High throughput screening identifies modulators of histone deacetylase inhibitors

Background Previous studies from our laboratory and others have demonstrated that in addition to altering chromatin acetylation and conformation, histone deacetylase inhibitors (HDACi) disrupt the acetylation status of numerous transcription factors and other proteins. A whole genome yeast deletion library screen was used to identify components of the transcriptional apparatus that modulate the sensitivity to the hydroxamic acid-based HDACi, CG-1521. Results Screening 4852 haploid Saccharomyces cerevisiae deletion strains for sensitivity to CG-1521 identifies 407 sensitive and 80 resistant strains. Gene ontology (GO) enrichment analysis shows that strains sensitive to CG-1521 are highly enriched in processes regulating chromatin remodeling and transcription as well as other ontologies, including vacuolar acidification and vesicle-mediated transport. CG-1521-resistant strains include those deficient in the regulation of transcription and tRNA modification. Components of the SAGA histone acetyltransferase (HAT) complex are overrepresented in the sensitive strains, including the catalytic subunit, Gcn5. Cell cycle analysis indicates that both the wild-type and gcn5Δ strains show a G1 delay after CG-1521 treatment, however the gcn5Δ strain displays increased sensitivity to CG-1521-induced cell death compared to the wild-type strain. To test whether the enzymatic activity of Gcn5 is necessary in the response to CG-1521, growth assays with a yeast strain expressing a catalytically inactive variant of the Gcn5 protein were performed and the results show that this strain is less sensitive to CG-1521 than the gcn5Δ strain. Conclusion Genome-wide deletion mutant screening identifies biological processes that affect the sensitivity to the HDAC inhibitor CG-1521, including transcription and chromatin remodeling. This study illuminates the pathways involved in the response to CG-1521 in yeast and provides incentives to understand the mechanisms of HDAC inhibitors in cancer cells. The data presented here demonstrate that components of the SAGA complex are involved in mediating the response to CG-1521. Additional experiments suggest that functions other than the acetyltransferase activity of Gcn5 may be sufficient to attenuate the effects of CG-1521 on cell growth

Societal effects of transdisciplinary sustainability research—How can they be strengthened during the research process?

Transdisciplinary sustainability research aims to mitigate or to solve complex societal problems and advance the production of scientific knowledge. Reflexive approaches to transdisciplinary research processes are outlined to systematically strengthen the potential for societal effectiveness. So far, it is rare to find empirically based analyses of the links between the quality of the research process and the methods applied on the one hand and the effects achieved on the other. This paper thus addresses the issue of heightening the societal effects of transdisciplinary sustainability research. The objective is to explore ways of consciously promoting societal effectiveness in transdisciplinary research. We argue that these possibilities evolve at the intersection between the general project framework and an adaptive shaping of transdisciplinary research processes. A reflexive approach of this kind proactively considers the dynamics of interests and concerns, roles and responsibilities, the collaboration culture within a project, and the connectivity to the context of action addressed. Its deployment presupposes an appreciation of the basic conditions, i.e. the historical development of the respective problem, the heterogeneity of actors involved, the general environment and, finally, the funding conditions

Aktivitas Antibakteri Ekstrak Kulit Manggis (Garcinia mangostana L.) terhadap Methicillin-resistant Staphylococcus aureus ATCC 33591

Infeksi termasuk dalam permasalahan kesehatan yang terus meningkat di negara tropis termasuk Indonesia. WHO merekomendasikan untuk pengobatan alternatif dengan memanfaatkan bahan alam. Ekstrak kulit manggis diketahui memiliki beberapa kandungan senyawa dengan efek farmakologi salah satunya adalah antimikroba. Penelitian ini dilakukan untuk mengetahui aktivitas antibakteri dari ekstrak kulit manggis (Garcinia mangostana L.) terhadap pertumbuhan bakteri MRSA. Penelitian ini termasuk dalam jenis eksperimental secara in vitro dengan metode Kirby-Bauer. Menurut tabel Greenwood, hasil uji antibakteri ekstrak kulit manggis dengan berbagai konsentrasi diperoleh rata-rata zona hambat pada konsentrasi 100 mg/ml hingga 25 mg/ml termasuk kategori lemah, kategori 6,25 mg/ml sampai 1,56 mg/ml termasuk kategori yang tidak terdapat aktivitas antibakteri, sedangkan pada kontrol positif termasuk kategori sedang. Menurut hasil penelitian, ekstrak metanol kulit manggis (Garcinia mangostana L.) memiliki kemampuan untuk menghambat pertumbuhan bakteri Methicillin-resistant Staphylococcus aureus (MRSA) sehingga berpotensi sebagai antibakteri. Kata kunci: antibakteri, Garcinia mangostana L., Methicillin-resistant Staphylococcus aureus (MRSA). / Infection is increasing health problems in tropical countries including Indonesia. WHO recommends for alternative medicine by utilizing natural ingredients. Mangosteen peel extract consists of compounds that have pharmacological effects, one of which is antimicrobial. The purpose of this research was to determine the antibacterial activity of mangosteen peel extract (Garcinia mangostana L.) against the growth of MRSA bacteria. This research is included in the in vitro experimental type with the Kirby-Bauer method. According to the Greenwood table, antibacterial test results of mangosteen peel extract with various concentrations were obtained on average inhibition zones at concentrations of 100 mg/ml to 25 mg/ml including the weak category, category 6.25 mg/ml to 1.56 mg/ml including categories with no antibacterial activity, while positive controls included the medium category. According to the research results, methanol extract of mangosteen peel (Garcinia mangostana L.) can inhibit the growth of Methicillin-resistant Staphylococcus aureus (MRSA) bacteria so that it has the potential as an antibacterial. Keywords: antibacterial, Garcinia mangostana L., Methicillin-resistant Staphylococcus aureus (MRSA

Pengaruh Kecakapan Mengajar Guru PAK Terhadap Minat dan Hasil Belajar Siswa

This study aims to find the contribution of students 'perceptions about the teaching skills of PAK (X) teachers to students' interest in learning (Y1) class VII SMP Era Ibang Medan, second; the contribution of students' perceptions about the teaching skills of PAK teachers to the learning outcomes of PAK students (Y2) grade VII SMP Era Ibang Medan. Third: the contribution of students' perceptions about the teaching skills of PAK teachers to the interests and learning outcomes of class VII students of SMP Era Ibang Medan. The sample of this research is 130 people. To determine whether there is a relationship between independent and dependent variables, analyzed using the product correlation formula from Person's Moment. Based on the results of the research, the contribution of students 'perceptions about the teaching skills of PAK teachers to the learning interest of grade VII students of SMP Era Ibang Medan obtained a value of 0.382> 0.361, the contribution of students' perceptions to the teaching skills of PAK teachers on the learning outcomes of students in class VII SMP Era Ibang Medan was obtained. the value of 0.698> 13.040 and the contribution of students' perceptions about the teaching skills of PAK teachers to the interests and learning outcomes of class VII students of SMP Era Ibang Medan. Therefore, it is necessary to have a measured evaluation to see the skills of PAK teachers in teaching to increase student interest and learning outcomes. 

Acculturation, out-group positivity and eating disorders symptoms among Emirati women

© 2017, Springer International Publishing Switzerland. Western acculturation has been implicated in the development of eating disorders among populations living outside Europe and North America. This study explored the relationship between Western acculturation, in-group/out-group evaluations and eating disorders symptoms among female citizens of the United Arab Emirates (UAE). Emirati college women (N = 209) completed an affective priming task, designed to implicitly assess in-group (Emirati) and out-group (American) evaluations. Participants also completed the Westernization Survey, a widely used self-report measure of acculturation, and the Eating Attitudes Test (EAT-26). Across the whole sample, out-group positivity was correlated with higher levels of eating disorder symptoms. Participants classified as at risk for eating disorders showed a clear out-group preference (out-group positivity greater than in-group positivity). Western acculturation was also positively correlated with eating disorder symptoms. Overall, these findings lend further support to the acculturation hypothesis of eating disorders in the context of Emirati college women

Improving Privacy Settings for Facebook by Using Interpersonal Distance as Criterion

The possibility to define custom privacy settings in Facebook has been improved over the last years. Still,numerous users do not know how to change those settings or do not use the settings because they are cumbersome to use. Within this paper a new method for defining the privacy settings in online social networks is presented that uses the social distance between users as setting criterion. This approach was tested as a paper prototype in a first user study with 10 participants. Results show that the number of errors was significantly decreased and that the subjective evaluation of the interface was promising

Chytrid parasitism facilitates trophic transfer between bloom-forming cyanobacteria and zooplankton (Daphnia)

Parasites are rarely included in food web studies, although they can strongly alter trophic interactions. In aquatic ecosystems, poorly grazed cyanobacteria often dominate phytoplankton communities, leading to the decoupling of primary and secondary production. Here, we addressed the interface between predator-prey and host-parasite interactions by conducting a life-table experiment, in which four Daphnia galeata genotypes were maintained on quantitatively comparable diets consisting of healthy cyanobacteria or cyanobacteria infected by a fungal (chytrid) parasite. In four out of five fitness parameters, at least one Daphnia genotype performed better on parasitised cyanobacteria than in the absence of infection. Further treatments consisting of purified chytrid zoospores and heterotrophic bacteria suspensions established the causes of improved fitness. First, Daphnia feed on chytrid zoospores which trophically upgrade cyanobacterial carbon. Second, an increase in heterotrophic bacterial biomass, promoted by cyanobacterial decay, provides an additional food source for Daphnia. In addition, chytrid infection induces fragmentation of cyanobacterial filaments, which could render cyanobacteria more edible. Our results demonstrate that chytrid parasitism can sustain zooplankton under cyanobacterial bloom conditions, and exemplify the potential of parasites to alter interactions between trophic levels

Efficient probabilistic joint inversion of direct current resistivity and small-loop electromagnetic data

Often, multiple geophysical measurements are sensitive to the same subsurface parameters. In this case, joint inversions are mostly preferred over two (or more) separate inversions of the geophysical data sets due to the expected reduction of the non-uniqueness in the joint inverse solution. This reduction can be quantified using Bayesian inversions. However, standard Markov chain Monte Carlo (MCMC) approaches are computationally expensive for most geophysical inverse problems. We present the Kalman ensemble generator (KEG) method as an efficient alternative to the standard MCMC inversion approaches. As proof of concept, we provide two synthetic studies of joint inversion of frequency domain electromagnetic (FDEM) and direct current (DC) resistivity data for a parameter model with vertical variation in electrical conductivity. For both studies, joint results show a considerable improvement for the joint framework over the separate inversions. This improvement consists of (1) an uncertainty reduction in the posterior probability density function and (2) an ensemble mean that is closer to the synthetic true electrical conductivities. Finally, we apply the KEG joint inversion to FDEM and DC resistivity field data. Joint field data inversions improve in the same way seen for the synthetic studies

Influence of P and Ti on phase formation at solidification of synthetic slag containing Li, Zr, La, and Ta

In the future, it will become increasingly important to recover critical elements from waste materials. For many of these elements, purely mechanical processing is not efficient enough. An already established method is pyrometallurgical processing, with which many of the technologically important elements, such as Cu or Co, can be recovered in the metal phase. Ignoble elements, such as Li, are known to be found in the slag. Even relatively base or highly redox-sensitive elements, such as Zr, REEs, or Ta, can be expected to accumulate in the slag. In this manuscript, the methods for determining the phase formation and the incorporation of these elements were developed and optimized, and the obtained results are discussed. For this purpose, oxide slags were synthesized with Al, Si, Ca, and the additives, P and Ti. To this synthetic slag were added the elements, Zr and La (which can be considered proxies for the light REEs), as well as Ta. On the basis of the obtained results, it can be concluded that Ti or P can have strong influences on the phase formation. In the presence of Ti, La, and Ta, predominantly scavenged by perovskite (Ca1−wLa2/3wTi1−(x+y+z)Al4/3xZryTa4/5zO3), and Zr predominantly as zirconate (Ca1−wLa2/3wZr4−(x+y+z)Al4/3xTiyTa4/5zO9), with the P having no effect on this behavior. Without Ti, the Zr and Ta are incorporated into the pyrochlore (La2−xCa3/2x−yZr2+2/4y−zTa4/5zO7), regardless of the presence of phosphorus. In addition to pyrochlore, La accumulates primarily in britholite-type La oxy- or phosphosilicates. Without P and Ti, similar behavior is observed, except that the britholite-like La silicates do not contain P, and the scavenging of La is less efficient. Lithium, on the other hand, forms its own compounds, such as LiAlO2(Si), LiAl5O8, eucryptite, and Li silicate. Additionally, in the presence of P, Li3PO4 is formed, and the eucryptite incorporates P, which indicates an additional P-rich eutectic melt

In vitro induction of Entamoeba gingivalis cyst-like structures from trophozoites in response to antibiotic treatment

Background: Entamoeba gingivalis (E. gingivalis) is an anaerobic protozoan that is strongly associated with inflamed periodontal pockets. It is able to invade the mucosal epithelium of the human host, where it can feed on epithelial cells and elicit a severe innate immune response. Unlike other Entamoeba species, it is considered that E. gingivalis cannot form cysts, because it is a non-infectious protozoan. The lack of encystation capability would make it susceptible to periodontal treatment. However, it is not clear how the human host becomes infected with E. gingivalis trophozoites. We investigated the ability of E. gingivalis to encapsulate in response to an unfavorable environment in vitro. Methods: Different strains of E. gingivalis, isolated from inflamed periodontal pocket samples, were cultured for 8 days in the presence or absence of the antimicrobials amoxycillin and metronidazole. To reveal cyst formation, we investigated the morphology and ultrastructure of the amoeba by light, fluorescence, transmission and scanning electron microscopy. We also used the fluorescent dye calcofluor white M2R to demonstrate chitin present in the cyst wall. Results: We observed exocysts and an intra-cystic space separating the encapsulated trophozoite from the environment. Remarkably, cysts showed a smooth surface, polygonal edges and smaller size compared to free-living trophozoites. In addition, encapsulated trophozoites that detached from the cyst wall had a dense cytoplasma without phagocytic vesicles. The cyst walls consisted of chitin as in other Entamoba species. The encapsulated trophozoids were mononuclear after antibioticinduced encapsulation. Discussion: We conclude that E. gingivalis cyst formation has significant implications for dissemination and infection and may explain why established treatment approaches often fail to halt periodontal tissue destruction during periodontitis and peri-implantitis.Peer Reviewe