Alpha-synuclein mutations mislocalize cytoplasmic p300 compromising autophagy, which is rescued by ACLY inhibition.

Triplications and certain point mutations in the SNCA gene, encoding alpha-synuclein (α-Syn), cause Parkinson's disease (PD). Here, we demonstrate that the PD-causing A53T α-Syn mutation and elevated α-Syn expression perturb acetyl-coenzyme A (CoA) and p300 biology in human neurons and in the CNS of zebrafish and mice. This dysregulation is mediated by activation of ATP-citrate lyase (ACLY), a key enzyme that generates acetyl-CoA in the cytoplasm, via two mechanisms.

Fluorescent/ Photoluminescent Carbon Dots as a Sensor for the Selective and Sensitive Detection of Fe/Fe Metal Ions. A Review of the Last Decade.

Particularly in the numerous biomedical application sectors, the special advantages of an absorbing group of fluorescence carbon dots (CDs), such as their low toxicity, physicochemical stability, photostability, and remarkable biocompatibility, are currently garnering a lot of study focus. Because imbalance of Fe and Fe ions are more hazardous than other ions, they are crucial for maintaining human health. CDs were used as a fluorescent probe to detect these metal ions, Fe/ Fe.

Unravelling cell type-specific responses to Parkinson's Disease at single cell resolution.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD is loss of dopaminergic neurons and the presence of aggregated α-synuclein, primarily in the substantia nigra pars compacta (SNpc) of the midbrain. However, the molecular mechanisms that underlie the pathology in different cell types is not currently understood.

Single-cell transcriptomics identifies perturbed molecular pathways in midbrain organoids using α-synuclein triplication Parkinson's disease patient-derived iPSCs.

Three-dimensional (3D) brain organoids provide a platform to study brain development, cellular coordination, and disease using human tissue. Here, we generate midbrain dopaminergic (mDA) organoids from induced pluripotent stem cells (iPSC) from healthy and Parkinson's Disease (PD) donors and assess them as a human PD model using single-cell RNAseq. We characterize cell types in our organoid cultures and analyze our model's Dopamine (DA) neurons using cytotoxic and genetic stressors.

CRISPR-Cas9 genetic screen leads to the discovery of L-Moses, a KAT2B inhibitor that attenuates Tunicamycin-mediated neuronal cell death.

Accumulation of aggregated and misfolded proteins, leading to endoplasmic reticulum stress and activation of the unfolded protein response, is a hallmark of several neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Genetic screens are powerful tools that are proving invaluable in identifying novel modulators of disease associated processes. Here, we performed a loss-of-function genetic screen using a human druggable genome library, followed by an arrayed-screen validation, in human iPSC-derived cortical neurons.

A suspension technique for efficient large-scale cancer organoid culturing and perturbation screens.

Organoid cell culture methodologies are enabling the generation of cell models from healthy and diseased tissue. Patient-derived cancer organoids that recapitulate the genetic and histopathological diversity of patient tumours are being systematically generated, providing an opportunity to investigate new cancer biology and therapeutic approaches. The use of organoid cultures for many applications, including genetic and chemical perturbation screens, is limited due to the technical demands and cost associated with their handling and propagation.

Azotobacter: A potential bio-fertilizer for soil and plant health management.

Stressor (biotic as well as abiotic) generally hijack the plant growth and yield characters in hostile environment leading to poor germination of the plants and yield. Among the plant growth promoting rhizobacteria, spp. (Gram-negative prokaryote) are considered to improve the plant health.

Identifying Informal Settlements Using Contourlet Assisted Deep Learning.

As the global urban population grows due to the influx of migrants from rural areas, many cities in developing countries face the emergence and proliferation of unplanned and informal settlements. However, even though the rise of unplanned development influences planning and management of residential land-use, reliable and detailed information about these areas is often scarce. While formal settlements in urban areas are easily mapped due to their distinct features, this does not hold true for informal settlements because of their microstructure, instability, and variability of shape and texture.

Incidence Of Paraphenylene-Diamine Poisoning In Three Districts Headquarter Hospitals Of Pakistan.

Background: Paraphenylene-diamine (PPD) poisoning is an emerging problem of developing African and South Asian countries. This study was done with the objective to determine the clinical lab diagnostic accuracy of serum creatinine phosphokinase in cases initially reporting facial oedema followed by renal failure and rhabdomyolysis due to paraphenylene-diamine (PPD) poisoning.

Methods: It was a cross-sectional study in which data was retrospectively collected at District Head Quarter (DHQ) Hospitals.

Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens.

Functional genomics approaches can overcome limitations-such as the lack of identification of robust targets and poor clinical efficacy-that hamper cancer drug development. Here we performed genome-scale CRISPR-Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritize candidates for cancer therapeutics. We integrated cell fitness effects with genomic biomarkers and target tractability for drug development to systematically prioritize new targets in defined tissues and genotypes.

Unsupervised correction of gene-independent cell responses to CRISPR-Cas9 targeting.

Background: Genome editing by CRISPR-Cas9 technology allows large-scale screening of gene essentiality in cancer. A confounding factor when interpreting CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes within copy number amplified regions of the genome. We have developed the computational tool CRISPRcleanR which is capable of identifying and correcting gene-independent responses to CRISPR-Cas9 targeting.

Successful Generation of Human Induced Pluripotent Stem Cell Lines from Blood Samples Held at Room Temperature for up to 48 hr.

The collection sites of human primary tissue samples and the receiving laboratories, where the human induced pluripotent stem cells (hIPSCs) are derived, are often not on the same site. Thus, the stability of samples prior to derivation constrains the distance between the collection site and the receiving laboratory. To investigate sample stability, we collected blood and held it at room temperature for 5, 24, or 48 hr before isolating peripheral blood mononuclear cells (PBMCs) and reprogramming into IPSCs.

Nordihydroguiaretic acid attenuates skin tumorigenesis in Swiss albino mice with the condition of topical co-administration of an immunosuppressant.

Drug and chemically-induced immunosuppression has been implicated as a confounding factor for cancer development. Management of cancer in such situation is often a challenging task. We tested the efficacy of nordihydroguiaretic acid (NDGA) against immunosuppressant tacrolimus-induced augmentation of mouse skin tumorigenesis.

Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse.

Bisphenol A (BPA) is a monomer of polycarbonate plastic used to manufacture plastic baby bottles and lining of food cans. It has endocrine-disrupting potential and exerts both toxic and estrogenic effects on mammalian cells. We studied BPA-induced perturbation of mitochondrial marker enzymes in testes of Swiss albino mice and its amelioration by melatonin.

The interactive effect of elevated temperature on deltamethrin-induced biochemical stress responses in Channa punctata Bloch.

There are reports showing interactive effect of environmental factors with the toxic outcome of chemicals. We studied the interactive effect of elevated temperature as an abiotic stressor on deltamethrin-induced biochemical stress responses in a freshwater fish, Channa punctata Bloch. Heat stress (∼12°C above ambient temperature for 3h) and pesticide exposure (deltamethrin 0.

In vivo cytogenetic and oxidative stress-inducing effects of cypermethrin in freshwater fish, Channa punctata Bloch.

Synthetic pyrethroids are considered to be safe over other insecticides. Many of the newest pyrethroids lack ecotoxicity data. However, animal data indicate that their use may pose risk to environmental biota.

Nordihydroguaiaretic Acid from Creosote Bush (Larrea tridentata) Mitigates 12-O-Tetradecanoylphorbol-13-Acetate-Induced Inflammatory and Oxidative Stress Responses of Tumor Promotion Cascade in Mouse Skin.

Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It has a long history of traditional medicinal use by the Native Americans and Mexicans.

Iron deficiency augments bisphenol A-induced oxidative stress in rats.

Bisphenol A (BPA), an estrogenic environmental contaminant is also known for oxidative stress-inducing effect. Malnutrition is recognized as a confounding factor in oxidative stress. However, little is known about effect of malnutrition on oxidative stress induced by BPA or other endocrine disrupting chemicals (EDCs).

Genotoxic and oxidative stress-inducing effects of deltamethrin in the erythrocytes of a freshwater biomarker fish species, Channa punctata Bloch.

Deltamethrin, an alpha-cyano class of pyrethroid insecticide is used in insect pest control and antimalaria programs in several countries including India. Although various toxic manifestations of deltamethrin are reported in mammals, its ecotoxicologic dimensions are not adequately researched in ecologically and commercially important fishes. In this study, we report genotoxic effect of deltamethrin in a biomarker fish Channa punctata (Bloch).

Effects of exposure to multiple trace metals on biochemical, histological and ultrastructural features of gills of a freshwater fish, Channa punctata Bloch.

The trace metals are frequently encountered as mixtures of essential and non-essential elements. Therefore, evaluation of their toxic effects individually does not offer a realistic estimate of their impact on biological processes. We studied effects of a mixture of four essential and toxic metals (Cu, Cd, Fe and Ni) on biochemical and morphological characteristics of the gills of a biomarker freshwater fish Channa punctata (Bloch) using environmentally relevant concentrations.

Channa punctata brain metallothionein is a potent scavenger of superoxide radicals and prevents hydroxyl radical-induced in vitro DNA damage.

Mammalian brain metallothioneins (MTs) have been shown to scavenge free radicals. However, a similar role for fish brain MT has not been established yet. Previously, we have reported that MT from the liver of a freshwater fish, Channa punctata Bloch, had free-radical-scavenging activity in vitro.

Pro-apoptotic effect of fly ash leachates in hepatocytes of freshwater fish (Channa punctata Bloch).

The pro-apoptotic effect of fly ash leachates (FAL) was studied in the hepatocytes of an Indian freshwater fish, Channa punctata Bloch. Hepatocytes were exposed to different concentrations of '7-day' FAL for 24 and 48h and various parameters of apoptosis were studied using standardized procedures. FAL-induced apoptosis in hepatocytes was indicated by cytological examination, DNA fragmentation and DNA laddering.