PENERAPAN ABSENSI FINGER PRINT UNTUK MENINGKATKAN DISIPLIN KERJA PEGAWAI

This study found out the application of fingerprint attendance to improve employee work discipline at SMA 2 Batang Kapas. In this study, we used qualitative descriptive method, illustrates the phenomenon of the application of fingerprint-based attendance to improve employee work discipline at the SMA 2 Batang Kapas School. The results obtained indicate that (1) fingerprint attendance system is very easy to use; (2) the presence of fingerprints can make employees avoid cheating; (3) the application of fingerprint attendance to improve employee work discipline has run quite well although there are still some shortcomings

Identifikasi Dan Prevalensi Protozoa Parasitik Pada Sampel Feses Gajah Sumatera (Elephas Maximus Sumatranus) Di Pusat Konservasi Gajah, Taman Nasional Way Kambas

Research to observe parasitic protozoa, oocyst, and prevalencesumatran elephants (Elephas maximus sumatranus) has been done in Elephant Conservation Center, Way Kambas National Park, Lampung. Native examination was used for identification and floating method for protozoa counting. There were twoprotozoa families, Eimeriidae and Ophryoscolecidae, six genus Triplumaria, Tripalmaria, Prototapirella, Didesmis, Polydinium, Oxytricha, and three species Entamoeba coli, Entamoeba dispar, and Balantidium coli. Prevalence infected by parasitic protozoa was 41.8% on infant, 47.2% on male and 47.2% on female.Keywords: Elephas maximus sumatranus, Elephant Conservation Center, WayKambas National Park, parasitic protozo

The effect of ethanolic leaves extract of soursop (Annona muricata L.) on human colorectal cancer cell line: cell viability and in silico study to cyclin D1 protein

Latar Belakang: Kanker kolorektal merupakan transformasi patologis dari epitel kolon dan rektum normal menjadi massa jaringan abnormal, perubahan ini terjadi karena ekspresi berlebih dari protein cyclin D1 yang menginduksi proliferasi sel kolorektal secara berlebihan. Pengobatan dan pencegahan kanker kolorektal dapat dilakukan secara alami dengan mengonsumsi ekstrak daun Annona muricata L. (sirsak). Sirsak dikenal karena banyak komponen fitokimia yang berfungsi sebagai anti kanker. Metode: Penelitian ini menggunakan sel kanker kolorektal HT-29 yang diberi ekstrak etanol daun sirsak dan 5 Fluorourasil (5-FU). Tujuannya untuk menemukan konsentrasi sitotoksisitas yang dapat menghambat 50% populasi sel HT-29 (CC50) dan konsentrasi yang didapat sebelumnya akan diuji dengan metode uji MTT. Analisis docking molekuler dilakukan antara molekul-molekul dari ekstrak etanol daun sirsak terhadap protein Cyclin D1 menggunakan perangkat lunak molecular operating environment (MOE) 2013.08. Hasil: CC50 ekstrak etanol daun sirsak adalah 278 μg / mL dan 5-FU adalah 88 μg / mL. Persentase terendah sel HT-29 yang layak adalah 2 x CC50 setelah perlakuan ekstrak etanol daun sirsak (40,4 ± 1,3%) dibandingkan dengan 5-FU (52,8 ± 4,3%), kontrol pelarut ( 97,2 ± 1,4%), dan kontrol sel (100%). Analisis docking molekuler untuk protein cyclin D1 diperoleh asam N-hexadecanoic dan molekul phytol sebagai kandidat yang baik untuk menghambat protein cyclin D1. Kesimpulan: Ekstrak etanol daun sirsak dapat menurunkan viabilitas sel kultur kanker kolon HT-29 dan berdasarkan analisis molekular docking dilihat dari energi bebas gibbs (ΔG) dan afinitas tertinggi (pKi) diperoleh N-hexadecanoic dan molekul phytol sebagai penghambat protein cyclin D1. (Health Science Journal of Indonesia 2019;10(2):96-102) Kata Kunci: Kanker kolorektal HT-29, ekstrak etanol daun sirsak, viabilitas sel, molecular docking, cyclin D1   Abstract Introduction: Colorectal cancer is a pathological transformation of normal colon and rectum epithelial that becomes an abnormal tissue mass, due to the overexpression of cyclin D1 protein that inducing excessive proliferation of colorectal cell. The treatment and prevention of colorectal cancer could be done naturally by consuming leaves extract of Annona muricata L. (soursop). Soursop is known for many phytochemical components that serve as an anti-cancer. Methods: This study was used HT-29 colorectal cancer cell that treated with ethanolic leaves extract of soursop and 5-Fluorourasil (5-FU) to find the cytotoxicity concentration that can inhibit 50% of HT-29 cell population (CC50) and the next concentrations of them were treated for next treatment with MTT assay. Molecular docking analysis of the compounds of ethanolic leaves extract of soursop to cyclin D1 protein used molecular operating environment (MOE) 2013.08 software. Results: CC50 of ethanolic leaves extracts of soursop was 278 μg/mL dan 5-FU was 88 μg/mL. The lowest percentage of viable HT-29 cell was 2 x CC50 after ethanolic leaves extract of soursop treatment (40,4±1,3%) was compared to 5-FU (52,8±4,3%), solvent control (97,2±1,4%), and cells control (100%). Analysis of molecular docking to cyclin D1 protein was obtained N-hexadecanoic acid and phytol molecules as good candidates to inhibit cyclin D1 protein. Conclusions: The ethanolic leaves extract of soursop could be a good alternative treatment for colorectal cancer and its compounds had ability to inhibit cyclin D1 protein (the highest gibbs free energy (ΔG) and affinity (pKi)). (Health Science Journal of Indonesia 2019;10(2):96-102) Keywords: Colorectal cancer, ethanolic leaves extract of soursop, cell viability, molecular docking, cyclin D

Identification of a major IP5 kinase in Cryptococcus neoformans confirms that PP-IP5/IP7, not IP6, is essential for virulence

Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP3 to inositol pyrophosphate, PP-IP5/IP7, which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the kinase converting IP5 to IP6 is unknown. Deletion of a putative IP5 kinase-encoding gene (IPK1) alone (ipk1Δ), and in combination with KCS1 (ipk1Δkcs1Δ), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenuation than that of IPK1 alone. ipk1Δkcs1Δ and kcs1Δ lung burdens were also lower than those of ipk1Δ. Unlike ipk1Δ, ipk1Δkcs1Δ and kcs1Δ failed to disseminate to the brain. IP profiling confirmed Ipk1 as the major IP5 kinase in C. neoformans: ipk1Δ produced no IP6 or PP-IP5/IP7 and, in contrast to ipk1Δkcs1Δ, accumulated IP5 and its pyrophosphorylated PP-IP4 derivative. Kcs1 is therefore a dual specificity (IP5 and IP6) kinase producing PP-IP4 and PP-IP5/IP7. All mutants were similarly attenuated in virulence phenotypes including laccase, urease and growth under oxidative/nitrosative stress. Alternative carbon source utilisation was also reduced significantly in all mutants except ipk1Δ, suggesting that PP-IP4 partially compensates for absent PP-IP5/IP7 in ipk1Δ grown under this condition. In conclusion, PP-IP5/IP7, not IP6, is essential for fungal virulence

Siaga Penanganan Awal Mengenal Faktor Penyebab Gagal Jantung

Pandemic Covid 19 menyebabkan kegiatan pengabdian masyarakat yang rutin diadakan oleh prodi farmasi harus dilakukan secara daring. Pengabdian masyarakat yang dilakukan dalam bentuk webinar ini bertujuan agar masyarakat dapat memahami terkait penyebab dari gagal jantung dan pertolongan pertama yang dapat dilakukan dirumah saat orang terdekat mengalami serangan jantung. Kegiatan pengabdian masyarakat dilakukan dengan memanfaatkan tekhnologi digital, yaitu zoom dengan total peserta 65 orang. Abdimas dilaksanakan pada tanggal 16 November 2021 jam 09.00 wib sampai 10.00 wib. Metode penelitian yang digunakan yakni berupa pre test dan postest yang di isi oleh peserta webinar melalui google form. Hasil dari webinar ini yaitu peserta webinar telah mampu memahami materi yang disampaikan terkait penyebab gagal jantung dan cara awal mengatasi serangan jantung. Kesimpulan dari webinar ini adalah webinar telah berjalan lancar dan berhasil menciptakan pemahaman kepada masyarakat tentang pentingnya mengetahui penyebab gagal jantung dan upaya yang dapat dilakukan untuk pencegahan dan penanganan awal

IP7-SPX Domain Interaction Controls Fungal Virulence by Stabilizing Phosphate Signaling Machinery

In the human-pathogenic fungus Cryptococcus neoformans, the inositol polyphosphate signaling pathway is critical for virulence. We recently demonstrated the key role of the inositol pyrophosphate IP7 (isomer 5-PP-IP5) in driving fungal virulence; however, the mechanism of action remains elusive. Using genetic and biochemical approaches, and mouse infection models, we show that IP7 synthesized by Kcs1 regulates fungal virulence by binding to a conserved lysine surface cluster in the SPX domain of Pho81. Pho81 is the cyclin-dependent kinase (CDK) inhibitor of the phosphate signaling (PHO) pathway. We also provide novel mechanistic insight into the role of IP7 in PHO pathway regulation by demonstrating that IP7 functions as an intermolecular "glue" to stabilize Pho81 association with Pho85/Pho80 and, hence, promote PHO pathway activation and phosphate acquisition. Blocking IP7-Pho81 interaction using site-directed mutagenesis led to a dramatic loss of fungal virulence in a mouse infection model, and the effect was similar to that observed following PHO81 gene deletion, highlighting the key importance of Pho81 in fungal virulence. Furthermore, our findings provide additional evidence of evolutionary divergence in PHO pathway regulation in fungi by demonstrating that IP7 isomers have evolved different roles in PHO pathway control in C. neoformans and nonpathogenic yeast.IMPORTANCE Invasive fungal diseases pose a serious threat to human health globally with >1.5 million deaths occurring annually, 180,000 of which are attributable to the AIDS-related pathogen, Cryptococcus neoformans Here, we demonstrate that interaction of the inositol pyrophosphate, IP7, with the CDK inhibitor protein, Pho81, is instrumental in promoting fungal virulence. IP7-Pho81 interaction stabilizes Pho81 association with other CDK complex components to promote PHO pathway activation and phosphate acquisition. Our data demonstrating that blocking IP7-Pho81 interaction or preventing Pho81 production leads to a dramatic loss in fungal virulence, coupled with Pho81 having no homologue in humans, highlights Pho81 function as a potential target for the development of urgently needed antifungal drugs

IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote clearance of Cryptococcus neoformans infection in a mouse model

We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans. Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain. We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5. We showed previously that IP5 is further phosphorylated by Ipk1 to produce IP6, which is a substrate for the synthesis of PP-IP5 by Kcs1. Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ. The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model. This observation is in contrast to kcs1Δ, which we previously reported establishes a chronic, confined lung infection. In summary, we show that Arg1 is the most crucial IPK for cryptococcal virulence, conveying PP-IP5-dependent and novel PP-IP5-independent functions

Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans

Fungal glucosylceramide (GlcCer) is a plasma membrane sphingolipid in which the sphingosine backbone is unsaturated in carbon position 8 (C8) and methylated in carbon position 9 (C9). Studies in the fungal pathogen, Cryptococcus neoformans, have shown that loss of GlcCer synthase activity results in complete loss of virulence in the mouse model. However, whether the loss of virulence is due to the lack of the enzyme or to the loss of the sphingolipid is not known. In this study, we used genetic engineering to alter the chemical structure of fungal GlcCer and studied its effect on fungal growth and pathogenicity. Here we show that unsaturation in C8 and methylation in C9 is required for virulence in the mouse model without affecting fungal growth in vitro or common virulence factors. However, changes in GlcCer structure led to a dramatic susceptibility to membrane stressors resulting in increased cell membrane permeability and rendering the fungal mutant unable to grow within host macrophages. Biophysical studies using synthetic vesicles containing GlcCer revealed that the saturated and unmethylated sphingolipid formed vesicles with higher lipid order that were more likely to phase separate into ordered domains. Taken together, these studies show for the first time that a specific structure of GlcCer is a major regulator of membrane permeability required for fungal pathogenicity

Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1)-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK), which are involved in synthesizing inositol polyphosphates (IP). We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P) and pyrophosphate (PP) groups covalently attached at different positions. This review focuses on (1) the characterization of the Plc1/IPK pathway in C. neoformans; (2) the identification of PP-IP5 (IP7) as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3) why IPK enzymes represent suitable candidates for drug development

Bulu tangkis: Petunjuk praktis untuk pemula dan lanjut

xvi+345hlm.;26c