Epigenetic Modulation in Parkinson’s Disease and Potential Treatment Therapies

In the recent past, huge emphasis has been given to the epigenetic alterations of the genes responsible for the cause of neurological disorders. Earlier, the scientists believed somatic changes and modifications in the genetic makeup of DNA to be the main cause of the neurodegenerative diseases. With the increase in understanding of the neural network and associated diseases, it was observed that alterations in the gene expression were not always originated by the change in the genetic sequence. For this reason, extensive research has been conducted to understand the role of epigenetics in the pathophysiology of several neurological disorders including Alzheimer’s disease, Parkinson’s disease and, Huntington’s disease. In a healthy person, the epigenetic modifications play a crucial role in maintaining the homeostasis of a cell by either up-regulating or down-regulating the genes. Therefore, improved understanding of these modifications may provide better insight about the diseases and may serve as potential therapeutic targets for their treatment. The present review describes various epigenetic modifications involved in the pathology of Parkinson’s Disease (PD) backed by multiple researches carried out to study the gene expression regulation related to the epigenetic alterations. Additionally, we will briefly go through the current scenario about the various treatment therapies including small molecules and multiple phytochemicals potent enough to reverse these alterations and the future directions for a better management of PD.

     

Ensuring the adaptive potential of Coastal wetlands of India- the need of the hour for sustainable management

India is endowed with a variety of coastal wetlands viz., mangroves, seagrasses, saltmarshes, coral reefs, lagoons and tidal flats, and the country is also a signatory to the Ramsar Convention on Wetlands and the Convention of Biological Diversity, besides having a robust framework of laws and policies, governing the wetland conservation. However, the conservation strategies can better be improved in the context of increasing pressures and threats and limited success of restoration/rehabilitation. Land conversion and ecological degradation of coastal wetlands are the stressors, associated with rapid coastal developmental activities and climate change. The coastal wetlands require desired habitat niche and hence, the conversion of coastal wetlands to other land uses (including agricultural and urban lands) may lead to permanent loss, whereas ecologically degraded coastal wetlands may be resilient if supported by effective protection measures. Preventing the habitat conversion and maximizing the adaptive potential (viz., the ability of populations or species to adapt to rapid environmental change with minimal disruption) by preserving the ecological health are the need of the hour to safeguard the existing coastal wetlands and sustain the provisional ecosystem services offered by them rather than short-term increase in area by unproductive restoration/rehabilitation efforts. Since coastal wetlands are flow through ecosystems, preserving the hydrological connectivity, facilitating the connectivity between adjacent ecosystems and protection of natural corridors are potential strategies that are required to enhance the adaptive potential of coastal wetlands. This analysis calls for site-specific, long-term and integrated ecosystem-based protection, management and rehabilitation strategies based on scientific principles and enforcing the effective legislative measures to regularize the coastal developmental activities in India.

     

Structural evolution and function of stress associated proteins in regulating biotic and abiotic stress responses in plants

Adverse environmental conditions greatly influence crop production every year and threaten food security. Plants have a range of signaling networks to combat these stresses, in which several stress-responsive genes and regulatory proteins function together. One such important family of proteins, the Stress Associated Protein (SAP) family, has been identified as a novel regulator of multiple stresses. The SAPs possess a characteristic N-terminal A20 zinc-finger domain combined with either AN1 or C₂H₂ at the C-terminus. SAPs provide tolerance against various abiotic stresses, including cold, salt, drought, heavy metal, and wounding. The majority of SAPs are stress-inducible and have a function in conferring stress tolerance in transgenics. The role of SAPs in regulating biotic stress responses is a newly emerging field among researchers. SAPs interact with many other proteins to execute their functions; however, the detailed mechanism of these interactions needs to be elucidated. In this context, the present review provides a detailed view of the evolution and functions of SAPs in plants. The involvement in crosstalk between abiotic and biotic stress signaling pathways makes SAPs ideal targets to develop crops with tolerance against multiple stresses without any yield penalty. Altogether, we provide current knowledge on SAPs for investigating their role in stress response, which can further be exploited to develop climate-resilient crops through transgene-based, breeding-mediated, or genome-editing approaches.

     

Testing the short-term effects of a fish invader on the trophic ecology of a closely related species

The effects of invaders on native species are usually tested using species mean trait values over long time scales. However, considering individual variation over short timescales can help us better understand the interaction between invaders and native species. We compared trophic traits of the non-native guppy (Poecilia reticulata) and the native Brazilian poeciliid Phalloceros harpagos using experiments simulating the early stages of an invasive process. We used short-term mesocosms to simulate an early invasion scenario, where the two species were placed together, and a pre-invasion scenario, where species were kept separated, and analyzed interspecific and intraspecific trophic variability. We also compared the foraging efficiency of species in laboratory experiments. We found no differences on the mean diet of both species between pre and early invasion treatments. At the individual level, in the early invasion scenario, individuals of both species reduced their trophic niche as a probable effect of the presence of the heterospecific. Phalloceros harpagos had higher consumption rates than guppies indicating greater efficiency in feeding on invertebrates. Our results suggest that non-native species were not intrinsically better consumers of high-quality resources. Instead, intraspecific variation might be playing an overlooked role in shaping interactions between species during the early stages of invasion.

     

Geoclimatic factors influence the population genetic connectivity of Incarvillea arguta (Bignoniaceae) in the Himalaya–Hengduan Mountains biodiversity hotspot

Geoclimatic factors related to the uplift of the Himalaya and the Quaternary climatic oscillations influence the population genetic connectivity in the Himalaya–Hengduan Mountains (HHM) biodiversity hotspot. Therefore, to explore the relative roles played by these two factors, we examined the population dynamics and dispersal corridors of Incarvillea arguta (Royle) Royle incorporating ensemble species distribution modelling (SDM). Thirty‐seven populations were genotyped using plastid chloroplast DNA and low copy nuclear gene (ncpGS) sequences. Phylogeographic analysis was carried out to reveal the genetic structure and lineage differentiation. Ensemble SDMs were carried out for distributional change in the last glacial maximum, present, and future. Finally, the least cost path method was used to trace out possible dispersal corridors. The haplotypes were divided into four clades with strong geographical structure. The late Miocene origin of I. arguta in the western Himalaya ca. 7.92 Ma indicates lineage diversification related to the uplift of the HHM. The variability in habitat connectivity revealed by SDM is due to change in suitability since the Pleistocene. A putative dispersal corridor was detected along the drainage systems and river valleys, with strong support in the eastern Hengduan Mountains group. Our results support the signature of geoclimatic influence on population genetic connectivity of I. arguta in the HHM. We proposed that the major drainage systems might have assisted the rapid dispersal of isolated riverine plant species I. arguta in the HHM. The population genetic connectivity, using the fine‐tuned ensemble SDMs, enables scientists and policymakers to develop conservation strategies for the species gene pool in the HHM biodiversity hotspots.     

Calcium/Calmodulin-Dependent Protein Kinase Is Negatively and Positively Regulated by Calcium,Providing a Mechanism for Decoding Calcium Responses during Symbiosis Signaling

The establishment of symbiotic associations in plants requires calcium oscillations that must be decoded to invoke downstream developmental programs. In animal systems, comparable calcium oscillations are decoded by calmodulin (CaM)–dependent protein kinases, but symbiotic signaling involves a calcium/CaM–dependent protein kinase (CCaMK) that is unique to plants. CCaMK differs from the animal CaM kinases by its dual ability to bind free calcium, via calcium binding EF-hand domains on the protein, or to bind calcium complexed with CaM, via a CaM binding domain. In this study, we dissect this dual regulation of CCaMK by calcium. We find that calcium binding to the EF-hand domains promotes autophosphorylation, which negatively regulates CCaMK by stabilizing the inactive state of the protein. By contrast, calcium-dependent CaM binding overrides the effects of autophosphorylation and activates the protein. The differential calcium binding affinities of the EF-hand domains compared with those of CaM suggest that CCaMK is maintained in the inactive state at basal calcium concentrations and is activated via CaM binding during calcium oscillations. This work provides a model for decoding calcium oscillations that uses differential calcium binding affinities to create a robust molecular switch that is responsive to calcium concentrations associated with both the basal state and with oscillations.     

Molecular diversity in rice blast resistance gene Pi-ta makes it highly effective against dynamic population of Magnaporthe oryzae

Rice blast is one of the important diseases of rice which can be effectively managed by the deployment of resistance genes. Pi-ta is one of the major blast resistant genes effective against pathogen populations in different parts of India. We analysed allelic variants of Pi-ta from 48 rice lines selected after phenotyping of 529 rice landraces across three eco-geographical blast hot spot regions. Besides, Pi-ta orthologue sequences of 220 rice accessions belonging to wild and cultivated species of rice were also included in the study for a better evo–devo perspective of the diversity present in the gene and the selection pressures acting on this locus. We obtained high nucleotide variations (SNPs and insertion–deletions) in the intronic region. We also identified 64 haplotypes based on nucleotide polymorphism in these alleles. Pi-ta orthologues of Indian landraces were scattered in eight major haplotypes indicating its heterogenous nature. We identified a total of 47 different Pi-ta protein variants on the basis of deduced amino acid residues amongst the orthologues. Five unique and novel Pi-ta variants were identified for the first time in rice landraces exhibiting different reaction types against the Magnaporthe oryzae population. A high value of Pi_non/syn was observed only in the leucine-rich domain of the alleles cloned from Indian landraces, indicating strong selective forces acting on this region. The detailed molecular analysis of the Pi-ta orthologues provides insights to a high degree of inter- and intraspecific relationships amongst the Oryza species. We identified rice landraces possessing the effective alleles of this resistance gene which can be used in future blast resistance breeding programmes.     

Isoaspartate Accumulation in Mouse Brain Is Associated with Altered Patterns of Protein Phosphorylation and Acetylation,Some of Which Are Highly Sex-Dependent

Isoaspartate (isoAsp) formation is a major source of protein damage that is kept in check by the repair function of protein L-isoaspartyl methyltransferase (PIMT). Mice deficient in PIMT accumulate isoAsp-containing proteins, resulting in cognitive deficits, abnormal neuronal physiology and cytoarchitecture, and fatal epileptic seizures 30–60 days after birth. Synapsins I and II, dynamin-1, collapsin response mediator protein 2 (CRMP2), and α/β-tubulin are major targets of PIMT in brain. To investigate links between isoAsp accumulation and the neurological phenotype of the KO mice, we used Western blotting to compare patterns of in vivo phosphorylation or acetylation of the major PIMT targets listed above. Phosphorylations of synapsins I and II at Ser-9 were increased in female KO vs. WT mice, and acetylation of tubulin at Lys-40 was decreased in male KO vs. WT mice. Average levels of dynamin-1 phosphorylation at Ser-778 and Ser-795 were higher in male KO vs. WT mice, but the statistical significance (P>0.1) was low. No changes in phosphorylation were found in synapsins I and II at Ser-603, in CRMP2 at Ser-522 or Thr-514, in DARPP-32 at Thr-34, or in PDK1 at Ser-241. General levels of phosphorylation assessed with Pro-Q Diamond stain, or an anti-phosphotyrosine antibody, appeared similar in the WT and KO mice. We conclude that isoAsp accumulation is associated with altered functional status of several neuronal proteins that are highly susceptible to this type of damage. We also uncovered unexpected differences in how male and female mice respond to isoAsp accumulation in the brain.     

405 nm-Excited Fluorescence Spectra of the Juice of the Lemon (Citrus x Limon)

A 405 nm diode laser is used to excite fluorescence of juices of raw and ripe lemons. Emission bands appear approximately at 520 nm and 670 nm. Fluorescence intensity ratio F520/F670 is determined for the two stages. Variation in the fluorescence intensity ratio is observed during the process of ripening or growth of the fruit. Time-resolved spectra at this excitation wavelength reveal two decay times at both the stages at the emission wavelength of 520 nm, and two decay times at the raw stage and one decay time at the ripe stage at 670 nm.