Publications by authors named "Chekuri A"
Article Synopsis
- - Familial dysautonomia (FD) is a serious inherited disorder caused by a specific genetic mutation that leads to neurological and systemic issues, resulting in shorter life expectancy for those affected.
- - Researchers developed a CRISPR base editor that can precisely correct the T-to-C mutation causing FD, achieving up to 70% successful editing in cell tests and improving the inclusion of a specific gene exon by over 50%.
- - The study also included an effective delivery method using engineered adeno-associated virus vectors, demonstrating that this approach can correct genetic defects in neurons and shows promise for a potential permanent treatment for FD with minimal side effects.
Article Synopsis
- * Researchers have developed a new gene expression vector, CPP16, which effectively delivered the human gene responsible for MLIV in preclinical mouse models.
- * The treatment improved brain function and motor skills, preventing paralysis, although it did not restore retinal thickness despite some positive effects on retinal tissue degeneration.
Familial dysautonomia (FD) is a rare recessive neurodevelopmental disease caused by a splice mutation in the Elongator acetyltransferase complex subunit 1 (ELP1) gene. This mutation results in a tissue-specific reduction of ELP1 protein, with the lowest levels in the central and peripheral nervous systems (CNS and PNS, respectively). FD patients exhibit complex neurological phenotypes due to the loss of sensory and autonomic neurons.
View Article and Find Full Text PDFFamilial dysautonomia (FD) is a rare recessive neurodevelopmental disease caused by a splice mutation in the Elongator acetyltransferase complex subunit 1 ( ) gene. This mutation results in a tissue-specific reduction of ELP1 protein, with the lowest levels in the central and peripheral nervous systems (CNS and PNS, respectively). FD patients exhibit complex neurological phenotypes due to the loss of sensory and autonomic neurons.
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- Late-onset retinal degeneration (L-ORD) is a genetic eye condition caused by mutations in the CTRP5 gene, leading to macular dystrophy.
- Researchers created a new mouse model (Ctrp5 knock-out) that lacks the CTRP5 gene to investigate the disease's mechanisms more thoroughly.
- The study found that the absence of CTRP5 caused significant retinal damage and stress, including early cell changes and the buildup of harmful deposits, which supports the idea that CTRP5 is essential for maintaining healthy retinal function.
Article Synopsis
- researchers discovered kinetin, a small molecule that can correct the ELP1 splicing defect, and have developed more effective derivatives called splicing modulator compounds (SMCs).
- The new compound PTC258 not only restores correct ELP1 splicing in mouse brains but also significantly improves survival, gait, and retinal function in mice with FD, demonstrating its potential as a therapeutic treatment.
Article Synopsis
- - Familial dysautonomia (FD) is a genetic neurodegenerative disorder caused by a mutation in the ELP1 gene, leading to reduced ELP1 protein, especially in the nervous system, which affects sensory and autonomic neurons.
- - One of the major issues for FD patients is progressive vision loss that can lead to blindness, greatly impacting their quality of life.
- - Researchers developed a new mouse model, TgFD9; IkbkapΔ20/flox, to study FD and found that a compound called BPN-15477 can correct the splicing defect in the retina, offering potential for targeted treatments.
Article Synopsis
- Familial dysautonomia (FD) is a genetic condition caused by a mutation in the ELP1 gene, which leads to reduced protein levels crucial for sensory and autonomic functions.
- Researchers created mouse models to study FD and found that a complete loss of the Elp1 gene causes early embryonic death, while introducing human ELP1 in varying amounts can rescue embryonic development.
- The study revealed that ELP1 is vital for nervous system gene expression, especially for longer genes, and identified specific gene sets that change in response to ELP1 levels.
Article Synopsis
- * Researchers discovered a compound called BPN-15477 that can correct splicing issues in a gene called ELP1, and they used advanced techniques to find genetic signatures responsive to this compound.
- * Validation experiments showed that BPN-15477 successfully fixed splicing problems in several disease-related genes, suggesting it has potential as a therapeutic treatment for certain genetic disorders.
Late-onset retinal degeneration (L-ORD) is an autosomal dominant macular degeneration characterized by the formation of sub-retinal pigment epithelium (RPE) deposits and neuroretinal atrophy. L-ORD results from mutations in the C1q-tumor necrosis factor-5 protein (CTRP5), encoded by the CTRP5/C1QTNF5 gene. To understand the mechanism underlying L-ORD pathology, we used a human cDNA library yeast two-hybrid screen to identify interacting partners of CTRP5.
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- Patients with homozygous c.498_499insC mutations experience various eye issues like hyperopia, microphthalmia, and retinitis pigmentosa, but some maintain good vision for a long time.
- A genetic mouse model mimicking these mutations showed similar eye characteristics as humans, such as reduced eye length and retinal degeneration, along with worse refractive error than typical mice.
- Gene therapy using a specific virus helped improve retinal health and function in these mice, suggesting a potential treatment for human patients with similar eye conditions.
Article Synopsis
- - Whole genome sequencing (WGS) identified specific genetic variants linked to inherited retinal degeneration (IRD) in a Caucasian family, particularly focusing on mutations in the IFT88 gene.
- - The study confirmed that the mutations p.Arg266* and p.Ala568Thr in IFT88 lead to abnormal ciliary structures, indicating a disruption in cellular function.
- - Results showed that the p.Arg266* mutation causes significant loss of IFT88 mRNA due to nonsense-mediated decay, highlighting its role in retinal disease mechanisms.
Article Synopsis
- * The study identifies Rac1 as a crucial regulator in this process, showing that it becomes misdirected to the nucleus under high glucose conditions, promoting harmful signaling pathways.
- * Metformin may help protect β-cells from glucotoxic damage by preventing Rac1 activation and maintaining cellular integrity, suggesting new therapeutic strategies for diabetes management.
Article Synopsis
- - Topoisomerase IIβ (TopoIIβ) plays a significant role in HIV-1 infection, with its increased expression leading to higher viral replication and virion production.
- - Downregulation of TopoIIβ through methods like siRNA or inhibitors like ICRF-193 negatively affects HIV-1 replication, suggesting its crucial role in the virus's life cycle.
- - Experimental methods like co-immunoprecipitation, ChIP assays, and luciferase assays demonstrated that TopoIIβ interacts with the HIV-1 transcription factor Tat and is essential for the activation of HIV-1 long terminal repeat (LTR) regions, underscoring its importance in the viral replication process.
Article Synopsis
- Senescence is a key factor in the loss of neurons during aging, influenced by multiple causes including gene expression and DNA damage.
- DNA damage, especially in nuclear and mitochondrial DNA, disrupts cellular functions and contributes to aging through apoptosis or cellular senescence.
- The study highlights that suppressing certain genes, Npy and Slit2, in aged neurons can improve cell viability and restore the expression of crucial DNA repair enzymes like Topo IIβ.
Article Synopsis
- The study investigates the effectiveness of two mouse monoclonal antibodies targeting the oncofetal antigen immature laminin receptor protein (OFA/iLRP) in suppressing tumor growth and metastasis in leukemia and melanoma models.
- The antibodies showed modest success in preventing tumor growth at the original site but significantly reduced tumor formation in other organs after tumor cells were injected into the bloodstream.
- These findings indicate that anti-OFA/iLRP antibodies may serve as a potential therapy for patients with leukemia and could also be beneficial in treating solid tumors with metastatic spread.
Article Synopsis
- - KIBRA (WWC1) is a scaffolding protein that helps regulate cell transport, polarity, and is an upstream regulator of the Hippo signaling pathway, impacting cell growth and organ size in animals.
- - The WWC protein family includes KIBRA, WWC2, and WWC3, with KIBRA being well studied while the roles of WWC2 and WWC3 remain unclear.
- - The evolutionary origin of the WWC family can be traced back to a common ancestor of bilateral animals, with all three proteins present in tetrapods, though WWC3 is missing in mice due to a genomic deletion.
Cervical cancer remains a major reproductive health problem among women especially in developing countries where about 190,000 women die from this disease annually. Despite efforts to reduce the burden of this disease, most attempts in low-resourced countries have not been successful partly from lack of awareness by women of this common cancer, as well as the role the human papilloma virus (HPV) plays in its aetiology and pathogenesis. To determine knowledge, attitudes and practice of women in Trinidad (a developing country) on HPV, cervical cancer and the HPV vaccine, we conducted a cross-sectional survey among 426 women in the reproductive age.
View Article and Find Full Text PDFWe performed a prospective study involving 400 consecutive pregnant patients to determine whether the administration of a lime-flavoured glucose drink followed by a blood test 1 h later was a better method of screening for gestational diabetes (GDM) than the use of selective screening based on risk factors (maternal age over 30 years, East Indian ancestry and obesity). Complete data were available for 388 women, 76 were screen positive (1 h blood glucose ≥ 140 mg/dl) and GDM was diagnosed in 42 (using a 75 g oral glucose tolerance test) giving a positive predictive value of 55%. Selective screening applied to the same population would have identified only 34 cases, eight fewer with GDM.
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- * Results show that TopoIIβ levels increase during recovery from DNA damage and its knock-down makes neurons more vulnerable to this damage.
- * The research highlights that TopoIIβ plays a crucial role in both Ku70 and PARP-1 dependent DSB repair pathways, potentially stabilizing the repair complex and protecting genomic DNA integrity.
A prototype time cycled, constant volume, closed circuit perfluorocarbon (PFC) total liquid ventilator system is described. The system utilizes microcontroller-driven display and master control boards, gear motor pumps, and three-way solenoid valves to direct flow. A constant tidal volume and functional residual capacity (FRC) are maintained with feedback control using end-expiratory and end-inspiratory stop-flow pressures.
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