Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770

Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients

Beyond Climatic Variation: Human Disturbances Alter the Effectiveness of a Protected Area to Reduce Fires in a Tropical Peatland

This is the final version. Available from Frontiers Media via the DOI in this record. Publicly available datasets were analyzed in this study, with no new data collected. This data can be found here: https://id.weatherspark.com/h/y/149125/2015/Cuaca-Historis-selama-2015-di-Sultan-Mahmud-Badaruddin-II-Airport-Indonesia#Figures-Rainfall, www.openstreetmap.org, https://balaiksdasumsel.org/, https://tanahair.indonesia.go.id/portal-web, https://earthdata.nasa.gov/earth-observation-data/near-real-time/firms/active-fire-datahttps://landsat.usgs.gov, and https://ggweather.com/enso/oni.htm.Fire is considered a major threat to biodiversity in many habitats and the occurrence of fire has frequently been used to investigate the effectiveness of protected areas. Yet, despite the known importance of tropical peatlands for biodiversity conservation and serious threat that anthropogenically induced fires pose to this ecosystem, the influence of protected area designation on fire occurrence in tropical peatland has been poorly assessed thus far. Our study addresses this knowledge gap through providing a novel assessment of fire patterns from a tropical peatland protected area and surrounding landscape. We investigated the importance of both climatic factors (top-down mechanism) and human interventions (bottom-up mechanism) on fire occurrence through analyzing 20-years (2001–2020) of LANDSAT and Moderate Resolution Imaging Spectrometer (MODIS) images of the Padang Sugihan Wildlife Reserve and a 10-km buffer area surrounding this in Sumatra, Indonesia. Fire density was assessed in relation to road and canal construction. Monthly and annual precipitation was compared between wet and dry years. The reserve was effective in limiting fire compared to surrounding landscapes only in wet years. We revealed that peat fire occurrence in the protected area and buffer zone was not due to climatic factors alone, with distance from canals and roads also contributing toward fire occurrence. Our results suggest that it is essential to address tropical peatland fire processes at a landscape level, particularly at the surroundings of protected areas, in order to increase the effectiveness of fire protection, improve fire risk classification maps, and conserve threatened tropical peatland wildlife such as the Sumatran elephant.UKRI GCRFThe Lembaga Pengelola Dana Pendidikan (LPDP)The Indonesian Science Fund (DIPI

Atomic Layer Deposition of 2D Metal Dichalcogenides for Electronics, Catalysis, Energy Storage, and Beyond

2D transition metal dichalcogenides (TMDCs) are among the most exciting materials of today. Their layered crystal structures result in unique and useful electronic, optical, catalytic, and quantum properties. To realize the technological potential of TMDCs, methods depositing uniform films of controlled thickness at low temperatures in a highly controllable, scalable, and repeatable manner are needed. Atomic layer deposition (ALD) is a chemical gas-phase thin film deposition method capable of meeting these challenges. In this review, the applications evaluated for ALD TMDCs are systematically examined, including electronics and optoelectonics, electrocatalysis and photocatalysis, energy storage, lubrication, plasmonics, solar cells, and photonics. This review focuses on understanding the interplay between ALD precursors and deposition conditions, the resulting film characteristics such as thickness, crystallinity, and morphology, and ultimately device performance. Through rational choice of precursors and conditions, ALD is observed to exhibit potential to meet the varying requirements of widely different applications. Beyond the current state of ALD TMDCs, the future prospects, opportunities, and challenges in different applications are discussed. The authors hope that the review aids in bringing together experts in the fields of ALD, TMDCs, and various applications to eventually realize industrial applications of ALD TMDCs.Peer reviewe

Persepsi Masyarakat terhadap Aktivitas Pembuatan Sekat Kanal di Kawasan Taman Nasional Sebangau Provinsi Kalimantan Tengah

Taman Nasional Sebangau (TNS) merupakan salah satu taman nasional yang terdapat di Kalimantan Tengah dan merupakan lahan rawa gambut yang berfungsi sebagai kawasan konservasi. Sekat kanal merupakan salah satu program pemerintah yang bertujuan untuk memulihkan ekosistem rawa gambut yang telah rusak akibat kebakaran hutan dan lahan. Penelitian ini bertujuan untuk mengetahui persepsi masyarakat terhadap aktivitas pembuatan sekat kanal aspek ekologi lingkungan, sosial ekonomi dan tingkat capaian program restorasi gambut serta mengetahui faktor-faktor yang mempengaruhi persepsi masyarakat. Penelitian ini merupakan penelitian survei dengan teknik penentuan sampel menggunakan sistem acak. Jumlah sampel dalam penelitian ini yaitu sebanyak 100 orang responden. Teknik pengumpulan data yaitu menggunakan kuisioner dan observasi. Teknik analisis data menggunakan analisis deskriptif dan analisis regresi linier berganda. Hasil penelitian menunjukkan bahwa persepsi masyarakat pada kategori sangat tinggi pada semua aspek yaitu sebesar 80,09% (aspek sosial ekonomi); 81,10% (aspek ekologi lingkungan); dan 80,17% (aspek tingkat capaian program). Berdasarkan hasil analisis regresi berganda menunjukkan bahwa variabel penelitian berpengaruh secara semultan terhadap persepsi masyarakat dengan nilai F hitung sebesar 6.571 (aspek sosial ekonomi); 6.431 (aspek ekologi lingkungan); dan 4.564 (aspek tingkat capaian program). Adapun faktor-faktor yang mempengaruhi persepsi masyarakat yaitu faktor pendidikan, pendapatn, kepemilikan lahan dan pengetahuan

Highly efficient photoelectrochemical and photocatalytic anodic TiO2 nanotube layers with additional TiO2 coating

In this work, strong beneficial effects of thin and uniform TiO2 coatings within TiO2 nanotube layers for photocurrent generation and photocatalytical degradation of methylene blue are demonstrated for the first time. TiO2 nanotube layers were coated by TiO2 of various thicknesses (from 2.8 nm to 22 nm) using atomic layer deposition (ALD) and compared with TiO2 nanotube layers decorated by TiO2 nanoparticles (using established TiCl4 treatment) and with blank (uncoated) layers. By means of photocurrent measurements and cyclic voltammetry, it is demonstrated that the most efficient charge carrier separation can be achieved for TiO2 nanotube layers with an optimal ALD TiO2 coating thickness ≈11 nm. Significant differences in flatband potentials and carrier density among all nanotube layers were revealed by Mott-Schottky measurements. Photocatalytic decomposition rates for methylene blue solutions were significantly enhanced for ALD TiO2 coated TiO2 nanotube layers compared to their uncoated or TiO2 nanoparticles - decorated counterparts. A perfect agreement in trends was obtained for photocurrent and photocatalytic results