bluuebunny/crossref_metadata_2025 huggingface dataset:
Salidroside stimulates DNA repair enzyme Parp-1 activity in mouse HSC maintenance
Authors: Li Xue , Sipple Jared , Pang Qishen , Du Wei
Published: March 2012

Salidroside is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea, which has potent antioxidant properties. Here we show that salidroside prevented the loss of hematopoietic stem cells (HSCs) in mice under oxidative stress. Quiescent HSCs were recruited into cell cycling on in vivo challenge with oxidative stress, which was blocked by salidroside. Surprisingly, salidroside does not prevent the production of reactive oxygen species but reduces hydrogen peroxide–induced DNA-strand breaks in bone marrow cells enriched for HSCs. We tested whether salidroside enhances oxidative DNA damage repair in mice deficient for 5 DNA repair pathways known to be involved in oxidative DNA damage repair; we found that salidroside activated poly(ADP-ribose)polymerase-1 (PARP-1), a component of the base excision repair pathway, in mouse bone marrow HSCs as well as primary fibroblasts and human lymphoblasts. PARP-1 activation by salidroside protects quiescent HSCs from oxidative stress–induced cycling in native animals and self-renewal defect in transplanted recipients, which was abrogated by genetic ablation or pharmacologic inhibition of PARP-1. Together, these findings suggest that activation of PARP-1 by salidroside could affect the homeostasis and function of HSCs and contribute to the antioxidant effects of salidroside.
β3-integrin is required for differentiation in OC-2 cells derived from mammalian embryonic inner ear
Authors: Brunetta Ivan , Casalotti Stefano O , Hart Ian R , Forge Andrew , Reynolds Louise E
Published: March 2012

Background

The mammalian inner ear contains the organ of Corti which is responsible for the conversion of sound into neuronal signals. This specialised epithelial tissue is the product of a complex developmental process where a common precursor cell type differentiates into the sound transducing hair cells and the non-innervated supporting cells. We hypothesised that integrin proteins, which are involved in cell attachment to extracellular matrix proteins and cellular signalling, play a role in the differentiation process of the precursor inner ear epithelial cells. To test our hypothesis we have utilised a cell line (OC-2) derived from E13 embryonic immortomouse inner ears. In vitro, by switching the incubation temperature from 33°C to 39°C, the OC-2 cells can be induced to differentiate and express hair cells markers, such as Myosin VIIa. The OC-2 cells are thus a useful model system for testing mechanism of hair cells differentiation.

Results

We have identified 4 integrin subunits which are expressed in OC-2 cells: α6, αv, β1 and β3. Among these, the relative level of expression of the αv, β1 and β3 subunits increased in a time dependent manner when the cells were exposed to the differentiating temperature of 39°C, most notably so for β3 which was not detectable at 33°C. Treatment of fully differentiated OC-2 cells with siRNA against the four integrin subunits reduced the expression of not only the respective integrin proteins but also of the hair cell marker Myosin VIIa. Conversely over-expression of β3 was sufficient to induce the expression of Myosin VIIa at 33°C.

Conclusions

Our data demonstrate that modulation of integrin expression is associated with the differentiation process of the OC-2 cells. This suggests that the maturation of the organ of Corti, from where OC-2 cells are derived, may also depend on changes of gene expression associated with integrin expression.
Functional interconnections of HY1 with MYC2 and HY5 in Arabidopsis seedling development
Authors: Prasad Babu Rajendra V , Kumar Selva V , Nandi Ashis , Chattopadhyay Sudip
Published: March 2012

Arabidopsis seedling development is controlled by many regulatory genes involved in multiple signaling pathways. The functional relationships of these genes working in multiple signaling cascades have started to be unraveled. Arabidopsis HY1/HO1 is a rate-limiting enzyme involved in biosynthesis of phytochrome chromophore. HY5 (a bZIP protein) promotes photomorphogenesis, however ZBF1/MYC2 (a bHLH protein) works as a negative regulator of photomorphogenic growth and light regulated gene expression. Further, MYC2 and HY1 have been shown to play important roles in jasmonic acid (JA) signaling pathways. Here, we show the genetic interactions of HY1 with two key transcription factor genes of light signaling, HY5 and MYC2, in Arabidopsis seedling development. Our studies reveal that although HY1 acts in an additive manner with HY5, it is epistatic to MYC2 in light-mediated seedling growth and gene expression. This study further demonstrates that HY1 additively or synergistically functions with HY5, however it works upstream to MYC2 in JA signaling pathways. Taken together, this study demonstrates the functional interrelations of HY1, MYC2 and HY5 in light and JA signaling pathways.
Polymorphic genes of detoxification and mitochondrial enzymes and risk for progressive supranuclear palsy: a case control study
Authors: Potts Lisa F , Cambon Alex C , Ross Owen A , Rademakers Rosa , Dickson Dennis W , Uitti Ryan J , Wszolek Zbigniew K , Rai Shesh N , Farrer Matthew J , Hein David W , Litvan Irene
Published: March 2012

Background

There are no known causes for progressive supranuclear palsy (PSP). Themicrotubule associated protein tau(MAPT)H1 haplotype is the major genetic factor associated with risk of PSP, with both oxidative stress and mitochondrial dysfunction also implicated. We investigated whether specific single nucleotide polymorphisms (SNPs) in genes encoding enzymes of xenobiotic detoxification, mitochondrial functioning, or oxidative stress response, includingdebrisoquine 4-hydroxylase, paraoxonase 1and2, N-acetyltransferase 1and2 (NAT2), superoxide dismutase 1and2, and PTEN-induced putative kinaseare associated with PSP.

Methods

DNA from 553 autopsy-confirmed Caucasian PSP cases (266 females, 279 males; age at onset 68 ± 8 years; age at death 75 ± 8) from the Society for PSP Brain Bank and 425 clinical control samples (197 females, 226 males; age at draw 72 ± 11 years) from healthy volunteers were genotyped using Taqman PCR and the SequenomiPLEX Gold assay.

Results

The proportion of NAT2 rapid acetylators compared to intermediate and slow acetylators was larger in cases than in controls (OR = 1.82, p < 0.05). There were no allelic or genotypic associations with PSP for any other SNPs tested with the exception ofMAPT(p < 0.001).

Conclusions

Our results show that NAT2 rapid acetylator phenotype is associated with PSP, suggesting that NAT2 may be responsible for activation of a xenobiotic whose metabolite is neurotoxic. Although our results need to be further confirmed in an independent sample, NAT2 acetylation status should be considered in future genetic and epidemiological studies of PSP.
The impact of population-based disease management services for selected chronic conditions: the Costs to Australian Private Insurance - Coaching Health (CAPICHe) study protocol
Authors: Byrnes Joshua M , Goldstein Stan , Venator Benjamin , Pollicino Christine , Ng Shu-Kay , Veroff David , Bennett Christine , Scuffham Paul A
Published: March 2012

Background

Recent evidence from a large scale trial conducted in the United States indicates that enhancing shared decision-making and improving knowledge, self-management, and provider communication skills to at-risk patients can reduce health costs and utilisation of healthcare resources. Although this trial has provided a significant advancement in the evidence base for disease management programs it is still left for such results to be replicated and/or generalised for populations in other countries and other healthcare environments. This trial responds to the limited analyses on the effectiveness of providing chronic disease management services through telephone health coaching in Australia. The size of this trial and it's assessment of cost utility with respect to potentially preventable hospitalisations adds significantly to the body of knowledge to support policy and investment decisions in Australia as well as to the international debate regarding the effect of disease management programs on financial outcomes.

Methods

Intention to treat study applying a prospective randomised design comparing usual care with extensive outreach to encourage use of telephone health coaching for those people identified from a risk scoring algorithm as having a higher likelihood of future health costs. The trial population has been limited to people with one or more of the following selected chronic conditions: namely, low back pain, diabetes, coronary artery disease, heart failure, and chronic obstructive pulmonary disease. This trial will enrol at least 64,835 sourced from the approximately 3 million Bupa Australia private health insured members located across Australia. The primary outcome will be the total (non-maternity) cost per member as reported to the private health insurer (i.e. charged to the insurer) 12 months following entry into the trial for each person. Study recruitment will be completed in early 2012 and the results will be available in late 2013.

Discussion

If positive, CAPICHe will represent a potentially cost-effective strategy to improve health outcomes in higher risk individuals with a chronic condition, in a private health insurance setting.

Trial Registration

Australian New Zealand Clinical Trials Registry reference: ACTRN12611000580976
Inhibiting Mer receptor tyrosine kinase suppresses STAT1, SOCS1/3, and NF-κB activation and enhances inflammatory responses in lipopolysaccharide-induced acute lung injury
Authors: Lee Ye-Ji , Han Ji-Young , Byun Jiyeon , Park Hyun-Jeong , Park Eun-Mi , Chong Young Hae , Cho Min-Sun , Kang Jihee Lee
Published: March 2012

Mer signaling participates in a novel inhibitory pathway in TLR activation. The purpose of the present study was to examine the role of Mer signaling in the down-regulation of TLR4 activation-driven immune responses in mice, i.t.-treated with LPS, using the specific Mer-blocking antibody. At 4 h and 24 h after LPS treatment, expression of Mer protein in alveolar macrophages and lung tissue decreased, sMer in BALF increased significantly, and Mer activation increased. Pretreatment with anti-Mer antibody did not influence the protein levels of Mer and sMer levels. Anti-Mer antibody significantly reduced LPS-induced Mer activation, phosphorylation of Akt and FAK, STAT1 activation, and expression of SOCS1 and -3. Anti-Mer antibody enhanced LPS-induced inflammatory responses, including activation of the NF-κB pathway; the production of TNF-α, IL-1β, and MIP-2 and MMP-9 activity; and accumulation of inflammatory cells and the total protein levels in BALF. These results indicate that Mer plays as an intrinsic feedback inhibitor of the TLR4- and inflammatory mediator-driven immune responses during acute lung injury.
Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression
Authors: Philibert Robert A , Sears Rory A , Powers Linda S , Nash Emma , Bair Thomas , Gerke Alicia K , Hassan Ihab , Thomas Christie P , Gross Thomas J , Monick Martha M
Published: March 2012

Altered CpG DNA methylation contributes to phenotypic changes in smokerˈs alveolar macrophages.

Cigarette smoking is implicated in numerous diseases, including emphysema and lung cancer. The clinical expression of lung disease in smokers is not well explained by currently defined variations in gene expression or simple differences in smoking exposure. Alveolar macrophages play a critical role in the inflammation and remodeling of the lung parenchyma in smoking-related lung disease. Significant gene expression changes in alveolar macrophages from smokers have been identified. However, the mechanism for these changes remains unknown. One potential mechanism for smoking-altered gene expression is via changes in cytosine methylation in DNA regions proximal to gene-coding sequences. In this study, alveolar macrophage DNA from heavy smokers and never smokers was isolated and methylation status at 25,000 loci determined. We found differential methylation in genes from immune-system and inflammatory pathways. Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune-system and inflammatory pathways. A significant number of genes with smoking-altered mRNA expression had inverse changes in methylation status. One gene highlighted by this data was the FLT1, and further studies found particular up-regulation of a splice variant encoding a soluble inhibitory form of the receptor. In conclusion, chronic cigarette smoke exposure altered DNA methylation in specific gene promoter regions in human alveolar macrophages.
Zds1 regulates PP2ACdc55 activity and Cdc14 activation during mitotic exit via its Zds_C motif
Authors: Calabria Ines , Baro Barbara , Rodriguez-Rodriguez Jose-Antonio , Russiñol Nuria , Queralt Ethel
Published: March 2012

At anaphase onset, highly active mitotic cyclin-dependent kinase (Cdk) is inactivated to promote exit from mitosis and completion of cytokinesis. The budding yeast Cdc14p phosphatase is a key mitotic regulator that counteracts cyclin-dependent kinase (Cdk) activity during mitotic exit. Separase, together with Zds1p, promotes the down-regulation of PP2ACdc55 in early anaphase, enabling accumulation of phosphorylated forms of Net1p and nucleolar release of Cdc14p. Here we show that the C-terminal domain of Zds1p, called the Zds_C motif, is required for Zds1-induced release of Cdc14p, while the N-terminal domain of the protein might be involved in regulating this activity. More interestingly, Zds1p physically interacts with Cdc55p, and regulates its localization via the Zds_C motif. Nevertheless, expression of the Zds_C motif at endogenous levels cannot induce timely nucleolar release of Cdc14, despite the proper (nucleolar) localization of Cdc55p. Our results suggest that the activity of PP2ACdc55 cannot be modulated solely through regulation of its localization, and that an additional regulatory step may be required. These results suggest that Zds1p recruits PP2ACdc55 to the nucleolus and induces its inactivation by an unknown mechanism.
Various p53 mutant types differently regulate the Ras circuit to induce a cancer-related gene signature
Authors: Solomon Hilla , Buganim Yosef , Pomeraniec Leslie , Beatus Tsevi , Assia Yael , Kogan-Sakin Ira , Madar Shalom , Goldstein Ido , Brosh Ran , Kalo Eyal , Goldfinger Naomi , Rotter Varda
Published: March 2012

Concomitant expression of mutant p53 and oncogenic Ras, leading to cellular transformation, is well documented. However, the mechanisms by which the various mutant p53 categories cooperate with Ras remain largely obscure. In this study we suggest that different mutant p53 categories cooperate with H-Ras in different manners to induce a unique expression pattern of a cancer related gene signature (CGS). The DNA-contact p53 mutants (p53R248Q and p53R273H) exhibited the highest level of CGS expression by cooperating with NFκB. Furthermore, the Zn+2 region conformational p53 mutants (p53R175H and p53H179R) induced the CGS by elevating H-Ras activity. This elevation in H-Ras activity stemmed from a perturbed function of the p53 transcription target gene, BTG2. In contrast, the L3 loop region conformational mutant (p53G245S) did not affect the CGS expression. Our findings were further corroborated in human tumor-derived cell lines expressing Ras and the aforementioned mutated p53 proteins. These data might assist in future tailor-made therapy which targets the mutant p53-Ras axis in cancer.
The late endosomal adaptor p14 is a macrophage host defense factor against Salmonella Typhimurium infection
Authors: Taub Nicole , Nairz Manfred , Hilber Diana , Hess Michael W. , Weiss Günter , Huber Lukas A.
Published: March 2012

The outcome of an infection depends on the balance between host resistance and bacterial virulence. Here, we show that the late endosomal adaptor p14 (also known as LAMTOR2) is one of the components for cellular host defense against the intracellular pathogen Salmonella Typhimurium. During Salmonella infection, the complex of p14 and MP1 is required for the accurately timed transport of Salmonella through the endolysosomal system. Loss of p14 opens a time window that allows Salmonella to populate a replication niche, in which early and late antimicrobial effector systems, comprising NADPH phagocytic oxidase and inducible nitric oxide synthase, respectively, are inappropriately activated. Thus, p14 supports the accurate transport of Salmonella through the endolysosomal system, thereby limiting bacterial replication in both, professional phagocytes and in non-phagocytic cells in vitro, and helps mice to successfully battle Salmonella infection in vivo.
Polo-like kinase is necessary for flagellum inheritance in Trypanosoma brucei
Authors: Ikeda Kyojiro N. , de Graffenried Christopher L.
Published: March 2012

Polo-like kinases play an important role in a variety of mitotic events in mammalian cells, ranging from centriole separation and chromosome congression to abscission. To fulfill these roles, PLK homologs move to different cellular locations as the cell cycle progresses, starting at the centrosome, progressing to the spindle poles and then the midbody. In the protist parasite Trypanosoma brucei, the single polo-like kinase homolog TbPLK is essential for cytokinesis and is necessary for the correct duplication of a centrin-containing cytoskeletal structure known as the bilobe. We show that TbPLK has a dynamic localization pattern during the cell cycle. The kinase localizes to the basal body, which nucleates the flagellum, and then successively localizes to a series of cytoskeletal structures that regulate the position and attachment of the flagellum to the cell body. The kinase localizes to each of these structures as they are duplicating. TbPLK associates with a specialized set of microtubules, known as the microtubule quartet, which may transport the kinase during its migration. Depletion of TbPLK causes defects in basal body segregation and blocks the duplication of the regulators that position the flagellum, suggesting that its presence on these structures might be necessary for their proper biogenesis. The ability of PLKs to migrate throughout the cell is preserved in T. brucei, but the specific locations to which it targets and functions are geared towards the inheritance of a properly positioned and attached flagellum.
TOR Signaling Regulates Planarian Stem Cells and Controls Localized and Organismal Growth
Authors: Peiris T. Harshani , Weckerle Frank , Ozamoto Elyse , Ramirez Daniel , Davidian Devon , García-Ojeda Marcos E. , Oviedo Néstor J.
Published: March 2012

The Target of Rapamycin (TOR) controls an evolutionarily conserved signaling pathway that modulates cellular growth and division by sensing levels of nutrients, energy and stress. As such, TOR signaling is a crucial component of tissues and organs that translates systemic signals into cellular behavior. The ubiquitous nature of TOR signaling, together with the difficulty to analyze tissue during cellular turnover and repair, have limited our understanding on how this kinase operates throughout the body. Here, we use the planarian model system to address TOR regulation at the organismal level. The planarian TOR homolog (Smed-TOR) is ubiquitously expressed, including stem cells (neoblasts) and differentiated tissues. Inhibition of TOR with RNA-interference severely restricts cell proliferation, allowing the study of neoblasts with restricted proliferative capacity during regeneration and systemic cell turnover. Strikingly, TOR signaling is required for neoblast response to amputation and localized growth (blastema). However, in the absence of TOR signaling, regeneration takes place only within differentiated tissues. In addition, TOR is essential to maintain the balance between cell division and cell death and its dysfunction leads to tissue degeneration and lack of organismal growth in the presence of nutrients. Finally, TOR function is likely mediated through TOR Complex 1 as its disruption recapitulates signs of TOR-phenotype. Our data reveal novel roles for TOR signaling in controlling adult stem cells at a systemic level and suggest a new paradigm to study TOR function during physiological turnover and regeneration.
Actin coating and compression of fused secretory vesicles are essential for surfactant secretion: a role for Rho, formins and myosin II
Authors: Miklavc Pika , Hecht Elena , Hobi Nina , Wittekindt Oliver H. , Dietl Paul , Kranz Christine , Frick Manfred
Published: March 2012

Secretion of vesicular contents via exocytosis is a fundamental cellular process. Increasing evidence suggests that post-fusion events play an important role in determining the composition and quantity of the secretory output. In particular, regulation of fusion pore dilation/closure is considered a key regulator of the post-fusion phase. However, dependent on the nature of the cargo additional mechanisms might be essential to facilitate effective release. We have recently described that in alveolar type II (ATII) cells lamellar bodies (LBs), secretory vesicles that store lung surfactant, are coated with actin following fusion with the plasma membrane (PM). Surfactant, a lipoprotein complex, does not readily diffuse out of fused LBs following opening and dilation of the fusion pore. Using fluorescence microscopy, atomic force microscopy and biochemical assays we present evidence that actin coating and subsequent contraction of the actin coat is essential to facilitate surfactant secretion. Preventing actin coating of fused LBs with latrunculin B (latB) inhibits surfactant secretion almost completely. Simultaneous imaging of the vesicle membrane and the actin coat revealed that contraction of the actin coat compresses the vesicle following fusion. This leads to active extrusion of vesicle contents. Initial actin coating of fused vesicles is dependent on activation of Rho and formin-dependent actin nucleation. Actin coat contraction is facilitated by myosin II. In summary, our data suggest that fusion pore opening and dilation itself is not sufficient for release of bulky vesicle cargos and that active extrusion mechanisms are required.
Determination of sex from an autopsy sample of adult hyoid bones
Authors: Mukhopadhyay Partha Pratim
Published: March 2012

Determination of sex is the first and crucial step in the process of identifying human remains in forensic casework. Sex determination from skeletal remains is well studied and an extensively documented subject. The hyoid bone, however, has drawn less attention in studies of this nature. The present study was designed to derive a model for the determination of sex from the adult hyoid in a sample of the Indian Bengali population using discriminant function analysis on 50 adult bones (38 men and 12 women). The following discriminant function was obtained: DF = 0.103 W + 0.118AP + 0.130CR + 0.483AW + 0.117DR − 20.64. Overall, 90% of the cases could be correctly classified into the two sexes by means of five predictors (overall width, length of the greater cornu, anteroposterior length, width of the body of hyoid and the distance between the lesser cornua) in the model. Cross-validated results showed correct classification in 90% of the cases. The results of this preliminary study show that these variables contribute to discrimination between the two sexes in the study population. Sexing of the adult human hyoid bone is thus possible with reasonable accuracy using the discriminant function on a sample obtained from the same population.
An analysis of fingerprint ridge density in the Indo-Mauritian population and its application to gender determination
Authors: Agnihotri Arun Kumar , Jowaheer Vandna , Allock Anishta
Published: March 2012

Gender determination is an important aspect of personal identification, which is often required in medicolegal practice. Many experts believe that there are finer and more epidermal ridges on the fingers of women as compared with men. However, it is important to establish numerical cut-off values in terms of ridge counts to facilitate the gender determination within a particular population. The present study was conducted in the Department of Forensic Medicine, SSR Medical College, Mauritius with the objective to describe the ridge density in the Indo-Mauritian population and to devise a numerical model which is capable of identifying the sex of an individual from this population on the basis of the ridge counts obtained from the corresponding finger prints. The study was focused on 200 healthy medical students (100 men and 100 women) within the age range of 20–30 years. Multivariate analysis of variance results shows a significant gender difference in the sense that women tend to have higher ridge density then men in the distal region of all 10 digits ( F = 41.83, P ≤ 0.005). The maximum mean ridge density over all fingers in men (12.26∼12) is less than the minimum mean ridge density over all fingers in women (12.71∼13). A linear discriminant function is derived from numerical modelling, which is used to predict (with a high reliability index, 0.92) the sex of the person whose fingerprints are obtained.
The Nearly Neutral and Selection Theories of Molecular Evolution Under the Fisher Geometrical Framework: Substitution Rate, Population Size, and Complexity
Authors: Razeto-Barry Pablo , Díaz Javier , Vásquez Rodrigo A
Published: March 2012

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population’s phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models.
Modular TRAPP Complexes Regulate Intracellular Protein Trafficking Through Multiple Ypt/Rab GTPases in Saccharomyces cerevisiae
Authors: Zou Shenshen , Liu Yutao , Zhang Xiu Qi , Chen Yong , Ye Min , Zhu Xiaoping , Yang Shu , Lipatova Zhanna , Liang Yongheng , Segev Nava
Published: March 2012

Ypt/Rab are key regulators of intracellular trafficking in all eukaryotic cells. In yeast, Ypt1 is essential for endoplasmic reticulum (ER)-to-Golgi transport, whereas Ypt31/32 regulate Golgi-to-plasma membrane and endosome-to-Golgi transport. TRAPP is a multisubunit complex that acts as an activator of Ypt/Rab GTPases. Trs85 and Trs130 are two subunits specific for TRAPP III and TRAPP II, respectively. Whereas TRAPP III was shown to acts as a Ypt1 activator, it is still controversial whether TRAPP II acts as a Ypt1 or Ypt31/32 activator. Here, we use GFP-Snc1 as a tool to study transport in Ypt and TRAPP mutant cells. First, we show that expression of GFP-Snc1 in trs85Δ mutant cells results in temperature sensitivity. Second, we suggest that in ypt1ts and trs85Δ, but not in ypt31Δ/32ts and trs130ts mutant cells, GFP-Snc1 accumulates in the ER. Third, we show that overexpression of Ypt1, but not Ypt31/32, can suppress both the growth and GFP-Snc1 accumulation phenotypes of trs85Δ mutant cells. In contrast, overexpression of Ypt31, but not Ypt1, suppresses the growth and GFP-Snc1 transport phenotypes of trs130ts mutant cells. These results provide genetic support for functional grouping of Ypt1 with Trs85-containing TRAPP III and Ypt31/32 with Trs130-containing TRAPP II.
APJ1 and GRE3 Homologs Work in Concert to Allow Growth in Xylose in a Natural Saccharomyces sensu stricto Hybrid Yeast
Authors: Schwartz Katja , Wenger Jared W , Dunn Barbara , Sherlock Gavin
Published: March 2012

Creating Saccharomyces yeasts capable of efficient fermentation of pentoses such as xylose remains a key challenge in the production of ethanol from lignocellulosic biomass. Metabolic engineering of industrial Saccharomyces cerevisiae strains has yielded xylose-fermenting strains, but these strains have not yet achieved industrial viability due largely to xylose fermentation being prohibitively slower than that of glucose. Recently, it has been shown that naturally occurring xylose-utilizing Saccharomyces species exist. Uncovering the genetic architecture of such strains will shed further light on xylose metabolism, suggesting additional engineering approaches or possibly even enabling the development of xylose-fermenting yeasts that are not genetically modified. We previously identified a hybrid yeast strain, the genome of which is largely Saccharomyces uvarum, which has the ability to grow on xylose as the sole carbon source. To circumvent the sterility of this hybrid strain, we developed a novel method to genetically characterize its xylose-utilization phenotype, using a tetraploid intermediate, followed by bulk segregant analysis in conjunction with high-throughput sequencing. We found that this strain’s growth in xylose is governed by at least two genetic loci, within which we identified the responsible genes: one locus contains a known xylose-pathway gene, a novel homolog of the aldo-keto reductase gene GRE3, while a second locus contains a homolog of APJ1, which encodes a putative chaperone not previously connected to xylose metabolism. Our work demonstrates that the power of sequencing combined with bulk segregant analysis can also be applied to a nongenetically tractable hybrid strain that contains a complex, polygenic trait, and identifies new avenues for metabolic engineering as well as for construction of nongenetically modified xylose-fermenting strains.
Synthesis and Characterization of Novel Graphene Silicon Oxide Nanocomposite Material
Authors: Alam Tanvir E , Ram Manoj K. , Ladanov Mikhail , Alvi Farah , Mujumdar Ajit , Kumar Ashok
Published: March 2012

The primary objective of our work is to understand the nanocomposite structure of SiO2 coated over graphene (G) nanoplatelets. An attempt has been made to synthesize G-SiO2 nanocomposite using sol-gel technique. The G-SiO2 nanocomposite is characterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Raman spectroscopy, FTIR spectroscopy, and Electrochemical and Electrical measurement technique, respectively. The G-SiO2 nanocomposite reveals platelets characteristics much larger in size than the graphene nanoplatelets. The conductivity of G-SiO2 has been found to increase with an increase in the graphene ratio to SiO2 in nanocomposite material. The G-SiO2 has revealed interesting feature vibrational bands of graphene with SiO2 by varying the precursor of SiO2 with graphene moieties. The cyclic voltammetry studies have indicated the diffusion controlled system. The G-SiO2 nanocomposite shows interesting current–voltage characteristics with variation of graphene in nanocomposite. Our result is indicative of a transformable and viable G-SiO2 material for energy and electrical relay applications.
Redução das desigualdades sociais na utilização de serviços odontológicos no Brasil entre 1998 e 2008
Authors: Peres Karen Glazer , Peres Marco Aurélio , Boing Antonio Fernando , Bertoldi Andréa Dâmaso , Bastos João Luiz , Barros Aluisio J D
Published: March 2012

OBJETIVO: Analisar o acesso e utilização de serviços odontológicos no Brasil. MÉTODOS: Foram utilizados os dados da Pesquisa Nacional por Amostra de Domicílios de 2003 e 2008, comparando-os com os de 1998. Investigaram-se as variáveis de acesso e uso de serviços odontológicos nas idades de três, seis, nove, 12, 15 e 19 anos e no primeiro (Q1) e no quinto (Q5) quintis de renda familiar per capita. As análises consideraram o desenho amostral complexo. RESULTADOS: A proporção de pessoas que nunca consultaram o dentista diminuiu (18,7% em 1998, 15,9% em 2003 e 11,7% em 2008). Houve importante redução na diferença absoluta de não utilização do serviço odontológico a partir dos nove anos entre Q1 e Q5 de 1998 a 2008, diminuindo para cerca de metade aos 15 (30,3 pontos percentuais - pp para 16,1 pp) e aos 19 anos (20,4 pp para 9,9 pp). As razões entre Q1 e Q5 para consulta recente ao dentista diminuíram em todas as idades, principalmente entre zero e seis anos (Q5/Q1 de 3,2 para 2,6); a utilização do Sistema Único de Saúde para atendimento odontológico aumentou nos Q1 e Q5, com redução na razão entre os grupos Q1/Q5 de cerca de 20%. A utilização do Sistema Único de Saúde para atendimento odontológico aumentou cerca de 8% no Q1 e 35% no Q5 entre 2003 e 2008. CONCLUSÕES: Houve avanço considerável na redução das desigualdades no acesso e aumento na utilização de serviços odontológicos no Brasil entre 1998 e 2008. Entretanto, as iniquidades entre os grupos sociais ainda é expressiva.
Dopplerfluxometria de artérias oftálmicas e avaliação da função endotelial nas formas precoce e tardia da pré-eclâmpsia
Authors: Brandão Augusto Henriques Fulgêncio , Barbosa Alexandre Simão , Lopes Ana Paula Brum Miranda , Leite Henrique Vitor , Cabral Antônio Carlos Vieira
Published: March 2012

OBJETIVO: Avaliar possíveis diferenças entre a disfunção endotelial, avaliada pela dilatação fluxo-mediada, e hiperperfusão central, avaliada por dopplerfluxometria da artéria oftálmica, entre pacientes portadoras da forma precoce e tardia da pré-eclâmpsia. MATERIAIS E MÉTODOS: O teste de dilatação fluxo-mediada e a dopplerfluxometria da artéria oftálmica foram obtidos de 81 gestantes, sendo 56 portadoras de pré-eclâmpsia (26 na forma precoce e 30 na forma tardia) e 25 gestantes saudáveis (grupo controle). RESULTADOS: Portadoras de pré-eclâmpsia apresentaram valores menores de dilatação fluxo-mediada quando comparadas ao grupo controle, tanto na forma precoce (7,62 ± 5,42% × 14,12 ± 6,14%; p = 0,02) como na forma tardia (5,83 ± 4,12% × 14,12 ± 6,14%; p = 0,00). Não houve diferença quando foram comparadas as duas formas (7,62 ± 5,42% × 5,83 ± 4,12%; p = 0,09). A dopplerfluxometria da artéria oftálmica apresentou-se significativamente menor nas pacientes portadoras de pré-eclâmpsia quando comparadas ao grupo controle, tanto na forma precoce (0,631 ± 0,024 × 0,737 ± 0,032; p = 0,01) como na forma tardia (0,653 ± 0,019 × 0,737 ± 0,032; p = 0,03). Não houve diferença entre as duas formas de apresentação (0,631 ± 0,024 × 0,653 ± 0,019; p = 0,12). Os resultados basicamente demonstram redução nos valores de dilatação fluxo-mediada e dopplerfluxometria da artéria oftálmica nas formas tardia e precoce da pré-eclâmpsia quando comparadas ao grupo controle, sem, contudo, diferenças significativas entre as duas formas de apresentação da doença. CONCLUSÃO: Os resultados indicam a presença de disfunção endotelial e hiperperfusão central em gestantes com pré-eclâmpsia, tanto na forma precoce como na tardia.
Controle de qualidade de monitores de diagnóstico por imagem e iluminância nos espaços de pós-processamento em serviços de imagiologia
Authors: Pinto Márcia , Pedro Maria , Santos António , Saraiva António
Published: March 2012

OBJETIVO: Avaliar a qualidade dos monitores de diagnóstico e tratamento de imagem digital em radiologia convencional (raios X) com base nos níveis de luminância. Fez-se a medição da iluminância dos postos de trabalho onde estavam os monitores. MATERIAIS E MÉTODOS: A medição da luminância foi realizada usando-se um detector Unfors Xi Light em cinco instituições, com 23 monitores primários e 22 secundários, sendo 6 usados em urgência, seguindo o método descrito no relatório TG18 da American Association of Physicists in Medicine (AAPM). O instrumento de medida utilizado foi o Delta Ohm HD 9221 luximeter. RESULTADOS: Para as recomendações da AAPM, tanto monitores primários como secundários cumpriram, no geral, os níveis de tolerância. No caso dos níveis de iluminância, nos locais de trabalho dos monitores primários encontravam-se ligeiramente acima do intervalo recomendado. Quanto às recomendações do The Royal College of Radiologists (RCR), os monitores que respeitaram os níveis recomendados estavam em minoria, embora as diferenças não fossem significativas. CONCLUSÃO: Em geral, os resultados foram satisfatórios, embora os monitores não fossem adequados para atingir as recomendações exigentes do RCR. Os níveis de referência entre os monitores primários e secundários deveriam aproximar-se, de modo a garantir a qualidade de imagem. Os monitores para visualização e diagnóstico de imagens médicas devem ser regularmente avaliados para manter um sistema com a qualidade exigida, dada a função que desempenham.
Caracterização dosimétrica de feixes de fótons com detector de diamante
Authors: Sabino Talita , Rodrigues Laura Natal , Furnari Laura , Watanabe Érika Yumi , Menegussi Gisela
Published: March 2012

OBJETIVO: Este trabalho foi realizado com o objetivo de caracterizar o detector de diamante, bem como observar seu comportamento. MATERIAIS E MÉTODOS: As características dosimétricas de feixes de fótons de 6 MV de energia foram medidas utilizando o sistema automático de varredura MP3 da PTW com um detector de diamante e foram comparadas com medidas usando uma câmara de ionização 31010 da PTW. RESULTADOS: As características dosimétricas do detector de diamante foram observadas por meio de medidas de linearidade com a dose, dependência com a taxa de dose e distribuições de dose em profundidade, bem como perfis. CONCLUSÃO: Algumas medidas com diamante e câmara de ionização foram validadas com resultados publicados na literatura, o que demonstrou um bom comportamento do detector de diamante na comparação com a câmara de ionização, muito utilizada para dosimetria em radioterapia, evidenciando que o diamante é uma boa escolha de detector para dosimetria de campos pequenos.
Perfusão por tomografia computadorizada do abdome: aplicações clínicas, princípios e técnica do exame
Authors: Sousa João Paulo Lira Barros Almeida de , Bekhor Daniel , Saito Filho Celso Fernando , Bretas Elisa Almeida Sathler , D'Ippolito Giuseppe
Published: March 2012

Novas técnicas de exames têm sido desenvolvidas com o objetivo de se obter não apenas uma avaliação estrutural, mas também uma análise funcional e metabólica de diversos órgãos e tipos de lesões. Entre estas ferramentas, a perfusão por tomografia computadorizada (PTC) tem despertado o interesse de muitos pesquisadores em estudar a sua aplicabilidade em órgãos e doenças abdominais. Entre estas aplicações podemos citar a avaliação do comportamento biológico de tecidos sadios e doentes, a diferenciação de processos inflamatórios de tumorais e o diagnóstico da recidiva tumoral após terapêuticas minimamente invasivas. A principal característica da PTC reside na sua capacidade de caracterizar comportamentos perfusionais distintos e que traduzem alterações biológicas de determinadas lesões e tecidos doentes. Dessa forma, o nosso objetivo foi realizar uma ampla revisão da literatura, mostrando as principais técnicas e protocolos utilizados nos exames de PTC, as principais indicações, vantagens e desvantagens do método, além de propor um protocolo de exame que possa ser introduzido na rede privada e pública de saúde, com reprodutibilidade e simplicidade de implementação.
Modeling of allergen proteins found in sea food products
Authors: Galán-Freyle Nataly , Olivero-Verbel Jesús , Díaz-López Liney
Published: March 2012

Shellfish are a source of food allergens, and their consumption is the cause of severe allergic reactions in humans. Tropomyosins, a family of muscle proteins, have been identified as the major allergens in shellfish and mollusks species. Nevertheless, few experimentally determined three-dimensional structures are available in the Protein Data Base (PDB). In this study, 3D models of several homologous of tropomyosins present in marine shellfish and mollusk species (Chaf 1, Met e1, Hom a1, Per v1, and Pen a1) were constructed, validated, and their immunoglobulin E binding epitopes were identified using bioinformatics tools. All protein models for these allergens consisted of long alpha-helices. Chaf 1, Met e1, and Hom a1 had six conserved regions with sequence similarities to known epitopes, whereas Per v1 and Pen a1 contained only one. Lipophilic potentials of identified epitopes revealed a high propensity of hydrophobic amino acids in the immunoglobulin E binding site. This information could be useful to design tropomyosin-specific immunotherapy for sea food allergies.
Effect of process variables on the osmotic dehydration of star-fruit slices
Authors: Campos Camila Dalben Madeira , Sato Ana Carla Kawazoe , Tonon Renata Valeriano , Hubinger Míriam Dupas , Cunha Rosiane Lopes da
Published: March 2012

The objective of this work was to study the effect of blanching and the influence of temperature, solution concentration, and the initial fruit:solution ratio on the osmotic dehydration of star-fruit slices. For blanching, different concentrations of citric and ascorbic acids were studied. The samples immersed in 0.75% citric acid presented little variation in color in relation to the fresh star-fruit. Osmotic dehydration was carried out in an incubator with orbital shaking, controlled temperature, and constant shaking at 120 rpm. The influence of process variables was studied in trials defined by a complete 23 central composite design. In general, water loss and solids gain were positively influenced by temperature and by solution concentration. Nevertheless, lower temperatures reduced water loss throughout the osmotic dehydration process. An increase in the amount of dehydrating solution (initial fruit:solution ratio) slightly influenced the evaluated responses. The process carried out at 50 ºC with a solution concentration of 50% resulted in a product with lower solids gain and greater water loss. Under these conditions, blanching minimized the effect of the osmotic treatment on star-fruit browning, and therefore the blanched fruits showed little variation in color in relation to the fresh fruit.
Influence of the use of rice bran extract as a source of nutrients on xylitol production
Authors: Martínez Ernesto Acosta , Santos Juliana Aparecida Frade
Published: March 2012

Xylose-to-xylitol bioconversion using 2.5 or 10% (v/v) rice bran extract was performed to verify the influence of this source of nutrients on Candida guilliermondii metabolism. Semisynthetic medium (SM) and sugarcane bagasse hemicellulosic hydrolysate detoxified with ion-exchange resins (HIE) or with alteration in pH combined with adsorption onto activated charcoal (HAC) were fermented in 125 mL Erlenmeyer flasks at 30 ºC and 200 rpm for 72 hours. Activated charcoal supplemented with 2.5% (v/v) rice bran extract was fermented by C. guilliermondii in a MULTIGEN stirred tank reactor using pH 5.0 and 22.9/hour oxygen transfer volumetric coefficient. Higher values of xylitol productivity (0.70, 0.71, and 0.62 g.Lh-1) and xylose-to-xylitol conversion yield (0.71, 0.69, and 0.63 g.g-1) were obtained with 2.5% (v/v) rice bran in semisynthetic medium, ion-exchange resins, and activated charcoal, respectively. Moreover, during batch fermentation, the xylitol volumetric productivity and fermentation efficiency values obtained were 0.53 g.Lh-1 and 61.1%, respectively.
O "homem dos riscos" e o "homem lento" e a teorização sobre o risco epidemiológico em tempos de globalização
Authors: Sevalho Gil
Published: March 2012

Utilizando o tempo como elemento de composição interdisciplinar, discute-se o conceito de risco epidemiológico reconhecendo-se o "homem dos riscos", criado pelo epidemiologista Naomar de Almeida-Filho, e o "homem lento", criado pelo geógrafo Milton Santos. A crítica de Jean-François Lyotard apontando a ciência como discurso que desconsidera a narrativa popular é usada na argumentação. O homem lento resiste à fragmentação das identidades imposta pela globalização, tecendo criativamente a solidariedade no lugar; o homem dos riscos será o da velocidade, da modernidade, impondo uma ordem padronizadora, individualista e competitiva. O risco epidemiológico é pensado na proximidade do território e do lugar, contrapondo-se a concretude do homem lento à artificialidade do discurso epidemiológico povoado pelo homem dos riscos. A Epistemologia do Sul de Boaventura de Sousa Santos, com suas sociologias das ausências e das emergências, toma por base esta perspectiva crítica, propondo uma prática científica politicamente comprometida com a justiça social, privilegiando o saber popular.
Sentidos do trabalho e racionalidades instrumental e substantiva: interfaces entre a administração e a psicologia
Authors: Andrade Sílvia Patricia Cavalheiro de , Tolfo Suzana da Rosa , Dellagnelo Eloise Helena Livramento
Published: March 2012

Os debates sobre racionalidade e seus conceitos são clássicos em administração. Em contrapartida, os estudos sobre os significados e os sentidos atribuídos ao trabalho, na psicologia, são da década de 1970. Ao estudar os sentidos do trabalho, os autores não têm se remetido à questão das racionalidades instrumental e substantiva, mas priorizado a identificação daquilo que caracteriza um trabalho com sentido. Neste ensaio teórico, tem-se como pressuposto que os sentidos atribuídos ao trabalho estão relacionados aos tipos de racionalidades presentes na sociedade e nas organizações de trabalho. Pretende-se, assim, identificar aproximações entre os traços que caracterizam os sentidos atribuídos ao trabalho e as racionalidades instrumental e substantiva. Apresentam-se elementos que caracterizam os sentidos do trabalho com base em referências da psicologia, enfocando as pesquisas de Morin (1996, 2001), bem como estudos que caracterizam os traços constitutivos das racionalidades em questão, tradicionalmente estudados na administração, com ênfase em Serva (1993, 1996, 1997a, 1997b). Essa tentativa de articulação possibilitou também o desenvolvimento da concepção de sentidos do trabalho do tipo instrumental e do trabalho do tipo substantivo; destacando-se que há uma imbricação entre ambos os tipos de sentidos nas organizações.