bluuebunny/crossref_metadata_2025 huggingface dataset:
Core Criminal Law Provisions in the United Nations Convention Against Corruption
Authors: Kubiciel Michael
Published: March 2009

With the adoption of the UNCAC in 2003, the international legal development in the fight against corruption has reached its peak. Now the convention has to be filled with life. This is the task of national law-makers, law enforcement bodies and courts. They all need substantial information concerning the content of the convention's articles. Unfortunately, an offical or semi-official commentary to the UNCAC does not exist. This study aims at filling that gap by providing substanial information for the core criminal law provisions “bribery of public offical” and “active bribery of foreign public officials”. To this end, the study reveals cross-relations between the UNCAC and international conventions whose articles have been used as examples for the legal design of the UNCAC. Since several of the preceding conventions are accompanied by official commentaries or explanatory reports, these documents also offer a deep insight into the UNCAC.
International Criminal Due Process in the Making: New Tendencies in the Law of Non-Disclosure in the Proceedings before the ICC
Authors: Kuschnik Bernhard
Published: March 2009

In the everyday trial practice before the International Criminal Court, the issue of non-disclosure of evidence is highly technically regulated and creates problems due to the ambiguities of the provisions governing the process. This article will display the legal systematic of the applicable law to clarify established findings of the Court and discuss new tendencies. Discussed problems include, to what extent “potential Prosecution witnesses” and “innocent third parties” can be integrated into the dogmatic of the law of non-disclosure, and whether non-disclosure should be granted on grounds of Article 54(3)(f) of the ICC Statute.
Territorial Jurisdiction Over Cross-frontier Offences: Revisiting a Classic Problem of International Criminal Law
Authors: Ryngaert Cedric
Published: March 2009

The principle of territoriality is the cornerstone of the law of criminal jurisdication. The question arises, however, how the principle ought to be applied to cross-frontier offences which have connections to more than one territory. It is demonstrated that, from a study of six Western States, it transpires that the constituent elements approach (pursuant to which jurisdiction is found as soon as a constituent element of the crime has occurred on the territory) is the dominant approach, with the exception of England. As far as cross-frontier participation and inchoate offences are concerned, however, solutions diverge considerably among States.
The Return and Removal of Irregular Migrants under EU Law: An Analysis of the Returns Directive
Authors: Baldaccini Anneliese
Published: March 2009

After protracted negotiations, in June 2008, agreement between the European Parliament and the Council cleared the way for the adoption of the Directive setting out common standards and procedures in the Member States for returning irregularly staying third country nationals (the Returns Directive). While its impact in terms of harmonising national legal frameworks can be questioned, from the Member States’ point of view the agreed standards will underpin their common efforts at removing a higher number of irregular immigrants. From the point of view of immigrants, it will mean longer pre-removal detention periods and a ban on re-entering legally the Union’s territory for the foreseeable future.
The Good, the Bad and the Ugly in EU Migration Law: Is the European Parliament Becoming Bad and Ugly? (The Adoption of Directive 2008/15: The Returns Directive)
Authors: Acosta Diego
Published: March 2009

Historically, the European Union has had a dichotomy between the liberal view in immigration management represented by the Parliament (‘the good’) and the Commission (‘the ugly’), and the conservative approach embodied by the Council (‘the bad’). This article deals with the first important immigration instrument adopted under co-decision: Directive 2008/115 (the so-called ‘Returns Directive’). This Directive has received a great deal of criticism addressed to the European Parliament in its approval of the text negotiated with the Council in the first reading, without introducing a single amendment. This behaviour has cast doubts as to whether the future involvement of this institution will result in a more migrant-friendly approach in the European Union. The reasons why the European Parliament voted in favour of the Directive will be analysed in the following pages. But first, a question arises: Is the European Parliament becoming ‘bad’ and ‘ugly’ or has its involvement improved the Council’s position in a way which would not have been possible without its participation? This is the main issue that this article, in the following pages, will try to answer by analysing the different steps in the adoption of the Directive from the Commission proposal until its official publication.
Theorizing About Theorizing: an Examination of the Contributions of William I. Grossman To Psychoanalysis
Authors: Wilson Arnold
Published: March 2009

William Grossman's contributions to psychoanalysis are studied in the light of an interest that suffuses his papers: the remarkably complex ways an analyst develops his or her mind in order to become an effective analyst. Grossman sought to detail the many subtle factors infusing Freudian theory, from its initial sources to its consolidation as a system, to its embrace in the mind of an analyst who will use it, and on to the many iterations of its progress on the way to being applied in the clinical situation. This progression assumes a recognition of the analyst's need to be at once both experiencer and observer. Implicit in the attempt to understand another is a self-reflective taking of oneself as an object of analysis. How an essential tension is worked out between the subjective and objective points of view is an issue that pervades Grossman's writings. This is but one instance of a larger tendency characterizing his ideas—thinking psychoanalytically about psychoanalysis itself. Factors he implicated in being a contemporary Freudian analyst are then taken up.
Amoxicillin May Cause Molar Incisor Hypomineralization
Authors: Laisi S. , Ess A. , Sahlberg C. , Arvio P. , Lukinmaa P.-L. , Alaluusua S.
Published: March 2009

The etiology of molar incisor hypomineralization (MIH) is unclear. Our hypothesis was that certain antibiotics cause MIH. We examined 141 schoolchildren for MIH and, from their medical files, recorded the use of antibiotics under the age of 4 yrs. MIH was found in 16.3% of children. MIH was more common among those children who had taken, during the first year of life, amoxicillin (OR = 2.06; 95% CI, 1.01–4.17) or the rarely prescribed erythromycin (OR = 4.14; 95% CI, 1.05–16.4), compared with children who had not received treatment. Mouse E18 teeth were cultured for 10 days with/without amoxicillin at concentrations of 100 μg/mL–4 mg/mL. Amoxicillin increased enamel but not dentin thickness. An altered pattern of amelogenesis may have interfered with mineralization. We conclude that the early use of amoxicillin is among the causative factors of MIH.
Don Quixote’s Countenance Before and After Losing His Teeth
Authors: del Valle A. , Romero M.
Published: March 2009

The authors of this paper wish to draw attention to certain not-so-well-known aspects concerning the epithet “Knight of the Woeful Countenance”, by which Cervantes’ character Don Quixote is universally known. Cervantes used it to highlight the loss of his hero’s molars and incisors; thus, the reduced vertical dimension of his face, along with his sagging cheeks and deepened facial furrows, was the reason for his permanently sorrowful countenance. Luis Martínez, a professional illustrator following instructions from the authors of this paper, has recreated the face of Don Quixote as Miguel de Cervantes may well have imagined it for his celebrated character.
Risks for Early Childhood Caries Analyzed by Negative Binomial Models
Authors: Thitasomakul S. , Piwat S. , Thearmontree A. , Chankanka O. , Pithpornchaiyakul W. , Madyusoh S.
Published: March 2009

Because of the high incidence of early childhood caries (ECC), a longitudinal study to identify risk factors from the prenatal period to the child’s first birthday among 9- to 18-month-old children was conducted with negative binomial modeling. Overall, 495 children had dental examinations at ages 9, 12, and 18 months. Mothers were interviewed during the 2nd trimester of pregnancy and when the children had dental examinations. The highest incidence of caries was found among children who were born to mothers with ≥ 10 decayed teeth and who never received calcium supplements during pregnancy, and children who were not fed supplementary foods at age 3 months, had sweet-tasting foods at 5 months, started snacking at 5 months, had sugary snacks, had soft drinks, and did not have their teeth brushed daily at 9 months. Thus, prenatal care and child-rearing-practices during and after birth are important risk factors for the incidence and incremental rate of ECC.
Durability of Resin-Dentin Bonds to Water- vs. Ethanol-saturated Dentin
Authors: Hosaka K. , Nishitani Y. , Tagami J. , Yoshiyama M. , Brackett W.W. , Agee K.A. , Tay F.R. , Pashley D.H.
Published: March 2009

Higher 24-hour resin-dentin bond strengths are created when ethanol is used to replace water during wet bonding. This in vitro study examined if ethanol-wet-bonding can increase the durability of resin-dentin bonds over longer times. Five increasingly hydrophilic experimental resin blends were bonded to acid-etched dentin saturated with water or ethanol. Following composite build-ups, the teeth were reduced into beams for 24-hour microtensile bond strength evaluation, and for water-aging at 37°C for 3, 6, or 12 months before additional bond strength measurements. Although most bonds made to water-saturated dentin did not change over time, those made to ethanol-saturated dentin exhibited higher bond strengths, and none of them fell over time. Decreased collagen fibrillar diameter and increased interfibrillar spacing were seen in hybrid layers created with ethanol-wet-bonding. Increases in bond strength and durability in ethanol-wet-bonding may be due to higher resin uptake and better resin sealing of the collagen matrix, thereby minimizing endogenous collagenolytic activities.
Molecular and Cellular Mechanisms That Lead to Candida Biofilm Formation
Authors: ten Cate J.M. , Klis F.M. , Pereira-Cenci T. , Crielaard W. , de Groot P.W.J.
Published: March 2009

Fungal infections in the oral cavity are mainly caused by C. albicans, but other Candida species are also frequently identified. They are increasing in prevalence, especially in denture-wearers and aging people, and may lead to invasive infections, which have a high mortality rate. Attachment to mucosal tissues and to abiotic surfaces and the formation of biofilms are crucial steps for Candida survival and proliferation in the oral cavity. Candida species possess a wide arsenal of glycoproteins located at the exterior side of the cell wall, many of which play a determining role in these steps. In addition, C. albicans secretes signaling molecules that inhibit the yeast-to-hypha transition and biofilm formation. In vivo, Candida species are members of mixed biofilms, and subject to various antagonistic and synergistic interactions, which are beginning to be explored. We believe that these new insights will allow for more efficacious treatments of fungal oral infections. For example, the use of signaling molecules that inhibit biofilm formation should be considered. In addition, cell-wall biosynthetic enzymes, wall cross-linking enzymes, and wall proteins, which include adhesins, proteins involved in biofilm formation, fungal-bacterial interactions, and competition for surface colonization sites, offer a wide range of potential targets for therapeutic intervention.
The Quality of Guest Comment Cards
Authors: Bartkus Kenneth R. , Howell Roy D. , Barlow Hills Stacey , Blackham Jeanette
Published: March 2009

This study examines the quality of guest comment cards used by major U.S. lodging chains. To accomplish this objective, guidelines for comment card design were developed through a review of the relevant literature. The guidelines focus on eight issues: (1) return methods, (2) introductory statements, (3) contact information, (4) number of questions, (5) space for open comments, (6) number of response categories for closed-ended questions, (7) balanced versus unbalanced response categories for closed-ended questions, and (8) question wording. Using a sample of 63 lodging chains, the most common deviations from guidelines include a lack of secure return methods, the use of positively biased response categories, and insufficient writing space for open comments. To improve the quality of comment card feedback, these and other limitations should be corrected. Managerial implications and directions for future research are included.
Television Viewing and People With Dementia Living in Long-Term Care
Authors: de Medeiros Kate , Beall Erica , Vozzella Stephen , Brandt Jason
Published: March 2009

Although televisions are commonplace in many long-term care facilities for people with dementia, little research has been done on the possible effects of television viewing on residents’ behaviors. The authors’ study aims were to document observable behaviors and activities of residents before, during, and after viewing television programs and to determine whether programs had an observable effect on behaviors. The authors enrolled 22 residents in a residential dementia care facility (4 to 5 people in each of the five residential wings). Two raters completed systematic observations for 5 consecutive days at baseline, during the presentation of eight television programs, and for 30 minutes following the program. The authors found that “dozing” was the most common activity during program viewing. In addition, many participants remained in the television area, “watching” a blank television screen in the 30 minutes following the program viewing. Further investigation on television’s effect on sleep or participation in other social activities is needed.
Family Firms' International Commitment
Authors: Claver Enrique , Rienda Laura , Quer Diego
Published: March 2009

Few studies have dealt with family businesses and internationalization theories. The aim of this article is to bridge this gap by examining the family-related factors that have an impact on the international commitment level of these companies. From a sample of Spanish family firms, findings show that long-term vision and the presence of nonfamily managers are positively related to entry modes involving stronger international commitment, although self-financing limits this commitment.
The United States Army and Urban Combat in the Nineteenth Century
Authors: Beall Jonathan A.
Published: March 2009

Scholars have investigated the effectiveness of military organizations in twentieth-century warfare and have evaluated their ability to defeat their enemies in wartime or adapt to changes that developed in peacetime. Few have studied the military effectiveness of nineteenth-century armies as closely. This paper examines the operational and tactical effectiveness of two American armies in the mid-1800s by comparing how they approached urban combat, something for which the United States military was not prepared. This paper compares how Americans reacted to urban combat in the battle of Monterrey in 1846 with urban combat in the battle of Fredericksburg in 1862. It also seeks to explain why one army fought effectively and the other did not.
Still a Movement After All These Years?
Authors: Lehrner Amy , Allen Nicole E.
Published: March 2009

The domestic violence movement began as a social change movement with dual goals of social change and service provision. Despite concerns about a devolution of the movement into apolitical service provision, few studies have investigated the current status of the movement as a social change movement. Through interviews with advocates, the current study explores the degree to which domestic violence work can still be characterized as a social change movement, illuminates some central tensions within the movement, and lays a foundation for debate among those responding to domestic violence. This research also highlights movement leaders' visions for a reenergized movement.
Violence During Pregnancy in Jordan
Authors: Clark Cari Jo , Hill Allan , Jabbar Khelda , Silverman Jay G.
Published: March 2009

This study estimates the lifetime prevalence of physical violence during pregnancy and examines risk and protective factors among women ( N = 390) attending reproductive health clinics in Jordan. Approximately 15% reported physical violence during pregnancy. The husband was the sole perpetrator in 83% of the cases. A high frequency of quarreling, the husband's use of alcohol, attitudes supportive of a woman's duty to obey her husband, infrequent communication between the respondent and her family, and exposure to violence as a child increased the risk of violence. Consanguinity (marriage to a blood relative) and higher education levels were protective against violence during pregnancy.
The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors
Authors: Perez-Campo Flor M. , Borrow Julian , Kouskoff Valerie , Lacaud Georges
Published: March 2009

The monocytic leukemia zinc finger (MOZ) gene encodes a large multidomain protein that contains, besides other domains, 2 coactivation domains for the transcription factor Runx1/acute myeloid leukemia 1 and a histone acetyl transferase (HAT) catalytic domain. Recent studies have demonstrated the critical requirement for the complete MOZ protein in hematopoietic stem cell development and maintenance. However, the specific function of the HAT activity of MOZ remains unknown, as it has been shown that MOZ HAT activity is not required either for its role as Runx1 coactivator or for the leukemic transformation induced by MOZ transcriptional intermediary factor 2 (TIF2). To assess the specific requirement for this HAT activity during hematopoietic development, we have generated embryonic stem cells and mouse lines carrying a point mutation that renders the protein catalytically inactive. We report in this study that mice exclusively lacking the HAT activity of MOZ exhibit significant defects in the number of hematopoietic stem cells and hematopoietic committed precursors as well as a defect in B-cell development. Furthermore, we demonstrate that the failure to maintain a normal number of hematopoietic precursors is caused by the inability of HAT−/− cells to expand. These results indicate a specific role of MOZ-driven acetylation in controlling a desirable balance between proliferation and differentiation during hematopoiesis.
Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy
Authors: Pérez-Andreu Virginia , Roldán Vanessa , Antón Ana Isabel , García-Barberá Nuria , Corral Javier , Vicente Vicente , González-Conejero Rocio
Published: March 2009

VKORC1 and CYP2C9 polymorphisms are used to predict the safe dose of oral anticoagulant therapy. A new variant of CYP4F2 (V433M) has recently been related to the required warfarin dose. We evaluated its influence in earliest response to acenocoumarol in 100 selected men who started anticoagulation (3 mg for 3 consecutive days). V433M genotype exerted a gene dosage-dependent effect on the decrease of factors II, VII, IX, and X in the earliest response to acenocoumarol, with homozygous 433V subjects being the most sensitive. Similarly, after the initiation of therapy, international normalized ratio also experienced a gene dosage-dependent effect (P = .015), and 433V subjects needed 4 mg/week less than 433M carriers to achieve a steady anticoagulation (P = .043). Multivariate linear regression analysis revealed a significant contribution of V433M polymorphism to variability of both early international normalized ratio value (R2 = 0.14) and dose requirements (R2 = 0.19). Our data underline the relevant role of CYP4F2 V433M polymorphism in the pharmacogenetics of coumarin anticoagulants.
Influence of genetic background on the occurrence of chromosomal rearrangements in Saccharomyces cerevisiae
Authors: Fritsch Emilie S , Schacherer Joseph , Bleykasten-Grosshans Claudine , Souciet Jean-Luc , Potier Serge , de Montigny Jacky
Published: March 2009

Background

Chromosomal rearrangements such as duplications and deletions are key factors in evolutionary processes because they promote genomic plasticity. Although the genetic variations in the Saccharomyces cerevisiae species have been well documented, there is little known to date about the impact of the genetic background on the appearance of rearrangements.

Results

Using the same genetic screening, the type of rearrangements and the mutation rates observed in the S288c S. cerevisiae strain were compared to previous findings obtained in the FL100 background. Transposon-associated rearrangements, a major chromosomal rearrangement event selected in FL100, were not detected in S288c. The mechanisms involved in the occurrence of deletions and duplications in the S288c strain were also tackled, using strains deleted for genes implicated in homologous recombination (HR) or non-homologous end joining (NHEJ). Our results indicate that an Yku80p-independent NHEJ pathway is involved in the occurrence of these rearrangements in the S288c background.

Conclusion

The comparison of two different S. cerevisiae strains, FL100 and S288c, allowed us to conclude that intra-species genomic variations have an important impact on the occurrence of chromosomal rearrangement and that this variability can partly be explained by differences in Ty1 retrotransposon activity.
Genomic expression profiling of mature soybean (Glycine max) pollen
Authors: Haerizadeh Farzad , Wong Chui E , Bhalla Prem L , Gresshoff Peter M , Singh Mohan B
Published: March 2009

Background

Pollen, the male partner in the reproduction of flowering plants, comprises either two or three cells at maturity. The current knowledge of the pollen transcriptome is limited to the model plant systemsArabidopsis thalianaandOryza sativawhich have tri-cellular pollen grains at maturity. Comparative studies on pollen of other genera, particularly crop plants, are needed to understand the pollen gene networks that are subject to functional and evolutionary conservation. In this study, we used the Affymetrix Soybean GeneChip®to perform transcriptional profiling on mature bi-cellular soybean pollen.

Results

Compared to the sporophyte transcriptome, the soybean pollen transcriptome revealed a restricted and unique repertoire of genes, with a significantly greater proportion of specifically expressed genes than is found in the sporophyte tissue. Comparative analysis shows that, among the 37,500 soybean transcripts addressed in this study, 10,299 transcripts (27.46%) are expressed in pollen. Of the pollen-expressed sequences, about 9,489 (92.13%) are also expressed in sporophytic tissues, and 810 (7.87%) are selectively expressed in pollen. Overall, the soybean pollen transcriptome shows an enrichment of transcription factors (mostly zinc finger family proteins), signal recognition receptors, transporters, heat shock-related proteins and members of the ubiquitin proteasome proteolytic pathway.

Conclusion

This is the first report of a soybean pollen transcriptional profile. These data extend our current knowledge regarding regulatory pathways that govern the gene regulation and development of pollen. A comparison between transcription factors up-regulated in soybean and those inArabidopsisrevealed some divergence in the numbers and kinds of regulatory proteins expressed in both species.
Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia
Authors: Øyan Anne Margrete , Ånensen Nina , Bø Trond Hellem , Stordrange Laila , Jonassen Inge , Bruserud Øystein , Kalland Karl-Henning , Gjertsen Bjørn Tore
Published: March 2009

Background

The molecular changes in vivo in acute myeloid leukemia cells early after start of conventional genotoxic chemotherapy are incompletely understood, and it is not known if early molecular modulations reflect clinical response.

Methods

The gene expression was examined by whole genome 44 k oligo microarrays and 12 k cDNA microarrays in peripheral blood leukocytes collected from seven leukemia patients before treatment, 2–4 h and 18–24 h after start of chemotherapy and validated by real-time quantitative PCR. Statistically significantly upregulated genes were classified using gene ontology (GO) terms. Parallel samples were examined by flow cytometry for apoptosis by annexin V-binding and the expression of selected proteins were confirmed by immunoblotting.

Results

Significant differential modulation of 151 genes were found at 4 h after start of induction therapy with cytarabine and anthracycline, including significant overexpression of 31 genes associated with p53 regulation. Within 4 h of chemotherapy the BCL2/BAX and BCL2/PUMA ratio were attenuated in proapoptotic direction. FLT3 mutations indicated that non-responders (5/7 patients, 8 versus 49 months survival) are characterized by a unique gene response profile before and at 4 h. At 18–24 h after chemotherapy, the gene expression of p53 target genes was attenuated, while genes involved in chemoresistance, cytarabine detoxification, chemokine networks and T cell receptor were prominent. No signs of apoptosis were observed in the collected cells, suggesting the treated patients as a physiological source of pre-apoptotic cells.

Conclusion

Pre-apoptotic gene expression can be monitored within hours after start of chemotherapy in patients with acute myeloid leukemia, and may be useful in future determination of therapy responders. The low number of patients and the heterogeneity of acute myeloid leukemia limited the identification of gene expression predictive of therapy response. Therapy-induced gene expression reflects the complex biological processes involved in clinical cancer cell eradication and should be explored for future enhancement of therapy.
A pharmaco-economic analysis of patients with schizophrenia switching to generic risperidone involving a possible compliance loss
Authors: Treur Maarten , Heeg Bart , Möller Hans-Jürgen , Schmeding Annette , van Hout Ben
Published: March 2009

Background

As schizophrenia patients are typically suspicious of, or are hostile to changes they may be reluctant to accept generic substitution, possibly affecting compliance. This may counteract drug costs savings due to less symptom control and increased hospitalization risk. Although compliance losses following generic substitution have not been quantified so far, one can estimate the possible health-economic consequences. The current study aims to do so by considering the case of risperidone in Germany.

Methods

An existing DES model was adapted to compare staying on branded risperidone with generic substitution. Differences include the probability of non-compliance and medication costs. Incremental probability of non-compliance after generic substitution was varied between 2.5% and 10%, while generic medication costs were assumed to be 40% lower. Effect of medication price was assessed as well as the effect of applying compliance losses to all treatment settings. The probability of staying on branded risperidone being cost-effective was calculated for various outcomes of a hypothetical study that would investigate non-compliance following generic substitution of risperidone.

Results

If the incremental probability of non-compliance after generic substitution is 2.5%, 5.0%, 7.5% and 10% respectively, incremental effects of staying on branded risperidone are 0.004, 0.007, 0.011 and 0.015 Quality Adjusted Life Years (QALYs). Incremental costs are €757, €343, -€123 and -€554 respectively. Benefits of staying on branded risperidone include improved symptom control and fewer hospitalizations. If generic substitution results in a 5.2% higher probability of non-compliance, the model predicts staying on branded risperidone to be cost-effective (NICE threshold of ₤30,000 per QALY gained). Compliance losses of more than 6.9% makes branded risperidone the dominant alternative. Results are sensitive to the locations at which compliance loss is applied and the price of generic risperidone. The probability that staying on branded risperidone is cost-effective would increase with larger compliance differences and more patients included in the hypothetical study.

Conclusion

The model predicts that it is cost-effective to keep a patient with schizophrenia in Germany on branded risperidone instead of switching him/her to generic risperidone (assuming a 40% reduction in medication costs), if the incremental probability of becoming non-compliant after generic substitution exceeds 5.2%.
Ciliary neurotrophic factor (CNTF) plus soluble CNTF receptor α increases cyclooxygenase-2 expression, PGE2release and interferon-γ-induced CD40 in murine microglia
Authors: Lin Hsiao-Wen , Jain Mohit Raja , Li Hong , Levison Steven W
Published: March 2009

Background

Ciliary neurotrophic factor (CNTF) has been regarded as a potent trophic factor for motor neurons. However, recent studies have shown that CNTF exerts effects on glial cells as well as neurons. For instance, CNTF stimulates astrocytes to secrete FGF-2 and rat microglia to secrete glial cell line-derived neurotrophic factor (GDNF), which suggest that CNTF exerts effects on astrocytes and microglia to promote motor neuron survival indirectly. As CNTF is structurally related to IL-6, which can stimulate immune functions of microglia, we hypothesized that CNTF might exert similar effects.

Methods

We performed 2-D and 1-D proteomic experiments with western blotting and flow cytometry to examine effects of CNTF on primary microglia derived from neonatal mouse brains.

Results

We show that murine microglia express CNTF receptor α (CNTFRα), which can be induced by interferon-γ (IFNγ). Whereas IL-6 activated STAT-3 and ERK phosphorylation, CNTF did not activate these pathways, nor did CNTF increase p38 MAP kinase phosphorylation. Using 2-D western blot analysis, we demonstrate that CNTF induced the dephosphorylation of a set of proteins and phosphorylation of a different set. Two proteins that were phosphorylated upon CNTF treatment were the LYN substrate-1 and β-tubulin 5. CNTF weakly stimulated microglia, whereas a stronger response was obtained by adding exogenous soluble CNTFRα (sCNTFRα) as has been observed for IL-6. When used in combination, CNTF and sCNTFRα collaborated with IFNγ to increase microglial surface expression of CD40 and this effect was quite pronounced when the microglia were differentiated towards dendritic-like cells. CNTF/sCNTFRα complex, however, failed to increase MHC class II expression beyond that induced by IFNγ. The combination of CNTF and sCNTFRα, but not CNTF alone, enhanced microglial Cox-2 protein expression and PGE2secretion (although CNTF was 30 times less potent than LPS). Surprisingly, Cox-2 production was enhanced 2-fold, rather than being inhibited, upon addition of a gp130 blocking antibody.

Conclusion

Our studies indicate that CNTF can activate microglia and dendritic-like microglia similar to IL-6; however, unlike IL-6, CNTF does not stimulate the expected signaling pathways in microglia, nor does it appear to require gp130.
Trend tests for the evaluation of exposure-response relationships in epidemiological exposure studies
Authors: Hothorn Ludwig A , Vaeth Michael , Hothorn Torsten
Published: March 2009

One possibility for the statistical evaluation of trends in epidemiological exposure studies is the use of a trend test for data organized in a 2 × k contingency table. Commonly, the exposure data are naturally grouped or continuous exposure data are appropriately categorized. The trend test should be sensitive to any shape of the exposure-response relationship. Commonly, a global trend test only determines whether there is a trend or not. Once a trend is seen it is important to identify the likely shape of the exposure-response relationship. This paper introduces a best contrast approach and an alternative approach based on order-restricted information criteria for the model selection of a particular exposure-response relationship. For the simple change point alternative H1 : π1 = ...= π
q
<πq+1 = ... = π
k
an appropriate approach for the identification of a global trend as well as for the most likely shape of that exposure-response relationship is characterized by simulation and demonstrated for real data examples. Power and simultaneous confidence intervals can be estimated as well. If the conditions are fulfilled to transform the exposure-response data into a 2 × k table, a simple approach for identification of a global trend and its elementary shape is available for epidemiologists.
Long-term surveillance of sulfate-reducing bacteria in highly saline industrial wastewater evaporation ponds
Authors: Ben-Dov Eitan , Kushmaro Ariel , Brenner Asher
Published: March 2009

Abundance and seasonal dynamics of sulfate-reducing bacteria (SRB), in general, and of extreme halophilic SRB (belonging to Desulfocella halophila) in particular, were examined in highly saline industrial wastewater evaporation ponds over a forty one month period. Industrial wastewater was sampled and the presence of SRB was determined by quantitative real-time PCR (qPCR) with a set of primers designed to amplify the dissimilatory sulfite reductase (dsrA) gene. SRB displayed higher abundance during the summer (106–108 targets ml-1) and lower abundance from the autumn-spring (103–105 targets ml-1). However, addition of concentrated dissolved organic matter into the evaporation ponds during winter immediately resulted in a proliferation of SRB, despite the lower wastewater temperature (12–14°C). These results indicate that the qPCR approach can be used for rapid measurement of SRB to provide valuable information about the abundance of SRB in harsh environments, such as highly saline industrial wastewaters. Low level of H2S has been maintained over five years, which indicates a possible inhibition of SRB activity, following artificial salination (≈16% w/v of NaCl) of wastewater evaporation ponds, despite SRB reproduction being detected by qPCR.
Amino acid racemization reveals differential protein turnover in osteoarthritic articular and meniscal cartilages
Authors: Stabler Thomas V , Byers Samuel S , Zura Robert D , Kraus Virginia Byers
Published: March 2009

Introduction

Certain amino acids within proteins have been reported to change from the L form to the D form over time. This process is known as racemization and is most likely to occur in long-lived low-turnover tissues such as normal cartilage. We hypothesized that diseased tissue, as found in an osteoarthritic (OA) joint, would have increased turnover reflected by a decrease in the racemized amino acid content.

Methods

Using high-performance liquid chromatography methods, we quantified the L and D forms of amino acids reported to racemize in vivo on a biological timescale: alanine, aspartate (Asp), asparagine (Asn), glutamate, glutamine, isoleucine, leucine (Leu), and serine (Ser). Furthermore, using a metabolically inactive control material (tooth dentin) and a control material with normal metabolism (normal articular cartilage), we developed an age adjustment in order to make inferences about the state of protein turnover in cartilage and meniscus.

Results

In the metabolically inactive control material (n = 25, ages 13 to 80 years) and the normal metabolizing control material (n = 19, ages 17 to 83 years), only Asp + Asn (Asx), Ser, and Leu showed a significant change (increase) in racemization with age (P < 0.01). The age-adjusted proportions of racemized to total amino acid (D/D+L expressed as a percentage of the control material) for Asx, Ser, and Leu when compared with the normal articular cartilage control were 97%, 74%, and 73% in OA meniscal cartilage and 97%, 70%, and 78% in OA articular cartilage. We also observed lower amino acid content in OA articular and meniscal cartilages compared with normal articular cartilage as well as a loss of total amino acids with age in the OA meniscal but not the OA articular cartilage.

Conclusions

These data demonstrate comparable anabolic responses for non-lesioned OA articular cartilage and OA meniscal cartilage but an excess of catabolism over anabolism for the meniscal cartilage.
DISTILLER: a data integration framework to reveal condition dependency of complex regulons in Escherichia coli
Authors: Lemmens Karen , De Bie Tijl , Dhollander Thomas , De Keersmaecker Sigrid C , Thijs Inge M , Schoofs Geert , De Weerdt Ami , De Moor Bart , Vanderleyden Jos , Collado-Vides Julio , Engelen Kristof , Marchal Kathleen
Published: March 2009

We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity.
Aripiprazole for schizophrenia
Authors: El-Sayeh H. G. , Morganti C. , Adams C. E.
Published: March 2009

Background

Aripiprazole is an atypical antipsychotic that is reported to be
effective in the treatment of schizophrenia.

Aims

To investigate the effects of aripiprazole on patients with schizophrenia
and schizophrenia-like psychoses by conducting a systematic review of
randomised controlled trials (RCTs).

Method

Database and manual searches and direct contact were used to identify
relevant RCTs.

Results

We included 10 randomised controlled studies (involving a total of 4125
patients), but study attrition was large and the standard of data
reporting was poor. Compared with placebo, aripiprazole treatment was
associated with a significant decrease in relapse rates, increased
compliance with the study protocol, and a decrease in prolactin levels
below the expected values. Compared with risperidone, aripiprazole caused
less elevation of prolactin levels and less prolongation of the average
QTc interval.

Conclusions

Aripiprazole has been licensed despite the fact that few reliable data on
this drug are publicly available. It may be effective for treatment of
schizophrenia, but in terms of tolerability and global outcomes it shows
little difference from existing antipsychotics.
Health service use by adults with depression: community survey in five European countries
Authors: McCracken Cherie , Dalgard Odd Steffen , Ayuso-Mateos Jose Luis , Casey Patricia , Wilkinson Greg , Lehtinen Ville , Dowrick Christopher
Published: March 2009

Background

Little is known about patterns of healthcare use by people with depression in Europe.

Aims

To examine the use and cost of services by adults with depressive or adjustment disorders in five European countries, and predictive factors.

Method

People aged 18–65 years with depressive or adjustment disorders (n=427) in Ireland, Finland, Norway, Spain and the UK provided information on predisposition (demographics, social support), enablement (country, urban/rural, social function) and need (symptom severity, perceived health status) for services. Outcome measures were self-reported use Client Services Receipt Interview and costs of general practice, generic, psychiatric or social services in the past 6 months.

Results

Less frequent use was made of generic services in Norway and psychiatric services in the UK. Severity of depression, perceived health status, social functioning and level of social support were significant predictors of use; the number of people able to provide support was positively associated with greater health service use.

Conclusions

Individual participant factors provided greater explanatory power than national differences in healthcare delivery. The association between social support and service use suggests that interventions may be needed for those who lack social support.
Generic clozapine: outcomes after switching
formulations
Authors: Paton Carol
Published: March 2009

Two generic preparations of clozapine have been licensed in the UK. The
bioequivalence of these products compared with Clozaril® has not
been unequivocally demonstrated. Clinical equivalence has also been
questioned. The objective of this study was to determine clinical outcomes
for all patients switched from Clozaril® to a generic formulation
in one mental health service. We examined dosage data and Clinical Global
Impression (CGI) of Severity of Illness scores for 337 patients before and
after the switch and CGI change scores after the switch. There was no
evidence of clinical deterioration or need to use higher dosages. Generic
clozapine is not inferior to Clozaril®.
Estrogen-Dependent and -Independent Estrogen Receptor-α Signaling Separately Regulate Male Fertility
Authors: Sinkevicius Kerstin W. , Laine Muriel , Lotan Tamara L. , Woloszyn Karolina , Richburg John H. , Greene Geoffrey L.
Published: March 2009

Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERα pathways. Surprisingly, we found that ligand-independent ERα signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERα signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERα knock-in (ENERKI) mice with the ERα selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERα in vivo, we discovered male fertility required neonatal estrogen-mediated ERα signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERα in human infertility should be examined more closely.
Heterogeneity in Mitotic Activity and Telomere Length Implies an Important Role of Young Islets in the Maintenance of Islet Mass in the Adult Pancreas
Authors: Peng Si-wu , Zhu Lin-yun , Chen Miao , Zhang Mei , Li Di-zheng , Fu Yu-cai , Chen Shen-ren , Wei Chi-ju
Published: March 2009

Understanding the mechanisms of β-cell dynamics in postnatal animals is central to cure diabetes. A major obstacle in evaluating the status of pancreatic cells is the lack of surface markers. Here we performed quantitative measurements of two internal markers to follow the developmental history of islets. One marker, cell-cycle activity, was established by measuring expression of Ki67 and the incorporation of 5-bromodeoxyuridine. The other marker, the aging process, was delineated by the determination of telomere length. Moreover, islet neogenesis, possibly from ductal precursors, was monitored by pancreatic duct labeling with an enhanced green fluorescence protein (EGFP) transgene. We found that islets from younger animals, on average, expressed higher Ki67 transcripts, displayed elevated 5-bromodeoxyuridine incorporation, and had longer telomeres. However, significant heterogeneity of these parameters was observed among islets from the same mouse. In contrast, the levels of proinsulin-1 transcripts in islets of different ages did not change significantly. Moreover, mitotic activities correlated significantly with telomere lengths of individual islets. Lastly, after 5.5 d pancreatic duct labeling, a few EGFP-positive islets could be identified in neonatal but not from adult pancreases. Compared with unlabeled control islets, EGFP-positive islets had higher mitotic activities and longer telomeres. The results suggest that islets are born at different time points during the embryonic and neonatal stages and imply that young islets might play an important role in the maintenance of islet mass in the adult pancreas.
Molecules and mechanisms of dendrite development inDrosophila
Authors: Corty Megan M. , Matthews Benjamin J. , Grueber Wesley B.
Published: March 2009

Neurons are one of the most morphologically diverse cell types, in large part owing to their intricate dendrite branching patterns. Dendrites are structures that are specialized to receive and process inputs in neurons, thus their specific morphologies reflect neural connectivity and influence information flow through circuits. Recent studies in Drosophila on the molecular basis of dendrite diversity, dendritic guidance, the cell biology of dendritic branch patterning and territory formation have identified numerous intrinsic and extrinsic cues that shape diverse features of dendrites. As we discuss in this review, many of the mechanisms that are being elucidated show conservation in diverse systems.
Target recognition at the tips of postsynaptic filopodia: accumulation and function of Capricious
Authors: Kohsaka Hiroshi , Nose Akinao
Published: March 2009

While much evidence suggests that postsynaptic dynamism contributes to the formation of synapses, few studies have addressed its possible role in target selection. Do postsynaptic motile structures seek specific synaptic partner cells, as does the presynaptic growth cone? Here we studied the dynamics of myopodia, postsynaptic filopodia in Drosophila muscles, and the role of Capricious (CAPS) during the process of synaptic matchmaking. CAPS is a target recognition molecule with an extracellular domain containing leucine-rich repeat sequences. It is expressed in specific subsets of embryonic/larval body wall muscles, including muscle 12 (M12). We provide evidence that implicates the tips of myopodia as loci of initial neuromuscular recognition: (1) CAPS, expressed as a GFP-fusion protein in M12, accumulated at the tips of myopodia; and (2) simultaneous live imaging of presynaptic motoneurons and postsynaptic myopodia revealed that initial neuromuscular contacts occur at the tips of myopodia. The live imaging also showed that individual postsynaptic myopodia appear to be able to discriminate partner and non-partner presynaptic cells: whereas many myopodial contacts with the partner motoneurons are stabilized to form synapses, those with non-partner neurons are retracted. In caps mutants, or in double mutants lacking both CAPS and the closely related protein Tartan, we observed fewer contacts between myopodia of M12 and the presynaptic growth cones during the process of initial neuromuscular interaction. The nascent synaptic sites of M12 were also reduced. These results provide evidence for the sensing function of postsynaptic filopodia, and implicate Caps-mediated recognition at the tips of myopodia in synaptic matching.