Establishment of contamination-free culture and induction of shoot regeneration in vitro in Kapur Bukit (Dryobalanops beccarii Dyer)

Kapur Bukit (Dryobalanops beccarii Dyer) has been identified as one of the timber species to be used in forest plantation and reforestation in Sarawak. To meet the high demand of planting stock, there is a need to mass produce this species. Since clonal propagation of this species is difficult and slow using conventional methods, micropropagation has been explored as an alternative to mass produce this species. The objective of this study is to establish a protocol to obtain axenic explants from fieldgrown materials and proceed to induce multiple shoot proliferation. Various factors such as serious contamination and browning influence the establishment of axenic explants of this species. These factors have successfully been addressed after a fast and effective protocol has been developed. The present study showed that 20 % Clorox surface sterilization for 15 min, supplementing 2 ml/L PPM and 10 mg/L TET to the culture medium were able to reduce contamination problem. Incorporation of 0.5 % PVP10 into the media, handling of explants under cool condition (approximately 15°C) during surface sterilization steps, culturing explants in dark condition and frequent transfer were found to be helpful in obtaining maximum survival of explants. No sign of multiple shoot formation was observed so far. However, vigorous cell growth, callus formation and growth of leaf primordia observed in medium containing cytokinin. The results showed that high concentration of BAP (3 mg/L), TDZ (3 mg/L) and combination of BAP and NAA (at 3 mg/L and 0.3 mg/L respectively) induced more response in the shoot tips in culture. The combination of BAP and NAA was considered as the most effective treatment in inducing the explants to respond

A Rice Immunophilin Homolog, OsFKBP12, Is a Negative Regulator of Both Biotic and Abiotic Stress Responses

A class of proteins that were discovered to bind the immunosuppressant drug FK506, called FK506-binding proteins (FKBPs), are members of a sub-family of immunophilins. Although they were first identified in human, FKBPs exist in all three domains of life. In this report, a rice FKBP12 homolog was first identified as a biotic stress-related gene through suppression subtractive hybridization screening. By ectopically expressing OsFKBP12 in the heterologous model plant system, Arabidopsis thaliana, for functional characterization, OsFKBP12 was found to increase susceptibility of the plant to the pathogen, Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). This negative regulatory role of FKBP12 in biotic stress responses was also demonstrated in the AtFKBP12-knockout mutant, which exhibited higher resistance towards Pst DC3000. Furthermore, this higher-plant FKBP12 homolog was also shown to be a negative regulator of salt tolerance. Using yeast two-hybrid tests, an ancient unconventional G-protein, OsYchF1, was identified as an interacting partner of OsFKBP12. OsYchF1 was previously reported as a negative regulator of both biotic and abiotic stresses. Therefore, OsFKBP12 probably also plays negative regulatory roles at the convergence of biotic and abiotic stress response pathways in higher plants

pmwd: A Differentiable Cosmological Particle-Mesh NN-body Library

The formation of the large-scale structure, the evolution and distribution of galaxies, quasars, and dark matter on cosmological scales, requires numerical simulations. Differentiable simulations provide gradients of the cosmological parameters, that can accelerate the extraction of physical information from statistical analyses of observational data. The deep learning revolution has brought not only myriad powerful neural networks, but also breakthroughs including automatic differentiation (AD) tools and computational accelerators like GPUs, facilitating forward modeling of the Universe with differentiable simulations. Because AD needs to save the whole forward evolution history to backpropagate gradients, current differentiable cosmological simulations are limited by memory. Using the adjoint method, with reverse time integration to reconstruct the evolution history, we develop a differentiable cosmological particle-mesh (PM) simulation library pmwd (particle-mesh with derivatives) with a low memory cost. Based on the powerful AD library JAX, pmwd is fully differentiable, and is highly performant on GPUs

pmwd: A Differentiable Cosmological Particle-Mesh NN-body Library

The formation of the large-scale structure, the evolution and distribution of galaxies, quasars, and dark matter on cosmological scales, requires numerical simulations. Differentiable simulations provide gradients of the cosmological parameters, that can accelerate the extraction of physical information from statistical analyses of observational data. The deep learning revolution has brought not only myriad powerful neural networks, but also breakthroughs including automatic differentiation (AD) tools and computational accelerators like GPUs, facilitating forward modeling of the Universe with differentiable simulations. Because AD needs to save the whole forward evolution history to backpropagate gradients, current differentiable cosmological simulations are limited by memory. Using the adjoint method, with reverse time integration to reconstruct the evolution history, we develop a differentiable cosmological particle-mesh (PM) simulation library pmwd (particle-mesh with derivatives) with a low memory cost. Based on the powerful AD library JAX, pmwd is fully differentiable, and is highly performant on GPUs

Treatment Adherence and Health-Related Quality of Life in Patients with Hemophilia in Hong Kong

Background: This study aims to identify factors affecting health-related quality of life (HRQoL) in Chinese patients with hemophilia in Hong Kong, and to examine the association between treatment adherence and HRQoL outcomes. Methods: Patients with hemophilia A or B from a non-governmental organization reported their HRQoL and treatment adherence to prophylactic therapy using validated tools. Univariate tests and multivariable regression analysis were used to compare differences in outcomes across clinically relevant subgroups. Results: Fifty-six patients were recruited (mean age 30.4 [17.4] years; majority hemophilia A: 75%; moderate-to-severe severity: 88%). Patients who received prophylactic treatment reported fewer work/school problems (25.8 [18.9] versus 51.5 [26.3]; p = 0.001) than those who received on-demand therapy. The multivariable model showed that older age (B = 0.42, 95% CI = 0.093–0.75) and living in public housing (B = 10.24, 95% CI = 0.70–19.77) were associated with worse HRQoL. Older age was associated with treatment non-adherence (r = 0.66, p < 0.0001). Patients with poor adherence tended to report worse functioning in sports/leisure (r = 0.31, p = 0.033). Conclusions: Our results suggest that patients who were older, had lower education attainment and received on-demand treatment had poorer perception of their health. Improving adherence may lead to better HRQoL. Future work includes evaluating the occupational needs prospectively in this population

SaeR as a Novel Target for Antivirulence Therapy against Staphylococcus aureus

ABSTRACT:Staphylococcus aureus is a major human pathogen responsible for a wide range of clinical infections. SaeRS is one of the two-component systems in S. aureus that modulate multiple virulence factors. Although SaeR is required for S. aureus to develop an infection, inhibitors have not been reported. Using an in vivo knockdown method, we demonstrated that SaeR is targetable for the discovery of antivirulence agent. HR3744 was discovered through a high-throughput screening utilising a GFP-Lux dual reporter system driven by saeP1 promoter. ,. The antivirulence efficacy of HR3744 was tested using Western blot, Quantitative Polymerase Chain Reaction, leucotoxicity, and hemolysis tests. In electrophoresis mobility shift assay, HR3744 inhibited SaeR-DNA probe binding. WaterLOGSY-NMR test showed HR3744 directly interacted with SaeR's DNA-binding domain When saeR was deleted, HR3744 lost its antivirulence property, validating the target specificity. Virtual docking and mutagenesis were used to confirm the target's specificity. When Glu159 was changed to Asn, the bacteria developed resistance to HR3744. A structure-activity relationship study revealed that a molecule with a slight modification did not inhibit SaeR, indicating the selectivity of HR3744. Interestingly, we found that SAV13, an analogue of HR3744, was four-times more potent than the HR3744 and demonstrated identical antivirulence property and target specificity. In a mouse bacteraemia model, both HR3744 and SAV13 exhibited in vivo effectiveness. Collectively, we identified the first SaeR inhibitor, which exhibited in vitro and in vivo antivirulence property, and proved that SaeR could be a novel target for developing antivirulence drugs against S. aureus infections