PEMBELAJARAN BAGI ANAK-ANAK YANG BELUM LANCAR MEMBACA DAN MENULIS DI DESA GENTONG KECAMATAN PAKIS KABUPATEN MALANG

Di dalam sebuah negara, pendidikan memang sangat penting untuk dilakukan. Karena hal itu, saya berinisiatif untuk mengadakan pembelajaran bagi anak-anak yang tinggal di desa yang masih minim dengan kesadaran akan pendidikan. Hal ini saya lakukan sebagai bentuk pengabdian kepada masyarakat. Kegiatan pembelajaran yang saya lakukan ini ditujukan bagi anak-anak yang berusia antara 5-7 tahun. Dari pembelajaran yang saya lakukan, terdapat beberapa hasil yang cukup memuaskan. Yaitu: 1) siswa mengikuti setiap kegiatan dan hadir dalam pembelajaran yang dilakukan. Hal ini, menjadi indikator bahwa siswa memiliki minat yang baik untuk mengikuti pembelajaran; 2) siswa bisa menulis dengan baik dan benar, meski beberapa kali mengalami kesalahan pada awalnya. Siswa juga bisa mengerjakan soal berhitung sederhana dengan baik dan benar; 3) siswa mampu membuat dan menyusun kalimat sederhana dengan baik, selain itu siswa juga mampu membuat susunan angka puluhan maupun ratusan

Prenylated Flavin-dependent decarboxylases: Structure-guided engineering and synthetic applicability

The recently discovered prenylated flavin (prFMN) cofactor is utilised by UbiD enzyme family to catalyse non-oxidative decarboxylation of precursors of respiratory quinones. Mechanistic aspect of prFMN-mediated decarboxylation has attracted interests and studies of fungal ferulic acid decarboxylases (FDCs), members of the UbiD enzyme family reveal a rare enzymatic 1,3-dipolar cycloaddition mechanism for the decarboxylation of cinnamic aid. Please click Additional Files below to see the full abstract

Stereoselectivity and Structural Characterisation of an Imine Reductase (IRED) from Amycolatopsis orientalis

The imine reductase AoIRED from Amycolatopsis orientalis (Uniprot R4SNK4) catalyzes the NADPH-dependent reduction of a wide range of prochiral imines and iminium ions, predominantly with (S)-selectivity and with e.e.s of up to >99%. AoIRED displays up to 100-fold greater catalytic efficiency for 2-methyl-1-pyrroline (2MPN) compared to other IREDs, such as the enzyme from Streptomyces sp. GF3546, which also exhibits (S)-selectivity, and thus AoIRED is an interesting candidate for preparative synthesis. AoIRED exhibits unusual catalytic properties, with inversion of stereoselectivity observed between structurally similar substrates, and also, in the case of 1-methyl-3,4-dihydroisoquinoline, for the same substrate, dependent on the age of the enzyme after purification. The structure of AoIRED has been determined in an ‘open’ apo-form, revealing a canonical dimeric IRED fold in which the active site is formed between the N- and C-terminal domains of participating monomers. Co-crystallisation with NADPH gave a ‘closed’ form in complex with the cofactor, in which a relative closure of domains, and associated loop movements, has resulted in a much smaller active site. A ternary complex was also obtained by co-crystallization with NADPH and 1-methyl-1,2,3,4-tetrahydroisoquinoline [(MTQ], and reveals a binding site for the (R)-amine product which places the chiral carbon within 4 Å of the putative location of the C4 atom of NADPH that delivers hydride to the C=N bond of the substrate. The ternary complex has permitted structure-informed mutation of the active site, resulting in mutants including Y179A, Y179F and N241A, of altered activity and stereoselectivity

Az ügyészi fellépés

Az ügyészi fellépésnek jelenleg három törvényi meghatározása is elkülöníthető. Az első az ügyészségről szóló 2011. évi CLXIII. törvény (a továbbiakban: Ütv.) 26. §-ának (1) bekezdése szerinti fellépés fogalom. Eszerint „az ügyészségnek e törvényben nem szabályozott, az igazságszolgáltatás közreműködőjeként gyakorolt büntetőjogon kívüli közérdekű feladat- és hatásköreiről külön törvények rendelkeznek. Az ügyész ezeket a hatásköreit a törvénysértés kiküszöbölése érdekében elsősorban bírósági peres és nemperes eljárások megindításával (perindítási jog), valamint hatósági eljárások kezdeményezésével és jogorvoslat előterjesztésével gyakorolja (a továbbiakban együtt: fellépés)”. Ez felöleli tehát a büntetőjogon kívüli ügyészi megjelenés, részvétel szinte valamennyi lehetséges formáját, nem csupán a keresetindítást, vagy a polgári perrendtartás szerinti fellépést, perbe lépést, illetve beavatkozást

HIV Point Of Care Diagnostics: Meeting The Special Needs Of Sub-Saharan Africa

Sub-Saharan Africa, accounting for 70% of the 35 million people living with HIV worldwide, obviously carries the heaviest burden of the HIV epidemic. Moreover, the region’s poor health system occasioned by limited resources and inadequate skilled clinical personnel usually makes decentralization of HIV care difficult. Therefore, quality diagnostics that are easy to use, inexpensive, and amenable for use at point of care (POC) are a dire necessity. Clearly, such diagnostics will significantly lessen the pressure on the existing over-stretched centralized HIV laboratory services. Thankfully, some POC diagnostics are already being validated, while others are in the pipeline. As POC test kits emerge, implementation hurdles should be envisaged and planned for. This review examines emerging HIV diagnostic platforms, HIV POC product pipelines, gaps, perceived POC implementation challenges, and general recommendations for quality care.</jats:p

Antibacterial and Anti-Biofilm Activities of Neocarya Macrophylla Against Clinical Bacterial Isolates

Background: The increasing threat of bacteria resistant to current antibiotics underscores the need for an alternative source of antimicrobial agents. This study was designed to investigate the antibacterial and antibiofilm activity of Neocarya macrophylla against two important human pathogens commonly associated with biofilm-related infections.Methods: The methanolic extract of N. macrophylla leaves and its n-butanol and ethylacetate fractions were screened in-vitro for their antimicrobial activity using agar well diffusion technique while the antibacterial and antibiofilm activity of the extract and its fractions were investigated against clinical isolates of S. aureus and P. aeruginosa using microbroth dilution technique and microtiter plate method respectively.Results: The methanolic leaf extract and its fractions exhibited substantial antimicrobial activity. The n-butanol and ethylacetate fractions showed highest activity against P. aeruginosa and S. aureus respectively. The MIC and MBC of the extract and its fractions against both S. aureus and P. aeruginosa ranged from 3.125-37.5 mg/ml and 6.25-75 mg/ml respectively. In addition, a concentration-dependent antibiofilm activity against the test organisms was also observed with the ethylacetate fraction exhibiting the highest antibiofilm activity.Conclusion: The extracts and fractions of N. macrophylla exhibited remarkable antibacterial and antibiofilm activities against S. aureus and P. aeruginosa. The plant thus can be considered as a potential source of bioactive principles in the continuous fight against bacterial virulence and resistance.Keywords: Neocarya macrophylla, Antimicrobial activity, Antibiofilm activity, Antimicrobial resistance

A reductive aminase from Aspergillus oryzae

Reductive amination is one of the most important methods for the synthesis of chiral amines. Here we report the discovery of an NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm, Uniprot code Q2TW47) that can catalyse the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines with up to &gt;98% conversion and with up to &gt;98% enantiomeric excess. In cases where both carbonyl and amine show high reactivity, it is possible to employ a 1:1 ratio of the substrates, forming amine products with up to 94% conversion. Steady-state kinetic studies establish that the enzyme is capable of catalysing imine formation as well as reduction. Crystal structures of AspRedAm in complex with NADP(H) and also with both NADP(H) and the pharmaceutical ingredient (R)-rasagiline are reported. We also demonstrate preparative scale reductive aminations with wild-type and Q240A variant biocatalysts displaying total turnover numbers of up to 32,000 and space time yields up to 3.73 g l−1 d−1

SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers

SLN124, an N-acetylgalactosamine conjugated 19-mer short interfering RNA, is being developed to treat iron-loading anemias (including beta-thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first-in-human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1.0, 3.0, and 4.5 mg/kg) in healthy volunteers. Twenty-four participants were randomized in three sequential cohorts of eight subjects, each to receive a single dose of either SLN124 or placebo (6:2 randomization), administered subcutaneously. There were no serious or severe adverse events, or discontinuations due to adverse events, and most treatment-emergent adverse events were mild, including transient mild injection site reactions, resolving without intervention. SLN124 was rapidly absorbed, with a median tmax of 4–5 h across all treatment groups, and largely eliminated from plasma by 48 h. Plasma concentrations increased in a greater than dose proportional fashion between treatment groups. In all SLN124 groups, a dose-related effect was observed across iron metabolism markers, and across erythroid markers, SLN124 resulted in increased plasma hepcidin levels, peaking around Day 29, and consequent dose-related sustained reductions in plasma iron and transferrin saturation with decreased reticulocyte production, MCHC, and MCV. Results suggest duration of action lasting up to 56 days after a single SLN124 dose, on hepcidin and hematological parameters of iron metabolism (serum iron and TSAT)