Supporting Clean Energy in the ASEAN: Policy Opportunities from Sustainable Aviation Fuels Initiatives in Indonesia and Malaysia

Sustainable aviation fuels is a strategic long-term solution for zero-carbon aviation industry by 2050, thus underscoring the need to accelerate the deployment through reforms in the relevant key areas. Aligned to the agenda, this paper aims to study the policy opportunities for drop-in sustainable aviation fuel (SAF) deployment in the ASEAN by considering the initiatives undertaken. by Indonesia and Malaysia. Four areas are used as coding framework to assess the current status, challenges, and policy opportunities, namely (1) policy, strategy, and reforms; (2) standards and certification system; (3) economic instruments; and (4) international integration. First, the current status and challenges within each country is assessed. Indonesia has shown a more command-and-control approach with an upfront SAF blending mandate. However, it needs to be supported by several compliance measures. Malaysia, on the other hand, has conducted country assessments but no SAF-specific policy has been issued yet. Both countries still lack the economic instruments, while international integration is still relatively under-explored with only limited inter-regional partnerships. As the biggest palm-oil producing countries, Indonesia and Malaysia possess enormous potentials to lead the region in deploying SAF, thus more initiatives are urged

In-vitro Antibacterial Activities of Selected Traditional Plants

The present research work was focused on the antibacterial activity of medicinal plants (Aegle marmelos, Citrus aurantifolia, Piper sarmentosum, Sesbania grandiflora, Carthamus tinctorius, Piper longum, Morus alba, Green tea and Oolong tea). Extracts were examined using water, methanol and ethanol as solvents and tested against six human pathogens (Staphylococcus aureus DMST4212, Bacillus cereus DMST5040, Staphylococcus epidermidis DMST518, Escherichia coli ATCC25922, Methicillin-resistant Staphylococcus aureus (MRSA) DMST20625 and Pseudomonas aeruginosa DMST4739) using the agar well diffusion method. The five day methanol extracts of green tea showed significant activity against MRSA and S. aureus of around 28.3 mm. The five day methanol extracts of A. marmelos exhibited the highest antibacterial activity against S. epidermidis (29.7 mm) and lowest in E. coli (no inhibition zone). The drop plate technique found that three day ethanol and three day methanol extracts of P. longum; water, three day and five day methanol and three day and five day ethanol extracts of green tea and oolong tea; three day and five day methanol and three day and five day ethanol extracts of C. aurantifolia; and three day ethanol extract of S. grandiflora had no growth for all six human pathogens. The results demonstrated that this plant has strong antibacterial potential against all tested bacteria

Exposure to the oral host niche yields rapid phenotypic and genotypic diversification in Candida albicans

In vitro studies suggest that stress may generate random standing variation, and that different cellular and ploidy states may evolve more rapidly under stress. Yet this idea has not been tested with pathogenic fungi growing within their host niche in vivo . Here, we analyzed the generation of both genotypic and phenotypic diversity during exposure of Candida albicans to the mouse oral cavity. Ploidy, aneuploidy, loss of heterozygosity (LOH) and recombination were determined using flow cytometry and ddRADseq. Colony phenotypic changes (CPs) in size and filamentous growth were evident without selection, and were enriched among colonies selected for LOH of the GAL1 marker. Aneuploidy and LOH occurred on all chromosomes (Chrs), with aneuploidy more frequent for smaller Chrs and whole Chr LOH more frequent for larger Chrs. Large genome shifts in ploidy to haploidy often maintained one or more heterozygous disomic Chrs, consistent with random Chr missegregation events. Most isolates displayed several different types of genomic changes, suggesting that the oral environment rapidly generates diversity de novo. In sharp contrast, following in vitro propagation isolates were not enriched for multiple LOH events, except in those that underwent haploidization and/or had high levels of Chr loss. The frequency of events was overall 100 times higher for C. albicans populations following in vivo passage compared to in vitro . These hyperdiverse in vivo isolates likely provide C. albicans with the ability to adapt rapidly to the diversity of stress environments it encounters inside the host. Author summary Adaption is a continuous dynamic process that requires genotypic and phenotypic variation. Here we studied the effects of a single passage in a mouse oropharyngeal model of infection on the appearance of diversity in C. albicans, a common commensal of the human oral cavity and GI tract. We found that variation could be rapidly detected following oral colonization, with the frequency of genome change being considerably higher with pre-selection for recombination and colony phenotypic changes. Importantly, one third of all isolates had multiple genome changes, significantly higher than expected by chance alone. We suggest that some cells in the population are naturally hypervariable and that they are a major source of diversity upon which selection can act in stressful conditions in vivo and in vitro

Macrophage Subpopulation Dynamics Shift following Intravenous Infusion of Mesenchymal Stromal Cells

Intravenous infusion of mesenchymal stromal cells (MSCs) is thought to be a viable treatment for numerous disorders. Although the intrinsic immunosuppressive ability of MSCs has been credited for this therapeutic effect, their exact impact on endogenous tissue-resident cells following delivery has not been clearly characterized. Moreover, multiple studies have reported pulmonary sequestration of MSCs upon intravenous delivery. Despite substantial efforts to improve MSC homing, it remains unclear whether MSC migration to the site of injury is necessary to achieve a therapeutic effect. Using a murine excisional wound healing model, we offer an explanation of how sequestered MSCs improve healing through their systemic impact on macrophage subpopulations. We demonstrate that infusion of MSCs leads to pulmonary entrapment followed by rapid clearance, but also significantly accelerates wound closure. Using single-cell RNA sequencing of the wound, we show that following MSC delivery, innate immune cells, particularly macrophages, exhibit distinctive transcriptional changes. We identify the appearance of a pro-angiogenic CD9(+) macrophage subpopulation, whose induction is mediated by several proteins secreted by MSCs, including COL6A1, PRG4, and TGFB3. Our findings suggest that MSCs do not need to act locally to induce broad changes in the immune system and ultimately treat disease

Supplemental Material for Forche et al., 2018

Figure S1 provides detailed overview of experiment. Supplemental figure 2 shows <i>GAL1</i> LOH frequencies <br>Supplemental figure 3 shows examples of single and double aneuploidies<br>Supplemental figure 4 shows frequency of whole Chr LOH<br>Supplemental figure 5 shows a map with LOH breaks along Chr1<br>Supplemental figure 6 shows frequency of recurrent missegregation events <br><div>Table S1 contains strains, primers and plasmids for construction of strain YJB9318<br>Table S2 contains overview of ploidy and colony phenotypes<br>Table S3 provides summary of all detected events<br>Table S4 shows position and frequency of break regions<br>Table S5 shows frequency of recurrent missegregation events<br>Table S6 shows summary of multiple event frequency by mouse</div><div>File S1 is the custom R script<br></div

Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells

The original version of this Article omitted the following from the Acknowledgements: “G.B. acknowledges the support from the Cancer Prevention and Research Institute of Texas (RR140081 and RR170721).”This has now been corrected in both the PDF and HTML versions of the Article

Gene correction for SCID-X1 in long-term hematopoietic stem cells.

Gene correction in human long-term hematopoietic stem cells (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system. Here we describe an approach for X-linked sSevere cCombined iImmunodeficiency (SCID-X1) using targeted integration of a cDNA into the endogenous start codon to functionally correct disease-causing mutations throughout the gene. Using a CRISPR-Cas9/AAV6 based strategy, we achieve up to 20% targeted integration frequencies in LT-HSCs. As measures of the lack of toxicity we observe no evidence of abnormal hematopoiesis following transplantation and no evidence of off-target mutations using a high-fidelity Cas9 as a ribonucleoprotein complex. We achieve high levels of targeting frequencies (median 45%) in CD34+ HSPCs from six SCID-X1 patients and demonstrate rescue of lymphopoietic defect in a patient derived HSPC population in vitro and in vivo. In sum, our study provides specificity, toxicity and efficacy data supportive of clinical development of genome editing to treat SCID-Xl

Gene correction for SCID-X1 in long-term hematopoietic stem cells

Gene correction in hematopoietic stem cells could be a powerful way to treat monogenic diseases of the blood and immune system. Here the authors develop a strategy using CRISPR-Cas9 and an aAdeno-Associated vVirus(AAV)-delivered IL2RG cDNA to correct X-linked sSevere Ccombined iImmunodeficiency (SCID-X1) with a high success rate