Allosteric regulation of the Golgi-localized PPM1H phosphatase by Rab GTPases modulates LRRK2 substrate dephosphorylation in Parkinson's disease.

PPM1H phosphatase reverses Parkinson's disease-associated, Leucine Rich Repeat Kinase 2-mediated, Rab GTPase phosphorylation. We showed previously that PPM1H relies on an N-terminal amphipathic helix for Golgi membrane localization and this helix enables PPM1H to associate with liposomes in vitro; binding to highly curved liposomes activates PPM1H's phosphatase activity. We show here that PPM1H also contains an allosteric binding site for its non-phosphorylated reaction products, Rab8A and Rab10.

Lysosomal glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway contributing to Parkinson's disease.

Parkinson's disease is characterized by loss of dopamine neurons that project to the dorsal striatum, and mutations in and are the most common genetic causes of familial Parkinson's disease. Previously, we showed that pathogenic mutations inhibit primary cilia formation in rare interneurons and astrocytes of the mouse and human dorsal striatum. This blocks Hedgehog signaling and reduces synthesis of neuroprotective GDNF and NRTN, which normally support dopamine neurons vulnerable in PD.

PPM1M, an LRRK2-counteracting, phosphoRab12-preferring phosphatase with a potential link to Parkinson's disease.

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking, and LRRK2-activating mutations are linked to Parkinson's disease. Rab phosphorylation is a transient event that can be reversed by phosphatases, including protein phosphatase, Mg2/Mn2 dependent 1H (PPM1H), which acts on phosphorylated Rab 8A (phosphoRab8A) and phosphoRab10. Here, we report a phosphatome-wide small interfering RNA (siRNA) screen that identified PPM1M as a phosphoRab12-preferring phosphatase that also acts on phosphoRab8A and phosphoRab10.

End-product inhibition of the LRRK2-counteracting PPM1H phosphatase.

PPM1H phosphatase reverses Parkinson's disease-associated, Leucine Rich Repeat Kinase 2-mediated, Rab GTPase phosphorylation. We showed previously that PPM1H relies on an N-terminal amphipathic helix for Golgi membrane localization and this helix enables PPM1H to associate with liposomes ; binding to highly curved liposomes activates PPM1H's phosphatase activity. We show here that PPM1H also contains an allosteric binding site for its non-phosphorylated reaction products, Rab8A and Rab10.

PPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinson's disease.

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking; activating mutations in are linked to Parkinson's disease. Rab phosphorylation is a transient event that can be reversed by phosphatases, including PPM1H, that acts on phosphoRab8A and phosphoRab10. Here we report a phosphatome-wide siRNA screen that identified PPM1M as a phosphoRab12-preferring phosphatase that also acts on phosphoRab8A and phosphoRab10.

Impact of Invasive Weeds Lantana camara L. and Parthenium hysterophorus L. on the Secondary Metabolite Profiles of Okra (Abelmoschus esculentus L.).

The impact of two invasive weed species, Lantana camara and Parthenium hysterophorus, on the development and secondary metabolism of okra (Abelmoschus esculentus) is the focus of this study. We explored the potential role of secondary metabolites as antioxidants to mitigate the stress induced by these common weeds on okra plants with special emphasis on chlorogenic acid (CGA). The study has been done with six experimental setups.

Untying arsenite tolerance mechanisms in contrasting maize genotypes attributed to NIPs-mediated controlled influx and root-to-shoot translocation, redox homeostasis and phytochelatin-mediated detoxification pathway.

Contamination of ground water and soil with toxic metalloids like arsenic (As) poses a serious hazard to the global agricultural food production. One of the best ways to restrict entry of As into the food chain is selection of germplasms which accrue extremely low level of As in grains. Here, we screened diverse maize genotypes under high arsenite (100 μM AsIII) stress and identified PMI-PV-9 and PMI-PV-3 as AsIII-tolerant and -sensitive maize genotype respectively.

Untying the regulatory roles of miRNAs in CuO-NPs stress response mechanism in maize: A genome-wide sRNA transcriptome analysis.

MicroRNAs (miRNAs), a group of tiny non-coding RNAs play pivotal role in plant responses to environmental stress. The present small RNA transcriptome study aims to untie the role of miRNAs in CuO-NPs stress adaptation in maize seedlings. Restricted seedling growth, enhanced ROS generation and higher membrane damage were recorded under CuO-NPs [<50 nm, 8 mM] treatment.

Localization of PPM1H phosphatase tunes Parkinson's disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis.

PPM1H phosphatase reverses Parkinson's disease-associated, Leucine Rich Repeat Kinase 2-mediated Rab GTPase phosphorylation. We show here that PPM1H relies on an N-terminal amphipathic helix for Golgi localization. The amphipathic helix enables PPM1H to bind to liposomes in vitro, and small, highly curved liposomes stimulate PPM1H activity.

Large area multi-filamentary plasma source for large volume plasma device-upgrade.

This paper discusses the salient features and plasma performance of the newly installed Large Area Multi-Filamentary Plasma Source (LAMPS) in large volume plasma device-upgrade. The plasma source is designed to exhibit a plasma electron density of ∼10 m, low electron temperature (∼eV), and a uniform plasma cross section of 2.54 m.

A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation.

Activating mutations in the leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease, and previously we showed that activated LRRK2 phosphorylates a subset of Rab GTPases (Steger et al., 2017). Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation.

Impact of CuO nanoparticles on maize: Comparison with CuO bulk particles with special reference to oxidative stress damages and antioxidant defense status.

The present study aimed to systematically investigate the particle size effects of copper (II) oxide [CuO nanoparticles (<50 nm) and CuO bulk particles (<10 μm)] on maize (Zea mays L.). Bioaccumulation of Cu, in vivo ROS generation, membrane damage, transcriptional modulation of antioxidant genes, cellular redox status of glutathione and ascorbate pool, expression patterns of COPPER TRANSPORTER 4 and stress responsive miRNAs (miR398a, miR171b, miR159f-3p) with their targets were investigated for better understanding of the underlying mechanisms and the extent of CuO nanoparticles and CuO bulk particles induced oxidative stress damages.

Development of electronic record-keeping software for remote participation in Large Volume Plasma Device upgrade using Angular 2 and NodeJS web technologies.

In an era of digital transformation and collaborations, the Web Information System (WIS) becomes an essential requirement for the information and data sharing of large experimental facilities among users. With the enhancement in the capabilities and performance of web technologies, sharing of experimental data using a flexible, modular, secure, and robust mechanism is feasible. In this direction, the Large Volume Plasma Device (LVPD), an experimental device dedicated for carrying out investigations for unfolding physical phenomena of relevance to Earth's magnetosphere and fusion plasmas, also adopts web-based electronic record keeping for its operation.

Assessment of ZnO-NPs toxicity in maize: An integrative microRNAomic approach.

Rapid expansion of nanotechnology and indiscriminate discharge of metal oxide nanoparticles (NPs) into the environment pose a serious hazard to the ecological receptors including plants. To better understand the role of miRNAs in ZnO-NPs stress adaptation, two small RNA libraries were prepared from control and ZnO-NPs (800 ppm, <50 nm particle size) stressed maize leaves. Meager performance of ZnO-NPs treated seedlings was associated with elevated tissue zinc accumulation, enhanced ROS generation, loss of root cell viability, increased foliar MDA content, decrease in chlorophyll and carotenoids contents.

PAS domain-containing phosphoglycerate kinase deficiency in results in increased autophagosome formation and cell death.

Per-Arnt-Sim (PAS) domains are structurally conserved and present in numerous proteins throughout all branches of the phylogenetic tree. Although PAS domain-containing proteins are major players for the adaptation to environmental stimuli in both prokaryotic and eukaryotic organisms, these types of proteins are still uncharacterized in the trypanosomatid parasites, and In addition, PAS-containing phosphoglycerate kinase (PGK) protein is uncharacterized in the literature. Here, we report a PAS domain-containing PGK (LmPAS-PGK) in the unicellular pathogen The modeled structure of N-terminal of this protein exhibits four antiparallel β sheets centrally flanked by α helices, which is similar to the characteristic signature of PAS domain.

Loss of virulence in NAD(P)H cytochrome b5 oxidoreductase deficient Leishmania major.

Leishmania promastigotes have the ability to synthesize essential polyunsaturated fatty acids de novo and can grow in lipid free media. Recently, we have shown that NAD(P)H cytochrome b5 oxidoreductase (Ncb5or) enzyme in Leishmania acts as the redox partner for Δ12 fatty acid desaturase, which catalyses the conversion of oleate to linoleate. So far, the exact role of Leishmania derived linoleate synthesis is still incomplete in the literature.

Control of catalysis in globin coupled adenylate cyclase by a globin-B domain.

The globin coupled heme containing adenylate cyclase from Leishmania major (HemAC-Lm) has two globin domains (globin-A and globin-B). Globin-B domain (210-360 amino acids) may guide the interaction between globin-A and adenylate cyclase domains for the regulation of catalysis. We investigated the role of globin-B domain in HemAC-Lm by constructing a series of mutants namely Δ209 (209 amino acids deleted), Δ360 (360 amino acids deleted), H161A, H311A and H311A-Δ209.