TEORI PERTUKARAN SOSIAL TENTANG FENOMENA DAKWAH DI EKS LOKALISASI DADAPAN

This study aims to find out how the role of the preacher in bringing changes to the social conditions of the people who used to work in the Dadapan prostitution localization, Kediri City. Da'i plays an important role as a propagator of religion to protect the community. Thus, the relationship between the preacher and his community must be close regardless of the background or social conditions of the community. This research uses a qualitative approach with a case study method and is equipped with George Homans' social exchange theory, namely as an analytical tool to understand and seek clarity of cases so that researchers know more clearly about the phenomenon of da'wah in the ex-Dadapan localization community. The results of this study conclude that the da'wah process that occurs in Dadapan Village in social exchange theory explains that they are willing to interact when the interaction produces benefits for themselves. Therefore, in the dynamics of increasing religious understanding in the ex-Dadapan localization, it is necessary to have a reward given so that people want to interact in discussing religious studies

Analisis Tingkat Efisiensi Pusat Kesehatan Masyarakat (Puskesmas) Dengan Metode Data Envelopment Analysis (Dea) (Studi Kasus: Puskesmas Kota Surabaya)

Puskesmas seluruh Surabaya pada tahun 2013 mempunyai rasio tenaga medis dengan pengunjung yang cukup besar terutama untuk area Surabaya Utara. Selama ini puskesmas di Kota Surabaya belum pernah dilakukan proses pengukuran efisiensi secara bersamaan antara puskesmas yang satu dengan yang lainnya. Hal ini menimbulkan pertanyaan apakah area yang lain sudah optimal dalam menggunakan sumber daya kesehatan. Maka untuk mengukur sekaligus membandingkan efisiensi antara puskesmas, penelitian ini menggunakan metode Data Envelopment Analysis (DEA). DEA merupakan metodologi nonparametrik yang didasarkan pada linear programming dan digunakan untuk menganalisis fungsi produksi melalui suatu pemetaan frontier produksi. Pada penelitian ini dipilih 10 puskesmas yang telah memiliki sertifikat ISO 9001:2008 dan memiliki fasilitas rawat inap (persalinan). Berdasarkan analisis dan pengolahan data dengan metode DEA-CCR dan DEA-BCC yang berorientasi output dapat diketahui bahwa seluruh puskesmas berada pada kondisi efisien kecuali puskesmas Tanjunsari dan Balongsari.Kedua puskesmas tersebut dinilai kurang mampu memanfaatkan sumber daya yang ada untuk bisa menghasilkan jumlah pasien yang maksimal seperti puskesmas lain yang berada pada kategori efisien. Proses perbaikan kedua puskesmas tersebut menggunakan 2 metode yakni analisis slack dan peer group

Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity

Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen (4-HT)-responsive intein at specific positions in Cas9. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9

Structure and Engineering of Francisella novicida Cas9

Summary The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 Å resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-containing DNA targets. A structural comparison of FnCas9 with other Cas9 orthologs revealed striking conserved and divergent features among distantly related CRISPR-Cas9 systems. We found that FnCas9 recognizes the 5′-NGG-3′ PAM, and used the structural information to create a variant that can recognize the more relaxed 5′-YG-3′ PAM. Furthermore, we demonstrated that the FnCas9-ribonucleoprotein complex can be microinjected into mouse zygotes to edit endogenous sites with the 5′-YG-3′ PAM, thus expanding the target space of the CRISPR-Cas9 toolbox

An efficient and scalable pipeline for epitope tagging in mammalian stem cells using Cas9 ribonucleoprotein

AbstractCRISPR/Cas9 can be used for precise genetic knock-in of epitope tags into endogenous genes, simplifying experimental analysis of protein function. However, Cas9-assisted epitope tagging in primary mammalian cell cultures is often inefficient and reliant on plasmid-based selection strategies. Here we demonstrate improved knock-in efficiencies of diverse tags (V5, 3XFLAG, Myc, HA) using co-delivery of Cas9 protein pre-complexed with two-part synthetic modified RNAs (annealed crRNA:tracrRNA) and single-stranded oligodeoxynucleotide (ssODN) repair templates. Knock-in efficiencies of ~5-30%, were achieved without selection in embryonic stem (ES) cells, neural stem (NS) cells, and brain tumour-derived stem cells. Biallelic-tagged clonal lines were readily derived and used to define Olig2 chromatin-bound interacting partners. Using our novel web-based design tool, we established a 96-well format pipeline that enabled V5-tagging of sixty different transcription factors. This efficient, selection-free and scalable epitope tagging pipeline enables systematic surveys of protein expression levels, subcellular localization, and interactors across diverse mammalian stem cells.</jats:p

Continuous directed evolution of DNA-binding proteins to improve TALEN specificity

Nucleases containing programmable DNA-binding domains can alter the genomes of model organisms and have the potential to become human therapeutics. Here we present DNA-binding phage-assisted continuous evolution (DB-PACE) as a general approach for the laboratory evolution of DNA-binding activity and specificity. We used this system to generate TALE nucleases with broadly improved DNA cleavage specificity, establishing DB-PACE as a versatile approach for improving the accuracy of genome-editing agents

Multidimensional chemical control of CRISPR–Cas9

Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions-including dose, time, specificity, and mutually exclusive modulation of multiple genes-are still lacking. We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains. Application of our strategy to both Cas9-mediated genome editing and transcriptional activities opens new avenues for systematic genome interrogation

Structure and Molecular Evolution of CDGSH Iron-Sulfur Domains

The recently discovered CDGSH iron-sulfur domains (CISDs) are classified into seven major types with a wide distribution throughout the three domains of life. The type 1 protein mitoNEET has been shown to fold into a dimer with the signature CDGSH motif binding to a [2Fe-2S] cluster. However, the structures of all other types of CISDs were unknown. Here we report the crystal structures of type 3, 4, and 6 CISDs determined at 1.5 Å, 1.8 Å and 1.15 Å resolution, respectively. The type 3 and 4 CISD each contain one CDGSH motif and adopt a dimeric structure. Although similar to each other, the two structures have permutated topologies, and both are distinct from the type 1 structure. The type 6 CISD contains tandem CDGSH motifs and adopts a monomeric structure with an internal pseudo dyad symmetry. All currently known CISD structures share dual iron-sulfur binding modules and a β-sandwich for either intermolecular or intramolecular dimerization. The iron-sulfur binding module, the β-strand N-terminal to the module and a proline motif are conserved among different type structures, but the dimerization module and the interface and orientation between the two iron-sulfur binding modules are divergent. Sequence analysis further shows resemblance between CISD types 4 and 7 and between 1 and 2. Our findings suggest that all CISDs share common ancestry and diverged into three primary folds with a characteristic phylogenetic distribution: a eukaryote-specific fold adopted by types 1 and 2 proteins, a prokaryote-specific fold adopted by types 3, 4 and 7 proteins, and a tandem-motif fold adopted by types 5 and 6 proteins. Our comprehensive structural, sequential and phylogenetic analysis provides significant insight into the assembly principles and evolutionary relationship of CISDs

Engineering the Redox Potential over a Wide Range within a New Class of FeS Proteins

Abstract: MitoNEET is a newly discovered mitochondrial protein and a target of the TZD class of antidiabetes drugs. MitoNEET is homodimeric with each protomer binding a [2Fe-2S] center through a rare 3-Cys and 1-His coordination geometry. Both the fold and the coordination of the [2Fe-2S] centers suggest that it could have novel properties compared to other known [2Fe-2S] proteins. We tested the robustness of mitoNEET to mutation and the range over which the redox potential (EM) could be tuned. We found that the protein could tolerate an array of mutations that modified the EM of the [2Fe-2S] center over a range of ∼700 mV, which is the largest EM range engineered in an FeS protein and, importantly, spans the cellular redox range (+200 to-300 mV). These properties make mitoNEET potentially useful for both physiological studies and industrial applications as a stable, water-soluble, redox agent