bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Role of Glia in Cognitive Impairment in Schizophrenia
Authors: Mitterauer Bernhard J.
Published: June 2011

Cognitive impairment is a core disorder of the schizophrenia syndrome. Based on glial‐neuronal interactions, a pathophysiological model is proposed that could be explanatory for cognitive impairment in schizophrenia. The model consists of three main hypotheses concerning the pathophysiology in tripartite synapses, oligodendrocyte‐axonic interactions, and in the glial networks (astrocytic syncytium). In tripartite synapses nonfunctional astrocytic receptors may cause an unconstrained synaptic information flux, since they cannot be occupied by neurotransmitters (NTs). Therefore, a generalization of information processing may occur in the brain causing hallucinations, delusions, and thought disorder. If the oligodendrocyte‐axonic system decomposes, the brain is unable to process information in qualitative domains or categories. This may lead to severe incoherence phenomena such as thought disorder. Supposing that in the astrocytic syncytium gap junctions (g.js) normally form plaques functioning as memory devices, loss of function of g.j. may also cause cognitive impairment, since the syncytium decomposes and g.j. plaques cannot be generated. These hypotheses are experimentally testable. Finally, the problem of treatment of patients with schizophrenia is discussed, in case the presented model of schizophrenia might be verified.
Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis
Authors: Nagao Yoshihiro , Akahoshi Tomohiko , Kamori Masahiro , Uehara Hideo , Hashimoto Naotaka , Kinjo Nao , Shirabe Ken , Taketomi Akinobu , Tomikawa Morimasa , Hashizume Makoto , Maehara Yoshihiko
Published: June 2011

Aim:  Liver cirrhosis clinically shows thrombocytopenia and hypersplenism. Although splenectomy is performed to achieve higher platelet count and better hemostasis, the effect of splenectomy for liver cirrhosis remains unclear. The aim of the present study that was focused on serotonin was to investigate the relationship between splenectomy and liver regeneration in rats with secondary biliary cirrhosis.

Methods:  Liver cirrhosis was induced in Sprague–Dawley rats by bile duct ligation (BDL). In addition, splenectomy and administration of ketanserin, which selectively antagonizes 5‐HT2A and 2B serotonin receptors, were performed. Three weeks after the interventions, whole blood, plasma, serum, and liver specimens were obtained for the following studies: peripheral platelet counts, hemodynamics of serotonin, histopathological examination, immunostaining, and quantification of mRNA expression.

Results:  Splenectomy induced thrombocytosis, and increased serotonin content in cirrhotic liver. Stimulation of liver regeneration was indicated by the following parameters: hepatocyte ratio to the entire liver area, Ki67‐positive hepatocyte count, and expression of phosphorylated extracellular signal‐regulated kinases. This enhancement of liver regeneration was negated by ketanserin.

Conclusion:  Our results showed that splenectomy promoted liver regeneration by increasing serotonin content in liver even under cirrhotic conditions.
Clarification of interspousal hepatitis C virus infection in acute hepatitis C patients by molecular evolutionary analyses: Consideration on sexual and non‐sexual transmission between spouses
Authors: Nakamura Ikuo , Tanaka Yasuhito , Ochiai Kaori , Moriyasu Fuminori , Mizokami Masashi , Imawari Michio
Published: June 2011

Aim:  Previous studies evaluating the possibilities of interspousal sexual transmission of hepatitis C virus (HCV) have yielded many conflicting results. The aim of this study was to clarify the source of HCV infection in acute hepatitis C patients using phylogenetic analyses of nucleotide sequences of HCV E1 region.

Methods:  Four acute hepatitis C patients were hospitalized in 2002–2007. The diagnosis was based on medical records, laboratory tests including HCV markers, and ultrasonographic examination of the liver. In each spouse of four patients, serum HCV antibody was assayed. In the subjects whose serum HCV antibody was positive, additional tests on HCV viral load and genotype were carried out. Then phylogenetic analyses of nucleotide sequences of partial HCV E1 region (440 nucleotides) of the patients and their spouses were performed.

Results:  Hepatitis C virus antibody changed from negative to positive in the course of hospitalization and HCV RNA could be detected in every patient. Therefore they were diagnosed as acute hepatitis caused by HCV infection. In every spouse of four patients, HCV antibody and HCV RNA were positive. Three of four couples had the identical genotype and homogeneity of nucleotide sequences of HCV E1 region in three couples ranged from 97.9% to 100%. The results of phylogenic analyses suggested that interspousal HCV infection occurred in the three couples.

Conclusion:  In conclusion, interspousal infection might be one of the important sources of acute HCV infection in Japan. The usefulness of phylogenetic analysis of nucleotide sequences of HCV E1 region for clarifying interspousal HCV infection was validated.
A-Site and B-Site Non-stoichiometry and Sintering Characteristics of (Sr1−xLax)1−yTi1−zO3 Perovskites
Authors: Mori Masashi , Wang Zhenwei , Itoh Takanori , Yabui Shintarou , Murai Kei-ichiro , Moriga Toshihiro
Published: June 2011

The A-Site and B-Site non-stoichiometry and sintering characteristics of (Sr1−xLax)1−yTi1−zO3 perovskites were studied using samples prepared by solid-state mixing. A-Site or B-Site deficiency was observed for La-doped SrTiO3 perovskites, and this increased with increasing La content. For A-Site deficient (Sr1−xLax)1−yTiO3 perovskites, the cell volumes decreased although the reverse was observed for B-Site deficient (Sr1−xLax)Ti1−zO3 perovskites. This may be related to number of B-Site vacancies in the perovskites through charge compensation. It was found that A-Site and B-Site deficiencies increase the density of (Sr1−xLax)1−yTi1−zO3 perovskites. These characteristics may prove useful in the development of solid oxide fuel cell interconnect materials.
Microstructure and Surface Treatment of 304 Stainless Steel for Electronic Packaging
Authors: Sha Chu-Hsuan , Lee Chin C.
Published: June 2011

A fundamental study is carried out to investigate the microstructure and surface treatment possibilities of 304 stainless steel (304SS) substrates. To expose the microstructure, mirror-finished 304SS is applied with a self-mixed etchant containing ammonium sulfite ((NH4)2SO3), iron chloride (FeCl3), hydrochloric acid (HCl), and nitric acid (HNO3). Scanning electron microscope (SEM) images exhibit quite clear rocky-wall-like structure. Grain boundaries are clearly observed. Each grain contains many subgrains and the average grain size is 10 μm. Energy dispersive X-ray analysis determines the composition as 69 wt. % iron (Fe), 19 wt. % chromium (Cr), 10 wt. % nickel (Ni), around 2 wt. % manganese (Mn), and less than 0.08 wt. % carbon (C), which agrees well with the data provided by the manufacturer. Diffraction peaks produced by X-ray diffraction (XRD) are able to correspond to profiles found in XRD database, showing that 304SS has face-centered cubic crystal lattice. The Ni strike technique is used as surface treatment to make 304SS bondable to other metals, such as silver (Ag), copper (Cu), and gold (Au), commonly used in electronic packaging. Cross section SEM images show that thick Ag, Cu, up to 50 μm, and Au, up to 70 μm, were successfully plated over the thin Ni layer that was plated on 304SS.
Palladium Thiolate Bonding of Carbon Nanotube Thermal Interfaces
Authors: Hodson Stephen L. , Bhuvana Thiruvelu , Cola Baratunde A. , Xu Xianfan , Kulkarni G. U. , Fisher Timothy S.
Published: June 2011

Carbon nanotube (CNT) arrays can be effective thermal interface materials with high compliance and conductance over a wide temperature range. Here, we study CNT interface structures in which free CNT ends are bonded using Pd hexadecanethiolate, Pd(SC16H35)2, to an opposing substrate (one-sided interface) or opposing CNT array (two-sided interface) to enhance contact conductance while maintaining a compliant joint. The Pd weld is particularly attractive for its mechanical stability at high temperatures. A transient photoacoustic (PA) method is used to measure the thermal resistance of the palladium-bonded CNT interfaces. The interfaces were bonded at moderate pressures and then tested at 34 kPa using the PA technique. At an interface temperature of approximately 250°C, one-sided and two-sided palladium-bonded interfaces achieved thermal resistances near 10 mm2 K/W and 5 mm2 K/W, respectively.
The management of tumor motions in the stereotactic irradiation to lung cancer under the use of Abches to control active breathing
Authors: Tarohda Tohru I. , Ishiguro Mitsuru , Hasegawa Kouhei , Kohda Yukihiko , Onishi Hiroaki , Aoki Tetsuya , Takanaka Tsuyoshi
Published: June 2011

Purpose: Breathing control is crucial to ensuring the accuracy of stereotactic irradiation for lung cancer. This study monitored respiration in patients with inoperable nonsmall‐cell lung cancer using a respiration‐monitoring apparatus, Abches, and investigated the reproducibility of tumor position in these patients.Methods: Subjects comprised 32 patients with nonsmall‐cell lung cancer who were administered stereotactic radiotherapy under breath‐holding conditions monitored by Abches. Computed tomography (CT) was performed under breath‐holding conditions using Abches (Abches scan) for treatment planning. A free‐breathing scan was performed to determine the range of tumor motions in a given position. After the free‐breathing scan, Abches scan was repeated and the tumor position thus defined was taken as the intrafraction tumor position. Abches scan was also performed just before treatment, and the tumor position thus defined was taken as the interfraction tumor position. To calculate the errors, tumor positions were compared based on Abches scan for the initial treatment plan. The error in tumor position was measured using the BrainSCAN treatment‐planning device, then compared for each lung lobe.Results: Displacements in tumor position were calculated in three dimensions (i.e., superior–inferior (S–I), left–right (L–R), and anterior–posterior (A–P) dimensions) and recorded as absolute values. For the whole lung, average intrafraction tumor displacement was 1.1 mm (L–R), 1.9 mm (A–P), and 2.0 mm (S–I); the average interfraction tumor displacement was 1.1 mm (L–R), 2.1 mm (A–P), and 2.0 mm (S–I); and the average free‐breathing tumor displacement was 2.3 mm (L–R), 3.5 mm (A–P), and 7.9 mm (S–I). The difference between using Abches and free breathing could be reduced from approximately 20 mm at the maximum to approximately 3 mm in the S–I direction for both intrafraction and interfraction positions in the lower lobe. In addition, maximum intrafraction tumor displacement with the use of Abches was 4.5 mm (S–I) in the lingular segment. These results suggest that use of the Abches system can reduce deviations in tumor position to levels below those achieved under free breathing, irrespective of the tumor location.Conclusions: Respiratory control with high accuracy and reproducibility is required for high‐precision radiotherapy of inoperable nonsmall‐cell lung cancer and was achieved using Abches in this study.
Sleep and Synaptic Homeostasis: Structural Evidence in
Drosophila
Authors: Bushey Daniel , Tononi Giulio , Cirelli Chiara
Published: June 2011

Flies’ need for sleep depends on how many synapses are formed while awake.
Abiotic Pyrite Formation Produces a Large Fe Isotope Fractionation
Authors: Guilbaud Romain , Butler Ian B. , Ellam Rob M.
Published: June 2011

Iron isotope signatures may not differentiate abiotic and biological processes in sediments.
Self-Recognition in Social Amoebae Is Mediated by Allelic Pairs of
Tiger
Genes
Authors: Hirose Shigenori , Benabentos Rocio , Ho Hsing-I , Kuspa Adam , Shaulsky Gad
Published: June 2011

Polymorphic receptors prevent cheaters by avoiding altruistic cell death in
Dictyostelium
.
Education Is Not a Race
Authors: Stipek Deborah
Published: June 2011

In the United States and elsewhere, the competitive pressures placed on young people in school are damaging many otherwise promising lives. In addition to generating debilitating anxiety and encouraging a culture of cheating, this competition takes the joy out of learning. The film
Race to Nowhere
, which continues to receive attention since its release a year ago, documents the unhealthy consequences of the competitive “teach to the test” climate that many U.S. students experience. The film, in which I was interviewed, puts in clear relief the pressures that youth are under to amass large numbers of Advanced Placement (college-equivalent) classes, win science fairs, excel in the arts and sports, and in other ways distinguish themselves from the competition for admission into a few select universities that parents and schools believe are critical for future success. Research on motivation makes it clear that focusing attention entirely on performance, whether grades or test scores, destroys whatever intrinsic interest the subject matter might have had.
*
There are certainly students whose passions spur them to realize their full potential in rigorous academic courses and other impressive activities. But how many potential Nobel Prize winners have written off science before the end of high school because their only exposure to the subject had been in test preparation courses rather than in classes that delved into meaningful questions? It doesn't have to be this way, but change will require coordinated efforts at many levels.
NIH's Secondhand Shop for Tried-and-Tested Drugs
Authors: Kaiser Jocelyn
Published: June 2011

A new project by the National Institutes of Health aims to persuade drug companies to open up their troves of abandoned drugs to academics, who would look for new uses.
Counteractive Balancing of Transcriptome Expression Involving CodY and CovRS in Streptococcus pyogenes
Authors: Kreth Jens , Chen Zhiyun , Ferretti Joseph , Malke Horst
Published: June 2011

Streptococcus pyogenes
(group A streptococcus [GAS]) responds to environmental changes in a manner that results in an adaptive regulation of the transcriptome. The objective of the present study was to understand how two global transcriptional regulators, CodY and CovRS, coordinate the transcriptional network in
S. pyogenes
. Results from expression microarray data and quantitative reverse transcription-PCR (qRT-PCR) showed that the global regulator CodY controls the expression of about 250 genes, or about 17% of the genome of strain NZ131. Additionally, the
codY
gene was shown to be negatively autoregulated, with its protein binding directly to the promoter region with a CodY binding site. In further studies, the influence of
codY
,
covRS
, and
codY-covRS
mutations on gene expression was analyzed in growth phase-dependent conditions using C medium, reported to mimic nutritional abundance and famine conditions similar to those found during host GAS infection. Additional biological experiments of several virulence phenotypes, including pilin production, biofilm formation, and NAD glycohydrolase activity, demonstrated the role that both CodY and CovRS play in their regulation. Correlation analysis of the overall data revealed that, in exponentially growing cells, CodY and CovRS act in opposite directions, with CodY stimulating and CovRS repressing a substantial fraction of the core genome, including many virulence factors. This is the first report of counteractive balancing of transcriptome expression by global transcription regulators and provides important insight into how GAS modulates gene expression by integrating important extracellular and intracellular information.
The Bradyrhizobium japonicum frcB Gene Encodes a Diheme Ferric Reductase
Authors: Small Sandra K. , O'Brian Mark R.
Published: June 2011

Iron utilization by bacteria in aerobic environments involves uptake as a ferric chelate from the environment, followed by reduction to the ferrous form. Ferric iron reduction is poorly understood in most bacterial species. Here, we identified
Bradyrhizobium japonicum frcB
(bll3557) as a gene adjacent to, and coregulated with, the
pyoR
gene (blr3555) encoding the outer membrane receptor for transport of a ferric pyoverdine. FrcB is a membrane-bound, diheme protein, characteristic of eukaryotic ferric reductases. Heme was essential for FrcB stability, as were conserved histidine residues in the protein that likely coordinate the heme moieties. Expression of the
frcB
gene in
Escherichia coli
conferred ferric reductase activity on those cells. Furthermore, reduced heme in purified FrcB was oxidized by ferric iron
in vitro
.
B. japonicum
cells showed inducible ferric reductase activity in iron-limited cells that was diminished in an
frcB
mutant. Steady-state levels of
frcB
mRNA were strongly induced under iron-limiting conditions, but transcript levels were low and unresponsive to iron in an
irr
mutant lacking the global iron response transcriptional regulator Irr. Thus, Irr positively controls the
frcB
gene. FrcB belongs to a family of previously uncharacterized proteins found in many proteobacteria and some cyanobacteria. This suggests that membrane-bound, heme-containing ferric reductase proteins are not confined to eukaryotes but may be common in bacteria.
CsrA and TnaB Coregulate Tryptophanase Activity To Promote Exotoxin-Induced Killing of Caenorhabditis elegansby Enteropathogenic Escherichia coli
Authors: Bhatt Shantanu , Anyanful Akwasi , Kalman Daniel
Published: June 2011

EnteropathogenicEscherichia coli(EPEC) requires thetnaA-encoded enzyme tryptophanase and its substrate tryptophan to synthesize diffusible exotoxins that kill the nematodeCaenorhabditis elegans. Here, we demonstrate that the RNA-binding protein CsrA and the tryptophan permease TnaB coregulate tryptophanase activity, through mutually exclusive pathways, to stimulate toxin-mediated paralysis and killing ofC. elegans.
Treatment of ruptured and unruptured cerebral aneurysms in the USA: a paradigm shift
Authors: Lin Ning , Cahill Kevin S , Frerichs Kai U , Friedlander Robert M , Claus Elizabeth B
Published: June 2011

Background

Integration of data from clinical trials and advancements in technology predict a change in selection for treatment of patients with cerebral aneurysm.

Objective

To describe patterns of use and in-hospital mortality associated with surgical and endovascular treatments of cerebral aneurysms over the past decade.

Materials and methods

The data are 34 899 hospital discharges with a diagnosis of ruptured or unruptured cerebral aneurysm from 1998 to 2007 identified from the Nationwide Inpatient Sample (NIS). The rates of endovascular coiling and surgical clipping and in-hospital mortality among patients with an aneurysm are examined over a decade by hospital and patient demographic characteristics.

Results

From 1998 to 2007, 20 134 discharges with a ruptured aneurysm and 14 765 discharges with an unruptured aneurysm were identified. Over this decade, the number of patients discharged with a ruptured aneurysm was stable while the number discharged with an unruptured aneurysm increased significantly. The use of endovascular coiling increased at least twofold for both groups of patient (p<0.001) with the majority of unruptured aneurysms treated with coiling by 2007. Although whites were more likely than non-whites to undergo coiling versus clipping for a ruptured aneurysm (OR=1.30; 95% CI 1.13 to 1.48) and men with unruptured aneurysms were more likely than women to undergo coiling (OR=1.26; 95% CI 1.13 to 1.40), by 2007 differences in treatment selection by gender and racial subgroups were decreased or statistically non-significant. Over time the use of coiling spread from primarily large, teaching hospitals to smaller, non-teaching hospitals.

Conclusions

The majority of unruptured aneurysms in the USA are now treated with endovascular coiling. Although surgical clipping is used for treatment of most ruptured aneurysms, its use is decreasing over time. Dissemination of endovascular procedures appears widespread across patient and hospital subgroups.
The design of the STenting in Aneurysm Treatments (STAT) trial
Authors: Darsaut Tim E , Raymond Jean ,   for the STAT Collaborative Group
Published: June 2011

Unruptured intracranial aneurysms (UIA) are increasingly treated with endovascular treatment although this method continues to be associated with aneurysm recurrences in up to 30–40%, especially for large aneurysms or those with wide (>4 mm) necks. Although the significance of a recurrence remains unknown, they not only require angiographic follow-up but discovery sometimes leads to retreatment, with associated risks. Several strategies have been developed to decrease recurrence rates, including the addition of an endovascular stent to standard coiling. Stents may permit more complete coil occlusion, form a neointimal scaffold at the aneurysm neck and normalize blood flows. A randomized study of endovascular treatment of UIAs for aneurysms treated with or without stenting has not been performed. The design of the STenting in Aneurysm Treatments (STAT) trial is reported, which compares angiographic and clinical outcomes following endovascular treatment of UIAs with or without stents. The first phase of this pragmatic management trial will examine angiographic outcomes, in order to determine whether the addition of a stent to standard coiling can decrease recurrence rates, while the second phase of the study will determine if stenting is associated with increased patient morbidity and mortality. The STAT trial collaborators intend to enroll 600 patients, a size sufficient (at 80% power and 0.05 significance) to detect a decrease in recurrences from 33% to 20% by 1 year, and to verify that stenting does not result in an increase in the proportion of patients experiencing neurological disability (modified Rankin Scale score >2), from 6% to 12%.

Trial Registration No:

ClinicalTrials.gov Identifier:NCT01340612.
Palladium(0) catalyzed 2,2′-bipyrrole syntheses
Authors: Jiao Lijuan , Hao Erhong , Fronczek Frank R. , Vicente M. Graça H. , Smith Kevin M.
Published: June 2011

Several 2-iodopyrroles are used in Pd (0) catalyzed homocoupling reactions at room temperature in the presence of water to efficiently synthesize 2,2′-bipyrroles. These 2,2′-bipyrroles are strongly luminous materials and have high fluorescence quantum yields.
FINITE ELEMENT MODEL TO STUDY THERMAL EFFECT OF UNIFORMLY PERFUSED TUMOR IN DERMAL LAYERS OF ELLIPTICAL SHAPED HUMAN LIMB
Authors: AGRAWAL MAMTA , ADLAKHA NEERU , PARDASANI K. R.
Published: June 2011

In this paper, a two-dimensional finite element model has been developed to study thermal disturbances in elliptical shaped human limbs involving uniformly perfused tumor. The model incorporates the effect of important physiological parameters like blood mass flow rate, self-controlled metabolic activity and thermal conductivity in dermal regions. For tumor regions the uncontrolled rate of metabolic activity and abnormal rate of blood flow have been incorporated. The outer surface of the limb is exposed to the environment where heat loss takes place via the conduction, convection, radiation and evaporation. Appropriate boundary conditions have been framed. The model has been simulated using MATLAB 7.5 to obtain numerical results.
GLOBAL DYNAMICS OF A MALARIA MODEL WITH PARTIAL IMMUNITY AND TWO DISCRETE TIME DELAYS
Authors: CHIYAKA CHRISTINAH , MUKANDAVIRE ZINDOGA , DAS PRASENJIT
Published: June 2011

Asymptotic properties of a malaria model with partial immunity and two discrete time delays are investigated. The time delays represent latent period and partial immunity period in the human population. The results obtained show that the global dynamics are completely determined by the values of the reproductive number. Using a suitable Lyapunov function the endemic equilibrium is shown to be globally asymptotically stable under certain conditions. Moreover, we show that when the partially immune humans are assumed to be noninfectious, the disease is uniformly persistent if the corresponding reproductive number is greater than unity.
RELAY FEEDBACK-BASED CRITICAL PARAMETER ESTIMATION FOR FIRST ORDER PLUS DEAD TIME TYPE PLANT IN NETWORKED CONTROL SYSTEM CONFIGURATION
Authors: YADAV RISHI PAL , VARDE P. V. , CHAUHAN AMIT , FATNANI PRAVIN
Published: June 2011

Most control strategies for networked control systems (NCS) assume that system model is known "a priori" which is, however, impractical in many industrial applications. To obtain the model of First Order Plus Dead Time type plant for networked control, this paper concentrates on model identification under the networked control environment. Ideal-relay feedback-based networked identification scheme is proposed here along with the new packet-based real-time queuing protocol to identify the plant's critical parameters, which takes into account the effect of nondeterministic factors such as network-induced delay, data packet disordering, and limited data packet loss between the sensor and controller as well as the controller and the actuator. Experimental results show that the proposed networked identification scheme can effectively overcome the impact of various network-induced nondeterministic factors for ideal-relay-based model identification in NCS.
(Invited) Success in Measurement the Lowest Off-state Current of Transistor in the World
Authors: Sekine Yusuke , Furutani Kazuma , Shionoiri Yutaka , Kato Kiyoshi , Koyama Jun , Yamazaki Shunpei
Published: June 2011

An oxide semiconductor has a wide band gap and low off-state current. We focused on the off-state characteristics of a transistor including an oxide semiconductor and concentrated on measuring the off-state current. We fabricated a circuit TEG that had an In-Ga-Zn-Oxide TFT (IGZO-TFT) with a large channel width of 100,000 micro meter over a glass substrate and estimated the amount of electric charge flowing through the circuit TEG for a long time. As a result, we discovered that an IGZO-TFT had off-state current as small as 50yA/micro meter (at 85 degrees of Centigrade). We are the first to measure off-state current on the order of yA; "y" is the SI prefix representing 10e-24
The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?
Authors: Azcárate-Peril M. Andrea , Sikes Michael , Bruno-Bárcena José M.
Published: June 2011

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5–15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” ( 219 ), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.
Transition from parenteral to enteral nutrition induces immediate diet-dependent gut histological and immunological responses in preterm neonates
Authors: Siggers Jayda , Sangild Per T. , Jensen Tim K. , Siggers Richard H. , Skovgaard Kerstin , Støy Ann Cathrine F. , Jensen Bent B. , Thymann Thomas , Bering Stine B. , Boye Mette
Published: June 2011

Necrotizing enterocolitis (NEC) in preterm infants develops very rapidly from a mild intolerance to enteral feeding into intestinal mucosal hemorrhage, inflammation, and necrosis. We hypothesized that immediate feeding-induced gut responses precede later clinical NEC symptoms in preterm pigs. Fifty-six preterm pigs were fed total parenteral nutrition (TPN) for 48 h followed by enteral feeding for 0, 8, 17, or 34 h with either colostrum (Colos, n = 20) or formula (Form, n = 31). Macroscopic NEC lesions were detected in Form pigs throughout the enteral feeding period (20/31, 65%), whereas most Colos pigs remained protected (1/20, 5%). Just 8 h of formula feeding induced histopathological lesions, as evidenced by capillary stasis and necrosis, epithelial degeneration, edema, and mucosal hemorrhage. These immediate formula-induced changes were paralleled by decreased digestive enzyme activities (lactase and dipeptidylpeptidase IV), increased nutrient fermentation, and altered expression of innate immune defense genes such as interleukins (IL-1α, IL-6, IL-18), nitric oxide synthetase, tight junction proteins (claudins), Toll-like receptors (TLR-4), and TNF-α. In contrast, the first hours of colostrum feeding induced no histopathological lesions, increased maltase activity, and induced changes in gene expressions related to tissue development. Total bacterial density was high after 2 days of parenteral feeding and was not significantly affected by diet (colostrum, formula) or length of enteral feeding (8–34 h), except that a few bacterial groups ( Clostridium, Enterococcus, Streptococcus species) increased with time. We conclude that a switch from parenteral to enteral nutrition rapidly induces diet-dependent histopathological, functional, and proinflammatory insults to the immature intestine. Great care is required when introducing enteral feeds to TPN-fed preterm infants, particularly when using formula, because early feeding-induced insults may predispose to NEC lesions that are difficult to revert by later dietary or medical interventions.
The structures of marialite (Me6) and meionite (Me93) in space groupsP42/nandI4/m, and the absence of phase transitions in the scapolite series
Authors: Antao Sytle M. , Hassan Ishmael
Published: June 2011

The crystal structures of marialite (Me6) from Badakhshan, Afghanistan and meionite (Me93) from Mt. Vesuvius, Italy were obtained using synchrotron high-resolution powder X-ray diffraction (HRPXRD) data and Rietveld structure refinements. Their structures were refined in space groupsI4/mandP42/n, and similar results were obtained. TheMe6sample has a formula Ca0.24Na3.37K0.24[Al3.16Si8.84O24]Cl0.84(CO3)0.15, and its unit-cell parameters area=12.047555(7),c=7.563210(6) Å, andV=1097.751(1) Å3. The average ⟨T1-O⟩ distances are 1.599(1) Å inI4/mand 1.600(2) Å inP42/n, indicating that the T1 site contains only Si atoms. InP42/n, the average distances of ⟨T2-O⟩=1.655(2) and ⟨T3-O⟩=1.664(2) Å are distinct and are not equal to each other. However, the mean ⟨T2,3-O⟩=1.659(2) Å inP42/nand is identical to the ⟨T2′-O⟩=1.659(1) Å inI4/m. The ⟨M-O⟩ [7]=2.754(1) Å (M site is coordinated to seven framework O atoms) and M-A=2.914(1) Å; these distances are identical in both space groups. TheMe93sample has a formula of Na0.29Ca3.76[Al5.54Si6.46O24]Cl0.05(SO4)0.02(CO3)0.93, and its unit-cell parameters area=12.19882(1),c=7.576954(8) Å, andV=1127.535(2) Å3. A similar examination of theMe93sample also shows that both space groups give similar results; however, the C–O distance is more reasonable inP42/nthan inI4/m. Refining the scapolite structure nearMe0orMe100inI4/mforces the T2 and T3 sites (both with multiplicity 8 inP42/n) to be equivalent and form the T2′ site (with multiplicity 16 inI4/m), but ⟨T2-O⟩ is not equal to ⟨T3-O⟩ inP42/n. Using different space groups for different regions across the series implies phase transitions, which do not occur in the scapolite series.
Binding of Mn-deoxyribonucleoside triphosphates to the active site of the DNA polymerase of bacteriophage T7
Authors: Akabayov Barak , Richardson Charles C.
Published: June 2011

Divalent metal ions are crucial as cofactors for a variety of intracellular enzymatic activities. Mg2+, as an example, mediates binding of deoxyribonucleoside 5′-triphosphates followed by their hydrolysis in the active site of DNA polymerase. It is difficult to study the binding of Mg2+to an active site because Mg2+is spectroscopically silent and Mg2+binds with low affinity to the active site of an enzyme. Therefore, we substituted Mg2+with Mn2+:Mn2+that is not only visible spectroscopically but also provides full activity of the DNA polymerase of bacteriophage T7. In order to demonstrate that the majority of Mn2+is bound to the enzyme, we have applied site-directed titration analysis of T7 DNA polymerase using X-ray near edge spectroscopy. Here we show how X-ray near edge spectroscopy can be used to distinguish between signal originating from Mn2+that is free in solution and Mn2+bound to the active site of T7 DNA polymerase. This method can be applied to other enzymes that use divalent metal ions as a cofactor.
In situ high-temperature X-ray diffraction characterization of silver sulfide, Ag2S
Authors: Blanton Thomas , Misture Scott , Dontula Narasimharao , Zdzieszynski Swavek
Published: June 2011

Silver sulfide, Ag2S, is most commonly known as the tarnish that forms on silver surfaces due to the exposure of silver to hydrogen sulfide. The mineral acanthite is a monoclinic crystalline form of Ag2S that is stable to 176°C. Upon heating above 176°C, there is a phase conversion to a body-centered cubic (bcc) form referred to as argentite. Further heating above 586°C results in conversion of the bcc phase to a face-centered cubic (fcc) phase polymorph. Both high-temperature cubic phases are solid-state silver ion conductors. In situ high-temperature X-ray diffraction was used to better understand the polymorphs of Ag2S on heating. The existing powder diffraction file (PDF) entries for the high-temperature fcc polymorph are of questionable reliability, prompting a full Rietveld structure refinement of the bcc and fcc polymorphs. Rietveld analysis was useful to show that the silver atoms are largely disordered and can only be described by unreasonably large isotropic displacement parameters or split site models.
Development of an in situ X-ray diffraction system for hydrothermal reactions and its application to autoclaved aerated concrete formation
Authors: Kikuma J. , Tsunashima M. , Ishikawa T. , Matsuno S. , Ogawa A. , Matsui K.
Published: June 2011

An in situ time-resolved XRD system for hydrothermal reaction has been developed in order to investigate the phase evolution during autoclave process in autoclaved aerated concrete (AAC) formation. The system includes a novel autoclave cell for transmission XRD with thin beryllium windows, a two-dimensional photon-counting pixel array detector, and uses high energy X-rays from a synchrotron radiation source. The temperature and pressure inside the cell are extremely stable during hydrothermal reaction over the course of several hours. The system was utilized for the formation reaction of AAC. Phase evolution was clearly observed, including several intermediate phases, and detailed information on the structural changes during the hydrothermal reaction were obtained.
BRCA1 Loss Induces GADD153-Mediated Doxorubicin Resistance in Prostate Cancer
Authors: De Luca Paola , Vazquez Elba S. , Moiola Cristian P. , Zalazar Florencia , Cotignola Javier , Gueron Geraldine , Gardner Kevin , De Siervi Adriana
Published: June 2011

BRCA1 plays numerous roles in the regulation of genome integrity and chemoresistance. Although BRCA1 interaction with key proteins involved in DNA repair is well known, its role as a coregulator in the transcriptional response to DNA damage remains poorly understood. In this study, we show that BRCA1 plays a central role in the transcriptional response to genotoxic stress in prostate cancer. BRCA1 expression mediates apoptosis, cell-cycle arrest, and decreased viability in response to doxorubicin treatment. Xenograft studies using human prostate carcinoma PC3 cells show that BRCA1 depletion results in increased tumor growth. A focused survey of BRCA1-regulated genes in prostate carcinoma reveals that multiple regulators of genome stability and cell-cycle control, including BLM, FEN1, DDB2, H3F3B, BRCA2, CCNB2, MAD2L1, and GADD153, are direct transcriptional targets of BRCA1. Furthermore, we show that BRCA1 targets GADD153 promoter to increase its transcription in response to DNA damage. Finally, GADD153 depletion significantly abrogates BRCA1 influence on cell-cycle progression and cell death in response to doxorubicin treatment. These findings define a novel transcriptional pathway through which BRCA1 orchestrates cell fate decisions in response to genotoxic insults, and suggest that BRCA1 status should be considered for new chemotherapeutic treatment strategies in prostate cancer. Mol Cancer Res; 9(8); 1078–90. ©2011 AACR.
Brain Activity Supporting Working Memory Accuracy in Patients with Paranoid Schizophrenia: A Functional Magnetic Resonance Imaging Study
Authors: Wolf Claudia , Linden Stefanie , Jackson Margaret C. , Healy David , Baird Alison , Linden David E.J. , Thome Johannes
Published: June 2011

Background: Dysfunctional working memory (WM) has been recognized as one of the most consistent deficits in schizophrenia. Studies that investigated the neural correlates of WM-related pathology by comparing patients with schizophrenia and control participants have produced controversial results, reporting task-related hyper- or hypoactivity in frontoparietal networks. Method: We addressed this question by comparing BOLD signals for accurate responses during a WM task for emotional faces between a homogeneous group of high-performing patients and a control group. Results: Our results confirm previous findings of left prefrontal hyperactivity contrasted with hypoactivity in right prefrontal cortex to support WM performance. We also extend previous work by reporting enhanced activity in higher visual areas of patients during encoding and maintenance. Conclusion: Our findings and those of the literature can be integrated into a model, where preserved visual cognition in high-functioning patients with hypofrontality is explained by activation of contralateral homologue areas combined with enhanced recruitment of sensory areas.
Chorioamnionitis – New Ideas from Experimental Models
Authors: Kramer Boris W.
Published: June 2011

Antenatal inflammation may be associated with adverse neonatal outcomes in several organ systems. Bacteria and a few viruses have been detected in cases of microbial invasion of the amniotic cavity which is referred to as chorioamnionitis. Many aspects of this disease remain unclear such as the causes, time of onset and the fetal responses. Chorioamnionitis was therefore induced in pregnant sheep by injections of lipopolysaccharide (LPS) or Ureaplasma species into the amniotic cavity under ultrasound guidance. LPS-induced chorioamnionitis caused a cascade of organ injury, inflammation, and remodeling. The organ-specific changes were accompanied by systemic effects. The systemic effects after LPS-induced chorioamnionitis resulted in immune suppression against several Toll-like receptor agonists (cross-tolerance). Ureaplasma induced chorioamnionitis made changes in the fetal lung structure depending on the time of infection during pregnancy. The mechanisms of inflammation, structural damage and decreased expression of growth factors need to be further studied to determine therapeutic targets in suitable animal models.
Surfactant Replacement Therapy in Developing Countries
Authors: Vidyasagar Dharmapuri , Velaphi Sithembiso , Bhat Vishnu B.
Published: June 2011

Background: Since the first successful report of surfactant replacement therapy (SRT) in infants with respiratory distress syndrome (RDS), numerous randomized clinical trials have shown that SRT reduces mortality and morbidity in RDS. Surfactant is now a standard therapy for RDS. However, the use of SRT in the developing world has been extremely slow. Objective: The objective of this paper is to review the published information regarding the usage and barriers encountered in the use of SRT in developing countries. Methods: We reviewed the available literature and also gathered information from countries with a high burden of prematurity and high infant mortality rate regarding replacement therapy and the barriers to use of SRT. Results: We reviewed the available literature and found that developing countries bear a high burden of prematurity and RDS that contribute to high neonatal and infant mortality rates. Based on the effectiveness of SRT in RDS, surfactant preparations were included in the Essential Drug List of WHO in 2008. However, the use of SRT in developing countries is still limited because of (1) high cost, (2) lack of skilled personnel to administer SRT, and (3) lack of support systems after the SRT. The cost of SRT may exceed the per-capita GNP (300–500 USD) in some countries. Data from India and South Africa suggests that SRT is limited to rescue therapy in babies with potential for better survival, usually >28 weeks’ gestation. Recent studies show that infants with RDS respond well to initial continuous positive airway pressure (CPAP) followed by SRT for those who do not respond. Conclusions: In developing countries, CPAP may be used as the primary mode of management of RDS. SRT may be reserved for non-responders to CPAP. Alternate simpler methods of delivery of surfactant (aerosol technique) are also being explored. There is a need for further studies to develop and assess efficient and less expensive methods of application of CPAP and SRT in developing countries.
Striatal Neuroprotection from Neonatal Hypoxia-Ischemia in Piglets by Antioxidant Treatment with EUK-134 or Edaravone
Authors: Ni Xinli , Yang Zeng-Jin , Carter Erin L. , Martin Lee J. , Koehler Raymond C.
Published: June 2011

Striatal neurons are highly vulnerable to hypoxia-ischemia (HI) in term newborns. In a piglet model of HI, striatal neurons develop oxidative stress and organelle disruption by 3–6 h of recovery and ischemic cytopathology over 6–24 h of recovery. We tested the hypothesis that early treatment with the antioxidants EUK-134 (a manganese-salen derivative that acts as a scavenger of superoxide, hydrogen peroxide, nitric oxide or NO and peroxynitrite) or edaravone (MCI-186, a scavenger of hydroxyl radical and NO) protects striatal neurons from HI. Anesthetized newborn piglets were subjected to 40 min of hypoxia and 7 min of airway occlusion. At 30 min after resuscitation, the piglets received vehicle, EUK-134 or edaravone. Drug treatment did not affect arterial blood pressure, blood gases, blood glucose or rectal temperature. At 4 days of recovery, the density of viable neurons in the putamen of vehicle-treated piglets was 12 ± 6% (±SD) of sham-operated control density. Treatment with EUK-134 increased viability to 41 ± 17%, and treatment with edaravone increased viability to 39 ± 19%. In the caudate nucleus, neuronal viability was increased from 54 ± 11% in the vehicle group to 78 ± 15% in the EUK-134 group and to 73 ± 13% in the edaravone group. Antioxidant drug treatment accelerated recovery from neurologic deficits and decreased oxidative and nitrative damage to nucleic acids. Treatment with EUK-134 reduced the HI-induced formation of protein carbonyl groups and tyrosine nitration at 3 h of recovery. We conclude that systemic administration of antioxidant agents by 30 min after resuscitation from HI can reduce oxidative stress and salvage neurons in the highly vulnerable striatum in a large-animal model of neonatal HI. Therefore, oxidative stress is an important mechanism for this injury, and antioxidant therapy is a rational, mechanism-based approach to neuroprotection in the newborn brain.
Stroke Awareness in Urban and Rural Populations from Northern Portugal: Knowledge and Action Are Independent
Authors: Moreira Emília , Correia Manuel , Magalhães Rui , Silva M. Carolina
Published: June 2011

Background: Several studies conducted in hospital emergency departments have shown that most patients delay in responding to stroke symptoms. In the general population, recognition of stroke and the appropriate reactions are important for prevention and acute treatment, particularly in areas with a high stroke incidence. The objective of this study was to compare general knowledge about stroke/TIA and prompt action in urban and rural populations. Methods: In the first half of 2007, a cross-sectional study on stroke knowledge was undertaken in rural and urban populations from the Viana do Castelo district. About 1% of people aged at least 18 years registered at three community health centers were asked to check a list of vascular risk factors (VRF), stroke/TIA warning signs, and other non-specific signs, as well as indicate how they would react in the presence of warning signs or stroke/TIA. Results: The 347 urban participants were on average younger than the 316 rural participants (46 vs. 51 years) and fewer had a low educational level (44 vs. 62% had less than 5 years of full education). About 50% identified at least 8 out of 13 VRF and indicated the brain as the body location; 39.7% recognized simultaneously the three key warning signs of the FAST campaign – irrespective of gender, educational level, and residential area. Education and urban environment increased the odds of calling the emergency medical services (EMS), while age had the opposite effect. After adjustment, recognition of brain location and calling EMS in case of paralysis/weakness or dizziness/vertigo increased the odds of calling the EMS in case of stroke, while recognition of the warning signs was not associated with an EMS call. Conclusions: People’s reaction to stroke depends mostly on their sociodemographic profile and their reaction to specific warning signs, independently of recognizing them as ‘originating from stroke’.
Phenotypic Manifestations of Mutations in Genes Encoding Subunits of Cardiac Potassium Channels
Authors: Shimizu Wataru , Horie Minoru
Published: June 2011

Since 1995, when a potassium channel gene,
hERG
(human ether-à-go-go-related gene), now referred to as
KCNH2
, encoding the rapid component of cardiac delayed rectifier potassium channels was identified as being responsible for type 2 congenital long-QT syndrome, a number of potassium channel genes have been shown to cause different types of inherited cardiac arrhythmia syndromes. These include congenital long-QT syndrome, short-QT syndrome, Brugada syndrome, early repolarization syndrome, and familial atrial fibrillation. Genotype-phenotype correlations have been investigated in some inherited arrhythmia syndromes, and as a result, gene-specific risk stratification and gene-specific therapy and management have become available, particularly for patients with congenital long-QT syndrome. In this review article, the molecular structure and function of potassium channels, the clinical phenotype due to potassium channel gene mutations, including genotype-phenotype correlations, and the diverse mechanisms underlying the potassium channel gene–related diseases will be discussed.