bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole in preventing rebleeding among low risk patients with a bleeding peptic ulcer after initial endoscopic hemostasis
Authors: Liang Chih-Ming , Lee Jyong-Hong , Kuo Yuan-Hung , Wu Keng-Liang , Chiu Yi-Chun , Chou Yeh-Pin , Hu Ming-Luen , Tai Wei-Chen , Chiu King-Wah , Hu Tsung-Hui , Chuah Seng-Kee
Published: March 2012

Background

Many studies have shown that high-dose proton-pumps inhibitors (PPI) do not further reduce the rate of rebleeding compared to non-high-dose PPIs but we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates among patients at low risk (Rockall score < 6) or among those at high risk, both compared to high-dose PPIs. This retrospective case-controlled study aimed to identify the subgroups of these patients that might benefit from treatment with non-high-dose PPIs.

Methods

Subjects who received high dose and non-high-dose pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and rebleeding groups (n = 89). The greedy method was applied to allow treatment-control random matching (1:1). Patients were randomly selected from the non-high-dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104 in each group), and these were then subdivided to two subgroups (Rockall score ≥ 6 vs. < 6, n = 77 vs. 27).

Results

An initial low hemoglobin level, serum creatinine level, and Rockall score were independent factors associated with rebleeding. After case-control matching, the significant variables between the non-high-dose and high-dose PPI groups for a Rockall score ≥ 6 were the rebleeding rate, and the amount of blood transfused. Case-controlled matching for the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar for both groups (11.1% in each group).

Conclusion

Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole when treating low risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk stigmata after endoscopic hemostasis.
[11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein
Authors: Froklage Femke E , Syvänen Stina , Hendrikse N Harry , Huisman Marc C , Molthoff Carla FM , Tagawa Yoshihiko , Reijneveld Jaap C , Heimans Jan J , Lammertsma Adriaan A , Eriksson Jonas , de Lange Elizabeth CM , Voskuyl Rob A
Published: March 2012

Background

[11C]Flumazenil and positron emission tomography (PET) are used clinically to assess gamma-aminobutyric acid (GABA)-ergic function and to localize epileptic foci prior to resective surgery. Enhanced P-glycoprotein (P-gp) activity has been reported in epilepsy and this may confound interpretation of clinical scans if [11C]flumazenil is a P-gp substrate. The purpose of this study was to investigate whether [11C]flumazenil is a P-gp substrate.

Methods

[11C]Flumazenil PET scans were performed in wild type (WT) (n = 9) and Mdr1a/1b, (the genes that encode for P-gp) double knockout (dKO) (n = 10) mice, and in naive rats (n = 10). In parallel to PET scanning, [11C]flumazenil plasma concentrations were measured in rats. For 6 of the WT and 6 of the dKO mice a second, [11C]flumazenil scan was acquired after administration of the P-gp inhibitor tariquidar. Cerebral [11C]flumazenil concentrations in WT and Mdr1a/1b dKO mice were compared (genetic disruption model). Furthermore, pre and post P-gp-blocking cerebral [11C]flumazenil concentrations were compared in all animals (pharmacological inhibition model).

Results

Mdr1a/1b dKO mice had approximately 70% higher [11C]flumazenil uptake in the brain than WT mice. After administration of tariquidar, cerebral [11C]flumazenil uptake in WT mice increased by about 80% in WT mice, while it remained the same in Mdr1a/1b dKO mice. In rats, cerebral [11C]flumazenil uptake increased by about 60% after tariquidar administration. Tariquidar had only a small effect on plasma clearance of flumazenil.

Conclusions

The present study showed that [11C]flumazenil is a P-gp substrate in rodents. Consequently, altered cerebral [11C]flumazenil uptake, as observed in epilepsy, may not reflect solely GABAA receptor density changes but also changes in P-gp activity.
Dietary Vitamin D3 and 1,25-Dihydroxyvitamin D3 (Calcitriol) Exhibit Equivalent Anticancer Activity in Mouse Xenograft Models of Breast and Prostate Cancer
Authors: Swami Srilatha , Krishnan Aruna V. , Wang Jennifer Y. , Jensen Kristin , Horst Ronald , Albertelli Megan A. , Feldman David
Published: March 2012

1,25-dihydroxyvitamin D3 [1,25(OH)2D3 or calcitriol], the hormonally active vitamin D metabolite, exhibits anticancer actions in models of breast cancer and prostate cancer. Because CYP27B1 (1α-hydroxylase), the enzyme catalyzing 1,25(OH)2D3 formation in the kidney, is also expressed in extrarenal tissues, we hypothesize that dietary vitamin D3 will be converted to 25(OH)D3 in the body and then to 1,25(OH)2D3 locally in the cancer microenvironment in which it will exert autocrine/paracrine anticancer actions. Immunocompromised mice bearing MCF-7 breast cancer xenografts showed significant tumor shrinkage (>50%) after ingestion of a vitamin D3-supplemented diet (5000 IU/kg) compared with a control diet (1000 IU/kg). Dietary vitamin D3 inhibition of tumor growth was equivalent to administered calcitriol (0.025, 0.05, or 0.1 μg/mouse, three times a week). Both treatments equivalently inhibited PC-3 prostate cancer xenograft growth but to a lesser extent than the MCF-7 tumors. Calcitriol at 0.05 μg and 0.1 μg caused modest but statistically significant increases in serum calcium levels indicating that the dietary vitamin D3 comparison was to a maximally safe calcitriol dose. Dietary vitamin D3 did not increase serum calcium, demonstrating its safety at the concentration tested. The vitamin D3 diet raised circulating 1,25 dihydroxyvitamin D levels and did not alter CYP27B1 mRNA in the kidney but increased it in the tumors, suggesting that extrarenal sources including the tumors contributed to the elevated circulating 1,25 dihydroxyvitamin D3. Both calcitriol and dietary vitamin D3 were equipotent in suppressing estrogen synthesis and signaling and other proinflammatory and growth signaling pathways. These preclinical data demonstrate the potential utility of dietary vitamin D3 supplementation in cancer prevention and therapy.
The Dorsomedial Suprachiasmatic Nucleus Times Circadian Expression of Kiss1 and the Luteinizing Hormone Surge
Authors: Smarr Benjamin L. , Morris Emma , de la Iglesia Horacio O.
Published: March 2012

Ovulation in mammals is gated by a master circadian clock in the suprachiasmatic nucleus (SCN). GnRH neurons represent the converging pathway through which the brain triggers ovulation, but precisely how the SCN times GnRH neurons is unknown. We tested the hypothesis that neurons expressing kisspeptin, a neuropeptide coded by the Kiss1 gene and necessary for the activation of GnRH cells during ovulation, represent a relay station for circadian information that times ovulation. We first show that the circadian increase of Kiss1 expression, as well as the activation of GnRH cells, relies on intact ipsilateral neural input from the SCN. Second, by desynchronizing the dorsomedial (dm) and ventrolateral (vl) subregions of the SCN, we show that a clock residing in the dmSCN acts independently of the light-dark cycle, and the vlSCN, to time Kiss1 expression in the anteroventral periventricular nucleus of the hypothalamus and that this rhythm is always in phase with the LH surge. In addition, we show that although the timing of the LH surge is governed by the dmSCN, its amplitude likely depends on the phase coherence between the vlSCN and dmSCN. Our results suggest that whereas dmSCN neuronal oscillators are sufficient to time the LH surge through input to kisspeptin cells in the anteroventral periventricular nucleus of the hypothalamus, the phase coherence among dmSCN, vlSCN, and extra-SCN oscillators is critical for shaping it. They also suggest that female reproductive disorders associated with nocturnal shift work could emerge from the desynchronization between subregional oscillators within the master circadian clock.
AMPK Activation by Dihydrotestosterone Reduces FSH-Stimulated Cell Proliferation in Rat Granulosa Cells by Inhibiting ERK Signaling Pathway
Authors: Kayampilly Pradeep P. , Menon K. M. J.
Published: March 2012

We have previously reported that 5α-dihydrotestosterone (DHT) inhibits FSH-mediated granulosa cell proliferation by reducing cyclin D2 mRNA expression and blocking cell cycle progression at G1/S phase. The present study investigated the role of AMP activated protein kinase (AMPK) in DHT-mediated inhibition of granulosa cell proliferation. Granulosa cells harvested from 3-d estradiol primed immature rats were exposed to different concentrations of DHT (0, 45, and 90 ng/ml) for 24 h. Western blot analysis of immunoprecipitated AMPK showed a dose-dependent activation (P < 0.05) as evidenced by the increased phosphorylation at thr 172. In addition, time-courses studies (0, 6, 12, and 24 h) using DHT (90 ng/ml) showed a time-dependent increase in AMPK activation with maximum effect at 24 h. FSH inhibited AMPK phosphorylation and promoted granulosa cell proliferation, but pretreatment with DHT (90 ng/ml) for 24 h prior to FSH treatment reduced this effect. Pharmacological activation of AMPK with 5-aminoimidazole-4-carboxamide-1-β4-ribofuranoside abolished FSH-mediated ERK phosphorylation, indicating that AMPK is a negative upstream regulator of ERK. Furthermore, inhibition of AMPK activation by compound C reversed the DHT-mediated reduction in positive cell cycle regulator, cyclin D2, and 5-bromo-2′-deoxyuridine incorporation. These results suggest that elevated levels of DHT activate AMPK, which in turn inhibits ERK phosphorylation. Thus, inhibition of ERK phosphorylation by activated AMPK in response to DHT might contribute to decreased granulosa cell mitogenesis and ovulatory dysfunction seen in hyperandrogenic states.
The DSPII splice variant is critical for desmosome-mediated HaCaT keratinocyte adhesion
Authors: Cabral Rita M. , Tattersall Daniel , Patel Vishal , McPhail Graham D. , Hatzimasoura Elizabeth , Abrams Dominic J. , South Andrew P. , Kelsell David P.
Published: March 2012

Desmosomes are intercellular junctions specialised for strong adhesion that are prominent in the epidermis and heart muscle. Defective desmosomal function due to inherited mutations in the constitutive desmosomal gene desmoplakin (DSP) causes skin or heart disorders and in some instances both. Different mutations have different disease-causing molecular mechanisms as evidenced by the varying phenotypes resulting from mutations affecting different domains of the same protein, but the majority of these mechanisms remain to be determined. Here we studied two mutations in DSP which lead to different dosages of the two major DSP splice variants, DSPI and DSPII, and compared their molecular mechanisms. One of the mutations results in total DSP haploinsufficiency and is associated with autosomal dominant striate palmoplantar keratoderma (PPK). The other leads to complete absence of DSPI and the minor isoform DSPIa but normal levels of DSPII, and is associated with autosomal recessive epidermolytic PPK, woolly hair and severe arrhythmogenic dilated cardiomyopathy. Using siRNA to mimic these two mutations and additionally a DSPII-specific siRNA, we found striking differences between DSP isoforms with respect to keratinocyte adhesion upon cellular stress with DSPII being the key component in IF stability and desmosome mediated adhesion. In addition, reduction in DSP expression reduced the amount of plakophilin 1, desmocollin (DSC) 2 and DSC3 with DSPI having a greater influence than DSPII on the expression levels of DSC3. These results suggest that the two major DSP splice variants are not completely redundant in function and that DSPII dosage is particularly important for desmosomal adhesion in the skin.
Caveolar domain organization and trafficking is regulated by Abl kinases and mDia1
Authors: Echarri Asier , Muriel Olivia , Pavón Dácil M. , Azegrouz Hind , Escolar Fernando , Terrón María C. , Sanchez-Cabo Fátima , Martínez Fernando , Montoya María C. , Llorca Oscar , Del Pozo Miguel A
Published: March 2012

Caveolin-1 (Cav1)/caveolae biology is intimately linked to actin dynamics and adhesion receptors. Caveolar domains are organized in hierarchical levels of complexity from curved or flatten caveolae to large, higher-order caveolar rosettes. We report that stress fibers controlled by Abl kinases and mDia1 determine the level of caveolar domain organization, which conditions the subsequent inward trafficking of caveolar domains induced upon loss of cell adhesion from the extracellular matrix. Abl-deficient cells show decreased content of stress fibers, a smaller stress-fiber co-aligned Cav1 pool and increased clustering of Cav1/caveolae at the cell surface. Defective caveolar linkage to stress fibers prevents the formation of big caveolar rosettes upon loss of cell adhesion, correlating with a lack of inward trafficking. Live imaging of stress fibers and Cav1 showed that the actin-linked Cav1 pool loses its spatial organization in the absence of actin polymerization and is dragged and clustered by depolymerizing filaments. We identify mDia1 as the actin polymerization regulator downstream of Abl kinases that controls the stress fiber-linked Cav1 pool. mDia1 knockdown results in Cav1/caveolae clustering and defective inward trafficking upon loss of cell adhesion. In contrast, cell elongation imposed by the excess of stress fibers induced by active mDia1 flattens caveolae. Furthermore, active mDia1 rescues the actin co-aligned Cav1 pool and Cav1 inward trafficking upon loss of adhesion in Abl-deficient cells. Thus, caveolar domain organization and trafficking are tightly coupled to adhesive and stress fiber regulatory pathways.
Phosphoinositide specificity determines which cytohesins regulate β1 integrin recycling
Authors: Oh Seung Ja , Santy Lorraine C.
Published: March 2012

Recycling of internalized integrins is a critical step in adhesion remodeling and cell movement. Recently, we determined that the ARF-GEFs Cytohesin 2/ ARNO and cytohesin 3/ GRP1 have opposing effects on adhesion and stimulated β1 integrin recycling even though they are very closely related proteins (80% sequence identity). We have now determined the sequence differences underlying the differential actions of cytohesin 2/ ARNO and cytohesin 3/ GRP1. We find that the ability of cytohesins to promote β1 integrin recycling and adhesion depends upon the presence or absence of a key glycine residue in their PH domains. This glycine residue determines the phosphoinositide specificity and affinity of cytohesin PH domains. Switching the number of glycines in the PH domains of cytohesin 2 and cytohesin 3 is sufficient to reverse their effects on adhesion and spreading and to reverse their sub-cellular locations. Importantly, we also find that a mutant form of cytohesin 3/ GRP1 that has 3 rather than 2 glycines in its PH domain rescues β1 integrin recycling in cytohesin 2/ ARNO knockdown cells. Conversely, a mutant form of cytohesin 2/ARNO with 2 glycines in its PH domain fails to rescue β1 integrin recycling. Therefore, we conclude that phosphoinositide specificity is the sole functional difference that determines which cytohesin can promote integrin recycling.
Amyotrophic Lateral Sclerosis Mutant VAPB Causes a Nuclear Envelope Defect
Authors: Tran Duvinh , Chalhoub Antonious , Schooley Allana , Zhang Wendy , Ngsee Johnny K.
Published: March 2012

A proline to serine substitution (P56S) in VAPB causes an autosomal dominant form of Amyotrophic Lateral Sclerosis (ALS). We show that the mutation also causes a nuclear envelope (NE) defect. Transport of Nucleoporins (Nups) and Emerin (EMD) to the NE is blocked, resulting in their sequestration in dilated cytoplasmic membranes. Simultaneous overexpression of the FFAT motif (two phenylalanines on an acidic track) antagonizes this mutant VAPB effect and restores transport to the NE. VAPB function is required for transport to the NE with knockdown of endogenous VAPB recapitulating this phenotype. Moreover, we identified this compartment as ER-Golgi intermediate compartment (ERGIC) with NE membrane proteins transiting to ERGIC before VAPB-dependent retrograde transport to the NE.
Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells
Authors: Ohta Shigeki , Misawa Aya , Fukaya Raita , Inoue Satoshi , Kanemura Yonehiro , Okano Hideyuki , Kawakami Yutaka , Toda Masahiro
Published: March 2012

In a previous study, we showed that murine dendritic cells (DCs) can increase the number of neural stem/progenitor cells (NSPCs) in vitro and in vivo. In the present study, we identified macrophage migration inhibitory factor (MIF) as a novel factor that can support the proliferation and/or survival of NSPCs in vitro. MIF is secreted by DCs and NSPCs, and its function in the normal brain remains largely unknown. It was previously shown that in macrophages, MIF binds to a CD74-CD44 complex. Here, we observed the expression of MIF receptors in mouse ganglionic eminence (GE)-derived neurospheres using flow cytometry in vitro. We also found CD74 expression in the GE of E14 mouse brains, suggesting that MIF play a physiological role in vivo. MIF increased the number of primary and secondary neurospheres. In contrast, retrovirally-expressed MIF shRNA and MIF inhibitor (ISO-1) suppressed primary and secondary neurosphere formation, as well as cell proliferation. In the neurospheres, MIF knock-down by shRNA increased caspase 3/7 activity, and MIF increased the phosphorylation of Akt, Erk, AMPK, and Stat3 (Ser727), as well as gene expression of Hes3 and Egfr, which are known to support cell survival, proliferation and/or maintenance of NSPCs. MIF also acted as a chemoattractant for NSPCs. Taken together, MIF can induce NSPC proliferation and maintenance by using multiple-signaling pathways synergistically, and it may be a potential therapeutic factor capable for NSPC activation for the treatment of degenerative brain disorders.
Nck and Cdc42 co-operate to recruit N-WASP to promote FcγR-mediated phagocytosis
Authors: Dart Anna E. , Donnelly Sara K. , Holden David W. , Way Michael , Caron Emmanuelle
Published: March 2012

The adaptor protein Nck has been shown to link receptor ligation to actin-based signalling in a diverse range of cellular events, such as changes in cell morphology and motility. It has also been implicated in phagocytosis. However, its molecular role in controlling actin remodelling associated with phagocytic uptake remains to be clarified. We show that Nck, which is recruited to phagocytic cups, is required for FcγR but not CR3 induced phagocytosis. Nck recruitment in response to FcγR ligation is mediated by the phosphorylation of tyrosine 282 and 298 in the ITAM motif in the cytoplasmic tail of the receptor. In the absence of FcγR phosphorylation, there is also no recruitment of N-WASP or Cdc42 to phagocytic cups. Nck promotes FcγR-mediated phagocytosis by recruiting N-WASP to phagocytic cups. Efficient phagocytosis, however, only occurs, if the CRIB domain of N-WASP can also interact with Cdc42. Our observations demonstrate that Nck and Cdc42 collaborate to stimulate N-WASP dependent FcγR-mediated phagocytosis.
Trimethylsumanene: Enantioselective Synthesis, Substituent Effect on Bowl Structure, Inversion Energy, and Electron Conductivity
Authors: Higashibayashi Shuhei , Tsuruoka Ryoji , Soujanya Yarasi , Purushotham Uppula , Sastry G Narahari , Seki Shu , Ishikawa Takeharu , Toyota Shinji , Sakurai Hidehiro
Published: March 2012

C 3 symmetric chiral trimethylsumanene was enantioselectively synthesized through Pd-catalyzed syn-selective cyclotrimerization of an enantiomerically pure iodonorbornenone, ring-opening/closing olefin metathesis, and oxidative aromatization where the sp3 stereogenic center was transmitted to the bowl chirality. Chiral HPLC analysis/resolution of the derivatives were also achieved. Based on theoretical calculations, the columnar crystal packing structure of sumanene and trimethylsumanene was interpreted as due to attractive electrostatic or CH–π interaction. According to the experimental and theoretical studies, the bowl depth and inversion energy were found to increase on methylation for sumanene in contrast to corannulene. Dissimilarities of the effect of methylation on the bowl structure and inversion energy of sumanene and corannulene were ascribed to differences in steric repulsion. A double-well potential model was fitted to the bowl structure–inversion energy correlation of substituted sumanenes, with a small deviation. The effects of various substituents on the sumanene structure and bowl-inversion energy were analyzed by density functional theory calculations, and it was shown that the bowl rigidity is controlled by a combination of electronic and steric effects of the substituents. The electron conductivity of trimethylsumanene was investigated by time-resolved microwave conductivity method, compared with that of sumanene.
Fighting Poverty One Experiment at a Time: A Review of Abhijit Banerjee and Esther Duflo's Poor Economics: A Radical Rethinking of the Way to Fight Global Poverty
Authors: Ravallion Martin
Published: March 2012

Abhijit Banerjee and Esther Duflo offer a coherent vision for an economics of poverty and antipoverty policy. Their economics is grounded in an effort to understand the economic and psychological complexities in the lives of poor people, informed by social experiments and field observations. Their preferred policies entail small reforms at the margin, also informed by experiments—specifically randomized control trials. While the book provides some interesting insights, I question how far its approach will get us in fighting global poverty. (JEL I32, I38, O15, P36)
Thinking Small: A Review of Poor Economics: A Radical Rethinking of the Way to Fight Global Poverty by Abhijit Banerjee and Esther Duflo
Authors: Rosenzweig Mark R
Published: March 2012

In Poor Economics, Abhijit Banerjee and Esther Duflo eschew grand theorizing about poverty reduction in favor of an approach in which intelligently designed and tested small interventions, based on a scientific understanding of the lives of the poor, marginally improve their welfare. In so doing, they describe the findings from the recent large literature describing the behavior and institutions of the poor and the consequences of policy and experimental interventions targeted to poverty populations. In this review, I assess whether “thinking small” with its associated policy regime of transfers, subsidies, and nudges, is both a practical and effective policy prescription for “fighting” poverty and whether the set of studies that have focused on populations that have not escaped poverty has improved our fundamental understanding of both the consequences and causes of poverty. (JEL I32, I38, O15)
The Elasticity of Taxable Income with Respect to Marginal Tax Rates: A Critical Review
Authors: Saez Emmanuel , Slemrod Joel , Giertz Seth H
Published: March 2012

This paper critically surveys the large and growing literature estimating the elasticity of taxable income with respect to marginal tax rates using tax return data. First, we provide a theoretical framework showing under what assumptions this elasticity can be used as a sufficient statistic for efficiency and optimal tax analysis. We discuss what other parameters should be estimated when the elasticity is not a sufficient statistic. Second, we discuss conceptually the key issues that arise in the empirical estimation of the elasticity of taxable income using the example of the 1993 top individual income tax rate increase in the United States to illustrate those issues. Third, we provide a critical discussion of selected empirical analyses of the elasticity of taxable income in light of the theoretical and empirical framework we laid out. Finally, we discuss avenues for future research. (JEL H24, H31, J22)
Identification of a macro-alkaline phosphatase complex in a patient with inflammatory bowel disease
Authors: McTaggart Malcolm P , Rawson Catherine , Lawrence David , Raney Barbara S , Jaundrill Linnet , Miller Lorna A , Murtinho-Braga Joseph , Kearney Edward M
Published: March 2012

We report the rare finding of a macro-alkaline phosphatase (macroALP) complex in a patient with a previously unexplained raised alkaline phosphatase activity. The clinical symptoms were persistent, daily diarrhoea for two months with blood in the stool. The patient was subsequently diagnosed with inflammatory bowel disease, specifically ulcerative colitis, following a rectal biopsy and colonoscopy. Two cases of macroALP associated with ulcerative colitis have been reported before, suggesting there could be an increased prevalence of macroALP in these patients.
Primary prevention of venous thromboembolism
Authors: Figueiredo R S , Stansby G , Bhattacharya V
Published: March 2012

Venous thromboembolism (VTE) is the most common cause of preventable in-hospital mortality and all hospitalized patients should be VTE risk assessed. The VTE risk should be weighed up against risk of bleeding on an individualized basis to guide choice of prophylaxis. The most common method of mechanical thromboprophylaxis is graduated compression stockings, although others, such as intermittent pneumatic devices, are available. Stockings have the greatest benefit when used in combination with pharmacological prophylaxis. However, stockings are contraindicated in some patients, including those with stroke or peripheral arterial disease. Various options for pharmacological thromboprophylaxis are available. The most commonly used agents are the low-molecular-weight heparins, but newer orally active agents may play an increasing role in the future.
The ubiquitous hammerhead ribozyme
Authors: Hammann Christian , Luptak Andrej , Perreault Jonathan , de la Peña Marcos
Published: March 2012

The hammerhead ribozyme is a small catalytic RNA motif capable of endonucleolytic (self-) cleavage. It is composed of a catalytic core of conserved nucleotides flanked by three helices, two of which form essential tertiary interactions for fast self-scission under physiological conditions. Originally discovered in subviral plant pathogens, its presence in several eukaryotic genomes has been reported since. More recently, this catalytic RNA motif has been shown to reside in a large number of genomes. We review the different approaches in discovering these new hammerhead ribozyme sequences and discuss possible biological functions of the genomic motifs.
The functional Hfq-binding module of bacterial sRNAs consists of a double or single hairpin preceded by a U-rich sequence and followed by a 3′ poly(U) tail
Authors: Ishikawa Hirokazu , Otaka Hironori , Maki Kimika , Morita Teppei , Aiba Hiroji
Published: March 2012

Hfq-dependent sRNAs contain, at least, an mRNA base-pairing region, an Hfq-binding site, and a Rho-independent terminator. Recently, we found that the terminator poly(U) of Escherichia coli sRNAs is essential for Hfq binding and therefore for riboregulation. In this study, we tried to identify additional components within Hfq-binding sRNAs required for efficient Hfq binding by using SgrS as a model. We demonstrate by mutational and biochemical studies that an internal hairpin and an immediately upstream U-rich sequence also are required for efficient Hfq binding. We propose that the functional Hfq-binding module of SgrS consists of an internal hairpin preceded by a U-rich sequence and a Rho-independent terminator with a long poly(U) tail. We also show that the Rho-independent terminator alone can act as a functional Hfq-binding module when it is preceded by an internal U-rich sequence. The 3′ region of most known sRNAs share the features corresponding to either a double- or single-hairpin-type Hfq-binding module. We also demonstrate that increasing the spacing between the base-pairing region and the Hfq-binding module reduces or impairs the silencing ability. These findings allowed us to design synthetic Hfq-binding sRNAs to target desired mRNAs.
Alternative splicing networks regulated by signaling in human T cells
Authors: Martinez Nicole M. , Pan Qun , Cole Brian S. , Yarosh Christopher A. , Babcock Grace A. , Heyd Florian , Zhu William , Ajith Sandya , Blencowe Benjamin J. , Lynch Kristen W.
Published: March 2012

The formation and execution of a productive immune response requires the maturation of competent T cells and a robust change in cellular activity upon antigen challenge. Such changes in cellular function depend on regulated alterations to protein expression. Previous research has focused on defining transcriptional changes that regulate protein expression during T-cell maturation and antigen stimulation. Here, we globally analyze another critical process in gene regulation during T-cell stimulation, alternative splicing. Specifically, we use RNA-seq profiling to identify 178 exons in 168 genes that exhibit robust changes in inclusion in response to stimulation of a human T-cell line. Supporting an important role for the global coordination of alternative splicing following T-cell stimulation, these signal-responsive exons are significantly enriched in genes with functional annotations specifically related to immune response. The vast majority of these genes also exhibit differential alternative splicing between naive and activated primary T cells. Comparison of the responsiveness of splicing to various stimuli in the cultured and primary T cells further reveals at least three distinct networks of signal-induced alternative splicing events. Importantly, we find that each regulatory network is specifically associated with distinct sequence features, suggesting that they are controlled by independent regulatory mechanisms. These results thus provide a basis for elucidating mechanisms of signal pathway–specific regulation of alternative splicing during T-cell stimulation.
Push–Pull Control of Motor Output
Authors: Johnson Michael D. , Hyngstrom Allison S. , Manuel Marin , Heckman C. J.
Published: March 2012

Inhibition usually decreases input–output excitability of neurons. If, however, inhibition is coupled to excitation in a push–pull fashion, where inhibition decreases as excitation increases, neuron excitability can be increased. Although the presence of push–pull organization has been demonstrated in single cells, its functional impact on neural processing depends on its effect on the system level. We studied push–pull in the motor output stage of the feline spinal cord, a system that allows independent control of inhibitory and excitatory components. Push–pull organization was clearly present in ankle extensor motoneurons, producing increased peak-to-peak modulation of synaptic currents. The effect at the system level was equally strong. Independent control of the inhibitory component showed that the stronger the background of inhibition, the greater the peak force production. This illustrates the paradox at the heart of push–pull organization: increased force output can be achieved by increasing background inhibition to provide greater disinhibition.
Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells
Authors: Rousseau Charly V. , Dugué Guillaume P. , Dumoulin Andréa , Mugnaini Enrico , Dieudonné Stéphane , Diana Marco A.
Published: March 2012

Inhibitory synapses display a great diversity through varying combinations of presynaptic GABA and glycine release and postsynaptic expression of GABA and glycine receptor subtypes. We hypothesized that increased flexibility offered by this dual transmitter system might serve to tune the inhibitory phenotype to the properties of afferent excitatory synaptic inputs in individual cells. Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic synapse from a mossy fiber (MF), which makes them an ideal model to study excitatory–inhibitory interactions. We examined the functional phenotypes of mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices. We show that glycinergic IPSCs are present in all cells. An additional GABAergic component of large amplitude is only detected in a subpopulation of UBCs. This GABAergic phenotype is strictly anti-correlated with the expression of type II, but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse. Immunohistochemical stainings and agonist applications show that global UBC expression of glycine and GABAAreceptors matches the pharmacological profile of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic origin of the inhibitory phenotype, including the slow kinetics of glycinergic components. These results strongly suggest the presence of a functional coregulation of excitatory and inhibitory phenotypes at the single-cell level. We propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in addition control spike timing in mGluRII-negative UBCs.
Network Analysis of Corticocortical Connections Reveals Ventral and Dorsal Processing Streams in Mouse Visual Cortex
Authors: Wang Quanxin , Sporns Olaf , Burkhalter Andreas
Published: March 2012

Much of the information used for visual perception and visually guided actions is processed in complex networks of connections within the cortex. To understand how this works in the normal brain and to determine the impact of disease, mice are promising models. In primate visual cortex, information is processed in a dorsal stream specialized for visuospatial processing and guided action and a ventral stream for object recognition. Here, we traced the outputs of 10 visual areas and used quantitative graph analytic tools of modern network science to determine, from the projection strengths in 39 cortical targets, the community structure of the network. We found a high density of the cortical graph that exceeded that shown previously in monkey. Each source area showed a unique distribution of projection weights across its targets (i.e., connectivity profile) that was well fit by a lognormal function. Importantly, the community structure was strongly dependent on the location of the source area: outputs from medial/anterior extrastriate areas were more strongly linked to parietal, motor, and limbic cortices, whereas lateral extrastriate areas were preferentially connected to temporal and parahippocampal cortices. These two subnetworks resemble dorsal and ventral cortical streams in primates, demonstrating that the basic layout of cortical networks is conserved across species.
Synergy between Electrical Coupling and Membrane Properties Promotes Strong Synchronization of Neurons of the Mesencephalic Trigeminal Nucleus
Authors: Curti Sebastian , Hoge Gregory , Nagy James I. , Pereda Alberto E.
Published: March 2012

Electrical synapses are known to form networks of extensively coupled neurons in various regions of the mammalian brain. The mesencephalic trigeminal (MesV) nucleus, formed by the somata of primary afferents originating in jaw-closing muscles, constitutes one of the first examples supporting the presence of electrical synapses in the mammalian CNS; however, the properties, functional organization, and developmental emergence of electrical coupling within this structure remain unknown. By combining electrophysiological, tracer coupling, and immunochemical analysis in brain slices of rat and mouse, we found that coupling is mostly restricted to pairs or small clusters of MesV neurons. Electrical transmission is supported by connexin36 (Cx36)-containing gap junctions at somato-somatic contacts where only a small proportion of channels appear to be open (∼0.1%). In marked contrast with most brain structures, coupling among MesV neurons increases with age, such that it is absent during early development and appears at postnatal day 8. Interestingly, the development of coupling parallels the development of intrinsic membrane properties responsible for repetitive firing in these neurons. We found that, acting together, sodium and potassium conductances enhance the transfer of signals with high-frequency content via electrical synapses, leading to strong spiking synchronization of the coupled neurons. Together, our data indicate that coupling in the MesV nucleus is restricted to mostly pairs of somata between which electrical transmission is supported by a surprisingly small fraction of the channels estimated to be present, and that coupling synergically interacts with specific membrane conductances to promote synchronization of these neurons.
Global Not Local Masker Features Govern the Auditory Continuity Illusion
Authors: Riecke Lars , Micheyl Christophe , Oxenham Andrew J.
Published: March 2012

When an acoustic signal is temporarily interrupted by another sound, it is sometimes heard as continuing through, even when the signal is actually turned off during the interruption—an effect known as the “auditory continuity illusion.” A widespread view is that the illusion can only occur when peripheral neural responses contain no evidence that the signal was interrupted. Here we challenge this view using a combination of psychophysical measures from human listeners and computational simulations with a model of the auditory periphery. The results reveal that the illusion seems to depend more on the overall specific loudness than on the peripheral masking properties of the interrupting sound. This finding indicates that the continuity illusion is determined by the global features, rather than the fine-grained temporal structure, of the interrupting sound, and argues against the view that the illusion arises in the auditory periphery.
Concerted Cultivation and Teachers' Evaluations of Students: Exploring the Intersection of Race and Parents' Educational Attainment
Authors: Dumais Susan A. , Kessinger Richard J. , Ghosh Bonny
Published: March 2012

Using data from the Early Childhood Longitudinal Survey and Lareau's concept of concerted cultivation—the idea that educational and financial resources result in different cultural logics in the approach to parenting—the authors examine racial and educational differences in the relationship between parenting practices during elementary school and teachers' evaluations of students' (1) language and literacy skills, (2) approaches to learning, and (3) interpersonal skills. The authors find that both race and education affect the relationship between parenting practices and teachers' evaluations. Children in college-educated white families whose parents volunteer receive higher scores on all dependent variables, while white children in high-school-educated families receive lower evaluations the more often their parents attend conferences. Children in college-educated African American families consistently experience negative academic consequences when their parents make special requests of the school. These findings imply that parental investments do not necessarily translate into equal educational rewards.
Cultural Expectations and Urban Development: The Role of “Cultural Sensitivity” and “Cultural Sincerity” in Local Growth Politics
Authors: Douglas Gordon C. C.
Published: March 2012

This article examines the role of culture in the local urban development process through a case study of recent proposals in Davis, California. The author argues that community cultural expectations—of environmental leadership and the preservation of local character—had an important impact on project proposals and the political campaigns that followed, including the ability of an unlikely corporate developer to win public approval from this town with a vocal and usually powerful anti-corporate character. While on the surface the local growth coalition came together as expected in the literature, this study demonstrates that development organizations operate within cultural contexts that are more complex than the existing discourse has accounted for. Factors that the author calls “cultural sensitivity” and “cultural sincerity” both play a role. As concerns with environmental sustainability and preservation of local character gain prominence in development politics, the insights drawn from these cases are of particular value.
Domestic Violence, Contested Custody, and the Courts: A Review of Findings from Five Studies with Accompanying Documentary
Authors: Araji Sharon K.
Published: March 2012

In keeping with the 2011 PSA meeting's theme, “Sociologists as Claims Makers: Turning Theory Into Action,” the presidential address reported research findings (scientific sociology) that were accompanied by a documentary that represented the research results (applied sociology). Guided by a social constructionist perspective, findings from five studies were organized into seven themes to demonstrate the problems domestic violence victims, or protective parents, encounter when their abusers entangle them in contested custody battles. The documentary shown in the presidential address can be viewed in this article by connecting to a link provided. It is noted that the focus of the research and documentary remain at the social issue level—a phenomenon that exists in society, but has not yet been defined as a social problem. It is argued that the problems identified in the research are affecting many thousands of domestic violence victims and their children, yet the issue has received minimal attention in the discipline of sociology.
Embodying 'health citizenship' in health knowledge to fight health inequalities
Authors: Groleau Danielle
Published: March 2012

This paper wishes to contribute to the debate around citizen participation in health system decision-making that has been present internationally for the last 30 years. I argue that if we aim to change health inequalities, health professionals and planners need to understand the illness and health service experience of citizens. The concept of 'health citizenship' introduced here refers to health knowledge that integrates the lay knowledge of patients and that this integration is translated into health actions such as clinical communication and the planning of health care, programs, and policy. We illustrate our argument with the two cases: health literacy and the promotion of breastfeeding in a Canadian population living in context of poverty. This paper then concludes by addressing the leadership role, Brazilian graduate nursing schools can play in promoting 'health citizenship' and by doing so, contribute to fight health inequalities.
Óbitos associados à infecção hospitalar, ocorridos em um hospital geral de Sumaré-SP, Brasil
Authors: Guimarães Aline Caixeta , Donalisio Maria Rita , Santiago Thaiana Helena Roma , Freire June Barreiros
Published: March 2012

Este estudo investigou o perfil sócio-demográfico, clínico e etiológico dos óbitos associados à infecção hospitalar ocorridos no Hospital Estadual Sumaré, SP, de 2007 a 2008. O estudo retrospectivo dos prontuários (n = 133) mostrou média de 35 dias e desvio padrão de 32,4 dias de internação. A maioria dos pacientes (97%) foi submetida a procedimento invasivo, associados à infecção hospitalar (p≤0,05), entre as quais: 90 (67,7%) pneumonias, 62 (46,6%) infecções urinárias e 97 (73%) infecções de corrente sanguínea. Os óbitos foram associados à infecção hospitalar sendo que, em 75 (56,4%), a infecção foi a causa básica, com etiologia definida em 110 (82,7%), das quais 34 (30,9%) ocorreu por microrganismos multirresistentes. O microorganismo mais freqüente foi Staphylococcus aureus (25%) associado a pneumonias e infecção de corrente sanguínea. O monitoramento da infecção hospitalar contribuiu com a intervenção em situação de risco de complicações clínicas e morte.
Desvelando o saber/ fazer sobre diagnósticos de enfermagem: experiência vivida em neurocirurgia oncológica
Authors: Souza Angeli Soares de , Valadares Glaucia Valente
Published: March 2012

Artigo extraído de dissertação de mestrado, cujo objetivo foi caracterizar a interação dos enfermeiros com os diagnósticos de enfermagem em neurocirurgia oncológica, considerando comportamentos, manifestações, atitudes e práticas. Participaram da pesquisa dezesseis enfermeiros que atuam com igual ou mais de cinco anos em neurocirurgia oncológica no Instituto Nacional de Câncer. Utilizou-se como referencial teórico o Interacionismo Simbólico e como abordagem metodológica a Teoria Fundamentada nos Dados. Os achados apontaram que, o enfermeiro está desvelando possibilidades de cuidar do cliente de neurocirurgia oncológica, não somente na perspectiva do sofrimento, mas, sobretudo, na perspectiva do cuidado existencial, abarcando as suas necessidades e singularidades, respeitando as suas limitações.
Gerenciamento do pessoal de enfermagem com estabilidade no emprego: percepção de enfermeiros
Authors: Guimarães Amanda Troca , Vaghetti Helena Heidtmann , Lunardi Filho Wilson Danilo , Gomes Giovana Calcagno
Published: March 2012

Objetivou-se identificar a percepção de enfermeiros de um hospital universitário sobre o gerenciamento do pessoal de enfermagem com estabilidade no emprego. Pesquisa qualitativa desenvolvida em 2010 com dezesseis enfermeiros. Dados coletados por entrevistas semi-estruturadas e analisados pela Análise Temática geraram duas categorias empíricas: A segurança no trabalho versus a impunidade proporcionada pela estabilidade no emprego; e O (des)comprometimento no trabalho da enfermagem e a estabilidade no emprego. Verificou-se que estabilidade no emprego oferece segurança no trabalho; essa segurança produz impunidade, e os enfermeiros resistem em conduzir processos administrativos. Conclui-se que a segurança favorece a quebra de hierarquias, a impunidade gera a banalização das transgressões, pela falta de medidas administrativas ágeis para resolução de problemas; e a estabilidade no emprego não garante a qualidade da assistência.
Core sets da Classificação Internacional de Funcionalidade, Incapacidade e Saúde
Authors: Riberto Marcelo
Published: March 2012

A Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) propõe um modelo de entendimento da funcionalidade humana que integra aspectos biomédicos, sociais e pessoais, além de homogeneizar a terminologia que descreve as condições incapacitantes relacionadas à saúde. Todavia, em virtude de sua complexidade e da grande quantidade de aspectos contemplados, foi necessário desenvolver instrumentos práticos baseados nela. Os core sets da CIF são conjuntos de categorias da CIF que descrevem a funcionalidade de pessoas com determinadas condições de saúde. Eles vêm sendo desenvolvidos em processos de consenso com representação multiprofissional e internacional. Os core sets podem ser resumidos ou abrangentes, conforme o uso por apenas um ou mais profissionais. Seu uso permite ao profissional de saúde avaliar aspectos não contemplados por qualquer outro instrumento de avaliação funcional, como os fatores ambientais.
Políticas públicas e direitos dos usuários do Sistema Único de Saúde com diabetes mellitus
Authors: Santos Ellen Cristina Barbosa dos , Teixeira Carla Regina de Souza , Zanetti Maria Lúcia , Santos Manoel Antônio dos , Pereira Marta Cristiane Alves
Published: March 2012

Este estudo aborda a relação entre políticas públicas e direitos dos usuários com diabetes mellitus quanto aos insumos utilizados no tratamento da doença, sob o ponto de vista das normas e procedimentos legais de amparo a essa população. Preconiza-se que os profissionais de saúde devem constituir um elo entre os usuários e o atual modelo de saúde vigente, assumindo ativamente um papel de defesa dos direitos dos usuários com diabetes mellitus do sistema único de saúde. Essa postura é um ideal a ser conquistado e consolidado no movimento das práticas cotidianas. Para tanto, é preciso fortalecer o processo educativo, incluindo a dimensão ético-político durante as ações implementadas com os usuários do sistema de saúde.