. CBS is caused by the fungus Guignardia citricarpa (anamorph: Phyllosticta citricarpa) and its control is based on the use of fungicides, such as benzimidazoles. In South Africa, the disease was kept under control for 10 years with benomyl, until cases of resistance to high concentrations of this fungicide were reported from all citrus-producing areas. Azoxystrobin (a strobilurin) has been found effective in controlling phytopathogens, including CBS, in a wide range of economically important crops. The present study investigated in vitro the effects of the fungicides benomyl and azoxystrobin on 10 strains of G. citricarpa isolated from lesions in citrus plants from Brazil and South Africa. Benomyl at 0.5 μg/mL inhibited mycelial growth in all strains except PC3C, of African origin, which exhibited resistance to concentrations of up to 100.0 μg/mL. The spontaneous mutation frequency for resistance to benomyl was 1.25 × 10-7. Azoxystrobin, even at high concentrations, did not inhibit mycelial growth in any of the strains, but significantly reduced sporulation rates, by as much as 100%, at a concentration of 5.0 μg/mL. Variations in sensitivity across strains, particularly to the strobilurin azoxystrobin, are possibly related to genetic variability in G. citricarpa isolates. PMID:24031363

Direction of R&D and Current Status of Understanding of Advanced Gear Steels

DTIC Science & Technology

1986-02-01

our laboratory. A-Z 9-4 CBS600 was developed by Timken as a carburizing grade bearing steel for service above 150C. The philosophy used in designing...melted (VIM-VAR) steels . The effect of long time aging at 230C on the Charpy energy for CBS600 is currently underway at AMMRC. M50 NIL General Electric, in...contact fatigue life and hot hardness as high as for P50 (the high hot hardness bearing steel widely used in aircraft gas turbine engines in the USA) the

Isolation and identification of a thermophilic strain producing trehalose synthase from geothermal water in China.

PubMed

Zhu, Yueming; Zhang, Jun; Wei, Dongsheng; Wang, Yufan; Chen, Xiaoyun; Xing, Laijun; Li, Mingchun

2008-08-01

A slightly thermophilic strain, CBS-01, producing trehalose synthase (TreS), was isolated from geothermal water in this study. According to the phenotypic characteristics and phylogenetic analysis of the 16s rRNA gene sequence, it was identified as Meiothermus ruber. The trehalose synthase gene of Meiothermus ruber CBS-01 was cloned by polymerase chain reaction and sequenced. The TreS gene consisted of 2,895 nucleotides, which specified a 964-amino-acid protein. This novel TreS catalyzed reversible interconversion of maltose and trehalose.

Some predictions of Rafael Lorente de Nó 80 years later.

PubMed

Larriva-Sahd, Jorge A

2014-01-01

Rafael Lorente de Nó, the youngest of Santiago Ramón y Cajal disciples, was one of the last Century's more influential researches in neuroscience. This assay highlights two fundamental contributions of Rafael Lorente de Nó to neurobiology: the intrinsic organization of the mammalian cerebral cortex and the basic physiology of the neuron processes.

CT features, mimics and atypical presentations of gastrointestinal stromal tumor (GIST).

PubMed

Sripathi, Smiti; Rajagopal, Kv; Srivastava, Rajendra Kumar; Ayachit, Anurag

2011-07-01

The term stromal tumor was coined in 1983 by Clark and Mazur for smooth muscle neoplasm of the gastrointestinal tract (GIT). Gastrointestinal stromal tumors (GIST) are nonepithelial tumors arising from the interstitial cells of Cajal, which express KIT protein-CD117 on immunohistochemistry. GIST can arise anywhere in the GIT, including the mesentery, omentum, and retroperitoneum.

In Rwandese Women with Low Iron Status, Iron Absorption from Low-Phytic Acid Beans and Biofortified Beans Is Comparable, but Low-Phytic Acid Beans Cause Adverse Gastrointestinal Symptoms.

PubMed

Petry, Nicolai; Rohner, Fabian; Gahutu, Jean Bosco; Campion, Bruno; Boy, Erick; Tugirimana, Pierrot L; Zimmerman, Michael Bruce; Zwahlen, Christian; Wirth, James P; Moretti, Diego

2016-05-01

Phytic acid (PA) is a major inhibitor of iron bioavailability from beans, and high PA concentrations might limit the positive effect of biofortified beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase iron bioavailability. We set out to test whether lpa beans provide more bioavailable iron than a BB variety when served as part of a composite meal in a bean-consuming population with low iron status. Dietary iron absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and PA concentrations) was compared in 25 nonpregnant young women with low iron status with the use of a multiple-meal crossover design. Iron absorption was measured with stable iron isotopes. PA concentration in lpa beans was ∼10% of BBs and CBs, and iron concentration in BBs was ∼2- and 1.5-fold compared with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0% (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron absorbed from lpa beans and BBs was 421 μg (95% CI: 234, 756 μg) and 431 μg (95% CI: 237, 786 μg), respectively, and did not significantly differ, but was >50% higher (P < 0.005) than from CBs (278 μg; 95% CI: 150, 499 μg). In our trial, the lpa beans were hard to cook, and their consumption caused transient adverse digestive side effects in ∼95% of participants. Gel electrophoresis analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans. BBs and lpa beans provided more bioavailable iron than control beans and could reduce dietary iron deficiency. Digestive side effects of lpa beans were likely caused by PHA-L, but it is unclear to what extent the associated digestive problems reduced iron bioavailability. This trial was registered at clinicaltrials.gov as NCT02215278. © 2016 American Society for Nutrition.

Phylogenetic Analysis of Phenotypically Characterized Cryptococcus laurentii Isolates Reveals High Frequency of Cryptic Species

PubMed Central

Ferreira-Paim, Kennio; Ferreira, Thatiana Bragine; Andrade-Silva, Leonardo; Mora, Delio Jose; Springer, Deborah J.; Heitman, Joseph; Fonseca, Fernanda Machado; Matos, Dulcilena; Melhem, Márcia Souza Carvalho; Silva-Vergara, Mario León

2014-01-01

Background Although Cryptococcus laurentii has been considered saprophytic and its taxonomy is still being described, several cases of human infections have already reported. This study aimed to evaluate molecular aspects of C. laurentii isolates from Brazil, Botswana, Canada, and the United States. Methods In this study, 100 phenotypically identified C. laurentii isolates were evaluated by sequencing the 18S nuclear ribosomal small subunit rRNA gene (18S-SSU), D1/D2 region of 28S nuclear ribosomal large subunit rRNA gene (28S-LSU), and the internal transcribed spacer (ITS) of the ribosomal region. Results BLAST searches using 550-bp, 650-bp, and 550-bp sequenced amplicons obtained from the 18S-SSU, 28S-LSU, and the ITS region led to the identification of 75 C. laurentii strains that shared 99–100% identity with C. laurentii CBS 139. A total of nine isolates shared 99% identity with both Bullera sp. VY-68 and C. laurentii RY1. One isolate shared 99% identity with Cryptococcus rajasthanensis CBS 10406, and eight isolates shared 100% identity with Cryptococcus sp. APSS 862 according to the 28S-LSU and ITS regions and designated as Cryptococcus aspenensis sp. nov. (CBS 13867). While 16 isolates shared 99% identity with Cryptococcus flavescens CBS 942 according to the 18S-SSU sequence, only six were confirmed using the 28S-LSU and ITS region sequences. The remaining 10 shared 99% identity with Cryptococcus terrestris CBS 10810, which was recently described in Brazil. Through concatenated sequence analyses, seven sequence types in C. laurentii, three in C. flavescens, one in C. terrestris, and one in the C. aspenensis sp. nov. were identified. Conclusions Sequencing permitted the characterization of 75% of the environmental C. laurentii isolates from different geographical areas and the identification of seven haplotypes of this species. Among sequenced regions, the increased variability of the ITS region in comparison to the 18S-SSU and 28S-LSU regions reinforces its applicability as a DNA barcode. PMID:25251413

Bioaccumulation of hydroxylated polychlorinated biphenyls and pentachlorophenol in the serum of northern elephant seal pups (Mirounga angustirostris)

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

Louis, Caroline, E-mail: caroline.louis@uclouvain.be; Covaci, Adrian; Stas, Marie

Northern elephant seals (NES) (Mirounga angustirostris) from the Año Nuevo State Reserve (CA, USA) were sampled at 1-, 4-, 7- and 10-week post-weaning. Concentrations of hydroxylated polychlorinated biphenyls (HO-PCBs) and their parent PCBs were measured in the serum of each individual. The ΣHO-PCB concentrations in the serum increased significantly between early and late fast (from 282±20 to 529±31 pg/mL). This increase might result from a mobilisation of HO-PCBs transferred from the mother during gestation and/or lactation and stored in the pup's liver. Food deprivation has been shown to exacerbate biotransformation capacities in mammals, birds and fish. The HO-penta-CBs was themore » predominant homologue group, followed by HO-hexa-CBs and HO-hepta-CBs. No preferential pathway for the metabolism of HO-PCBs (HO-direct insertion or NIH-shift of a chlorine atom) could be evidenced. The concentrations of pentachlorophenol (PCP) in the serum of weaned NES increased from 103±7 pg/mL at early fast to 246±41 pg/mL at late fast, which is within the range of PCP concentrations usually encountered in marine mammals. - Highlights: • Σ HO-PCB concentrations in serum significantly increased between early and late fast. • The HO-penta-CBs were the predominant homologue group measured in serum. • No preferential pathway for the metabolism of HO-PCBs could be evidenced. • PCP concentrations in serum significantly increased between early and late fast.« less

Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress.

PubMed

Liu, Song; Xin, Danqing; Wang, Lingxiao; Zhang, Tiantian; Bai, Xuemei; Li, Tong; Xie, Yunkai; Xue, Hao; Bo, Shishi; Liu, Dexiang; Wang, Zhen

2017-10-01

Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H 2 S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H 2 S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H 2 S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER) stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H 2 S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Comparative genomics of citric-acid producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

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

Andersen, Mikael R.; Salazar, Margarita; Schaap, Peter

2011-06-01

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compels additional exploration. We therefore undertook whole genome sequencing of the acidogenic A. niger wild type strain (ATCC 1015), and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence and half the telomeric regionsmore » have been elucidated. Moreover, sequence information from ATCC 1015 was utilized to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 megabase of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis revealed up-regulation of the electron transport chain, specifically the alternative oxidative pathway in ATCC 1015, while CBS 513.88 showed significant up regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases and protein transporters.« less

A Multi-Region Magnetoimpedance-Based Bio-Analytical System for Ultrasensitive Simultaneous Determination of Cardiac Biomarkers Myoglobin and C-Reactive Protein.

PubMed

Yang, Zhen; Wang, Huanhuan; Guo, Pengfei; Ding, Yuanyuan; Lei, Chong; Luo, Yongsong

2018-06-01

Cardiac biomarkers (CBs) are substances that appear in the blood when the heart is damaged or stressed. Measurements of the level of CBs can be used in course of diagnostics or monitoring the state of the health of group risk persons. A multi-region bio-analytical system (MRBAS) based on magnetoimpedance (MI) changes was proposed for ultrasensitive simultaneous detection of CBs myoglobin (Mb) and C-reactive protein (CRP). The microfluidic device was designed and developed using standard microfabrication techniques for their usage in different regions, which were pre-modified with specific antibody for specified detection. Mb and CRP antigens labels attached to commercial Dynabeads with selected concentrations were trapped in different detection regions. The MI response of the triple sensitive element was carefully evaluated in initial state and in the presence of biomarkers. The results showed that the MI-based bio-sensing system had high selectivity and sensitivity for detection of CBs. Compared with the control region, ultrasensitive detections of CRP and Mb were accomplished with the detection limits of 1.0 pg/mL and 0.1 pg/mL, respectively. The linear detection range contained low concentration detection area and high concentration detection area, which were 1 pg/mL⁻10 ng/mL, 10⁻100 ng/mL for CRP, and 0.1 pg/mL⁻1 ng/mL, 1 n/mL⁻80 ng/mL for Mb. The measurement technique presented here provides a new methodology for multi-target biomolecules rapid testing.

Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site.

PubMed

Adams, Julian; Chen, Zhi-Ping; Van Denderen, Bryce J W; Morton, Craig J; Parker, Michael W; Witters, Lee A; Stapleton, David; Kemp, Bruce E

2004-01-01

AMP-activated protein kinase (AMPK) is a alphabetagamma heterotrimer that is activated in response to both hormones and intracellular metabolic stress signals. AMPK is regulated by phosphorylation on the alpha subunit and by AMP allosteric control previously thought to be mediated by both alpha and gamma subunits. Here we present evidence that adjacent gamma subunit pairs of CBS repeat sequences (after Cystathionine Beta Synthase) form an AMP binding site related to, but distinct from the classical AMP binding site in phosphorylase, that can also bind ATP. The AMP binding site of the gamma(1) CBS1/CBS2 pair, modeled on the structures of the CBS sequences present in the inosine monophosphate dehydrogenase crystal structure, contains three arginine residues 70, 152, and 171 and His151. The yeast gamma homolog, snf4 contains a His151Gly substitution, and when this is introduced into gamma(1), AMP allosteric control is substantially lost and explains why the yeast snf1p/snf4p complex is insensitive to AMP. Arg70 in gamma(1) corresponds to the site of mutation in human gamma(2) and pig gamma(3) genes previously identified to cause an unusual cardiac phenotype and glycogen storage disease, respectively. Mutation of any of AMP binding site Arg residues to Gln substantially abolishes AMP allosteric control in expressed AMPK holoenzyme. The Arg/Gln mutations also suppress the previously described inhibitory properties of ATP and render the enzyme constitutively active. We propose that ATP acts as an intrasteric inhibitor by bridging the alpha and gamma subunits and that AMP functions to derepress AMPK activity.

Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

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

Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp

2015-01-02

Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and themore » oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.« less

Adult classical homocystinuria requiring parenteral nutrition: Pitfalls and management.

PubMed

Tran, Christel; Bonafé, Luisa; Nuoffer, Jean-Marc; Rieger, Julie; Berger, Mette M

2017-07-25

Homocystinuria due to cystathionine beta synthase (CBS) deficiency presents with a wide clinical spectrum. Treatment by the enteral route aims at reducing homocysteine levels by using vitamin B6, possibly methionine-restricted diet, betaine and/or folate and vitamin B 12 supplementation. Currently no nutritional guidelines exist regarding parenteral nutrition (PN) under acute conditions. Exhaustive literature search was performed, in order to identify the relevant studies describing the pathogenesis and nutritional intervention of adult classical homocystinuria requiring PN. Description of an illustrative case of an adult female with CBS deficiency and intestinal perforation, who required total PN due to contraindication to enteral nutrition. Nutritional management of decompensated classical homocystinuria is complex and currently no recommendation exists regarding PN composition. Amino acid profile and monitoring of total homocysteine concentration are the main tools enabling a precise assessment of the severity of metabolic alterations. In case of contraindication to enteral nutrition, compounded PN will be required, as described in this paper, to ensure adequate low amounts of methionine and others essential amino acids and avoid potentially fatal toxic hypermethioninemia. By reviewing the literature and reporting successful nutritional management of a decompensated CBS deficiency using tailored PN with limited methionine intake and n-3 PUFA addition, we would like to underscore the fact that standard PN solutions are not adapted for CBS deficient critical ill patients: new solutions are required. High methionine levels (>800 μmol/L) being potentially neurotoxic, there is an urgent need to improve our knowledge of acute nutritional therapy. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The effect of choline and cystine on the utilisation of methionine for protein accretion, remethylation and trans-sulfuration in juvenile shrimp Penaeus monodon.

PubMed

Richard, Lenaïg; Vachot, Christiane; Surget, Anne; Rigolet, Vincent; Kaushik, Sadasivam J; Geurden, Inge

2011-09-01

This 35-d feeding experiment examined in juvenile shrimp Penaeus monodon (3·3 g initial body weight) the effects of methionine (Met), choline and cystine on protein accretion and the activity of two key enzymes of remethylation (betaine-homocysteine methyltransferase; BHMT) and trans-sulfuration (cystathionine β-synthase; CBS). The interaction between Met and choline was tested using semi-purified diets either adequate or limiting (30 or 50 %) in total sulphur amino acid (SAA) content with a constant cystine:Met ratio. The diets contained either basal or excess choline (3 v. 7 g/kg feed). Cystine was added to two other 30 and 50 % Met-limiting diets to adjust the SAA supply to that of the control diet in order to evaluate the interaction between Met and cystine. As expected, N accretion was significantly lower with the SAA-limiting diets but increased back to control levels by the extra choline or cystine, demonstrating their sparing effect on Met utilisation for protein accretion. We show, for the first time, the activities of BHMT and CBS in shrimp hepatopancreas. Only BHMT responded to the SAA deficiencies, whereas the extra choline and cystine did not stimulate remethylation or down-regulate trans-sulfuration. Our data also suggest the capacity of P. monodon to synthesise taurine, being significantly affected by the cystine level in the 30 % SAA-limiting diets. Further research is warranted to better understand the metabolic regulation of taurine synthesis in shrimp and of the observed Met-sparing effects.

Oleamide restores sleep in adult rats that were subjected to maternal separation.

PubMed

Reyes Prieto, Nidia M; Romano López, Antonio; Pérez Morales, Marcel; Pech, Olivia; Méndez-Díaz, Mónica; Ruiz Contreras, Alejandra E; Prospéro-García, Oscar

2012-12-01

Maternal separation (MS) induces a series of changes in rats' behavior; among them a reduction in spontaneous sleep. One potentially impaired system is the endocannabinoid system (eCBs), since it contributes to generate sleep. To investigate if there are situations early in life that affect the eCBs, which would contribute to make rats vulnerable to suffering insomnia, we studied the rodent model of MS. Rats were separated from their mothers for 3h-periods daily, from postnatal day (PND) 2 to PND 16. Once they gained 250g of body weight (adult rats), they were implanted with electrodes to record the sleep-waking cycle (SWC). MS rats and non-MS (NMS) siblings were assigned to one of the following groups: vehicle, oleamide (OLE, an agonist of the cannabinoid receptor 1, CB1R), OLE+AM251 (an antagonist of the CB1R) and AM251 alone. Expression of the CBR1 receptor was also analyzed in the frontal cortex (FCx) and in the hippocampus (HIP) of both NMS and MS rats. Results indicated that MS induced a reduction in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep with the consequent increase in waking (W) as compared to NMS siblings. OLE normalized the SWC, and AM251 blocked such an effect. CB1R expression was reduced in the FCx and in the HIP of MS rats. Our results indicate that MS reduces sleep and CB1R expression and OLE improves sleep in adult rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Candida chanthaburiensis sp. nov., Candida kungkrabaensis sp. nov. and Candida suratensis sp. nov., three novel yeast species from decaying plant materials submerged in water of mangrove forests.

PubMed

Limtong, Savitree; Yongmanitchai, Wichien

2010-10-01

In a taxonomic study of yeasts isolated from decaying plant materials submerged in water of mangrove forests in Thailand, three strains isolated from tree bark (EM33(T)), a fallen leaf (EM40(T)) and a detached branch (SM56(T)) were found to represent three novel yeast species. On the basis of morphological, biochemical, physiological and chemotaxonomic characteristics, the sequence analysis of the D1/D2 domain of the large subunit (LSU) rRNA gene, and the phylogenetic analysis, the three strains were assigned as three novel Candida species. They were named as Candida chanthaburiensis sp. nov. (type strain EM33(T) = BCC 23057(T) = NBRC 102176(T) = CBS 10926(T)), Candida kungkrabaensis sp. nov. (type strain EM40(T) = BCC 23060(T) = NBRC 102179(T) = CBS 10927(T)), and Candida suratensis sp. nov. (type strain SM56(T) = BCC 25961(T) = NBRC 103858(T) = CBS 10928(T)).

Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia.

PubMed

Holubiec, Mariana I; Romero, Juan I; Blanco, Eduardo; Tornatore, Tamara Logica; Suarez, Juan; Rodríguez de Fonseca, Fernando; Galeano, Pablo; Capani, Francisco

2017-07-13

Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα). We found a decrease in NAPE-PLD and PPARα expression. Since NAPE-PLD and PPARα take part in the production and reception of biochemical actions of AEs, such as oleoylethanolamide, these results may suggest that PA plays a key role in the regulation of this system. These data agree with previous results obtained in the hippocampus and encourage us to develop further studies using AEs as potential neuroprotective compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased hydrophobicity in Malassezia species correlates with increased proinflammatory cytokine expression in human keratinocytes.

PubMed

Akaza, Narifumi; Akamatsu, Hirohiko; Takeoka, Shiori; Mizutani, Hiroshi; Nakata, Satoru; Matsunaga, Kayoko

2012-11-01

Malassezia cells stimulate cytokine production by keratinocytes, although this ability differs among Malassezia species for unknown reasons. The aim of this study was to clarify the factors determining the ability to induce cytokine production by human keratinocytes in response to Malassezia species. M. furfur NBRC 0656, M. sympodialis CBS 7222, M. dermatis JCM 11348, M. globosa CBS 7966, M. restricta CBS 7877, and three strains each of M. globosa, M. restricta, M. dermatis, M. sympodialis, and M. furfur maintained under various culture conditions were used. Normal human epidermal keratinocytes (NHEKs) (1 × 10(5) cells) and the Malassezia species (1 × 10(6) cells) were co-cultured, and IL-1α, IL-6, and IL-8 mRNA levels were determined. Moreover, the hydrophobicity and β-1,3-glucan expression at the surface of Malassezia cells were analyzed. The ability of Malassezia cells to trigger the mRNA expression of proinflammatory cytokines in NHEKs differed with the species and conditions and was dependent upon the hydrophobicity of Malassezia cells not β-1,3-glucan expression.

Women and cosmetic breast surgery: weighing the medical, social, and lifestyle risks.

PubMed

Boulton, Tiffany N; Malacrida, Claudia

2012-04-01

In this article we provide a comparative analysis of qualitative, semistructured interviews with 24 women who had undergone different forms of cosmetic breast surgery (CBS). We argue that women must negotiate three types of risk: potential medical risks, lifestyle risks connected with choosing "frivolous" self-enhancements, and countervailing social risks affiliated with pressures to maximize one's feminine beauty. In addition, we highlight the challenges faced in negotiating these risks by examining the limits to traditional forms of medical informed consent provided to the women, who received little information on the medical risks associated with CBS, or who were given uncertain and contradictory risk information. Even respondents who felt that they were well informed expressed difficulties in making "wise" choices because the risks were distant or unlikely, and hence easily minimized. Given this, it is fairly understandable that the known social risks of "failed" beauty faced by the women often outweighed the ambiguous or understated risks outlined by medicine. We argue that traditional notions of informed consent and risk awareness might not be adequate for women choosing CBS.

Investigation of saponification for determination of polychlorinated biphenyls in marine sediments.

PubMed

Numata, Masahiko; Yarita, Takashi; Aoyagi, Yoshie; Yamazaki, Misako; Takatsu, Akiko

2005-02-01

The effects of saponification conditions (temperature and water content of saponifying solution) on the determination of chlorinated biphenyls (CBs) in marine sediments were investigated. Although highly chlorinated biphenyls (nona- to deca-CBs) decomposed during high-temperature saponification, the degree of degradation was reduced by adding water to the ethanolic potassium hydroxide saponifying solution. Room-temperature saponification yielded quantitative recovery of highly chlorinated biphenyl surrogates but low extraction efficiencies of lightly chlorinated biphenyls (mono- to di-CBs). The same samples were analyzed by other extraction techniques, for example, pressurized liquid extraction, and analytical results were compared. The mono- and di-CB concentrations were correlated with the extraction temperatures of various extraction techniques. In particular, the concentrations of some CB congeners (CB11, CB14) were higher with saponification. The low degree of degradation of highly chlorinated biphenyls and the high recovery of lightly chlorinated biphenyls were compatible when room-temperature and high-temperature saponification were combined. Except for the anomalies of CB11 and CB14, the combined method gave satisfactory results for analysis of PCBs.

Galactose utilization sheds new light on sugar metabolism in the sequenced strain Dekkera bruxellensis CBS 2499.

PubMed

Moktaduzzaman, Md; Galafassi, Silvia; Capusoni, Claudia; Vigentini, Ileana; Ling, Zhihao; Piškur, Jure; Compagno, Concetta

2015-03-01

Dekkera bruxellensis and Saccharomyces cerevisiae are considered two phylogenetically distant relatives, but they share several industrial relevant traits such as the ability to produce ethanol under aerobic conditions (Crabtree effect), high tolerance towards ethanol and acids, and ability to grow without oxygen. Beside a huge adaptability, D. bruxellensis exhibits a broader spectrum in utilization of carbon and nitrogen sources in comparison to S. cerevisiae. With the aim to better characterize its carbon source metabolism and regulation, the usage of galactose and the role that glucose plays on sugar metabolism were investigated in D. bruxellensis CBS 2499. The results indicate that in this yeast galactose is a non-fermentable carbon source, in contrast to S. cerevisiae that can ferment it. In particular, its metabolism is affected by the nitrogen source. Interestingly, D. bruxellensis CBS 2499 exhibits the 'short-term Crabtree effect', and the expression of genes involved in galactose utilization and in respiratory metabolism is repressed by glucose, similarly to what occurs in S. cerevisiae. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Application of Fracture Mechanics to Specify the Proof Load Factor for Clamp Band Systems of Launch Vehicles

NASA Astrophysics Data System (ADS)

Singaravelu, J.; Sundaresan, S.; Nageswara Rao, B.

2013-04-01

This article presents a methodology for evaluation of the proof load factor (PLF) for clamp band system (CBS) made of M250 Maraging steel following fracture mechanics principles.CBS is most widely used as a structural element and as a separation system. Using Taguchi's design of experiments and the response surface method (RSM) the compact tension specimens were tested to establish an empirical relation for the failure load ( P max) in terms of the ultimate strength, width, thickness, and initial crack length. The test results of P max closely matched with the developed RSM empirical relation. Crack growth rates of the maraging steel in different environments were examined. Fracture strength (σf) of center surface cracks and through-crack tension specimens are evaluated utilizing the fracture toughness ( K IC). Stress induced in merman band at flight loading conditions is evaluated to estimate the higher load factor and PLF. Statistical safety factor and reliability assessments were made for the specified flaw sizes useful in the development of fracture control plan for CBS of launch vehicles.

Breaking the bottleneck: Use of molecular tailoring approach for the estimation of binding energies at MP2/CBS limit for large water clusters

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

Singh, Gurmeet; Nandi, Apurba; Gadre, Shridhar R., E-mail: gadre@iitk.ac.in

2016-03-14

A pragmatic method based on the molecular tailoring approach (MTA) for estimating the complete basis set (CBS) limit at Møller-Plesset second order perturbation (MP2) theory accurately for large molecular clusters with limited computational resources is developed. It is applied to water clusters, (H{sub 2}O){sub n} (n = 7, 8, 10, 16, 17, and 25) optimized employing aug-cc-pVDZ (aVDZ) basis-set. Binding energies (BEs) of these clusters are estimated at the MP2/aug-cc-pVNZ (aVNZ) [N = T, Q, and 5 (whenever possible)] levels of theory employing grafted MTA (GMTA) methodology and are found to lie within 0.2 kcal/mol of the corresponding full calculationmore » MP2 BE, wherever available. The results are extrapolated to CBS limit using a three point formula. The GMTA-MP2 calculations are feasible on off-the-shelf hardware and show around 50%–65% saving of computational time. The methodology has a potential for application to molecular clusters containing ∼100 atoms.« less

Preparation and characterization of poly(methyl methacrylate) and poly(maleic anhydride-co-diallyl phthalate) grafted carbon black through γ-ray irradiation

NASA Astrophysics Data System (ADS)

Bo, Yang; Cui, Jiayang; Cai, Yangben; Xu, Shiai

2016-02-01

In this study, the grafting polymerization of methyl methacrylate (MMA) monomer and maleic anhydride/diallyl phthalate (MAH/DAP) co-monomer onto the surface of carbon black (CB) were carried out at room temperature and normal pressure by γ-ray irradiation. The surface chemistry of grafted CBs were characterized by infrared spectroscopy (IR), thermo-gravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). The results show that there are some remanent polymers on the surface of modified CBs after extract for 48 h, indicating that poly(methyl methacrylate) (PMMA) and poly(MAH-co-DAP) have been successfully grafted onto the surface of CB without using initiator due to the high energy of γ-ray irradiation. Dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) reveal that the grafted CBs have smaller average aggregate size and better dispersibility than that of CB in absolute ethanol. In addition, it was found that the amount of oxygen groups and the irradiation doses/dose rates have little effect on the grafting degree of CB.

The therapeutic potential of targeting the peripheral endocannabinoid/CB1 receptor system.

PubMed

Tam, Joseph; Hinden, Liad; Drori, Adi; Udi, Shiran; Azar, Shahar; Baraghithy, Saja

2018-03-01

Endocannabinoids (eCBs) are internal lipid mediators recognized by the cannabinoid-1 and -2 receptors (CB 1 R and CB 2 R, respectively), which also mediate the different physiological effects of marijuana. The endocannabinoid system, consisting of eCBs, their receptors, and the enzymes involved in their biosynthesis and degradation, is present in a vast number of peripheral organs. In this review we describe the role of the eCB/CB 1 R system in modulating the metabolism in several peripheral organs. We assess how eCBs, via activating the CB 1 R, contribute to obesity and regulate food intake. In addition, we describe their roles in modulating liver and kidney functions, as well as bone remodeling and mass. Special importance is given to emphasizing the efficacy of the recently developed peripherally restricted CB 1 R antagonists, which were pre-clinically tested in the management of energy homeostasis, and in ameliorating both obesity- and diabetes-induced metabolic complications. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Structural basis for substrate placement by an archaeal box C/D ribonucleoprotein particle.

PubMed

Xue, Song; Wang, Ruiying; Yang, Fangping; Terns, Rebecca M; Terns, Michael P; Zhang, Xinxin; Maxwell, E Stuart; Li, Hong

2010-09-24

Box C/D small nucleolar and Cajal body ribonucleoprotein particles (sno/scaRNPs) direct site-specific 2'-O-methylation of ribosomal and spliceosomal RNAs and are critical for gene expression. Here we report crystal structures of an archaeal box C/D RNP containing three core proteins (fibrillarin, Nop56/58, and L7Ae) and a half-mer box C/D guide RNA paired with a substrate RNA. The structure reveals a guide-substrate RNA duplex orientation imposed by a composite protein surface and the conserved GAEK motif of Nop56/58. Molecular modeling supports a dual C/D RNP structure that closely mimics that recently visualized by electron microscopy. The substrate-bound dual RNP model predicts an asymmetric protein distribution between the RNP that binds and methylates the substrate RNA. The predicted asymmetric nature of the holoenzyme is consistent with previous biochemical data on RNP assembly and provides a simple solution for accommodating base-pairing between the C/D guide RNA and large ribosomal and spliceosomal substrate RNAs. Copyright © 2010 Elsevier Inc. All rights reserved.

The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts.

PubMed

Silla, Toomas; Karadoulama, Evdoxia; Mąkosa, Dawid; Lubas, Michal; Jensen, Torben Heick

2018-05-15

Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA + ) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA + RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence, selected pA + RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export factor AlyREF. Our results establish ZFC3H1 as a central nuclear pA + RNA retention factor, counteracting nuclear export activity. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Blushing and the philosophy of mind.

PubMed

Bunge, Mario

2007-01-01

The introduction, an imaginary dialogue between a philosopher and a scientist, is followed by a brief discussion of the interactions between science, philosophy, and religion. Next comes an analysis of the three most popular philosophies of mind: classical mind-body dualism, computerism, and psychoneural monism. It is argued that the latter, held by medical psychologists since Hippocrates, and formulated explicitly by Cajal and Hebb, is the philosophy of mind that underlies contemporary cognitive and affective neuroscience. The standard objections to psychoneural monism (or materialism) are examined. Evolutionary psychology, though promissory, is judged to be more fancy than fact at its present stage. The conclusion is that the philosophy of mind is still in a poor shape, but that it can advance if it learns more from the science of mind. It would also help if scientific psychologists were to replace such tacitly dualistic expressions as "organ N instantiates (or subserves) mental function M" with "organ N performs mental function M", just as we say "the legs walk" instead of "walking is subserved by legs," and "the lungs breathe" instead of "the lungs instantiate breathing."

The IASI cold box subsystem (CBS) a passive cryocooler for cryogenic detectors and optics

NASA Astrophysics Data System (ADS)

Bailly, B.; Courteau, P.; Maciaszek, T.

2017-11-01

In space, cooling down Infra Red detectors and optics to cryogenic temperature raises always the same issue : what is the best way to manage simultaneously thermal cooling, stability, mechanical discoupling and accurate focal plane components location, in a lightweight and compact solution? The passive cryocooler developed by Alcatel SPace Industries under CNES contract in the frame of the IASI instrument (Infrared Atmospheric Sounding Interferometer), offers an efficient solution for 90K to 100K temperature levels. We intend you to present the architecture and performance validation plan of the CBS.

Military Personnel Dilemmas: Perspectives on Gender-Related Issues. A selected List of Resource Materials Prepared for the Human Resources Division, HQ FORSCOM

DTIC Science & Technology

1983-08-01

interfered with his performance of his duties. " "- "Army Discharges’ Woman After Marriage to Alleged Transsexual ." CBS NEWS (MORNING NEWS). July 23...1977. p. 11. A WAC is discharged because of her marriage to a former WAC who now claims to be a transsexual man. The Army says that there may have been...a . .- psycholoqical transition but not a physical one. "Army Seeks Dismissal of Woman Married to Transsexual ." CBS NEWS (MORNING NEWS). June 6, 1977

High-level ab initio predictions for the ionization energy, electron affinity, and heats of formation of cyclopentadienyl radical, cation, and anion, C5H5/C5H5+/C5H5-.

PubMed

Lo, Po-Kam; Lau, Kai-Chung

2014-04-03

The ionization energy (IE), electron affinity (EA), and heats of formation (ΔH°f0/ΔH°f298) for cyclopentadienyl radical, cation, and anion, C5H5/C5H5(+)/C5H5(-), have been calculated by wave function-based ab initio CCSDT/CBS approach, which involves approximation to complete basis set (CBS) limit at coupled-cluster level with up to full triple excitations (CCSDT). The zero-point vibrational energy correction, core-valence electronic correction, scalar relativistic effect, and higher-order corrections beyond the CCSD(T) wave function are included in these calculations. The allylic [C5H5((2)A2)] and dienylic [C5H5((2)B1)] forms of cyclopentadienyl radical are considered: the ground state structure exists in the dienyl form and it is about 30 meV more stable than the allylic structure. Both structures are lying closely and are interconvertible along the normal mode of b2 in-plane vibration. The CCSDT/CBS predictions (in eV) for IE[C5H5(+)((3)A1')←C5H5((2)B1)] = 8.443, IE[C5H5(+)((1)A1)←C5H5((2)B1)] = 8.634 and EA[C5H5(-)((1)A1')←C5H5((2)B1)] = 1.785 are consistent with the respective experimental values of 8.4268 ± 0.0005, 8.6170 ± 0.0005, and 1.808 ± 0.006, obtained from photoelectron spectroscopic measurements. The ΔH°f0/ΔH°f298's (in kJ/mol) for C5H5/C5H5(+)/C5H5(-) have also been predicted by the CCSDT/CBS method: ΔH°f0/ΔH°f298[C5H5((2)B1)] = 283.6/272.0, ΔH°f0/ΔH°f298[C5H5(+)((3)A1')] = 1098.2/1086.9, ΔH°f0/ΔH°f298[C5H5(+)((1)A1)] = 1116.6/1106.0, and ΔH°f0/ΔH°f298[C5H5(-)((1)A1')] = 111.4/100.0. The comparisons between the CCSDT/CBS predictions and the experimental values suggest that the CCSDT/CBS procedure is capable of predicting reliable IE(C5H5)'s and EA(C5H5) with uncertainties of ± 17 and ± 23 meV, respectively.

CT features, mimics and atypical presentations of gastrointestinal stromal tumor (GIST)

PubMed Central

Sripathi, Smiti; Rajagopal, KV; Srivastava, Rajendra Kumar; Ayachit, Anurag

2011-01-01

The term stromal tumor was coined in 1983 by Clark and Mazur for smooth muscle neoplasm of the gastrointestinal tract (GIT). Gastrointestinal stromal tumors (GIST) are nonepithelial tumors arising from the interstitial cells of Cajal, which express KIT protein-CD117 on immunohistochemistry. GIST can arise anywhere in the GIT, including the mesentery, omentum, and retroperitoneum. PMID:22013291

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures

PubMed Central

Park, Paul J.; Fuchs, Robert; Wei, Lai; Jorgensen, Brian G.; Redelman, Doug; Ward, Sean M.; Sanders, Kenton M.

2017-01-01

Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies. PMID:28426719

Aqueous Extracts of Herba Cistanche Promoted Intestinal Motility in Loperamide-Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal

PubMed Central

Yan, Shuai

2017-01-01

Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c-kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved. PMID:29445412

Changing views of Cajal's neuron: the case of the dendritic spine.

PubMed

Segal, Menahem

2002-01-01

Ever since dendritic spines were first described in detail by Santiago Ramón y Cajal, they were assumed to underlie the physical substrate of long term memory in the brain. Recent time-lapse imaging of dendritic spines in live tissue, using confocal microscopy, have revealed an amazingly plastic structure, which undergoes continuous changes in shape and size, not intuitively related to its assumed role in long term memory. Functionally, the spine is shown to be an independent cellular compartment, able to regulate calcium concentration independently of its parent dendrite. The shape of the spine is instrumental in regulating the link between the synapse and the parent dendrite such that longer spines have less impact on the dendrite than shorter ones. The spine can be formed, change its shape and disappear in response to afferent stimulation, in a dynamic fashion, indicating that spine morphology is an important vehicle for structuring synaptic interactions. While this role is crucial in the developing nervous system, large variations in spine densities in the adult brain indicate that tuning of synaptic impact may be a role of spines throughout the life of a neuron.

Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha.

PubMed

Fernández, Ricardo; González, Sergio; Rey, Sergio; Cortés, Paula P; Maisey, Kevin R; Reyes, Edison-Pablo; Larraín, Carolina; Zapata, Patricio

2008-07-01

In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N(2) for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O(2) tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS i.v.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-alpha receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-alpha, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-alpha injections. The results suggest that the CB may operate as a sensor for immune signals, that the CB exhibits histological features of acute inflammation induced by LPS, that TNF-alpha may participate in LPS-induced changes in chemosensory activity and that some pathophysiological reactions to high levels of LPS in the bloodstream may originate from changes in CB function.

Sensory Processing and Integration at the Carotid Body Tripartite Synapse: Neurotransmitter Functions and Effects of Chronic Hypoxia.

PubMed

Leonard, Erin M; Salman, Shaima; Nurse, Colin A

2018-01-01

Maintenance of homeostasis in the respiratory and cardiovascular systems depends on reflexes that are initiated at specialized peripheral chemoreceptors that sense changes in the chemical composition of arterial blood. In mammals, the bilaterally-paired carotid bodies (CBs) are the main peripheral chemoreceptor organs that are richly vascularized and are strategically located at the carotid bifurcation. The CBs contribute to the maintenance of O 2 , CO 2 /H + , and glucose homeostasis and have attracted much clinical interest because hyperactivity in these organs is associated with several pathophysiological conditions including sleep apnea, obstructive lung disease, heart failure, hypertension, and diabetes. In response to a decrease in O 2 availability (hypoxia) and elevated CO 2 /H + (acid hypercapnia), CB receptor type I (glomus) cells depolarize and release neurotransmitters that stimulate apposed chemoafferent nerve fibers. The central projections of those fibers in turn activate cardiorespiratory centers in the brainstem, leading to an increase in ventilation and sympathetic drive that helps restore blood PO 2 and protect vital organs, e.g., the brain. Significant progress has been made in understanding how neurochemicals released from type I cells such as ATP, adenosine, dopamine, 5-HT, ACh, and angiotensin II help shape the CB afferent discharge during both normal and pathophysiological conditions. However, type I cells typically occur in clusters and in addition to their sensory innervation are ensheathed by the processes of neighboring glial-like, sustentacular type II cells. This morphological arrangement is reminiscent of a "tripartite synapse" and emerging evidence suggests that paracrine stimulation of type II cells by a variety of CB neurochemicals may trigger the release of "gliotransmitters" such as ATP via pannexin-1 channels. Further, recent data suggest novel mechanisms by which dopamine, acting via D2 receptors (D2R), may inhibit action potential firing at petrosal nerve endings. This review will update current ideas concerning the presynaptic and postsynaptic mechanisms that underlie chemosensory processing in the CB. Paracrine signaling pathways will be highlighted, and particularly those that allow the glial-like type II cells to participate in the integrated sensory response during exposures to chemostimuli, including acute and chronic hypoxia.

On the validity of the basis set superposition error and complete basis set limit extrapolations for the binding energy of the formic acid dimer

NASA Astrophysics Data System (ADS)

Miliordos, Evangelos; Xantheas, Sotiris S.

2015-03-01

We report the variation of the binding energy of the Formic Acid Dimer with the size of the basis set at the Coupled Cluster with iterative Singles, Doubles and perturbatively connected Triple replacements [CCSD(T)] level of theory, estimate the Complete Basis Set (CBS) limit, and examine the validity of the Basis Set Superposition Error (BSSE)-correction for this quantity that was previously challenged by Kalescky, Kraka, and Cremer (KKC) [J. Chem. Phys. 140, 084315 (2014)]. Our results indicate that the BSSE correction, including terms that account for the substantial geometry change of the monomers due to the formation of two strong hydrogen bonds in the dimer, is indeed valid for obtaining accurate estimates for the binding energy of this system as it exhibits the expected decrease with increasing basis set size. We attribute the discrepancy between our current results and those of KKC to their use of a valence basis set in conjunction with the correlation of all electrons (i.e., including the 1s of C and O). We further show that the use of a core-valence set in conjunction with all electron correlation converges faster to the CBS limit as the BSSE correction is less than half than the valence electron/valence basis set case. The uncorrected and BSSE-corrected binding energies were found to produce the same (within 0.1 kcal/mol) CBS limits. We obtain CCSD(T)/CBS best estimates for De = - 16.1 ± 0.1 kcal/mol and for D0 = - 14.3 ± 0.1 kcal/mol, the later in excellent agreement with the experimental value of -14.22 ± 0.12 kcal/mol.

Two new anamorphic yeasts species, Cyberlindnera samutprakarnensis sp. nov. and Candida thasaenensis sp. nov., isolated from industrial wastes in Thailand.

PubMed

Poomtien, Jamroonsri; Jindamorakot, Sasitorn; Limtong, Savitree; Pinphanichakarn, Pairoh; Thaniyavarn, Jiraporn

2013-01-01

Three yeast strains were isolated from industrial wastes in Thailand. Based on the phylogenetic sequence analysis of the D1/D2 region of the large subunit rRNA gene, the internal transcribed spacer (ITS1-5.8S rRNA gene-ITS2; ITS1-2) region, and their physiological characteristics, the three strains were found to represent two novel species of the ascomycetous anamorphic yeast. Strain JP52(T) represent a novel species which was named Cyberlindnera samutprakarnensis sp. nov. (type strain JP52(T); = BCC 46825(T) = JCM 17816(T) = CBS 12528(T), MycoBank no. MB800879), which was differentiated from the closely related species Cyberlindnera mengyuniae CBS 10845(T) by 2.9 % sequence divergence in the D1/D2 region and 4.4 % sequence divergence in the ITS1-2. Strain JP59(T) and JP60 were identical in their D1/D2 and ITS1-2 regions, which were closely related to those of Scheffersomyces spartinae CBS 6059(T) by 0.9 and 1.0 % sequence divergence, respectively. In addition, supportive evidence of actin gene and translational elongation factor gene by sequence divergence of 6.5 % each confirmed their distinct status. Furthermore, JP59(T) and JP60 differentiated from the closely related species in some biochemical and physiological characteristics. These two strains were assigned as a single novel species which was named Candida thasaenensis sp. nov. (type JP59(T) = BCC 46828(T) = JCM 17817(T) = CBS 12529(T), MycoBank no. MB800880).

Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

PubMed Central

Andersen, Mikael R.; Salazar, Margarita P.; Schaap, Peter J.; van de Vondervoort, Peter J.I.; Culley, David; Thykaer, Jette; Frisvad, Jens C.; Nielsen, Kristian F.; Albang, Richard; Albermann, Kaj; Berka, Randy M.; Braus, Gerhard H.; Braus-Stromeyer, Susanna A.; Corrochano, Luis M.; Dai, Ziyu; van Dijck, Piet W.M.; Hofmann, Gerald; Lasure, Linda L.; Magnuson, Jon K.; Menke, Hildegard; Meijer, Martin; Meijer, Susan L.; Nielsen, Jakob B.; Nielsen, Michael L.; van Ooyen, Albert J.J.; Pel, Herman J.; Poulsen, Lars; Samson, Rob A.; Stam, Hein; Tsang, Adrian; van den Brink, Johannes M.; Atkins, Alex; Aerts, Andrea; Shapiro, Harris; Pangilinan, Jasmyn; Salamov, Asaf; Lou, Yigong; Lindquist, Erika; Lucas, Susan; Grimwood, Jane; Grigoriev, Igor V.; Kubicek, Christian P.; Martinez, Diego; van Peij, Noël N.M.E.; Roubos, Johannes A.; Nielsen, Jens; Baker, Scott E.

2011-01-01

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi. PMID:21543515

Hypokalemic paralysis in a middle-aged female with classic Bartter syndrome.

PubMed

Chiang, Wen-Fang; Lin, Shih-Hung; Chan, Jenq-Shyong; Lin, Shih-Hua

2014-02-01

Inherited classic Bartter syndrome (cBS) is an autosomal recessive renal tubular disorder resulting from inactivating mutations in the asolateral chloride channel (C1C-Kb) and usually presents in early infancy or childhood with mild to moderate hypokalemia. Profound hypokalemic paralysis in patients with cBS is extremely rare, especially in middle age. A 45-year-old Chinese female patient was referred for evaluation of chronic severe hypokalemia despite regular K+ supplementation (1 mmol/kg/d). She had had two episodes of muscle paralysis due to severe hypokalemia (K+ 1.9 - 2.1 mmol/l) in the past 3 years. She denied vomiting, diarrhea, or the use of laxatives or diuretics. Her blood pressure was normal. Biochemical studies showed hypokalemia (K+ 2.5 mmol/l) with renal potassium wasting, metabolic alkalosis (HCO3- 32 mmol/l), normomagnesemia (Mg2+ 0.8 mmol/l), hypercalciuria (calcium to creatinine ratio 0.5 mmol/mmol; normal < 0.22 mmol/mol), high plasma renin activity, but normal plasma aldosterone concentration. Abdominal sonography revealed neither renal stones nor nephrocalcinosis. Acquired causes of cBS such as autoimmune disease and drugs were all excluded. Molecular analysis of the CLCNKB gene, encoding ClC-Kb, and SLC12A3, encoding the thiazide-sensitive sodium chloride cotransporter (NCC), revealed compound heterozygous mutations in CLCNKB (L335P and G470E) inherited from her parents; her SLC12A3 was normal. These two mutations were not identified in 100 healthy subjects. Her plasma K+ concentration rose to 3 - 3.5 mmol/l after the addition of spironolactone. Inherited cBS may present with hypokalemic paralysis and should be considered in adult patients with hypokalemia and metabolic alkalosis.

Physiologic Levels of Endogenous Hydrogen Sulfide Maintain the Proliferation and Differentiation Capacity of Periodontal Ligament Stem Cells.

PubMed

Su, Yingying; Liu, Dayong; Liu, Yi; Zhang, Chunmei; Wang, Jinsong; Wang, Songlin

2015-11-01

Many invading oral bacteria are known to produce considerable amounts of hydrogen sulfide (H2S). The toxic activity of exogenous H2S in periodontal tissue has been demonstrated, but the role of endogenous H2S in the physiologic function of periodontal tissue remains poorly understood. The purpose of the present study is to investigate the biologic functions of H2S in the proliferation and differentiation of human periodontal ligament stem cells (PDLSCs). PDLSCs were isolated from periodontal ligament tissues of periodontally healthy volunteers or patients with periodontitis. Immunocytochemical staining, flow cytometry, and Western blot analysis were used to examine the expression of H2S-synthesizing enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). The proliferation capacity of PDLSCs was determined by cell counting kit-8 assay, carboxyfluorescein succinimidyl ester analysis, and 5-ethynyl-2'-deoxyuridine assay. The osteogenic potential of PDLSCs was tested using alkaline phosphatase staining, Alizarin Red staining, and in vivo transplantation experiments. Oil Red O staining was used to analyze adipogenic ability. The results show that human PDLSCs express both CBS and CSE and produce H2S. Blocking the generation of endogenous H2S with CBS inhibitor hydroxylamine significantly attenuated PDLSC proliferation and reduced the osteogenic and adipogenic differentiation capacity of PDLSCs. In contrast, CSE inhibitor DL-propargylglycine had no effect on PDLSC function. Exogenous H2S could inhibit the production of endogenous H2S and impair PDLSC function in a dose-dependent manner. Physiologic levels of endogenous H2S maintain the proliferation and differentiation capacity of PDLSCs, and CBS may be the main source of endogenous H2S in PDLSCs.

Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism.

PubMed

Li, Da; Liu, Hong-Xiang; Fang, Yuan-Yuan; Huo, Jia-Ning; Wu, Qi-Jun; Wang, Tian-Ren; Zhou, Yi-Ming; Wang, Xiu-Xia; Ma, Xiao-Xin

2018-05-22

What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD). It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia. These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Candida alocasiicola sp. nov., Candida hainanensis sp. nov., Candida heveicola sp. nov. and Candida musiphila sp. nov., novel anamorphic, ascomycetous yeast species isolated from plants.

PubMed

Wang, Shi-An; Jia, Jian-Hua; Bai, Feng-Yan

2008-08-01

In a taxonomic study on the ascomycetous yeasts isolated from plant materials collected in tropical forests in Yunnan and Hainan Provinces, southern China, four strains isolated from tree sap (YJ2E(T)) and flowers (YF9E(T), YWZH3C(T) and YYF2A(T)) were revealed to represent four undescribed yeast species. Molecular phylogenetic analysis based on the large subunit (26S) rRNA gene D1/D2 domain sequences showed that strain YJ2E(T) was located in a clade together with Candida haemulonii and C. pseudohaemulonii. Strain YF9E(T) was most closely related to C. azyma and strain YWZH3C(T) to C. sorbophila and C. spandovensis. Strain YYF2A(T) was clustered in a clade containing small-spored Metschnikowia species and related anamorphic Candida species. The new strains differed from their closely related described species by more than 10% mismatches in the D1/D2 domain. No sexual states were observed for the four strains on various sporulation media. The new species are therefore assigned to the genus Candida and described as Candida alocasiicola sp. nov. (type strain, YF9E(T) = AS 2.3484(T) = CBS 10702(T)), Candida hainanensis sp. nov. (type strain, YYF2A(T) = AS 2.3478(T) = CBS 10696(T)), Candida heveicola sp. nov. (type strain, YJ2E(T) = AS 2.3483(T) = CBS 10701(T)) and Candida musiphila sp. nov. (type strain, YWZH3C(T) = AS 2.3479(T) = CBS 10697(T)).

RehAtt - scanning training for neglect enhanced by multi-sensory stimulation in Virtual Reality.

PubMed

Fordell, Helena; Bodin, Kenneth; Eklund, Anders; Malm, Jan

2016-06-01

There is a lack of effective treatment for neglect. We have developed a new training method, RehAtt™. The objective of this study was to determine whether RehAtt™ improves spatial attention in chronic neglect after stroke. RehAtt™ consists of a computer with monitor, 3D glasses, and a force feedback interface (Robotic pen) giving sensory motor activation to the contra-lesional arm. The software combines visual scanning training with multi-sensory stimulation in 3D virtual reality (VR) game environment. Fifteen stroke patients with chronic neglect (duration > 6 month) had repeated baseline evaluations to confirm stability of symptoms. There were no test-retest effects for any of the tests. Thereafter, all patients trained 15 h in RehAtt™ (3 × 1 h for 5 weeks). A neglect test battery and Catherine Bergego Scale, CBS, were used to assess behavioral outcome after intervention. CBS was also used at a 6-month follow-up. Using repeated measurement analysis improvements due to the training were found for Star cancellation test (p = 0.006), Baking tray task (p < 0.001), and Extinction test (p = 0.05). In the Posner task improvements were seen fewer missed targets (p = 0.024). CBS showed improvements in activities of daily life immediately after training (p < 0.01). After 6 months the patients still reported improvement in CBS. RehAtt™ is a new concept for rehabilitation of neglect. Training with the VR-method improved spatial attention and showed transfer to improved spatial attention in activities of daily living in chronic neglect. Our results are promising and merit further studies.

The construction of a high resolution crystal backscattering spectrometer HERMES I

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

Larese, J.Z.

There is a need in the United States for a state-of-the-art, cold-neutron, crystal backscattering spectrometer (CBS) designed to investigate the structure and dynamics of condensed matter systems by the simultaneous utilization of long wavelength elastic diffraction and high-energy-resolution inelastic scattering. Cold neutron spectroscopy with CBS-type instruments has already made many important contributions to the study of atomic and molecular diffusion in biomaterials, polymers, semiconductors, liquid crystals, superionic conductors and the like. Such instruments have also been invaluable for ultra high resolution investigations of the low-lying quantum tunneling processes that provide direct insight into the dynamical response of solids at themore » lowest energies. Until relatively recently, however, all such instruments were located at steady-state reactors. This proposal describes HERMES I (High Energy Resolution Machines I) a CBS intended for installation at the LANSCE pulsed neutron facility of Los Alamos National Laboratory. As explained in detail in the main text, the authors propose to construct an updated, high-performance CBS which incorporates neutron techniques developed during the decade since IRIS was built, i.e., improved supermirror technology, a larger area crystal analyzer and high efficiency wire gas detectors. The instrument is designed in such a way as to be readily adaptable to future upgrades. HERMES I, they believe, will substantially expand the range and flexibility of neutron investigations in the United States and open new and potentially fruitful directions for condensed matter exploration. This document describes a implementation plan with a direct cost range between $4.5 to 5.6 M and scheduled duration of 39--45 months for identified alternatives.« less

Analysis of functioning and efficiency of a code blue system in a tertiary care hospital.

PubMed

Monangi, Srinivas; Setlur, Rangraj; Ramanathan, Ramprasad; Bhasin, Sidharth; Dhar, Mridul

2018-01-01

"Code blue" (CB) is a popular hospital emergency code, which is used by hospitals to alert their emergency response team of any cardiorespiratory arrest. The factors affecting the outcomes of emergencies are related to both the patient and the nature of the event. The primary objective was to analyze the survival rate and factors associated with survival and also practical problems related to functioning of a CB system (CBS). After the approval of hospital ethics committee, an analysis and audit was conducted of all patients on whom a CB had been called in our tertiary care hospital over 24 months. Data collected were demographic data, diagnosis, time of cardiac arrest and activation of CBS, time taken by CBS to reach the patient, presenting rhythm on arrival of CB team, details of cardiopulmonary resuscitation (CPR) such as duration and drugs given, and finally, events and outcomes. Chi-square test and logistic regression analysis were used to analyze the data. A total of 720 CB calls were initiated during the period. After excluding 24 patients, 694 calls were studied and analyzed. Six hundred and twenty were true calls and 74 were falls calls. Of the 620, 422 were cardiac arrests and 198 were medical emergencies. Overall survival was 26%. Survival in patients with cardiac arrests was 11.13%. Factors such as age, presenting rhythm, and duration of CPR were found to have a significant effect on survival. Problems encountered were personnel and equipment related. A CBS is effective in improving the resuscitation efforts and survival rates after inhospital cardiac arrests. Age, presenting rhythm at the time of arrest, and duration of CPR have significant effect on survival of the patient after a cardiac arrest. Technical and staff-related problems need to be considered and improved upon.

Metschnikowia drakensbergensis sp. nov. and Metschnikowia caudata sp. nov., endemic yeasts associated with Protea flowers in South Africa.

PubMed

de Vega, Clara; Guzmán, Beatriz; Steenhuisen, Sandy-Lynn; Johnson, Steven D; Herrera, Carlos M; Lachance, Marc-André

2014-11-01

In a taxonomic study of yeasts recovered from nectar of flowers and associated insects in South Africa, 11 strains were found to represent two novel species. Morphological and physiological characteristics and sequence analyses of the large-subunit rRNA gene D1/D2 region, as well as the actin, RNA polymerase II and elongation factor 2 genes, showed that the two novel species belonged to the genus Metschnikowia. Metschnikowia drakensbergensis sp. nov. (type strain EBD-CdVSA09-2(T) =CBS 13649(T) =NRRL Y-63721(T); MycoBank no. MB809688; allotype EBD-CdVSA10-2(A) =CBS13650(A) =NRRL Y-63720(A)) was recovered from nectar of Protea roupelliae and the beetle Heterochelus sp. This species belongs to the large-spored Metschnikowia clade and is closely related to Metschnikowia proteae, with which mating reactions and single-spored asci were observed. Metschnikowia caudata sp. nov. (type strain EBD-CdVSA08-1(T) =CBS 13651(T) =NRRL Y-63722(T); MycoBank no. MB809689; allotype EBD-CdVSA57-2(A) =CBS 13729(A) =NRRL Y-63723(A)) was isolated from nectar of Protea dracomontana, P. roupelliae and P. subvestita and a honeybee, and is a sister species to Candida hainanensis and Metschnikowia lopburiensis. Analyses of the four sequences demonstrated the existence of three separate phylotypes. Intraspecies matings led to the production of mature asci of unprecedented morphology, with a long, flexuous tail. A single ascospore was produced in all compatible crosses, regardless of sequence phylotype. The two species appear to be endemic to South Africa. The ecology and habitat specificity of these novel species are discussed in terms of host plant and insect host species. © 2014 IUMS.

Crystal structure of Halobacterium salinarum halorhodopsin with a partially depopulated primary chloride-binding site.

PubMed

Schreiner, Madeleine; Schlesinger, Ramona; Heberle, Joachim; Niemann, Hartmut H

2016-09-01

The transmembrane pump halorhodopsin in halophilic archaea translocates chloride ions from the extracellular to the cytoplasmic side upon illumination. In the ground state a tightly bound chloride ion occupies the primary chloride-binding site (CBS I) close to the protonated Schiff base that links the retinal chromophore to the protein. The light-triggered trans-cis isomerization of retinal causes structural changes in the protein associated with movement of the chloride ion. In reverse, chemical depletion of CBS I in Natronomonas pharaonis halorhodopsin (NpHR) through deprotonation of the Schiff base results in conformational changes of the protein: a state thought to mimic late stages of the photocycle. Here, crystals of Halobacterium salinarum halorhodopsin (HsHR) were soaked at high pH to provoke deprotonation of the Schiff base and loss of chloride. The crystals changed colour from purple to yellow and the occupancy of CBS I was reduced from 1 to about 0.5. In contrast to NpHR, this chloride depletion did not cause substantial conformational changes in the protein. Nevertheless, two observations indicate that chloride depletion could eventually result in structural changes similar to those found in NpHR. Firstly, the partially chloride-depleted form of HsHR has increased normalized B factors in the region of helix C that is close to CBS I and changes its conformation in NpHR. Secondly, prolonged soaking of HsHR crystals at high pH resulted in loss of diffraction. In conclusion, the conformation of the chloride-free protein may not be compatible with this crystal form of HsHR despite a packing arrangement that hardly restrains helices E and F that presumably move during ion transport.

The state of cell block variation and satisfaction in the era of molecular diagnostics and personalized medicine

PubMed Central

Crapanzano, John P.; Heymann, Jonas J.; Monaco, Sara; Nassar, Aziza; Saqi, Anjali

2014-01-01

Background: In the recent past, algorithms and recommendations to standardize the morphological, immunohistochemical and molecular classification of lung cancers on cytology specimens have been proposed, and several organizations have recommended cell blocks (CBs) as the preferred modality for molecular testing. Based on the literature, there are several different techniques available for CB preparation-suggesting that there is no standard. The aim of this study was to conduct a survey of CB preparation techniques utilized in various practice settings and analyze current issues, if any. Materials and Methods: A single E-mail with a link to an electronic survey was distributed to members of the American Society of Cytopathology and other pathologists. Questions pertaining to the participants’ practice setting and CBs-volume, method, quality and satisfaction-were included. Results: Of 95 respondents, 90/95 (94%) completed the survey and comprise the study group. Most participants practice in a community hospital/private practice (44%) or academic center (41%). On average, 14 CBs (range 0-50; median 10) are prepared by a laboratory daily. Over 10 methods are utilized: Plasma thrombin (33%), HistoGel (27%), Cellient automated cell block system (8%) and others (31%) respectively. Forty of 90 (44%) respondents are either unsatisfied or sometimes satisfied with their CB quality, with low-cellular yield being the leading cause of dissatisfaction. There was no statistical significance between the three most common CB preparation methods and satisfaction with quality. Discussion: Many are dissatisfied with their current method of CB preparation, and there is no consistent method to prepare CBs. In today's era of personalized medicine with an increasing array of molecular tests being applied to cytological specimens, there is a need for a standardized protocol for CB optimization to enhance cellularity. PMID:24799951

The state of cell block variation and satisfaction in the era of molecular diagnostics and personalized medicine.

PubMed

Crapanzano, John P; Heymann, Jonas J; Monaco, Sara; Nassar, Aziza; Saqi, Anjali

2014-01-01

In the recent past, algorithms and recommendations to standardize the morphological, immunohistochemical and molecular classification of lung cancers on cytology specimens have been proposed, and several organizations have recommended cell blocks (CBs) as the preferred modality for molecular testing. Based on the literature, there are several different techniques available for CB preparation-suggesting that there is no standard. The aim of this study was to conduct a survey of CB preparation techniques utilized in various practice settings and analyze current issues, if any. A single E-mail with a link to an electronic survey was distributed to members of the American Society of Cytopathology and other pathologists. Questions pertaining to the participants' practice setting and CBs-volume, method, quality and satisfaction-were included. Of 95 respondents, 90/95 (94%) completed the survey and comprise the study group. Most participants practice in a community hospital/private practice (44%) or academic center (41%). On average, 14 CBs (range 0-50; median 10) are prepared by a laboratory daily. Over 10 methods are utilized: Plasma thrombin (33%), HistoGel (27%), Cellient automated cell block system (8%) and others (31%) respectively. Forty of 90 (44%) respondents are either unsatisfied or sometimes satisfied with their CB quality, with low-cellular yield being the leading cause of dissatisfaction. There was no statistical significance between the three most common CB preparation methods and satisfaction with quality. Many are dissatisfied with their current method of CB preparation, and there is no consistent method to prepare CBs. In today's era of personalized medicine with an increasing array of molecular tests being applied to cytological specimens, there is a need for a standardized protocol for CB optimization to enhance cellularity.

Effects of Oxygen Availability on Acetic Acid Tolerance and Intracellular pH in Dekkera bruxellensis.

PubMed

Capusoni, Claudia; Arioli, Stefania; Zambelli, Paolo; Moktaduzzaman, M; Mora, Diego; Compagno, Concetta

2016-08-01

The yeast Dekkera bruxellensis, associated with wine and beer production, has recently received attention, because its high ethanol and acid tolerance enables it to compete with Saccharomyces cerevisiae in distilleries that produce fuel ethanol. We investigated how different cultivation conditions affect the acetic acid tolerance of D. bruxellensis We analyzed the ability of two strains (CBS 98 and CBS 4482) exhibiting different degrees of tolerance to grow in the presence of acetic acid under aerobic and oxygen-limited conditions. We found that the concomitant presence of acetic acid and oxygen had a negative effect on D. bruxellensis growth. In contrast, incubation under oxygen-limited conditions resulted in reproducible growth kinetics that exhibited a shorter adaptive phase and higher growth rates than those with cultivation under aerobic conditions. This positive effect was more pronounced in CBS 98, the more-sensitive strain. Cultivation of CBS 98 cells under oxygen-limited conditions improved their ability to restore their intracellular pH upon acetic acid exposure and to reduce the oxidative damage to intracellular macromolecules caused by the presence of acetic acid. This study reveals an important role of oxidative stress in acetic acid tolerance in D. bruxellensis, indicating that reduced oxygen availability can protect against the damage caused by the presence of acetic acid. This aspect is important for optimizing industrial processes performed in the presence of acetic acid. This study reveals an important role of oxidative stress in acetic acid tolerance in D. bruxellensis, indicating that reduced oxygen availability can have a protective role against the damage caused by the presence of acetic acid. This aspect is important for the optimization of industrial processes performed in the presence of acetic acid. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks.

PubMed

Borm, Paul J A; Cakmak, Gonca; Jermann, Erich; Weishaupt, Christel; Kempers, Pascal; van Schooten, Frederik Jan; Oberdörster, Günter; Schins, Roel P F

2005-06-01

The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m(3)). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 microM) and a mixture of 16 PAHs (0.1 microM) were used. No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 microg/cm(2)) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely.

Effects of Oxygen Availability on Acetic Acid Tolerance and Intracellular pH in Dekkera bruxellensis

PubMed Central

Capusoni, Claudia; Arioli, Stefania; Zambelli, Paolo; Moktaduzzaman, M.; Mora, Diego

2016-01-01

ABSTRACT The yeast Dekkera bruxellensis, associated with wine and beer production, has recently received attention, because its high ethanol and acid tolerance enables it to compete with Saccharomyces cerevisiae in distilleries that produce fuel ethanol. We investigated how different cultivation conditions affect the acetic acid tolerance of D. bruxellensis. We analyzed the ability of two strains (CBS 98 and CBS 4482) exhibiting different degrees of tolerance to grow in the presence of acetic acid under aerobic and oxygen-limited conditions. We found that the concomitant presence of acetic acid and oxygen had a negative effect on D. bruxellensis growth. In contrast, incubation under oxygen-limited conditions resulted in reproducible growth kinetics that exhibited a shorter adaptive phase and higher growth rates than those with cultivation under aerobic conditions. This positive effect was more pronounced in CBS 98, the more-sensitive strain. Cultivation of CBS 98 cells under oxygen-limited conditions improved their ability to restore their intracellular pH upon acetic acid exposure and to reduce the oxidative damage to intracellular macromolecules caused by the presence of acetic acid. This study reveals an important role of oxidative stress in acetic acid tolerance in D. bruxellensis, indicating that reduced oxygen availability can protect against the damage caused by the presence of acetic acid. This aspect is important for optimizing industrial processes performed in the presence of acetic acid. IMPORTANCE This study reveals an important role of oxidative stress in acetic acid tolerance in D. bruxellensis, indicating that reduced oxygen availability can have a protective role against the damage caused by the presence of acetic acid. This aspect is important for the optimization of industrial processes performed in the presence of acetic acid. PMID:27235432

Physiological Importance of Hydrogen Sulfide: Emerging Potent Neuroprotector and Neuromodulator

PubMed Central

Chung, Hyung-Joo

2016-01-01

Hydrogen sulfide (H2S) is an emerging neuromodulator that is considered to be a gasotransmitter similar to nitrogen oxide (NO) and carbon monoxide (CO). H2S exerts universal cytoprotective effects and acts as a defense mechanism in organisms ranging from bacteria to mammals. It is produced by the enzymes cystathionine β-synthase (CBS), cystathionine ϒ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (MST), and D-amino acid oxidase (DAO), which are also involved in tissue-specific biochemical pathways for H2S production in the human body. H2S exerts a wide range of pathological and physiological functions in the human body, from endocrine system and cellular longevity to hepatic protection and kidney function. Previous studies have shown that H2S plays important roles in peripheral nerve regeneration and degeneration and has significant value during Schwann cell dedifferentiation and proliferation but it is also associated with axonal degradation and the remyelination of Schwann cells. To date, physiological and toxic levels of H2S in the human body remain unclear and most of the mechanisms of action underlying the effects of H2S have yet to be fully elucidated. The primary purpose of this review was to provide an overview of the role of H2S in the human body and to describe its beneficial effects. PMID:27413423

Human cerebral cortex Cajal-Retzius neuron: development, structure and function. A Golgi study.

PubMed

Marín-Padilla, Miguel

2015-01-01

The development, morphology and possible functional activity of the Cajal-Retzius cell of the developing human cerebral cortex are explored herein. The C-RC, of extracortical origin, is the essential neuron of the neocortex first lamina. It receives inputs from afferent fibers that reach the first lamina early in development. Although the origin and function of these original afferent fibers remain unknown, their target is the first lamina sole neuron: the C-RC. This neuron orchestrates the arrival, size and stratification of all pyramidal neurons (of ependymal origin) of the neocortex gray matter. Its axonic terminals spread radially and horizontally throughout the entirety of the first lamina establishing contacts with the dendritic terminals of all gray matter pyramidal cells regardless of size, location and/or eventual functional roles. While the neuron axonic terminals spread radially and horizontally throughout the first lamina, the neuronal' body undergoes progressive developmental dilution and locating any of them in the adult brain become quite difficult. The neuron bodies are probably retained in the older regions of the neocortex while their axonic collaterals will spread throughout its more recent ones and eventually will extend to great majority of the cortical surface. The neocortex first lamina evolution and composition and that of the C-RC are intertwined and mutually interdependent. It is not possible to understand the C-RC evolving morphology without understanding that of the first lamina. The first lamina composition and its structural and functional organizations obtained with different staining methods may be utterly different. These differences have added unnecessary confusion about its nature. The essential emptiness observed in hematoxylin and eosin preparations (most commonly used) contrast sharply with the concentration of dendrites (the cortex' largest) obtained using special (MAP-2) stain for dendrites. Only Golgi preparations demonstrate the numerous dendritic and axonic terminals that compose the first lamina basic structure. High power microscopic views of Golgi preparations demonstrate the intimate anatomical and functional interrelationships among dendritic and axonic terminals as well as synaptic contacts between them. The C-RC' essential morphology does not changes but it is progressively modified by the first lamina increase in thickness and in number of terminal dendrites and their subsequent maturation. This neuron variable morphologic appearance has been the source of controversy. Its morphology depends on the first lamina thickness that may be quite variable among different mammals. In rodents (most commonly used experimental mammal), the first lamina thickness, number and horizontal expansion of dendrites is but a fraction of those in humans. This differences are reflected in the C-RC' morphology among mammals (including humans) and should not be thought as representing new types of neurons.

[Charles Bonnet syndrome precipitated by brimonidine].

PubMed

García-Catalán, M R; Arriola-Villalobos, P; Santos-Bueso, E; Gil-de-Bernabé, J; Díaz-Valle, D; Benítez-del-Castillo, J M; García-Sánchez, J

2013-09-01

An 81-year-old woman with age-related macular degeneration and pseudoexfoliative glaucoma developed visual hallucinations (faces, flowers and frames) shortly after beginning brimonidine drops. Neurologic and psychiatric examination was normal. Visual hallucinations disappeared within 10 days after discontinuing the drug. The Charles Bonnet syndrome (CBS) is characterised by complex visual hallucinations in elderly patients in the setting of significant visual impairment without any psychiatric symptoms. Awareness of CBS among ophthalmologist is essential. Clinicians should treat visual impairment and be aware of possible visual hallucinations in patients treated with brimonidine. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Ogataea phyllophila sp. nov., Candida chumphonensis sp. nov. and Candida mattranensis sp. nov., three methylotrophic yeast species from phylloplane in Thailand.

PubMed

Koowadjanakul, Nampueng; Jindamorakot, Sasitorn; Yongmanitchai, Wichien; Limtong, Savitree

2011-08-01

Five strains (LN12, LN14(T), LN15(T), LN16 and LN17(T)) representing three novel methylotrophic yeast species were isolated from the external surface of plant leaves by three-consecutive enrichments. On the basis of morphological, biochemical, physiological and chemotaxonomic characteristics, the sequence analysis of the D1/D2 domain of the large subunit (LSU) rRNA gene and the phylogenetic analysis, the five strains were assigned to be one novel Ogataea species and two novel Candida species. Three strains (LN12, LN14(T) and LN16) represent a single novel species of the genus Ogataea, for which the name Ogataea phyllophila sp. nov. is proposed. The type strain is LN14(T) (= BCC 42666(T) = NBRC 107780(T) = CBS 12095(T)). Strain LN15(T) was assigned to be Candida chumphonensis sp. nov. (type strain LN15(T) = BCC 42667(T) = NBRC 107781(T) = CBS 12096(T)). Strain LN17(T) represented another novel species of Candida that was named Candida mattranensis sp. nov. (type strain LN17(T) = BCC 42668(T) = NBRC 107782(T) = CBS 12097(T)).

Change in single cystathionine β-synthase domain-containing protein from a bent to flat conformation upon adenosine monophosphate binding.

PubMed

Jeong, Byung-Cheon; Park, Si Hoon; Yoo, Kyoung Shin; Shin, Jeong Sheop; Song, Hyun Kyu

2013-07-01

Cystathionine β-synthase (CBS) domains are small intracellular modules that can act as binding domains for adenosine derivatives, and they may regulate the activity of associated enzymes or other functional domains. Among these, the single CBS domain-containing proteins, CBSXs, from Arabidopsis thaliana, have recently been identified as redox regulators of the thioredoxin system. Here, the crystal structure of CBSX2 in complex with adenosine monophosphate (AMP) is reported at 2.2Å resolution. The structure of dimeric CBSX2 with bound-AMP is shown to be approximately flat, which is in stark contrast to the bent form of apo-CBSXs. This conformational change in quaternary structure is triggered by a local structural change of the unique α5 helix, and by moving each loop P into an open conformation to accommodate incoming ligands. Furthermore, subtle rearrangement of the dimer interface triggers movement of all subunits, and consequently, the bent structure of the CBSX2 dimer becomes a flat structure. This reshaping of the structure upon complex formation with adenosine-containing ligand provides evidence that ligand-induced conformational reorganization of antiparallel CBS domains is an important regulatory mechanism. Copyright © 2013 Elsevier Inc. All rights reserved.

Experimental investigation of conical bubble structure and acoustic flow structure in ultrasonic field.

PubMed

Ma, Xiaojian; Huang, Biao; Wang, Guoyu; Zhang, Mindi

2017-01-01

The objective of this paper is to investigate the transient conical bubble structure (CBS) and acoustic flow structure in ultrasonic field. In the experiment, the high-speed video and particle image velocimetry (PIV) techniques are used to measure the acoustic cavitation patterns, as well as the flow velocity and vorticity fields. Results are presented for a high power ultrasound with a frequency of 18kHz, and the range of the input power is from 50W to 250W. The results of the experiment show the input power significantly affects the structures of CBS, with the increase of input power, the cavity region of CBS and the velocity of bubbles increase evidently. For the transient motion of bubbles on radiating surface, two different types could be classified, namely the formation, aggregation and coalescence of cavitation bubbles, and the aggregation, shrink, expansion and collapse of bubble cluster. Furthermore, the thickness of turbulent boundary layer near the sonotrode region is found to be much thicker, and the turbulent intensities are much higher for relatively higher input power. The vorticity distribution is prominently affected by the spatial position and input power. Copyright © 2016 Elsevier B.V. All rights reserved.

An ab initio benchmark study of the H + CO --> HCO reaction

NASA Technical Reports Server (NTRS)

Woon, D. E.

1996-01-01

The H + CO --> HCO reaction has been characterized with correlation consistent basis sets at five levels of theory in order to benchmark the sensitivities of the barrier height and reaction ergicity to the one-electron and n-electron expansions of the electronic wave function. Single and multireference methods are compared and contrasted. The coupled cluster method RCCSD(T) was found to be in very good agreement with Davidson-corrected internally-contracted multireference configuration interaction (MRCI+Q). Second-order Moller-Plesset perturbation theory (MP2) was also employed. The estimated complete basis set (CBS) limits for the barrier height (in kcal/mol) for the five methods, including harmonic zero-point energy corrections, are MP2, 4.66; RCCSD, 4.78; RCCSD(T), 4.15; MRCI, 5.10; and MRCI+Q, 4.07. Similarly, the estimated CBS limits for the ergicity of the reaction are: MP2, -17.99; RCCSD, -13.34; RCCSD(T), -13.79; MRCI, -11.46; and MRCI+Q, -13.70. Additional basis set explorations for the RCCSD(T) method demonstrate that aug-cc-pVTZ sets, even with some functions removed, are sufficient to reproduce the CBS limits to within 0.1-0.3 kcal/mol.

Theoretical investigation of gas-phase molecular complex formation between 2-hydroxy thiophenol and a water molecule.

PubMed

Kumar Deb, Debojit; Sarkar, Biplab

2017-01-18

The torsional potential of OH and SH rotations in 2-hydroxy thiophenol is systematically studied using the MP2 ab initio method. The outcome of state-of-the-art calculations is used in the investigation of the structures and conformational preferences of 2-hydroxy thiophenol and aims at further interaction studies with a gas phase water molecule. SCS-MP2 and CCSD(T) complete basis set (CBS) limit interaction energies for these complexes are presented. The SCS-MP2/CBS limit is achieved using various two-point extrapolation methods with aug-cc-pVDZ and aug-cc-pVTZ basis sets. The CCSD(T) correction term is determined as the difference between CCSD(T) and SCS-MP2 interaction energies calculated using a smaller basis set. The effect of counterpoise correction on the extrapolation to the CBS limit is discussed. The performance of DFT based wB97XD, M06-2X and B3LYP-D3 functionals is tested against the benchmark energy from ab initio calculations. Hydrogen bond interactions are characterized by carrying out QTAIM, NCIPLOT, NBO and SAPT analyses.

Effect of oxygenation and temperature on glucose-xylose fermentation in Kluyveromyces marxianus CBS712 strain

PubMed Central

2014-01-01

Background The yeast Kluyveromyces marxianus features specific traits that render it attractive for industrial applications. These include production of ethanol which, together with thermotolerance and the ability to grow with a high specific growth rate on a wide range of substrates, could make it an alternative to Saccharomyces cerevisiae as an ethanol producer. However, its ability to co-ferment C5 and C6 sugars under oxygen-limited conditions is far from being fully characterized. Results In the present study, K. marxianus CBS712 strain was cultivated in defined medium with glucose and xylose as carbon source. Ethanol fermentation and sugar consumption of CBS712 were investigated under different oxygen supplies (1.75%, 11.00% and 20.95% of O2) and different temperatures (30°C and 41°C). By decreasing oxygen supply, independently from the temperature, both biomass production as well as sugar utilization rate were progressively reduced. In all the tested conditions xylose consumption followed glucose exhaustion. Therefore, xylose metabolism was mainly affected by oxygen depletion. Loss in cell viability cannot explain the decrease in sugar consumption rates, as demonstrated by single cell analyses, while cofactor imbalance is commonly considered as the main cause of impairment of the xylose reductase (KmXR) - xylitol dehydrogenase (KmXDH) pathway. Remarkably, when these enzyme activities were assayed in vitro, a significant decrease was observed together with oxygen depletion, not ascribed to reduced transcription of the corresponding genes. Conclusions In the present study both oxygen supply and temperature were shown to be key parameters affecting the fermentation capability of sugars in the K. marxianus CBS712 strain. In particular, a direct correlation was observed between the decreased efficiency to consume xylose with the reduced specific activity of the two main enzymes (KmXR and KmXDH) involved in its catabolism. These data suggest that, in addition to the impairment of the oxidoreductive pathway being determined by the cofactor imbalance, post-transcriptional and/or post-translational regulation of the pathway enzymes contributes to the efficiency of xylose catabolism in micro-aerobic conditions. Overall, the presented work provides novel information on the fermentation capability of the CBS712 strain that is currently considered as the reference strain of the genus K. marxianus. PMID:24712908

The challenges of reshaping disease specific and care oriented community based services towards comprehensive goals: a situation appraisal in the Western Cape Province, South Africa.

PubMed

Schneider, Helen; Schaay, Nikki; Dudley, Lilian; Goliath, Charlyn; Qukula, Tobeka

2015-09-30

Similar to other countries in the region, South Africa is currently reorienting a loosely structured and highly diverse community care system that evolved around HIV and TB, into a formalized, comprehensive and integrated primary health care outreach programme, based on community health workers (CHWs). While the difficulties of establishing national CHW programmes are well described, the reshaping of disease specific and care oriented community services, based outside the formal health system, poses particular challenges. This paper is an in-depth case study of the challenges of implementing reforms to community based services (CBS) in one province of South Africa. A multi-method situation appraisal of CBS in the Western Cape Province was conducted over eight months in close collaboration with provincial stakeholders. The appraisal mapped the roles and service delivery, human resource, financing and governance arrangements of an extensive non-governmental organisation (NGO) contracted and CHW based service delivery infrastructure that emerged over 15-20 years in this province. It also gathered the perspectives of a wide range of actors - including communities, users, NGOs, PHC providers and managers - on the current state and future visions of CBS. While there was wide support for new approaches to CBS, there are a number of challenges to achieving this. Although largely government funded, the community based delivery platform remains marginal to the formal public primary health care (PHC) and district health systems. CHW roles evolved from a system of home based care and are limited in scope. There is a high turnover of cadres, and support systems (supervision, monitoring, financing, training), coordination between CHWs, NGOs and PHC facilities, and sub-district capacity for planning and management of CBS are all poorly developed. Reorienting community based services that have their origins in care responses to HIV and TB presents an inter-related set of resource mobilisation, system design and governance challenges. These include not only formalising community based teams themselves, but also the forging of new roles, relationships and mind-sets within the primary health care system, and creating greater capacity for contracting and engaging a plural set of actors - government, NGO and community - at district and sub-district level.

Structure and binding energy of the H2S dimer at the CCSD(T) complete basis set limit.

PubMed

Lemke, Kono H

2017-06-21

This study presents results for the binding energy and geometry of the H 2 S dimer which have been computed using Møller-Plesset perturbation theory (MP2, MP4) and coupled cluster (CCSD, CCSD(T)) calculations with basis sets up to aug-cc-pV5Z. Estimates of D e , E ZPE , D o , and dimer geometry have been obtained at each level of theory by taking advantage of the systematic convergence behavior toward the complete basis set (CBS) limit. The CBS limit binding energy values of D e are 1.91 (MP2), 1.75 (MP4), 1.41 (CCSD), and 1.69 kcal/mol (CCSD[T]). The most accurate values for the equilibrium S-S distance r SS (without counterpoise correction) are 4.080 (MP2/aug-cc-pV5Z), 4.131 (MP4/aug-cc-pVQZ), 4.225 (CCSD/aug-cc-pVQZ), and 4.146 Å (CCSD(T)/aug-cc-pVQZ). This study also evaluates the effect of counterpoise correction on the H 2 S dimer geometry and binding energy. As regards the structure of (H 2 S) 2 , MPn, CCSD, and CCSD(T) level values of r SS , obtained by performing geometry optimizations on the counterpoise-corrected potential energy surface, converge systematically to CBS limit values of 4.099 (MP2), 4.146 (MP4), 4.233 (CCSD), and 4.167 Å (CCSD(T)). The corresponding CBS limit values of the equilibrium binding energy D e are 1.88 (MP2), 1.76 (MP4), 1.41 (CCSD), and 1.69 kcal/mol (CCSD(T)), the latter in excellent agreement with the measured binding energy value of 1.68 ± 0.02 kcal/mol reported by Ciaffoni et al. [Appl. Phys. B 92, 627 (2008)]. Combining CBS electronic binding energies D e with E ZPE predicted by CCSD(T) vibrational second-order perturbation theory calculations yields D o = 1.08 kcal/mol, which is around 0.6 kcal/mol smaller than the measured value of 1.7 ± 0.3 kcal/mol. Overall, the results presented here demonstrate that the application of high level calculations, in particular CCSD(T), in combination with augmented correlation consistent basis sets provides valuable insight into the structure and energetics of the hydrogen sulfide dimer.

Effect of oxygenation and temperature on glucose-xylose fermentation in Kluyveromyces marxianus CBS712 strain.

PubMed

Signori, Lorenzo; Passolunghi, Simone; Ruohonen, Laura; Porro, Danilo; Branduardi, Paola

2014-04-08

The yeast Kluyveromyces marxianus features specific traits that render it attractive for industrial applications. These include production of ethanol which, together with thermotolerance and the ability to grow with a high specific growth rate on a wide range of substrates, could make it an alternative to Saccharomyces cerevisiae as an ethanol producer. However, its ability to co-ferment C5 and C6 sugars under oxygen-limited conditions is far from being fully characterized. In the present study, K. marxianus CBS712 strain was cultivated in defined medium with glucose and xylose as carbon source. Ethanol fermentation and sugar consumption of CBS712 were investigated under different oxygen supplies (1.75%, 11.00% and 20.95% of O2) and different temperatures (30°C and 41°C). By decreasing oxygen supply, independently from the temperature, both biomass production as well as sugar utilization rate were progressively reduced. In all the tested conditions xylose consumption followed glucose exhaustion. Therefore, xylose metabolism was mainly affected by oxygen depletion. Loss in cell viability cannot explain the decrease in sugar consumption rates, as demonstrated by single cell analyses, while cofactor imbalance is commonly considered as the main cause of impairment of the xylose reductase (KmXR) - xylitol dehydrogenase (KmXDH) pathway. Remarkably, when these enzyme activities were assayed in vitro, a significant decrease was observed together with oxygen depletion, not ascribed to reduced transcription of the corresponding genes. In the present study both oxygen supply and temperature were shown to be key parameters affecting the fermentation capability of sugars in the K. marxianus CBS712 strain. In particular, a direct correlation was observed between the decreased efficiency to consume xylose with the reduced specific activity of the two main enzymes (KmXR and KmXDH) involved in its catabolism. These data suggest that, in addition to the impairment of the oxidoreductive pathway being determined by the cofactor imbalance, post-transcriptional and/or post-translational regulation of the pathway enzymes contributes to the efficiency of xylose catabolism in micro-aerobic conditions. Overall, the presented work provides novel information on the fermentation capability of the CBS712 strain that is currently considered as the reference strain of the genus K. marxianus.

Structure and binding energy of the H2S dimer at the CCSD(T) complete basis set limit

NASA Astrophysics Data System (ADS)

Lemke, Kono H.

2017-06-01

This study presents results for the binding energy and geometry of the H2S dimer which have been computed using Møller-Plesset perturbation theory (MP2, MP4) and coupled cluster (CCSD, CCSD(T)) calculations with basis sets up to aug-cc-pV5Z. Estimates of De, EZPE, Do, and dimer geometry have been obtained at each level of theory by taking advantage of the systematic convergence behavior toward the complete basis set (CBS) limit. The CBS limit binding energy values of De are 1.91 (MP2), 1.75 (MP4), 1.41 (CCSD), and 1.69 kcal/mol (CCSD[T]). The most accurate values for the equilibrium S-S distance rSS (without counterpoise correction) are 4.080 (MP2/aug-cc-pV5Z), 4.131 (MP4/aug-cc-pVQZ), 4.225 (CCSD/aug-cc-pVQZ), and 4.146 Å (CCSD(T)/aug-cc-pVQZ). This study also evaluates the effect of counterpoise correction on the H2S dimer geometry and binding energy. As regards the structure of (H2S)2, MPn, CCSD, and CCSD(T) level values of rSS, obtained by performing geometry optimizations on the counterpoise-corrected potential energy surface, converge systematically to CBS limit values of 4.099 (MP2), 4.146 (MP4), 4.233 (CCSD), and 4.167 Å (CCSD(T)). The corresponding CBS limit values of the equilibrium binding energy De are 1.88 (MP2), 1.76 (MP4), 1.41 (CCSD), and 1.69 kcal/mol (CCSD(T)), the latter in excellent agreement with the measured binding energy value of 1.68 ± 0.02 kcal/mol reported by Ciaffoni et al. [Appl. Phys. B 92, 627 (2008)]. Combining CBS electronic binding energies De with EZPE predicted by CCSD(T) vibrational second-order perturbation theory calculations yields Do = 1.08 kcal/mol, which is around 0.6 kcal/mol smaller than the measured value of 1.7 ± 0.3 kcal/mol. Overall, the results presented here demonstrate that the application of high level calculations, in particular CCSD(T), in combination with augmented correlation consistent basis sets provides valuable insight into the structure and energetics of the hydrogen sulfide dimer.

Multi-temporal Scale Analysis of Environmental Control on Net Ecosystem Exchange of CO2 in Forest Ecosystems

NASA Astrophysics Data System (ADS)

Zhang, Mi; Yu, Guirui; Zhuang, Jie; Gentry, Randy; Koirala, Shesh; Zhang, Leiming; Sun, Xiaomin; Han, Shijie; Yan, Junhua

2013-04-01

Multi-temporal scale analysis of environmental control on forest ecosystem carbon budget is a basis for understanding the responses and adaptation of forest carbon cycle to climate change. In this study, we chose two typical forest ecosystems, Changbaishan temperate mixed forest (CBS) in northeastern China and Dinghushan subtropical evergreen broad-leaved forest (DHS) in southern China to identify the changes in environmental control on net ecosystem exchange of carbon dioxide (NEE) with the temporal scales. The analysis was made based on the flux and routine meteorological data measured during the period from 2005 to 2008. These time series data were analyzed using wavelet and cross wavelet transform. The results showed that NEE had significant daily and annual periodic variation in the two types of forest ecosystem. NEE at CBS and DHS showed semi-annual (176 days) and seasonal (88-104 days) periodic variations, respectively. Photosynthetically active radiation (PAR), vapor pressure deficient (VPD), air temperature (Ta), soil temperature (Ts, at 5-cm depth) controlled daily variation of NEE as indicated by the significant high common power of cross wavelet transform spectrums between NEE and these factors. Similarly, Ta, VPD, and precipitation (P) controlled annual variation of NEE at CBS. However, Ta, PAR, and soil water content (SWC, at 5-cm depth) dominated the annual variation of NEE at DHS. An anti-phase between NEE and PAR at daily scale in the two forest ecosystems demonstrated an agreement of the variation of NEE with PAR, with rising sunlight corresponding with increased net carbon uptake. At annual scale, phase angles between NEE and Ta and between NEE and P were -170° and 176°, respectively at CBS. At DHS, phase angle between NEE and VPD was smallest at annual scale. The results indicated that the peak of net carbon uptake seasonal variation and the peaks of P and Ta seasonal variations occurred at the same month at CBS. But, at DHS, seasonal variation of net carbon uptake was in agreement with that of VPD at annual scale. This study showed that wavelet analysis was an effective approach to identifying the temporal pattern of environmental control on carbon exchange between ecosystem and the atmosphere.

Hemizygosity of transsulfuration genes confers increased vulnerability against acetaminophen-induced hepatotoxicity in mice

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

Hagiya, Yoshifumi; Kamata, Shotaro; Mitsuoka, Saya

2015-01-15

The key mechanism for acetaminophen hepatotoxicity is cytochrome P450 (CYP)-dependent formation of N-acetyl-p-benzoquinone imine, a potent electrophile that forms protein adducts. Previous studies revealed the fundamental role of glutathione, which binds to and detoxifies N-acetyl-p-benzoquinone imine. Glutathione is synthesized from cysteine in the liver, and N-acetylcysteine is used as a sole antidote for acetaminophen poisoning. Here, we evaluated the potential roles of transsulfuration enzymes essential for cysteine biosynthesis, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), in acetaminophen hepatotoxicity using hemizygous (Cbs{sup +/−} or Cth{sup +/−}) and homozygous (Cth{sup −/−}) knockout mice. At 4 h after intraperitoneal acetaminophen injection, serum alaninemore » aminotransferase levels were highly elevated in Cth{sup −/−} mice at 150 mg/kg dose, and also in Cbs{sup +/−} or Cth{sup +/−} mice at 250 mg/kg dose, which was associated with characteristic centrilobular hepatocyte oncosis. Hepatic glutathione was depleted while serum malondialdehyde accumulated in acetaminophen-injected Cth{sup −/−} mice but not wild-type mice, although glutamate–cysteine ligase (composed of catalytic [GCLC] and modifier [GCLM] subunits) became more activated in the livers of Cth{sup −/−} mice with lower K{sub m} values for Cys and Glu. Proteome analysis using fluorescent two-dimensional difference gel electrophoresis revealed 47 differentially expressed proteins after injection of 150 mg acetaminophen/kg into Cth{sup −/−} mice; the profiles were similar to 1000 mg acetaminophen/kg-treated wild-type mice. The prevalence of Cbs or Cth hemizygosity is estimated to be 1:200–300 population; therefore, the deletion or polymorphism of either transsulfuration gene may underlie idiosyncratic acetaminophen vulnerability along with the differences in Cyp, Gclc, and Gclm gene activities. - Highlights: • Cbs{sup +/−}, Cth{sup +/−}, and especially Cth{sup −/−} mice were susceptible to APAP hepatic injury. • Hepatic glutathione became rapidly depleted upon APAP injection in Cth{sup −/−} mice. • Hepatic glutamate–cysteine ligase was activated by APAP injection and CTH deletion. • 2D DIGE identified 47 differentially expressed hepatic proteins by APAP injection. • Both transsulfuration enzymes are essential for protection against APAP injury.« less

Influence of Chlorine Substituents on Rates of Oxidation of Chlorinated Biphenyls by the Biphenyl Dioxygenase of Burkholderia sp. Strain LB400

PubMed Central

Arnett, Clint M.; Parales, Juan V.; Haddock, John D.

2000-01-01

Biphenyl dioxygenase from Burkholderia (Pseudomonas) sp. strain LB400 catalyzes the first reaction of a pathway for the degradation of biphenyl and a broad range of chlorinated biphenyls (CBs). The effect of chlorine substituents on catalysis was determined by measuring the specific activity of the enzyme with biphenyl and 18 congeners. The catalytic oxygenase component was purified and incubated with individual CBs in the presence of electron transport proteins and cofactors that were required for enzyme activity. The rate of depletion of biphenyl from the assay mixture and the rate of formation of cis-biphenyl 2,3-dihydrodiol, the oxidation product, were almost equal, indicating that the assay accurately measured enzyme-specific activity. Four classes of CBs were defined based on their oxidation rates. Class I contained 3-CB and 2,5-CB, which gave rates that were approximately twice that of biphenyl. Class II contained 2,5,3′,4′-CB, 2,3,2′,5′-CB, 2,3,4,5-CB, 2,3,2′,3′-CB, 2,4,5,2′,5′-CB, 2,5,3′-CB, 2,5,4′-CB, 2-CB, and 3,4,5-CB, which gave rates that ranged from 97 to 35% of the biphenyl rate. Class III contained only 2,3,4,2′,5′-CB, which gave a rate that was 4% of the biphenyl rate. Class IV contained 2,4,4′-CB, 2,4,2′,4′-CB, 3,4,5,2′-CB, 3,4,5,3′-CB, 3,5,3′,5′-CB, and 3,4,5,2′,5′-CB, which showed no detectable depletion. Rates were not significantly correlated with the aqueous solubilities of the CBs or the number of chlorine substituents on the rings. Oxidation products were detected for all class I, II, and III congeners and were identified as chlorinated cis-dihydrodiols for classes I and II. The specificity of biphenyl dioxygenase for the CBs examined in this study was determined by the relative positions of the chlorine substituents on the aromatic rings rather than the number of chlorine substituents on the rings. PMID:10877788

Modeling σ-Bond Activations by Nickel(0) Beyond Common Approximations: How Accurately Can We Describe Closed-Shell Oxidative Addition Reactions Mediated by Low-Valent Late 3d Transition Metal?

PubMed

Hu, Lianrui; Chen, Kejuan; Chen, Hui

2017-10-10

Accurate modelings of reactions involving 3d transition metals (TMs) are very challenging to both ab initio and DFT approaches. To gain more knowledge in this field, we herein explored typical σ-bond activations of H-H, C-H, C-Cl, and C-C bonds promoted by nickel(0), a low-valent late 3d TM. For the key parameters of activation energy (ΔE ‡ ) and reaction energy (ΔE R ) for these reactions, various issues related to the computational accuracy were systematically investigated. From the scrutiny of convergence issue with one-electron basis set, augmented (A) basis functions are found to be important, and the CCSD(T)/CBS level with complete basis set (CBS) limit extrapolation based on augmented double-ζ and triple-ζ basis pair (ADZ and ATZ), which produces deviations below 1 kcal/mol from the reference, is recommended for larger systems. As an alternative, the explicitly correlated F12 method can accelerate the basis set convergence further, especially after its CBS extrapolations. Thus, the CCSD(T)-F12/CBS(ADZ-ATZ) level with computational cost comparable to the conventional CCSD(T)/CBS(ADZ-ATZ) level, is found to reach the accuracy of the conventional CCSD(T)/A5Z level, which produces deviations below 0.5 kcal/mol from the reference, and is also highly recommendable. Scalar relativistic effects and 3s3p core-valence correlation are non-negligible for achieving chemical accuracy of around 1 kcal/mol. From the scrutiny of convergence issue with the N-electron basis set, in comparison with the reference CCSDTQ result, CCSD(T) is found to be able to calculate ΔE ‡ quite accurately, which is not true for the ΔE R calculations. Using highest-level CCSD(T) results of ΔE ‡ in this work as references, we tested 18 DFT methods and found that PBE0 and CAM-B3LYP are among the three best performing functionals, irrespective of DFT empirical dispersion correction. With empirical dispersion correction included, ωB97XD is also recommendable due to its improved performance.

PCB and DDE methyl sulfones in mammals from Canada and Sweden

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

Bergman, A.; Kuroki, Hiroaki; Norstrom, R.J.

1994-01-01

Levels of PCB methyl sulfones (MeSO[sub 2]-CBs) and DDE methyl sulfones (MeSO[sub 2]-DDEs) have been determined in tissues from polar bear (Ursus martimus), beluga whale (Delphinapterus leucas), and false killer whale (Pseudorca crassidens) from the Canadian environment, and grey seal (Halichoerus grypus), otter (Lutra lutra), and wild mink (Mustela vison) from the Swedish environment. Up to 30 MeSO[sub 2]-CB congeners and three MeSO[sub 2]-DdE isomers were shown to be present in the analyzed tissues. The concentration of total MeSO[sub 2]-CBs ranged from 0.1 to 21 [mu]g/g extracted lipids. 3-MeSO[sub 2]-2,5,2[prime],4[prime],5[prime]-penta-CB is the dominating MeSO[sub 2]-CB congener in all the analyzedmore » samples, but the corresponding 4-MeSO[sub 2]-CB also is present in high concentrations. A smaller number of MeSO[sub 2]-CBs, always dominated by the meta-substituted MeSO[sub 2]-CBs, were present in livers of grey seal, otter, and mink than in adipose tissue or muscle. In all studied mammals the concentration of MeSO[sub 2]-CBs were higher in liver than in blubber or muscle. Seven PCB congeners were identified as precursors of the PCB methyl sulfones: 2,4,2[prime],5[prime]-tetra-CB (CB-49),2,5,3[prime],4[prime]-tetra-CB (CB-70), 2,4,5,2[prime],5[prime]-penta-CB (CB-101),2,3,4,5,2[prime],5[prime]-penta-CB (CB-87),2,3,6,2[prime],4[prime],5[prime]-hexa-CB (CB-149),2,3,4,2[prime],3[prime],6[prime]-hexa-CB (CB-132), and 2,3,4,2[prime],5[prime]-hexa-CB (CB-141). All species except beluga whale contained 3-MeSO[sub 2]-4,4[prime]-DDE, but at a much lower concentration in mink and otter than in the other mammals. Polar bear and grey seal liver also contained 2-MeSO[sub 2]-4,4[prime]-DDE. The concentration of 2- and 3-MeSo[sub 2]-DDE ranged from 0.01 to 1.3 [mu]g/g extracted lipids.« less

Advances in Oculomotor and Vestibular Physiology

DTIC Science & Technology

1980-11-24

and nucleus reticularis tegmenti pontis in serving as an input to the flocculus and in mediating visual-vestibular interactions. Karten showed direct...demonstrated that the region in an around the Interstitial Nucleus of Cajal is important for the generation of torsional or rolling eye movements. 3...demonstrated that activity related to full field motion reaches the flocculus of mammals over mossy fiber Lnpits that arise from cells in nucleus

Summary Report on Visit to Departamento de Investigation Centro Ramon Y Cajal Madrid, Spain.

DTIC Science & Technology

1984-10-30

Over one hundred colonies of Gram negative bacteria ( Lactobacillus acidophilus ) were cultured at 380 C in Petri dishes for 72 hours. The inoculum...within the various laboratories. He was particularly excited about studies using Lactobacillus bacteria and the work involving Drosophila melanogaster...therapy (0-40 Gauss) caUsed a 40 %reduction in the number of Lactobacillus colonies. ........................ . . .. . .. . .. . .. . . RAT MODEL TO

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

Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

PubMed

Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

2015-08-01

There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Predicting protein subnuclear location with optimized evidence-theoretic K-nearest classifier and pseudo amino acid composition.

PubMed

Shen, Hong-Bin; Chou, Kuo-Chen

2005-11-25

The nucleus is the brain of eukaryotic cells that guides the life processes of the cell by issuing key instructions. For in-depth understanding of the biochemical process of the nucleus, the knowledge of localization of nuclear proteins is very important. With the avalanche of protein sequences generated in the post-genomic era, it is highly desired to develop an automated method for fast annotating the subnuclear locations for numerous newly found nuclear protein sequences so as to be able to timely utilize them for basic research and drug discovery. In view of this, a novel approach is developed for predicting the protein subnuclear location. It is featured by introducing a powerful classifier, the optimized evidence-theoretic K-nearest classifier, and using the pseudo amino acid composition [K.C. Chou, PROTEINS: Structure, Function, and Genetics, 43 (2001) 246], which can incorporate a considerable amount of sequence-order effects, to represent protein samples. As a demonstration, identifications were performed for 370 nuclear proteins among the following 9 subnuclear locations: (1) Cajal body, (2) chromatin, (3) heterochromatin, (4) nuclear diffuse, (5) nuclear pore, (6) nuclear speckle, (7) nucleolus, (8) PcG body, and (9) PML body. The overall success rates thus obtained by both the re-substitution test and jackknife cross-validation test are significantly higher than those by existing classifiers on the same working dataset. It is anticipated that the powerful approach may also become a useful high throughput vehicle to bridge the huge gap occurring in the post-genomic era between the number of gene sequences in databases and the number of gene products that have been functionally characterized. The OET-KNN classifier will be available at www.pami.sjtu.edu.cn/people/hbshen.

The Cajal School in the Peripheral Nervous System: The Transcendent Contributions of Fernando de Castro on the Microscopic Structure of Sensory and Autonomic Motor Ganglia

PubMed Central

de Castro, Fernando

2016-01-01

The fine structure of the autonomic nervous system was largely unknown at the beginning of the second decade of the 20th century. Although relatively anatomists and histologists had studied the subject, even the assays by the great Russian histologist Alexander Dogiel and the Spanish Nobel Prize laureate, Santiago Ramón y Cajal, were incomplete. In a time which witnessed fundamental discoveries by Langley, Loewi and Dale on the physiology of the autonomic nervous system, both reputed researchers entrusted one of their outstanding disciples to the challenge to further investigate autonomic structures: the Russian B.I. Lawrentjew and the Spanish Fernando de Castro developed new technical approaches with spectacular results. In the mid of the 1920’s, both young neuroscientists were worldwide recognized as the top experts in the field. In the present work we describe the main discoveries by Fernando de Castro in those years regarding the structure of sympathetic and sensory ganglia, the organization of the synaptic contacts in these ganglia, and the nature of their innervation, later materialized in their respective chapters, personally invited by the editor, in Wilder Penfield’s famous textbook on Neurology and the Nervous System. Most of these discoveries remain fully alive today. PMID:27147984

Expression of the Intermediate Filament Nestin in Gastrointestinal Stromal Tumors and Interstitial Cells of Cajal

PubMed Central

Tsujimura, Tohru; Makiishi-Shimobayashi, Chiaki; Lundkvist, Johan; Lendahl, Urban; Nakasho, Keiji; Sugihara, Ayako; Iwasaki, Teruo; Mano, Masayuki; Yamada, Naoko; Yamashita, Kunihiro; Toyosaka, Akihiro; Terada, Nobuyuki

2001-01-01

It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype. PMID:11238030

Biophysically based mathematical modeling of interstitial cells of Cajal slow wave activity generated from a discrete unitary potential basis.

PubMed

Faville, R A; Pullan, A J; Sanders, K M; Koh, S D; Lloyd, C M; Smith, N P

2009-06-17

Spontaneously rhythmic pacemaker activity produced by interstitial cells of Cajal (ICC) is the result of the entrainment of unitary potential depolarizations generated at intracellular sites termed pacemaker units. In this study, we present a mathematical modeling framework that quantitatively represents the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC operating over the physiological membrane potential range. The mathematical model presented here extends our recently developed biophysically based pacemaker unit modeling framework by including mechanisms necessary for coordinating unitary potential events, such as a T-Type Ca2+ current, Vm-dependent K+ currents, and global Ca2+ diffusion. Model simulations produce spontaneously rhythmic slow wave depolarizations with an amplitude of 65 mV at a frequency of 17.4 cpm. Our model predicts that activity at the spatial scale of the pacemaker unit is fundamental for ICC slow wave generation, and Ca2+ influx from activation of the T-Type Ca2+ current is required for unitary potential entrainment. These results suggest that intracellular Ca2+ levels, particularly in the region local to the mitochondria and endoplasmic reticulum, significantly influence pacing frequency and synchronization of pacemaker unit discharge. Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations.

Effects of Electroacupuncture on Interstitial Cells of Cajal (ICC) Ultrastructure and Connexin 43 Protein Expression in the Gastrointestinal Tract of Functional Dyspepsia (FD) Rats.

PubMed

Zhang, Guoshan; Xie, Shen; Hu, Wei; Liu, Yuer; Liu, Mailan; Liu, Mi; Chang, Xiaorong

2016-06-14

BACKGROUND Gastrointestinal motility disorder is the main clinical manifestation in functional dyspepsia (FD) patients. Electroacupuncture is effective in improving gastrointestinal motility disorder in FD; however, the underlying mechanism remains unclear. It has been demonstrated that interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract, and the pacemaker potential is transmitted to nearby cells through gap junctions between ICC or ICC and the smooth muscle. Therefore, this study aimed to assess the effects of electroacupuncture on ICC ultrastructure and expression of the gap junction protein connexin 43 (Cx43) in FD rats. MATERIAL AND METHODS The animals were randomized into 3 groups: control, model, and electroacupuncture. Electroacupuncture was applied at Zusanli (ST36) in the electroacupuncture group daily for 10 days, while no electroacupuncture was applied to model group animals. RESULTS Ultrastructure of ICC recovered normally in gastric antrum and small intestine specimens was improved, with Cx43 expression levels in these tissues significantly increased in the electroacupuncture group compared with the model group. CONCLUSIONS These findings indicated that electroacupuncture is effective in alleviating ICC damage and reduces Cx43 levels in FD rats, and suggest that ICC and Cx43 are involved in electroacupuncture treatment in rats with FD to improve gastrointestinal motility disorders.

C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal.

PubMed

Feng, Hua; Wang, Fang; Wang, Changmiao

2016-07-01

To study the c-Kit expression in the gallbladder of cholesterol lithogenic guinea pig model and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal (ICCs). A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with A. capillaris through intragastric administration, therapy group). Each group had 15 guinea pigs. The gallbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry staining, real-time PCR, and Western blot analyses. The effect of A. capillaris on ICCs was evaluated by muscle strip contraction experiments. C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group. Our results indicated that A. capillaris improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of in vitro guinea pig gallbladder muscle strips.

Measuring ECS Interaction with Biomembranes.

PubMed

Angelucci, Clotilde B; Sabatucci, Annalaura; Dainese, Enrico

2016-01-01

Understanding the correct interaction among the different components of the endocannabinoid system (ECS) is fundamental for a proper assessment of the function of endocannabinoids (eCBs) as signaling molecules. The knowledge of how membrane environment is able to modulate intracellular trafficking of eCBs and their interacting proteins holds a huge potential in unraveling new mechanisms of ECS modulation.Here, fluorescence resonance energy transfer (FRET) technique is applied to measure the binding affinity of ECS proteins to model membranes (i.e., large unilamellar vesicles, LUVs). In particular, we describe in details the paradigmatic example of the interaction of recombinant rat FAAH-ΔTM with LUVs constituted by 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC).

Fostering public cord blood banking and research in Canada.

PubMed

Isasi, Rosario; Dalpe, Gratien; Knoppers, Bartha M

2013-12-01

In June 2013, Canadian Blood Services (CBS) established the National Public Cord Blood Bank (NPCBB) accessible to Canadian and international patients and researchers. The NPCBB promotes efforts that contribute to research and improved clinical care by making units not suitable for banking or transplantation available for research. In the context of the NPCBB of the CBS, this article will focus on the practical tools (e.g., consent protocols) developed to optimize umbilical cord blood (UCB) banking and research while enabling ethical provenance of UCB stem cells. The Canadian approach represents an ideal model for comparison as it is a country in which the national public bank (and other regional/provincial public banks) coexists with private companies.

Early intranuclear replication of African swine fever virus genome modifies the landscape of the host cell nucleus.

PubMed

Simões, Margarida; Martins, Carlos; Ferreira, Fernando

2015-12-02

Although African swine fever virus (ASFV) replicates in viral cytoplasmic factories, the presence of viral DNA within the host cell nucleus has been previously reported to be essential for productive infection. Herein, we described, for the first time, the intranuclear distribution patterns of viral DNA replication events, preceding those that occur in the cytoplasmic compartment. Using BrdU pulse-labelling experiments, newly synthesized ASFV genomes were exclusively detected inside the host cell nucleus at the early phase of infection, both in swine monocyte-derived macrophages (MDMs) and Vero cells. From 8hpi onwards, BrdU labelling was only observed in ASFV cytoplasmic factories. Our results also show that ASFV specifically activates the Ataxia Telangiectasia Mutated Rad-3 related (ATR) pathway in ASFV-infected swine MDMs from the early phase of infection, most probably because ASFV genome is recognized as foreign DNA. Morphological changes of promyelocytic leukaemia nuclear bodies (PML-NBs), nuclear speckles and Cajal bodies were also found in ASFV-infected swine MDMs, strongly suggesting the viral modulation of cellular antiviral responses and cellular transcription, respectively. As described for other viral infections, the nuclear reorganization that takes place during ASFV infection may also provide an environment that favours its intranuclear replication events. Altogether, our results contribute for a better understanding of ASFV replication strategies, starting with an essential intranuclear DNA replication phase which induces host nucleus changes towards a successful viral infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of B2O3 content and sintering temperature on crystallization and microstructure of CBS glass-ceramic coatings

NASA Astrophysics Data System (ADS)

Li, Pengyang; Wang, Shubin; Liu, Jianggao; Feng, Mengjie; Yang, Xinwang

2015-11-01

Borosilicate glass-ceramics precursors with varying compositional ratios in the CaO-SiO2-B2O3 (CBS) system were synthesized by sol-gel method. The precursors were calcined at 1200 °C for 2 h to form glass powders. The glass-ceramics were prepared by overlaying glass slurries on the substrates before sintering at different temperatures. The as-prepared glasses and glass-ceramics were characterized by differential scanning calorimetry and X-ray diffraction. The crystallization activation energies (Ec) were calculated using the Kissinger method from DSC results. The morphology and crystallization behavior of the glass-ceramics were monitored by scanning electron microscopy. Both glass transition and crystallization temperatures decreased, however, the metastable zone increased. The Ec values of CBS glasses and glass-ceramics were 254.1, 173.2 and 164.4 kJ/mol with increasing B2O3 content, whereas that of the calcined G3 glass was 104.9 kJ/mol. Finally, the coatings were prepared at a low temperature (700 °C). The crystals that grew on the surface of multilayer coatings demonstrated heterogeneous surface nucleation and crystallization after heat-treatment from 700 °C to 850 °C for 4 h.

Genetic characterization of strains of Saccharomyces uvarum from New Zealand wineries.

PubMed

Zhang, Hanyao; Richards, Keith D; Wilson, Sandra; Lee, Soon A; Sheehan, Hester; Roncoroni, Miguel; Gardner, Richard C

2015-04-01

We present a genetic characterization of 65 isolates of Saccharomyces uvarum isolated from wineries in New Zealand, along with the complete nucleotide sequence of a single sulfite-tolerant isolate. The genome of the New Zealand isolate averaged 99.85% nucleotide identity to CBS7001, the previously sequenced strain of S. uvarum. However, three genomic segments (37-87 kb) showed 10% nucleotide divergence from CBS7001 but 99% identity to Saccharomyces eubayanus. We conclude that these three segments appear to have been introgressed from that species. The nucleotide sequence of the internal transcribed spacer (ITS) region from other New Zealand isolates were also very similar to that of CBS7001, and hybrids showed complete genetic compatibility for some strains, with tetrads giving four viable progeny that showed 2:2 segregations of marker genes. Some strains showed high tolerance to sulfite, with genetic analysis indicating linkage of this trait to the transcription factor FZF1, but not to SSU1, the sulfite efflux pump that it regulates in order to confer sulfite tolerance in Saccharomyces cerevisiae. The fermentation characteristics of selected strains of S. uvarum showed exceptionally good cold fermentation characteristics, superior to the best commercially available strains of S. cerevisiae. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Neuroglial Dialog Between Cannabinoids and Hemichannels

PubMed Central

Labra, Valeria C.; Santibáñez, Cristian A.; Gajardo-Gómez, Rosario; Díaz, Esteban F.; Gómez, Gonzalo I.; Orellana, Juan A.

2018-01-01

The formation of gap junctions was initially thought to be the central role of connexins, however, recent evidence had brought to light the high relevance of unopposed hemichannels as an independent mechanism for the selective release of biomolecules during physiological and pathological conditions. In the healthy brain, the physiological opening of astrocyte hemichannels modulates basal excitatory synaptic transmission. At the other end, the release of potentially neurotoxic compounds through astroglial hemichannels and pannexons has been insinuated as one of the functional alterations that negatively affect the progression of multiple brain diseases. Recent insights in this matter have suggested encannabinoids (eCBs) as molecules that could regulate the opening of these channels during diverse conditions. In this review, we discuss and hypothesize the possible interplay between the eCB system and the hemichannel/pannexon-mediated signaling in the inflamed brain and during event of synaptic plasticity. Most findings indicate that eCBs seem to counteract the activation of major neuroinflammatory pathways that lead to glia-mediated production of TNF-α and IL-1β, both well-known triggers of astroglial hemichannel opening. In contrast to the latter, in the normal brain, eCBs apparently elicit the Ca2+-activation of astrocyte hemichannels, which could have significant consequences on eCB-dependent synaptic plasticity. PMID:29662436

The texture, sensory properties and stability of cookies prepared with wax oleogels.

PubMed

Yılmaz, Emin; Öğütcü, Mustafa

2015-04-01

Shortening is the essential component of high quality baked foods. Its effects on dough structure formation and the desired final product attributes depend mostly on its solid fat content and β' crystalline polymorphs. Saturated and trans fatty acids present in shortening pose some important negative health considerations. Hence, alternative plastic fats with lower or zero quantity of saturated and trans fatty acids are in high demand. Oleogels are gel networks of liquid edible oils with no trans and very low saturated fatty acids. In this study, sunflower wax (SW) and beeswax (BW) oleogels of hazelnut oil were used in cookie preparation against commercial bakery shortening (CBS) as the control, to compare the textural, sensory and stability properties of the cookies. The basic chemical composition, textural properties, and some physical attributes of the cookies were compared. Sensory texture/flavor profile analysis (T/FPA) and consumer hedonic tests were also accomplished. Furthermore, the changes in cookie texture and stability were monitored during 30 day storage at room temperature. It was found out that in almost all properties, the oleogel cookies resembled CBS cookies. T/FPA results present detailed data for literature. Consumer hedonic scores indicated that oleogel cookies were better than CBS cookies and were also well accepted by consumers. Wax oleogels can be used as cookie shortening successfully.

The electronic and transport properties of monolayer transition metal dichalcogenides: a complex band structure analysis

NASA Astrophysics Data System (ADS)

Szczesniak, Dominik

Recently, monolayer transition metal dichalcogenides have attracted much attention due to their potential use in both nano- and opto-electronics. In such applications, the electronic and transport properties of group-VIB transition metal dichalcogenides (MX2 , where M=Mo, W; X=S, Se, Te) are particularly important. Herein, new insight into these properties is presented by studying the complex band structures (CBS's) of MX2 monolayers while accounting for spin-orbit coupling effects. By using the symmetry-based tight-binding model a nonlinear generalized eigenvalue problem for CBS's is obtained. An efficient method for solving such class of problems is presented and gives a complete set of physically relevant solutions. Next, these solutions are characterized and classified into propagating and evanescent states, where the latter states present not only monotonic but also oscillatory decay character. It is observed that some of the oscillatory evanescent states create characteristic complex loops at the direct band gaps, which describe the tunneling currents in the MX2 materials. The importance of CBS's and tunneling currents is demonstrated by the analysis of the quantum transport across MX2 monolayers within phase field matching theory. Present work has been prepared within the Qatar Energy and Environment Research Institute (QEERI) grand challenge ATHLOC project (Project No. QEERI- GC-3008).

World distribution of the T833C/844INS68 CBS in cis double mutation: a reliable anthropological marker.

PubMed

Pepe, G; Vanegas, O C; Rickards, O; Giusti, B; Comeglio, P; Brunelli, T; Marcucci, R; Prisco, D; Gensini, G F; Abbate, R

1999-02-01

Mild hyperhomocysteinemia is associated to mutations either in cystathionine beta-synthase (CBS) or in 5,10-methylenetetrahydrofolate reductase (MTHFR) genes. In 1995, Sebastio et al. characterized a 68 bp insertion in cis with the most common CBS mutation (T833C) detected in homocystinuric patients. Recently, this double mutation has been detected in Italian and North-American controls. Compared to a group of patients affected by coronary artery disease, North-American controls showed not statistically significant difference. Moreover, Italian controls displayed a microheterogeneity in the mutant allele frequency distribution depending on their geographical origin (North or South of Italy). Aim of our study was to evaluate the prevalence of the double in cis mutation in different populations. We studied 377 healthy subjects belonging to various human groups. Genomic DNA, extracted from peripheral blood samples, was amplified using specific primers; PCR fragments were digested with Bsr I restriction enzyme to detect the double mutation. Our data show a significant heterogeneity among the populations studied, therefore this mutation turned out to be a reliable anthropogenetic marker. The distribution of the double mutation will contribute, with other DNA polymorphisms, to evaluate the genetic admixture of mixed populations such as Afro-Americans.

Ultrastructural and chemotaxonomic analysis of a xylanolytic strain of Cryptococcus adeliensis isolated from sheep droppings in Spain.

PubMed

Velázquez, Encarna; del Villar, María; Grondona, Isabel; Monte, Enrique; González-Villa, Tomás

2006-09-01

Cryptococcus adeliensis was initially described as a psycrophilic species containing a single strain CBS 8351(T) isolated from decayed algae in Terre Adelie (Antartida). Later, a second strain of this species was isolated from an immunosuppressed patient affected by leukaemia in Germany and recently several strains from this species have been found in human patients and pigeon droppings of the same country. In this study, we isolated from sheep droppings in Spain a xylanolytic strain named LEVX01 that was phenotypically related to the strain CBS 8351(T) and showed a 100% similarity in the D1/D2 domain and 5.8S-ITS region sequences with respect to the remaining described strains of C. adeliensis. These findings suggest that this species has a wide geographical distribution and that the animal faeces are a common habitat for C. adeliensis. The chemotaxonomic analyses showed the absence of detectable amounts of xylose in the cell walls of the strains LEVX01 and CBS8351(T) in contrast to other Cryptococcus species. Interestingly, the ultrastructural study showed the presence of fimbriae in these two strains that could be involved in the attachment to the host cells and, as occurs in Candida albicans, they could also be a pathogenicity factor for the man.

Improved oil-off survivability of tapered roller bearings

NASA Technical Reports Server (NTRS)

Kreider, Gary E.; Lee, Peter W.

1987-01-01

The aim of this program is to improve the oil-off survivability of a tapered roller bearing when applied to a helicopter transmission, since the tapered bearing has shown a performance advantage in this application. However, the critical roller end-rib conjunction is vulnerable to damage in an oil-off condition. Three powdered metal materials were selected to use as the rib material for oil-off evaluation. These were: M2 steel to a 65% density, CBS 1000M 65% density, and CBS 1000M 75% density. The bearing styles tested were ribbed cone (inner race) and ribbed cup (outer race). Carburized solid CBS 600 was also used as a ribbed material for comparison of oil-off results. The tests were conducted at six speeds from 4000 rpm (0.26 million DN) through 37000 rpm (2.4 million DN).The ribbed cup style bearing achieved longer lives than the ribbed cone style. A standard bearing lasted only 10 minutes at 4000 rpm; however, the 30-min oil-off goal was achieved through 11000 rpm using the survivable ribbed cup bearing. The oil-off lives at 37000 rpm were less than 10 seconds. The grinding of the powder metal materials and surface preparation to achieve an open porosity is extremely critical to the oil-off performance of the powder metal component.

Estimation of community-level influenza-associated illness in a low resource rural setting in India.

PubMed

Saha, Siddhartha; Gupta, Vivek; Dawood, Fatimah S; Broor, Shobha; Lafond, Kathryn E; Chadha, Mandeep S; Rai, Sanjay K; Krishnan, Anand

2018-01-01

To estimate rates of community-level influenza-like-illness (ILI) and influenza-associated ILI in rural north India. During 2011, we conducted household-based healthcare utilization surveys (HUS) for any acute medical illness (AMI) in preceding 14days among residents of 28villages of Ballabgarh, in north India. Concurrently, we conducted clinic-based surveillance (CBS) in the area for AMI episodes with illness onset ≤3days and collected nasal and throat swabs for influenza virus testing using real-time polymerase chain reaction. Retrospectively, we applied ILI case definition (measured/reported fever and cough) to HUS and CBS data. We attributed 14days of risk-time per person surveyed in HUS and estimated community ILI rate by dividing the number of ILI cases in HUS by total risk-time. We used CBS data on influenza positivity and applied it to HUS-based community ILI rates by age, month, and clinic type, to estimate the community influenza-associated ILI rates. The HUS of 69,369 residents during the year generated risk-time of 3945 person-years (p-y) and identified 150 (5%, 95%CI: 4-6) ILI episodes (38 ILI episodes/1,000 p-y; 95% CI 32-44). Among 1,372 ILI cases enrolled from clinics, 126 (9%; 95% CI 8-11) had laboratory-confirmed influenza (A (H3N2) = 72; B = 54). After adjusting for age, month, and clinic type, overall influenza-associated ILI rate was 4.8/1,000 p-y; rates were highest among children <5 years (13; 95% CI: 4-29) and persons≥60 years (11; 95%CI: 2-30). We present a novel way to use HUS and CBS data to generate estimates of community burden of influenza. Although the confidence intervals overlapped considerably, higher point estimates for burden among young children and older adults shows the utility for exploring the value of influenza vaccination among target groups.

Effects of methionine supplementation on the expression of oxidative stress-related genes in acute heat stress-exposed broilers.

PubMed

Del Vesco, Ana Paula; Gasparino, Eliane; Grieser, Daiane de Oliveira; Zancanela, Vittor; Soares, Maria Amélia Menck; Neto, Adhemar Rodrigues de Oliveira

2015-02-28

The aim of the present study was to evaluate the effects of heat stress (HS) and methionine supplementation on the markers of stress and on the gene expression levels of uncoupling proteins (UCP), betaine-homocysteine methyltransferase (BHMT), cystathionine β-synthase (CBS), glutathione synthetase (GSS) and glutathione peroxidase 7 (GPx7). Broilers from 1 to 21 d and from 22 to 42 d of age were divided into three treatment groups related to methionine supplementation: without methionine supplementation (MD); recommended level of methionine supplementation (DL1); excess methionine supplementation (DL2). The broilers were either kept at a comfortable thermal temperature or exposed to HS (38°C for 24 h). During the starter period, we observed the effects of the interaction between diet and environment on the gene expression levels of UCP, BHMT and GSS. Higher gene expression levels of UCP and BHMT were observed in broilers that were maintained at thermal comfort conditions and received the MD diet. HS broilers fed the DL1 and DL2 diets had the highest expression level of GSS. The expression levels of the CBS and GPx7 genes were influenced by both the environment and methionine supplementation. During the grower period, the gene expression levels of BHMT, CBS, GSS and GPx7 were affected by the diet × environment interaction. A higher expression level of BHMT was observed in broilers maintained at thermal comfort conditions and on the MD diet. HS induced higher expression levels of CBS, GSS and GPx7 in broilers that received the DL1 and DL2 diets. The present results suggest that under HS conditions, methionine supplementation could mitigate the effects of stress, since methionine contributed to the increased expression levels of genes related to antioxidant activity.

Heat inactivation of wine spoilage yeast Dekkera bruxellensis by hot water treatment.

PubMed

Fabrizio, V; Vigentini, I; Parisi, N; Picozzi, C; Compagno, C; Foschino, R

2015-08-01

Cell suspensions of four Dekkera bruxellensis strains (CBS 2499, CBS 2797, CBS 4459 and CBS 4601) were subjected to heat treatment in deionized water at four different temperatures (55·0, 57·5, 60·0 and 62·5°C) to investigate their thermal resistance. The decimal reduction times at a specific temperature were calculated from the resulting inactivation curves: the D-values at 55·0°C ranged from 63 to 79·4 s, at 57·5°C from 39·6 to 46·1 s, at 60·0°C from 19·5 to 20·7 s, at 62·5°C from 10·2 to 13·7 s. The z-values were between 9·2 and 10·2°C, confirming that heat resistance is a strain-dependent character. A protocol for the sanitization of 225 l casks by immersion in hot water was set up and applied to contaminated 3-year-old barrels. The heat penetration through the staves was evaluated for each investigated temperature by positioning a thermal probe at 8 mm deep. A treatment at 60°C for an exposure time of 19 min allowed to eliminate the yeast populations up to a log count reduction of 8. Brettanomyces/Dekkera bruxellensis is the main yeast involved in red wine spoilage that occurs during ageing in barrel, generating considerable economic losses. Current sanitization protocols, performed using different chemicals, are ineffective due to the porous nature of the wood. The thermal inactivation of D. bruxellensis cells by hot water treatment proves to be efficacious and easy to perform, provided that the holding time at the killing temperature takes into account the filling time of the vessel and the time for the heat penetration into the wood structure. © 2015 The Society for Applied Microbiology.

Relationship of the MTHFD1 (rs2236225), eNOS (rs1799983), CBS (rs2850144) and ACE (rs4343) gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects.

PubMed

Khatami, Mehri; Ratki, Farzaneh Morteza; Tajfar, Saba; Akrami, Fatemeh

2017-09-01

Congenital heart defects are structural cardiovascular malformations that arise from abnormal formation of the heart or major blood vessels during the fetal period. To investigate the association of 4 single nucleotide polymorphisms (SNPs) in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients. In this case-control study, a total of 102 children with CHD and 98 control children were enrolled. Four SNPs including MTHFD1 G1958A, eNOS G894T, CBS C-4673G and ACE A2350G were genotyped by PCR-SSCP, Multiplex ARMS PCR and PCR-RFLP methods and confirmed by direct sequencing. We genotyped 102 patients and 98 controls for four polymorphisms by statistically analysis. There were three SNPs including MTHFD1 G1958A, eNOS G894T and ACE A2350G which might increase the risk of CHD, but CBS C-4673G was not significantly different between patients and controls. (P = 0.017, P = 0.048, P = 0.025 and P = 0.081 respectively). The allele frequencies of three SNPs for MTHFD1 G1958A, eNOS G894T and ACE A2350G in CHD are higher than that in control. Our results show that there is a significant relationship between MTHFD1 G1958A, eNOS G894T and ACE A2350G polymorphisms with CHD. Therefore, The AA and GA genotypes of MTHFD1 G1958A, TT and GT genotypes of eNOS G894T and the AA and GA genotypes of ACE A2350G are susceptible factors for CHD and may increase the risk of CHD. Copyright © 2017. Published by Elsevier Taiwan.

Molecular characterization of twelve patients affected by homocystinuria due to cystathionine beta-synthase deficiency: Report of two novel mutations

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

Sebastio, G.; Sperandeo, M.P.; Panico, M.

1994-09-01

Cystathionine beta-synthase (CBS) deficiency, an autosomal recessive disorder of sulfur amino acid metabolism (MIM 236200), causes homocystinuria and a clinical presentation involving eye, skeleton, central nervous and vascular systems. Less that 20 mutations of CBS gene have been characterized so far, G919A and T833C being the most commonly reported (36 and 9 out of 62 identified alleles, respectively). We have investigated 12 patients (10 Italians, 1 Jewish-French, 1 Italian-Spanish) and one allele of each patient has been characterized at least. T833C has been found in 7 independent alleles (6 in heterozygosity and 1 in homozygosity); G9191A, the most common mutationmore » in Irish and North-European patients, has never been detected in the present survey. C341T (previously reported in 1 Irish-German patient only) has been found in 3 patients in heterozygosity. Besides the two new mutations previously described, i.e. G374A and C770T, we have identified two additional new missense mutations: C869T, a transition in exon 8, causing a P290L amino acid substitution, and C262T, a transition in exon 2, causing a P88S amino acid change. In 4 additional Italian patients, none of the known mutations have been detected; in one of them, a 50 bp deletion has been found in intron 11. The deletion involves the entire sequence of the second element of a tandem repeat. Conclusions: T833C is the most common panethnic mutation; C341T is relatively widespread, while G919A appears to be restricted to North-European patients. Exons 3 and 8 of the CBS gene are the hot-spots of mutational events leading to CBS deficiency.« less

Gain and Bandwidth Enhancement of Ferrite-Loaded CBS Antenna Using Material Shaping and Positioning

NASA Astrophysics Data System (ADS)

Askarian Amiri, Mikal

Loading a cavity-backed slot (CBS) antenna with ferrite material and applying a biasing static magnetic field can be used to control its resonant frequency. Such a mechanism results in a frequency reconfigurable antenna. However, placing a lossy ferrite material inside the cavity can reduce the gain or negatively impact the impedance bandwidth. This thesis develops guidelines, based on a non-uniform applied magnetic field and non-uniform magnetic field internal to the ferrite specimen, for the design of ferrite-loaded CBS antennas which enhance their gain and tunable bandwidth by shaping the ferrite specimen and judiciously locating it within the cavity. To achieve these objectives, it is necessary to examine the influence of the shape and relative location of the ferrite material, and also the proximity of the ferrite specimen from the probe on the DC magnetic field and RF electric field distributions inside the cavity. The geometry of the probe and its impacts on figures-of-merit of the antenna is of interest as well. Two common cavity backed-slot antennas (rectangular and circular cross-section) were designed, and corresponding simulations and measurements were performed and compared. The cavities were mounted on 30 cm × 30 cm perfect electric conductor (PEC) ground planes and partially loaded with ferrite material. The ferrites were biased with an external magnetic field produced by either an electromagnet or permanent magnets. Simulations were performed using FEM-based commercial software, Ansys' Maxwell 3D and HFSS. Maxwell 3D is utilized to model the non-uniform DC applied magnetic field and non-uniform magnetic field internal to the ferrite specimen; HFSS however, is used to simulate and obtain the RF characteristics of the antenna. To validate the simulations they were compared with measurements performed in ASU's EM Anechoic Chamber. After many examinations using simulations and measurements, some optimal designs guidelines with respect to the gain, return loss and tunable impedance bandwidth, were obtained and recommended for ferrite-loaded CBS antennas.

Hypoxia regulates microRNA expression in the human carotid body

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

Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se; Lee, Kian Leong, E-mail: csilkl@nus.edu.sg; Kåhlin, Jessica

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentiallymore » regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.« less

The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

PubMed Central

Kalinina, Natalia O.; Makarova, Svetlana; Makhotenko, Antonida; Love, Andrew J.; Taliansky, Michael

2018-01-01

The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribose)polymerase (PARP), which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses. PMID:29479362

Derivation and characterization of gut-like structures from embryonic stem cells.

PubMed

Yamada, Takatsugu; Nakajima, Yoshiyuki

2006-01-01

Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages of all three embryonic germ layers in vitro. The hanging drop culture of ES cell suspension in the absence of leukemia inhibitory factor induces aggregation and differentiation of the cells into simple or cystic embryoid bodies (EBs). After 6 d of hanging drop culture, the resulting EBs are plated onto plastic dishes for the outgrowth culture. At d 21 after outgrowth culture, cell populations of EBs can give rise to three-dimensional gut-like structures that exhibit spontaneous contraction and highly coordinated peristalsis. The gut-like structures have large lumens surrounded by three layers: epithelium, lamina propria, and muscularis. Ganglia are scattered along the periphery, and interstitial cells of Cajal are distributed among the smooth muscle cells. The fundamental process of formation of the in vitro organized gut-like structures is similar to embryonic gastrointestinal development in vivo. The EBs at the 6-d egg-cylinder stage may have the potential to regulate developmental programs associated with cell lineage commitment and provide an appropriate microenvironment to differentiate ES cells into enteric derivatives of all three embryonic germ layers and reproduce the gut organization process in vitro.

Coelomic epithelium-derived cells in visceral morphogenesis.

PubMed

Ariza, Laura; Carmona, Rita; Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón

2016-03-01

Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. © 2015 Wiley Periodicals, Inc.

Thermochemistry and electronic structure of small boron clusters (B(n), n = 5-13) and their anions.

PubMed

Truong, Ba Tai; Grant, Daniel J; Nguyen, Minh Tho; Dixon, David A

2010-01-21

Thermochemical parameters of a set of small-sized neutral (B(n)) and anionic (B(n)(-)) boron clusters, with n = 5-13, were determined using coupled-cluster theory CCSD(T) calculations with the aug-cc-pVnZ (n = D, T, and Q) basis sets extrapolated to the complete basis set limit (CBS) plus addition corrections and/or G3B3 calculations. Enthalpies of formation, adiabatic electron affinities (EA), vertical (VDE), and adiabatic (ADE) detachment energies were evaluated. Our calculated EAs are in good agreement with recent experiments (values in eV): B(5) (CBS, 2.29; G3B3, 2.48; exptl., 2.33 +/- 0.02), B(6) (CBS, 2.59; G3B3, 3.23; exptl., 3.01 +/- 0.04), B(7) (CBS, 2.62; G3B3, 2.67; exptl., 2.55 +/- 0.05), B(8) (CBS, 3.02; G3B3, 3.11; exptl., 3.02 +/- 0.02), B(9) (G3B3, 3.03; exptl., 3.39 +/- 0.06), B(10) (G3B3, 2.85; exptl., 2.88 +/- 0.09), B(11) (G3B4, 3.48;, exptl., 3.43 +/- 0.01), B(12) (G3B3, 2.33; exptl., 2.21 +/- 0.04), and B(13) (G3B3, 3.62; exptl., 3.78 +/- 0.02). The difference between the calculated adiabatic electron affinity and the adiabatic detachment energy for B(6) is due to the fact that the geometry of the anion is not that of the ground-state neutral. The calculated adiabatic detachment energies to the (3)A(u), C(2h) and (1)A(g), D(2h) excited states of B(6), which have geometries similar to the (1)A(g), D(2h) state of B(6)(-), are 2.93 and 3.06 eV, in excellent agreement with experiment. The VDEs were also well reproduced by the calculations. Partitioning of the electron localization functions into pi and sigma components allows probing of the partial and local delocalization in global nonaromatic systems. The larger clusters appear to exhibit multiple aromaticity. The binding energies per atom vary in a parallel manner for both neutral and anionic series and approach the experimental value for the heat of atomization of B. The resonance energies and the normalized resonance energies are convenient indices to quantify the stabilization of a cluster of elements.

Comparative genomics of citric-acid producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

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

Grigoriev, Igor V.; Baker, Scott E.; Andersen, Mikael R.

2011-04-28

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compels additional exploration. We therefore undertook whole genome sequencing of the acidogenic A. niger wild type strain (ATCC 1015), and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence and half the telomeric regionsmore » have been elucidated. Moreover, sequence information from ATCC 1015 was utilized to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 megabase of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis revealed up-regulation of the electron transport chain, specifically the alternative oxidative pathway in ATCC 1015, while CBS 513.88 showed significant up-regulation of genes relevant to glucoamylase A production, such as tRNA-synthases and protein transporters. Our results and datasets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi.[Supplemental materials (10 figures, three text documents and 16 tables) have been made available. The whole genome sequence for A. niger ATCC 1015 is available from NBCI under acc. no ACJE00000000. The up-dated sequence for A. niger CBS 513.88 is available from EMBL under acc. no AM269948-AM270415. The sequence data from the phylogeny study has been submitted to NCBI (GU296686-296739). Microarray data from this study is submitted to GEO as series GSE10983. Accession for reviewers is possible through: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi token GSE10983] The dsmM_ANIGERa_coll511030F library and platform information is deposited at GEO under number GPL6758« less

HExpoChem: a systems biology resource to explore human exposure to chemicals.

PubMed

Taboureau, Olivier; Jacobsen, Ulrik Plesner; Kalhauge, Christian; Edsgärd, Daniel; Rigina, Olga; Gupta, Ramneek; Audouze, Karine

2013-05-01

Humans are exposed to diverse hazardous chemicals daily. Although an exposure to these chemicals is suspected to have adverse effects on human health, mechanistic insights into how they interact with the human body are still limited. Therefore, acquisition of curated data and development of computational biology approaches are needed to assess the health risks of chemical exposure. Here we present HExpoChem, a tool based on environmental chemicals and their bioactivities on human proteins with the objective of aiding the qualitative exploration of human exposure to chemicals. The chemical-protein interactions have been enriched with a quality-scored human protein-protein interaction network, a protein-protein association network and a chemical-chemical interaction network, thus allowing the study of environmental chemicals through formation of protein complexes and phenotypic outcomes enrichment. HExpoChem is available at http://www.cbs.dtu.dk/services/HExpoChem-1.0/.

Preclinical Polymodal Hallucinations for 13 Years before Dementia with Lewy Bodies

PubMed Central

Abbate, Carlo; Trimarchi, Pietro Davide; Inglese, Silvia; Viti, Niccolò; Cantatore, Alessandra; De Agostini, Lisa; Pirri, Federico; Marino, Lorenza; Bagarolo, Renzo

2014-01-01

Objective. We describe a case of dementia with Lewy bodies (DLB) that presented long-lasting preclinical complex polymodal hallucinations. Background. Few studies have deeply investigated the characteristics of hallucinations in DLB, especially in the preclinical phase. Moreover, the clinical phenotype of mild cognitive impairment-(MCI-) DLB is poorly understood. Methods. The patient was followed for 4 years and a selective phenomenological and cognitive study was performed at the predementia stage. Results. The phenomenological study showed the presence of hypnagogic and hypnopompic hallucinations that allowed us to make a differential diagnosis between DLB and Charles Bonnet syndrome (CBS). The neuropsychological evaluation showed a multiple domain without amnesia MCI subtype with prefrontal dysexecutive, visuoperceptual, and visuospatial impairments and simultanagnosia, which has not previously been reported in MCI-DLB. Conclusions. This study extends the prognostic value of hallucinations for DLB to the preclinical phases. It supports and refines the MCI-DLB concept and identifies simultanagnosia as a possible early cognitive marker. Finally, it confirms an association between hallucinations and visuoperceptual impairments at an intermediate stage of the disease course and strongly supports the hypothesis that hallucinations in the earliest stages of DLB may reflect a narcolepsy-like REM-sleep disorder. PMID:24868122

Candida laoshanensis sp. nov. and Candida qingdaonensis sp. nov., anamorphic, ascomycetous yeast species isolated from decayed wood.

PubMed

Wang, Shi-An; Li, Fu-Li; Bai, Feng-Yan

2010-07-01

During a study of newly isolated yeast strains utilizing d-xylose as sole carbon source, eight strains, isolated from decayed wood, were found to represent two novel anamorphic, ascomycetous yeast species based on sequence analysis of the 26S rDNA D1/D2 domain and internal transcribed spacer region, and phenotypic characterization. The names Candida laoshanensis sp. nov. (type strain MLRW 6-2(T)=AS 2.4030(T)=CBS 11389(T)) and Candida qingdaonensis sp. nov. (type strain MLRW 7-1(T)=AS 2.4031(T)=CBS 11390(T)) are proposed for these two novel species; the closest relatives of the two novel species are Candida pomicola and Candida marilandica, respectively.

An automated exploration of the isomerization and dissociation pathways of (E)-1,2-dichloroethene cations and anions

NASA Astrophysics Data System (ADS)

Kishimoto, Naoki; Nishi, Yuito

2017-04-01

Isomerization and dissociation pathways after the photoionization or electron attachment of (E)-1,2-dichloroethene were calculated with an automated exploration method utilizing a scaled hypersphere search of the anharmonic downward distortion following algorithm at the UB3LYP/6-311G(2d,d,p) level of theory. The potential energies of transition states and dissociation channels were calculated by a composite method ((RO)CBS-QB3) and compared with the breakdown diagrams and electron attachment spectra observed in previous spectroscopic studies. The results of single point calculations with several DFT and post-SCF methods are compared using the root mean square deviations from the (RO)CBS-QB3 energies for six states of anionic dichloroethene.

Applying the health belief model to examine news coverage regarding steroids in sports by ABC, CBS, and NBC between March 1990 and May 2008.

PubMed

Quick, Brian L

2010-04-01

The investigation described here examined ABC, CBS, and NBC news coverage of steroids in sports between March 1990 and May 2008. Employing a framing analysis guided by the health belief model (HBM), coverage of the barriers and benefits of using steroids is reported. Overall, the trend by these three news affiliates was to emphasize the illegality of using steroids, whereas considerably less coverage was devoted to the health costs, in terms of both severity and susceptibility, of using steroids. Furthermore, of the health costs reported, the specific consequences of steroid use varied considerably. The results are reported across four timeframes: 1990-2008, 1990-1996, 1997-2002, and 2003-2008.

Chemical Composition and Medicinal Value of Fruiting Bodies and Submerged Cultured Mycelia of Caterpillar Medicinal Fungus Cordyceps militaris CBS-132098 (Ascomycetes).

PubMed

Chan, Jannie Siew Lee; Barseghyan, Gayane S; Asatiani, Mikheil D; Wasser, Solomon P

2015-01-01

In this paper, we report the results of a proximate analysis (i.e., moisture, ash, protein, fat, carbohydrates, and energy); a bioactive compounds analysis (i.e., cordycepin and ergothioneine); fatty and amino acid analysis; and analyses of vitamin content, macro- and microelement composition of fruiting body (FB), and mycelial biomass (MB) of medicinal caterpillar fungus Cordyceps militaris strain CBS-132098. These results demonstrate that the FB and MB of C. militaris are good sources of proteins: 59.8% protein content in the FB and 39.5% in the MB. The MB was distinguished by its carbohydrate content (39.6%), which was higher than that of the FB (29.1% carbohydrate). In the FB of C. militaris, the total amino acid content was 57.39 mg/g and in the MB it was 24.98 mg/g. The quantification of the identified fatty acids indicated that palmitic acid, oleic acid, linoleic acid, and linolenic acid were the major fatty acids. The micro- and macroelement compositions were studied. The highest results were calcium (797 mg/kg FB; 11 mg/kg MB); potassium (15,938 mg/kg FB 12,183 mg/kg MB); magnesium (4,227 mg/kg FB; 3,414 mg/kg MB); sodium (171 mg/kg FB; 1,567 mg/kg MB); phosphorus (7,196 mg/kg FB; 14,293 mg/kg MB); and sulfur (5,088 mg/kg FB; 2,558 mg/kg MB). The vitamin composition was studied, and the most abundant vitamins were vitamin A, vitamin B3, and vitamin E. The bioactive components were cordycepin, cordycepic acid (D-mannitol), and ergothioneine. There were differences in cordycepin and ergothioneine contents between the FB and the MB. The cordycepin concentration was 0.11% in the FB and 0.182% in the MB, the cordycepic acid was 4.7 mg/100g in the FB and 5.2 mg/100 g in the MB, and the ergothioneine content was 782.37 mg/kg in the FB and 130.65 mg/kg in the MB. The nutritional values of the FB and the MB of C. militaris detected indicate its potential use in well-balanced diets and sources of bioactive compounds.

Insect Optic Glomeruli: Exploration of a Universal Circuit for Sensorimotor Processing

DTIC Science & Technology

2012-01-20

based  on  an  algorithm   published  by  Cohen...Cajal,  SR,  Sánchez  D  (1915)  Contribucion  al   conocimiento  de  los  centros  nerviosos   de  los  insectos...Drosophila   revealed  by  green  fluorescent  protein-­‐ based  Ca2+  imaging.  J  Neurosci  24:   6507–6514.    

[Convergence nystagmus and vertical gaze palsy of vascular origin].

PubMed

Jouvent, E; Benisty, S; Fenelon, G; Créange, A; Pierrot-Deseilligny, C

2005-05-01

A case of convergence-retraction nystagmus with upward vertical gaze paralysis and skew deviation (right hypotropia), without any other neurological signs, is reported. The probably vascular lesion was located at the mesodiencephalic junction, lying between the right border of the posterior commissure, the right interstitial nucleus of Cajal and the periaqueductal grey matter, accounting for the three ocular motor signs. The particular interest of this case is due to the relative smallness of the lesion.

Neuron Learning to Network Organization.

DTIC Science & Technology

1983-12-20

02912 N 0-8 1t COTOLIGOF 1HV AflRS 12. REPORT OATE Pesne an ann Research Program December 20, 1983 Office of Naval Research , Code 442PT 13. NUMBER...visual cortc\\ from R. Cajal, Histologie du Systete Nerveux. mostly hard-wired and perform a great variety of control functions took hundreds of millions of...certain sense there is much that is known. A set of coupled non -linear differential equations. including time delays, can be written down that in

Effects of Electroacupuncture on Interstitial Cells of Cajal (ICC) Ultrastructure and Connexin 43 Protein Expression in the Gastrointestinal Tract of Functional Dyspepsia (FD) Rats

PubMed Central

Zhang, Guoshan; Xie, Shen; Hu, Wei; Liu, Yuer; Liu, Mailan; Liu, Mi; Chang, Xiaorong

2016-01-01

Background Gastrointestinal motility disorder is the main clinical manifestation in functional dyspepsia (FD) patients. Electroacupuncture is effective in improving gastrointestinal motility disorder in FD; however, the underlying mechanism remains unclear. It has been demonstrated that interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract, and the pacemaker potential is transmitted to nearby cells through gap junctions between ICC or ICC and the smooth muscle. Therefore, this study aimed to assess the effects of electroacupuncture on ICC ultrastructure and expression of the gap junction protein connexin 43 (Cx43) in FD rats. Material/Methods The animals were randomized into 3 groups: control, model, and electroacupuncture. Electroacupuncture was applied at Zusanli (ST36) in the electroacupuncture group daily for 10 days, while no electroacupuncture was applied to model group animals. Results Ultrastructure of ICC recovered normally in gastric antrum and small intestine specimens was improved, with Cx43 expression levels in these tissues significantly increased in the electroacupuncture group compared with the model group. Conclusions These findings indicated that electroacupuncture is effective in alleviating ICC damage and reduces Cx43 levels in FD rats, and suggest that ICC and Cx43 are involved in electroacupuncture treatment in rats with FD to improve gastrointestinal motility disorders. PMID:27297942

Biophysically Based Mathematical Modeling of Interstitial Cells of Cajal Slow Wave Activity Generated from a Discrete Unitary Potential Basis

PubMed Central

Faville, R.A.; Pullan, A.J.; Sanders, K.M.; Koh, S.D.; Lloyd, C.M.; Smith, N.P.

2009-01-01

Abstract Spontaneously rhythmic pacemaker activity produced by interstitial cells of Cajal (ICC) is the result of the entrainment of unitary potential depolarizations generated at intracellular sites termed pacemaker units. In this study, we present a mathematical modeling framework that quantitatively represents the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC operating over the physiological membrane potential range. The mathematical model presented here extends our recently developed biophysically based pacemaker unit modeling framework by including mechanisms necessary for coordinating unitary potential events, such as a T-Type Ca2+ current, Vm-dependent K+ currents, and global Ca2+ diffusion. Model simulations produce spontaneously rhythmic slow wave depolarizations with an amplitude of 65 mV at a frequency of 17.4 cpm. Our model predicts that activity at the spatial scale of the pacemaker unit is fundamental for ICC slow wave generation, and Ca2+ influx from activation of the T-Type Ca2+ current is required for unitary potential entrainment. These results suggest that intracellular Ca2+ levels, particularly in the region local to the mitochondria and endoplasmic reticulum, significantly influence pacing frequency and synchronization of pacemaker unit discharge. Moreover, numerical investigations show that our ICC model is capable of qualitatively replicating a wide range of experimental observations. PMID:19527643

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

PubMed Central

Zhang, Wenyi; Zhu, Zhaojin; Xie, Bin; Yu, Jun

2017-01-01

Background This study aimed to evaluate the therapeutic effects of abdominal manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI), investigating interstitial cells of Cajal (ICCs) and related c-kit expression. Methods Model rats were divided as SCI and SCI with drug treatment (intragastric mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were evaluated. Morphological structure of spinal cord and colon tissues were examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit expression. Results In SCI rats, AMT could not restore BBB, but it significantly increased weight, shortened time to defecation, increased feces amounts, and improved fecal pellet traits and colon histology. AMT improved the number, distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI + HMT group showed better therapeutic effect in improving intestinal transmission function and promoting c-kit expression. Conclusions AMT is an effective therapy for recovery of intestinal transmission function. It could repair ICCs and increase c-kit expression in colon tissues after SCI, in a frequency-dependent and pressure-dependent manner. PMID:29349063

Decreased number of interstitial cells of Cajal play an important role in the declined intestinal transit during cholesterol gallstone formation in guinea pigs fed on high cholesterol diet

PubMed Central

Fan, Ying; Wu, Shuo-Dong; Fu, Bei-Bei; Weng, Chao; Wang, Xin-Peng

2014-01-01

To study the changes of interstitial cells of Cajal (ICCs) and expression of c-kt and scf mRNA in terminal ileum tissue during cholesterol gallstone formation in guinea pigs fed on high cholesterol diet, forty guinea pigs were divided into the gallstone group and the control group. The animals in the gallstone group were fed on a high cholesterol diet (HCD), while those in the control group fed on a standard diet (StD). The guinea pigs were sacrificed at the 8th week. The expression of c-kit and scf in terminal ileum were determined by RT-PCR and the morphological characteristics and number of ICCs were observed and calculated by using immunohistochemistry. RT-PCR showed that, compared with the control group, the c-kit and scf mRNA expression levels in the gallstone group were significantly declined. In the animal assay, the decreased number of ICCs was present obviously in the gallstone group. We concluded from the study that decreased number of ICCs, decreased expression of c-kit and scf in terminal ileum are present in guinea pigs fed on high cholesterol diet. The c-kit/scf pathway inhibition might be involved in the decline of intestinal transit function during cholesterol gallstone formation. PMID:24995081

TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal.

PubMed

Ren, Keyu; Yong, Chunming; Yuan, Hao; Cao, Bin; Zhao, Kun; Wang, Jin

2018-01-01

Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.

Distribution and morphological characteristics of the interstitial cells of Cajal in the ileocaecal junction of the guinea-pig.

PubMed

Miyamoto-Kikuta, Sachiko; Ezaki, Taichi; Komuro, Terumasa

2009-10-01

The guinea-pig ileocaecal junction including the valve was studied by immunohistochemistry to clarify the organization of the muscle bundles, the enteric nerves and the interstitial cells of Cajal (ICC). This region clearly exhibited characteristic features in the distribution patterns of ICC in a proximal to distal direction: (1) the thickened portion of the terminal ileum immediately adjacent to the ileocecal junction contained many ICC throughout the circular (ICC-CM) and longitudinal (ICC-LM) muscle layers, but ICC were few or absent in the rest of the ileum; (2) the ileal side of the valve contained ICC associated with the deep muscular plexus (ICC-DMP) as in the small intestine, whereas ICC-DMP were absent in the caecal side as in the caecum; (3) the valve contained many ICC-CM and ICC-LM in both the ileal and caecal sides; (4) many ICC associated with the myenteric plexus were observed in both the ileal and caecal sides of the valve, whereas they were only sparsely found in the caecum; (5) ICC were also observed around the submucosal plexus in a confined area of the terminal ileum and the ileocaecal valve. These observations provide morphological evidence that the terminal ileum and ileocaecal valve are specially equipped for their active involvement in the movement of the junctional area.

Carbachol regulates pacemaker activities in cultured interstitial cells of Cajal from the mouse small intestine.

PubMed

So, Keum Young; Kim, Sang Hun; Sohn, Hong Moon; Choi, Soo Jin; Parajuli, Shankar Prasad; Choi, Seok; Yeum, Cheol Ho; Yoon, Pyung Jin; Jun, Jae Yeoul

2009-05-31

We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and Ca2+-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of-70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents. The effects of carbachol were blocked by 1-dimethyl-4-diphenylacetoxypiperidinium, a muscarinic M(3) receptor antagonist, but not by methotramine, a muscarinic M(2) receptor antagonist. Intracellular GDP-beta-S suppressed the carbachol-induced effects. Carbachol-induced effects were blocked by external Na+-free solution and by flufenamic acid, a non-selective cation channel blocker, and in the presence of thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum. However, carbachol still produced tonic inward pacemaker currents with the removal of external Ca2+. In recording of intracellular Ca2+ concentrations using fluo 3-AM dye, carbachol increased intracellular Ca2+ concentrations with increasing of Ca2+ oscillations. These results suggest that carbachol modulates the pacemaker activity of ICC through the activation of non-selective cation channels via muscarinic M(3) receptors by a G-protein dependent intracellular Ca2+ release mechanism.

Development of layer 1 neurons in the mouse neocortex.

PubMed

Ma, Jian; Yao, Xing-Hua; Fu, Yinghui; Yu, Yong-Chun

2014-10-01

Layer 1 of the neocortex harbors a unique group of neurons that play crucial roles in synaptic integration and information processing. Although extensive studies have characterized the properties of layer 1 neurons in the mature neocortex, it remains unclear how these neurons progressively acquire their distinct morphological, neurochemical, and physiological traits. In this study, we systematically examined the dynamic development of Cajal-Retzius cells and γ-aminobutyric acid (GABA)-ergic interneurons in layer 1 during the first 2 postnatal weeks. Cajal-Retzius cells underwent morphological degeneration after birth and gradually disappeared from layer 1. The majority of GABAergic interneurons showed clear expression of at least 1 of the 6 distinct neurochemical markers, including Reelin, GABA-A receptor subunit delta (GABAARδ), neuropeptide Y, vasoactive intestinal peptide (VIP), calretinin, and somatostatin from postnatal day 8. Furthermore, according to firing pattern, layer 1 interneurons can be divided into 2 groups: late-spiking (LS) and burst-spiking (BS) neurons. LS neurons preferentially expressed GABAARδ, whereas BS neurons preferentially expressed VIP. Interestingly, both LS and BS neurons exhibited a rapid electrophysiological and morphological development during the first postnatal week. Our results provide new insights into the molecular, morphological, and functional developments of the neurons in layer 1 of the neocortex. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease

PubMed Central

Wang, Jian; Mou, Yaru; Zhang, Qiangye; Zhang, Fan; Yang, Hongchao; Zhang, Wentong; Li, Aiwu

2013-01-01

Purpose The aim of this study was to investigate the expression and significance of neuroligins in myenteric cells of Cajal (ICC-MY) in Hirschsprung’s disease (HSCR). Methods Longitudinal muscle with adherent myenteric plexus (LMMP) from surgical excision waste colon of HSCR children were prepared by peeling off the mucous layer, sub-mucosal layer and circular muscle. Neuroligins, c-Kit (c-Kit-immunoreactivity representing ICC) and their relationship were assessed by double labeling immunofluorescence staining. ICC-MY were dissociated and cultured from LMMP by enzymolysis method, and were purified and analyzed using a combination of magnetic-activated cell sorting (MACS) and flow cytometry (FCM). Western-blot analysis was applied to compare and evaluate the expression levels of neuroligins in ICC-MY which were dissociated from different segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment). Results Neuroligins and c-Kit were expressed on the same cells (ICC-MY); ICC-MY were dissociated, cultured and purified. For HSCR, neuroligins were expressed significantly in ICC-MY from ganglionic colonic segments, moderately in those from transitional colonic segments and down-regulated significantly in those from aganglionic colonic segments. Conclusions Neuroligins were expressed in ICC-MY of human beings, and the expression varies from different segments of HSCR. This abnormal expression might play an important role in the pathogenesis of this disease through affecting the synaptic function of ICC-MY. PMID:23840625