Comprehensive in silico modeling of the rice plant PRR Xa21 and its interaction with RaxX21-sY and OsSERK2

The first layer of defense that plants deploy to ward off a microbial invasion comes in the form of pattern-triggered immunity (PTI), which is initiated when the pattern-recognition receptors (PRRs) bind with the pathogen-associated molecular patterns (PAMPs) and co-receptor proteins, and transmit a defense signal. Although several plant PRRs have been discovered, very few of them have been fully characterized, and their functional parameters assessed. In this study, the 3D-model prediction of an entire plant PRR protein, Xa21, was done by implementing multiple in silico modeling techniques. Subsequently, the PAMP RaxX21-sY (sulphated RaxX21) and leucine-rich repeat (LRR) domain of the co-receptor OsSERK2 were docked with the LRR domain of Xa21. The docked complex of these three proteins formed a heterodimer that closely resembles the other crystallographic PTI complexes available. Molecular dynamics simulations and MM/PBSA calculations were applied for an in-depth analysis of the interactions between Xa21 LRR, RaxX21-sY, and OsSERK2 LRR. Arg230 and Arg185 from Xa21 LRR, Val2 and Lys15 from RaxX21-sY and Lys164 from OsSERK2 LRR were found to be the prominent residues which might contribute significantly in the formation of a heterodimer during the PTI process mediated by Xa21. Additionally, RaxX21-sY interacted much more favorably with Xa21 LRR in the presence of OsSERK2 LRR in the complex, which substantiates the necessity of the co-receptor in Xa21 mediated PTI to recognize the PAMP RaxX21-sY. However, the free energy binding calculation reveals the favorability of a heterodimer formation of PRR Xa21 and co-receptor OsSERK2 without the presence of PAMP RaxX21-sY, which validate the previous lab result.

This study exhausts bioinformatics tools to acquire the entire multi-domain rice Xa21 protein structure and analyzes its interactions with its PAMP RaxX21-sY and co-receptor OsSERK2.     

Discovery of 4-(2-(dimethylamino)ethoxy)benzohydrazide derivatives as prospective microtubule affinity regulating kinase 4 inhibitors

Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase, considered as a potential drug target for cancer, diabetes and neurodegenerative diseases. Due to its significant role in the development and progression of cancer, different in-house libraries of synthesized small molecules were screened to identify potential MARK4 inhibitors. A small library of hydrazone compounds showed a considerable binding affinity to MARK4. The selected compounds were further scrutinized using an enzyme inhibition assay and finally two hydrazone derivatives (H4 and H19) were selected that show excellent inhibition (nM range). These compounds have a strong binding affinity for MARK4 and moderate binding with human serum albumin. Anticancer studies were performed on MCF-7 and A549 cells, suggesting H4 and H19 selectively inhibit the growth of cancer cells. The IC₅₀ value of compound H4 and H19 was found to be 27.39 μM and 34.37 μM for MCF-7 cells, while for A549 cells it was 45.24 μM and 61.50 μM, respectively. These compounds inhibited the colonogenic potential of cancer cells and induced apoptosis. Overall findings reflect that hydrazones/hydrazone derivatives could be exploited as potential lead molecules for developing effective anticancer therapies via targeting MARK4.

Inhibition studies of MARK4 with selected hydrazone derivatives.     

Bi-doping improves the magnetic properties of zinc oxide nanowires

Room-temperature ferromagnetism in the large and direct bandgap diluted magnetic semiconductor zinc oxide (ZnO) is attributed to the intrinsic defects and p-orbital–p-orbital (p–p) coupling interaction. However, due to oxidation, the ferromagnetism induced by defects is unstable. In the present work, the solution process synthesis route was utilized to grow pristine and bismuth-doped, highly crystalline ZnO nanowire (ZnO NW)-based samples. The FE-SEM images showed that the grown ZnO NWs have a preferred orientation along the c-axis in the (001) direction due to the anisotropic crystal nature of ZnO. X-ray photoelectron spectroscopy (XPS) confirmed the presence of Bi, and at a higher doping content, the bismuth oxide phase appeared. The XRD patterns showed the wurtzite crystal structure, and the large intensity of the (002) peak suggests that most of the reflection was from the top hexagonal face of the NWs, and thus, the wires are predominantly aligned along the c-axis. The TEM analysis further confirmed the crystal growth direction along the (001) direction. The UV-Visible absorption and PL measurements also showed a decrease in the bandgap with an increase in doping concentration, which may be associated with the sp–d exchange interaction between the localized d-electrons and band electrons of the Bi ions. Bi-doping tended to increase the PL intensity in the visible region. The magnetic properties measured by SQUID at 4 and 300 K showed ferromagnetic behaviour for both the pristine and Bi-doped samples. However, the saturation magnetization for the Bi-doped samples was higher compared to that of the pristine ZnO samples until the threshold doping value. The obtained results demonstrated that Bi-doping can be used to tune both the optical and magnetic properties of ZnO NWs, hence paving the way for future spintronics and spin-polarized optoelectronics applications.

Room-temperature ferromagnetism in the large and direct bandgap diluted magnetic semiconductor zinc oxide (ZnO) is attributed to the intrinsic defects and p-orbital–p-orbital (p–p) coupling interaction.     

Correction: Pharmacophore-based approaches in the rational repurposing technique for FDA approved drugs targeting SARS-CoV-2 Mpro

Correction for ‘Pharmacophore-based approaches in the rational repurposing technique for FDA approved drugs targeting SARS-CoV-2 M^pro’ by Vishal M. Balaramnavar et al., RSC Adv., 2020, 10, 40264–40275, DOI: 10.1039/D0RA06038K.

The authors regret that the name of one of the authors (Talha Jawaid) was shown incorrectly in the original article. The corrected author list is as shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Parental Feeding Practices and Child-Related Factors are Associated with Overweight and Obesity in Children and Adolescents with Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - Atypical eating behaviors displayed by children with autism spectrum disorder (ASD) predispose them to unhealthy weight gain. We determined the...     

Assessing the Validity of Western Measurement of Online Risks to Children in an Asian Context

Before the advent of the Internet, television and film was the only audio-visual medium to which most children were exposed. The risks were primarily limited to children being exposed to sexual and violent materials, the nature of which were known and easy to control. Nowadays, children are surrounded by a variety of digital media and are exposed to different risks, many of which are still unknown. The Internet is fully integrated into children’s daily lives, along with the potential risks. The present study aimed to (i) describe the level of risks children are exposed to, and (ii) test the measurement validity of a total of 45 items assessing nine scales of online risk to children that were adapted from studies carried out in Europe and the United States. The study comprised 420 schoolchildren. The results showed that children were more exposed to ‘unwanted exposure to pornography’ and less to ‘conduct risk’ (e.g., accidental illegal downloading; creating profiles on inappropriate websites). Boys and older children were more exposed to the risks compared to girls and younger children. The study validated five dimensions (inappropriate materials, sexting, contact-related risks, risky online sexual behavior, and bullying/being bullied) assessing online risk to children by using exploratory and confirmatory factor analyses. The study found that scales developed in Europe and the United States are not wholly suitable to an Asian context and needed to be modified. Further investigation to classify online risks to children and offer a solutions to reducing the online risks.     

Rats exposed to cocaine during late gestation and early postnatal life show deficits in hippocampal pyramidal and granule cells in later life

In humans, the offspring of maternal cocaine misusers are known to have subtle cognitive and motor impairments in later life. It was therefore hypothesized that such exposure in animals would also affect the morphological structure of the brain. This possibility was investigated by exposing rats to cocaine between embryonic day 15 and postnatal day 6. Samples of the cocaine-exposed and control rats were killed for examination at 22 and 150 postnatal days of age. Stereological procedures (the Cavalieri principle together with the physical disector method) were utilized to estimate the total number of pyramidal and granule cells in defined regions of the hippocampal formation. At 22 days of age, the control offspring had about 373 000 pyramidal cells whereas the cocaine-treated animals only had about 310,000 cells in the CA1 + CA2 + CA3 region. By 150 days of age the values were about 396,000 and 348,000, respectively. The differences between age-matched groups were statistically significant. There were about 626,000 and 687,000 dentate gyrus granule cells in the 22-day-old control and cocaine-treated groups, respectively. By postnatal day 150 the control rats had about 832,000 granule cells whilst the cocaine-treated rats had about 693,000. There was a significant main effect of age as well as group-age interaction in this measure. These results show that even moderate exposure to cocaine during the late gestation and early postnatal period in rats is a potent teratogen and can markedly influence the development of neurons in the hippocampal formation.