bluuebunny/crossref_metadata_2025 huggingface dataset:
“Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions”
Authors: Domingos Renan F , Vieira Monica L , Romero Eliete C , Gonçales Amane Paldes , de Morais Zenaide M , Vasconcellos Silvio A , Nascimento Ana L T O
Published: March 2012

Background

Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have the ability to survive and disseminate to multiple organs after penetrating the host. Leptospires were shown to express surface proteins that interact with the extracellular matrix (ECM) and to plasminogen (PLG). This study examined the interaction of two putative leptospiral proteins with laminin, collagen Type I, collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and C4bp.

Results

We show that two leptospiral proteins encoded by LIC11834 and LIC12253 genes interact with laminin in a dose - dependent and saturable mode, with dissociation equilibrium constants (K
D) of 367.5 and 415.4 nM, respectively. These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand participate in this interaction. The Lsa33 is also PLG - binding receptor, with a K
D of 23.53 nM, capable of generating plasmin in the presence of an activator. Although in a weak manner, both proteins interact with C4bp, a regulator of complement classical route. In silico analysis together with proteinase K and immunoflorescence data suggest that these proteins might be surface exposed. Moreover, the recombinant proteins partially inhibited leptospiral adherence to immobilized laminin and PLG.

Conclusions

We believe that these multifunctional proteins have the potential to participate in the interaction of leptospires to hosts by mediating adhesion and by helping the bacteria to escape the immune system and to overcome tissue barriers. To our knowledge, Lsa33 is the first leptospiral protein described to date with the capability of binding laminin, PLG and C4bp in vitro.
Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer
Authors: Hu Bang , Ren Donglin , Su Dan , Lin Hongcheng , Xian Zhenyu , Wan Xingyang , Zhang Junxiao , Fu Xinhui , Jiang Li , Diao Dechan , Fan Xinjuan , Wang Lei , Wang Jianping
Published: March 2012

Background

Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues and correlated it with clinicopathologic data.

Methods

pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively.

Results

pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues (6 out of 80, 7.5%; P < 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5 in CRC tissues was significantly correlated to the depth of invasion (P = 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and high preoperative CEA level (P < 0.001). Consistently, the pMEK5 level in CRC tissues was increased following stage progression of the disease (P < 0.001). Analysis of the survival curves showed a significantly worse 5-year disease-free (P = 0.002) and 5-year overall survival rate (P < 0.001) for patients whose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic factor for CRC (DFS: P = 0.139; OS: P = 0.071).

Conclusions

pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.
AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model
Authors: Wu Qin Jie , Gong Chang Yang , Luo Shun Tao , Zhang Dong Mei , Zhang Shuang , Shi Hua Shan , Lu Lian , Yan Heng Xiu , He Sha Sha , Li Dan Dan , Yang Li , Zhao Xia , Wei Yu Quan
Published: March 2012

Background

Angiogenesis plays an important role in tumor growth and metastasis, therefore antiangiogenic therapy was widely investigated as a promising approach for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus (AAV) vectors have been intensively studied due to their wide tropisms, nonpathogenicity, and long-term transgene expression in vivo. The objective of this work was to evaluate the ability of AAV-mediated human PEDF (hPEDF) as a potent tumor suppressor and a potential candidate for cancer gene therapy.

Methods

Recombinant AAV2 encoding hPEDF (rAAV2-hPEDF) was constructed and produced, and then was assigned for in vitro and in vivo experiments. Conditioned medium from cells infected with rAAV2-hPEDF was used for cell proliferation and tube formation tests of human umbilical vein endothelial cells (HUVECs). Subsequently, colorectal peritoneal carcinomatosis (CRPC) mouse model was established and treated with rAAV2-hPEDF. Therapeutic efficacy of rAAV2-hPEDF were investigated, including tumor growth and metastasis, survival time, microvessel density (MVD) and apoptosis index of tumor tissues, and hPEDF levels in serum and ascites.

Results

rAAV2-hPEDF was successfully constructed, and transmission electron microscope (TEM) showed that rAAV2-hPEDF particles were non-enveloped icosahedral shape with a diameter of approximately 20 nm. rAAV2-hPEDF-infected cells expressed hPEDF protein, and the conditioned medium from infected cells inhibited proliferation and tube-formation of HUVECs in vitro. Furthermore, in CRPC mouse model, rAAV2-hPEDF significantly suppressed tumor growth and metastasis, and prolonged survival time of treated mice. Immunofluorescence studies indicated that rAAV2-hPEDF could inhibit angiogenesis and induce apoptosis in tumor tissues. Besides, hPEDF levels in serum and ascites of rAAV2-hPEDF-treated mice were significant higher than those in rAAV2-null or normal saline (NS) groups.

Conclusions

Thus, our results suggest that rAAV2-hPEDF may be a potential candidate as an antiangiogenic therapy agent.
Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium falciparum malaria in India
Authors: Anvikar Anupkumar R , Sharma Bhawna , Shahi Bhartendu H , Tyagi Prajesh K , Bose Tarit K , Sharma Surya K , Srivastava Prakriti , Srivastava Bina , Kiechel Jean R , Dash Aditya P , Valecha Neena
Published: March 2012

Background

Artemisinin-based combination therapy (ACT) has been recommended for the treatment of falciparum malaria by the World Health Organization. Though India has already switched to ACT for treating falciparum malaria, there is need to have multiple options of alternative forms of ACT. A randomized trial was conducted to assess the safety and efficacy of the fixed dose combination of artesunate-amodiaquine (ASAQ) and amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria for the first time in India. The study sites are located in malaria-endemic, chloroquine-resistant areas.

Methods

This was an open label, randomized trial conducted at two sites in India from January 2007 to January 2008. Patients between six months and 60 years of age having Plasmodium falciparum mono-infection were randomly allocated to ASAQ and AQ arms. The primary endpoint was 28-day PCR-corrected parasitological cure rate.

Results

Three hundred patients were enrolled at two participating centres, Ranchi, Jharkhand and Rourkela, Odisha. Two patients in AQ arm had early treatment failure while there was no early treatment failure in ASAQ arm. Late treatment failures were seen in 13 and 12 patients in ASAQ and AQ arms, respectively. The PCR-corrected cure rates in intent-to-treat population were 97.51% (94.6-99.1%) in ASAQ and 88.65% (81.3-93.9%) in AQ arms. In per-protocol population, they were 97.47% (94.2-99.2%) and 88.30% (80-94%) in ASAQ and AQ arms respectively. Seven serious adverse events (SAEs) were reported in five patients, of which two were reported as related to the treatment. All SAEs resolved without sequel.

Conclusion

The fixed dose combination of ASAQ was found to be efficacious and safe treatment for P. falciparum malaria. Amodiaquine also showed acceptable efficacy, making it a suitable partner of artesunate. The combination could prove to be a viable option in case India opts for fixed dose combination ACT.

Clinical trial registry

ISRCTN84408319
Could gender equality in parental leave harm off-springs' mental health? a registry study of the Swedish parental/child cohort of 1988/89
Authors: Norström Lisa , Lindberg Lene , Månsdotter Anna
Published: March 2012

Introduction

Mental ill-health among children and young adults is a growing public health problem and research into causes involves consideration of family life and gender practice. This study aimed at exploring the association between parents' degree of gender equality in childcare and children's mental ill-health.

Methods

The population consisted of Swedish parents and their firstborn child in 1988-1989 (N = 118 595 family units) and the statistical method was multiple logistic regression. Gender equality of childcare was indicated by the division of parental leave (1988-1990), and child mental ill-health was indicated by outpatient mental care (2001-2006) and drug prescription (2005-2008), for anxiety and depression.

Results

The overall finding was that boys with gender traditional parents (mother dominance in childcare) have lower risk of depression measured by outpatient mental care than boys with gender-equal parents, while girls with gender traditional and gender untraditional parents (father dominance in childcare) have lower risk of anxiety measured by drug prescription than girls with gender-equal parents.

Conclusions

This study suggests that unequal parenting regarding early childcare, whether traditional or untraditional, is more beneficial for offspring's mental health than equal parenting. However, further research is required to confirm our findings and to explore the pathways through which increased gender equality may influence child health.
New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon
Authors: Liégeois Florian , Boué Vanina , Mouacha Fatima , Butel Christelle , Ondo Bertrand Mve , Pourrut Xavier , Leroy Eric , Peeters Martine , Rouet François
Published: March 2012

Background

Human retroviral infections such as Human Immunodeficiency Virus (HIV) or Human T-cell Lymphotropic Virus (HTLV) are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP) or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV) and Simian T-cell Lymphotropic Viruses (STLV) to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country.

Results

SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus). We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (sub)species can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively.

Conclusions

Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to document SIV strains to which humans are exposed. We also show that within one species, a high genetic diversity may exist for SIVs and STLVs and observe a high genetic diversity in the SIVgsn/mon/mus lineage, ancestor of HIV-1/SIVcpz/SIVgor.
Screening and functional analysis of differentially expressed genes in EBV-transformed lymphoblasts
Authors: Dai Yongming , Tang Yunlian , He Fei , Zhang Yang , Cheng Ailan , Gan Runliang , Wu Yimou
Published: March 2012

Background

Epstain-Barr virus (EBV) can transform human B lymphocytes making them immortalized and inducing tumorigenic abilityin vitro, but the molecular mechanisms remain unclear. The aim of the present study is to detect and analyze differentially expressed genes in two types of host cells, normal human lymphocytes and coupled EBV-transformed lymphoblastsin vitrousing gene chips, and to screen the key regulatory genes of lymphocyte transformation induced by EB virus.

Methods

Fresh peripheral blood samples from seven healthy donors were collected. EBV was used to transform lymphocytesin vitro. Total RNA was extracted from 7 cases of the normal lymphocytes and transformed lymphoblasts respectively, marked with dihydroxyfluorane after reverse transcription, then hybridized with 4 × 44 K Agilent human whole genome microarray. LIMMA, String, Cytoscape and other softwares were used to screen and analyze differentially expressed genes. Real-time PCR was applied to verify the result of gene expression microarrays.

Results

There were 1745 differentially expressed genes that had been screened, including 917 up-regulated genes and 828 down-regulated genes. According to the results of Generank, String and Cytoscape analyses, 38 genes may be key controlled genes related to EBV-transformed lymphocytes, including 22 up-regulated genes(PLK1, E2F1, AURKB, CDK2, PLCG2, CD80, PIK3R3, CDC20, CDC6, AURKA, CENPA, BUB1B, NUP37, MAD2L1, BIRC5, CDC25A, CCNB1, RPA3, HJURP, KIF2C, CDK1, CDCA8) and 16 down-regulated genes(FYN, CD3D, CD4, CD3G, ZAP70, FOS, HCK, CD247, PRKCQ, ITK, LCP2, CXCL1, CD8A, ITGB5, VAV3, CXCR4), which primarily control biological processes such as cell cycle, mitosis, cytokine-cytokine pathway, immunity response and so on.

Conclusions

Human lymphocyte transformation induced by EB virus is a complicated process, involving multiple-genes and –pathways in virus-host interactions. Global gene expression profile analysis showed that EBV may transform human B lymphocytes by promoting cell cycle and mitosis, inhibiting cell apoptosis, hindering host immune function and secretion of cytokines.
Black rice (Oryza sativa L.) extract attenuates hepatic steatosis in C57BL/6 J mice fed a high-fat diet via fatty acid oxidation
Authors: Jang Hwan-Hee , Park Mi-Young , Kim Heon-Woong , Lee Young-Min , Hwang Kyung-A , Park Jae-Hak , Park Dong-Sik , Kwon Oran
Published: March 2012

Background

Two major risk factors for the onset of fatty liver disease are excessive alcohol intake and obesity, the latter being associated with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the effects of black rice extract (BRE) on hepatic steatosis and insulin resistance in high-fat diet-fed mice, providing a model of NAFLD.

Methods

Twenty-four mice were randomly divided into three groups (n = 8 in each group): normal fat diet (ND), high fat diet (HF), and high fat diet supplemented with 1% (w/w) BRE (HF +1% BRE). The experimental diets were fed for seven weeks.

Results

A HF induced hepatic steatosis with significant increases in the serum levels of free fatty acids (FFAs), triglyceride (TG), total cholesterol (TC), and insulin. By contrast, supplementary BRE (10 g/kg of diet) included in the HF alleviated hepatic steatosis and significantly decreased serum TG and TC levels (p < 0.01 for both). Dietary BRE also increased expression of fatty acid metabolism-related genes, including carnitine palmitoyltransferase (CPT1A), acyl-CoA oxidase (ACO), cytochrome P450 (CYP4A10), and peroxisome proliferator activated receptor (PPAR)-α (p < 0.05 for all).

Conclusions

Dietary BRE supplementation improved serum lipid profiles and significantly enhanced mRNA expression levels of fatty acid metabolism-related genes, primarily via β-oxidation and ω-oxidation in the liver. Taken together, these findings suggest that a BRE-supplemented diet could be useful in reducing the risks of hepatic steatosis and related disorders, including hyperlipidemia and hyperglycemia.
Satellite Glial Cell P2Y12 Receptor in the Trigeminal Ganglion is Involved in Lingual Neuropathic Pain Mechanisms in Rats
Authors: Katagiri Ayano , Shinoda Masamichi , Honda Kuniya , Toyofuku Akira , Sessle Barry J , Iwata Koichi
Published: March 2012

Background:

It has been reported that the P2Y12 receptor (P2Y12R) is involved in satellite glial cells (SGCs) activation, indicating that P2Y12R expressed in SGCs may play functional roles in orofacial neuropathic pain mechanisms. However, the involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown. We therefore studied the reflex to noxious mechanical or heat stimulation of the tongue, P2Y12R and glial fibrillary acidic protein (GFAP) immunohistochemistries in the trigeminal ganglion (TG) in a rat model of unilateral lingual nerve crush (LNC) to evaluate role of P2Y12R in SGC in lingual neuropathic pain.

Results:

The head-withdrawal reflex thresholds to mechanical and heat stimulation of the lateral tongue were significantly decreased in LNC-rats compared to sham-rats. These nocifensive effects were apparent on day 1 after LNC and lasted for 17 days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons encircled with GFAP-immunoreactive (IR) cells significantly increased in the ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC, P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN)-IR cells (i.e. neurons) in TG. After 3 days of successive administration of the P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly decreased coincident with a significant reversal of the lowered head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue compared to vehicle-injected rats. Furthermore, after 3 days of successive administration of the P2YR agonist 2-MeSADP into the TG in naïve rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly increased and head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue were significantly decreased in a dose-dependent manner compared to vehicle-injected rats.

Conclusions:

The present findings provide the first evidence that the activation of P2Y12R in SGCs of TG following lingual nerve injury is involved in the enhancement of TG neuron activity and nocifensive reflex behavior, resulting in neuropathic pain in the tongue.
Finding relevant semantic association paths through user-specific intermediate entities
Authors: V Viswanathan , Krishnamurthi Ilango
Published: March 2012

Semantic Associations are complex relationships between entities over metadata represented in a RDF graph. While searching for complex relationships, it is possible to find too many relationships between entities. Therefore, it is important to locate interesting and meaningful relations and rank them before presenting to the end user. In recent years e-learning systems have become very popular in all fields of higher education. In an e-learning environment, user may expect to search the semantic relationship paths between two concepts or entities. There may be numerous relationships between two entities which involve more intermediate entities. In order to filter the size of results set based on user's relevance, user may introduce one or more known intermediate entities.In this paper, we present a Modified bidirectional Breadth-First-Search algorithm for finding paths between two entities which pass through other intermediate entities and the paths are ranked according to the users' needs. We have evaluated our system through empirical evaluation. We have compared the execution time to discover the paths between entities for our proposed search method and existing method. According to our experiments our proposed algorithm improves search efficiently. The average correlation coefficient between the proposed system ranking and the human ranking is 0.69. It explains that our proposed system ranking is highly correlated with human ranking.
GATA4 Is a Critical Regulator of Gonadectomy-Induced Adrenocortical Tumorigenesis in Mice
Authors: Krachulec Justyna , Vetter Melanie , Schrade Anja , Löbs Ann-Kathrin , Bielinska Malgorzata , Cochran Rebecca , Kyrönlahti Antti , Pihlajoki Marjut , Parviainen Helka , Jay Patrick Y. , Heikinheimo Markku , Wilson David B.
Published: March 2012

In response to gonadectomy certain inbred mouse strains develop sex steroidogenic adrenocortical neoplasms. One of the hallmarks of neoplastic transformation is expression of GATA4, a transcription factor normally present in gonadal but not adrenal steroidogenic cells of the adult mouse. To show that GATA4 directly modulates adrenocortical tumorigenesis and is not merely a marker of gonadal-like differentiation in the neoplasms, we studied mice with germline or conditional loss-of-function mutations in the Gata4 gene. Germline Gata4 haploinsufficiency was associated with attenuated tumor growth and reduced expression of sex steroidogenic genes in the adrenal glands of ovariectomized B6D2F1 and B6AF1 mice. At 12 months after ovariectomy, wild-type B6D2F1 mice had biochemical and histological evidence of adrenocortical estrogen production, whereas Gata4+/− B6D2F1 mice did not. Germline Gata4 haploinsufficiency exacerbated the secondary phenotype of postovariectomy obesity in B6D2F1 mice, presumably by limiting ectopic estrogen production in the adrenal glands. Amhr2-cre-mediated deletion of floxed Gata4 (Gata4F) in nascent adrenocortical neoplasms of ovariectomized B6.129 mice reduced tumor growth and the expression of gonadal-like markers in a Gata4F dose-dependent manner. We conclude that GATA4 is a key modifier of gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex steroidogenic cell differentiation.
Deliberation and Acting for Reasons
Authors: Arpaly Nomy , Schroeder Timothy
Published: March 2012

Theoretical and practical deliberation are voluntary activities, and like all voluntary activities, they are performed for reasons. To hold that all voluntary activities are performed for reasons in virtue of their relations to past, present, or even merely possible acts of deliberation thus leads to infinite regresses and related problems. As a consequence, there must be processes that are nondeliberative and nonvoluntary but that nonetheless allow us to think and act for reasons, and these processes must be the ones that generate the voluntary activities making up ordinary deliberation. These nondeliberative, nonvoluntary processes by means of which we are able to deliberate for reasons are the fundamental processes by means of which we can think or do anything for a reason: once it has been seen that they must exist, it can be recognized that they are ubiquitous. As a result, the usefulness of deliberation to rational belief and action is intermittent, contingent, and modest. Deliberation is a tremendously valuable tool for increasing human capacities to think and act for good reasons in challenging contexts, but in the end it is merely a tool, wielded by people through the same nondeliberative, nonvoluntary capacities to think and act for reasons that they are enhancing the effectiveness of by deliberating.
p120-catenin is essential for terminal end bud function and mammary morphogenesis
Authors: Kurley Sarah J. , Bierie Brian , Carnahan Robert H. , Lobdell Nichole A. , Davis Michael A. , Hofmann Ilse , Moses Harold L. , Muller William J. , Reynolds Albert B.
Published: March 2012

Although p120-catenin (p120) is crucial for E-cadherin function, ablation experiments in epithelial tissues from different organ systems reveal markedly different effects. Here, we examine for the first time the consequences of p120 knockout during mouse mammary gland development. An MMTV-Cre driver was used to target knockout to the epithelium at the onset of puberty. p120 ablation was detected in approximately one-quarter of the nascent epithelium at the forth week post-partum. However, p120 null cells were essentially nonadherent, excluded from the process of terminal end bud (TEB) morphogenesis and lost altogether by week six. This elimination process caused a delay in TEB outgrowth, after which the gland developed normally from cells that had retained p120. Mechanistic studies in vitro indicate that TEB dysfunction is likely to stem from striking E-cadherin loss, failure of cell-cell adhesion and near total exclusion from the collective migration process. Our findings reveal an essential role for p120 in mammary morphogenesis.
The regulation of glial-specific splicing ofNeurexin IVrequires HOW and Cdk12 activity
Authors: Rodrigues Floriano , Thuma Leila , Klämbt Christian
Published: March 2012

The differentiation of the blood-brain barrier (BBB) is an essential process in the development of a complex nervous system and depends on alternative splicing. In the fly BBB, glial cells establish intensive septate junctions that require the cell-adhesion molecule Neurexin IV. Alternative splicing generates two different Neurexin IV isoforms: Neurexin IVexon3, which is found in cells that form septate junctions, and Neurexin IVexon4, which is found in neurons that form no septate junctions. Here, we show that the formation of the BBB depends on the RNA-binding protein HOW (Held out wings), which triggers glial specific splicing of Neurexin IVexon3. Using a set of splice reporters, we show that one HOW-binding site is needed to include one of the two mutually exclusive exons 3 and 4, whereas binding at the three further motifs is needed to exclude exon 4. The differential splicing is controlled by nuclear access of HOW and can be induced in neurons following expression of nuclear HOW. Using a novel in vivo two-color splicing detector, we then screened for genes required for full HOW activity. This approach identified Cyclin-dependent kinase 12 (Cdk12) and the splicesosomal component Prp40 as major determinants in regulating HOW-dependent splicing of Neurexin IV. Thus, in addition to the control of nuclear localization of HOW, the phosphorylation of the C-terminal domain of the RNA polymerase II by Cdk12 provides an elegant mechanism in regulating timed splicing of newly synthesized mRNA molecules.
Functional parameters of Dicer-independent microRNA biogenesis
Authors: Yang Jr-Shiuan , Maurin Thomas , Lai Eric C.
Published: March 2012

Until recently, a Dicer-class RNase III enzyme was believed to be essential for microRNA (miRNA) biogenesis in all animals. The conserved vertebrate locus mir-451 defies this expectation and instead matures by direct cleavage of its pre-miRNA hairpin via the Slicer activity of Argonaute2 (Ago2). In this study, we used structure–function analysis to define the functional parameters of Ago2-mediated miRNA biogenesis. These include (1) the requirement for base-pairing at most, but not all, positions within the pre-mir-451 stem; (2) surprisingly little influence of the 5′-nucleotide on Ago sorting; (3) substantial influence of Ago protein stoichiometry on mir-451 maturation; (4) strong influence of G:C content in the distal stem on 3′ resection of cleaved mir-451 substrates; and (5) the influence of hairpin length on substrate utilization by Ago2 and Dicer. Unexpectedly, we find that certain hairpin lengths confer competence to mature via both Dicer-mediated and Ago2-mediated pathways, and we show, in fact, that a conventional shRNA can traverse the Dicer-independent pathway. Altogether, these data inform the design of effective Dicer-independent substrates for gene silencing and reveal novel aspects of substrate handling by Ago proteins.
Orthopaedics in the developing world
Authors: Carey Smith R. , Wood D.
Published: March 2012

Richard Carey Smith is an orthopaedic oncology surgeon with fellowship training in the UK, USA, Australia and Canada, and has worked in Zambia, Zimbabwe and Papa New Guinea. David Wood is head of the University Department of Orthopaedics in Perth, Western Australia. He did his masters in Africa, and first experienced Papa New Guinea on his medical elective, starting a lifelong commitment to medical aid work there.
Climate Statistics and Public Policy
Authors: Guttorp Peter
Published: March 2012

The main lines of evidence for climate change are outlined. Alternative
explanations to increased greenhouse gas concentrations are described. After
discussing some statistical issues, attribution approaches are briefly
described. Policy issues dealing with mitigation and adaptation are
mentioned.
An adaptive wavelet solver for a nonlinear parameter identification problem
for a parabolic differential equation with sparsity constraints
Authors: Dahlke Stephan , Friedrich Ulrich , Maass Peter , Raasch Thorsten , Ressel Rudolf A.
Published: March 2012

In this paper, we combine concepts from two different mathematical research topics: adaptive wavelet techniques for well-posed problems and regularization theory for nonlinear inverse problems with sparsity constraints. We are concerned with identifying certain parameters in a parabolic reaction-diffusion equation from measured data. Analytical properties of the related parameter-to-state operator are summarized, which justify the application of an iterated soft shrinkage algorithm for minimizing a Tikhonov functional with sparsity constraints. The forward problem is treated by means of a new adaptive wavelet algorithm which is based on tensor wavelets.
In its general form, the underlying PDE describes gene concentrations in embryos at an early state of development. We implemented an algorithm for the related nonlinear parameter identification problem and
numerical results are presented for a simplified test equation.
Role of sex hormones in modulation of brown adipose tissue activity
Authors: Quarta Carmelo , Mazza Roberta , Pasquali Renato , Pagotto Uberto
Published: March 2012

The recent demonstration that metabolically active brown adipose tissue (BAT) is present with a high prevalence in humans undoubtedly represents one of the major advancements in the field of metabolic research in the last few years. The increasing interest in BAT is justified by preclinical observations highlighting an important role of this tissue in energy dissipation and metabolic clearance of substrates from the blood. These findings imply that stimulation of BAT activity may represent a new therapeutic approach for obesity and associated comorbidities. However, before proposing BAT as a target organ for therapeutics in a clinical setting, many further notions about BAT function and modulation need to be explored. Keeping in mind the importance of sex dimorphism in energy metabolism control under physiological and pathological conditions, sex hormones may play a relevant role in the regulation of BAT activity in both males and females. Much of the evidence acquired in the past supports the concept of an important role for different sex hormones in BAT thermogenesis and indicates that this tissue mediates the ability of sex hormones to modulate energy balance. These findings make it plausible that a modified interaction between BAT and sex hormones may contribute to the development and the maintenance of obesity and associated metabolic complications.
Creation of Face-to-face π-π Stacking of Fused Acene Backbones by Aryl-perfluoroaryl Interactions and Induction of Charge Transport Properties
Authors: Okamoto Toshihiro , Nakahara Katsumasa , Saeki Akinori , Seki Shu , Oh Joon H. , Akkerman Hylke B. , Bao Zhenan , Miwa Kazumoto , Takeya Junichi , Matsuo Yutaka
Published: March 2012

The charge transport properties critically depend on the degree of ordering of the chains in the solid state as well as on the density of chemical or structural defects. In general, goodelectronic performance requires strong electronic coupling between adjace nt molecules in the solid-state that yield strong intermolecular π-overlap. Herein, we newly designed and synthesized organic semiconducting materials having both aryl (Ar) and perfluoroaryl (FAr) as substituents for organic electronics along with molecular packing control. Regarding this molecular design, we hypothesized and expected that the Ar and FAr substituents would induce well-defined π-π stacking structure of charge transport units for high performance organic electronics devices.
Mechanisms of Oxidation of Fuel Cladding Alloys Revealed by High Resolution APT, TEM and SIMS Analysis
Authors: Grovenor Chris R. M. , Ni Na , Hudson Daniel , Yardley Sean S. , Moore Katie L. , Smith George D. W. , Lozano-Perez Sergio , Sykes John M.
Published: March 2012

Aqueous corrosion of zirconium alloys has become the major factor limiting prolonged fuel campaigns in nuclear plant. Studies using SEM, TEM and electrochemical impedance measurements have been interpreted as showing a dense inner-most oxide layer, and an increased thickness of the layer has been correlated to a better corrosion resistance. Many authors have reported that an ‘intermediate layer’ at the metal oxide interface has a complex structure or/and stochiometry different to that of both the bulk oxide and bulk metal, sometimes claimed to be a suboxide phase. Diffraction evidence has suggested the presence of both cubic ZrO and rhombohedral Zr3O phases, and compositional analysis has revealed similar variations in local oxygen stoichiometry.

We have carried out a systematic investigation of the structure and chemistry of the metal/oxide interface in samples of commercial ZIRLO corroded for times up to 180 days. We have developed new experimental techniques for the study of these interfaces both by Electron Energy Loss Spectroscopy (EELS) analysis in the Transmission Electron Microscope (TEM) and by Atom Probe Tomography (APT), and exactly the same samples have been investigated by both techniques. Our results show the development of a clearly defined suboxide layer of stoichiometry close to ZrO, and the subsequent disappearance of this layer at the first of the characteristic ‘breakaway’ transitions in the oxidation kinetics. We can correlate this behaviour with changes in the structure of the oxide layer, and particularly the development of interconnected porosity that links the corroding interface with the aqueous environment. Using high resolution SIMS analysis of isotopically spiked samples we demonstrate the penetration of the oxidising species through these porous outer oxide layers.
Face to face with enemy – analysis of aqua carbonate hydroxide second surface phases in proton conducting perovskite ceramic electrolytic membrane.
Authors: Slodczyk Aneta , Tran Caroline , Colomban Philippe
Published: March 2012

The various perovskite ceramic electrolytic membranes, (Ba,Sr)(Zr,Ce,Nb,In,Sn)O3 modified by incorporation of Ln/RE elements, are widely investigated due to their high industrial potential for H2 production and CO2 conversion. One of the most important criteria to classify such ceramic as a good membrane is its high mechanical and chemical stability over thousands hours in severe operating conditions: high temperature and (high water) vapour pressure cycling. It is well known that the Ba- and Sr-based materials can easily form the mixed carbonates, hydroxides, hydrates, hydroxycarbonates, … The presence of undesirable phases, even limited to traces, on the ceramic surface, and/or at the grain boundary, may lead directly to the premature degradation. Since such mixed, hydrated, poorly crystallized phases cannot be detected by diffraction experiments, we have performed thermogravimetric analysis as well as IR and Raman spectroscopic study. The comparison of vibrational and TGA signatures characteristic of complex secondary phases i.e. (Sr/ Ba)(OH)x(CO3)y, nH2O and of proton conducting perovskite reveals that the ignorance of a second phase presence can lead to wrong conclusion concerning the bulk proton nature and understanding of associated conductivity mechanisms.
Fabrication of Graphene Network via Nanoimprint Lithography
Authors: Zou Liumin , Konishi Keita , Hoga Morihisa , Yoh Kanji
Published: March 2012

We have investigated the hexagonal graphene network (GNW) structure for the possible opening of the graphene bandgap. We have fabricated GNW by nanoimprint lithography and compared with previous GNW results based on electron beam (EB) lithography. Hall-bar device with GNW was successfully fabricated using nanoimprint lithography and verified mobility of 1,220 cm2 V-1 s-1 with graphene nanoribbon (GNR) width of 40 nm. The mobility improvement compared with GNW by EB lithography indicates the effectiveness of nanoimprint method for the hexagonal GNW approach.
CVD-Graphene Complementary Logic on Ultra-thin Multilayer Hexagonal Boron Nitride
Authors: Kim Edwin , Jain Nikhil , Xu Yang , Han Yan , Yu Bin
Published: March 2012

Graphene, a two-dimensional carbon allotrope, has raised great interests as a material candidate for future electronics due to its superb carrier transport and unique physics. The demand for future-generation large-scale carbon-based electronics motivates assembly of large-area graphene and selection of ideal substrate material that best preserves the transport property of graphene. In this work, CVD-assembled large-area graphene on thin multilayer hexagonal boron nitride (h-BN) is employed to demonstrate the basic building block of digital circuit - inverter prototype made of two graphene-channel field-effect transistors (GFETs). The doping in the CVD-grown graphene, probed via electrical measurements, is implemented through non-uniform local surface chemistry. The full transfer response of the graphene logic inverter is demonstrated in the localized P/N doping region.
Fabrication of Complex Hydrogel Materials by Utilizing Microfluidics and Micromolding
Authors: Yamada Masumi , Sugaya Sari , Kobayashi Aoi , Miyama Ayaki , Naganuma Yoji , Yamada Emi , Kakegawa Shunta , Seki Minoru
Published: March 2012

Here, we present microfluidic methods to fabricate complex hydrogel structures for 3D tissue or organ-like cell structures in vitro. First, a microfluidic system to continuously synthesize chemically and physically anisotropic Ca–alginate hydrogel microfibers is proposed to enable the guidance of cell proliferation and differentiation. Next, the microfluidic preparation methods for yarn-ball-shape hydrogel particles and extremely-small hydrogel microspheres. Finally, a newly developed micro-molding and bonding method for hydrogel micro-patterned plates is reported.
Nanomodified Endotracheal Tubes: Spatial Analysis of Reduced Bacterial Colonization in a Bench Top Airway Model
Authors: Machado Mary C. , Tarquinio Keiko M. , Webster Thomas J.
Published: March 2012

Ventilator associated pneumonia (VAP) is a serious and costly clinical problem. Specifically, receiving mechanical ventilation for over 24 hours increases the risk of VAP and is associated with high morbidity, mortality and medical costs. Cost effective endotracheal tubes (ETTs) that are resistant to bacterial infection could help prevent this problem. The objective of this study was to determine differences in the growth ofStaphylococcus aureus(S. aureus) on nanomodified and unmodified polyvinyl chloride (PVC) ETTs under dynamic airway conditions. PVC ETTs were modified to have nanometer surface features by soaking them inRhizopus arrhisus,a fungal lipase. Twenty-four hour experiments (supported by computational models) showed that air flow conditions within the ETT influenced both the location and concentration of bacterial growth on the ETTs especially within areas of tube curvature. More importantly, experiments revealed a 1.5 log reduction in the total number ofS. aureuson the novel nanomodified ETTs compared to the conventional ETTs after 24 hours of air flow. This dynamic study showed that lipase etching can create nano-rough surface features on PVC ETTs that suppressS. aureusgrowth and, thus, may provide clinicians with an effective and inexpensive tool to combat VAP.
Improvement of Adhesive Strength of Polyacetal by Irradiation of Vacuum Ultra-Violet Light and Deposition of Nanometer-Sized Particles Simultaneously using Laser Ablation
Authors: Takeichi Akihiro , Okamoto Yasushi , Azuma Hirozumi
Published: March 2012

Polyacetal is a resin which has excellent property. However, polyacetal has a poor adherence property using adhesive material. Therefore, for the improvement of the adhesive strength, simultaneous surface treatments of polyacetal by irradiation of vacuum ultra-violet (VUV) light and deposition of nanometer-sized particles using laser ablation with C, Si and Ti targets were carried out. The surface treatments were carried out with different wavelengths, energies, processing times and substrate locations from normal direction of targets. The targets were irradiated with a pulsed laser from Nd-YAG laser. After surface treatments, tensile test pieces of polyacetal were bonded by epoxide-based adhesive. And, longitudinal shear strengths were measured. As a result, after surface treatment of polyacetal using C target, the highest shear bond strength which is approximately 8 times larger than that of untreated polyacetal sample was measured (5.6 MPa). It was found that increasing functional groups and increasing surface roughness are affecting improvement of the adhesive strength. The improvement of the adhesive strength is also caused by the new-creation of the dangling-bonds on the polymer surface by VUV irradiation and preservation of each dangling-bonds from re-bonding each other by a separation effect of deposited nanometer-sized particles. This method can be expected for new applications of polymers.
Shape Memory Behavior of Ultra-High Molecular Weight Polyethylene
Authors: Kaloshkin Sergey , Maksimkin Aleksey , Kaloshkina Maria , Zadorozhnyy Mihail , Churyukanova Margarita
Published: March 2012

Shape memory effect in pure ultra-high molecular weight polyethylene (UHMWPE) has been studied using dynamic mechanical analysis. Temperature dependencies of properties that define functional characteristics of shape memory polymers (SMP) such as recovery stress, recovery strain and activation temperature of transition were determined for UHMWPE. The recovery stress in UHMWPE deformed by 200% achieved rather high values, up to 7 MPa.
Understanding MOCVD Gas Chemistry to Reduce the Cost of Ownership for GaN LED and AsP CPV Technologies
Authors: Armour E.A. , Mitrovic B. , Zhang A. , Ebert C. , Pophristic M. , Paranjpe A.
Published: March 2012

As compound semiconductors continue to make inroads into common electronic devices, it is critically important to lower the cost of the primary metal-organic chemical vapor deposition (MOCVD) epitaxial process, which creates the foundation for the devices. Both GaN-based light-emitting diode (LED) and AsP-based concentrator photovoltaic (CPV) markets have been focused on simultaneous cost-reduction, cycle time reductions, and device efficiency improvements, which can be realized utilizing higher growth rates and operating pressures. To achieve these goals, it has become increasingly important to understand the underlying growth mechanisms that drive the chemistry within the MOCVD process.

Higher growth rates and higher operating pressures both result in parasitic gas-phase particle formation, which degrades the physical, electrical and optical properties of the deposited layers. In extreme cases, it can reduce the deposition efficiency to the point where increasing the reactant constituents results in reduced growth rates. In this paper, we will examine the tradeoffs that need to be made to achieve good crystal quality with abrupt interfaces, smooth surface morphology, and good minority carrier properties for films deposited at high growth rates and high pressure. While exceptional device performance has been achieved for both GaN-based LEDs and AsP-based CPV cells, it is primarily cost that is limiting full-scale adoption of compound semiconductors into these potentially enormous markets.
Em busca de um ponto cego: notas sobre a sociologia da cultura no Brasil e a diluição da mídia como objeto sociológico
Authors: Rocha Maria Eduarda da Mota
Published: March 2012

Este texto discute as possíveis causas e consequências do fraco estatuto da mídia como objeto na área acadêmica da sociologia. Para tanto, analisa certas tendências recentes do campo cultural brasileiro que apontam para um desgaste do cânone modernista diante da emergência de gerações de artistas, intelectuais e públicos que sofrem influência decisiva da indústria cultural.
Arte e geopolítica: a lógica das interpretações
Authors: Villas Bôas Glaucia
Published: March 2012

O artigo tem o objetivo de discutir os critérios geopolíticos de classificação da arte, argumentando que tais critérios obstaculizam a apreciação das artes na sua dimensão estética e sociológica. Os critérios de natureza geopolítica se fundamentam em pares dicotômicos tais como exotismo vs. civilização, centro vs. periferia, nação vs. universalismo, que há mais de um século vêm sendo utilizados, por diretores de museus, historiadores, críticos de arte e curadores. Procura-se demonstrar o uso sistemático dessas categorias que servem tanto aos discursos críticos da pintura colonial quanto aqueles relacionados ao modernismo brasileiro. Conclui-se que somente o estudo das nuanças finas das interações entre os indivíduos e os grupos leva à compreensão da complexidade dos processos de criação artística, pondo fim aos constrangimentos das categorias geopolíticas de classificação e permitindo o trânsito em áreas ainda desconhecidas.
A construção da autoridade entre os donos de barco no Aventureiro, Ilha Grande - RJ: uma etnografia das relações de poder
Authors: Costa Gustavo Villela Lima da
Published: March 2012

Este artigo propõe analisar a articulação entre as esferas de poder local e o poder público, a partir de uma descrição etnográfica da organização social e de como, nesta, se estrutura a autoridade política local. Nesse processo de construção da autoridade local, na praia do Aventureiro, Ilha Grande - RJ, o poder político e a autoridade legitimada pelos moradores estão diretamente ligados à posse dos barcos e dos campings mais prósperos. Os donos de barco no Aventureiro assumem, nesse contexto, o papel de representantes legítimos do povoado na negociação com órgãos da Prefeitura e do Estado, na defesa dos direitos dos moradores, assumindo um papel de representação da organização doméstica (em famílias e grupos vicinais) nas relações políticas com o Estado.