Study of the Scope, Sequence, and Objectives of Elementary School Science as Revealed by State Science Guides

Higher Education (Science Education

AKUNTABILITAS PENGELOLAAN KEUANGAN PADA PAROKI SANTO PETRUS DAN PAULUS KELOR

Penelitian ini merupakan penelitian kualitatif deskriptif yang bertujuan untuk menganalisis dan mengevaluasi pelaksanaan akuntabilitas pengelolaan keuangan Paroki. Penelitian ini dilaksanakan di Paroki Santo Petrus dan Paulus Kelor, Gunung Kidul. Data penelitian ini menggunakan data primer berupa jawaban responden atas wawancara dan data sekunder berupa Pedoman Pelaksanaan Pelayanan Pastoral Paroki (P5) Kelor dan Pedoman Pengelolaan Keuangan Paroki Kelor. Pengumpulan data dilakukan dengan wawancara, dokumentasi dan observasi. Metode analisis data yang digunakan adalah metode Miles and Huberman, yang terdiri dari empat tahapan, yaitu: (1) Pengumpulan Data, (2) Reduksi Data, (3) Penyajian Data dan (4) Penarikan Kesimpulan. Hasil penelitian menunjukkan bahwa akuntabilitas yang dilaksanakan oleh Paroki Santo Petrus dan Paulus Kelor telah berjalan dengan baik, namun terdapat dua hal yang mengakibatkan keterlambatan dalam mengirimkan laporan kepada Keuskupan. Pertama, data keuangan dari Bendahara lainnya terlambat diserahkan pada Bendahara Umum. Kedua, untuk memasukkan data keuangan Paroki yang sangat banyak hanya dilakukan oleh Bendahara Umum

Repair of oxidatively damaged guanine in Saccharomyces cerevisiae by an alternative pathway

AbstractBackground: Transversion mutations are caused by 8-oxoguanine (OG), a DNA lesion produced by the spontaneous oxidation of guanine nucleotides, which mis-pairs with adenine during replication. Resistance to this mutagenic threat is mediated by the GO system, the components of which are functionally conserved in bacteria and mammals. To date, only one of three GO system components has been identified in the budding yeast Saccharomyces cerevisiae, namely the OG:C-specific glycosylase/lyase yOgg1. Furthermore, S. cerevisiae has been reported to contain a unique glycosylase/lyase activity, yOgg2, which excises OG residues opposite adenines. Paradoxically, according to the currently accepted model, yOgg2 activity should increase the mutagenicity of OG lesions. Here we report the isolation of yOgg2 and the elucidation of its role in oxidative mutagenesis.Results: Borohydride-dependent cross-linking using an OG-containing oligonucleotide substrate led to the isolation of yOgg1 and a second protein, Ntg1, which had previously been shown to process oxidized pyrimidines in DNA. We demonstrate that Ntg1 has OG-specific glycosylase/lyase activity indistinguishable from that of yOgg2. Targeted disruption of the NTG1 gene resulted in complete loss of yOgg2 activity and yeast lacking NTG1 had an elevated rate of A:T to C:G transversions.Conclusions: The Ntg1 and yOgg2 activities are encoded by a single gene. We propose that yOgg2 has evolved to process OG:A mis-pairs that have arisen through mis-incorporation of 8-oxo-dGTP during replication. Thus, the GO system in S. cerevisiae is fundamentally distinct from that in bacteria and mammals

A structural snapshot of base-pair opening in DNA

The response of double-helical DNA to torsional stress may be a driving force for many processes acting on DNA. The 1.55-A crystal structure of a duplex DNA oligonucleotide d(CCAGGCCTGG)(2) with an engineered crosslink in the minor groove between the central guanine bases depicts how the duplex can accommodate such torsional stress. We have captured in the same crystal two rather different conformational states. One duplex contains a strained crosslink that is stabilized by calcium ion binding in the major groove, directly opposite the crosslink. For the other duplex, the strain in the crosslink is relieved through partial rupture of a base pair and partial extrusion of a cytosine accompanied by helix bending. The sequence used is the target sequence for the HaeIII methylase, and this partially flipped cytosine is the same nucleotide targeted for extrusion by the enzyme. Molecular dynamics simulations of these structures show an increased mobility for the partially flipped-out cytosine

In vitro selection of RNA aptamers against a composite small molecule-protein surface

A particularly challenging problem in chemical biology entails developing systems for modulating the activity of RNA using small molecules. One promising new approach towards this problem exploits the phenomenon of ‘surface borrowing,’ in which the small molecule is presented to the RNA in complex with a protein, thereby expanding the overall surface area available for interaction with RNA. To extend the utility of surface borrowing to include potential applications in synthetic biology, we set out to create an ‘orthogonal’ RNA-targeting system, one in which all components are foreign to the cell. Here we report the identification of small RNA modules selected in vitro to bind a surface-engineered protein, but only when the two macromolecules are bound to a synthetic bifunctional small molecule

Inhibition of Oncogenic Wnt Signaling through Direct Targeting of β-Catenin

Aberrant activation of signaling by the Wnt pathway is strongly implicated in the onset and progression of numerous types of cancer. Owing to the persistent dependence of these tumors on Wnt signaling for growth and survival, inhibition of this pathway is considered an attractive mechanism-based therapeutic approach. Oncogenic activation of Wnt signaling can ensue from a variety of distinct aberrations in the signaling pathway, but most share the common feature of causing increased cellular levels of β-catenin by interfering with its constitutive degradation. β-Catenin serves as a central hub in Wnt signaling by engaging in crucial protein–protein interactions with both negative and positive effectors of the pathway. Direct interference with these protein–protein interactions is a biologically compelling approach toward suppression of β-catenin hyperactivity, but such interactions have proven intransigent with respect to small-molecule targeting. Hence β-catenin remains an elusive target for translational cancer therapy. Here we report the discovery of a hydrocarbon-stapled peptide that directly targets β-catenin and interferes with its ability to serve as a transcriptional coactivator for T-cell factor (TCF) proteins, the downstream transcriptional regulators of the Wnt pathway.Chemistry and Chemical BiologyStem Cell and Regenerative Biolog

Let’s Chat: On-Screen Social Responsiveness Is Not Sufficient to Support Toddlers’ Word Learning From Video

Joint engagement with a speaker is one cue children may use to establish that an interaction is relevant to them and worthy of attention. People on pre-recorded video cannot engage contingently with a viewer in shared experiences, possibly leading to deficits in learning from video relative to learning from responsive face-to-face encounters. One hundred and seventy-six toddlers (24 and 30 months old) were offered referential social cues disambiguating a novel word’s meaning in one of four conditions: responsive live (a speaker was present and engaged with children); unresponsive video (a speaker on video looked at the camera and smiled at scripted times); unresponsive live (although present, the speaker behaved as she did on the unresponsive video), and responsive video (a speaker on closed-circuit video engaged with children, as in video chat). Children of both ages reliably learned the word in the responsive live condition, and older children (30 months) learned in the unresponsive live condition. Neither group learned in the responsive or unresponsive video conditions. The results show that the addition of communicative social cues to the video presentation via video chat was not sufficient to support learning in this case. Rather, toddlers’ transfer and generalization of words presented on video chat may depend on other contextual factors, such as co-viewers who scaffold their learning. Live, responsive video as implemented in this and prior studies is compared, with implications for the use of video chat via the Internet with young children

Do very young children learn from video?

This paper summarizes research on infants' early behavior toward televised images, and explores a "video deficit" in toddlers' learning from video. A shift in recognizing video images as representations allows older children to learn educational content from television programs and to distinguish realistic programming (e.g., the news) from fantasy (e.g., cartoons and dramas)

An engineered protein antagonist of K-Ras/B-Raf interaction

Ras is at the hub of signal transduction pathways controlling cell proliferation and survival. Its mutants, present in about 30% of human cancers, are major drivers of oncogenesis and render tumors unresponsive to standard therapies. Here we report the engineering of a protein scaffold for preferential binding to K-Ras G12D. This is the first reported inhibitor to achieve nanomolar affinity while exhibiting specificity for mutant over wild type (WT) K-Ras. Crystal structures of the protein R11.1.6 in complex with K-Ras WT and K-Ras G12D offer insight into the structural basis for specificity, highlighting differences in the switch I conformation as the major defining element in the higher affinity interaction. R11.1.6 directly blocks interaction with Raf and reduces signaling through the Raf/MEK/ERK pathway. Our results support greater consideration of the state of switch I and provide a novel tool to study Ras biology. Most importantly, this work makes an unprecedented contribution to Ras research in inhibitor development strategy by revealing details of a targetable binding surface. Unlike the polar interfaces found for Ras/effector interactions, the K-Ras/R11.1.6 complex reveals an extensive hydrophobic interface that can serve as a template to advance the development of high affinity, non-covalent inhibitors of K-Ras oncogenic mutants.National Institutes of Health (U.S.) (Grant 5-R01-CA096504-15

All-Atom Model for Stabilization of α-Helical Structure in Peptides by Hydrocarbon Staples

Recent work has shown that the incorporation of an all-hydrocarbon “staple” into peptides can greatly increase their α-helix propensity, leading to an improvement in pharmaceutical properties such as proteolytic stability, receptor affinity and cell-permeability. Stapled peptides thus show promise as a new class of drugs capable of accessing intractable targets such as those that engage in intracellular protein-protein interactions. The extent of α-helix stabilization provided by stapling has proven to be substantially context dependent, requiring cumbersome screening to identify the optimal site for staple incorporation. In certain cases, a staple encompassing one turn of the helix (attached at residues i and i+4) furnishes greater helix stabilization than one encompassing two turns (i,i+7 staple), which runs counter to expectation based on polymer theory. These findings highlight the need for a more thorough understanding of the forces that underlie helix stabilization by hydrocarbon staples. Here we report all-atom Monte Carlo folding simulations comparing unmodified peptides derived from RNAse A and BID BH3 with various i,i+4 and i,i+7 stapled versions thereof. The results of these simulations were found to be in quantitative agreement with experimentally determined helix propensities. We also discovered that staples can stabilize quasi-stable decoy conformations, and that the removal of these states plays a major role in determining the helix stability of stapled peptides. Finally, we critically investigate why our method works, exposing the underlying physical forces that stabilize stapled peptides.Chemistry and Chemical Biolog